Predictors of surgical site skin infection and clinical outcome at caesarean section in the very severely obese : A retrospective cohort study

Introduction The optimal surgical approach for caesarean section is uncertain in women with very severe obesity (body mass index (BMI) >40kg/m2). We aimed to assess maternal and surgical predictors of surgical site skin infection (SSSI) in very severely obese women and to undertake an exploratory evaluation of clinical outcomes in women with a supra-panniculus transverse compared to an infra-panniculus transverse skin incision. Material and methods Using a retrospective cohort design, case-records were reviewed of very severely obese women with a singleton pregnancy delivered by caesarean between August 2011 and December 2015 (n = 453) in two maternity hospitals in Scotland. Logistic regression analysis was used to determine predictors for SSSI. Outcomes were compared between women who had a supra-panniculus transverse compared to infra-panniculus transverse skin incision. Results Lower maternal age was predictive of SSSI, with current smoking status and longer wound open times being marginally significant. Maternal BMI, suture method and material demonstrated univariate associations with SSSI but were not independent predictors. Women with a supra-panniculus transverse skin incision were older (32.9 (4.4), vs. 30.6 (5.7), p = 0.002), had higher BMI (49.2 (7.1), vs. 43.3 (3.3), pPeer reviewe

Marine heatwaves redistribute pelagic fishing fleets

Marine heatwaves (MHWs) have measurable impacts on marine ecosystems and reliant fisheries and associated communities. However, how MHWs translate to changes in fishing opportunities and the displacement of fishing fleets remains poorly understood. Using fishing vessel tracking data from the automatic identification system (AIS), we developed vessel distribution models for two pelagic fisheries targeting highly migratory species, the U.S. Atlantic longline and Pacific troll fleets, to understand how MHW properties (intensity, size, and duration) influence core fishing grounds and fleet displacement. For both fleets, MHW size had the largest influence on fishing ground area with northern fishing grounds gaining and southern fishing grounds decreasing in area. However, fleet displacement in response to MHWs varied between coasts, as the Atlantic longline fleet displaced farther in southern regions whereas the most northern and southern regions of the Pacific troll fleet shifted farther. Characterizing fishing fleet responses to these anomalous conditions can help identify regional vulnerabilities under future extreme events and aid in supporting climate-readiness and resilience in pelagic fisheries

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses

Characteristics of undiagnosed diseases network applicants: implications for referring providers

Abstract Background The majority of undiagnosed diseases manifest with objective findings that warrant further investigation. The Undiagnosed Diseases Network (UDN) receives applications from patients whose symptoms and signs have been intractable to diagnosis; however, many UDN applicants are affected primarily by subjective symptoms such as pain and fatigue. We sought to characterize presenting symptoms, referral sources, and demographic factors of applicants to the UDN to identify factors that may determine application outcome and potentially differentiate between those with undiagnosed diseases (with more objective findings) and those who are less likely to have an undiagnosed disease (more subjective symptoms). Methods We used a systematic retrospective review of 151 consecutive Not Accepted and 50 randomly selected Accepted UDN applications. The primary outcome was whether an applicant was Accepted, or Not Accepted, and, if accepted, whether or not a diagnosis was made. Objective and subjective symptoms and information on prior specialty consultations were collected from provider referral letters. Demographic data and decision data on network acceptance were gathered from the UDN online portal. Results Fewer objective findings and more subjective symptoms were found in the Not Accepted applications. Not Accepted referrals also were from older individuals, reported a shorter period of illness, and were referred to the UDN by their primary care physicians. All of these differences reached statistical significance in comparison with Accepted applications. The frequency of subspecialty consults for diagnostic purposes prior to UDN application was similar in both groups. Conclusions The preponderance of subjective and lack of objective findings in the Not Accepted applications distinguish these from applicants that are accepted for evaluation and diagnostic efforts through the UDN. Not Accepted applicants are referred primarily by their primary care providers after multiple specialist consultations fail to yield answers. Distinguishing between patients with undiagnosed diseases with objective findings and those with primarily subjective findings can delineate patients who would benefit from further diagnostic processes from those who may have functional disorders and need alternative pathways for management of their symptoms. Trial registration clinicaltrials.gov NCT02450851 , posted May 21st 2015

Pathogenic SPTBN1 variants cause an autosomal dominant neurodevelopmental syndrome

SPTBN1 mutations cause a neurodevelopmental syndrome characterized by intellectual disability, language and motor delays, autism, seizures and other features. The variants disrupt beta II-spectrin function and disturb cytoskeletal organization and dynamics. SPTBN1 encodes beta II-spectrin, the ubiquitously expressed beta-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal beta II-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays;mild to severe intellectual disability;autistic features;seizures;behavioral and movement abnormalities;hypotonia;and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect beta II-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of beta II-spectrin in the central nervous system

Vitamin D Level and Risk of Community-Acquired Pneumonia and Sepsis

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A window into living with an undiagnosed disease: illness narratives from the Undiagnosed Diseases Network

Abstract Background Patients’ stories of their illnesses help bridge the divide between patients and providers, facilitating more humane medical care. Illness narratives have been classified into three types: restitution (expectation of recovery), chaos (suffering and loss), and quest (unexpected positive effect from illness). Undiagnosed patients have unique illness experiences and obtaining their narratives would provide insights into the medical and emotional impact of living with an undiagnosed illness. Adults and children with undiagnosed diseases apply to be evaluated by the Undiagnosed Diseases Network (UDN). Written illness narratives from 40 UDN applicants, including 20 adult probands who applied for themselves and 20 parents who applied for their children, were analyzed for: 1) narrative content and 2) narrative type. Results Narrative content: could be grouped into three themes: 1) Expectations of the UDN: the majority felt they had no further healthcare options and hoped the UDN would provide them with a diagnosis, with the adults expecting to return to their previously healthy life and the parents wanting information to manage their child’s healthcare. 2) Personal medical information: the narratives reported worsening of symptoms and some offered opinions regarding the cause of their illness. The proband narratives had few objective findings, while parental narratives had detailed objective information. 3) Experiences related to living with their undiagnosed illness: frustration at being undiagnosed was expressed. The adults felt they had to provide validation of their symptoms to providers, given the lack of objective findings. The parents worried that something relevant to their child’s management was being overlooked. Narrative type: All the narratives were of the chaos type, but for different reasons, with the probands describing loss and suffering and the parents expressing fear for their child’s future. The parental narratives also had elements of restitution and quest, with acceptance of “a new normal”, and an emphasis on the positive aspects of their child’s illness which was absent from the probands. Conclusions These narratives illustrate the chaos that coexists with being undiagnosed. The differences between the proband and parental narratives suggest that these two groups have different needs that need to be considered during their evaluation and management

Clinical application of a scale to assess genomic healthcare empowerment (GEmS): Process and illustrative case examples

The Genome Empowerment Scale (GEmS), developed as a research tool, assesses perspectives of parents of children with undiagnosed disorders about to undergo exome or genome sequencing related to the process of empowerment. We defined genomic healthcare empowerment as follows: perceived ability to understand and seek new information related to the genomic sequencing, manage emotions related to the diagnostic process and outcomes, and utilize genomic sequencing information to the betterment of the individual/child and family. The GEmS consists of four scales, two are primarily emotion-focused (Meaning of a Diagnosis, and Emotional Management of the Process) and two are action-oriented (Seeking Information and Support, and Implications and Planning). The purpose of this research was to provide a strategy for interpreting results from the GEmS and present illustrative cases. These illustrations should serve to facilitate use of the GEmS in the clinical and research arena, particularly with respect to guiding genetic counseling processes for parents of children with undiagnosed conditions