Despite the increased use of sedation in children undergoing stressful procedures, reduction of ileocolic intussusception (RII) is usually performed on awake children without any form of sedation.
To ...evaluate the incidence of severe complications of RII under sedation or anaesthesia.
A systematic review including English language original articles of any date.
Children undergoing RII (pneumatic or hydrostatic) under sedation or anaesthesia.
Ovid Embase, Scopus, PubMed, the Cochrane Database of Systematic Reviews and the internet search engine Google Scholar.
Three authors independently reviewed each article for eligibility. The Newcastle-Ottawa Scale was used to assess the quality of included studies.
The primary outcome was the incidence of intestinal perforation during RII. The secondary outcomes were the incidence of sentinel adverse events defined as death, cardiopulmonary resuscitation, permanent neurological deficit and pulmonary aspiration syndrome.
The search yielded 368 articles. Nine studies with 1391 cases were included in the analysis. Of the nine studies, six had a score of ≤6 stars in the Newcastle-Ottawa Scale assessment, indicating low-to-moderate quality. Propofol-based sedation was used in 849 (59.2%) cases; 5 (0.6%) had intestinal perforation. Intestinal perforation was not reported in patients who were sedated with other sedatives. One patient had pulmonary aspiration syndrome.
Although caution remains warranted, current data suggest that the incidence of severe complications due to RII under sedation or anaesthesia is low. Due to the lack of prospective data, it is difficult to ascertain the exact incidence of severe complications.
In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2 . For ...carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts ( P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.
Significance Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to very high risks of breast and ovarian cancer. For carriers of these mutations, risk-reducing surgery significantly reduces morbidity and mortality. General population screening for BRCA1 and BRCA2 mutations in young adult women could be feasible if accurate estimates of cancer risk for mutation carriers could be obtained. We determined that risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained from the general population are as high as for mutation carriers ascertained through personal or family history of cancer. General screening of BRCA1 and BRCA2 would identify many carriers who are currently not evaluated and could serve as a model for population screening for genetic predisposition to cancer.
•37% of caregivers opposed vaccine mandates at all school levels.•Only 20% of caregivers agreed with immediate vaccine mandates.•Vaccine safety was the most important concern regarding vaccine ...mandates.•26% of caregivers would remove their child from school if vaccines became mandated.
Caregiver attitudes toward mandating COVID-19 vaccines for their children are poorly understood. We aimed to determine caregiver acceptability of COVID-19 vaccine mandates for schools/daycares and assess if opposition to mandates would result in removal of children from the educational system.
Perform a cross-sectional, anonymous survey of adult caregivers with children ≤ 18 years presenting to 21 pediatric emergency departments in the United States, Canada, Israel, and Switzerland, November 1st through December 31st, 2021. The primary outcome was caregiver acceptance rates for school vaccine mandates, and the secondary outcomes included factors associated with mandate acceptance and caregiver intention to remove the child from school.
Of 4,393 completed surveys, 37% of caregivers were opposed to any school vaccine mandate. Caregiver acceptance was lowest for daycare settings (33%) and increased as the child’s level of education increased, college (55%). 26% of caregivers report a high likelihood (score of 8–10 on 0–10 scale) to remove their child from school if the vaccine became mandatory. Child safety was caregivers’ greatest concern over vaccine mandates. A multivariable model demonstrated intent to vaccinate their child for COVID-19 (OR = 8.9, 95% CI 7.3 to 10.8; P < 0.001) and prior COVID-19 vaccination for the caregiver (OR = 3.8, 95% CI 3.0 to 4.9; P < 0.001) had the greatest odds of increasing mandate acceptance for any school level.
Many caregivers are resistant to COVID-19 vaccine mandates for schools, and acceptance varies with school level. One-fourth of caregivers plan to remove their child from the educational system if vaccines become mandated.
Neural progenitor cells undergo somatic retrotransposition events, mainly involving L1 elements, which can be potentially deleterious. Here, we analyze the whole genomes of 20 brain samples and 80 ...non-brain samples, and characterized the retrotransposition landscape of patients affected by a variety of neurodevelopmental disorders including Rett syndrome, tuberous sclerosis, ataxia-telangiectasia and autism. We report that the number of retrotranspositions in brain tissues is higher than that observed in non-brain samples and even higher in pathologic vs normal brains. The majority of somatic brain retrotransposons integrate into pre-existing repetitive elements, preferentially A/T rich L1 sequences, resulting in nested insertions. Our findings document the fingerprints of encoded endonuclease independent mechanisms in the majority of L1 brain insertion events. The insertions are ＂non-classical＂ in that they are truncated at both ends, integrate in the same orientation as the host element, and their target sequences are enriched with a CCATT motif in contrast to the classical endonuclease motif of most other retrotranspositions. We show that LIHs elements integrate preferentially into genes associated with neural functions and diseases. We propose that pre-existing retrotransposons act as ＂lightning rods＂ for novel insertions, which may give fine modulation of gene expression while safeguarding from deleterious events. Overwhelmingly uncontrolled retrotransposition may breach this safeguard mechanism and increase the risk of harmful mutagenesis in neurodevelopmental disorders.
The aim of this study was to assess the performance of the Pediatric Canadian Triage and Acuity Scale (PaedCTAS) in adolescent patients with severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) infection.
A time-series study was conducted in the Emergency Departments (EDs) of 17 public hospitals during the Delta (B.1.617.2) variant spread in Israel. Data were collected prospectively from June 11, 2021 to August 15, 2021. Multivariate regression analyses were performed to identify independent variables associated with hospital admission and with admission to an Intensive Care Unit (ICU).
During the study period, 305 SARS-CoV-2 patients ages 12–18 years presenting to the ED were included, and 267 (87.5%) were unvaccinated. Sixty-seven (22.0%) and 12 (3.9%) patients were admitted to pediatric wards and ICUs, respectively. PaedCTAS level 1–2 and the presence of chronic disease increased the odds of hospital admission (adjusted odds ratio (aOR) 5.74, 95% CI, 2.30–14.35, p < 0.0001), and (aOR 2.9, 95% CI, 1.48–5.67, p < 0.02), respectively. PaedCTAS level 1–2 and respiratory symptoms on presentation to ED increased the odds of ICU admission (aOR 27.79; 95% CI, 3.85–176.91, p < 0.001), and (aOR 26.10; 95% CI, 4.47–172.63, p < 0.0001), respectively. PaedCTAS level 3–5 was found in 217/226 (96%) of the patients who were discharged home from the ED.
The findings suggest that PaedCTAS level 1–2 was the strongest factor associated with hospital and ICU admission. Almost all the patients who were discharged home had PaedCTAS level 3–5. Study findings suggest good performance of the PaedCTAS in this cohort.
Ohtahara syndrome, early infantile epileptic encephalopathy with a suppression burst EEG pattern, is an aetiologically heterogeneous condition starting in the first weeks or months of life with ...intractable seizures and profound developmental disability. Using whole exome sequencing, we identified biallelic DMXL2 mutations in three sibling pairs with Ohtahara syndrome, belonging to three unrelated families. Siblings in Family 1 were compound heterozygous for the c.5135C>T (p.Ala1712Val) missense substitution and the c.4478C>G (p.Ser1493*) nonsense substitution; in Family 2 were homozygous for the c.4478C>A (p.Ser1493*) nonsense substitution and in Family 3 were homozygous for the c.7518-1G>A (p.Trp2507Argfs*4) substitution. The severe developmental and epileptic encephalopathy manifested from the first day of life and was associated with deafness, mild peripheral polyneuropathy and dysmorphic features. Early brain MRI investigations in the first months of life revealed thin corpus callosum with brain hypomyelination in all. Follow-up MRI scans in three patients revealed progressive moderate brain shrinkage with leukoencephalopathy. Five patients died within the first 9 years of life and none achieved developmental, communicative or motor skills following birth. These clinical findings are consistent with a developmental brain disorder that begins in the prenatal brain, prevents neural connections from reaching the expected stages at birth, and follows a progressive course. DMXL2 is highly expressed in the brain and at synaptic terminals, regulates v-ATPase assembly and activity and participates in intracellular signalling pathways; however, its functional role is far from complete elucidation. Expression analysis in patient-derived skin fibroblasts demonstrated absence of the DMXL2 protein, revealing a loss of function phenotype. Patients' fibroblasts also exhibited an increased LysoTracker® signal associated with decreased endolysosomal markers and degradative processes. Defective endolysosomal homeostasis was accompanied by impaired autophagy, revealed by lower LC3II signal, accumulation of polyubiquitinated proteins, and autophagy receptor p62, with morphological alterations of the autolysosomal structures on electron microscopy. Altered lysosomal homeostasis and defective autophagy were recapitulated in Dmxl2-silenced mouse hippocampal neurons, which exhibited impaired neurite elongation and synaptic loss. Impaired lysosomal function and autophagy caused by biallelic DMXL2 mutations affect neuronal development and synapse formation and result in Ohtahara syndrome with profound developmental impairment and reduced life expectancy.
Abstract
This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–associated emergency department visits and hospitalizations in ...pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2–related pediatric morbidity.
This multicenter, cross-sectional study provides evidence on SARS-CoV-2-associated ED visits and hospitalizations in pediatric wards and intensive care units, after school reopening during the ...SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2-related pediatric morbidity.
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