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Multiple randomized controlled trials (RCTs) have examined first-line pharmacological agents such as anticholinergics and β3 agonists for the management of overactive bladder symptoms (OAB). Although earlier systematic reviews and (network) meta-analyses aimed to summarize the evidence, a substantial number of trials were not included, so a comprehensive and methodologically rigorous evaluation of the comparative effectiveness of all first-line pharmacological treatments is lacking. We aim to conduct a series of systematic reviews and network meta-analyses (NMAs) for a comprehensive assessment of the effectiveness and safety of first-line pharmacological treatments for OAB. Eligible studies will include RCTs comparing anticholinergics and β3 agonists to one another or to placebo in adults with OAB or detrusor overactivity. Pairs of reviewers with methodological training will independently evaluate candidate studies to determine eligibility and extract relevant data. We will incorporate patient-important outcomes, including urinary urgency episodes, urgency incontinence episodes, any type of incontinence episodes, urinary frequency, nocturia, and adverse events. We will conduct the NMAs using a frequentist framework and a graph theory model for each outcome. Analysis will follow rigorous methodologies, including handling of missing data and assessment of the risk of bias. We will conduct sensitivity and subgroup analyses and will apply the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to rate evidence certainty. Our approach aims to address the knowledge gap in the treatment of OAB by synthesizing evidence from RCTs worldwide. We will employ robust statistical methods, including frequentist NMA, to general clinically relevant and patient-important insights. Sensitivity and subgroup analyses will enhance the robustness and generalizability of our findings. Our reviews strive to inform evidence-based decisions in the management of OAB, to ultimate improve patient outcomes. Our study results may guide health policy decisions, such as reimbursement policies, and future studies in functional urology.The protocol for the review series is registered on PROSPERO as CRD42023266915.

Abstract Auxetic metamaterials are a unique class of materials or structures with a negative Poisson’s ratio and a wide array of functionalities. However, their inherent porosity presents challenges in practical applications. Filling the inherent perforations while preserving their unique auxeticity is difficult because it demands the seamless integration of components that have highly distinct mechanical characteristics. Here we introduce a seamless auxetic substrate film capable of achieving a negative Poisson’s ratio of −1, the theoretical limit of isotropic materials. This breakthrough is realized by incorporating a highly rigid auxetic structure reinforced by glass-fabric, with surface-flattening soft elastomers. We effectively optimize the mechanical properties of these components by systematic experimental and theoretical investigations into the effects of relative differences in the moduli of the constituents. Using the developed auxetic film we demonstrate an image distortion-free display having 25 PPI resolution of micro-LEDs that is capable of 25% stretching without performance degradation.

Objective: Due to its video based approach, YouTube has become a widely accessed educational resource for patients and trainees. This systematic review characterised and evaluated the peer reviewed literature investigating YouTube as a source of patient or trainee education in vascular surgery. Data sources: A comprehensive literature search was conducted using EMBASE, MEDLINE, and Ovid HealthStar from inception until 19 January 2023. All primary studies and conference abstracts evaluating YouTube as a source of vascular surgery education were included. Review methods: Video educational quality was analysed across several factors, including pathology, video audience, and length. Results: Overall, 24 studies were identified examining 3 221 videos with 123.1 hours of content and 37.1 million views. Studies primarily examined YouTube videos on diabetic foot care (7/24, 29%), peripheral arterial disease (3/24, 13%), carotid artery stenosis (3/24, 13%), varicose veins (3/24, 13%), and abdominal aortic aneurysm (2/24, 8%). Video educational quality was analysed using standardised assessment tools, author generated scoring systems, or global author reported assessment of quality. Six studies assessed videos for trainee education, while 18 studies evaluated videos for patient education. Among the 20 studies which reported on the overall quality of educational content, 10/20 studies deemed it poor, and 10/20 studies considered it fair, with 53% of studies noting poor educational quality for videos intended for patients and 40% of studies noting poor educational quality in videos intended for trainees. Poor quality videos had more views than fair quality videos (mean 27 348, 95% CI 15 154–39 543 views vs. 11 372, 95% CI 3 115–19 629 views, p = .030). Conclusion: The overall educational quality of YouTube videos for vascular surgery patient and trainee education is suboptimal. There is significant heterogeneity in the quality assessment tools used in their evaluation. A standardised approach to online education with a consistent quality assessment tool is required to better support online patient and trainee education in vascular surgery.

Background: Although hydrocele is one of the most common urologic pathologies, it is seldom studied, and the major urologic associations have no guidelines for the management of adult hydroceles. Objective: To characterize international practice variation in the treatment of adult hydroceles. Design, setting, and participants: An international survey was conducted addressing the management of hydroceles among urologists in Belgium, Denmark, Finland, Iceland, Japan, and the Netherlands from September to December 2020. We invited a random sample of 170 urologists from each country (except Iceland). Outcome measurements and statistical analysis: Urologists’ treatment options, factors relevant for decision-making, expected patient satisfaction, and outcomes after aspiration versus surgery were assessed. Results and limitations: Of the 864 urologists contacted, 437 (51%) participated. Of the respondents, 202 (53%) performed both hydrocelectomies and aspiration, 147 (39%) performed hydrocelectomies only, and 30 (8%) performed aspiration only. In Belgium (83%), the Netherlands (75%), and Denmark (55%), urologists primarily performed hydrocelectomies only, whereas in Finland (84%), Japan (61%), and Iceland (91%), urologists performed both hydrocelectomies and aspiration. Urologists favored hydrocelectomy for large hydroceles (78.8% vs 37.5% for small), younger patients (66.0% for patients

Introduction Large language model (LLM)-linked chatbots are being increasingly applied in healthcare due to their impressive functionality and public availability. Studies have assessed the ability of LLM-linked chatbots to provide accurate clinical advice. However, the methods applied in these Chatbot Assessment Studies are inconsistent due to the lack of reporting standards available, which obscures the interpretation of their study findings. This protocol outlines the development of the Chatbot Assessment Reporting Tool (CHART) reporting guideline.Methods and analysis The development of the CHART reporting guideline will consist of three phases, led by the Steering Committee. During phase one, the team will identify relevant reporting guidelines with artificial intelligence extensions that are published or in development by searching preprint servers, protocol databases, and the Enhancing the Quality and Transparency of health research Network. During phase two, we will conduct a scoping review to identify studies that have addressed the performance of LLM-linked chatbots in summarising evidence and providing clinical advice. The Steering Committee will identify methodology used in previous Chatbot Assessment Studies. Finally, the study team will use checklist items from prior reporting guidelines and findings from the scoping review to develop a draft reporting checklist. We will then perform a Delphi consensus and host two synchronous consensus meetings with an international, multidisciplinary group of stakeholders to refine reporting checklist items and develop a flow diagram.Ethics and dissemination We will publish the final CHART reporting guideline in peer-reviewed journals and will present findings at peer-reviewed meetings. Ethical approval was submitted to the Hamilton Integrated Research Ethics Board and deemed “not required” in accordance with the Tri-Council Policy Statement (TCPS2) for the development of the CHART reporting guideline (#17025).Registration This study protocol is preregistered with Open Science Framework: https://doi.org/10.17605/OSF.IO/59E2Q.

Background and Objectives: The number of lymph nodes found harboring metastasis can be impacted by the extent of harvest. Guidelines recommend 12 lymph nodes for adequate lymphadenectomy to predict long-term oncologic outcomes, yet different cut-offs remain unevaluated. The aim of this review was to determine cut-offs that may predict survival outcomes. Methods: Medline, Embase, and CENTRAL were systematically searched. Articles were included if they compared overall survival (OS) or disease-free survival (DFS) above and below a lymph node harvest cut-off. Studies solely examining rectal cancer or stage-IV disease were excluded. Pairwise meta-analyses using inverse variance random effects were performed. Results: From 2587 citations, 20 studies with 854,359 patients (51.9% female, mean age: 68.9) were included, with 19 studies included in quantitative synthesis. A lymph node harvest cut-off of 12 predicted improved five-year OS (7 studies; OR 1.11, 95% CI 1.08–1.14, p

PurposeTo optimize patients prior to bariatric surgery, very low energy diets (VLEDs) are often employed for 2–4 weeks preoperatively. They are known to result in preoperative weight loss, decrease liver volume, and decrease surgeon-perceived operative difficulty. Their impact on postoperative morbidity has been less extensively studied. We performed a focused systematic review and meta-analysis with the aim of comparing preoperative VLEDs prior to bariatric surgery with controls in terms of overall postoperative morbidity.MethodsMEDLINE, Embase, and CENTRAL were searched from database inception to February 2023. Articles were eligible for inclusion if they were randomized controlled trials (RCTs) comparing postoperative morbidity in adult patients (i.e., over the age of 18) receiving a VLED with liquid formulation to those receiving a non-VLED control prior to elective bariatric surgery. Outcomes included overall 30-day postoperative morbidity and preoperative weight loss. An inverse variance meta-analysis was performed with GRADE assessment of the quality of evidence.ResultsAfter reviewing 2,525 citations, four RCTs with 294 patients receiving preoperative VLEDs with liquid formulation and 294 patients receiving a non-VLED control met inclusion. Patients receiving VLED experienced significantly more preoperative weight loss than patients receiving control (mean difference (MD) 3.38 kg, 95% confidence interval (CI) 1.06–5.70, p = 0.004, I2 = 95%). According to low certainty evidence, there was a non-significant reduction in 30-day postoperative morbidity in patients receiving VLED prior to bariatric surgery (risk ratio (RR) 0.67, 95%CI 0.39–1.17, p = 0.16, I2 = 0%).ConclusionThe impact of preoperative VLEDs on postoperative outcomes following bariatric surgery remains unclear. It is possible that VLEDs may contribute to decreased postoperative morbidity, but further larger prospective trials are required to investigate the signal identified in this study.

Background: Loop ileostomies (LIs) are used for temporary fecal diversion to protect downstream colorectal anastomoses. Standard operative approach for LI reversal has been through an open technique. Recently, laparoscopic LI reversal has been employed and studied. The aim of this systematic review was to compare laparoscopic and open LI reversal. Methods: Medline, Embase, and CENTRAL were systematically searched. Articles were included if they compared rate of postoperative morbidity and/or length of stay (LOS) in patients undergoing laparoscopic or open LI reversal. Pairwise meta-analyses using inverse variance random effects was performed. The Grading of Recommendations, Assessment, Development, and Evidence (GRADE) approach was conducted to assess quality of evidence. Results: From 410 citations, four observational studies with 213 patients undergoing laparoscopic LI reversal and 176 patients undergoing open LI reversal met inclusion. Patients in the laparoscopic group had significantly shorter LOS (MD -0.39, 95%CI -0.73 to -0.04, p = 0.03). Laparoscopic and open LI reversal were comparable in postoperative morbidity, aside from a decrease of superficial surgical site infection (sSSI) with the use of laparoscopy (OR 0.22, 95%CI 0.07 to 0.71, p = 0.01). Operative time was not significantly different between groups (MD 11.91, 95%CI -1.87 to 25.70, p = 0.09). The GRADE quality of evidence was low to very low. Conclusions: This review presents low quality evidence that laparoscopic LI reversal is a feasible approach that may reduce postoperative LOS and sSSI compared to open LI reversal without increasing operative time. Future prospective comparative studies are required to confirm the findings of the present review.

Abstract Background Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. Methods We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. Discussion This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. Systematic review registration PROSPERO CRD42021234119

Psoriasis is a chronic inflammatory skin disorder characterized by the hyperproliferation of keratinocytes and immune system dysregulation, with significant needs due to the limitations and adverse effects of current treatments. In this study, we sought to discover novel herbal candidates and their active compounds for psoriasis by leveraging a multiscale network analysis. We conducted a comprehensive analysis of data from 348 medicinal herbs and their active compounds, identifying Piperis longi fructus, Pini koraiensis semen, Schisandrae fructus, and Cnidi fructus as top candidates without reported evidence. Key active compounds, such as piperine, piperlongumine, α-humulene, schizandrin A, schizandrin II, and torilin, were prioritized for their ability to target psoriasis-associated proteins, including STAT3, TNF, IL-6, and NF-κB. These compounds are involved in the modulation of critical inflammatory pathways, notably the MAPK signaling cascade, which plays a central role in psoriasis pathogenesis. Our findings suggest that these herbal compounds may not only mitigate inflammation but also regulate keratinocyte hyperproliferation, addressing fundamental mechanisms underlying the disease. This approach highlights the utility of multiscale network analysis in identifying promising natural therapies, offering new insights and potential avenues for safer and more effective psoriasis management.

Docosahexaenoic acid (DHA) plays important roles in the prevention of ageing and ageing-related diseases. In this work, the anti-ageing effect of Schizochytrium mangrovei (SM), a marine microalga with high contents of DHA was investigated for the first time. In vitro results showed that SM enhanced the vitality of healthy pheochromocytoma (PC12) cells, whereas it had no protective effect under H2O2-induced oxidative stress. Meanwhile, SM exerted neuroprotective actions in vivo: the supplementation of SM significantly extended the lifespan of both wild type and SODn108 mutant flies Drosophila melanogaster, and ameliorated the age-related decline of locomotor function. This lifespan-extending activity was associated with the mRNA up-regulation of endogenous stress-defense genes such as CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2), as well as the down-regulation of Methuselah (MTH) gene. Therefore, it was concluded that the anti-ageing capability of DHA-rich SM was mediated through the cooperation with endogenous stress-defense system rather than the direct interaction with oxidative free radicals.

JUSTIFICATIVA E OBJETIVOS: Os efeitos do IMC na dispersão subaracnóidea de bupivacaína são controversos. O presente estudo avaliou a ED95 de bupivacaína subaracnóidea em cesarianas eletivas em mulheres obesas e naquelas com peso normal. MÉTODO: Foram avaliadas gestantes com peso normal (IMC < 25 kg.m-2) e obesas (IMC > 30 kg.m-2) com feto único de termo, submetidas a cesarianas eletivas. Esse foi um estudo encoberto e de alocação sequencial usando o método up-and-down (modificado pela regra de Narayana). Todas as pacientes receberam bloqueio combinado raquiperidural com administração subaracnóidea de doses variáveis de bupivacaína hiperbárica a 0,75% mais 10 µg de fentanil e 100 µg de morfina. A primeira paciente recebeu 9 mg de bupivacaína. A anestesia foi suplementada quando necessário por meio de um cateter peridural. O sucesso da anestesia, definido como bloqueio sensitivo até pelo menos T6 sem necessidade de anestesia suplementar, foi o objetivo primário. A ED95 para resultado satisfatório foi determinada por modelo logístico sem transformação logarítmica das doses. RESULTADOS: Vinte e quatro gestantes com peso normal e dezesseis gestantes obesas participaram deste estudo. A ED95 estimada para todas as pacientes foi de 12,92 mg (IC 95%: 11,49 a 34,77). A ED95 estimada para as gestantes com peso normal e as gestantes obesas foi semelhante, 12,78 mg (IC 95%: 10,75 a + infinito) e 11,86 mg (CI 95%: 11,31 a 15,61), respectivamente. CONCLUSÕES: Se a anestesia subaracnóidea com injeção única for utilizada em cesarianas, pacientes com peso normal e obesas devem receber doses semelhantes de bupivacaína hiperbárica. Apesar de não ter sido possível determinar com precisão a ED95 nesse estudo, é possível afirmar que ela é de pelo menos 11,49 mg.JUSTIFICATIVA Y OBJETIVOS: Los efectos del IMC en la dispersión intratecal de bupivacaína son controvertidos. El presente estudio evaluó la ED95 de bupivacaína intratecal en cesáreas de elección en mujeres obesas y con peso normal. MÉTODO: Evaluamos embarazadas con peso normal (IMC < 25 kg.m-2) y obesas (IMC > 30 kg.m-2), con feto único a término, sometidas a cesáreas de elección. Ese fue un estudio mono ciego y de ubicación secuencial, usando el método up-down (modificado por la regla de Narayana). Todas las pacientes recibieron bloqueo combinado raquiepidural con administración intratecal de dosis variables de bupivacaína hiperbárica a 0.75% más 10 µg de fentanil y 100 µg de morfina. La primera paciente recibió 9 mg de bupivacaína. La anestesia se suplementó cuando fue necesario, a través de un catéter epidural. El éxito de la anestesia, definido como bloqueo sensitivo hasta por lo menos T6, sin necesidad de anestesia suplementaria, fue el objetivo primario. La ED95 para un resultado satisfactorio fue determinada por un modelo logístico sin transformación logarítmica de las dosis. RESULTADOS: Veinte y cuarto embarazadas con peso normal y dieciséis embarazadas obesas participaron en este estudio. La ED95 estimada para todas las pacientes fue de 12,92 mg (IC 95%: 11,49 a 34,77). La ED95 estimada para las embarazadas con peso normal y las embarazadas obesas fue similar, 12,78 mg (IC 95%: 10,75 a + infinito) y 11,86 mg (CI 95%: 11,31 a 15,61), respectivamente. CONCLUSIONES: Si la anestesia raquídea con inyección única es utilizada en cesáreas, las pacientes con peso normal y obesas deben recibir dosis parecidas de bupivacaína hiperbárica. A pesar de que no fuimos capaces de determinar con exactitud la ED95 en nuestro estudio, sí que podemos afirmar que es de por lo menos 11,49 mg.BACKGROUND AND OBJECTIVES: The effect of BMI on the spread of intrathecal bupivacaine is controversial. This study assessed the ED95 of intrathecal bupivacaine for elective cesarean delivery in obese and normal weight women. METHODS: We studied normal weight (BMI < 25 kg.m-2) and obese (BMI > 30 kg.m-2) women with singleton term pregnancies undergoing elective cesarean delivery. The study was conducted as a single blinded, up-down sequential allocation study (modified by the Narayana rule). All patients received a combined spinal-epidural anesthesia with a variable intrathecal dose of hyperbaric 0.75% bupivacaine, plus fentanyl 10 µg and morphine 100 µg. The first patient received 9 mg of bupivacaine. Supplemental anesthesia was provided through the epidural catheter if required. The primary outcome was successful analgesia, defined as a sensory block to at least T6, and no request for supplemental anesthesia. The ED95 for the satisfactory outcome was determined by a logistic model with non-log-transformed doses. RESULTS: Twenty-four normal weight and sixteen obese patients were enrolled. The estimated ED95 for all forty patients was 12.92 mg (95% CI: 11.49 to 34.77). The estimated ED95 for the normal weight and the obese subgroups were similar at 12.78 mg (95% CI: 10.75 to + infinity) and 11.86 mg (95%CI: 11.31 to 15.61), respectively. CONCLUSIONS: If single shot spinal anesthesia is used for cesarean delivery, obese and normal weight patients should receive similar doses of hyperbaric bupivacaine. Although in our study the effective dose 95% could not be precisely determined, it is possible to state that it is at least 11.49 mg.

The lower female reproductive tract (FRT) is comprised of the cervix and vagina, surfaces that are continuously exposed to a variety of commensal and pathogenic organisms. Sexually transmitted viruses, such as herpes simplex virus type 2 (HSV-2), have to traverse the mucosal epithelial lining of the FRT to establish infection. The majority of current culture systems that model the host-pathogen interactions in the mucosal epithelium have limitations in simulating physiological conditions as they employ a liquid-liquid interface (LLI), in which both apical and basolateral surfaces are submerged in growth medium. We designed the current study to simulate in vivo conditions by growing an immortalized vaginal epithelial cell line (Vk2/E6E7) in culture with an air-liquid interface (ALI) and examined the effects of female sex hormones on their growth, differentiation, and susceptibility to HSV-2 under these conditions, in comparison to LLI cultures. ALI conditions induced Vk2/E6E7 cells to grow into multi-layered cultures compared to the monolayers present in LLI conditions. Vk2 cells in ALI showed higher production of cytokeratin in the presence of estradiol (E2), compared to cells grown in progesterone (P4). Cells grown under ALI conditions were exposed to HSV-2-green fluorescent protein (GFP) and the highest infection and replication was observed in the presence of P4. Altogether, this study suggests that ALI cultures more closely simulate the in vivo conditions of the FRT compared to the conventional LLI cultures. Furthermore, under these conditions P4 was found to confer higher susceptibility to HSV-2 infection in vaginal cells. The vaginal ALI culture system offers a better alternative to study host-pathogen interactions.

Background: Acute necrotizing encephalopathy (ANE), a fulminant encephalopathy, is often found in childhood. It is still uncertain whether adult patients with ANE display clinical features different from patients with typical pediatric onset. Furthermore, alterations in neuroinflammatory factors in patients with ANE have not been well-characterized. Here, we present an adult patient with ANE, and review all reported adult ANE cases in the literature. Methods: Serum levels of five cytokines were checked in an adult patient with ANE and compared with gender/age-matched controls. Literature search was performed with PubMed, using the term as “acute necrotizing encephalopathy” with the filter of adult 19 + years. Results: A total of 13 adult patients were reviewed. Compared with pediatric patients, adult ANE patients had similar clinical symptoms, biochemical data, and neuroimage findings, whereas adult ANE were more female-biased (female:male, 9:4) with a worse prognosis. Elevated cytokine levels in the serum and/or CSF is found in both adult-onset and pediatric-onset ANE. We found significantly elevated serum levels of IL-6 (17.17 pg/mL; healthy control: 1.43 ± 1.22 pg/mL) and VCAM-1 (3033.92 ng/mL; healthy control: 589.71 ± 133.13 ng/mL), and decreased serum TGF-β1 level (14.78 ng/mL, healthy controls: 25.81 ± 6.97 ng/mL) in our patient. Conclusions: Our findings clearly delineate the clinical features and further indicate the potential change in cytokine levels in adult patients with ANE, advancing our understanding of this rare disease. Keywords: Acute necrotizing encephalopathy, Adult, Cytokine, VCAM-1

Vitamin E is one of the most popular fat-soluble vitamins in pathological research and has been under scrutiny since the 1980s as a vital dietary component of food. The antioxidant effect of vitamin E has been widely studied due to its benefits in the prevention of various cardiovascular diseases. In recent years, alternative effects of vitamin E, in terms of anti-inflammatory pathways and gene regulation, have also been of interest to researchers. This review examines the role of dietary vitamin E (α-tocopherol) as an antioxidant and bioactive molecule in promoting vascular health. While the antioxidant effect of vitamin E is well established, knowledge about its capacity as a promising regulatory molecule in the control of the vascular system is limited. The aim of this review is to discuss some of these mechanisms and summarize their role in the prevention of cardiovascular diseases (CVD). Here, we also briefly discuss foods rich in vitamin E, and deliberate some potential toxicological effects of excessive supplemental vitamin E in the body.

Cerebral adrenoleukodystrophy (ALD) is a rare neuroinflammatory disorder characterized by progressive demyelination. Mutations within the ABCD1 gene result in very long-chain fatty acid (VLCFA) accumulation within the peroxisome, particularly in the brain. While this VLCFA accumulation is known to be the driving cause of the disease, oxidative stress can be a contributing factor. For patients with early cerebral disease, allogeneic hematopoietic stem cell transplantation (HSCT) is the standard of care, and this can be supported by antioxidants. To evaluate the involvement of fatty acid oxidation in the disease, F2-isoprostanes (F2-IsoPs), F2-dihomo-isoprostanes (F2-dihomo-IsoPs) and F4-neuroprostanes (F4-NeuroPs)—which are oxygenated metabolites of arachidonic (ARA), adrenic (AdA) and docosahexaenoic (DHA) acids, respectively—in plasma samples from ALD subjects (n = 20)—with various phenotypes of the disease-were measured. Three ALD groups were classified according to patients with: (1) confirmed diagnosis of ALD but without cerebral disease; (2) cerebral disease in early period post-HSCT (n = 29), in ALD (i), F2-IsoPs levels were significantly (p < 0.01) increased in all patients, with the single exception of the early ALD and on NAC subjects; (ii) significant elevated (p < 0.0001) amounts of F2-dihomo-IsoPs were detected, with the exception of patients with a lack of cerebral disease; (iii), a significant increase (p < 0.003) in F4-NeuroP plasma levels was detected in all ALD patients. Moreover, F2-IsoPs plasma levels were significantly higher (p = 0.038) in early ALD in comparison to late ALD stage, and F4-NeuroPs were significantly lower (p = 0.012) in ALD subjects with a lack of cerebral disease in comparison to the late disease stage. Remarkably, plasma amounts of all investigated isoprostanoids were shown to discriminate ALD patients vs. healthy subjects. Altogether, isoprostanoids are relevant to the phenotype of X-ALD and may be helpful in predicting the presence of cerebral disease and establishing the risk of progression.

Objective: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. Background: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. Methods: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. Results: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. Conclusions: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding. [ABSTRACT FROM AUTHOR]

Etomidate is an anesthetic agent used in hemodynamically unstable patients, but its use has been controversial in septic patients. The response of high-mobility group box 1 (HMGB1), a late-phase lethal cytokine in sepsis, to etomidate has not been reported. This study investigated the effects of etomidate on the expression and release of HMGB1 and the underlying mechanism using a cecal ligation and puncture (CLP) model. Thirty-six male Sprague--Dawley rats were divided into sham, CLP, and Etomi groups. Sepsis was induced in the CLP and Etomi groups, and intravenous etomidate (4 mg/kg) was infused for 40 min immediately after operation in the Etomi group. Serum creatinine, alanine aminotransferase (ALT), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and HMGB1 levels were measured 6 and 24 hours after surgery. Activation of nuclear factor (NF)--B and HMGB1 mRNA expression in the liver, lung, kidney, and ileum tissues were measured, and immunohistochemical staining of HMGB1 was implemented. Increases of the TNF-α level 6 h after CLP and ALT and IL-6 levels 24 h after CLP were significantly inhibited by etomidate treatment. Etomidate treatment also significantly attenuated the increase in serum HMGB1 level at 6 and 24 h after CLP and suppressed the NF and HMGB1 mRNA in multiple organs 24 h after CLP. Immunohistochemical staining also revealed that etomidate treatment inhibited HMGB1 expression. Etomidate inhibited the systemic release of HMGB1 and its expression in various organs. The mechanism may be associated with the inhibitory effects of etomidate on proinflammatory cytokine release and NF-B activity. [ABSTRACT FROM AUTHOR]

F4-neuroprostanes (F4-NeuroPs), derived from the oxidative metabolization of docosahexaenoic acid (DHA), are considered biomarkers of oxidative stress in neurodegenerative diseases. Neurons and spermatozoa display a high DHA content. NeuroPs might possess biological activities. The aim of this in vitro study was to investigate the biological effects of chemically synthetized 4-F4t-NeuroP and 10-F4t-NeuroP in human sperm. Total progressive sperm motility (p < 0.05) and linearity (p = 0.016), evaluated by a computer-assisted sperm analyzer, were significantly increased in samples incubated with 7 ng F4-NeuroPs compared to non-supplemented controls. Sperm capacitation was tested in rabbit and swim-up-selected human sperm by chlortetracycline fluorescence assay. A higher percentage of capacitated sperm (p < 0.01) was observed in samples incubated in F4-NeuroPs than in the controls. However, the percentage of capacitated sperm was not different in F4-NeuroPs and calcium ionophore treatments at 2 h incubation. The phosphorylated form of AMPKα was detected by immunofluorescence analysis; after 2 h F4-NeuroP incubation, a dotted signal appeared in the entire sperm tail, and in controls, sperm were labeled in the mid-piece. A defined level of seminal F4-NeuroPs (7 ng) showed a biological activity in sperm function; its addition in sperm suspensions stimulated capacitation, increasing the number of sperm able to fertilize.

Study DesignRetrospective clinical study.PurposeThe purpose of this study was to determine what percentage of patients who underwent nonoperative management of unilateral non-displaced or minimally displaced facet fractures progressed radiographically and to determine what percentage of patients required surgical intervention and to identify risk factors for failure of conservative management.Overview of LiteratureAccording to most commonly used classification systems, unilateral, non-and minimally displaced facet fractures are be amendable to nonoperative management.MethodsA retrospective review of the Trauma Registry of a Level I trauma center was performed to identify all patients diagnosed with a non- or minimally displaced unilateral facet fracture which was managed nonoperatively. Several demographic variables and clinical outcomes were recorded. Using computed tomography scanning and plain radiographs, fracture pattern, listhesis, displacement, angle and percentage of the facet that included the fracture were determined. Radiographic progression was defined as the occurrence of listhesis of more than 10% of the anterior-posterior dimensions of the inferior vertebral body during radiographic follow-up. Failure of conservative management was defined as a patient requiring surgical intervention after initially being managed nonoperatively.ResultsSeventy-four patients were included. Fifteen patients (20%) progressed radiographically. However, only 2 developed radicular symptoms and none developed myelopathy or other catastrophic cord related symptoms. Seven patients (9%) underwent surgery. Indications for surgery included significant radiographic progression and/or radicular symptoms. Risk factors for failure of conservative management included presence of radiculopathy at the time of presentation, a higher body mass index, increased Injury Severity Score, greater initial fracture displacement and more than 2 mm of listhesis.ConclusionsPatients with non-displaced or minimally displaced facet fractures who do not have neurological symptoms at the time of presentation can safely be managed conservatively with careful observation and follow-up.