Search results
Found 30519 matches for
The Role of PTEN in Innate and Adaptive Immunity.
The lipid and protein phosphatase and tensin homolog (PTEN) controls the differentiation and activation of multiple immune cells. PTEN acts downstream from T- and B-cell receptors, costimulatory molecules, cytokine receptors, integrins, and also growth factor receptors. Loss of PTEN activity in human and mice is associated with cellular and humoral immune dysfunction, lymphoid hyperplasia, and autoimmunity. Although most patients with PTEN hamartoma tumor syndrome (PHTS) have no immunological symptoms, a subclinical immune dysfunction is present in many, and clinical immunodeficiency in few. Comparison of the immune phenotype caused by PTEN haploinsufficiency in PHTS, phosphoinositide 3-kinase (PI3K) gain-of-function in activated PI3K syndrome, and mice with conditional biallelic Pten deletion suggests a threshold model in which coordinated activity of several phosphatases control the PI3K signaling in a cell-type-specific manner. Emerging evidence highlights the role of PTEN in polygenic autoimmune disorders, infection, and the immunological response to cancer. Targeting the PI3K axis is an emerging therapeutic avenue.
A systematic review of sudden unexpected death in epilepsy (SUDEP) in childhood.
BACKGROUND: Sudden Unexpected Death in Epilepsy (SUDEP) is a significant cause of death in childhood epilepsy, and causes considerable concern to patients and their families. Despite this, the condition remains poorly understood. This systematic review investigates the risk factors, pathophysiology, and circumstances associated with childhood SUDEP. It aimed to explore the etiology of SUDEP and inform clinicians approaching SUDEP risk disclosure. METHODS: A structured electronic database search of MEDLINE, CENTRAL, EMBASE, and ISI web of science was conducted. Studies were included if they described clinical details of one or more patients, aged 18 years of age and below, who had SUDEP. Two reviewers independently reviewed each article for data extraction and quality assessment. RESULTS: Information on 108 cases of pediatric SUDEP was extracted from 22 included studies. These comprised five cohort studies, four retrospective case control studies, seven case series, and five case reports. Factors that appeared to be linked to pediatric SUDEP included those associated with severe epilepsy (early age of onset, high seizure frequency, intellectual impairment and developmental delay, multiple antiepileptic drug therapy, and structural abnormalities). The majority of included studies was noncomparative and had significant risk of bias. CONCLUSIONS: There is currently insufficient evidence to determine the etiology of pediatric SUDEP. Current best practice to prevent pediatric SUDEP is to optimize the management of epilepsy. A national SUDEP registry would provide invaluable high-quality data and insights into modifiable risk factors, genetic predispositions, and novel prevention strategies.
Neonatal outcomes of waterbirth: a systematic review and meta-analysis.
INTRODUCTION: In 2015, 9% of babies born in the UK were delivered underwater. Waterbirth is increasing in popularity, despite uncertainty regarding its safety for neonates. This systematic review and meta-analysis appraises the existing evidence for neonatal outcomes following waterbirth. METHODS: A structured electronic database search was performed with no language restrictions. All comparative studies which reported neonatal outcomes following waterbirth, and that were published since 1995, were included. Quality appraisal was performed using a modified Critical Appraisal Skills Programme scoring system. The primary outcome was neonatal mortality. Data for each neonatal outcome were tabulated and analysed. Meta-analysis was performed for comparable studies which reported sufficient data. RESULTS: The majority of the 29 included studies were small, with limited follow-up and methodological flaws. They were mostly conducted in Europe and high-income countries. Reporting of data was heterogeneous. No significant difference in neonatal mortality, neonatal intensive care unit/special care baby unit admission rate, Apgar scores, umbilical cord gases or infection rates was found between babies delivered into water and on land. CONCLUSIONS: This systematic review and meta-analysis did not identify definitive evidence that waterbirth causes harm to neonates compared with land birth. However, there is currently insufficient evidence to conclude that there are no additional risks or benefits for neonates when comparing waterbirth and conventional delivery on land.
Concurrent perforated Meckel's diverticulum and intestinal malrotation in an 8-year-old boy.
An 8-year-old boy with a history of recurrent abdominal pain presented with a 12 h history of severe periumbilical pain, nausea and vomiting. On examination, he was found to have a tender, erythematous, paraumbilical mass. At operative exploration, an abscess cavity was identified and followed to reveal a gangrenous Meckel's diverticulum, perforated at its tip to create the abscess. Around this Meckel's diverticulum, the small bowel had torted to produce a significant small bowel volvulus on a shortened mesentery. The caecum and ascending colon were found to be in the left upper quadrant and an intraoperative diagnosis of malrotation was made. Following resection of the Meckel's diverticulum and surgical correction of the malrotation, the child made an excellent recovery. His abdominal pain has not recurred in 6 months of follow-up since the operation.
Validity of self-reported hysterectomy: a prospective cohort study within the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
OBJECTIVE: To evaluate the validity of self-reported hysterectomy against the gold standard of uterine visualisation using pelvic ultrasound. DESIGN: Prospective cohort study. SETTING: UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) based in 13 National Health Service (NHS) Trusts in England, Wales and Northern Ireland. PARTICIPANTS: Between April 2001 and October 2005, 48 215 postmenopausal women aged 50-74 randomised to the ultrasound screening arm of UKCTOCS underwent the first (initial) scan on the trial. INTERVENTIONS: At recruitment, the women completed a recruitment questionnaire (RQ) which included previous hysterectomy. The sonographer asked each woman regarding previous hysterectomy (interview format, IF) prior to the scan. At the scan, in addition to ovarian morphology, endometrial thickness (ET)/endometrial abnormality were captured if the uterus was visualised at the scan. OUTCOME MEASURES: Self-reported hysterectomy at RQ or IF was compared to ultrasound data on ET/endometrial abnormality (as surrogate uterine visualisation markers) on the first (initial) scan. RESULTS: Of 48 215 women, 3 had congenital uterine agenesis and 218 inconclusive results. The uterus was visualised in 39 121 women. 8871 self-reported hysterectomy at RQ, 8641 at IF and 8487 at both. The uterus was visualised in 39 123, 39 353 and 38 969 women not self-reporting hysterectomy at RQ, IF or both. Validity, sensitivity, specificity, positive predictive value and negative predictive value of using RQ alone, IF or both RQ/IF were 99.6%, 98.9%, 99.7%, 98.9% and 99.7%; 98.9%, 98.4%, 99.1%, 95.9% and 99.7%; 99.8%, 99.6%, 99.9%, 99.4% and 99.9%, respectively. CONCLUSIONS: Self-reported hysterectomy is a highly accurate and valid source for studying long-term associations of hysterectomy with disease onset. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN)-22488978.
BESS Patient Care Pathway: Frozen Shoulder
Background Current guidelines from the British Elbow and Shoulder Society (BESS) were published in 2015 for managing frozen shoulder in the primary and secondary care setting. Updated guidelines have been developed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) methodology. Methods A multi-disciplinary BESS Working Group defined key management questions based on agreed outcome measures and time points. A literature search, conducted up to March 2023 following PRISMA guidelines, identified randomised controlled trials, systematic reviews, and meta-analyses. Quality assessments were performed using the GRADE Decision Framework, considering bias, imprecision, indirectness, and inconsistency. Data were extracted for meta-analysis. In the absence of high-quality trials, narrative reviews were created. Results Consensus opinions produced statements based on the quality and volume of evidence and the magnitude of desirable and undesirable effects. These statements form a comprehensive framework for managing frozen shoulder. Discussion This updated guideline provides evidence-based guidance for managing frozen shoulder and identifies key areas for future research.