Clinical Profile and Renal Survival of Anti-Glomerular Basement Membrane Disease Patients: A Retrospective Case Series from Northern India.

Introduction: Anti-glomerular basement membrane (anti-GBM) disease is a rare organ-specific autoimmune disease. The overall and renal outcomes of patients have mostly been reported in small-sized cohorts. We aimed to study the clinical profile, overall survival, and renal survival of anti-glomerular basement membrane disease patients at our center. Methods: We conducted a retrospective analysis of the data regarding the clinical profile and renal survival of patients diagnosed with anti-GBM disease from October 2019 to March 2022, having a minimum follow-up of 12 months. Results: There were 15 patients in the study, with the mean age of presentation being 51.6 ± 13.7 years. The median duration of symptoms onset to the nephrologist opinion was 15 (10-23) days. The extrarenal manifestations were seen in the respiratory, otorhinolaryngological, and neurological systems. The mean serum anti-GBM titers were 154.5 (14.9-263.5) U/mL. Serum anti-GBM titers were present in 13/15 (86.6%) patients, and 12/13 (92.3%) patients had above the reference range. Anti-neutrophil cytoplasm antibody (ANCA) levels were assessed in 12/15 (80%) patients, and 9/12 (75%) had higher levels. Renal biopsy was available in 14 patients with more than 50% crescents. Along with crescents, necrotizing lesions, rupture of the Bowman's capsule, and granulomatous lesions were also seen. Among the initial therapies, the steroid pulse was given to 13 (86.6%) patients, whereas membrane plasmapheresis was given to 8 (53.3%) patients. Inj. cyclophosphamide and inj. rituximab were given to 8 (53.3%) and 4 (26.6%) patients, respectively. No difference was seen in clinical characteristics, renal biopsy features, treatment received, and outcomes with ANCA positivity except for age, where patients who were ANCA positive were older compared to patients who were ANCA negative. One-year renal and patient survival was seen in 4 (26.6%) and 6 (40%) patients, respectively. Conclusion: Most patients of anti-GBM disease have active sediments, raised creatinine, and non-specific symptomatology. There is poor renal and patient outcome as most patients present with advanced renal failure.

Outcome of Therapies for Membranous Glomerulonephritis During Three Waves of COVID Pandemic.

There is lack of clarity on immunosuppressive therapy in glomerular diseases and concomitant corona-virus infection. We retrospectively evaluated 36 patients with primary membranous nephropathy from January 2020 to December 2021 who had received immunosuppression during this period. Diagnosis of COVID-19 was made based on self-reported history of being COVID positive. History of hospitalization and oxygen therapy was noted. Four patients developed COVID-19 in this cohort, and all were infected only once. Two patients had asymptomatic disease and two were hospitalized for severe COVID-19 and had complete recovery. In immunocompromised patients, there is a high risk of infection. This observational study is an attempt to bridge the gap that immunosuppression can precipitate COVID-19 infection.

Advances in Shock Management and Fluid Resuscitation in Children.

Shock in children is associated with significant mortality and morbidity, particularly in resource-limited settings. The principles of management include early recognition, fluid resuscitation, appropriate inotropes, antibiotic therapy in sepsis, supportive therapy for organ dysfunction, and regular hemodynamic monitoring. During the past decade, each step has undergone several changes and evolved as evidence that has been translated into recommendations and practice. There is a paradigm shift from protocolized-based care to personalized management, from liberal strategies to restrictive strategies in terms of fluids, blood transfusion, ventilation, and antibiotics, and from clinical monitoring to multimodal monitoring using bedside technologies. However, uncertainties are still prevailing in terms of the volume of fluids, use of steroids, and use of extracorporeal and newer therapies while managing shock. These changes have been summarized along with evidence in this article with the aim of adopting an evidence-based approach while managing children with shock.

Impulse oscillometry (IOS) for detection of exercise induced bronchoconstriction in children with asthma ages 6-15 years.

OBJECTIVES: To determine the discriminatory value of various impulse oscillometry (IOS) parameters, and to find the cutoff value of the appropriate parameter for identifying exercise-induced bronchoconstriction (EIB) in children with asthma. METHODS: This cross-sectional study was conducted in India from October 2016 to March 2018 in children with asthma who were 6-15 years of age. One hundred and five children were enrolled and subjected to pre-exercise IOS and spirometry followed by free running treadmill test as an exercise challenge. All children could achieve minute ventilation >17.5-21 times of FEV1 during the exercise challenge test. Then, IOS and spirometry were performed at 10 ± 2, 20 ± 2, and 30 ± 2 min post-exercise challenge. EIB was defined as reduction of FEV1 ≥10% within 30 min of exercise. For purposes of analysis, the children were grouped into two categories: "EIB Present" or "EIB Absent". RESULTS: The prevalence of EIB in our study was 20.95% (n = 22). ΔR5max percentage within 30 min post-exercise (AUC 0.74; 95% CI: 0.64, 0.84) had the best discriminating capacity among all IOS parameters for identifying EIB. A cutoff value of 14.1% increase in R5 within 30 min post-exercise was obtained for detection of EIB (sensitivity-95.45%, specificity-50.6%, PPV-33.87% and NPV-97.67%). CONCLUSIONS: A percentage change in R5 with a cutoff value of 14.1% increase post-exercise had the best discriminatory capacity among all IOS parameters for detection of EIB in children with asthma. However, low positive predictive value (PPV) with high negative predictive value (NPV) made this cutoff value more apt to rule out EIB.

Clinical and Laboratory Parameters Associated with Septic Myocardial Dysfunction in Children with Septic Shock.

The authors' objective was to determine the association of clinical and laboratory parameters at admission with septic myocardial dysfunction (SMD) in children with septic shock. A chart review of children aged 3 mo-17 y with fluid refractory septic shock who underwent echocardiography within 3 h of admission was undertaken (2015-2017). Univariate followed by multivariate analysis was performed to identify factors associated with SMD. Of the 95 children fulfilling the inclusion criteria, SMD was diagnosed in 44 (46%) children. Children 'with SMD' had longer capillary refill time (CRT), increased lactate, lower platelet count, increased blood urea, and increased alanine aminotransferase (ALT) (p < 0.05 for all) compared to those 'without SMD'. On multivariate analysis, none of these were significant. The mortality rate was higher in those 'with SMD' than 'without SMD' [36% vs. 20% (p = 0.07)]. Prolonged CRT, increased lactate, lower platelet count, increased blood urea and elevated liver enzymes at admission may be associated with SMD in children with septic shock and may warrant early assessment of cardiac function.

Outcomes of Severe PARDS on High-Frequency Oscillatory Ventilation - A Single Centre Experience.

OBJECTIVE: To describe experience with high-frequency oscillatory ventilation (HFOV) in children with acute respiratory distress syndrome (ARDS) transitioned from conventional mechanical ventilation (CMV) due to refractory hypoxemia and to assess factors associated with survival and also compare outcomes of patients who were managed with early HFOV (within 24 h of intubation) vs. late HFOV. METHODS: This retrospective, observational study was conducted in a tertiary care hospital's pediatric intensive care unit. Thirty-four children with pediatric acute respiratory distress syndrome (PARDS) managed with HFOV were included. RESULTS: Of 34 children with PARDS managed with HFOV after failure of conventional ventilation to improve oxygenation, 8 survived. Improvement in the Oxygenation Index (OI) at 48 h of initiation of HFOV along with percent increase in PaO2/FiO2 (P/F ratio) at 24 h of HFOV were predictors of survival. The response to HFOV, based on OI and P/F ratio, between 24 and 48 h of ventilation identified potential survivors. Also, lower positive end-expiratory pressure (PEEP) on CMV and shorter duration of CMV before initiation of HFOV were associated with survival. CONCLUSIONS: Survival in pediatric ARDS patients treated with HFOV could be predicted by using trends of OI - with survivors showing a more rapid decline in OI between 24 and 48 h of initiation compared to non-survivors.

Decreasing the Time to Administration of First Dose of Antibiotics in Children With Severe Sepsis.

OBJECTIVES: To measure difference in median time to antibiotic administration in severe sepsis before and after making process changes and clinical outcomes such as duration of hospitalization and mortality. METHODS: The study was carried out in the emergency department in children <17 years of age with severe sepsis/septic shock. In phase 1, data were collected and reasons for delayed antibiotic administration were identified. Following this, process changes like creating a triage tool, re-enforcing the severe sepsis protocol and increasing the number of nurses were made to correct the delay. In phase 2, we measured outcomes to compare the effect of the process changes. RESULTS: A total of 28 and 13 children each were included during phase 1 and phase 2 of the study respectively. The median interquartile range time to administration of antibiotics from the time of admission decreased significantly from 50 minutes (18, 65) to 20 minutes (15, 20) (p = .02). Duration of hospital stay was longer in phase 1 as compared to phase 2 (12 days vs. 6 days). However, the difference was not statistically significant (p = .1). CONCLUSIONS: Use of a triage tool, severe sepsis protocol, and increasing the number of nurses resulted in earlier recognition and administration of first dose of antibiotics in children with severe sepsis.

Antimicrobial Therapy in Community-Acquired Pneumonia in Children.

PURPOSE OF REVIEW: Empirical antibiotic therapy remains the cornerstone of treatment in community-acquired pneumonia (CAP). However, the best option for empirical antibiotics for treatment on an ambulatory basis, as well as in those requiring hospitalization, is still unclear. This review tries to answer the question regarding the most appropriate antibiotics in different settings in children with CAP as well as duration of therapy. RECENT FINDINGS: Recent studies have provided insights regarding use of oral antibiotics in children with mild to moderate CAP, and severe CAP with lower chest retractions but no hypoxia. In view of rapidly emerging resistance among various causative pathogens, several new drugs have been currently approved, or are under trial for CAP in children. Current knowledge suggests that the choice of antibiotics for ambulatory treatment of CAP is oral amoxicillin with a duration of 3-5 days. Children with CAP with lower chest retractions but no hypoxia can be treated with oral amoxicillin. Severe pneumonia can be treated with intravenous antibiotics consisting of penicillin/ampicillin with or without an aminoglycoside. Several new drugs have been developed and approved for use in CAP caused by multidrug-resistant organisms, but these should be used judiciously to avoid emergence of further resistance. Future research is needed regarding the safety and efficacy of newer drugs in children.

Comparison of Prevalence and Outcomes of Pediatric Acute Respiratory Distress Syndrome Using Pediatric Acute Lung Injury Consensus Conference Criteria and Berlin Definition.

OBJECTIVES: Our objective was to compare the prevalence and outcomes of pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference (PALICC) criteria and Berlin definitions. METHODS: We screened case records of all children aged 1 month to 17 years of age admitted to the Pediatric Intensive Care Unit (PICU) over a 3-year period (2015-2017) for presence of any respiratory difficulty at admission or during PICU stay. We applied both PALICC and Berlin criteria to these patients. Data collection included definition and outcome related variables. Data were compared between the "PALICC only group" and the "Berlin with or without PALICC" group using Stata 11. RESULTS: Of a total of 615 admissions, 246 were identified as having respiratory difficulty at admission or during PICU stay. A total of 61 children (prevalence 9.9%; 95% CI: 7.8-12.4) fulfilled the definition of acute respiratory distress syndrome (ARDS) with either of the two criteria. While 60 children (98%) fulfilled PALICC criteria, only 26 children (43%) fulfilled Berlin definition. There was moderate agreement between the two definitions (Kappa: 0.51; 95% CI: 0.40-0.62; observed agreement 85%). Greater proportion of patients had severe ARDS in the "Berlin with or without PALICC group" as compared to the "PALICC only" group (50 vs. 19%). There was no difference between the groups with regard to key clinical outcomes such as duration of ventilation (7 vs. 8 days) or mortality [51.4 vs. 57.7%: RR (95% CI): 0.99 (0.64-1.5)]. CONCLUSION: In comparison to Berlin definition, the PALICC criteria identified more number of patients with ARDS. Proportion with severe ARDS and complications was greater in the "Berlin with or without PALICC" group as compared to the "PALICC only" group. There were no differences in clinical outcomes between the groups.

Asthma, GERD and Obesity: Triangle of Inflammation.

There is increasing prevalence of both asthma and obesity in children globally in recent years. Various epidemiological studies link obesity as a risk factor for asthma and suggest a possible causal association. Obesity asthma phenotype is considered as distinct in view of greater severity and poor asthma control. Various mechanisms underlying this phenotype have been suggested including mechanical effects of obesity and systemic inflammation, but still the exact mechanism is unclear. Also, the comorbidities like gastroesophageal reflux disease (GERD) and sleep disordered breathing (SDB) lead to inflammation in airways and contribute to asthma obesity association. A better understanding of mechanisms by which obesity and GERD lead to inflammation in airways and increase the risk of asthma may provide insight towards targeted treatment approach of these patients.

Assessment of Musculoskeletal Function and its Correlation with Radiological Joint Score in Children with Hemophilia A.

OBJECTIVE: To evaluate the functional independence of children with hemophilia A and its correlation to radiological joint score. METHODS: The present cross sectional study was conducted at SPMCHI, SMS Medical College, Jaipur, India. Children in the age group of 4-18 y affected with severe, moderate and mild hemophilia A and with a history of hemarthrosis who attended the OPD, emergency or got admitted in wards of SPMCHI, SMS Medical College were examined. Musculoskeletal function was measured in 98 patients using Functional Independence Score in Hemophilia (FISH) and index joints (joints most commonly affected with repeated bleeding) were assessed radiologically with plain X rays using Pettersson score. RESULTS: The mean FISH score was 28.07 ± 3.90 (range 17-32) with squatting, running and step climbing as most affected tasks. The mean Pettersson score was 3.8 ± 3.2. A significant correlation was found between mean Pettersson score and FISH (r = -0.875, P < 0.001) with knee and elbow having r = -0.810 and -0.861 respectively, but not in case of ankle with r = -0.420 (P 0.174). CONCLUSIONS: The FISH and radiological joint (Pettersson's) scores may be extremely useful in the clinical practice in the absence of magnetic resonance imaging (MRI), which is considered very sensitive to detect early joint damage, but at a cost that makes it relatively inaccessible. FISH seems to be a reliable tool for assessment of functional independence in patients with hemophilia A.