D-lactic acidosis in short bowel syndrome: are probiotics friend or foe? A case report

Hong Kong Med J 2025;31:Epub 17 Jul 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
D-lactic acidosis in short bowel syndrome: are probiotics friend or foe? A case report
Bowie PY Leung, MRCPCH, FHKAM (Paediatrics)1; Bess SY Tsui, FHKAM (Surgery), FCSHK2; Ingrid Kan, MSc (Nutrition and Dietetics), APD3
1 Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
2 Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
3 Department of Dietetics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
 
Corresponding author: Dr Bowie PY Leung (bowieleung@cuhk.edu.hk)
 
 Full paper in PDF
 
 
Case presentation
A 6-year-old Chinese boy with short bowel syndrome (SBS) presented to the emergency department with excessive drowsiness. He was born full term with an unremarkable perinatal history and had good past health. At 3 years of age, he underwent extensive small bowel resection and a right hemicolectomy due to intestinal malrotation with midgut volvulus, resulting in a residual length of 66 cm of proximal small bowel and distal colon, with loss of the ileocaecal valve.
 
Initially dependent on total parenteral nutrition, he achieved enteral autonomy 3 years later, consuming an oral diet supplemented with vitamins, iron, and a hydrolysed formula of 1 kcal/mL, contributing approximately 20% of total energy intake. A timeline summarising key clinical events, including enteral and parenteral nutrition milestones, is presented in the Figure.
 

Figure. Summary of major events and respective percentages of total estimated energy requirement contributed by parenteral nutrition and enteral nutrition
 
He was reviewed monthly by a multidisciplinary team with regular assessments of his nutritional status, growth parameters, and biochemical profile. He demonstrated good growth, maintaining weight and height at the 50th percentile, with regular bowel movements with daily oral loperamide. His biochemical profile, including blood counts, liver function, electrolytes, blood gas, and trace elements, remained stable throughout the follow-up period.
 
On this admission, the patient was drowsy and lethargic but not confused. Blood tests indicated high anion gap metabolic acidosis, with a pH of 7.31, bicarbonate 10.8 mmol/L, pCO2 2.9 kPa, and L-lactate 1.6 mmol/L (reference range, 1.0-2.4 mmol/L). Complete blood counts, liver enzymes, ammonia, electrolytes, glucose levels, and computed tomography of the brain were normal. D-lactic acidosis (D-LA) was confirmed by an elevated serum D-lactate concentration of 1.7 mmol/L (normal range, <0.5 mmol/L). Further enquiry revealed that one week prior, his family had switched to an alternative commercially available enteral formula containing probiotics (Lactobacillus paracasei and Bifidobacterium longum) as the original formula was temporarily out of stock (Table). The rest of his oral diet remained unchanged. Total carbohydrate (CHO) intake accounted for 40% to 50% of his total enteral intake, with the formula contributing 20%.
 

Table. Comparison of contents of the original and new formula
 
His condition improved rapidly with bowel rest and oral sodium bicarbonate. He was treated with a course of oral metronidazole. The probiotic-containing formula was stopped, and he was instructed to resume the original probiotic-free hydrolysed formula along with CHO-restricted meals. His carers were re-educated on CHO counting and avoidance of simple sugars. He remained clinically stable the following months, during which he maintained good dietary compliance.
 
Discussion
Short bowel syndrome refers to a condition of intestinal malabsorption resulting from loss or surgical resection of the small intestine and is the leading cause of intestinal failure. It encompasses a heterogeneous group of patients with various aetiologies and bowel anatomies. Effective management requires a multidisciplinary approach to promote enteral autonomy, support growth, and prevent complications such as catheter-related bloodstream infections and intestinal failure–associated liver disease.
 
D-lactic acidosis, first described in SBS by Oh et al in 1979,1 has gained increasing recognition as a rare but serious metabolic complication. It results from intestinal malabsorption and overgrowth of colonic microbiota (eg, Lactobacillus spp, Bifidobacterium spp), leading to excessive fermentation of unabsorbed CHO. The process is exacerbated by factors such as high CHO intake, elevated gut pH, impaired gut motility, antimicrobials, probiotics, and intestinal infections. The overproduction of D-lactic acid leads to a neurological syndrome and high anion gap metabolic acidosis. Clinical manifestations include acidotic breathing, altered mental state, ataxia, slurred speech, nystagmus, gait disturbance, behavioural change, and fatigue. A high index of clinical suspicion and measurement of D-lactic acid are essential for diagnosis, as serum lactate concentration (reflecting L-lactate) is often normal.2 3
 
The mainstays of acute management of D-LA include correction of metabolic acidosis with bicarbonate and rehydration, restriction of enteral CHO intake, administration of poorly absorbed oral antibiotics, and avoidance of antimotility agents or lactate-containing solutions. Additional treatment may include thiamine and riboflavin supplementation, insulin, and short-chain fatty acids. Metabolic acidosis and neurological symptoms often improve rapidly with early and appropriate intervention. To prevent recurrence, CHO restriction and avoidance of D-lactate–containing foods (eg, pickles and yoghurt) are essential. In selected cases, suppression of abnormal gut flora with antimicrobials or surgery to increase bowel absorptive area may be considered.3 4
 
Probiotics have gained popularity as health-promoting agents in medicines and dietary supplements, including in the management of SBS to prevent and treat small intestinal bacterial overgrowth. Certain species, such as Lactobacillus casei, produce only L-lactate. Among commercially available probiotics, Lactobacillus and Bifidobacterium are the most commonly used genera.2 5 The European Society for Paediatric Gastroenterology, Hepatology and Nutrition has summarised the latest evidence on probiotic use across various paediatric gastrointestinal disorders.6 Strain-specific benefits have been demonstrated in conditions such as acute gastroenteritis, antibiotic-associated diarrhoea, infantile colic, functional abdominal disorders, and in the prevention of necrotising enterocolitis and nosocomial diarrhoea.6
 
Animal studies and clinical case reports suggest that probiotics may confer potential benefits in patients with SBS through mechanisms such as enhancement of gut barrier function, suppression of pathogens, and modulation of immune responses.7 Nevertheless, clinical studies evaluating their efficacy remain limited, and there is insufficient evidence to support the routine use in SBS. Conversely, case reports have raised safety concerns, such as the development of D-LA and sepsis in children with SBS following probiotic administration.7 In our case, the addition of probiotics via the new milk formula suggests a possible role of probiotics in the development of D-LA. This highlights the need for cautious and selective use of non–D-lactate–producing probiotic strains in patients at high risk of D-LA.
 
This report illustrates a case of D-LA in a paediatric patient with SBS, precipitated by the intake of a probiotic-containing enteral formula. Early recognition of D-LA, based on characteristic clinical features and confirmed by D-lactate measurement, with prompt treatment to normalise acidosis and suppress D-lactate production, is essential. Cautious dietary management, including caregiver awareness of formula contents and dietary CHO restriction, is equally important. Despite the increasing medical use of probiotics, there is a lack of clinical trials to support their routine use or provide clear guidance for their use in paediatric SBS. Careful consideration is warranted, with awareness of potential strain-specific benefits and risks, particularly in patients with altered intestinal microbiota and malabsorption.
 
Author contributions
Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: BPY Leung.
Critical revision for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Acknowledgement
The authors would like to acknowledge the multidisciplinary teams involved in the co-management of this case. Special thanks to the dietitians, Paediatric Surgery team, and Paediatric Gastroenterology team at Prince of Wales Hospital, as well as the Paediatric team at Princess Margaret Hospital, for their invaluable contributions to the care and management of the patient.
 
Declaration
Findings from this case were presented as a poster at the 23rd Congress of the Parenteral and Enteral Nutrition Society of Asia (PENSA 2023), 19-22 October 2023, Taipei, Taiwan.
 
Funding/support
This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided written informed consent for all treatments, procedures and the publication of this case report.
 
References
1. Oh MS, Phelps KR, Traube M, Barbosa-Saldivar JL, Boxhill C, Carroll HJ. D-lactic acidosis in a man with the short-bowel syndrome. N Engl J Med 1979;301:249-52. Crossref
2. Muto M, Kaji T, Onishi S, Yano K, Yamada W, Ieiri S. An overview of the current management of short-bowel syndrome in pediatric patients. Surg Today 2022;52:12-21. Crossref
3. Bianchetti DG, Amelio GS, Lava SA, et al. D-lactic acidosis in humans: systematic literature review. Pediatr Nephrol 2018;33:673-81. Crossref
4. Kowlgi NG, Chhabra L. D-lactic acidosis: an underrecognized complication of short bowel syndrome. Gastroenterol Res Pract 2015;2015:476215. Crossref
5. Höllwarth ME, Solari V. Nutritional and pharmacological strategy in children with short bowel syndrome. Pediatr Surg Int 2021;37:1-15. Crossref
6. Szajewska H, Berni Canani R, Domellöf M, et al. Probiotics for the management of pediatric gastrointestinal disorders: position paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. J Pediatr Gastroenterol Nutr 2023;76:232-47. Crossref
7. Reddy VS, Patole SK, Rao S. Role of probiotics in short bowel syndrome in infants and children—a systematic review. Nutrients 2013;5:679-99. Crossref

Mixed laterally spreading tumour and neuroendocrine tumour in the rectum: a case report

Hong Kong Med J 2025;31:Epub 11 Jul 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Mixed laterally spreading tumour and neuroendocrine tumour in the rectum: a case report
Weijie Zhou#, MM, Xueping Ke#, MD, Yuxuan Lin, MM, Guoyin Li, MM, Mingyun Zheng, MM, Guoxin Liufu, MM, Liu Liu, MM
Department of Gastroenterology, The Six Affiliated Hospital of South China University of Technology, Guangdong, China
# Equal contribution
 
Corresponding author: Mr Liu Liu (liuliu8495@163.com)
 
 Full paper in PDF
 
 
Case presentation
A 58-year-old female presented to our hospital with 1-year history of recurrent mucous stools. She had no significant medical or family history of cancer. Laboratory tests for intestinal pathogens, rheumatological markers, and tumour markers were all within normal limits. Abdominal imaging did not reveal any abnormalities. Colonoscopy showed a laterally spreading tumour measuring approximately 25 mm × 40 mm located about 5 cm from the anal verge. The tumour exhibited granular, nodular, and lobulated features with abundant mucus adhering to the surface (Fig 1a). Despite repeated washing, mucus remained attached to the tumour surface. Subsequently, we performed indigo carmine staining, which revealed well-delineated tumour margins (Fig 1b). Endoscopic ultrasound showed the lesion originated from the mucosal layer. A local biopsy revealed a tubulovillous adenoma with high-grade dysplasia. The patient was deemed suitable for endoscopic submucosal dissection (Fig 1c to e).
 

Figure 1. Tumour morphology and process of endoscopic submucosal dissection (ESD). (a) Endoscopic features; (b) indigo carmine staining; (c-e) ESD procedure; (f) follow-up endoscopy approximately 1.5 years after ESD
 
Whole tumour pathology was highly unusual, which showed a combination of tubulovillous adenoma with high-grade dysplasia and a neuroendocrine neoplasm (NEN) component. Interestingly, the neuroendocrine tumour had a maximum diameter of approximately 0.3 cm, representing around 3% of the lesion. Immunohistochemistry staining revealed positive expression of CK, Syn, CD56, CgA, Ki-67 (<1%) and CD34 (Fig 2). This pathological manifestation did not align with the current classification of NENs.
 

Figure 2. Pathology and immunohistochemistry staining of the tumour. (a, b) Haematoxylin-eosin staining (a: ×100; b: ×200); (c) chromogranin A staining (×200)
 
About 1.5 years postoperatively, colonoscopy showed a scar at the site of the previous rectal procedure (Fig 1f). Enhanced chest and abdominal computed tomography scans showed slight thickening of the rectal mucosa without evidence of regional or distant lymph node enlargement.
 
Discussion
Neuroendocrine neoplasms are a rare type of tumour and encompass three major subtypes: neuroendocrine tumours, neuroendocrine carcinomas and mixed neuroendocrine–non-neuroendocrine neoplasms (MiNEN). Among these, MiNENs are a special type with high invasiveness. Our case resembled a MiNEN but exhibited some distinct differences.
 
In this case, the pathology was special. It did not align with the current World Health Organization classification of NENs.1 These neoplasms, known as MiNENs, are characterised by a combination of neuroendocrine and non-neuroendocrine components, both of which comprise at least 30% of the neoplasm.1 Although our case shared similarities with MiNENs in terms of mixed histology, it differed significantly in the proportion of components, with the neuroendocrine tumour component constituting less than 30%. Evidently, this case did not meet the current definition of MiNENs. In fact, the definition of MiNENs remains controversial.
 
These mixed tumours (neuroendocrine–non-neuroendocrine neoplasms) were first described in 1924.2 In 2000, a classification system for endocrine tumours was implemented and defined mixed exocrine–endocrine carcinomas as tumours in which each component constitutes at least 30% of the neoplasm.2 In 2010, the World Health Organization classified mixed neuroendocrine and exocrine tumours as mixed adenoneuroendocrine carcinomas.2 Subsequently, in 2017, mixed adenoneuroendocrine carcinomas were reclassified as MiNENs. The term “exocrine” was replaced with “non-neuroendocrine” to encompass a broader range of possible histological variants, including glandular, squamous, mucinous, and sarcomatoid phenotypes.3 As for the threshold of at least 30% for each component, it is highly unusual for a component with a lower representation to affect the biological behaviour of a cancer.2 Nonetheless, the threshold was arbitrarily set without clinical or scientific evidence.4 Given the emergence of our case, we believe that this threshold requires further optimisation.
 
Regarding the pathology in our patient, we proposed the following explanations. First, there are two widely accepted hypotheses for the origin of MiNENs.5 6 7 8 The first posits that both tumour components originate from a single precursor cell but proliferate and differentiate along distinct pathways. The second hypothesis also suggests a common cellular origin. Nonetheless, it proposes that during tumour progression, a subset of the non-neuroendocrine component accumulates sufficient genetic mutations to transform into neuroendocrine cells. These theories suggest that the composition of MiNENs is dynamic, with potentially varying proportions of components at different stages of tumour development. Second, with growing health awareness and the widespread adoption of endoscopic screening, early-stage tumours are more readily identified. These early-stage neoplasms are typically smaller in size and exhibit a lower degree of malignancy. These factors collectively contribute to the evolving landscape of MiNENs diagnosis and classification, necessitating ongoing refinement of diagnostic criteria and classification systems.
 
In terms of endoscopic manifestation, there was something worth considering. In this case, the surface of the tumour was repeatedly washed, but mucus adhesion persisted, more similar to the manifestation of mucinous adenocarcinoma or serrated adenocarcinoma.9 Notably, the absence of classic carcinoid syndrome symptoms and negative tumour markers further set this case apart. Although villous tubular adenomas can secrete mucus, the tumour in this case exhibited unusually copious and rapid mucus production. We suspected the neuroendocrine tumour may possess paracrine functions that further stimulated secretion from the adenoma. Nonetheless, there have been no experiments supporting this viewpoint. Experimental validation in the future is needed to elucidate the potential interplay between these neoplastic entities and their secretory mechanisms.
 
In terms of treatment, although a definitive classification of this tumour type has not been established, the existing treatment principles for NENs remain applicable. For this patient, the neuroendocrine tumour lesion was less than 10 mm in size, with a Ki-67 index of less than 3%, classifying it as a G1 stage tumour, and there was no evidence of metastasis to other organs or tissues. We performed endoscopic submucosal dissection to remove the tumour. Nonetheless, it was important to consider the depth of resection. Resection above the muscularis mucosae may result in incomplete tumour removal, while excision below this layer risks vascular injury. We recommended resection close to the muscularis mucosa to minimise bleeding and to prevent tumour seeding into blood vessels. Another critical consideration was the extent of resection. It was imperative to ensure negative tumour margins to guarantee complete excision of the neoplasm.
 
Our case indicates that the current classification system for NENs remains inadequate. Specifically, there is no clear classification for tumours that contain a minor component of neuroendocrine cells, highlighting an urgent need for further refinement of MiNENs.
 
Author contributions
Concept or design: W Zhou, X Ke.
Acquisition of data: W Zhou, X Ke.
Analysis or interpretation of data: W Zhou, X Ke.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: L Liu.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. The patient provided informed consent for all procedures agreement for publication of this article.
 
References
1. Washington MK, Goldberg RM, Chang GJ, et al. Diagnosis of digestive system tumours. Int J Cancer 2021;148:1040-50. Crossref
2. Díaz-López S, Jiménez-Castro J, Robles-Barraza CE, Ayala-de Miguel C, Chaves-Conde M. Mixed neuroendocrine non-neuroendocrine neoplasms in gastroenteropancreatic tract. World J Gastrointest Oncol 2024;16:1166-79. Crossref
3. Kanthan R, Tharmaradinam S, Asif T, Ahmed S, Kanthan SC. Mixed epithelial endocrine neoplasms of the colon and rectum—an evolution over time: a systematic review. World J Gastroenterol 2020;26:5181-206. Crossref
4. Toor D, Loree JM, Gao ZH, Wang G, Zhou C. Mixed neuroendocrine–non-neuroendocrine neoplasms of the digestive system: a mini-review. World J Gastroenterol 2022;28:2076-87. Crossref
5. Frizziero M, Chakrabarty B, Nagy B, et al. Mixed neuroendocrine non-neuroendocrine neoplasms: a systematic review of a controversial and underestimated diagnosis. J Clin Med 2020;9:273. Crossref
6. Bazerbachi F, Kermanshahi TR, Monteiro C. Early precursor of mixed endocrine-exocrine tumors of the gastrointestinal tract: histologic and molecular correlations. Ochsner J 2015;15:97-101.
7. Scardoni M, Vittoria E, Volante M, et al. Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract: targeted next-generation sequencing suggests a monoclonal origin of the two components. Neuroendocrinology 2014;100:310-6. Crossref
8. Yuan W, Liu Z, Lei W, et al. Mutation landscape and intra-tumor heterogeneity of two MANECs of the esophagus revealed by multi-region sequencing. Oncotarget 2017;8:69610-21. Crossref
9. Lee CT, Huang YC, Hung LY, et al. Serrated adenocarcinoma morphology in colorectal mucinous adenocarcinoma is associated with improved patient survival. Oncotarget 2017;8:35165-75. Crossref

Rethink personalised sudden cardiac death risk assessment in non-dilated left ventricular cardiomyopathy: a case report

Hong Kong Med J 2025 Jun;31(3):236–9 | Epub 14 Apr 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Rethink personalised sudden cardiac death risk assessment in non-dilated left ventricular cardiomyopathy: a case report
Kevin WC Lun, MB, BS, MRCP1 #; Jonan CY Lee, MB, ChB, FRCR2; Eric CY Wong, MB, BS, FHKCP1; Michael KY Lee, MB, BS, FHKCP1; Derek PH Lee, MB, ChB, FHKCP1 #
1 Division of Cardiology, Department of Medicine, Queen Elizabeth Hospital, Hong Kong SAR, China
2 Department of Diagnostic and Interventional Radiology, Queen Elizabeth Hospital, Hong Kong SAR, China
# Equal contribution
 
Corresponding author: Dr Kevin WC Lun (lkw708@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentation
A 56-year-old man was presented to the emergency department of our institution in June 2023 and has had been followed up in our medical clinic for 1 year prior to his current hospital admission. He had been diagnosed with frequent symptomatic premature ventricular complexes with an ectopic burden of 8.2% on extended ambulatory rhythm monitoring. There were also multiple recorded episodes of non-sustained ventricular tachycardia. Beta-blocker was initiated and uptitrated according to clinical symptoms. His family history was remarkable for the sudden cardiac death of his father at the age of 64 years. Subsequent transthoracic echocardiogram of the patient revealed a global hypokinetic left ventricle with a biplane-measured left ventricular ejection fraction (LVEF) of 45%. There was mild left atrial enlargement with a two-dimensional area of 25.7 cm2 but no other structural abnormalities. Computed tomography coronary angiogram showed mild to moderate coronary artery disease in three vessels and guideline-directed medical treatment was initiated. Cardiac magnetic resonance imaging (CMR) was scheduled to assess cardiac structures and function, as well as tissue characterisation for features of non-ischaemic cardiomyopathy. He had been scheduled to undergo catheter ablation for frequent symptomatic premature ventricular complexes.
 
The patient presented to our emergency department with out-of-hospital cardiac arrest. He had been found collapsed adjacent to a swimming pool and a bystander had initiated cardiopulmonary resuscitation. Spontaneous circulation was restored shortly after a single defibrillation delivered by an automated external defibrillator and he was transferred to our hospital immediately. On arrival at the emergency department, he was hemodynamically stable with a Glasgow Coma Scale score of 15. High-sensitive troponin I level was elevated at 44.9 ng/L. Electrocardiogram showed sinus rhythm of 71 beats/min with occasional premature ventricular complexes. There was no ST-segment elevation or significant conduction abnormalities. Bedside echocardiogram showed a similar biplane-measured LVEF of 43% with global hypokinesia. Urgent coronary angiogram showed non-occlusive moderate to severe coronary artery disease in three vessels. Given his current presentation, together with angiographic progression in coronary artery disease, complete revascularisation was performed uneventfully. He was then transferred to our cardiac care unit postoperatively for close monitoring. Inpatient CMR revealed a non-dilated left ventricle with mildly reduced LVEF of 43% with global hypokinesia. There was multifocal patchy mid-wall and subepicardial late gadolinium enhancement (LGE) at the mid-ventricular anterior, anteroseptal and anterolateral walls, as well as basal to mid-ventricular inferior and inferolateral walls (Fig 1). There was no evidence of myocardial infarct. Parametric mapping showed a mild increase in myocardial T1 with values up to 1067 ms to 1080 ms (native T1 values in healthy subjects obtained in our Aera 1.5T magnetic resonance imaging scanner [Siemens, Munich, Germany] is 996±26 ms for males), suggestive of mild diffuse interstitial fibrosis (Fig 2). Prior to hospital discharge, a transvenous implantable cardioverter defibrillator (ICD) was implanted for secondary prevention. Subsequent genetic testing identified a heterozygous pathogenic truncating variant NM_001458.5(FLNC):c.3279del p.(Gly1094Alafs*4) in the filamin-C gene. The final clinical diagnosis was sudden cardiac arrest secondary to filamin-C variant–associated cardiomyopathy in a patient with non-dilated left ventricular cardiomyopathy (NDLVC) and mid-range ejection fraction.
 

Figure 1. Multifocal patchy mid-wall and subepicardial late gadolinium enhancement at mid-ventricular anterior, anteroseptal and anterolateral walls, as well as basal to mid-ventricular inferior and inferolateral walls (arrows). (a-c) Short axis views of the left ventricle. (d) Apical four-chamber view of the left ventricle. (e, f) Apical two-chamber view of the left ventricle
 

Figure 2. T1 mapping of the left ventricle. Parametric mapping shows mildly increased myocardial T1 values up to 1067 ms to 1080 ms, suggestive of mild diffuse interstitial fibrosis
 
Discussion
The filamin-C gene encodes the filamin-C protein that plays essential roles in the sarcomere stability in cardiac muscles. Filamin-C variants have been increasingly recognised as an important cause of cardiomyopathy. It has been identified in approximately 3% to 4% of patients with dilated cardiomyopathy and commonly presents in early-to-mid adulthood with high arrhythmic risks.1
 
According to the 2021 European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure,2 primary prevention ICD is indicated in patients with symptomatic heart failure with an LVEF of lower than 35% despite optimal medical treatment and a reasonable quality of life. Such recommendation is supported by numerous landmark trials including MADIT (Multicenter Automatic Defibrillator Implantation Trial),3 DEFINITE (DEFibrillators In Non-Ischemic Cardiomyopathy Treatment Evaluation),4 and SCD-HeFT (the Sudden Cardiac Death in Heart Failure Trial).5 In addition, several additional clinical risk factors should also be considered in sudden cardiac death risk assessment, especially in patients with non-ischaemic cardiomyopathy.2 These risk factors include significant LGE on CMR, younger age, and specific genotypes. Nonetheless these recommendations are ambiguous, and the guideline has not defined, for example, the burden of LGE and variant mechanisms in several high-risk genes that would warrant ICD implantation. Moreover, there are limited recommendations for primary prevention ICD in patients with heart failure with mid-range or preserved ejection fraction.
 
In the updated 2023 ESC Guidelines for the management of cardiomyopathies,6 a new entity of NDLVC is introduced. An algorithm for consideration of primary prevention ICD similar to that for patients with dilated cardiomyopathy is recommended in this patient population. Patient genotype and imaging features on CMR have been proposed in the early sudden cardiac death risk assessment for patients with NDLVC. A previous study has demonstrated a higher rate of malignant arrhythmic events in patients who are genotype-positive, compared with their genotype-negative counterparts.7 Such association has been observed irrespective of LVEF. Variants in certain genes including lamin A/C, phospholamban, filamin-C, RNA-binding motif protein 20, desmoplakin and plakophilin-2 are associated with a high risk of malignant ventricular arrhythmias and sudden cardiac death. Apart from genotype information, the presence and distribution of LGE on CMR, such as a ring-like pattern of LGE, has also been shown to be a strong risk marker for ventricular arrhythmias.8 Hence, based on the current ESC Guidelines,6 primary prevention ICD should be considered in patients with NDLVC and high-risk genotype and in the presence of additional risk factors such as syncope and LGE on CMR, irrespective of LVEF.
 
Our case highlights the need to incorporate a patient’s genotype and imaging features on CMR into the personalised risk assessment for sudden cardiac death in patients with NDLVC. This will facilitate a more comprehensive and informative discussion about the indication for primary prevention ICD and improve the clinical outcome for patients with cardiomyopathy.
 
Author contributions
Concept or design: KWC Lun, DPH Lee.
Acquisition of data: All authors.
Analysis or interpretation of data: KWC Lun, DPH Lee.
Drafting of the manuscript: KWC Lun, DPH Lee.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. The patient provided consent for all treatments and procedures, and consent for publication of the case report.
 
References
1. Agarwal R, Paulo JA, Toepfer CN, et al. Filamin C cardiomyopathy variants cause protein and lysosome accumulation. Circ Res 2021;129:751-66. Crossref
2. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726. Crossref
3. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83. Crossref
4. Kadish A, Dyer A, Daubert JP, et al. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med 2004;350:2151-8. Crossref
5. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-37. Crossref
6. Arbelo E, Protonotarios A, Gimeno JR, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J 2023;44:3503-626. Crossref
7. Escobar-Lopez L, Ochoa JP, Mirelis JG, et al. Association of genetic variants with outcomes in patients with nonischemic dilated cardiomyopathy. J Am Coll Cardiol 2021;78:1682-99. Crossref
8. Meier C, Eisenblätter M, Gielen S. Myocardial late gadolinium enhancement (LGE) in cardiac magnetic resonance imaging (CMR)—an important risk marker for cardiac disease. J Cardiovasc Dev Dis 2024;11:40. Crossref

Living donor renal transplantation in a patient with human immunodeficiency virus: a case report

Hong Kong Med J 2025 Jun;31(3):233–5 | Epub 12 Jun 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Living donor renal transplantation in a patient with human immunodeficiency virus: a case report
TL Leung, MB ChB, FHKAM (Medicine)1; Jacky MC Chan, FHKAM (Medicine), FRCP2; Ivy LY Wong, FHKAM (Medicine), FHKCP1; Clara KY Poon, FHKAM (Medicine), FRCP1; William Lee, FHKAM (Medicine), FHKCP1; KF Yim, FHKAM (Medicine), FHKCP1; Owen TY Tsang, FHKAM (Medicine), FRCP2; Samuel KS Fung, FHKAM (Medicine), FRCP1; A Cheuk, FHKAM (Medicine), FRCP1; HL Tang, FHKAM (Medicine), FRCP1
1 Renal Unit, Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong SAR, China
2 Infectious Disease Unit, Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong SAR, China
 
Corresponding author: Dr TL Leung (ltl125@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentation
The patient was diagnosed in 1989, at age 27 years, with human immunodeficiency virus–1 (HIV-1) infection. He later presented with hypertension and left loin discomfort. Workup revealed proteinuria of 0.51 g over 24 hours and impaired renal function, with serum creatinine of 230 μmol/L (normal range, 59-104). An ultrasound scan showed bilateral shrunken kidneys with loss of corticomedullary differentiation. Renal biopsy was not performed in view of the bilateral shrunken kidneys. His renal function progressively deteriorated, and he commenced automated peritoneal dialysis in June 2017 at age 55 years. His elder brother volunteered to donate a kidney. The patient’s HIV infection was well controlled with lamivudine, abacavir, lopinavir, and ritonavir. Lopinavir/ritonavir was switched to raltegravir in view of a potential drug-drug interaction between ritonavir and calcineurin inhibitors. Pre-transplantation CD4+ count was 717 cells/μL and HIV viral load was undetectable. Human leukocyte antigen matching revealed one mismatch between donor and recipient. Both donor and recipient tested cytomegalovirus antibody positive. The recipient was started on cyclosporine, mycophenolate mofetil, and prednisolone for immunosuppression according to our centre’s protocol.
 
Living donor renal transplantation was successfully performed in September 2018 when the patient was 56 years old. Postoperative ultrasound of the graft kidney and radioisotope scan showed good graft perfusion and function. Valganciclovir and pentamidine inhalation were given as prophylaxis against cytomegalovirus and Pneumocystis jirovecii, respectively, in view of his underlying glucose-6-phosphatase deficiency. The lowest creatinine level since hospital discharge was 112 μmol/L. At 6 months post-transplantation, he was found to have a low level of donor-specific anti-DQ7 antibody (DSA), which persisted at repeat testing 9 months post-transplantation. Cyclosporine was therefore switched to tacrolimus to optimise immunosuppression. The tacrolimus trough level has been maintained at 5 to 8 μg/L since commencement (Fig a). Despite the presence of DSA, the patient has enjoyed stable renal function with no proteinuria; thus, renal biopsy was not performed (Fig b). In his latest follow-up, at 51 months post-transplantation, his renal function remained stable with a creatinine level of 141 μmol/L. He also has excellent HIV control with abacavir, dolutegravir, and lamivudine. CD4+ cell count has been maintained in the range of 600 to 800 cells/μL since transplantation (Fig c). He did not experience any infections after transplantation.
 

Figure. (a) Tacrolimus trough levels over time. (b) Creatinine levels over time, starting 1 month after renal transplantation. (c) CD4+ cell counts before and after renal transplantation
 
Discussion
To the best of our knowledge, this is the first reported case of living donor renal transplantation in a patient with HIV in Hong Kong. The global prevalence of HIV is increasing, and its association with chronic kidney disease is notable. In a local cohort, 16.8% of Chinese HIV-infected patients developed chronic kidney disease.1 With the advancement of highly active antiretroviral therapy (HAART), life expectancy among people living with HIV (PLHIV) approaches that of the general population, leading to more cases of end-stage renal failure requiring management. The combination of intense immunosuppression and intrinsic immunodeficiency can expose HIV-infected transplant recipients to life-threatening opportunistic infections. It is crucial to achieve excellent HIV control before proceeding with transplantation. The American Society of Transplantation recommends that PLHIV achieve a CD4+ cell count of more than 200 cells/μL during the 3 months prior to transplantation and an undetectable HIV viral load while receiving HAART.2 Our patient met these criteria prior to transplantation.
 
Kidney transplantation in PLHIV has been explored in many Western countries over the past decades. In a systematic review, the 1- and 3-year patient survival rates after transplantation were reported at 97% and 94%, respectively, with graft survival at 91% and 81%.3 In another cohort study that compared 510 HIV-infected kidney transplant recipients with HIV-negative controls, comparable 5- and 10-year survival rates were reported; 5-year patient and graft survival were 88.7% and 75%, respectively. Co-infection of HIV and hepatitis C virus was an important prognostic marker for poor graft and patient survival.4 These excellent survival data encouraged us to perform the first kidney transplant in an HIV-infected patient. Despite these promising results, the rejection rate in HIV-infected recipients is significantly higher, up to 2- to 3-fold, potentially due to drug-drug interactions between HAART and immunosuppressants or immune dysregulation.5 6 The pathophysiology behind this increased rejection rate is unclear, but strategies such as induction therapy with anti-interleukin-2 receptor antibody or antithymocyte globulin and optimised immunosuppressive therapy are utilised to mitigate risks. Nonetheless, the use of antithymocyte globulin is controversial due to its association with marked CD4+ cell suppression (ie, <200 cells/μL), prolonged recovery, and subsequent infection risk.7 Therefore, antithymocyte globulin induction should be reserved for HIV-infected recipients with very high immunological risk.
 
The optimal immunosuppression regimen for HIV-infected recipients is yet to be determined. Tacrolimus is favoured over cyclosporine for reducing acute rejection risks.8 Observational studies and the landmark ELITE-Symphony trial suggest lower rejection rates with tacrolimus, up to 2-fold.6 8 Our centre initially chose cyclosporine due to the patient’s low immunological risk profile with only one human leukocyte antigen mismatch but switched to tacrolimus after the development of DSA 6 months post-transplantation. This case highlights the challenges of balancing overimmunosuppression and rejection risks in HIV-infected recipients. Ongoing evidence supports the use of tacrolimus as the first-line immunosuppressive agent, irrespective of immunological risk, with future randomised controlled trials needed to establish the best regimen.
 
Managing drug-drug interactions in HIV-infected transplant recipients is complex. Non-nucleoside reverse transcriptase inhibitors induce cytochrome P450 enzymes, while protease inhibitors significantly inhibit these enzymes, notably raising calcineurin inhibitor levels in the plasma. Ritonavir, a strong CYP3A4 inhibitor commonly used in HAART, requires a substantial increase in tacrolimus dosage up to 70-fold upon its discontinuation to maintain effective immunosuppression.9 To avoid drug-drug interactions, our patient was switched to an integrase strand transfer inhibitor-based HAART regimen prior to transplantation. Nonetheless, there was a risk of serum creatinine elevation. Dolutegravir has been shown to inhibit organic cation transporter 2, which inhibits active creatinine secretion into renal tubules, leading to a slight elevation in serum creatinine level without affecting the glomerular filtration rate. After administering dolutegravir, serum creatinine clearance in healthy subjects has been reported to decrease by 10% to 14%.10
 
In conclusion, renal transplantation in PLHIV can offer improved quality of life and survival compared with continued dialysis, provided there is excellent HIV control and careful management of immunosuppression and drug-drug interactions. Challenges remain in preventing and treating acute rejection to improve long-term graft survival. We observed an early appearance of DSA 6 months post-transplantation in our patient. Although the DSA was transiently suppressed after switching to tacrolimus, it reappeared later. The appearance of DSA and its potential long-term impact on graft survival require further investigation. Our experience, alongside data from Western cohorts, supports expanding renal transplantation among HIV-infected patients, with a focus on tailored immunosuppressive strategies and management of complications.
 
Author contributions
All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Declaration
This case has been presented during oral presentation at the 18th Congress of The Asian Society of Transplantation (CAST) in Hong Kong SAR, China, 25-28 July 2023.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki and provided informed consent for all procedures.
 
References
1. Cheung CY, Wong KM, Lee MP et al. Prevalence of chronic kidney disease in Chinese HIV-infected patients. Nephrol Dial Transplant 2007;22:3186-90. Crossref
2. Blumberg EA, Rogers CC; American Society of Transplantation Infectious Diseases Community of Practice. Solid organ transplantation in the HIV-infected patients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019;33:e13499. Crossref
3. Zheng X, Gong L, Xue W, et al. Kidney transplant outcomes in HIV-positive patients: a systematic review and meta-analysis. AIDS Res Ther 2019;16:37. Crossref
4. Locke JE, Mehta S, Reed RD, et al. A national study of outcomes among HIV-infected kidney transplant recipients. J Am Soc Nephrol 2015;26:2222-9. Crossref
5. Stock PG, Barin B, Murphy B, et al. Outcomes of kidney transplantation in HIV-infected recipients. N Engl J Med 2010;363:2004-14. Crossref
6. Gathogo E, Harber M, Bhagani S, et al. Impact of tacrolimus compared with cyclosporin on the incidence of acute allograft rejection in human immunodeficiency virus–positive kidney transplant recipients. Transplantation 2016;100:871-8. Crossref
7. Carter JT, Melcher ML, Carlson LL, Roland ME, Stock PG. Thymoglobulin-associated CD4+ T-cell depletion and infection risk in HIV-infected renal transplant recipients. Am J Transplant 2006;6:753-60. Crossref
8. Ekberg H, Tedesco-Silva H, Demirbas A, et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007;357:2562-75. Crossref
9. Jimenez HR, Natali KM, Zahran AA. Drug interaction after ritonavir discontinuation: considerations for antiretroviral therapy changes in renal transplant recipients. Int J STD AIDS 2019;30:710-4. Crossref
10. Koteff J, Borland J, Chen S, et al. A phase 1 study to evaluate the effect of dolutegravir on renal function via measurement of iohexol and para-aminohippurate clearance in healthy subjects. Br J Cli Pharmacol 2013;75:990-6. Crossref

Adrenal insufficiency due to etomidate inhalation via electronic cigarettes: three local cases

Hong Kong Med J 2025 Jun;31(3):229–32 | Epub 4 Jun 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Adrenal insufficiency due to etomidate inhalation via electronic cigarettes: three local cases
YK Chung, Cert HKCPaed (PE), FHKAM (Paediatrics)1; YT Cheung, MB, ChB2,3; Cindy SY Chan4, MB, BS, MRCPCH4; CC Wong, MB, BS5; Antony CC Fu, MB, ChB, FHKAM (Paediatrics)4; YY Lam, FRCPCH, FHKAM (Paediatrics)5; CY Lee, FRCP (Edin), FHKAM (Paediatrics)1
1 Department of Paediatrics and Adolescent Medicine, Caritas Medical Centre, Hong Kong SAR, China
2 Hospital Authority Toxicology Reference Laboratory, Hong Kong SAR, China
3 Hong Kong Poison Control Centre, Hospital Authority, Hong Kong SAR, China
4 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong SAR, China
5 Department of Paediatrics, Kwong Wah Hospital, Hong Kong SAR, China
 
Corresponding author: Dr YK Chung (cyk474@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentations
Etomidate is a non-barbiturate intravenous anaesthetic agent commonly used in emergency and critical care settings, due to its rapid onset, short duration of action, and minimal cardiorespiratory suppression. Adrenal suppression is a known side-effect. From April to May 2024, three adolescents presented to the paediatric departments of local hospitals with adrenal insufficiency due to etomidate inhalation via electronic cigarette (e-cigarette) vaping, a novel form of drug misuse emerging in Hong Kong.
 
In Case 1, a 17-year-old male with attention deficit hyperactivity disorder was admitted with ketamine cystitis. He had mild hypokalaemia, hypertension (137/84 mm Hg), and a positive urine toxicology screen by liquid chromatography–tandem mass spectrometry for cocaine, ketamine, and etomidate (Table). He reported daily vaping of ‘space oil’ via e-cigarettes for 4 months. Adrenal insufficiency was diagnosed based on elevated adrenocorticotropic hormone (ACTH) and a suboptimal response in a low-dose short Synacthen test. In Case 2, a 16-year-old male with autistic spectrum disorder presented with confusion, insomnia, and unsteady gait after vaping ‘space oil’ weekly for 1 month. Blood pressure and electrolytes were normal. Urine toxicology revealed etomidate and its analogue propoxate. Adrenal insufficiency was confirmed. In Case 3, a 15-year-old male with substance abuse–induced psychosis presented with emotional instability under drug effects. He reported vaping ‘space oil’ via e-cigarettes weekly for several months. Blood pressure and electrolytes were normal. Partial adrenal insufficiency was diagnosed with borderline results in the low-dose short Synacthen test. Two patients (Cases 1 and 2) required regular hydrocortisone replacement. In Case 1, repeated testing 5 months after cessation of etomidate revealed persistent adrenal insufficiency, likely due to second-hand smoke exposure from peers who used etomidate. For Cases 2 and 3, follow-up tests were planned after etomidate cessation. All patients received psychiatric follow-up.
 

Table. Initial and follow-up investigations and treatment of the three cases
 
Discussion
This is the first local paediatric report of adrenal insufficiency associated with etomidate misuse via e-cigarettes. Since its clinical introduction 40 years ago, recreational use via the intravenous route has been rare.1 Nonetheless, its misuse as ‘space oil’ via e-cigarette vaping has surged in Hong Kong and Mainland China since 2023. e-Cigarette use is relatively common among adolescents, with a local survey reporting that 5.3% of secondary school students have had experience with e-cigarettes.2 From May to December 2024, the Hong Kong Poison Control Centre recorded 45 cases of ‘space oil’ misuse presenting to Hospital Authority emergency departments, with a median patient age of 17 years.3 Our cases also illustrate that psychiatric co-morbidities and polysubstance misuse are not uncommon among adolescent etomidate users.
 
Knowledge about the pharmacology of inhaled etomidate is limited since historical studies have focused on its properties in the context of a single intravenous bolus or short-duration infusion,4 while inhalation may involve higher doses and prolonged use. Known toxicities include decreased consciousness, nausea, vomiting, myoclonus, and adrenal insufficiency. Respiratory suppression or bradycardia may develop in overdose. Long-term neurological and psychological effects, particularly dependence and withdrawal, remain poorly characterised.
 
Etomidate and its analogues, propoxate/isopropoxate, inhibit 11-beta-hydroxylase, causing adrenal insufficiency with consequent decreased cortisol and aldosterone production, and elevated precursors such as 11-deoxycorticosterone, 11-deoxycortisol, and 17-hydroxyprogesterone (Fig). Accumulation of deoxycorticosterone, the precursor to aldosterone, leads to mineralocorticoid excess. Marked elevation of androstenedione in Case 1 and urinary androgen metabolites in Case 3 suggested androgen excess, consistent with a recently reported local female adult case of hyperandrogenism from etomidate misuse.5
 

Figure. Pathway of steroidogenesis in 11-beta-hydroxylase suppression associated with etomidate use. Etomidate inhibits 11-beta-hydroxylase, blocking the conversion of 11-deoxycorticosterone (DOC) to corticosterone and 11-deoxycortisol to cortisol, and leading to elevation in adrenal precursor hormones, including DOC, 11-deoxycortisol and 17-hydroxyprogesterone
 
Adrenal suppression from etomidate is dose-dependent and reversible, lasting 6 to 8 hours after a single dose and up to 24 to 48 hours with continuous infusion.4 6 Effects after chronic inhalation are less clear due to the variable drug content of e-cigarettes and inconsistent inhalation routes. Adrenal hyperplasia has been observed on computed tomography examinations among chronic users,5 7 suggesting possible prolonged ACTH stimulation due to ongoing adrenal suppression beyond typical durations in clinical settings.
 
Etomidate-induced 11-beta-hydroxylase inhibition can resemble congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. In addition to adrenal insufficiency, features of mineralocorticoid excess include hypertension, hypokalaemia, and suppression of endogenous renin and aldosterone, as seen in Case 2. Although mild hypokalaemia was observed in Case 1, severe hypokalaemia has been reported.7 Cases 1 and 3 demonstrated significantly elevated 11-deoxycortisol, while 17-hydroxyprogesterone was normal to mildly elevated, suggesting the former is a more sensitive marker of enzyme inhibition, as it is immediately upstream of the inhibited enzyme (Fig). Urinary steroid profiling can identify abnormal precursor-to-product ratios. A short Synacthen test should be performed to confirm adrenal insufficiency. Cases 2 and 3 demonstrated that ACTH may be normal and cortisol response may be relatively preserved despite circumstantial evidence of 11-beta-hydroxylase inhibition, possibly reflecting less drug exposure or compensation between periods of drug use.
 
Given the uncertainty of the duration of adrenal suppression, hydrocortisone replacement and/or stress dose precautions should be given for confirmed adrenal insufficiency. Etomidate users should receive counselling on hydrocortisone’s role, as it does not mitigate the full spectrum of etomidate toxicities. After cessation of etomidate, follow-up testing is recommended to document adrenal recovery. Persistently abnormal results should prompt suspicion of ongoing drug use, with non-classic congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency being a rare differential diagnosis. Our cases highlight the challenges of achieving complete cessation of drug misuse due to peer influence and potential dependence. A multidisciplinary approach should be adopted to address the complex medical and psychosocial issues in adolescent etomidate users.
 
Etomidate and its three analogues—metomidate, propoxate, and isopropoxate—have been listed as dangerous drugs in Hong Kong since February 2025.8 It is expected that more stringent regulations, along with continued law enforcement on illegal drug production and distribution, may help deter etomidate misuse. Public education should also be strengthened to emphasise that substances in e-cigarettes are not harmless, even if they are not traditionally classified as drugs.
 
Etomidate misuse via e-cigarettes is an emerging public health issue. Clinicians should be alert to the risk of adrenal insufficiency among e-cigarette users, particularly those who present with unexplained hypertension or hypokalaemia. Additional testing, such as toxicology screening, 11-deoxycortisol measurement, and urinary steroid profiling may provide supportive evidence. Further research is warranted to understand the pharmacological properties and long-term effects of etomidate misuse.
 
Author contributions
Concept or design: All authors.
Acquisition of data: YK Chung, YT Cheung, CSY Chan, CC Wong.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: YK Chung.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patients were managed in accordance with the Declaration of Helsinki and provided informed consent for all treatments, procedures, and publication.
 
References
1. Uhm J, Hong S, Han E. The need to monitor emerging issues in etomidate usage: the misuse or abuse potential. Forensic Sci Med Pathol 2024;20:249-60. Crossref
2. Health Bureau, Hong Kong SAR Government. School-based survey on smoking among students in 2022/23. 2023. Available from: https://www.censtatd.gov.hk/wbr/B1130201/B11302012024XX01/att/en/78/School-based%20Survey%20on%20Smoking%20among%20Students%20in%202022-23%20-%20Key%20findings_7.pdf. Accessed 15 Aug 2024.
3. Wong IN, Chan CK, Tse ML. Spread of ‘space oil drug’ (etomidate) abuse in Hong Kong and consequent emergency department presentations. Hong Kong Med J 2025;31:173-4. Crossref
4. Forman SA. Clinical and molecular pharmacology of etomidate. Anesthesiology 2011;114:695-707. Crossref
5. Lau CY, Cheung YT, Han TM, Chung CM, Chong YK, Chen PL. Acquired 11β-hydroxylase deficiency by inhaled etomidate and its analogues: a mimic of congenital adrenal hyperplasia. JCEM Case Rep 2024;2:luae207. Crossref
6. Vinclair M, Broux C, Faure P, et al. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Med 2008;34:714-9. Crossref
7. Wu W, Xia C, Gan L, Liao S, Yan Y. Etomidate-induced hypokalemia in electronic cigarette users: two case reports and literature review. Front Endocrinol (Lausanne) 2024;15:1321610. Crossref
8. Hong Kong SAR Government. Dangerous Drugs Ordinance (Amendment of First Schedule) Order 2025. Available from: https://www.elegislation.gov.hk/hk/2025/ln13!en. Accessed 15 Feb 2025.

Multimodal imaging of a left anterior descending artery fistula with a dissecting interventricular septal aneurysm: a case report

© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Multimodal imaging of a left anterior descending artery fistula with a dissecting interventricular septal aneurysm: a case report
Danling Xie, MD; Guoliang Yang, PhD; Chun Li, MD; Hui Li, MS; Xianglin Hao, PhD; Yun Zhang, MD; Mingxun Xie, MD; Yali Xu, PhD
Department of Ultrasound, The Second Affiliated Hospital of Army Medical University (Third Military Medical University), Chongqing, China
 
Corresponding author: Dr Yali Xu (xuyali1976@163.com)
 
 Full paper in PDF
 
Case presentation
A 37-year-old male attended for evaluation of an interventricular septal (IVS) mass incidentally discovered during a routine physical examination. On admission he was hypertensive at 153/85 mm Hg) with heart rate 93 bpm. Electrocardiogram findings revealed occasional premature ventricular contractions with horizontal ST-segment depression and T-wave inversion, suggestive of myocardial ischaemia. Laboratory results were normal. Transthoracic echocardiography (TTE) identified a well-defined, ovoid mass within the inferior segment of the IVS, appearing as a complex solid-cystic mass lesion. The mass measured approximately 35 × 31 × 40 mm3 (anteroposterior × transverse × longitudinal) [Fig 1a]. The left ventricular apical cavity was compressed by the mass. Colour Doppler imaging showed blood flow within the lesion, with diastole filling and systole outflow (Fig 1b). Notably, the cystic cavity exhibited minimal changes during the cardiac cycle. Continuous-wave Doppler at the lesion (Fig 1c) revealed bidirectional blood flow across systole and diastole. Tracking revealed a 4.3-mm dilated coronary artery branch at the heart’s apex as the flow’s source, with no proximal stenosis or dilation in the coronary arteries. Contrast TTE (cTTE) detected a small (1-2 mm) left anterior descending (LAD) artery fistula within the IVS, with delayed cystic enhancement relative to the left ventricle but simultaneous with the IVS myocardium post-contrast, and no infiltration of the solid component (Fig 1d-e, SV1). These findings indicated the presence of a coronary artery fistula originating from the LAD artery that drains into an IVS forming a dissecting aneurysm.
 
Coronary computed tomography angiography showed no proximal left coronary artery dilation but mild distal dilation. The aneurysm showed significant enhancement and slight calcification, with no enhancement observed in the surrounding myocardium (Fig 1f). Cardiac magnetic resonance confirmed the findings, showing the mass with slightly high T1-weighted and predominantly high T2-weighted signal intensities, encircled by a low-signal intensity ring, with no significant myocardial enhancement post-contrast (Fig 1).
 

Figure 1. Preoperative imaging examination. (a) Transthoracic echocardiography (TTE) shows a cystic-solid echo area in the interventricular septum (IVS) at the apical four-chamber view (asterisk). (b) Colour Doppler demonstrates blood flow entering the cystic cavity (asterisk) through the fistula (yellow arrow). (c) Spectral Doppler shows bidirectional, high-velocity blood flow at the fistula site during systole and diastole. (d) Contrast TTE shows that the cystic cavity enhances later than the left ventricle, with no infiltration of the solid component. (e) Coronary computed tomography angiography confirms distal left anterior descending dilation into the IVS. (f) Cardiac magnetic resonance suggests a high signal in the cyst cavity, with surrounding myocardium showing low-signal intensity (blue arrow)
 
The patient underwent surgical correction of the coronary artery fistula and reduction of the dissecting aneurysm of the interventricular septum (DAIS). Intraoperatively, the LAD was observed penetrating the myocardium, forming a sac-like cavity due to the convergence of the coronary fistula into the myocardial layer of the IVS. Histopathology from a myocardial biopsy showed fibrosis (Fig 2a-d). At 3-month postoperative follow-up, TTE showed a reduced IVS cystic cavity (Fig 2e), and cTTE confirmed fistula closure with no contrast entering the cavity (Fig 2f).
 

Figure 2. Surgical and postoperative assessment. (a) Intraoperative image shows resection of the solid component within the dissected aneurysm (green arrow). (b, c) Histology reveals myocardial degeneration (yellow arrows, 40×) and interstitial fibrosis (20×, dashed line box). (d) Masson’s trichrome staining confirms interstitial fibrosis (20×, dashed line box). (e) Postoperative transthoracic echocardiography (TTE) demonstrates almost no visible interventricular septal cystic cavity, with no discernible colour Doppler flow signal (asterisk). (f) Contrast TTE confirms the absence of contrast in the fibrotic myocardium (white arrow)
 
Discussion
Cardiac space-occupying lesions include tumours and non-neoplastic conditions, occurring anywhere in the heart.1 Dissecting aneurysm of the interventricular septum often results from a ruptured Valsalva aneurysm, myocardial infarction, or trauma.2 Aneurysms within the IVS caused by congenital coronary artery fistulas are rare, with only a few reported cases.3 4 5 These cases often present with marked dilation of the involved coronary artery trunk and dynamic fluctuations in the cystic cavity dimensions throughout the cardiac cycle. The cavity typically expands during diastole and contracts during systole.
 
In this case, the absence of dilation in the main trunk of the coronary artery could be attributed to the fistula’s origin from a small branch of the LAD artery, with a narrow internal diameter and minimal shunting volume. As the patient was young, the coronary arteries exhibited greater elasticity, leading to a reduced propensity for dilation in the main trunk.
 
In this case, the cystic cavity in the IVS showed minimal size change throughout the cardiac cycle due to a blind-ending coronary artery fistula that prevented left ventricular communication. Chronic shunting from the coronary artery fistula led to the gradual enlargement of a dissecting aneurysm within the interventricular septum, compressing adjacent myocardium and branches of the coronary arteries. This compression resulted in localised myocardial ischaemia and subsequent myocardial fibrosis, as demonstrated by both the patient’s electrocardiogram and pathological findings. The fibrosis and high-velocity flow at the fistula site contributed to myocardial thickening and reduced elasticity, impairing the cavity’s expansion and contraction, and resulting in minimal size variation.
 
Transthoracic echocardiography is often the initial imaging choice for coronary artery fistulas into the IVS, providing critical haemodynamic and anatomical data, but its limitations may result in misdiagnosis. Coronary computed tomography angiography and cardiac magnetic resonance provide detailed assessments of coronary anatomy and myocardial fibrosis, complementing TTE. Coronary computed tomography angiography provides diagnostic clarity with the caveat of radiation exposure, especially for repeated scans. Cardiac magnetic resonance, while valuable for its soft tissue characterisation, presents cost considerations for patients. Contrast TTE, valued for its safety, cost-effectiveness, and timeliness, excels in visualising myocardial perfusion and detecting congenital cardiac defects, enhancing diagnostic precision when TTE results are indeterminate. In our case, cTTE, with its high sensitivity to blood flow signals, rapidly delineated the shunt and accurately mapped the fistula. The contrast agent, perfusing the myocardium via the coronary arteries, resulted in delayed opacification of the interventricular septum compared with the left ventricle, thereby disclosing DAIS. This comprehensive diagnostic profiling was pivotal for tailored treatment strategies and prognostic enhancement. This marks the first instance, to our knowledge, where cTTE has been utilised to diagnose DAIS.
 
Author contributions
Concept or design: D Xie, G Yang, C Li.
Acquisition of data: D Xie, C Li, H Li, X Hao, Y Zhang.
Analysis or interpretation of data: D Xie, H Li, X Hao, Y Zhang, M Xie, Y Xu.
Drafting of the manuscript: D Xie, G Yang, Y Xu.
Critical revision of the manuscript for important intellectual content: D Xie, G Yang, C Li, Y Xu.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
The authors declared no conflicts of interest.
 
Acknowledgement
The authors thank Prof Yunhua Gao who provided guidance and assistance in the diagnosis.
 
Funding/support
This study was supported by the Individualized Training Program for Key Supported Talents, part of the Excellent Talents Database at the Army Medical University (Grant No.: 2019R038).
 
Ethics approval
The patient was treated in accordance with the Declaration of Helsinki. The patient provided written consent for publication of this case report.
 
References
1. Maleszewski JJ, Anavekar NS, Moynihan TJ, Klarich KW. Pathology, imaging, and treatment of cardiac tumours. Nat Rev Cardiol 2017;14:536-49. Crossref
2. Zhang JP, Meng H, Wang H. Dissecting aneurysm of the interatrial and interventricular septum with concomitant ventricular septal defect-multimodality cardiac imaging and surgical repair. Echocardiography 2016;33:932-5. Crossref
3. Zhi Ku L, Xia J, Lv H, Song LC, Ma XJ. Giant interventricular septal dissecting aneurysm resulting from congenital coronary fistula. Circ Cardiovasc Imaging 2022;15:e013861. Crossref
4. Wu Q, Jin Y, Zhou L, Liu Y, Wu D. A dissecting aneurysm of interventricular septum resulting from congenital coronary artery fistula. J Clin Ultrasound 2019;47:55-8. Crossref
5. Tekinhatun M, Cihan F, Demir M. Interventricular septal dissecting aneurysm resulting from congenital coronary fistula: a case report. Echocardiography 2023;40:1140-3. Crossref

Frontal lobe epilepsy and hibernoma: a case report

Hong Kong Med J 2025 Apr;31(2):159–61 | Epub 3 Apr 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Frontal lobe epilepsy and hibernoma: a case report
Rongjun Zhang, M Med#; Zhigang Gong, PhD#; Wenbing Jiang, M Med
Department of Neurosurgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, China
# Equal contribution
 
Corresponding author: Dr Rongjun Zhang (zhangrongjun2000@163.com)
 
 Full paper in PDF
 
 
Case presentation
A 69-year-old female presented to the clinic with a 2-year history of intermittent headaches. Cranial computed tomography (CT) and magnetic resonance imaging (MRI) examination (Fig 1a and b) revealed a space-occupying lesion in the right frontal lobe, suggestive of a meningioma. Preoperatively, the patient experienced a single episode of epilepsy lasting for 2 minutes, relieved by antiepileptic medication.
 

Figure 1. (a, b) Preoperative magnetic resonance imaging (MRI) scan in the transverse position. The space-occupying lesion appears slightly hypointense on T1-weighted imaging, with significant and uniform enhancement on the contrast-enhanced scan. It seems to have a broad base connected to the dura mater. The adjacent brain parenchyma shows mild compression and displacement. (c, d) Postoperative MRI scan: transverse T1-weighted and contrast-enhanced images at 3 years postoperatively. The T1-weighted scan shows mixed, slightly hypointense signals in the surgical area. The contrast-enhanced scan reveals patchy enhancements around the surgical site, likely indicating gliosis. (e, f) Specimen images show the tumour is greyish-yellow in colour with a complete capsule. Numerous tiny blood vessels are distributed across the surface of the capsule. When cut open, lipid droplet-like fluid flows out, and scattered tiny vascular sections are visible within the sectioned tissue
 
Cranial surgery was performed based on the preoperative CT localisation. The tumour was completely separated and excised, measuring 4 × 3 × 2 cm3, greyish-yellow in colour, and encapsulated (Fig 1e). The encapsulated surface was rich in blood vessels. Upon opening, the tumour was yellow, and lipid droplet-like fluid was observed on the surface (Fig 1f).
 
Postoperative pathology indicated a hibernoma. Haematoxylin and eosin staining revealed a complete thin capsule attached to the outside of the tumour that was lobulated. A network of capillaries could be seen inside. Under the microscope, polygonal/round cells with eosinophilic granular cytoplasm were seen. The cell nuclei were round and centrally located. In addition, many small vacuolated brown adipocytes and unilocular adipocytes were seen, with a considerable amount of blood vessels, spindle cells, and collagen fibres infiltrating around the tumour cells (Fig 2).
 

Figure 2. (a) Microscopy following haematoxylin and eosin staining (100 μm) reveals polygonal/round cells with eosinophilic granular cytoplasm, and round nuclei centrally located in the cells under the microscope. Additionally, numerous small vacuolated brown adipocytes and unilocular adipocytes can be seen, along with a considerable amount of blood vessels, spindle cells, and collagen fibres infiltrating around the tumour cells. (b) Immunohistochemistry (50 μm) shows scattered positivity for Ki-67. (c) Immunohistochemistry (50 μm) shows CD34 positivity in the vessels
 
Immunohistochemistry showed CD34 to be positive in the vessels, and Ki-67 scattered positive with a proportion of <1%. Immunohistochemistry results were as follows: CK (-), S-100 (-), MDM2 (-), CDK4 (-), P53 (-), CD34 (vascular +), CD117 (-), and Ki -67 (+, <1%) [Fig 2].
 
Postoperative re-examination confirmed complete removal of the tumour, and the patient had no further epileptic seizures. Three years later, cranial MRI follow-up revealed no tumour recurrence (Fig 1c and d).
 
Discussion
Hibernomas are rare benign tumours composed of brown adipose tissue.1 They are asymptomatic and slow-growing. Compared with lipomas originating from white adipose tissue, hibernomas are exceedingly rare, with <200 cases reported in the literature.2 These tumours most commonly occur in the proximal axial skeleton, where fetal brown adipose tissue exists and continues into adulthood. They are most frequently found in the interscapular region, upper mediastinum, axilla, retroperitoneum, and neck. According to literature reports, hibernomas are extremely rare in the cranial cavity. In 1972, Vagn-Hansen et al3 reported a case of intracranial hibernoma. Due to medical constraints at the time, detailed case descriptions of CT and MRI images were not available. Therefore, the diagnosis of this patient has significant clinical significance and academic value. The rarity of intracranial hibernomas in clinical diagnosis can easily be overlooked or misdiagnosed as other more common intracranial tumours such as meningiomas. Clinicians and pathologists need to remain highly vigilant for this rare tumour to ensure timely and accurate diagnosis and treatment.
 
Imaging characteristics of hibernomas
In radiology, differentiation between hibernomas and meningiomas is challenging. Hibernomas typically present as low- to medium-intensity on T1-weighted MRI and high intensity on T2-weighted MRI. Due to their origin from adipose tissue, hibernomas may show signal suppression in the fat-suppressed sequence of MRI. Due to the rich vascular supply inside the tumour, MRI post-contrast enhancement is evident. Also, due to the high fat content of hibernomas, they may appear as low density or iso-density lesions on CT scans.
 
Meningiomas typically present as iso- to high-intensity on both T1- and T2-weighted MRI and show significant uniform enhancement following contrast administration. Meningiomas often accompany the dural tail sign, an important distinguishing feature in imaging. Furthermore, the density of meningiomas on CT scans is quite uniform, with significant enhancement following contrast administration. Therefore, while there is overlap in imaging between hibernomas and meningiomas, detailed radiological analysis, especially the combination of fat-suppressed sequences and tumour enhancement characteristics, can help distinguish the two and increase diagnostic accuracy.
 
Pathological characteristics of hibernomas
Pathological diagnosis is the gold standard for confirming hibernomas. Histological features include small multilocular brown adipocytes that have a rich granular cytoplasm and central or eccentric round or oval nuclei. Unlike the single large lipid droplet in white adipocytes, brown adipocytes contain multiple small lipid droplets and abundant mitochondria, giving the cytoplasm a granular appearance. In addition, hibernomas usually have a rich vascular network. Immunohistochemical staining showing vascular CD34 positivity can further confirm the diagnosis. Hibernoma cells have varying degrees of S-100 protein and CD34 expression according to the literature.4 5 Combining these pathological features can effectively distinguish hibernomas from other intracranial tumours such as meningiomas.
 
Conclusion
The diagnostic process of this case of intracranial hibernoma emphasises the importance of clinicians and pathologists when facing uncommon intracranial tumours. Detailed imaging analysis and pathological examination facilitate accurate differential diagnosis, providing the best treatment plan for patients. More case reports and research are needed to further enrich the understanding and treatment strategies of intracranial hibernomas.
 
Author contributions
All authors contributed to the concept or design, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
The authors declared no conflicts of interest.
 
Acknowledgement
The authors thank Dr Yanqing Li and Dr Qinyi Wang from the Department of Pathology at Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine for their expertise and assistance in the diagnosis and analysis of the patient’s condition.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The study was approved by the Ethics Committee of Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, China (Ref No.: 2024-005). The patient was treated in accordance with the Declaration of Helsinki. The patient provided written consent for publication of this case report.
 
References
1. Klevos G, Jose J, Pretell-Mazzini J, Conway S. Hibernoma. Am J Orthop (Belle Mead NJ) 2015;44:284-7.
2. Furlong MA, Fanburg-Smith JC, Miettinen M. The morphologic spectrum of hibernoma: a clinicopathologic study of 170 cases. Am J Surg Pathol 2001;25:809-14. Crossref
3. Vagn-Hansen PL, Osgård O. Intracranial hibernoma. Report of a case. Acta Pathol Microbiol Scand A 1972;80:145-9. Crossref
4. Vassos N, Lell M, Hohenberger W, Croner RS, Agaimy A. Deep-seated huge hibernoma of soft tissue: a rare differential diagnosis of atypical lipomatous tumor/well differentiated liposarcoma. Int J Clin Exp Pathol 2013;6:2178-84.
5. Suster S, Fisher C. Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors. Am J Surg Pathol 1997;21:195-200. Crossref

Pneumothorax associated with a displaced thoracoamniotic Somatex shunt in an infant with congenital pulmonary airway malformation: a case report

Hong Kong Med J 2025 Feb;31(1):68–71 | Epub 10 Feb 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Pneumothorax associated with a displaced thoracoamniotic Somatex shunt in an infant with congenital pulmonary airway malformation: a case report
Viola YT Chan, FHKAM (Obstetrics and Gynaecology)1; WT Tse, FHKAM (Obstetrics and Gynaecology)2; MC Chan, FHKAM (Paediatrics)3; Kenneth KY Wong, PhD, FHKAM (Surgery)4; WC Leung, FHKAM (Obstetrics and Gynaecology)1; TY Leung, FHKAM (Obstetrics and Gynaecology)2
1 Department of Obstetrics and Gynaecology, Kwong Wah Hospital, Hong Kong SAR, China
2 Department of Obstetrics and Gynaecology, Prince of Wales Hospital, Hong Kong SAR, China
3 Department of Paediatrics, Kwong Wah Hospital, Hong Kong SAR, China
4 Division of Paediatric Surgery, Department of Surgery, Queen Mary Hospital, Hong Kong SAR, China
 
Corresponding author: Dr Viola YT Chan (cyt141@ha.org.hk)
 
 Full paper in PDF
 
 
Case presentation
A 32-year-old nulliparous pregnant woman at 21 weeks of gestation was referred to Kwong Wah Hospital in March 2021 for fetal right cystic lung mass (2.16×1.99×2.50 cm3). Repeat examination at 22 weeks of gestation revealed a right multicystic lung mass (3.46×2.46×2.37 cm3) with a dominant 2-cm cyst, suggestive of macrocystic congenital pulmonary airway malformation (CPAM). There was mild mediastinal shift but no hydrops. The CPAM volume ratio, calculated as (length×height×width×0.52)/head circumference, was 0.51. Amniocentesis with chromosomal microarray analysis showed no copy number variants. At 26 weeks of gestation, the lesion had enlarged to 5.73×4.28×4.26 cm3 (CVR=2.16), with mediastinal shift and mild ascites but no polyhydramnios. At 27 weeks of gestation, the lesion was dominated by a single cyst that measured 6.15×4.25×4.1 cm3 (CPAM volume ratio=2.09), with moderate polyhydramnios, ascites and skin oedema suggestive of fetal hydrops. Intramuscular betamethasone was administered for fetal lung maturation in view of the high risk of preterm delivery. Fetal thoracoamniotic shunting was offered to relieve the mass effect and fetal hydrops. The next day, a Somatex shunt (SOMATEX Medical Technologies, Berlin, Germany) was inserted into the CPAM under ultrasound guidance and 800 mL amniotic fluid was drained via the shunt cannula. Examination 9 days later showed CPAM with reduced size (2.3×1.7×1.5 cm3; CVR=0.12), shunt in situ, and no hydrops (Table).
 

Table. Antenatal course of the congenital pulmonary airway malformation of the baby
 
At 29 weeks of gestation, the patient went into preterm prelabour with rupture of membrane that sealed off spontaneously. Serial ultrasound examinations showed satisfactory fetal growth, collapsed CPAM with shunt in situ, normal liquor volume and no hydrops (Table). Labour was induced at 38 weeks of gestation for oligohydramnios. A 2.75-kg female baby was delivered by vacuum extraction for maternal exhaustion, with paediatrician standby. The Apgar scores of the baby were 8 at 1 minute and 10 at 5 minutes and the arterial cord blood pH was 7.31, with base excess of -7.1 mmol/L. The shunt was specifically searched for immediately after delivery but the skin was intact (Fig a). The baby was given continuous positive airway pressure because of respiratory distress and was transferred to the neonatal intensive care unit. Urgent chest X-ray revealed the shunt in the right chest with right pneumothorax (Fig b). A chest drain was inserted and the baby was intubated. Computed tomography of the thorax of the baby on day 1 of life showed an irregular 4.2×3.5×2.5 cm3 cystic lesion in the right lung with the distal end of the shunt migrated between the chest wall and the scapular, abutting the right subscapularis muscle. Thoracoscopy on day 6 of life confirmed that one end of the shunt was within the CPAM in the right middle lobe, while the other end was at the subscapular space. The shunt was removed intact and near-total right middle lobe excision was performed thoracoscopically. The baby was successfully weaned off oxygen 3 weeks postoperatively and discharged 5 weeks later.
 

Figure. (a) Intact skin overlying the right chest wall of the newborn immediately after birth. (b) Chest X-ray showing the internally displaced Somatex shunt in the right middle lobe (arrow), with pneumothorax
 
Discussion
Congenital pulmonary airway malformations are uncommon lung lesions characterised by an overgrowth of terminal respiratory bronchioles that are often immature and non-functioning. A CPAM is considered macrocystic if at least one cyst is >5 mm and microcystic if the lesion appears echogenic on ultrasound examination. Although a microcystic CPAM may regress spontaneously after 26 to 28 weeks of gestation, most macrocystic CPAMs do not.1 Fetuses with large cystic lesions are also at risk of pulmonary hypoplasia and development of fetal hydrops due to compression of lung tissue and venous return. The survival of a hydropic fetus with congenital lung lesion has been reported to be 38%, compared with 87% for a fetus without hydrops.1 Studies have demonstrated a favourable outcome following thoracoamniotic shunting for macrocystic CPAM, with reduction in lesion volume, resolution of hydrops and improved survival.2 3 A systematic review showed an improved survival from 3% to 62% in hydropic fetuses treated with shunting.4 In a single-centre case series, survival was significantly associated with gestational age at birth, hydrops resolution and higher percent reduction in the size of the lung lesion following shunting.3
 
Although thoracoamniotic shunting improves fetal outcome, complications such as shunt occlusion, displacement, dislodgement, bleeding and chest wall deformation have been reported.3 5 6 7 Following successful drainage of the lesion, its surrounding normal lung parenchyma expands and grows. This may result in inward migration of the shunt. In a retrospective review,5 thoracoamniotic shunts inserted for primary pleural effusions and macrocystic CPAMs were antenatally displaced in 8.5% of fetuses, of which two-thirds migrated into the thorax. Re-shunting may be required if the displaced shunt fails to drain and fluid re-accumulates.5 Retained intrathoracic shunts may be managed conservatively as they are well tolerated without untoward postnatal sequalae.5 8 Nonetheless surgical removal may be necessary if the baby develops complications such as respiratory distress or tension pneumothorax.7 9
 
The Somatex shunt is commonly used to treat fetuses with obstructive urinary tract disorders. Recently, thoracoamniotic shunting with a Somatex shunt has been reported effective in relieving fetal pleural effusions with good survival rate although shunt dislodgement and entrapment has been reported in four of eight cases.10 Thoracoscopic removal of a displaced Somatex shunt has been reported necessary in a newborn with respiratory distress and progressive pleural effusion.7 In comparison with other commonly used shunts, such as Harrison and Rocket, Somatex insertion has multiple advantages including a finer introducer (1.2 mm) but a bigger shunt lumen (2.4 mm). It is also made of metal facilitating its easy identification antenatally on ultrasound or postnatally with X-rays or computed tomography.
 
A thoracoamniotic shunt should be clamped immediately following delivery to prevent air from entering the thorax and causing pneumothorax.2 In the current case, we did not expect air to enter the pleural cavity because the shunt was buried inside the skin of the baby. Our hypothesis is that air may have entered from the lung tissue into the pleural space via the displaced shunt. This is similar to the reported case of tension pneumothorax due to an internally displaced thoracoamniotic shunt communicating between the CPAM and the pleural cavity and diagnosed following neonatal resuscitation for apnoea.9 Both cases illustrate that pneumothorax is a possible and potentially life-threatening complication of an internally displaced shunt. It should be anticipated at birth and preparations made for emergency needle thoracocentesis. Obstetricians should be aware of the possible complications of thoracoamniotic shunts, and paediatricians should be alerted so that the newborn can receive prompt assessment and treatment.
 
Author contributions
Concept or design: VYT Chan, WC Leung, TY Leung.
Acquisition of data: VYT Chan, WT Tse, MC Chan, KKY Wong.
Analysis or interpretation of data: VYT Chan.
Drafting of the manuscript: All authors.
Critical revision of the manuscript for important intellectual content: KKY Wong, WC Leung, TY Leung.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
As an editor of the journal, KKY Wong was not involved in the peer review process. Other authors have disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patient and her baby were treated in accordance with the Declaration of Helsinki. Parental consent was obtained for the patient’s baby, and informed consent was obtained from the patient for all treatments and procedures, and publication of the case report.
 
References
1. Walker L, Cohen K, Rankin J, Crabbe D. Outcome of prenatally diagnosed congenital lung anomalies in the North of England: a review of 228 cases to aid in prenatal counselling. Prenat Diagn 2017;37:1001-7. Crossref
2. Schrey S, Kelly EN, Langer JC, et al. Fetal thoracoamniotic shunting for large macrocystic congenital cystic adenomatoid malformations of the lung. Ultrasound Obstet Gynecol 2012;39:515-20. Crossref
3. Peranteau WH, Adzick NS, Boelig MM, et al. Thoracoamniotic shunts for the management of fetal lung lesions and pleural effusions: a single-institution review and predictors of survival in 75 cases. J Pediatr Surg 2015;50:301-5. Crossref
4. Knox EM, Kilby MD, Martin WL, Khan KS. In-utero pulmonary drainage in the management of primary hydrothorax and congenital cystic lung lesion: a systematic review. Ultrasound Obstet Gynecol 2006;28:726-34. Crossref
5. Abbasi N, Windrim R, Keunen J, et al. Perinatal outcome in fetuses with dislodged thoraco-amniotic shunts. Fetal Diagn Ther 2021;48:430-9. Crossref
6. Makishi A, Kiyoshi K, Funakoshi T. EP21.22: Fetal chest wall deformity after thoracoamniotic shunting using a double-basket catheter for chylothorax: a case report. Ultrasound Obstet Gynecol 2016;48:362-3. Crossref
7. Sham GT, Chung PH, Chan IM, Leung WC, Wong KK. Thoracoscopic removal of a displaced thoracoamniotic shunt in a newborn with antenatal pleural effusion—a case report. Transl Pediatr 2020;9:702-6. Crossref
8. Tan AP, Tan B, Wright A, Kong JY. Management dilemma in thoracoamniotic shunt migrations. BMJ Case Rep 2023;16:e255760. Crossref
9. Law BH, Bratu I, Jain V, Landry MA. Refractory tension pneumothorax as a result of an internally displaced thoracoamniotic shunt in an infant with a congenital pulmonary airway malformation. BMJ Case Rep 2016:2016:bcr2016216324. Crossref
10. Chung MY, Leung WC, Tse WT, et al. The use of Somatex shunt for fetal pleural effusion: a cohort of 8 procedures. Fetal Diagn Ther 2021;48:440-7. Crossref

First experience using a wireless oesophageal pH monitoring system in children in Hong Kong: three case reports

Hong Kong Med J 2025 Feb;31(1):65–7 | Epub 11 Feb 2025
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
First experience using a wireless oesophageal pH monitoring system in children in Hong Kong: three case reports
Adrian CH Fung, MB, BS, FRCSEd (Paed); Kenneth KY Wong, PhD, FRCSEd (Paed)
Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
 
Corresponding author: Prof Kenneth KY Wong (kkywong@hku.hk)
 
 Full paper in PDF
 
 
Twenty-four–hour pH monitoring is indicated for evaluation of gastroesophageal reflux symptoms in children, as well as part of a preoperative work-up for those who require long-term nasogastric tube feeding or a gastrostomy. Its use is nonetheless restricted by the need to keep a nasal catheter in place for at least 24 hours. This can cause great discomfort and may be poorly tolerated by children, especially those with behavioural issues. Wireless pH monitoring can improve patient satisfaction and the overall sensitivity of diagnosing gastroesophageal reflux (Fig 1). Despite its rising popularity among adults, its use has been limited in children. This report documents the first experience in Hong Kong of a wireless oesophageal pH monitoring system in children with gastrointestinal symptoms and feeding problems.
 

Figure 1. Wireless pH monitoring capsule system
 
Case presentations
Case 1
A 9-year-old girl with good previous health and normal development presented to a surgical clinic in March 2023 with recurrent epigastric pain and heartburn. She was prescribed a proton pump inhibitor without symptom improvement. As her parents were keen to determine the cause of her symptoms, upper endoscopy and a pH study were offered. With consideration of patient comfort and the sensitivity of the test, wireless oesophageal pH monitoring was arranged. Endoscopy under general anaesthetic revealed mild antral gastritis but was otherwise unremarkable. An antral biopsy confirmed mild gastritis without Helicobacter pylori. The oesophagogastric junction (OGJ) was measured as 34 cm from the incisor, and a wireless pH monitoring capsule (Bravo; Medtronic Inc, Minneapolis [MN], United States) was inserted at 30 cm under direct endoscopic visualisation (Fig 2a). Post-insertion endoscopy confirmed secure placement at a satisfactory position (Fig 2b). An X-ray after the procedure further confirmed the good position of the capsule (Fig 2c). pH monitoring lasted 96 hours, with a DeMeester score of 6.8. The girl initially complained of mild chest discomfort and a globus sensation during swallowing on the first 2 days post procedure but this resolved spontaneously after 4 days. The capsule passed spontaneously within 3 weeks of the procedure. The diagnosis of gastritis was made after excluding gastroesophageal reflux by pH monitoring; the patient was prescribed a short course of a proton pump inhibitor that resolved the symptoms.
 

Figure 2. Case 1. (a) Deployment of wireless oesophageal pH monitoring capsule under endoscopic view (arrow showing a piece of mucosa in the suction chamber). (b) Endoscopic view following successful deployment of wireless oesophageal pH monitoring capsule. (c) Chest X-ray showing the position of the wireless oesophageal pH monitoring capsule (circle)
 
Case 2
A 6-year-old girl with known glucose phosphate isomerase deficiency, cerebral ataxia and mild intellectual impairment presented to the same surgical clinic in January 2023. She had feeding problems with failure to thrive and needed supplemental milk feeding via a nasogastric tube. Given her medical background and neurodevelopment, she could not tolerate nasogastric tube insertion during her regular revision and required frequent sedation during the procedure. Owing to the anticipated requirement for long-term tube feeding, her parents were advised of the need for gastrostomy tube insertion and a preoperative pH study. As both the patient and parents could not accept a conventional 24-hour pH study, a wireless oesophageal pH monitoring system was inserted under monitored anaesthetic care. The upper endoscopy was unremarkable with no sign of oesophagitis or gastritis. Bravo was inserted at 25 cm from the incisor (ie, 5 cm from the OGJ). Monitoring continued for 96 hours, with a DeMeester score of 0.7. The capsule passed without any complications within 3 weeks of the procedure. The patient was well and there were no adverse events during the study period. In view of the negative pH study, an anti-reflux procedure was deemed unnecessary and subsequently only a laparoscopic gastrostomy was performed.
 
Case 3
A 16-year-old boy with recurrent postprandial heartburn and vomiting presented to the same surgical clinic in March 2024. Medical treatment with proton pump inhibitors elicited no improvement and he was referred for work-up for an anti-reflux procedure. At the time of referral, as capsule pH monitoring was not available locally, a catheter-based 24-hour pH-impedance probe was attempted. Nonetheless the patient could not tolerate the procedure with repeated vomiting and failure of catheter insertion. Given the parents’ wish to have a definitive diagnosis prior to initiating an anti-reflux procedure, pH study was rearranged with the wireless oesophageal pH monitoring system under monitored anaesthesia care. The procedure was well tolerated and the patient was able to complete a 96-hour pH study. The overall DeMeester score was 16.1. During the study period, Day 2 was the patient’s worst day, with acid exposure time at 5.9% and DeMeester score at 22.1. There was significant improvement following resumption of a proton pump inhibitor on Day 3 with acid exposure time at 1% and DeMeester score at 3.5. With the diagnosis of significant gastroesophageal reflux disease confirmed, the parents agreed to proceed with laparoscopic fundoplication.
 
Discussion
According to the joint updated guidelines of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition in 2018,1 24-hour pH monitoring is indicated in children with persistent symptoms of gastroesophageal reflux disease despite proton pump inhibitor treatment. The aim is to correlate persistent troublesome symptoms with acid gastroesophageal reflux events, clarifying the role of acid reflux and determining the efficacy of acid suppression therapy.1 Twenty-four–hour pH monitoring is also recommended as pre-gastrostomy work-up in children to guide patient selection for a concomitant anti-reflux procedure.2 Nonetheless conventional transnasal catheter pH monitoring, although still widely used, is frequently criticised for causing great patient discomfort, limiting the patient’s mobility during the test and, more importantly, being neither tolerable nor inducing compliance by children with neurodevelopmental and behavioural issues,3 as illustrated by Case 2. Not only is the quality of life of patients jeopardised, the unpleasant experience may also restrict reflux-provoking activities, limiting the accuracy and sensitivity of the test and yielding false lower values, as illustrated by Case 3.
 
To overcome these difficulties, the wireless oesophageal pH monitoring system uses a capsule attached to the mucosal wall of the oesophagus for pH monitoring (Fig 1). It consists of a 6.0×6.3×26.0 mm3 capsule-based device, equipped with an internal battery and a pH electrode. The device is attached to the distal wall of the oesophagus, approximately 4 to 6 cm from the OGJ, under direct endoscopic visualisation.3 4 It transmits pH data to a mobile phone–sized recorder via radio telemetry, thus obviating the need for a transnasal pH probe. The capsule enables data to be recorded for at least 48 hours and up to 96 hours, with minimal patient discomfort. The capsule detaches from the oesophageal mucosa and is expelled in stools, with spontaneous sloughing of the oesophageal mucosa and uneventful healing, usually over 3 to 7 days. Its clinical use in children has been established in the United Kingdom and the United States, demonstrating a high success rate, with better tolerance than standard transnasal pH monitoring in children with behavioural issues and an improvement in the detection rate of gastroesophageal reflux disease by 16% through extended recording time.3 4 As illustrated by Case 3, not only is the procedure tolerated, the successful extension of study for a duration of 96 hours may result in a higher diagnostic yield and provision of more information, eg, effect of pump on and off (whether patient was on proton pump inhibitor).5 Currently, the wireless pH monitoring system is intended to be used in adults and children from 4 years of age but is contraindicated in those with bleeding diathesis, strictures, severe oesophagitis, varices, obstructions, pacemakers or implantable cardiac defibrillators. In situations where the wireless pH capsule needs to be removed, for instance in patients with severe discomfort or failure of spontaneous passage, cold snare and hot snare (when cold snare is not sufficient) can be applied to safely remove the capsule with only thin superficial oesophageal mucosal tissue.6
 
To the best of our knowledge, our centre is the first to introduce and report the use of the wireless oesophageal pH monitoring system in children in Hong Kong. The procedure was smooth, with no equipment or technical failure, and all patients could be discharged on the same day of the procedure. Since Case 1 was the first patient at our centre to receive the device, a chest X-ray was taken to double confirm its position. Nonetheless a post-procedure chest X-ray is not routine for the paediatric population since the device position can be confirmed with endoscopy, as in the adult population. All patients tolerated the pH study well except for the complaint of a self-limiting globus sensation in one patient (Case 1). All parents reported no difficulty in utilising the mobile pH recording system. All capsules were expelled from the patients within 3 weeks of the procedure without any complication.
 
Wireless oesophageal pH monitoring cannot easily diagnose some conditions such as functional belching and rumination syndrome due to the lack of impedance monitoring. Nonetheless these cases highlight that it is well tolerated and feasible in evaluating gastroesophageal reflux symptoms in children and provides a sensible alternative to standard transnasal pH monitoring. In addition, it may result in a higher diagnostic yield and more comprehensive clinical information. As clinicians, we are obliged to keep track of technological advancements and strive to provide holistic and optimal care for children, improve patient satisfaction and shorten their hospital stay.
 
Author contributions
Both authors contributed to the concept or design, acquisition of data, analysis or interpretation of data, drafting of the manuscript and critical revision of the manuscript for important intellectual content. Both authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
As an editor of the journal, KKY Wong was not involved in the peer review process. The other author has disclosed no conflicts of interest.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
The patients were treated in accordance with the Declaration of Helsinki. Verbal consent was obtained from the patients for the publication of the case reports.
 
References
1. Rosen R, Vandenplas Y, Singendonk M, et al. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2018;66:516-54. Crossref
2. Fung AC, Ooi YN, Hui HM, Mok MK, Chung PH, Wong KK. Prophylactic anti-reflux procedure for children undergoing laparoscopic gastrostomy: rethinking of the routine practice. World J Surg 2024;48:739-45. Crossref
3. Rodriguez L, Morley-Fletcher A, Winter H, Timothy B. Evaluation of gastroesophageal reflux disease in children on the autism spectrum: a study evaluating the tolerance and utility of the BRAVO wireless pH monitoring. J Pediatr Gastroenterol Nutr 2022;75:450-4. Crossref
4. Rao NM, Campbell DI, Rao P. Two years’ experience of using the Bravo wireless oesophageal pH monitoring system at a single UK tertiary centre. Acta Paediatr 2017;106:312-5. Crossref
5. Zeki SS, Miah I, Visaggi P, et al. Extended wireless pH monitoring significantly increases gastroesophageal reflux disease diagnoses in patients with a normal pH impedance study. J Neurogastroenterol Motil 2023;29:335-42. Crossref
6. de Hoyos A, Esparza EA, Loredo ML. Cold and hot snare endoscopic techniques for removal of the Bravo pH monitoring capsule. Digestion 2009;79:14-6. Crossref

Collapsing glomerulopathy as a rare cause of rapidly progressive renal failure in adolescence: two case reports

Hong Kong Med J 2024 Dec;30(6):502–5 | Epub 23 Dec 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
 
CASE REPORT
Collapsing glomerulopathy as a rare cause of rapidly progressive renal failure in adolescence: two case reports
Yeşim Özdemir Atikel, MD1; Betül Öğüt, MD2; İpek Işık Gönül, MD2; Necla Buyan, MD1; Sevcan A Bakkaloğlu, MD1
1 Department of Pediatric Nephrology, Gazi University Faculty of Medicine, Gazi University, Ankara, Turkey
2 Department of Pathology, Gazi University Faculty of Medicine, Gazi University, Ankara, Turkey
 
Corresponding author: Prof Yeşim Özdemir Atikel (yesozdemir@gmail.com)
 
 Full paper in PDF
 
 
Case presentations
Case 1
A 17-year-old male was referred to our institution in January 2016 due to elevated serum creatinine level of 1.85 mg/dL and nephrotic proteinuria level of 6839 mg/day. He had a history of epilepsy and had used various antiepileptic drugs (phenobarbital, valproic acid, and carbamazepine) from the ages 3 to 14 years. Physical examination revealed lower extremity oedema and a blood pressure of 140/90 mm Hg. Laboratory tests on admission showed a blood urea nitrogen level of 24 mg/dL, serum creatinine level of 1.68 mg/dL and a serum albumin level of 2.7 g/dL. Urine microscopy revealed three red blood cells per high-power field. A 24-hour urine collection revealed massive proteinuria level of 10.957 mg/day (296 mg/m2/h). Serum complement levels were normal and autoimmune tests (antinuclear antibodies, anti–double-stranded DNA antibodies, anti–glomerular basal membrane antibodies, and anti-neutrophil cytoplasmic antibodies) were negative. Viral serology, including hepatitis B virus, hepatitis C virus, human immunodeficiency virus, Epstein–Barr virus, cytomegalovirus, and parvovirus, was also negative. Abdominal ultrasound revealed increased echogenicity in the renal parenchyma.
 
Treatment with enalapril at a dose of 0.4 mg/kg/day was started. Kidney biopsy was performed on the seventh day after admission and showed compatibility with collapsing glomerulopathy (CG) [Fig 1]. Methylprednisolone boluses of 1 g were administered for 5 consecutive days, followed by oral prednisone at a dose of 60 mg/m2/day. By the 15th day, serum creatinine levels were at 2.1 mg/dL, serum albumin level at 1.9 g/dL, and 24-hour urine protein level at 17.8 g/day. Mycophenolate mofetil was added to the treatment regimen. On the 40th day, serum creatinine level had increased to 4.2 mg/dL with proteinuria of 13.3 g/day, leading to the initiation of rituximab and tapering of prednisolone. By the 60th day, mycophenolate mofetil was discontinued due to leukopenia; however, the patient had completed the 4 doses of weekly 375 mg/m2/dose rituximab treatment. Additionally, he received albumin infusions, diuretics, and antihypertensives. Since the clinical features and laboratory parameters did not improve, the patient underwent plasma exchange. After two sessions, haemodialysis was required due to worsening symptoms, uncontrolled hypervolaemia, and renal failure. No additional immunosuppressive was given at that time and the patient continued to receive haemodialysis. Genetic testing for mutations of the NPHS1 and NPHS2 genes were negative.
 

Figure 1. Case 1. Renal biopsy findings showing (a) a haematoxylin and eosin stain of a glomerulus with segmental podocyte hyperplasia (arrows) causing segmental collapse on the underlying capillary lumen (×200) and (b) periodic acid–Schiff stain revealing a segmental collapse (arrow) in the glomerular capillary walls with podocyte hyperplasia (×200)
 
Case 2
Another 17-year-old male was admitted to our institution in February 2016 for syncope. He had a history of headaches with intermittent vomiting for the previous 2 months and had been treated with metamizole, domperidone, zolmitriptan, and diclofenac. His mother had a history of minimal change disease aged 6 years. The patient’s blood pressure was measured as 200/120 mm Hg, and hypertensive retinopathy was observed during the ophthalmological examination. Initial serum creatinine level was 4.7 mg/dL and serum albumin level was 3.4 g/dL. Ferritin and parathyroid hormone levels were 274 ng/mL and 220 pg/mL, respectively. Microscopic urinalysis showed eight red blood cells per high-power field. He had nephrotic proteinuria of 3820 mg/day (91.5 mg/m2/h). Viral serology and autoimmune tests (antinuclear antibodies, anti–double-stranded DNA antibodies, anti–glomerular basal membrane antibodies, and anti-neutrophil cytoplasmic antibodies) were negative and complement levels were normal. Abdominal ultrasound revealed increased renal echogenicity. Cranial magnetic resonance imaging showed signs of posterior reversible encephalopathy syndrome. Hypertension was controlled using intravenous and oral antihypertensives (esmolol, captopril, amlodipine, doxazosin, and minoxidil). On the fourth day, the serum creatinine level increased to 5.9 mg/dL and the albumin level decreased to 2.4 g/dL. Kidney biopsy showed severe CG (Fig 2). Because the findings were chronic, no steroids or other immunosuppressive treatment were administered. Genetic testing for mutations of the NPHS1 and NPHS2 genes was negative. By the fifth month, the patient’s serum creatinine level had reached 6.9 mg/dL. After 1 year of peritoneal dialysis, he received a renal transplant.
 

Figure 2. Case 2. Renal biopsy findings showing (a) global glomerular collapse with pronounced podocyte hyperplasia (white arrows) filling the Bowman’s space in the form of pseudo-crescent formation (black arrows) [haematoxylin and eosin stain, ×400] and (b) the same glomerulus with periodic acid–Schiff stain (×400)
 
Discussion
Collapsing glomerulopathy is a histopathological pattern of podocytopathies.1 It was previously classified as a variant of focal segmental glomerulosclerosis (FSGS), known as collapsing FSGS.2 3 4 However, it is more severe at the initial stage and progresses more rapidly to end-stage kidney disease compared with non-collapsing FSGS, even when treatment is given.2 3 4 5 It typically presents with nephrotic proteinuria and elevated serum creatinine level, and is rare among children.3 5
 
Both patients had high serum creatinine level, nephrotic proteinuria, and hypertension. To establish the exact diagnosis and determine the prognosis, a kidney biopsy was performed as the gold standard for diagnosis. Histopathological findings of CG include glomerular capillary collapse in at least one glomerulus; hyperplasia and hypertrophy of visceral epithelial cells leading to pseudo-crescent formation; presence of periodic acid–Schiff-positive hyaline droplets in visceral epithelial cell cytoplasm; and severe tubulointerstitial inflammation in the early stages. Glomerulosclerosis and interstitial fibrosis are observed in the late stages, and immunofluorescence assay is typically negative.1 2 3 4 6 Kidney biopsies in both cases showed advanced CG with global glomerulosclerosis and interstitial fibrosis (Figs 1 and 2).
 
Collapsing glomerulopathy can be either idiopathic (primary), genetic (familial), or reactive (secondary).1 The idiopathic form is characterised by the loss of maturity markers and the re-expression of immaturity markers leading to the proliferation of immature podocytes.1 Secondary causes of CG include infections (human immunodeficiency virus, parvovirus B19, cytomegalovirus, hepatitis C virus, severe acute respiratory syndrome coronavirus 2), drugs (including valproic acid and anabolic steroids), autoimmune diseases (such as systemic lupus erythematosus), and malignancies.1 2 3 4 7 Genetic CG is associated with mitochondrial dysfunction that causes podocyte proliferation.1 Case 1 had a history of long-term use of antiepileptic drugs (phenobarbital, valproic acid, and carbamazepine). However, we found no other aetiological factors in either patient. Therefore, we concluded that while the aetiology in Case 1 could be idiopathic or valproic acid–related, it was idiopathic in Case 2.
 
There is no specific treatment for CG2; as such, the mainstay of therapy is for the disorders resulting from nephrotic syndrome (such as hypertension and oedema), treatment of the underlying conditions (such as infections and autoimmune diseases), and immunosuppressive therapy.8 Possible factors for progression to end-stage kidney disease in CG include a serum creatinine level >2 mg/dL at the time of biopsy, proteinuria >8 g/day and lack of remission, collapsing lesions in >20% of glomeruli, and the severe tubular changes and interstitial fibrosis.3 9 10 In Case 1, the rationale for aggressive immunosuppressive treatment was based on an initial serum creatinine level of 1.6 mg/dL, intense polymorphonuclear leukocytes and eosinophil infiltration, and 2 out of 24 glomeruli showing glomerulosclerosis. Case 2 did not receive immunosuppressive treatment due to the chronicity of the disease and advanced global glomerulosclerosis (67%). The Table summarises the clinical findings in both patients.
 

Table. Initial findings and clinical course of both patients
 
Conclusion
It is important to recognise that CG is a separate clinicopathological entity from FSGS. Due to the poor response to immunosuppressive drugs and the potential for renal transplantation, we recommend avoiding aggressive immunosuppressive therapy for patients with poor prognostic factors at the time of diagnosis. This approach helps minimise the side-effects of cumulative immunosuppression.
 
Author contributions
Concept or design: All authors.
Acquisition of data: All authors.
Analysis or interpretation of data: All authors.
Drafting of the manuscript: Y Özdemir Atikel, SA Bakkaloğlu.
Critical revision of the manuscript for important intellectual content: All authors.
 
All authors had full access to the data, contributed to the study, approved the final version for publication, and take responsibility for its accuracy and integrity.
 
Conflicts of interest
All authors have disclosed no conflicts of interest.
 
Declaration
The two cases have been presented during oral presentations at the IPNA Teaching Course of the 5th Southeastern Europe Pediatric Nephrology Working Group Meeting inSkopje, Macedonia, 10-11 June 2016.
 
Funding/support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
 
Ethics approval
Both patients were treated in accordance with the Declaration of Helsinki. Written informed consent for publication was obtained from both patients and their parents.
 
References
1. Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol 2007;2:529-42. Crossref
2. Albaqumi M, Soos TJ, Barisoni L, Nelson PJ. Collapsing glomerulopathy. J Am Soc Nephrol 2006;17:2854-63. Crossref
3. Mubarak M. Collapsing focal segmental glomerulosclerosis: current concepts. World J Nephrol 2012;1:35-42. Crossref
4. Ferreira AC, Carvalho D, Carvalho F, Galvão MJ, Nolasco F. Collapsing glomerulopathy in Portugal: a review of the histological and clinical findings in HIV and non-HIV patients. Nephrol Dial Transplant 2011;26:2209-15. Crossref
5. Gulati A, Sharma A, Hari P, Dinda AK, Bagga A. Idiopathic collapsing glomerulopathy in children. Clin Exp Nephrol 2008;12:348-53. Crossref
6. Fogo AB, Lusco MA, Najafian B, Alpers CE. AJKD Atlas of Renal Pathology: collapsing glomerulopathy. Am J Kidney Dis 2015;66:e3-4. Crossref
7. Nasr SH, Kopp JB. COVID-19–associated collapsing glomerulopathy: an emerging entity. Kidney Int Rep 2020;5:759-61. Crossref
8. Cutrim ÉM, Neves PD, Campos MA, et al. Collapsing glomerulopathy: a review by the Collapsing Brazilian Consortium. Front Med (Lausanne) 2022;9:846173. Crossref
9. Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999;56:2203-13. Crossref
10. Valeri A, Barisoni L, Appel GB, Seigle R, D’Agati V. Idiopathic collapsing focal segmental glomerulosclerosis: a clinicopathologic study. Kidney Int 1996;50:1734-46. Crossref

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