Identifying phenotypes of obstructive sleep apnea using cluster analysis.

PURPOSE: Over the last decade, advances in understanding the pathophysiology, clinical presentation, systemic consequences and treatment responses in obstructive sleep apnea (OSA) have made individualised OSA management plausible. As the first step in this direction, this study was undertaken to identify OSA phenotypes. METHODS: Patients diagnosed with OSA on level 1 polysomnography (PSG) were included. Clinical and co-morbidity profile, anthropometry and sleepiness scores were compiled. On PSG, apnea-hypopnea index, positional indices, sleep stages and desaturation indices (T90) were tabulated. Cluster analysis was performed to identify distinct phenotypes among included patients with OSA. RESULTS: One hundred patients (66 males) with a mean age of 49.5 ± 13.3 years were included. Snoring was reported by 94% subjects, and 50% were excessively sleepy. Two-thirds of subjects had co-morbidities, the most frequent being hypertension (55%) and dyslipidemia (53%). Severe OSA was diagnosed on PSG in 42%, while 29% each had mild and moderate OSA, respectively. On cluster analysis, 3 distinct clusters emerged. Cluster 1 consisted of older, obese subjects with no gender predilection, higher neck circumference, severe OSA with more co-morbidities and higher T90. Cluster 2 comprised of younger, less obese males with snoring, witnessed apnea, moderate and supine predominant OSA. Cluster 3 consisted of middle-aged, obese males with lesser co-morbidities, mild OSA and lower T90. CONCLUSIONS: This study revealed three OSA clusters with distinct demographic, anthropometric and PSG features. Further research with bigger sample size and additional parameters may pave the way for characterising distinct phenotypes and individualising OSA management.

A case of hoarseness of voice following COVID-19 infection.

Mucormycosis is a fatal angio-invasive fungal infection associated with a high mortality. Apart from the traditional risk factors, COVID-19 infection and steroid therapy for the same have been recently identified to predispose to this life-threatening infection. Usual presentations of mucormycosis include rhino-orbito-cerebral, pulmonary, gastrointestinal, renal and cutaneous involvement. We report an unusual case of mediastinal involvement by mucormycosis in a patient recovering from moderate COVID-19 pneumonia. Early diagnosis, prompt initiation of antifungal therapy accompanied by timely surgical debridement were pivotal in averting morbidity and mortality in this patient.

A simple high-volume culture technique-Good substitute for polymerase chain reaction for the detection of Aspergillus species in bronchoalveolar lavage samples.

BACKGROUND: Aspergillus species is the most common agent of invasive pulmonary fungal disease. Culture-based diagnosis considered as gold standard is limited by the fungal load in samples. Detection of Aspergillus by polymerase chain reaction (PCR) has been included as a diagnostic criterion by European Organisation for Research and Treatment of Cancer (EORTC). Most routine laboratories lack facilities for molecular diagnosis. Better yield using high-volume culture (HVC) technique has been reported. Studies have not compared HVC and PCR for detection of Aspergillus species in respiratory samples from patients with suspected invasive pulmonary Aspergillosis (IPA) not on antifungal therapy. OBJECTIVE: This pilot study compared HVC and PCR for the detection of Aspergillus species in respiratory samples from treatment naïve patients. METHODS: Bronchoalveolar lavage (BAL) samples from 30 patients with clinical suspicion of IPA were evaluated. Direct microscopy, culture both conventional (CC) and HVC and qualitative Pan Aspergillus PCR were performed. Latent class model was used for statistical analysis. RESULTS: Sensitivity of HVC (100%) was better compared with CC (60%) and comparable to that of PCR (100%). Specificities of CC, HVC and PCR were 100%, 100% and 25%, respectively. CONCLUSION: High-volume culture is a simple cost-effective technique with a high sensitivity and specificity. It can be easily introduced in routine microbiology laboratories. In centres with the availability of infrastructure for molecular analysis, Aspergillus PCR with other mycological techniques can be used for better diagnosis and management of patients with IPA.

The effect of CPAP therapy on excessive daytime sleepiness and quality of life in subjects with obstructive sleep apnoea: an AB design study.

BACKGROUND: Obstructive sleep apnoea (OSA) is a disorder characterized by apnoeas and hypopnoeas due to repetitive upper airway collapse during sleep. So far, there are no published data regarding quality of life (QoL) and adherence to CPAP among patients with OSA in India. This study aims to measure sleepiness and QoL of patients before and after effective CPAP use in patients with OSA. METHOD: Newly diagnosed subjects with OSA were included, and socio-demographic risk factors and anthropomorphic measures were collected. Epworth sleepiness scale (ESS) and short sleep apnoea quality of life index (SAQLI) were administered before and after a minimum of 4 weeks of domiciliary CPAP use. While short SAQLI is a disease-specific questionnaire, ESS measures excessive daytime sleepiness. RESULTS: In 92 subjects age range was 28-74 years, mean age 49.7 ± 11.3 years, and male:female ratio was 70:22. Mean BMI was 32.1 ± 6.4 kg/sq.m; mean neck circumference was 39.4 ± 3.4 cm; 56 subjects had Mallampati score of 3 or 4. One-month follow-up was completed by 34 subjects who reported a mean of 5.8 ± 1.1 hours/night usage of CPAP. Mean ESS score was 11.31 ± 5.6 at baseline vs 6.9 ± 3.3 after 1 month (p = 0.02), and baseline short SAQLI score was at 2.54 ± 1.26 vs 1.38 ± 0.87 after 1 month (p = 0.0001). CONCLUSIONS: Subjects reported adequate compliance with CPAP at 1 month, and both ESS and short SAQLI showed a significant improvement in these patients. CPAP compliance improved both QoL and sleepiness in patients with OSA.

A simple x-ray scoring system for the diagnosis of chronic pulmonary aspergillosis.

BACKGROUND: Chronic pulmonary aspergillosis (CPA) is a severe form of post-tuberculosis lung disease (PTBLD). Considering the high burden of TB in India, it can be concluded that the prevalence of CPA is also high. Chest x-ray though most feasible, interpretation is subjective. Therefore, decision on evaluation for CPA cannot be based on x-ray alone. OBJECTIVE: Present study evaluated an x-ray score as a marker for extent of lung damage in patients with PTBLD presenting with haemoptysis and its utility to predict Aspergillus serum IgG levels. METHODS: We used a modified scoring system developed by Anna Ralph et al X-ray score cut-offs of >71 and 40, with or without history of massive haemoptysis, were compared with serum IgG levels. RESULTS: With a chest x-ray score cut-off of 71, specificity was 88%. With an x-ray score of >71 combined with history of massive haemoptysis, 86% cases were found to be IgG positive. The specificity of this combination was 96%. CONCLUSION: This study concluded that a simple chest x-ray scoring system in addition to the symptom of massive haemoptysis helped in the decision on further evaluation of the subject for CPA, especially in resource constrained settings.

A filamentous trio.

Opportunistic infections caused by fungi and unusual bacteria are predominantly encountered in the setting of immunosuppressed host. Co-infections with multiple such organisms can pose multiple challenges even to the astute clinician from establishing the diagnosis to drug interactions during treatment of such infections. We hereby present one such case of a triple opportunistic infection in an immunocompetent host and the difficulties faced in the therapeutic decision making.

Chronic granulomatous 'Aspergillus lung mass'.

The diverse clinicopathological spectrum of pulmonary aspergillosis is a consequence of varying levels of invasiveness of this ubiquitous fungus, which largely depends on the host immune response and pre-existing lung disease. The clinical presentation of pulmonary aspergillosis spans a wide spectrum from hypersensitivity to life threatening angio-invasive and disseminated disease. We report the case of a young immunocompetent male with no underlying lung disease, who presented with an incidentally detected 'infective mass' lesion in the lung associated with minimal respiratory symptoms. The diagnostic challenges posed by the unusual clinical, radiological and histological picture as well as the therapeutic dilemmas faced are discussed in this report.

RNA-seq reveals outcome-specific gene expression of MMP7 and PCK1 in biliary atresia.

The disease phenotype in biliary atresia (BA) is caused by a fibro-inflammatory process leading to destruction of cholangiocytes, obstruction of ductular pathways and eventual progression to liver cirrhosis. The first line of management is a Kasai portoenterostomy (KPE) followed by liver transplantation (LT) in some children. Several factors have been postulated to affect the outcome of KPE and/or the subsequent progression of liver disease. However, no biomarkers have been identified in the liver for BA. We aimed to address this deficit. Whole transcriptome mRNA sequencing was performed for 29 samples (25 BA and 4 Controls) to identify the candidate genes predicting the prognosis of KPE. These results were further confirmed with quantitative Realtime PCR (qPCR). Analysis from RNA-sequencing data identified matrix metalloproteinase7 (MMP7) and phosphoenolpyruvate carboxykinase (PCK1) as potential determinants of the outcome of KPE. MMP7 expression was significantly elevated in patients who failed to clear jaundice after KPE as well as in patients with End Stage Liver Disease (ESLD). In contrast, PCK1 level was upregulated in patients who had successful KPE, while there was a significant down regulation in patients who failed KPE. MMP7 and PCK1 expression patterns had an inverse relation to the outcome of KPE and hence could potentially be used as biomarkers to predict KPE outcome and disease progression, enabling clinicians to design new treatment strategies for BA.

Age Is Not a Criterion in Patient Selection for Kasai Portoenterostomy.

AIMS: The aim of our study was to compare the outcome of Kasai portoenterostomy (KPE) in children with biliary atresia (BA) older than 90 days to children less than 90 days and to study its safety and efficacy in children older than 90 days. SUBJECTS AND METHODS: Relevant data were collected from our prospectively maintained database of all children with BA who underwent KPE over a 5-year period. Children were divided into two groups: Group 1 ≤90 days and Group 2 >90 days. Data analyzed and compared included total and direct bilirubin, aspartate aminotransferase-to-platelet ratio index (APRI), and the outcome of procedure which was defined as a serum direct bilirubin <2 mg/dl within 6 months after surgery. Standard statistical tests were used for analysis. RESULTS: Out of 62 children, 45 children were in Group 1 and 17 children were in Group 2. Children in Group 2 had similar total and direct bilirubin compared to children in Group 1. APRI, an indicator of fibrosis, was significantly increased in Group 2 (P = 0.08). About 47% of children in Group 2 had Stage III fibrosis on liver histology compared to 22% of children in Group 1. None of the children in Group 2 had synthetic liver failure (refractory ascites, hypoalbuminemia, or coagulopathy unresponsive to Vitamin K) or portal hypertension. KPE was successful in 29.4% of children in Group 2 and 44% in children in Group 1. There was no perioperative mortality in our group. CONCLUSIONS: KPE was successful in a third of children over 90 days of age and can be safely performed in this group. In the absence of synthetic liver failure, age should not be a disqualification for performing KPE.

Early Cholangitis after Portoenterostomy in Children with Biliary Atresia.

AIMS AND OBJECTIVES: Biliary atresia (BA) is a cholangiodestructive disease of the biliary tree. The first line of treatment is a Kasai portoenterostomy (PE) following which patients may develop cholangitis. We studied the effect of early cholangitis on the outcome of PE, namely jaundice clearance and early native liver survival (NLS). METHODS: We reviewed the data of all children who developed cholangitis after PE from our prospectively maintained database of children with BA. The standardized treatment of all children in the database is described. The frequency and nature of these episodes were characterized, and the outcome of PE and NLS 1 year after PE was calculated. RESULTS: Of 62 children who underwent PE in our institutions, 27 developed cholangitis. All episodes of cholangitis occurred within 14 months of PE. Of 25 children who cleared jaundice in the overall series, 19 had cholangitis. The incidence of cholangitis was significantly higher in children who cleared jaundice. Nine children who had cholangitis are alive with native livers for more than 1 year after PE. Twelve children had intractable cholangitis. Three of these children are alive with native liver 1 year after PE. CONCLUSION: In our series, cholangitis occurred in most children who cleared jaundice. Furthermore, the 1-year NLS of children who developed cholangitis was 33%.

Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.

BACKGROUND: Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. METHODS: All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. RESULTS: Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. CONCLUSION: Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation.

A Rare Case of Perinatal Intrarenal Neuroblastoma.

Perinatal neuroblastoma is the most common solid malignant tumor in infancy which comprises one fifth of all neuroblastomas. Most of them are of adrenal origin and extra-adrenal neuroblastoma is uncommon. We present a rare case of perinatal intrarenal neuroblastoma in a neonate who presented with an incidentally detected abdominal mass. These tumors cause diagnostic and therapeutic dilemma because of its uncommon location. Although very rare, neuroblastoma should be considered in the differential diagnosis of perinatally detected renal tumors.

Undiagnosed Obstructive Sleep Apnea and Postoperative Outcomes: A Prospective Observational Study.

BACKGROUND: The prevalence of undiagnosed obstructive sleep apnea (OSA) during preoperative evaluation and the best method to screen OSA and its association with postoperative complications remain unclear. OBJECTIVES: To determine the prevalence of undiagnosed OSA in preoperative Indian patients undergoing noncardiac surgery, to compare the diagnostic accuracy of the STOP-BANG questionnaire to a preoperative level III sleep study, and to assess the association of OSA with postoperative complications. METHODS: A prospective cohort of 245 consecutive adults with ≥2 risk factors for OSA who underwent noncardiac surgery between July 2011 and February 2013 were studied. The STOP-BANG questionnaire was administered to all patients, and 182/245 (74.2%) patients underwent a preoperative level III sleep study. Patients were followed for postoperative complications in hospital and contacted at 30 days after surgery. RESULTS: 70/182 (38.5%) obtained a new diagnosis of OSA, including 11/182 (6%) with moderate to severe OSA (apnea-hypopnea index ≥15/h). On logistic regression analyses, the presence of OSA was independently associated with postoperative oxygen desaturation (OR 5.96, 95% CI 2.35-15.1, p < 0.01), a postoperative complication within 7 days (OR 3.63, 95% CI 1.77-7.45, p < 0.01) and within 30 days (OR 3.5, 95% CI 1.74-7.1, p < 0.01). The STOP-BANG questionnaire did not identify 12/70 (17%) of the patients diagnosed with OSA and classified 28% of the cohort as OSA when the level III sleep study was negative. CONCLUSIONS: Unrecognized OSA is common in preoperative patients and is independently associated with postoperative complications. The STOP-BANG questionnaire had a lower performance in the diagnosis of OSA in a South Indian population than the level III sleep study.

Living donor liver transplantation for biliary atresia - An Indian experience.

LT has played a significant role in improving the outcome of children with BA. We review our five-yr experience of LDLT for children with BA. Records of all children who underwent LDLT in our institution over a five-yr period (August 2010-June 2015) were reviewed and those with a primary diagnosis of BA were selected for our study. Data were extracted from a prospectively maintained database. Additional data were collected by review of case notes and imaging studies. Analysis was carried out using standard statistical means. One hundred and thirty-two children underwent LDLT at our center over the study period, of which 58 children (31 females) had a primary diagnosis of BA. Thirty-three (56.9%) children had undergone a prior KPE and 25 (43.1%) had a primary LT. Thirty-four children had at least one post-op complication, of which 13 had minor complications (Clavien grades I and II) and 21 had major complications (Clavien grade >II). Thirty-day survival was 96.6% and one-yr survival was 91.4%. Univariate analysis of variables comparing children who did and did not have a KPE prior to LT showed that age at LT, weight at LT, PELD, and GRWR were significantly different. LDLT provides excellent outcomes in children with BA. Primary LDLT and LT after KPE provide equivalent results, although the former is technically more challenging as the child is younger.

The extended Kasai portoenterostomy for biliary atresia: A preliminary report.

AIMS: In 1955, Professor Morio Kasai first performed a hepatic portoenterostomy. Since then, the procedure has changed the lives of children with biliary atresia (BA). We report our initial experience in performing "extended" Kasai portoenterostomy (KPE), a modification of the original procedure. MATERIALS AND METHODS: Since 2013, we have used the technique of "extended KPE" and prospectively recorded data on all children undergoing this operation. Data on demographics, clinical features, liver function tests, and perioperative cholangiogram findings were collected. Outcome of KPE was measured by Jaundice Disappearance Rate (JDR) and Native Liver Survival Rate (NLSR). We present our preliminary results from a 30-month period (February 2013 to May 2015). RESULTS: Thirty-one children underwent KPE during this period (19 males) and only 1 child had biliary atresia splenic malformation (BASM). The mean age at KPE was 73 ± 24 days. Five (16.1%) children were more than 90 days old at the time of KPE. Fourteen children cleared jaundice (JDR 45.2%). Eleven (35.5%) children developed episodes of cholangitis, of whom 8 had early cholangitis (within 3 months of the operation). The proportion of children who survived with their own liver 6 months after KPE (NLSR) was 84.2%. Of those children older than 90 days, 2 cleared jaundice and have survived with their native livers for more than 16 months. CONCLUSION: In our preliminary report of 31 children, we conclude that the extended KPE leads to increased jaundice clearance and improved NLSR in children with BA.

Impact of ductal plate malformation on survival with native liver in children with biliary atresia.

PURPOSE: Ductal plate malformation (DPM) like arrays in the liver which resemble the characteristic persistent embryonal ductular structures have been shown to adversely affect the outcome of Kasai portoenterostomy (KPE) in biliary atresia (BA). We studied the impact of DPM on survival with native liver (SNL) in children with BA who underwent liver transplantation (LT) after KPE as well as those who underwent primary LT without KPE. METHODS: Records of children with BA who underwent LT in our institute were reviewed and divided into three groups-Group 1 had primary LT because of delayed diagnosis of BA and synthetic liver failure, Group 2 had LT for synthetic liver failure after a failed KPE, and Group 3 had LT despite clearing jaundice after KPE for other indications. The impact of DPM on SNL was analyzed using standard statistical means. RESULTS: In Group 1 (n = 26) and Group 2 (n = 26), the incidence of DPM was high and was associated with a significantly shorter SNL compared to children with no DPM. The incidence of DPM was significantly lower in Group 3 (n = 13). CONCLUSION: DPM shortens SNL and influences the pathogenesis of disease progression in children with BA who had synthetic liver failure requiring transplantation either because of a failed KPE or due to a delay in diagnosis. Its incidence is low in children who cleared jaundice after KPE and needed transplantation for other indications at a later age. The presence of DPM signifies an adverse outcome for the disease.

Impact of cancer support groups on childhood cancer treatment and abandonment in a private pediatric oncology centre.

AIMS: To analyze the impact of two cancer support groups in the treatment and abandonment of childhood cancer. MATERIALS AND METHODS: This is a retrospective review of children with cancer funded and non-funded who were treated at Kanchi Kamakoti CHILDS Trust Hospital from 2010 to 2013. A total of 100 patients were funded, 57 by Ray of Light Foundation and 43 by Pediatric Lymphoma Project and 70 non-funded. RESULTS: The total current survival of 80%, including those who have completed treatment and those currently undergoing treatment, is comparable in both the groups. Abandonment of treatment after initiating therapy was not seen in the financially supported group whereas abandonment of treatment after initiation was seen in one child in the non-funded group. CONCLUSIONS: Besides intensive treatment with good supportive care, financial support also has an important impact on compliance and abandonment in all socioeconomic strata of society. Financial support from private cancer support groups also has its impact beyond the patient and family, in reducing the burden on government institutions by non-governmental funding in private sector. Improvement in the delivery of pediatric oncology care in developing countries could be done by financial support from the private sector.

Surgical management of hepatic arterioportal fistula in a neonate.

Congenital arterioportal fistulae in the liver are rare malformations which can lead to portal hypertension. We report a hepatic arterioportal fistula in a neonate who presented with intestinal hypoperfusion. Computerised tomography angiography showed a fistulous communication between the left hepatic artery and portal vein with hypoperfusion of small and large bowel. A formal left hepatectomy was done followed by clinical improvement and reduction in portal venous pressures. The case and the literature pertaining to it are discussed.

The appendix conduit with a conflict of interests - An alternate strategy.

INTRODUCTION: Conventionally the split appendix has been used to address the need for dual conduits such as the Mitrofanoff and the ACE, however limited by its length. We present a video demonstration of an alternate solution. MATERIAL AND METHODS: Size-12 Nelaton catheter introduced via appendicular stump and skirted along the lateral wall of the caecum. Ethicon Endopath 35 mm Linear Stapler was used to create a caecal tube of about 3 cm based on the appendicular stump. RESULTS: From September 2019-January 2023, 6-patients, aged 5-18 years with a diagnoses of 4-spinal dysraphisms, 1-cloacal anomaly, and 1-urogenital sinus were included. FOLLOW UP: 5-45 months. Two patients had ACE site infection which resolved with antibiotics. One developed a stomal granuloma treated effectively with silver nitrate. All are clean with no stomal leaks and experience easy intubation. DISCUSSION: Alternatives to the split appendix include the Monti ACE, and Caecostomy tube/caecal flap when limited by appendicular length. The technique described is easy and quick however care must be taken to keep away from the ileo-caecal junction and to keep the tube length as short as possible or needed to preserve vascularity. CONCLUSIONS: The stapled caecal tube ACE is easy, quick, and safe especially when limited by appendicular length.

Mediastinal hematoma following thrombolysis for acute pulmonary thromboembolism.

Massive pulmonary thromboembolism (PE) is a cardiorespiratory emergency and can be fatal if left untreated. The recommended treatment for PE in the presence of right ventricular dysfunction and hemodynamic instability is thrombolysis. However, the latter is a double-edged sword as life-threatening bleeding manifestations can occur post-thrombolysis. Timely identification and management of these complications can prevent a catastrophic outcome. We report a case of mediastinal hematoma with new onset hemodynamic compromise following thrombolysis for acute massive pulmonary embolism. Clinico-radiological features and Point of Care Ultrasound (POCUS) findings helped in the identification of the bleeding site in our case. Despite early diagnosis and timely intervention, the patient succumbed to secondary complications.