Hypothermia for encephalopathy in low-income and middle-income countries: feasibility of whole-body cooling using a low-cost servo-controlled device

Although therapeutic hypothermia (TH) is the standard of care for hypoxic ischaemic encephalopathy in high-income countries, the safety and efficacy of this therapy in low-income and middle-income countries (LMICs) is unknown. We aimed to describe the feasibility of TH using a low-cost servo-controlled cooling device and the short-term outcomes of the cooled babies in LMIC. Design: We recruited babies with moderate or severe hypoxic ischaemic encephalopathy (aged <6 hours) admitted to public sector tertiary neonatal units in India over a 28-month period. We administered whole-body cooling (set core temperature 33.5°C) using a servo-controlled device for 72 hours, followed by passive rewarming. We collected the data on short-term neonatal outcomes prior to hospital discharge. Results: Eighty-two babies were included-61 (74%) had moderate and 21 (26%) had severe encephalopathy. Mean (SD) hypothermia cooling induction time was 1.7 hour (1.5) and the effective cooling time 95% (0.08). The mean (SD) hypothermia induction time was 1.7 hour (1.5 hour), core temperature during cooling was 33.4°C (0.2), rewarming rate was 0.34°C (0.16°C) per hour and the effective cooling time was 95% (8%). Twenty-five (51%) babies had gastric bleeds, 6 (12%) had pulmonary bleeds and 21 (27%) had meconium on delivery. Fifteen (18%) babies died before discharge from hospital. Heart rate more than 120 bpm during cooling (P=0.01) and gastric bleeds (P<0.001) were associated with neonatal mortality. Conclusions: The low-cost servo-controlled cooling device maintained the core temperature well within the target range. Adequately powered clinical trials are required to establish the safety and efficacy of TH in LMICs. Clinical trial registration number: NCT01760629

Hypothermia for encephalopathy in low and middle-income countries (HELIX): Study protocol for a randomised controlled trial

BACKGROUND: Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as standard therapy in these settings. However, the safety and efficacy of cooling therapy in low- and middle-income countries (LMICs), where 99% of the disease burden occurs, remains unclear. We will examine whether whole body cooling reduces death or neurodisability at 18-22 months after neonatal encephalopathy, in LMICs. METHODS: We will randomly allocate 408 term or near-term babies (aged ≤ 6 h) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries (India, Bangladesh or Sri Lanka), to either usual care alone or whole-body cooling with usual care. Babies allocated to the cooling arm will have core body temperature maintained at 33.5 °C using a servo-controlled cooling device for 72 h, followed by re-warming at 0.5 °C per hour. All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1-2 weeks after birth. Our primary endpoint is death or moderate or severe disability at the age of 18 months. DISCUSSION: Upon completion, HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs. The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02387385. Registered on 27 February 2015

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

Background: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. Methods: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18–22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. Findings: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87–1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. Interpretation: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. Funding: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. Translations: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section

Assessment of Phenotypic and Genotypic Diversity in Elite Temperate and Tropical Sweet Sorghum Cultivars

Sweet sorghum is one of the many types of cultivated sorghums and is a promising multipurpose biofuel feedstock. The objective of this study was to assess phenotypic and genotypic diversity among 75 selected diverse sweet sorghum genotypes available at ICRISAT-Patancheru. Genotyping-by-sequencing generated 135,162 SNPs having minor allele frequencies > 0.20. Cluster analysis grouped the genotypes into three distinct clusters, with some of the sweet sorghum lines falling in distinct clusters. This grouping pattern was in conformity with available race and pedigree information. Mean performance and analysis of variance for sugar yield-related traits shows considerable variability. The results also revealed close genetic relationships between elite genotypes such as ICSV 25316, ICSV 25311, SSV 74 and ICSV 25300 that are superior for various sugar yield-associated traits like plant height, biomass, juice yield and sugar content. Not surprisingly given their pedigrees, these elite materials grouped together tightly in a single sub-cluster

Needle in a haystack: migration of ventriculoperitoneal shunt into scrotum of infant

Abstract Background Ventriculoperitoneal shunt malpositions are known complications which tend to increase the morbidity and recovery time of an elegant procedure. Distal malpositions into subcutaneous space due to improper closure or positioning can lead to shunt failure. Migration to the scrotum due to a patent processus vaginalis is, however, reported only in a handful of cases and, thus, needs to be highlighted and reported. Results We report a case of congenital hydrocephalus that underwent shunting at the age of 3 months and reported to be 9 months later with the shunt tube being felt in the scrotum. Repositioning along with herniotomy was performed. Conclusions A rare occurrence, scrotal migration, needs to recognized and reported. Potential preventive measures include truncation stiches and laproscopic assisted insertion

Intraventricular ganglioglioma with bleed: A rare case report

Gangliogliomas are benign lesions that are predominantly temporal in location and present with chronic epilepsy. Intraventricular gangliogliomas are extremely rare and still rarer is intratumoral hemorrhage. Till date only 9 cases of lateral ventricular gangliogliomas have been reported. To the best of our knowledge only 1 case of intratumoral hemorrhage has been reported. We report a rare case of lateral ventricular ganglioglioma with intratumoral hemorrhage in a 27-year-old man

Rare Cranial Nerve Schwannomas: A Retrospective Review of Nontrigeminal, Nonvestibular Cranial Nerve Schwannomas

Introduction: Intracranial schwannomas arising from non-trigeminal and non-vestibular sources are extremely rare constituting <0.8% of all schwannomas. In this article, we have analyzed our experience in the management of these rare tumors over a 10-year period. Material and Methods: There were a total of 16 cases, with 11 of them undergoing microsurgical resection and 5 undergoing stereotactic radiosurgery (SRS). Results: There were no fresh neurological deficit in any of these patients and two patients underwent postoperative SRS for residual tumor. One patient died due to postoperative septicemia. Conclusion: Knowledge of these lesions along with their clinicoradiological profile is essential to maintain a high index of suspicion and understand the nuances of treatment