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Alcohol is the most widely abused substance in the world, the leading source of mortality in 15–49‐year‐olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long‐term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re‐defined as a manifestation of sickness behavior secondary to alcohol‐induced inflammation, using the Bradford‐Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol‐exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well‐characterized cascade of systemic inflammation, additionally activating toll‐like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol‐related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol‐mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol‐related diseases. [ABSTRACT FROM AUTHOR]

Surgical inpatients are at increased risk of venous thromboembolism (VTE). Current national guidelines recommend a combination of pharmacological (chemoprophylaxis) and mechanical thromboprophylaxis to reduce VTE risk. For most patients, mechanical thromboprophylaxis is provided via application of graduated compression stockings (GCS). This editorial reviews the evidence surrounding the efficacy and safety of GCS in VTE prevention, and makes a recommendation regarding their continued use in surgical inpatients. [ABSTRACT FROM AUTHOR]

Objective: To compare the rate of venous thromboembolism (VTE) in surgical inpatients with pharmacological thromboprophylaxis and additional graduated compression stockings (GCSs) versus pharmacological thromboprophylaxis alone. Background: Surgical inpatients have elevated VTE risk; recent studies cast doubt on whether GCS confers additional protection against VTE, compared with pharmacological thromboprophylaxis alone. Methods: The review followed "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines using a registered protocol (CRD42017062655). The MEDLINE and Embase databases were searched up to November 2022. Randomized trials reporting VTE rate after surgical procedures, utilizing pharmacological thromboprophylaxis, with or without GCS, were included. The rates of deep venous thrombosis (DVT), pulmonary embolism, and VTE-related mortality were pooled through fixed and random effects. Results: In a head-to-head meta-analysis, the risk of DVT for GCS and pharmacological thromboprophylaxis was 0.85 (95% CI: 0.54-1.36) versus for pharmacological thromboprophylaxis alone (2 studies, 70 events, 2653 participants). The risk of DVT in pooled trial arms forGCS and pharmacological thromboprophylaxis was 0.54 (95% CI: 0.23-1.25) versus pharmacological thromboprophylaxis alone (33 trial arms, 1228 events, 14,108 participants). The risk of pulmonary embolism for GCS and pharmacological prophylaxis versus pharmacological prophylaxis alone was 0.71 (95% CI: 0.0-30.0) (27 trial arms, 32 events, 11,472 participants). There were no between-group differences in VTE-relatedmortality (27 trial arms, 3 events, 12,982 participants). Conclusions: Evidence from head-to-headmeta-analysis and pooled trial arms demonstrates no additional benefit for GCS in preventing VTE and VTErelated mortality. GCS confer a risk of skin complications and an economic burden; current evidence does not support their use for surgical inpatients. [ABSTRACT FROM AUTHOR]

Background: Although splicing is an integral part of the expression of many genes in our body, genetic syndromes with spliceosomal defects affect only specific tissues. To help understand the mechanism, we investigated the expression pattern of a core protein of the major spliceosome, SmB/B′ (Small Nuclear Ribonucleoprotein Polypeptides B/B′), which is encoded by SNRPB. Loss‐of‐function mutations of SNRPB in humans cause cerebro‐costo‐mandibular syndrome (CCMS) characterized by rib gaps, micrognathia, cleft palate, and scoliosis. Our expression analysis focused on the affected structures as well as non‐affected tissues, using chick and mouse embryos as model animals. Results: Embryos at young stages (gastrula) showed ubiquitous expression of SmB/B′. However, the level and pattern of expression became tissue‐specific as differentiation proceeded. The regions relating to CCMS phenotypes such as cartilages of ribs and vertebrae and palatal mesenchyme express SmB/B′ in the nucleus sporadically. However, cartilages that are not affected in CCMS also showed similar expressions. Another spliceosomal gene, SNRNP200, which mutations cause retinitis pigmentosa, was also prominently expressed in cartilages in addition to the retina. Conclusion: The expression of SmB/B′ is spatiotemporally regulated during embryogenesis despite the ubiquitous requirement of the spliceosome, however, the expression pattern is not strictly correlated with the phenotype presentation. Key Findings: Spliceosomal protein SmB/B' is expressed in a tissue‐specific manner despite the requirement of splicing in all cells in our bodyIn cartilages and palatine mesenchyme cells, SmB/B' is expressed in a sporadic manner: some cells express it strongly while others express it only weakly or do not express itCartilages and tissues that are not affected in CCMS also express SmB/B' prominently, thus the expression is not correlated with the phenotype presentationThe expression of SmB/B' in the nucleus is correlated to the cell cycle [ABSTRACT FROM AUTHOR]

Ribs are seldom affected by developmental disorders, however, multiple defects in rib structure are observed in the spliceosomal disease cerebro‐costo‐mandibular syndrome (CCMS). These defects include rib gaps, found in the posterior part of the costal shaft in multiple ribs, as well as missing ribs, shortened ribs and abnormal costotransverse articulations, which result in inadequate ventilation at birth and high perinatal mortality. The genetic mechanism of CCMS is a loss‐of‐function mutation in SNRPB, a component of the major spliceosome, and knockdown of this gene in vitro affects the activity of the Wnt/β‐catenin and bone morphogenic protein (BMP) pathways. The aim of the present study was to investigate whether altering these pathways in vivo can recapitulate rib gaps and other rib abnormalities in the model animal. Chick embryos were implanted with beads soaked in Wnt/β‐catenin and BMP pathway modulators during somitogenesis, and incubated until the ribs were formed. Some embryos were harvested in the preceding days for analysis of the chondrogenic marker Sox9, to determine whether pathway modulation affected somite patterning or chondrogenesis. Wnt/β‐catenin inhibition manifested characteristic rib phenotypes seen in CCMS, including rib gaps (P < 0.05) and missing ribs (P < 0.05). BMP pathway activation did not cause rib gaps but yielded missing rib (P < 0.01) and shortened rib phenotypes (P < 0.05). A strong association with vertebral phenotypes was also noted with BMP4 (P < 0.001), including scoliosis (P < 0.05), a feature associated with CCMS. Reduced expression of Sox9 was detected with Wnt/β‐catenin inhibition, indicating that inhibition of chondrogenesis precipitated the rib defects in the presence of Wnt/β‐catenin inhibitors. BMP pathway activators also reduced Sox9 expression, indicating an interruption of somite patterning in the manifestation of rib defects with BMP4. The present study demonstrates that local inhibition of the Wnt/β‐catenin and activation of the BMP pathway can recapitulate rib defects, such as those observed in CCMS. The balance of Wnt/β‐catenin and BMP in the somite is vital for correct rib morphogenesis, and alteration of the activity of these two pathways in CCMS may perturb this balance during somite patterning, leading to the observed rib defects. [ABSTRACT FROM AUTHOR]

Evaluation of the literature assessing the use of thermography, a non-invasive imaging modality that detects pathological temperature variation, in recognising superficial venous insufficiency (SVI).A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were screened by two individuals and data was subsequently extracted. Methodological quality was assessed with Cochrane’s risk of bias tool.Four studies comprising 363 patients were included. Three studies identified increased temperature uptake in veins with incompetent valves on venous duplex (p < .05). One study reported sensitivity and specificity of thermal imaging in SVI as 98.30% (95% CI, 95.2%–99.4%) and 100% (95% CI 85.7%–100%) respectively.Thermal imaging could act as a screening tool in SVI. This review highlights a lack of high-quality prospective studies evaluating the role of thermal imaging as a diagnostic tool that could expedite the assessment of patients. [ABSTRACT FROM AUTHOR]

Objective: This systematic review and meta-analysis aimed to appraise recent evidence assessing patency outcomes at various time points in patients with superior vena cava, subclavian, and brachiocephalic vein stenosis who had undergone stenting., Data Sources: PubMed, Scopus, and Cochrane Library databases were searched for studies up to December 2022., Review Methods: Measured outcomes included technical success rate, primary, primary assisted, and secondary patency at various time points. A subgroup analysis was also conducted to compare malignant and benign obstruction. GRADE was used to assess the certainty of evidence., Results: Thirty nine studies reporting outcomes in 1 539 patients were included in the meta-analysis. Primary patency up to one year after the procedure was 81.5% (95% CI 74.5 - 86.9%). Primary patency declined after one year to 63.2% (95% CI 51.9 - 73.1%) at 12 - 24 months. Primary assisted patency and secondary patency at ≥ 24 months were 72.7% (95% CI 49.1 - 88.0%) and 76.6% (95% CI 51.1 - 91.1%). In the subgroup analysis, primary patency was significantly higher in patients with a malignant stenosis compared with a benign stenosis at 1 - 3 and 12 - 24 months. No significant difference was seen for pooled secondary patency rates when comparing the malignant and benign subgroups. GRADE analysis determined the certainty of evidence for all outcomes to be very low., Conclusion: Stenting is an effective intervention for benign and malignant stenosis of the superior vena cava, subclavian, and brachiocephalic veins. Primary patency rates were good up to one year after the procedure, with 81.5% of stents retaining patency at 6 - 12 months. Patency rates declined after one year, to 63.2% primary and 89.3% secondary patency at 12 - 24 months, showing improved outcomes following re-intervention. High quality evidence is lacking. More research is needed to investigate patency outcomes and the need for surveillance or re-intervention programs., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To identify the rate of post-thrombotic syndrome (PTS) after isolated distal deep venous thrombosis (IDDVT) by performing a meta-analysis of the rate of PTS across randomised and observational studies., Data Sources: MEDLINE, Embase, the Cochrane Controlled Trials Register, Clinicaltrials.gov, European Union Clinical Trials, International Standard Randomised Controlled Trial Number, and the Australian and New-Zealand Trials Registries., Review Methods: This review followed PRISMA guidelines using a registered protocol (CRD42021282136). Databases were searched up to December 2021 and prospective studies reporting the development of post-thrombotic syndrome were included; these were pooled with the meta-analysis., Results: The results showed a post-thrombotic rate of 17% (95% CI 11 - 26%) (seven studies, 217 cases, 1 105 participants). Heterogeneity was high (I 2  = 89%). On meta-regression, the rate of post-thrombotic syndrome was not correlated with the length of follow up (p = .71). Three studies (302 participants) reported the severity of post-thrombotic syndrome: 78% were mild (Villalta score 5 - 9); 11% were moderate (Villalta score 10 - 14), and 11% were severe (Villalta score ≥ 15)., Conclusion: The risk of post-thrombotic syndrome after IDDVT was one in five and the risk of severe clinical manifestations, including ulceration, was one in 50. There was significant clinical, methodological, and statistical heterogeneity between studies and a substantial risk of bias from pooled studies. Randomised trials to support interventions for prevention of post-thrombotic syndrome are urgently needed., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: National guidelines in the United Kingdom have recommended regular exercise for individuals with venous leg ulceration. However, data on the effects of exercise on ulcer healing and recurrence are sparse. In the present study, we aimed to quantify the evidence for exercise regarding venous ulcer healing with respect to the primary outcomes of the proportion of healed ulcers and rate of ulcer recurrence. The secondary outcomes were improvement in ulcer symptoms, ulcer healing time, quality of life, compliance, and adverse events reported., Methods: The review followed PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines using a registered protocol (CRD42021220925). The MEDLINE and Embase databases and Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, European Union Clinical Trials, and International Standard Randomised Controlled Trial Number registries were searched up to April 6, 2022 and included studies comparing exercise therapy and compression vs compression alone. Data for the proportion of healed ulcers were pooled using a fixed effects meta-analysis., Results: After screening 1046 reports, 7 were included, with 121 participants allocated to exercise therapy and 125 to compression alone. All the reports were of randomized controlled trials and had reported ulcer healing at 12 weeks, with a pooled relative risk of ulcer healing of 1.38 for exercise vs compression (95% confidence interval, 1.11-1.71). Only one study had reported on recurrence; thus, data pooling was not performed. No differences between exercise and usual care were demonstrated. Compliance with exercise ranged from 33% to 81%. The included studies demonstrated low enrollment and a high risk of bias. Also, most of the trials had failed to demonstrate any differences in activity completed between the intervention and control arms., Conclusions: A paucity of studies has examined leg ulcer recurrence after exercise programs, with no evidence to show that exercise is beneficial. Furthermore, the quality of evidence supporting exercise as an adjunct to ulcer healing is very low, and the trials demonstrated serious methodologic flaws, chiefly in recording the activity undertaken by the participants in the intervention arm. Future randomized controlled trials should implement activity monitoring and standardize the reporting of key patient, ulcer, and reflux characteristics to enable future meaningful meta-analyses to determine the role of exercise as an adjunct to venous leg ulceration healing., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)