Risk Factors for Procedural Complications of Pediatric Flexible Bronchoscopy: Experience From a Tertiary Care Centre in Northern India.

We analyzed the records of 869 children who underwent flexible bronchoscopy. We found procedural complications in 6.7% (n = 59), with severe events in 3.2% (n = 28). Age < 1 y, recurrent respiratory papillomatosis, and finding lower airway malacia on bronchoscopy were identified as independent risk factors for developing complications with adjusted odds ratio (95% CI) of [2.6 (1.3, 4.9); P = 0.004], [5.4 (1.7, 17.6); P = 0.005] and [2.1 (1.1, 4.0); P = 0.031], respectively.

Furosemide stress test to predict acute kidney injury progression in critically ill children.

BACKGROUND: Furosemide stress test (FST) is a novel functional biomarker for predicting severe acute kidney injury (AKI); however, pediatric studies are limited. METHODS: Children 3 months to 18 years of age admitted to the intensive care unit (ICU) of a tertiary care hospital from Nov 2019 to July 2021 were screened and those who developed AKI stage 1 or 2 within 7 days of admission underwent FST (intravenous furosemide 1 mg/kg). Urine output was measured hourly for the next 6 h; a value > 2 ml/kg within the first 2 h was deemed furosemide responsive. Other biomarkers like plasma neutrophil gelatinase-associated lipocalin (NGAL) and proenkephalin (PENK) were also evaluated. RESULTS: Of the 480 admitted patients, 51 developed AKI stage 1 or 2 within 7 days of admission and underwent FST. Nine of these patients were furosemide non-responsive. Thirteen (25.5%) patients (eight of nine from FST non-responsive group) developed stage 3 AKI within 7 days of FST, nine (17.6%) of whom (seven from non-responsive group) required kidney support therapy (KST). FST emerged as a good biomarker for predicting stage 3 AKI and need for KST with area-under-the-curve (AUC) being 0.93 ± 0.05 (95% CI 0.84-1.0) and 0.96 ± 0.03 (95% CI 0.9-1.0), respectively. FST outperformed NGAL and PENK in predicting AKI stage 3 and KST; however, the combination did not improve the diagnostic accuracy. CONCLUSIONS: Furosemide stress test is a simple, inexpensive, and robust biomarker for predicting stage 3 AKI and KST need in critically ill children. Further research is required to identify the best FST cut-off in children.

Infant Pulmonary Function Tests in Children with Airway Anomalies and Correlation with Bronchoscopy Findings.

OBJECTIVES: To evaluate the role infant pulmonary function tests (Tidal Breathing Flow Volume Loops, TBFVL) in children with airway anomalies and to correlate the TBFVL so obtained with bronchoscopy findings. METHODS: In this prospective cohort study, we enrolled children aged 0-2 years with airway anomalies and performed TBFVL and bronchoscopy. The primary outcome measure was graphic pattern of TBFVL in laryngomalacia. Secondary outcome measures were types of TBFVL results in various airway anomalies and controls. RESULTS: Out of 53 children enrolled, 28 (52.3%) had laryngomalacia. Pattern 3 (fluttering of inspiratory limb) was commonest TBFVL pattern in laryngomalacia. Among TBFVL parameters, the ratio of inspiratory time to expiratory time (Ti/Te) and tPTEF/tE was significantly high in children with isolated laryngomalacia compared to controls. At six months of follow-up, TBFVL pattern 1 (normal) became the commonest pattern. CONCLUSION: A particular type of airway anomaly may have a characteristic graphic pattern in TBFVL and TBFVL pattern may indicate improvement in airway anomalies in follow-up.

Knowledge, attitude, and practices among caregivers of children with Cystic Fibrosis.

BACKGROUND: Caregivers have crucial role in the care of the children with Cystic Fibrosis (CF), but there is limited knowledge about their knowledge, attitude, and practices (KAP) regarding chronic disease. This pilot study aimed to validate a self-developed KAP questionnaire for caregivers of young children with CF in India and determine factors associated with KAP. MATERIALS AND METHODS: A cross-sectional study was conducted among 95 caregivers of children with CF attending the specialty clinic of the pediatric outpatient department (OPD) in Northern India. Participants possessing certain characteristics such as willingness to participate and ability to understand Hindi or English language were enrolled in the study. Caregivers of children reported to the OPD with acute exacerbation requiring immediate hospitalization were excluded from the study. RESULTS: The self-developed KAP questionnaire had good content validity (CVI- 0.87-1.0) and internal consistency (Cronbach's α coefficient = 0.70, 0.71, 0.75 respectively). The majority of participants belonged to the Good KAP group (85.3%), while the remaining were in the Poor KAP group (14.7%). A χ2 test showed that KAP clusters vary significantly with sociodemographic variables like gender, marital status, educational status and monthly family income (p < .05). A weak negative correlation was found between knowledge and attitude scores in the Good KAP group (p < .001). Multiple linear regression analysis showed that the KAP of the caregivers was significantly influenced by knowledge related to clinical manifestation and complications, and attitude. CONCLUSION: All three sections of the KAP tool demonstrated good content validity and internal consistency. Caregivers had good knowledge, a positive attitude, and appropriate practices related to CF. However, targeted interventions are necessary to address specific areas for improvement, particularly for male caregivers with lower educational levels belonging to poor socioeconomic strata.

A randomized controlled trial to explore the safety and efficacy of irradiated buffy-coat granulocytes in pediatric patients with febrile neutropenia.

BACKGROUND: Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS: Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS: Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm3 in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION: Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.

Microsporidia in HIV-Positive and HIV-Negative Pediatric Patients with Diarrhea at a Tertiary Care Hospital.

Background Human microsporidiosis presents as an important and rapidly emerging opportunistic infection. However, the exact burden of this infection especially in the pediatric population of Northern India remains unknown. In this study, we investigated the prevalence of microsporidia among human immunodeficiency virus (HIV)-positive and HIV-negative pediatric patients who presented with diarrhea. Methods A total of 263 children were recruited consisting of 98 HIV seropositive with diarrhea and 165 HIV seronegative but with diarrhea. Morning stool samples were collected and both direct and formol ether concentrated samples were examined for the presence of intestinal parasites. The modified acid-fast staining was done for coccidian parasites and trichrome stain for microsporidia detection. Further, the species were detected using a real-time polymerase chain reaction (PCR) targeting a conserved region of the small ribosomal subunit rRNA gene of Enterocytozoon bieneusi , Encephalitozoon hellem , Encephalitozoon intestinalis , and Encephalitozoon cuniculi . Results Overall, one or more parasites were detected in 52.04% (51/98) of HIV seropositive and 53.33% (88/165) of seronegative children ( p = 0.8391). However, coccidian parasites were detected in a significantly huge number of HIV seropositive children (21.43% [21/98]) as compared with HIV seronegative children (4.24% [7/165]). Microsporidial DNA could be detected in HIV seropositive with diarrhea children (17.35% [17/98]) by PCR. A significant correlation between low CD4 count (≤ 200/µL) and intestinal parasite positivity could be established. Conclusion Microsporidia is a significant cause of diarrhea in HIV seropositive pediatric patients and should be kept in mind as one of the differential diagnoses in such patients.

Debate 1: Is the Management of Childhood Empyema Primarily Medical, or Surgical?

This review aims to discuss the role of medical and surgical therapy in the management of pediatric empyema. There is considerable debate on the optimal treatment for the same. Early intervention is crucial as it allows rapid recovery of these patients. Antibiotics and adequate pleural drainage form the two pillars in the management of empyema. Chest tube drainage alone has significant failure rates due to its inability to clear loculated effusion. The two main modalities which target these loculations to augment drainage are video-assisted thoracoscopic surgery (VATS) and intrapleural fibrinolytic therapy. The latest evidence shows that both these interventions are equally effective. Children who present late are usually not candidates for intrapleural fibrinolytic therapy or VATS; for them, decortication remains the only option.

Utility of Inferior Vena Cava Distensibility and Respiratory Variation in Peak Aortic Blood Flow Velocity to Predict Fluid Responsiveness in Children with Shock.

OBJECTIVES: To evaluate the sensitivity and specificity of inferior vena cava (IVC) distensibility index (∆IVC) and respiratory variation in peak aortic blood flow velocity (∆Vpeak) to predict fluid responsiveness in ventilated children with shock and to find out the best cut-off values for predicting fluid responsiveness. METHODS: In this prospective observational study, conducted in a pediatric ICU from January 2019 through May 2020, consecutive children aged 2 mo to 17 y with shock requiring fluid bolus were included. ∆IVC and ∆Vpeak were measured before and immediately after 10 ml/kg fluid bolus administration. ∆IVC and ∆Vpeak were compared between responders and non-responders, defined by a change in stroke volume index (SVI) of ≥10%. RESULTS: Thirty-seven ventilated children [26 (70.4%) boys] with median age of 60 (36, 108) mo were included. The median (IQR) ∆IVC was 21.7% (14.3, 30.9) and the median (IQR) ΔVpeak was 11.3% (7.2, 15.2). Twenty-three (62%) children were fluid responsive. The median (IQR) ∆IVC was higher in responders compared to non-responders [26% (16.9, 36.5) vs. 17.2% (8.4, 21.9); p = 0.018] and mean (SD) ΔVpeak was higher in responders [13.9% (6.1) vs. 8.4% (3.9), p = 0.004]. The prediction of fluid responsiveness with ΔIVC [ROC curve area 0.73 (0.56-0.9), p = 0.01] and ΔVpeak [ROC curve area 0.78 (0.63-0.94), p = 0.002] was similar. The best cut-off of ∆IVC to predict fluid responsiveness was 23% (sensitivity, 60.8%; specificity, 85.7%) and ΔVpeak was 11.3% (sensitivity, 74%; specificity, 86%). CONCLUSIONS: In this study, authors found that ∆IVC and ΔVpeak were good predictors of fluid responsiveness in ventilated children with shock.

Survival of Persons Living With HIV/AIDS: A Multicentric Study From India.

BACKGROUND: It has been more than 17 years since the introduction of free ART in India. At this point, it would be prudent to look at the factors associated with the survival of persons living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLHA) who are already enrolled in the ART program. METHODS: PLHAs enrolled from antiretroviral therapy (ART) centers located in three different cities in India - Delhi, Pune and Kolkata, and were followed up at six monthly intervals monitoring the WHO stage, CD4 counts, complete blood counts, and liver and kidney function tests, for a duration of three years. RESULTS AND DISCUSSION: The incidence of mortality among HIV/AIDS patients on ART was 5.0 per 1000 patient-years (21/1410, 1.4%). Age at initiation of ART, being above 35 years, was the only significant predictor of mortality (log-rank p = 0.018). Multivariable analysis showed a significant association of an unfavourable outcome (defined as mortality or development of opportunistic infection during follow-up) with male gender (adjusted odds ratio (AOR) = 5.26, p = <0.01) and being unmarried at ART initiation (AOR = 1.39, p = 0.005). CONCLUSION: The survival of PLHA with good adherence to ART is independent of the WHO stage or CD4 counts at the initiation of ART. Initiation of ART after 35 years of age was a significant predictor of mortality.

Feasibility and Efficacy of Sustained Low-Efficiency Dialysis in Critically Ill Children with Severe Acute Kidney Injury.

OBJECTIVES: To examine the feasibility, efficacy, and safety of sustained low-efficiency dialysis (SLED) in hemodynamically unstable, critically ill children. METHODS: Critically ill patients, 1-18 y old with hemodynamic instability (≥ 1 vasoactive drugs) and severe acute kidney injury (AKI) requiring kidney replacement therapy (KRT) in a tertiary care pediatric intensive care unit were prospectively enrolled. Patients weighing ≤ 8 kg or with mean arterial pressure < 5th percentile despite > 3 vasoactive drugs, were excluded. Patients underwent SLED until hemodynamically stable and off vasoactive drugs, or lack of need for dialysis. The primary outcome was the proportion of patients in whom the first session of SLED was initiated within 12 h of its indication and completed without premature (< 6 h) termination. Efficacy was estimated by ultrafiltration, urea reduction ratio (URR), and equilibrated Kt/V. Other outcomes included: changes in hemodynamic scores, circuit clotting, adverse events, and changes in indices on point-of-care ultrasonography and echocardiography. RESULTS: Between November 2018 and March 2020, 18 patients with median age 8.6 y and vasopressor dependency index of 83.2, underwent 41 sessions of SLED. In 16 patients, SLED was feasible within 12 h of indication. No session was terminated prematurely. Ultrafiltration achieved was 4.0 ± 2.2 mL/kg/h, while URR was 57.7 ± 16.2% and eKt/V 1.17 ± 0.56. Hemodynamic scores did not change significantly. Asymptomatic hypokalemia was the chief adverse effect. Sessions were associated with a significant improvement in indices on ultrasound and left ventricular function. Fourteen patients died. CONCLUSIONS: SLED is feasible, safe, and effective in enabling KRT in hemodynamically unstable children with severe AKI.

Generation of a Large Repertoire of Monoclonal Antibodies against Dengue Virus NS1 Antigen and the Development of a Novel NS1 Detection Enzyme-Linked Immunosorbent Assay.

Commercial dengue virus (DENV) nonstructural-1 (NS1) Ag detection immunoassays often perform poorly, particularly in secondary DENV infection. To develop a highly sensitive NS1 ELISA, we generated a large repertoire of anti-DENV NS1 mouse mAbs (n = 95) that falls into 36 mAb classes based on binding specificities. The identified mAb pair, capable of efficiently detecting NS1 from four DENV serotypes in an immunoassay, was selected based on multiparametric analysis. The selected mAbs have subnanomolar affinities for NS1 with recognition sites outside the immunodominant wing domain. The assay was converted to an ELISA kit, which showed higher analytical sensitivity (3-fold to 83-fold) for NS1 from four DENV serotypes than commercial Platelia NS1 ELISA (Bio-Rad Laboratories). Compared to RT-PCR, the developed NS1 ELISA showed 78.57% (66 of 84) sensitivity, whereas Platelia NS1 ELISA showed a sensitivity of 60.71% (51 of 84). In a subgroup of RT-PCR-positive secondary dengue samples, our ELISA showed a sensitivity of 70.18% (40 of 57), whereas Platelia ELISA detected only 47.37% (27 of 57) samples. Furthermore, unlike Platelia ELISA, our test equally detected NS1 from four serotypes; Platelia ELISA performed poorly for the DENV-2 serotype, in which only 8 of 21 (38.10%) samples were detected compared with 17 of 21 (80.95%) in our ELISA. Moreover, our ELISA showed 100% specificity in 342 challenging dengue-negative samples. The large and diverse mAb repertoire generated against DENV NS1 and the appropriate selection of mAbs allowed us to establish an ELISA that can efficiently detect NS1 Ag even in secondary dengue and without serotype level bias.

Development of algorithm for diagnosis of cystic fibrosis in absence of sweat chloride testing in resource-limited setting.

OBJECTIVE: To develop a diagnostic algorithm for cystic fibrosis (CF) in the setting of unavailability of sweat chloride, based on clinical features and basic laboratory investigations. METHODS: In a prospective observational study, we enrolled children with recurrent/persistent pneumonia with either malabsorption or poor growth, undergoing a sweat chloride test, between January 2019 and December 2020. They were simultaneously evaluated for aquagenic wrinkling of hands, stool fat globules, sputum for bacterial culture, blood gas, and serum electrolytes. Sensitivity and specificity were calculated for parameters having a significant difference between CF and non-CF groups. Scoring systems and algorithms for the diagnosis of CF were developed. RESULTS: Of 134 children enrolled, 46 (34%) had CF. The sensitivity and specificity of various parameters to diagnose CF was: sibling death due to respiratory illness (30.43%, 96.59%), aquagenic wrinkling (76.74%, 47.67%), metabolic alkalosis (17.78%, 94.12%), hyponatremia (28.89%, 89.41%), stool fat globules (38.46%, 81.18%), and presence of Pseudomonas in sputum culture (23.68%, 98.80%). Using coefficients of significant parameters on stepwise logistic regression, the composite score for diagnosis of CF was calculated as: 3X sibling death due to respiratory illness + 1.5X hyponatremia + 1.5X metabolic alkalosis + 1.5X aquagenic wrinkling + 1X stool fat globules + 2.5X presence of Pseudomonas in sputum culture (each of the variables scores 0 or 1 for absence and presence, respectively). The cut-off of ≥2.5 had sensitivity and specificity of 81.82% and 76.83%, respectively. CONCLUSIONS: In resource-limited settings, the proposed diagnostic algorithm can be used for the diagnosis of presumptive CF with fair sensitivity and specificity.

Allergic Bronchopulmonary Aspergillosis in Children Presenting as Lung Masses.

Allergic bronchopulmonary aspergillosis (ABPA) is an IgE-mediated hypersensitivity reaction predominantly occurring in patients of asthma and cystic fibrosis. The typical radiological findings in ABPA include central bronchiectasis and fleeting opacities. In this retrospective study, the aim was to describe cases of ABPA in children who had a mass-like lesion in the lung. There were 5 cases of ABPA in children, who presented as mass-like lesions that responded very well to treatment for ABPA. All cases, except 1, had asthma as the underlying disease. There was a delay in the diagnosis of ABPA in all 5 cases. There had been unnecessary invasive investigations in some of these cases before the diagnosis of ABPA was made. To conclude, children with ABPA may present with a mass-like lesion in the lung and high index of suspicion is required to diagnose ABPA timely to prevent its consequences.

A survey of pediatric flexible bronchoscopy in India.

BACKGROUND: A bronchoscopy is an essential tool in pediatric pulmonology. However, the practices involved in the procedure are variable. OBJECTIVE: To evaluate prevalent practices and variations in pediatric flexible bronchoscopy in India. METHODS: An online survey was conducted via Google forms between September 2018 and March 2019. We circulated the survey among members of various respiratory societies and personal contacts. Physicians performing pediatric flexible bronchoscopy were requested to respond. The survey had 95 questions in seven domains: demographics, patient preparation, sedation, procedural aspects, monitoring, bronchoscope cleaning, and complications. RESULTS: The survey received 24 complete responses; the respondents were from 14 cities. Pediatric bronchoscopy was done mainly for diagnostic purposes. Most (19, 79%) respondents reported using conscious sedation for the procedure. The preferred regimen for sedation was midazolam plus fentanyl [9 (37.5%)]. Atropine was used routinely by 4 (16%). For topical anesthesia, nebulized lignocaine only, both nebulized and spray as go lignocaine, and spray as go lignocaine only were used by 1 (4.2%), 6 (25%), and 17 (71%) respondents, respectively. The methods of providing oxygen during bronchoscopy were free flow (9, 37.5%), nasal prongs (8, 33.3%), mask (6, 25%), and laryngeal mask airway (1, 4.2%). The common therapeutic procedures included removal of mucus plugs (17, 71%), bronchoscopic intubation (11, 45%), and foreign body removal (10, 41%). The number of aliquots used by respondents for bronchoalveolar lavage varied from 2 to 6, and the volume for each aliquot was also varied (1-2 ml/kg or 5-10 ml). Almost all the respondents reported complication rates of less than 5%. CONCLUSION: There is a considerable variation in pediatric flexible bronchoscopy practices across the country, highlighting the need to develop a uniform guideline.

A Century With Craniopagus Twin Separation Surgeries: Nihilism to Optimism.

Craniopagus conjoined twins are extremely rare, reported 1 in 2.5 million live births. To date, 62 separation attempts in 69 well-documented cases of craniopagus twins have been made. Of these, 34 were performed in a single-stage approach, and 28 were attempted in a multistage approach. One or both twins died of massive intraoperative blood loss and cardiac arrest in 14 cases. We report our surgical experience with conjoined craniopagus twins (JB) with type III total vertical joining and shared circumferential/circular sinus with left-sided dominance. A brief review of the literature is also provided. In our twins, the meticulous preoperative study and planning by the multidisciplinary team consisting of 125-member, first-staged surgical separation consisted of creation of venous conduit to bypass part of shared circumferential sinus and partial hemispheric disconnection. Six weeks later, twin J manifested acute cardiac overload because of one-way fistula development from blocked venous bypass graft necessitating emergency final separation surgery. Unique perioperative issues were abnormal anatomy, hemodynamic sequelae from one-way fistula development after venous bypass graft thrombosis, cardiac arrest after massive venous air embolism requiring prolonged cardiopulmonary resuscitation, and return of spontaneous circulation at 15 minutes immediately after separation. This is the first Indian craniopagus separation surgery in a complex total vertical craniopagus twin reported by a single-center multidisciplinary team. Both twins could be sent home, but one remained severely handicapped. Adequate perioperative planning and multidisciplinary team approach are vital in craniopagus twin separation surgeries.

Identification of Human Case of Avian Influenza A(H5N1) Infection, India.

A 11-year-old boy with acute myeloid leukemia was brought for treatment of severe acute respiratory infection in the National Capital Region, New Delhi, India. Avian influenza A(H5N1) infection was laboratory confirmed. Complete genome analysis indicated hemagglutinin gene clade 2.3.2.1a. We found the strain to be susceptible to amantadine and neuraminidase inhibitors.

Role of procalcitonin in diagnosis of community acquired pneumonia in Children.

BACKGROUND: The role of serum Procalcitonin (PCT) in adults in diagnosis of Community acquired pneumonia (CAP) is well established, however, role in pediatric CAP remains controversial. OBJECTIVES: The objective of this study was to investigate the utility of serum procalcitonin in differentiating bacterial community-acquired lower respiratory tract infection from non-bacterial respiratory infection in children; radiologically confirmed pneumonia was used as the reference. In addition, we assessed the utility of adding the PCT assay to the clinical criteria for diagnosis of pneumonia. STUDY DESIGN: Subanalysis of a larger prospective,multicentriccohort study. PARTICIPANTS: Children, 2 months to 59 months of age, attending paediatric OPD of 5 urban tertiary care hospitals, suffering from acute respiratory infection (ARI). INTERVENTION: Detailed clinical history and examination findings of enrolled children were recorded on predesigned case record form. Samples for PCT were obtained at admission and were measured centrally at the end of the study except for one site using VIDAS® B.R.A.H.M.S PCT kit (Biomerieux SA, France). OUTCOMES: Sensitivity and specificity of procalcitonin for diagnosis of radiologically confirmed pneumonia. RESULTS: Serum Procalcitonin was measured in 370 patients; median (IQR) age of these children being 12 (7, 22) months, 235 (63.5%) were boys. The median (IQR) serum procalcitonin concentration was 0.1(0.05, 0.4) ng/mL.Sensitivity and specificity of raised PCT (> 0.5 ng/mL) for pneumonia as per any CXR abnormalities were 29.7% and87.5%,(P < 0.001) respectively. Raised PCT was also significantly associated with consolidation (34.5%,79.2%,P < 0.02)and pleural effusion(54.6%,79%,P < 001). Adding PCT to the existing clinical criteria of WHO did not improve the sensitivity for diagnosis of pneumonia. PCT was significantly higher in children with severe pneumonia. CONCLUSION: Positive PCT (> 0.5 ng/mL) is significantly associated with radiographic pneumonia but not with pneumonia based on WHO criteria.However, it can act as a surrogate marker for severe pneumonia.