Comparison of growth patterns in the first year of life between term small for gestational age and appropriate for gestational age South Indian infants.

BACKGROUND: Early life growth trajectories of Indian small for gestational age (SGA) infants are sparse. This study aimed to compare longitudinal growth in appropriate for gestational age (AGA) and SGA infants during their first year of life. METHODS: Apparently healthy term infants (52 SGA, 154 AGA) were recruited at birth and followed up till 1 year. Parental, sociodemographic characteristics and feeding patterns were recorded. Anthropometric measurements were assessed at birth, 3, 6, 9 and 12 months of age; Z scores and growth velocity at 3-month intervals were computed. Longitudinal measurements were compared between the two groups, using the two-way Friedmans test. Median regression with mixed effects was used to adjust covariates; p value <0.05 was considered statistically significant. RESULT: AGA infants had significantly higher median weight (kg) (2.87 (2.67, 3.04) vs 2.39 (2.25, 2.54)) at birth, (7.08 (6.50, 7.54) vs 6.49 (6.13, 6.78)) at 6 months, (8.64 (7.92, 9.14) vs 7.90 (7.36, 8.54)) at 12 months, median length (cm) ((48.10 (47.20, 49.30) vs 46.75 (45.43, 47.50)) at birth, (65.50 (64.23, 66.98) vs 63.33 (62.26, 65.28)) at 6 months, (73.30 (71.58, 74.66) vs 71.55 (70.00, 73.30)) at 12 months. SGA infants had comparable weight velocity at all intervals except 9-12 months (6.62 (6.45, 6.79) vs (6.70 (6.51, 6.85)), being significantly higher than AGA infants. Differences in skinfold thicknesses between groups were observed only at birth. Exclusivity of breast feeding was significantly higher at 3 months in AGA, compared to SGA infants (80.9% vs 57.8%). Length velocity was comparable at all ages between groups. Sexual dimorphism was observed in the growth velocities of both groups. CONCLUSION: SGA infants grew in parallel to AGA infants, having significantly lower anthropometric measurements at all time points. However, growth velocities were similar; SGA infants had significantly higher weight velocity from 9 to 12 months. Longitudinal studies beyond 1 year of age, using body composition are needed to determine the quality of growth in Indian infants.

Blood tumor mutational burden and response to pembrolizumab plus chemotherapy in non-small cell lung cancer: KEYNOTE-782.

BACKGROUND: First-line pembrolizumab plus chemotherapy has shown clinical benefit in patients with metastatic non-small cell lung cancer (NSCLC) regardless of tissue tumor mutational burden (tTMB) status. Blood tumor mutational burden (bTMB), assessed using plasma-derived circulating tumor DNA (ctDNA), may be a surrogate for tTMB. The KEYNOTE-782 study evaluated the correlation of bTMB with the efficacy of first-line pembrolizumab plus chemotherapy in NSCLC. METHODS: Previously untreated patients with stage IV nonsquamous NSCLC received pembrolizumab 200 mg plus pemetrexed 500 mg/m2 and investigator's choice of carboplatin area under the curve 5 mg/mL/min or cisplatin 75 mg/m2 for 4 cycles, then pembrolizumab plus pemetrexed for ≤31 additional cycles every 3 weeks. Study objectives were to evaluate the association of baseline bTMB with objective response rate (ORR) (RECIST v1.1 by investigator assessment; primary), progression-free survival (PFS; RECIST v1.1 by investigator assessment), overall survival (OS), and adverse events (AEs; all secondary). A next-generation sequencing assay (GRAIL LLC) with a ctDNA panel that included lung cancer-associated and immune gene targets was used to measure bTMB. RESULTS: 117 patients were enrolled; median time from first dose to data cutoff was 19.3 months (range, 1.0-35.5). ORR was 40.2 % (95 % CI 31.2-49.6 %), median PFS was 7.2 months (95 % CI 5.6-9.8) and median OS was 18.1 months (95 % CI 13.5-25.6). Treatment-related AEs occurred in 113 patients (96.6 %; grade 3-5, n = 56 [47.9 %]). Of patients with evaluable bTMB (n = 101), the area under the receiver operating characteristics curve for continuous bTMB to discriminate response was 0.47 (95 % CI 0.36-0.59). Baseline bTMB was not associated with PFS or OS (posterior probabilities of positive association: 16.8 % and 7.8 %, respectively). CONCLUSIONS: AEs were consistent with the established safety profile of first-line pembrolizumab plus chemotherapy in NSCLC. Baseline bTMB did not show evidence of an association with efficacy.

The beneficial effect of early and prolonged kangaroo mother care on long-term neuro-developmental outcomes in low birth neonates - A cohort study.

AIM: Kangaroo mother care (KMC) has immense short-term benefits, but data on long-term outcomes are scarce. Hence, this study aimed to compare the neurodevelopmental outcomes at 12 months of corrected age (CA) in infants <2000 g receiving early and prolonged KMC to a control group. METHODS: This was a cohort study that was conducted from January 2017 to November 2018. All neonates<2000 g were eligible for the study. Neonates that received early initiation (<72 h of life) and prolonged KMC comprised the intervention group and were compared to neonates without the intervention. Bayley Scales of Infant and Toddler Development, Third edition (BSID-III) was done at 12 months of CA, and this was analysed using t-test and multi-linear regression analysis. RESULTS: There were 75 neonates in the intervention and 69 in the control group. Baseline characteristics were comparable. We found higher composite scores for cognition (110.38 ± 9.89 vs. 105.44 ± 8.77, p value = 0.023), language (107.51 ± 10.72 vs. 101.05 ± 12.06, p value = 0.014) and adaptive behaviour (87.97 ± 9.97 vs. 80 ± 9.1, p value<0.001) in the early and prolonged KMC group in comparison to the control group. CONCLUSION: Infants with early and prolonged KMC have better neurodevelopmental outcomes in terms of cognition, language and adaptive behaviour at 12 months of CA.

Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study.

Background: It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India. Methods: Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, 'unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings: Among 2468 eligible children enrolled, 2148 were hospitalised. Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18.6%), severe acute COVID-19 (13.3%) and the unclassified severe COVID-19 disease (12.3%). Mortality remained high (17.5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14.1% mortality when associated with comorbidity. Interpretation: Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding: Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva, Switzerland.

Effect on neonatal sepsis following immediate kangaroo mother care in a newborn intensive care unit: a post-hoc analysis of a multicentre, open-label, randomised controlled trial.

Background: To implement the immediate Kangaroo mother care (iKMC) intervention in the previous multicentre, open-label, randomised controlled trial, the mother or a surrogate caregiver and neonate needed to be together continuously, which led to the concept of the Mother-Newborn Care Unit (MNCU). Health-care providers and administrators were concerned of the potential increase in infections caused by the continuous presence of mothers or surrogates in the MNCU. We aimed to assess the incidence of neonatal sepsis in sub-groups and the bacterial profile among intervention and control neonates in the study population. Methods: This is a post-hoc analysis of the previous iKMC trial, which was conducted in five level 2 Newborn Intensive Care Units (NICUs) one each in Ghana, India, Malawi, Nigeria, and Tanzania, in neonates with birth weight 1 to <1.8 kg. The intervention was KMC initiated immediately after birth and continued until discharge and compared to conventional care with KMC initiated after meeting stability criteria. The primary outcomes of this report were the incidence of neonatal sepsis in sub-groups, sepsis-related mortality and bacterial profile of isolates during hospital stay. The original trial is registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12618001880235) and the Clinical Trials Registry-India (CTRI/2018/08/01536). Findings: Between November 30, 2017, and January 20, 2020, 1609 newborns in the intervention group and in the control group 1602 newborns were enrolled in iKMC study. 1575 newborns in the intervention group and 1561 in the control group were clinically evaluated for sepsis. Suspected sepsis was 14% lower in intervention group in sub-group of neonates with birth weight 1.0-<1.5 kg; RR 0.86 (CI 0.75, 0.99). Among neonates with birth weight 1.5-<1.8 kg, suspected sepsis was reduced by 24%; RR 0.76 (CI 0.62, 0.93). Suspected sepsis rates were lower in intervention group than in the control group across all sites. Sepsis related mortality was 37% less in intervention group than the control group; RR 0.63 (CI 0.47-0.85) which was statistically significant. The intervention group had fewer cases of Gram-negative isolates (n = 9) than Gram positive isolates (n = 16). The control group had more cases of Gram-negative isolates (n = 18) than Gram positive (n = 12). Interpretation: Immediate Kangaroo Mother care is an effective intervention to prevent neonatal sepsis and sepsis related mortality. Funding: The original trial was funded by the Bill and Melinda Gates Foundation through a grant to the World Health Organization (grant No. OPP1151718).

Target product profile: aerosolized surfactant for neonatal respiratory distress.

Treatment with surfactant has been found to improve the survival rate of neonates with respiratory distress syndrome, particularly preterm infants. However, surfactant is usually administered by endotracheal intubation and generally only in level-3 neonatal intensive care units. Recent improvements in aerosolization technology have raised the possibility that aerosolized surfactant could now be given in wider range of settings, including resource-poor settings. Consequently, the World Health Organization has developed a target product profile for product developers that describes the optimal and minimal characteristics of an aerosolized surfactant for treating neonates with respiratory distress syndrome in low- and middle-income countries. Development of the target product profile involved a scoping review of systematic reviews and target product profiles of aerosolized surfactant, the constitution of an international expert advisory group, consultations with medical professionals from a wide range of countries and a public consultation. The resulting target product profile specifies that the surfactant and its associated aerosolization device should ideally, among other characteristics: (i) be at least as safe and effective as current intratracheal surfactant; (ii) produce a rapid clinical improvement; (iii) be easy to transport and use (e.g. by nurses in level-2 health-care facilities in low- and middle-income countries); (iv) be affordable for low- and middle-income countries; and (v) be stable when stored in hot and humid conditions. In addition, the aerosolization device should be capable of daily use for many years. The introduction of an effective aerosolized surfactant globally could substantially reduce neonatal mortality due to respiratory distress syndrome.

Le traitement par surfactant permet d'améliorer le taux de survie des nouveau-nés souffrant d'un syndrome de détresse respiratoire, en particulier les nourrissons prématurés. Pourtant, ce surfactant est généralement administré par intubation endotrachéale et, la plupart du temps, uniquement dans les unités de soins intensifs néonatals de niveau 3. Les récents progrès réalisés dans le domaine des technologies d'aérosolisation laissent entrevoir la possibilité d'administrer dorénavant un surfactant en aérosol dans d'autres cadres, y compris dans des lieux où les ressources sont limitées. L'Organisation mondiale de la Santé a donc développé un profil de produit cible à l'attention des laboratoires, qui détaille les caractéristiques minimales et optimales d'un surfactant en aérosol destiné à la prise en charge des nouveau-nés souffrant d'un syndrome de détresse respiratoire dans les pays à revenu faible et intermédiaire. Ce document est le fruit d'une analyse exploratoire de revues systématiques et de profils de surfactants en aérosol; un groupe consultatif d'experts internationaux a été constitué, des professionnels de la santé originaires de nombreux pays ont été sollicités, et une consultation publique a été organisée. Le profil de produit cible qui en résulte précise que le surfactant et son dispositif d'aérosolisation doivent idéalement présenter une série de caractéristiques, notamment: (i) être au moins aussi sûrs et efficaces que le surfactant intratrachéal actuel; (ii) entraîner une amélioration clinique rapide; (iii) être faciles à transporter et à utiliser (par exemple par le personnel infirmier de niveau 2, au sein d'établissements de santé dans des pays à revenu faible et intermédiaire); (iv) être abordables pour les pays à revenu faible et intermédiaire; et enfin, (v) demeurer stables quand ils sont stockés dans un environnement chaud et humide. En outre, le dispositif d'aérosolisation doit pouvoir être employé au quotidien pendant plusieurs années. Le lancement d'un surfactant en aérosol à l'échelle mondiale pourrait réduire considérablement la mortalité néonatale due au syndrome de détresse respiratoire.

Se ha observado que el tratamiento con sustancias tensioactivas mejora la tasa de supervivencia de los neonatos con síndrome de dificultad respiratoria, especialmente los prematuros. Sin embargo, la sustancia tensioactiva suele administrarse mediante intubación endotraqueal y, por lo general, solo en unidades de cuidados intensivos neonatales de nivel 3. Las mejoras recientes en la tecnología de aerosolización han planteado la posibilidad de que la sustancia tensioactiva en aerosol se pueda administrar ahora en más entornos, incluidos los de escasos recursos. En consecuencia, la Organización Mundial de la Salud ha desarrollado un perfil de producto específico para los desarrolladores de productos que describe las características óptimas y mínimas de una sustancia tensioactiva en aerosol para el tratamiento de neonatos con síndrome de dificultad respiratoria en países de ingresos bajos y medios. El desarrollo del perfil de producto específico implicó una revisión del alcance de las revisiones sistemáticas y los perfiles de producto específicos de la sustancia tensioactiva en aerosol, la constitución de un grupo asesor internacional de expertos, consultas con profesionales médicos de diversos países y una consulta pública. El perfil de producto específico obtenido indica que lo ideal sería que la sustancia tensioactiva y su dispositivo de aerosolización asociado tuvieran, entre otras, las siguientes características: (i) ser al menos tan seguros y eficaces como la sustancia tensioactiva intratraqueal actual; (ii) producir una mejora clínica rápida; (iii) ser fáciles de transportar y utilizar (p. ej. por el personal de enfermería de los centros sanitarios de nivel 2 de los países de ingresos bajos y medios); (iv) ser asequibles para los países de ingresos bajos y medios; y (v) ser estables cuando se almacenan en condiciones de calor y humedad. Además, el dispositivo de aerosolización se debería poder utilizar a diario durante muchos años. La introducción de una sustancia tensioactiva en aerosol eficaz a nivel mundial podría reducir de manera sustancial la mortalidad neonatal causada por el síndrome de dificultad respiratoria.

Immediate skin-to-skin contact for low birth weight infants is safe in terms of cardiorespiratory stability in limited-resource settings.

Aim: To investigate the safety of skin-to-skin contact initiated immediately after birth on cardiorespiratory parameters in unstable low birth weight infants. Methods: A randomized clinical trial was conducted in tertiary newborn units in Ghana, India, Malawi, Nigeria and Tanzania in 2017-2020, in infants with birth weight 1.0-1.799 kg. The intervention was Kangaroo mother care initiated immediately after birth and continued until discharge compared to conventional care with Kangaroo mother care initiated after meeting stability criteria. The results of the primary study showed that immediate Kangaroo mother care reduced neonatal mortality by 25% and the results have been published previously. The post-hoc outcomes of this study were mean heart rate, respiratory rate, oxygen saturation during the first four days and the need of respiratory support. Results: 1,602 infants were allocated to control and 1,609 to intervention. Mean birth weight was 1.5 kg (SD 0.2) and mean gestational age was 32.6 weeks (SD 2.9). Infants in the control group had a mean heart rate 1.4 beats per minute higher (95% CI -0.3-3.1, p = 0.097), a mean respiratory rate 0.4 breaths per minute higher (-0.7-1.5, p = 0.48) and a mean oxygen saturation 0.3% higher (95% CI -0.1-0.7, p = 0.14) than infants in the intervention group. Conclusion: There were no significant differences in cardiorespiratory parameters during the first four postnatal days. Skin-to-skin contact starting immediately after birth is safe in low birth weight infants in limited-resource settings.

Accelerated scale-up of Kangaroo Mother Care: Evidence and experience from an implementation-research initiative in south India.

AIM: Though Kangaroo Mother Care (KMC) has demonstrated benefits for low birth weight newborns, coverage continues to be low in India. As part of a World Health Organization (WHO) multi-country study, we explored intervention models to accelerate KMC coverage in a high priority district of Karnataka, India. METHODS: We used implementation-research methods, formative assessments and quality improvement approaches to design and scale-up interventions. Evaluation was done using prospective cohort study design; data were collected from facility records, and client interviews during KMC initiation, at discharge and at home after discharge. RESULTS: KMC was initiated at health facilities for 87.6% of LBW babies under 2000 g. At discharge, 85.0% received KMC; 67.9% continued to receive KMC at home on the 7th day post-discharge. The interventions included training, mentoring and constant advocacy at many levels: public health facilities, private sector and the community. Innovations like a KMC case sheet, counselling, peer support group triggered KMC in the facilities; a KMC-link card, a microplanning and communication tool for CHWs helped to sustain practice at homes. CONCLUSION: The study provides a novel approach to designing and scaling up interventions and suggests lessons that are applicable to KMC as well as to broader reproductive, maternal, neonatal and child health programmes.

Antenatal corticosteroids for early preterm birth: implementation strategy lessons from the WHO ACTION-I trial.

The WHO ACTION-I trial, the largest placebo-controlled trial on antenatal corticosteroids (ACS) efficacy and safety to date, reaffirmed the benefits of ACS on mortality reduction among early preterm newborns in low-income settings. We discuss here lessons learned from ACTION-I trial that are relevant to a strategy for ACS implementation to optimize impact. Key elements included (i) gestational age dating by ultrasound (ii) application of appropriate selection criteria by trained obstetric physicians to identify women with a likelihood of preterm birth for ACS administration; and (iii) provision of a minimum package of care for preterm newborns in facilities. This strategy accurately identified a large proportion of women who eventually gave birth preterm, and resulted in a 16% reduction in neonatal mortality from ACS use. Policy-makers, programme managers and clinicians are encouraged to consider this implementation strategy to effectively scale and harness the benefits of ACS in saving preterm newborn lives.

Universal screening for hyperbilirubinemia in term healthy newborns at discharge: A systematic review and meta-analysis.

Background: All term healthy neonates are screened for jaundice before hospital discharge as a standard clinical practice, but methods vary from clinical screening (visual inspection and/or risk factor assessment) to transcutaneous bilirubin (TcB) or total serum bilirubin (TSB) testing, depending on the setting. Methods: This systematic review of randomized and non-randomized studies evaluated the effectiveness of universal TcB and universal TSB screening at discharge compared to clinical screening alone for term healthy neonates. The outcomes were neonatal mortality, readmission for jaundice, severe hyperbilirubinemia (>20 mg/dL), jaundice requiring exchange transfusion, and bilirubin-induced neurological dysfunction (BIND). We searched MEDLINE via Ovid, EBM reviews, Embase, CINAHL, clinical trials databases, and reference lists of retrieved articles. Two authors separately evaluated the risk of bias, extracted data, and synthesized effect estimates using relative risk (RR) for randomized and odds ratio (OR) for non-randomized studies. Results: For universal TcB at discharge, we included one randomized trial enrolling 1858 participants and four non-randomized studies enrolling 375 956 participants. No study reported neonatal mortality. The randomized trial suggested that universal TcB at discharge may decrease readmission for jaundice (risk ratio (RR) = 0.24, 95% confidence interval (CI) = 0.13 to 0.46; low certainty evidence) and severe hyperbilirubinemia (RR = 0.27, 95% CI = 0.08 to 0.97; low certainty evidence), but the effect on jaundice requiring exchange transfusion (RR = 0.20, 95% CI = 0.01 to 41.6) and BIND (RR = 0.33, 95% CI = 0.01 to 8.17) was uncertain. Meta-analysis of non-randomized studies suggested that TcB may decrease severe hyperbilirubinemia (odds ratio (OR) = 0.25, 95% = CI 0.12 to 0.52; low certainty evidence) and jaundice requiring exchange transfusion (OR = 0.28, 95% CI = 0.19 to 0.42; low certainty evidence), but the effect on readmission for jaundice was uncertain (OR = 1.01, 95% CI = 0.38 to 2.7; very low certainty evidence). For universal TSB, we included three studies from the United States enrolling 490 426 participants. The effect on severe hyperbilirubinemia (OR = 0.37, 95% CI = 0.15 to 0.88), jaundice requiring exchange transfusion (OR = 0.53, 95% CI = 0.13 to 2.25) and readmission for jaundice (OR = 1.01, 95% CI = 0.62 to 1.67) was uncertain. Conclusions: Universal TcB at discharge may improve clinical outcomes for term healthy neonates. Evidence for universal TSB is uncertain. Registration: PROSPERO 2020 CRD42020187279.

HALT-D: a randomized open-label phase II study of crofelemer for the prevention of chemotherapy-induced diarrhea in patients with HER2-positive breast cancer receiving trastuzumab, pertuzumab, and a taxane.

PURPOSE: To assess whether crofelemer would prevent chemotherapy-induced diarrhea (CID) diarrhea in patients with HER2-positive, any-stage breast cancer receiving trastuzumab (H), pertuzumab (P), and a taxane (T; docetaxel or paclitaxel), with/without carboplatin (C; always combined with docetaxel rather than paclitaxel). METHODS: Patients scheduled to receive ≥ 3 consecutive TCHP/THP cycles were randomized to crofelemer 125 mg orally twice daily during chemotherapy cycles 1 and 2 or no scheduled prophylactic medication (control). All received standard breakthrough antidiarrheal medication (BTAD) as needed. The primary endpoint was incidence of any-grade CID for ≥ 2 consecutive days. Secondary endpoints were incidence of all-grade and grade 3/4 CID by cycle/stratum; time to onset and duration of CID; stool consistency; use of BTAD; and quality of life (Functional Assessment of Chronic Illness Therapy for Patients With Diarrhea [FACIT-D] score). RESULTS: Fifty-one patients were randomized to crofelemer (n = 26) or control (n = 25). There was no statistically significant difference between arms for the primary endpoint; however, incidence of grade ≥ 2 CID was reduced with crofelemer vs control (19.2% vs 24.0% in cycle 1; 8.0% vs 39.1%, in cycle 2). Patients receiving crofelemer were 1.8 times more likely to see their diarrhea resolved and had less frequent watery diarrhea. CONCLUSION: Despite the choice of primary endpoint being insensitive, crofelemer reduced the incidence and severity of CID in patients with HER2-positive breast cancer receiving P-based therapy. These data are supportive of further testing of crofelemer in CID. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02910219, prospectively registered September 21, 2016.

Global newborn health research priorities identified in 2014: A review to evaluate the uptake.

Background: In 2014, World Health Organization published global research priorities for newborn health till 2025. We conducted this review to summarize completed or ongoing research on the twenty priorities. Methods: We conducted searches for twenty questions on MEDLINE via PubMed, Cochrane CENTRAL, Web of Science, clinical trial registries, and funder websites between July 2014 and May 2022. Studies addressing research questions using adequate design were included. Adequacy of uptake of a priority was assessed based on predefined criteria. Findings: The uptake of research priorities was high for 8 (40%), moderate for 11 (55%), and one priority, effectiveness of training community health workers (CHWs) to treat neonatal sepsis at home remains unaddressed. Priorities with moderate uptake include effectiveness of simplified neonatal resuscitation programme, simple clinical algorithms for CHWs to neonatal infection, CHWs training in basic neonatal resuscitation, community-initiated kangaroo mother care, perinatal audits, and novel tocolytic agents, scaling-up chlorhexidine cord application, stable surfactant with simpler administration, accurate, affordable methods to diagnose fetal distress, strategies for prevention and treatment of intrauterine growth retardation, and causal pathways for antenatal stillbirths. Interpretation: Adequate research was undertaken on pressing global concerns in newborn health. Funders and researchers should reflect on and address less researched areas. Funding: None.

Impact of Baseline Clinical Biomarkers on Treatment Outcomes in Patients With Advanced NSCLC Receiving First-line Pembrolizumab-Based Therapy.

BACKGROUND: While the introduction of immune checkpoint inhibitors (ICI) such as pembrolizumab has significantly improved survival for patients with metastatic non-small cell lung cancer (NSCLC), there remains a need for improved predictive and prognostic biomarkers. PATIENTS AND METHODS: We conducted a retrospective, 3-center study using electronic medical record data for patients with stage IV NSCLC treated with first-line pembrolizumab, either as monotherapy or in combination with chemotherapy, between 2014 and 2019. We categorized variables as covariates or confounders. Covariates, which were the focus of analysis due to their emerging prognostic value, included pretreatment body mass index (BMI), neutrophil-to-lymphocyte ratio (NLR), albumin, and antibiotic exposure. Confounders, which highlighted characteristics for each patient and their cancer, included sex, age at start of immunotherapy, Programmed death-ligand 1 (PD-L1) expression, performance status (PS), tumor mutational burden and whether pembrolizumab was given as monotherapy or in combination with chemotherapy. The association between these variables with time to treatment failure (TTF) and overall survival (OS) was assessed using Kaplan-Meier method and Cox proportional hazards models. RESULTS: One hundred thirty-six patients were included in our study. Antibiotics usage, serum albumin, and NLR have univariate relationships with TTF. Serum albumin, NLR, and BMI were associated with OS in univariate analyses. In our multivariate analysis, antibiotic usage had a strong negative association with TTF when adjusting for all 6 confounders. CONCLUSION: Pretreatment usage of antibiotics, as well as albumin, NLR, and BMI have potential to predict treatment outcomes in patients with advanced NSCLC receiving first-line immunotherapy.

Displaced AICD Lead Presenting as Hiccups: A Rare Complication.

Ventricular fibrillation can lead to sudden cardiac death. Automatic implantable cardioverter defibrillator (AICD) devices have shown to be highly successful in the termination of these arrhythmias and are a first-line modality of treatment for the prevention of sudden cardiac death. We present the case of a 69-year-old female with a history of paroxysmal atrial fibrillation on anticoagulation with apixaban and rate controlled with metoprolol who presented from home with a chief complaint of hiccups. She had a prior admission to the hospital after she was found to have monomorphic ventricular tachycardia during a nuclear stress test. A cardiac work-up including cardiac catheterization and cardiac magnetic resonance imaging did not show any evidence of significant coronary artery disease or reversible cardiomyopathy. The patient underwent successful placement of a single chamber ICD and was discharged home. Twelve weeks after placement of the AICD, the patient was lifting furniture and experienced sudden onset of hiccups. A chest X-ray showed displacement of the AICD lead from the right ventricular apex to the superior vena cava. The patient underwent lead repositioning with complete resolution of her hiccups. The etiology hiccups was suspected to be secondary to irritation of the right phrenic nerve which travels along the anterolateral border of the superior vena cava. We present the case of hiccups following ICD lead displacement. This serves to highlight a rare complication of ICD displacement that healthcare providers should consider when patients with recently placed ICD devices complain of hiccups.

Heart Failure as the Initial Presentation of Anomalous Left Coronary Artery From the Pulmonary Artery.

Coronary arteries arising from the pulmonary artery have an incidence of 0.002% in the general population. We present a 29-year-old woman who presented to our hospital with acute decompensated heart failure and atrial fibrillation with a rapid ventricular rate. She underwent a cardiac catheterization to rule out ischemic disease, which revealed retrograde contrast flow through the left coronary artery from the right coronary artery. A coronary computed tomography (CT) angiogram was pursued which showed the presence of an anomalous left coronary artery arising from the pulmonary artery (ALCAPA). For the management of her atrial fibrillation, she was electrically cardioverted. She was discharged on guideline-directed medical therapy for her heart failure, with a cardiac surgery referral for the surgical fixation of her ALCAPA.

Short-term Outcome and Predictors of Survival Among Neonates with Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative.

BACKGROUND: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. OBJECTIVE: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. SETTING: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. OUTCOME: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. RESULTS: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. CONCLUSION: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds of survival.

Predisposing factors for excessive loss of weight in exclusively breastfed term and late preterm neonates - a case control study.

BACKGROUND: Exclusively breastfed healthy neonates can lose weight excessively due to poor milk production, inadequate enteral intake or due to poor milk transfer. The studies assessing risk factors for infants to lose weight excessively are diverse and results are highly varied. OBJECTIVES: We aimed to determine the risk factors for weight loss of over 10% in term and late preterm newborns who were exclusively breastfed. METHODS: This was a case-control study which was conducted in a tertiary care hospital. Exclusively breastfed neonates of ≥34 weeks having weight loss of >10% in the first 14 days of life comprised the study group with gestational age and weight-matched neonates without significant weight loss forming the control group. Demographic details, LATCH score, maternal EPDS (Edinburg postpartum depression score) and neonatal morbidities were assessed. RESULTS: Of the 53 mother-infant dyad in each group, baseline characteristics were similar. Gestational Diabetes Mellitus (GDM), Lower segment Caesarean section (LSCS) delivery, higher EPDS score, low LATCH score, absence of immediate skin to skin contact were associated with excessive weight loss and was found to be significant statistically. Babies in the study group had higher incidence of jaundice and hypernatremia and had longer duration of stay in hospital. CONCLUSION: Lack of early skin to skin contact, higher EPDS scores and lower LATCH scores are predisposing factors for exclusively breastfed infants to lose weight excessively.