Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis.

IMPORTANCE: Carboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial. METHODS: The study was prospectively registered at PROSPERO (CRD42021228386). We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes. RESULTS: Eight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I2 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I2 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44-3.08; I2 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm. CONCLUSION: and relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.

SARS-CoV-2 Reinfection Rate and Estimated Effectiveness of the Inactivated Whole Virion Vaccine BBV152 Against Reinfection Among Health Care Workers in New Delhi, India.

Importance: A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. Objective: To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. Design, Setting, and Participants: This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Exposures: Vaccination with 0, 1, or 2 doses of BBV152. Main Outcomes and Measures: The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Results: Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. Conclusions and Relevance: These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

Segmental Ileal Dilatation Presenting with Neonatal Intestinal Obstruction.

Segmental ileal dilatation is an uncommon cause of neonatal intestinal obstruction. This report highlights a rare combination of abnormal distribution of muscles in the muscularis propria and partial loss of interstitial cells of Cajal as causative factors for segmental intestinal dilatation.

Risk of Tuberculosis in Patients With Inflammatory Bowel Disease on Infliximab or Adalimumab Is Dependent on the Local Disease Burden of Tuberculosis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Infliximab (IFX) or adalimumab (ADA) use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB). This meta-analysis evaluated the factors which determine this risk, with special focus on local TB incidence. METHODS: All studies until January 31, 2019, which reported the development of TB in patients with IBD on IFX/ADA, were included after searching PubMed and Embase. Data regarding disease type, number of patients on IFX/ADA, number of patients who developed TB, mean age at IFX/ADA initiation, median duration of development of TB, and latent TB (LTB) were extracted. The details on local TB incidence were obtained from the World Health Organization database, and the studies were stratified into low (<10/100,000), intermediate (10-40/100,000), and high TB burden countries (>40/100,000). Random effect meta-analysis was performed to calculate the overall pooled prevalence and prevalence based on local TB burden. RESULTS: Of 130,114 patients (128 studies), 373 developed TB (pooled prevalence: 0.08% [95% confidence interval {CI}: 0.05%-0.10%]). The risk increased with increasing TB burden, pooled prevalence being 0.02% (95% CI: 0.02%-0.03%), 0.21% (95% CI: -0.02% to 0.43%), and 1.59% (95% CI: 1.19%-2.00%) for low, intermediate, and high TB burden countries, respectively. Seventy-three percent of patients who developed TB had no evidence of LTB on screening, the proportion being independent of TB burden. There was no effect of disease or treatment type, study type, gender, age at IFX/ADA initiation, and follow-up duration on TB prevalence. DISCUSSION: TB risk in patients with IBD on IFX/ADA depends on the local TB burden and is independent of disease/treatment type.

Can available interventions end preventable deaths in mothers, newborn babies, and stillbirths, and at what cost?

Progress in newborn survival has been slow, and even more so for reductions in stillbirths. To meet Every Newborn targets of ten or fewer neonatal deaths and ten or fewer stillbirths per 1000 births in every country by 2035 will necessitate accelerated scale-up of the most effective care targeting major causes of newborn deaths. We have systematically reviewed interventions across the continuum of care and various delivery platforms, and then modelled the effect and cost of scale-up in the 75 high-burden Countdown countries. Closure of the quality gap through the provision of effective care for all women and newborn babies delivering in facilities could prevent an estimated 113,000 maternal deaths, 531,000 stillbirths, and 1·325 million neonatal deaths annually by 2020 at an estimated running cost of US$4·5 billion per year (US$0·9 per person). Increased coverage and quality of preconception, antenatal, intrapartum, and postnatal interventions by 2025 could avert 71% of neonatal deaths (1·9 million [range 1·6-2·1 million]), 33% of stillbirths (0·82 million [0·60-0·93 million]), and 54% of maternal deaths (0·16 million [0·14-0·17 million]) per year. These reductions can be achieved at an annual incremental running cost of US$5·65 billion (US$1·15 per person), which amounts to US$1928 for each life saved, including stillbirths, neonatal, and maternal deaths. Most (82%) of this effect is attributable to facility-based care which, although more expensive than community-based strategies, improves the likelihood of survival. Most of the running costs are also for facility-based care (US$3·66 billion or 64%), even without the cost of new hospitals and country-specific capital inputs being factored in. The maximum effect on neonatal deaths is through interventions delivered during labour and birth, including for obstetric complications (41%), followed by care of small and ill newborn babies (30%). To meet the unmet need for family planning with modern contraceptives would be synergistic, and would contribute to around a halving of births and therefore deaths. Our analysis also indicates that available interventions can reduce the three most common cause of neonatal mortality--preterm, intrapartum, and infection-related deaths--by 58%, 79%, and 84%, respectively.

Management of neonatal seizures.

Seizures in the newborn period constitute a medical emergency. Subtle seizures are the commonest type of seizures occurring in the neonatal period. Myoclonic seizures carry the worst prognosis in terms of long-term neurodevelopmental outcome. Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Multiple etiologies often co-exist in neonates and hence it is essential to rule out common causes such as hypoglycaemia, hypocalcemia, and meningitis before initiating specific therapy. A comprehensive evidence based approach for management of neonatal seizures has been described in this protocol.

HIV infection mimicking autoimmune disorder.

A 13-yr-old girl born to healthy parents presented with cough, fever, easy fatiguability, photosensitivity and alopecia. She had clubbing and diffuse crackles in the chest on examination. Her CT scan of the chest showed evidence of bronchiectasis with consolidation. Investigations for tuberculosis and collagen vascular disease were negative. In due course she developed features of raised intracranial tension. Her blood for HIV ELISA was positive with CD4 counts of 17/ microL. Her CSF, sputum, blood and urine specimen were all positive for Cryptococcus neoformans on culture. HIV was not considered initially because of her atypical presentation. There was no history of sexual abuse, her parents were healthy and she did not receive any blood transfusion in the past.