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Reddy Bugge opublikował 1 rok, 3 miesiące temu
ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients’ lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.
The principal triggers for intervention in the setting of pediatric blunt solid organ injury (BSOI) are declining hemoglobin values and hemodynamic instability. The clinical management of BSOI is, however, complex. We therefore hypothesized that state-of-art machine learning (computer-based) algorithms could be leveraged to discover new combinations of clinical variables that might herald the need for an escalation in care. We developed algorithms to predict the need for massive transfusion (MT), failure of non-operative management (NOM), mortality, and successful non-operative management without intervention, all within 4 hours of emergency department (ED) presentation.
Children (≤18 years) who sustained a BSOI (liver, spleen, and/or kidney) between 2009 and 2018 were identified in the trauma registry at a pediatric level 1 trauma center. Deep learning models were developed using clinical values [vital signs, shock index-pediatric adjusted (SIPA), organ injured, and blood products received], laboratory rt the need for emergent intervention (MT, angioembolization, or operative management) and mortality with high accuracy and sensitivity using data available in the first 4 hours of admission. Further research is needed to externally validate and determine the feasibility of prospectively applying this framework to improve care and outcomes.
III STUDY TYPE Retrospective comparative study (Prognosis/Care Management).
III STUDY TYPE Retrospective comparative study (Prognosis/Care Management).Colorectal cancer (CRC) is one of the most commonly occurring cancers worldwide. Although several genetic alterations have been associated with CRC onset and progression, nowadays the reprogramming of cellular metabolism has been recognized as a fundamental step of the carcinogenic process. Intestinal tumor cells frequently display an aberrant activation of lipid metabolism. Indeed, to satisfy the growing needs of a continuous proliferation, cancer cells can either increase the uptake of exogenous lipids or upregulate the endogenous lipogenesis and cholesterol synthesis. Therefore, strategies aimed at limiting lipid accumulation are now under development in order to counteract malignancies. Two major players of lipids metabolism have been so far identified for their contribution to CRC development the nuclear receptor Liver X Receptor (LXRs) and the enzyme Stearoyl-CoA Desaturase 1 (SCD1). Whereas LXR is mainly recognized for its role as a cholesterol sensor, finally promoting the loss of cellular cholesterol and whole-body homeostasis, SCD1 acts as the major regulator of new fatty acids, finely tuning the monounsaturated fatty acids (MUFA) to saturated fatty acids (SFA) ratio. Intriguingly, SCD1 is directly regulated by LXRs. Despite LXRs agonists have elicited great interest as a promising therapeutic target for cancer, LXR’s ability to induce SCD1 and new fatty acids synthesis represent a major obstacle in the development of new effective treatments. Thus, further investigations are required to fully dissect the concomitant modulation of both players, to develop specific therapies aimed at blocking intestinal cancer cells proliferation, eventually counteracting CRC progression.
Duodenal complications of necrotizing pancreatitis (NP) are challenging and understudied. We sought to characterize the demographics and clinical course of NP patients with duodenal complications.
Single institution retrospective review of 687 NP patients treated from 2005 to 2018.
Duodenal complications developed in 40 (6%) patients including fistula in 11 (2%) and stricture in 29 (4%) patients. Patients with duodenal complications had increased computed tomography severity index (CTSI), degree of glandular necrosis, organ failure, infected necrosis, and disease duration. Mortality from NP was increased in patients with duodenal fistula (36%) compared to patients with duodenal stricture (7%) and patients without duodenal complications (9%). Surgical management of duodenal complications was required in 9/11 (82%) patients with fistula and 17/29 (59%) patients with stricture.
Duodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.
Duodenal complications occurred in 6% of necrotizing pancreatitis patients. Sixty five percent of patients with duodenal complications required surgical correction. Duodenal fistula was associated with increased mortality.
The COVID-19 pandemic has disrupted surgical practice worldwide. There is widespread concern for surgeon and provider safety, and the implications of hospital lockdown on patient care during epidemics.
Medline, EMBASE, CENTRAL, and PubMed were systematically searched from database inception to July 1, 2020 and ongoing monthly surveillance will be conducted. We included studies that assessed postoperative patient outcomes or protection measures for surgical personnel during epidemics.
We included 61 studies relevant to the COVID-19 pandemic and past epidemics. Lockdown measures were noted globally including cancellation of elective surgeries and outpatient clinics. The pooled postoperative complication rate during epidemics was 21.0% among 2095 surgeries. 31 studies followed the health of surgical workers with the majority noting no adverse outcomes with proper safety measures.
This review highlights postoperative patient outcomes during worldwide epidemics including the COVID-19 pandemic and identifies specific safety measures to minimize infection of healthcare workers.
This review highlights postoperative patient outcomes during worldwide epidemics including the COVID-19 pandemic and identifies specific safety measures to minimize infection of healthcare workers.
The application of selective laser melting (SLM) to dentistry has been rapidly expanding; however, SLM-processed parts possess orientation-dependent properties (i.e., anisotropy) that can affect the long-term reliability of the dental prostheses. This study aimed to evaluate the anisotropic corrosion response of SLM-processed Co-Cr-Mo alloys under various heat treatments.
Samples fabricated via SLM along the horizontal plane (x-y plane) and vertical plane (x-z plane), with respect to the build direction, were subjected to various heat treatments. The resulting microstructures of the samples were characterized, and their corrosion properties were evaluated using anodic polarization and immersion tests.
All samples showed similar transpassive behavior of the polarization curves. However, the immersion tests showed that the as-built x-z plane samples released significantly more metal ions than those fabricated on the x-y plane because of the larger area of preferentially corroded molten pool boundaries (MPes.
Epidural analgesia is associated with intrapartum hyperthermia, and chorioamnionitis is associated with neonatal brain injury. However, it is not known if epidural hyperthermia is associated with neonatal brain injury. This systematic review and meta-analysis investigated three questions (1) does epidural analgesia cause intrapartum hyperthermia, (2) is intrapartum hyperthermia associated with neonatal brain injury, and (3) is epidural-induced hyperthermia associated with neonatal brain injury?
PubMed, ISI Web of Knowledge, The Cochrane Library, and Embase were searched from inception to January 2020 using Medical Subject Headings (MeSH) terms relating to epidural analgesia, hyperthermia, labour, and neonatal brain injury. Studies were reviewed independently for inclusion and quality by two authors (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach). Two meta-analyses were performed using the Mantel-Haenszel fixed effect method to generate odds ratios (ORs) and 95% confida is a cause of neonatal brain injury.
Acute global shortages of neuromuscular blocking agents (NMBA) threaten to impact adversely on perioperative and critical care. The use of pharmacological adjuncts may reduce NMBA dose. However, the magnitude of any putative effects remains unclear.
We conducted a systematic review and meta-analysis of RCTs. We searched Medline, Embase, Web of Science, and Cochrane Database (1970-2020) for RCTs comparing use of pharmacological adjuncts for NMBAs. We excluded RCTs not reporting perioperative NMBA dose. The primary outcome was total NMBA dose used to achieve a clinically acceptable depth of neuromuscular block. We assessed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) criteria. Data are presented as the standardised mean difference (SMD); I
indicates percentage of variance attributable to heterogeneity.
From 3082 records, the full texts of 159 trials were retrieved. Thirty-one perioperative RCTs met the inclusion criteria for meta-analysis (n=1962). No studies were conducted in critically ill patients. Reduction in NMBA dose was associated with use of magnesium (SMD -1.10 [-1.44 to -0.76], P<0.001; I
=85%; GRADE=moderate), dexmedetomidine (SMD -0.89 [-1.55 to -0.22]; P=0.009; I
=87%; GRADE=low), and clonidine (SMD -0.67 [-1.13 to -0.22]; P=0.004; I
=0%; GRADE=low) but not lidocaine (SMD -0.46 [-1.01 to -0.09]; P=0.10; I
=68%; GRADE=moderate). Meta-analyses for nicardipine, diltiazem, and dexamethasone were not possible owing to the low numbers of studies. We estimated that 30-50 mg kg
magnesium preoperatively (8-15 mg kg h
intraoperatively) reduces rocuronium dose by 25.5% (inter-quartile range, 14.7-31).
Magnesium, dexmedetomidine, and clonidine may confer a clinically relevant sparing effect on the required dose of neuromuscular block ing drugs in the perioperative setting.
PROSPERO CRD42020183969.
PROSPERO CRD42020183969.
Proctologic issues entail a frequent reason for consultation in the emergency department (ED). We aim to analyze how the SARS-COV-2 pandemic has impacted in the demand for proctological consultations.
Descriptive comparative retrospective study of cross-sectional cohorts of patients attending the ED for proctological complaints from March to April in 2020 and 2019. Demographic variables, comorbidities, reasons for consultation and diagnosis, treatment and readmission were included. Four periods were analyzed according to the different stages of the pandemic derived limitations.
A total of 191 patients were reviewed, 58 in 2020 and 133 in 2019 with an average age of 48 years (SD 20.1) and 112 (58.6%) males. The average number of daily consultations was 2.18 patients in 2019 versus 0.95 in 2020 (p=0.025) meaning a 56% reduction in consultations for proctological reasons. This difference in average consultations was significant in both periods of lockout (p=0.001) and previous de-escalation (p=0.014). The diagnosis distribution was similar between both periods; however, perianal abscesses doubled their rate in 2020, 22.


