Transcriptome Sequencing Revealed Significant Alteration of Cortical Promoter Usage and Splicing in Schizophrenia

While hybridization based analysis of the cortical transcriptome has provided important insight into the neuropathology of schizophrenia, it represents a restricted view of disease-associated gene activity based on predetermined probes. By contrast, sequencing technology can provide un-biased analysis of transcription at nucleotide resolution. Here we use this approach to investigate schizophrenia-associated cortical gene expression.The data was generated from 76 bp reads of RNA-Seq, aligned to the reference genome and assembled into transcripts for quantification of exons, splice variants and alternative promoters in postmortem superior temporal gyrus (STG/BA22) from 9 male subjects with schizophrenia and 9 matched non-psychiatric controls. Differentially expressed genes were then subjected to further sequence and functional group analysis. The output, amounting to more than 38 Gb of sequence, revealed significant alteration of gene expression including many previously shown to be associated with schizophrenia. Gene ontology enrichment analysis followed by functional map construction identified three functional clusters highly relevant to schizophrenia including neurotransmission related functions, synaptic vesicle trafficking, and neural development. Significantly, more than 2000 genes displayed schizophrenia-associated alternative promoter usage and more than 1000 genes showed differential splicing (FDR<0.05). Both types of transcriptional isoforms were exemplified by reads aligned to the neurodevelopmentally significant doublecortin-like kinase 1 (DCLK1) gene.This study provided the first deep and un-biased analysis of schizophrenia-associated transcriptional diversity within the STG, and revealed variants with important implications for the complex pathophysiology of schizophrenia

Sedation and Analgesia for Reduction of Pediatric Ileocolic Intussusception

IMPORTANCE: Ileocolic intussusception is an important cause of intestinal obstruction in children. Reduction of ileocolic intussusception using air or fluid enema is the standard of care. This likely distressing procedure is usually performed without sedation or analgesia, but practice variation exists. OBJECTIVE: To characterize the prevalence of opioid analgesia and sedation and assess their association with intestinal perforation and failed reduction. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study reviewed medical records of children aged 4 to 48 months with attempted reduction of ileocolic intussusception at 86 pediatric tertiary care institutions in 14 countries from January 2017 to December 2019. Of 3555 eligible medical records, 352 were excluded, and 3203 medical records were eligible. Data were analyzed in August 2022. EXPOSURES: Reduction of ileocolic intussusception. MAIN OUTCOMES AND MEASURES: The primary outcomes were opioid analgesia within 120 minutes of reduction based on the therapeutic window of IV morphine and sedation immediately before reduction of intussusception. RESULTS: We included 3203 patients (median [IQR] age, 17 [9-27] months; 2054 of 3203 [64.1%] males). Opioid use was documented in 395 of 3134 patients (12.6%), sedation 334 of 3161 patients (10.6%), and opioids plus sedation in 178 of 3134 patients (5.7%). Perforation was uncommon and occurred in 13 of 3203 patients (0.4%). In the unadjusted analysis, opioids plus sedation (odds ratio [OR], 5.92; 95% CI, 1.28-27.42; P = .02) and a greater number of reduction attempts (OR, 1.48; 95% CI, 1.03-2.11; P = .03) were significantly associated with perforation. In the adjusted analysis, neither of these covariates remained significant. Reductions were successful in 2700 of 3184 attempts (84.8%). In the unadjusted analysis, younger age, no pain assessment at triage, opioids, longer duration of symptoms, hydrostatic enema, and gastrointestinal anomaly were significantly associated with failed reduction. In the adjusted analysis, only younger age (OR, 1.05 per month; 95% CI, 1.03-1.06 per month; P \u3c .001), shorter duration of symptoms (OR, 0.96 per hour; 95% CI, 0.94-0.99 per hour; P = .002), and gastrointestinal anomaly (OR, 6.50; 95% CI, 2.04-20.64; P = .002) remained significant. CONCLUSIONS AND RELEVANCE: This cross-sectional study of pediatric ileocolic intussusception found that more than two-thirds of patients received neither analgesia nor sedation. Neither was associated with intestinal perforation or failed reduction, challenging the widespread practice of withholding analgesia and sedation for reduction of ileocolic intussusception in children

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Lenalidomide after Stem-Cell Transplantation for Multiple Myeloma

Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma

Thyroid cancer has a small impact on patient-partner relationships and their frequency of sexual activity

OBJECTIVE: This cross-sectional survey examined changes in perceived relationships and sexual activity in a sample of thyroid cancer patients and their partners, taking into account sociodemographic and disease-related variables, as well as such outcome measures as anxiety, depression, fatigue, and quality of life (QoL). METHOD: A total of 38 patients with thyroid cancer who were being treated at the department of nuclear medicine in Zürich or Lucerne over the preceding seven years, as well as their partners, completed questionnaires about the quality of their relationships (RQ), about perceptions of changes in their relationships, and about their frequency of sexual activity. They also filled out prevalidated questionnaires related to anxiety, depression, fatigue, and QoL. RESULTS: Some 17 patients (44.7%) and 16 partners (42.1 %) reported that the cancer diagnosis had changed their relationships. Of these, 10 (26.3%) patients and 9 (23.7%) partners reported positive changes only, while 7 patients (18.4%) and 7 partners (18.4%) reported mixed or negative changes. A perceived mixed/negative relationship change was associated with increased depression and lower RQ in patients and partners, as well as with increased anxiety in patients. While the frequency of sexual activity only changed in roughly half of patients and partners (16 patients [42.1%] and 20 partners [52.6%]), increased sexual activity was associated with lower physical QoL scores and a higher depression score than in counterparts who reported no change. SIGNIFICANCE OF RESULTS: Compared to other cancer sites, in our sample thyroid cancer had a relatively small impact on patient-partner relationships and levels of intimacy. We found that screening patients and their partners with a simple question-"Did the diagnosis of cancer change your relationship?"-can lead to early detection of couples who are potentially at risk for perceived negative relationship changes and can facilitate timely psychosocial referral for couple's therapy

Performance of the pediatric-sized i-gel compared with the Ambu AuraOnce laryngeal mask in anesthetized and ventilated children

This prospective, randomized, controlled trial compares the performance of the pediatric i-gel (Intersurgical Ltd., Wokingham, United Kingdom) with the Ambu AuraOnce laryngeal mask (Ambu A/S, Ballerup, Denmark) in anesthetized and ventilated children

Patients’ early post-operative experiences with lung transplantation: a longitudinal qualitative study

BACKGROUND AND OBJECTIVES: Lung transplantation is a complex medical treatment, and for patients with end-stage lung diseases it is often the last therapeutic option available for survival. However, lung transplantation poses not only a physical but also a psychological challenge for patients. The aim of this study was to gain a deeper understanding of patients' individual concerns related to their lung transplantation within the first 6 months post-transplant. METHODS: Forty lung transplant patients were interviewed at three different measurement timepoints post-transplant (T1: 2 weeks; T2: 3 months; and T3: 6 months) using semi-structured interviews to address their thoughts, feelings, and attitudes with respect to the transplantation process, their new lungs, and their medication. Interviews were analyzed by means of qualitative content analysis. RESULTS: "Physical complaints", "fear of organ rejection", "side effects of medication", and "restrictions in everyday life" were the most frequently named concerns within the first 6 months post-transplant. Most themes remained unchanged over time, whereas mentions of restrictions in everyday life increased significantly over the three assessments. CONCLUSIONS: Although the majority of the patients experienced considerable improvements in physical health after transplantation, they simultaneously reported that they were suffering from physical complaints, fear of organ rejection and infections, medication adverse effects, and restrictions in everyday life. For patients, lung transplantation therefore often means replacing one disease with another. Healthcare providers are challenged to support patients in dealing with this unresolvable dilemma