Clinical usefulness of reintubation criteria in extremely preterm infants: a cohort study.

OBJECTIVE: To describe the thresholds of instability used by clinicians at reintubation and evaluate the accuracy of different combinations of criteria in predicting reintubation decisions. DESIGN: Secondary analysis using data obtained from the prospective observational Automated Prediction of Extubation Readiness study (NCT01909947) between 2013 and 2018. SETTING: Multicentre (three neonatal intensive care units). PATIENTS: Infants with birth weight ≤1250 g, mechanically ventilated and undergoing their first planned extubation were included. INTERVENTIONS: After extubation, hourly O2 requirements, blood gas values and occurrence of cardiorespiratory events requiring intervention were recorded for 14 days or until reintubation, whichever came first. MAIN OUTCOME MEASURES: Thresholds at reintubation were described and grouped into four categories: increased O2, respiratory acidosis, frequent cardiorespiratory events and severe cardiorespiratory events (requiring positive pressure ventilation). An automated algorithm was used to generate multiple combinations of criteria from the four categories and compute their accuracies in capturing reintubated infants (sensitivity) without including non-reintubated infants (specificity). RESULTS: 55 infants were reintubated (median gestational age 25.2 weeks (IQR 24.5-26.1 weeks), birth weight 750 g (IQR 640-880 g)), with highly variable thresholds at reintubation. After extubation, reintubated infants had significantly greater O2 needs, lower pH, higher pCO2 and more frequent and severe cardiorespiratory events compared with non-reintubated infants. After evaluating 123 374 combinations of reintubation criteria, Youden indices ranged from 0 to 0.46, suggesting low accuracy. This was primarily attributable to the poor agreement between clinicians on the number of cardiorespiratory events at which to reintubate. CONCLUSIONS: Criteria used for reintubation in clinical practice are highly variable, with no combination accurately predicting the decision to reintubate.

Monogenic Causes in the Type 1 Diabetes Genetics Consortium Cohort: Low Genetic Risk for Autoimmunity in Case Selection.

HYPOTHESIS: About 1% of patients clinically diagnosed as type 1 diabetes have non-autoimmune monogenic diabetes. The distinction has important therapeutic implications but, given the low prevalence and high cost of testing, selecting patients to test is important. We tested the hypothesis that low genetic risk for type 1 diabetes can substantially contribute to this selection. METHODS: As proof of principle, we examined by exome sequencing families with 2 or more children, recruited by the Type 1 Diabetes Genetics Consortium (T1DGC) and selected for negativity for 2 autoantibodies and absence of risk human leukocyte antigen haplotypes. RESULTS: We examined 46 families that met the criteria. Of the 17 with an affected parent, 7 (41.2%) had actionable monogenic variants. Of 29 families with no affected parent, 14 (48.3%) had such variants, including 5 with recessive pathogenic variants of WFS1 but no report of other features of Wolfram syndrome. Our approach diagnosed 55.8% of the estimated number of monogenic families in the entire T1DGC cohort, by sequencing only 11.1% of the autoantibody-negative ones. CONCLUSIONS: Our findings justify proceeding to large-scale prospective screening studies using markers of autoimmunity, even in the absence of an affected parent. We also confirm that nonsyndromic WFS1 variants are common among cases of monogenic diabetes misdiagnosed as type 1 diabetes.

Torpedo Maculopathy Associated with NEXMIF Mutation.

Mutations in the neurite extension and migration factor (NEXMIF) gene are associated with X-linked intellectual disability. Thus far, all males reported with NEXMIF mutations have mild to profound intellectual disability with varying combinations of autistic features, poor or absent speech, epilepsy, facial dysmorphism, and strabismus. Affected females tend to have milder intellectual disability but severe, drug-resistant epilepsy. Here, we present a 32-month-old boy with a novel de novo frameshift NEXMIF pathogenic variant (p.Glu375ArgfsX21) who has mild motor delay, language delay, autistic features, and strabismus. In addition to these commonly described findings of NEXMIF mutations, his fundus exam revealed a very rare ophthalmologic abnormality, torpedo maculopathy. This finding has not previously been reported with NEXMIF mutation; however, on literature review, 7/15 males with NEXMIF mutations had other ophthalmologic abnormalities. This patient expands the phenotypic spectrum for males with NEXMIF mutations and suggests that NEXMIF may play an important role in ocular development.

Five-year single center experience on surfactant treatment in preterm infants with respiratory distress syndrome: LISA vs INSURE.

BACKGROUND: Surfactant administration traditionally involved endotracheal intubation and mechanical ventilation, which is associated with a risk of barotrauma and volutrauma. OBJECTIVE: To compare the morbidity and mortality rates between LISA-treated and INSURE-treated premature babies with respiratory distress syndrome (RDS). METHODS: We assessed retrospectively the medical records of preterm infants who were born at 250/7 to 296/7 weeks of gestation and were administered surfactant initially either with LISA or INSURE method over a five-year period. RESULTS: Analysis of the data of 205 LISA-treated and 178 INSURE-treated infants revealed the mean gestational age as 28.1 ±â€¯1.3 and 28 ±â€¯1.3 weeks and mean birth weight as 1041 ±â€¯205 and 1029 ±â€¯222 g in LISA and INSURE groups, respectively. The mechanical ventilation requirement in the first 72 h of life (%26.8-%42.1, p = 0.002) and the incidence of moderate-severe BPD (%12.2-%21.9, p = 0.01) were lower in LISA-treated infants. LISA method was found as an independent factor in reducing mechanical ventilation requirement in the first 72 h of life and incidence of moderate-severe BPD [RR: -0.49 (%95 CI -0.28 to -0.85), p = 0.01]. CONCLUSION: Data obtained from our five-year clinical experience are comparable with the recent literature. LISA is currently the most suitable method of surfactant administration and it should be the first choice in spontaneously breathing infants considering its favorable effects on respiratory morbidities in preterm infants with RDS.

Evaluation of the Cytotoxic and Autophagic Effects of Atorvastatin on MCF-7 Breast Cancer Cells

Background: Recently, cytotoxic effects of statins on breast cancer cells have been reported. However, the mechanism of anti-proliferative effects is currently unknown. Autophagy is non-apoptotic programmed cell death, which is characterized by degradation of cytoplasmic components and as having a role in cancer pathogenesis. Aims: To investigate the anti-proliferative effects of atorvastatin on MCF-7 human breast adenocarcinoma cells with respect to both autophagy and apoptosis. Study Design: Cell culture study. Methods: Cell viability was analyzed using WST-1 cell proliferation assay. Apoptosis was determined by the TUNEL method, whereas autophagy was assessed by Beclin-1 and LC3B immunofluorescence staining. Ultrastructural analysis of cells was performed by electron microscopy. Results: Atorvastatin reduced MCF-7 cell proliferation in a dose- and time-dependent manner inducing TUNEL-, Beclin-1-, and LC3B-positive cells. Moreover, ultrastructural analysis showed apoptotic, autophagic, and necrotic morphological changes in treatment groups. A statistically significant increase in the apoptotic index was detected with higher concentrations of atorvastatin at 24 h and 48 h (p<0.05). Conclusion: The anti-proliferative effects of atorvastatin on breast cancer cells is mediated by the induction of both apoptosis and autophagy which shows statins as a potential treatment option for breast cancer.

Abnormal Capillary Vasodynamics Contribute to Ictal Neurodegeneration in Epilepsy.

Seizure-driven brain damage in epilepsy accumulates over time, especially in the hippocampus, which can lead to sclerosis, cognitive decline, and death. Excitotoxicity is the prevalent model to explain ictal neurodegeneration. Current labeling technologies cannot distinguish between excitotoxicity and hypoxia, however, because they share common molecular mechanisms. This leaves open the possibility that undetected ischemic hypoxia, due to ictal blood flow restriction, could contribute to neurodegeneration previously ascribed to excitotoxicity. We tested this possibility with Confocal Laser Endomicroscopy (CLE) and novel stereological analyses in several models of epileptic mice. We found a higher number and magnitude of NG2+ mural-cell mediated capillary constrictions in the hippocampus of epileptic mice than in that of normal mice, in addition to spatial coupling between capillary constrictions and oxidative stressed neurons and neurodegeneration. These results reveal a role for hypoxia driven by capillary blood flow restriction in ictal neurodegeneration.

Accidental oral administration of povidone iodine in a newborn: case report.

Iodine solutions are widely used as antiseptic for treating and preventing wound infections. Povidone iodine, one of the most common topical iodine solutions in emergency kits, can lead to several abnormalities as thyroid dysfunction. Povidone iodine poisoning is unusual and previously reported effects are mainly complications of topical usage during surgical procedures. Here we present the case of a newborn that was accidentally given oral povidone iodine, showing no signs or symptoms of toxicity after ingestion.

Las soluciones yodadas se utilizan ampliamente como antiséptico para el tratamiento y la prevención de infecciones en las heridas. La povidona yodada, una de las soluciones yodadas de aplicación tópica que más se encuentra en los botiquines de emergencia, podría producir anomalías graves, como disfunción tiroidea. La intoxicación por povidona yodada es poco frecuente; entre los efectos notificados previamente se incluyen complicaciones del uso tópico durante procedimientos quirúrgicos. Se describe el caso de un neonato que recibió povidona yodada por vía oral accidentalmente, sin signos ni síntomas de toxicidad después de la ingesta.

Administración oral accidental de povidona yodada a un neonato: a propósito de un caso / Accidental oral administration of povidone iodine in a newborn: Case report

Las soluciones yodadas se utilizan ampliamente como antiséptico para el tratamiento y la prevención de infecciones en las heridas. La povidona yodada, una de las soluciones yodadas de aplicación tópica que más se encuentra en los botiquines de emergencia, podría producir anomalías graves, como disfunción tiroidea. La intoxicación por povidona yodada es poco frecuente; entre los efectos notificados previamente se incluyen complicaciones del uso tópico durante procedimientos quirúrgicos. Se describe el caso de un neonato que recibió povidona yodada por vía oral accidentalmente, sin signos ni síntomas de toxicidad después de la ingesta.

Iodine solutions are widely used as antiseptic for treating and preventing wound infections. Povidone iodine, one of the most common topical iodine solutions in emergency kits, can lead to several abnormalities as thyroid dysfunction. Povidone iodine poisoning is unusual and previously reported effects are mainly complications of topical usage during surgical procedures. Here we present the case of a newborn that was accidentally given oral povidone iodine, showing no signs or symptoms of toxicity after ingestion.

Cholestasis in infants with immune hydrops fetalis.

Rhesus (Rh) hemolytic disease of the newborn represents a broad spectrum of symptoms in the fetus and newborn, ranging from mild to severe hemolytic anemia and hydrops fetalis. Cholestasis is a common problem in infants with immune hydrops fetalis (IHF). The aim of this study was to evaluate the incidence and course of cholestasis in infants with IHF due to Rh alloimmunization. Infants with IHF during the 10-year follow-up were retrospectively included in the study. Demographics, laboratory parameters, and prenatal and postnatal interventions were recorded. The incidence of cholestasis and certain risk factors were investigated. A total of 30 infants with IHF with a mean gestational age 33 ± 2.6 weeks were included. Of these, 15 infants (50%) survived to discharge. The incidence of cholestasis was 60% (18/30). Cholestasis was diagnosed within a median 3 (0-7) days. All cholestatic infants who survived recovered within three months. In conclusion, cholestasis in IHF is frequent, transient and has an early onset.