Feasibility and tolerability of anlotinib plus PD-1 blockades as rechallenge immunotherapy in previously treated advanced ESCC: a retrospective study.

BACKGROUND: Rechallenge with immune checkpoint inhibitor (ICI) seemed favorable in several tumors, but clinical experience on esophageal squamous cell carcinoma (ESCC) was scanty. This real-world study aimed to assess the feasibility and safety of anlotinib plus ICI for patients with previously ICI-treated advanced ESCC. MATERIALS AND METHODS: We retrospectively identified advanced ESCC patients who received anlotinib plus ICI in the rechallenge setting for evaluation of clinical outcomes and safety. Totally 110 ICI-pretreated patients, of which 89 (80.9%) received prior first- or second-line treatment, were included from September 9, 2019, to November 30, 2022. Most patients (63.6%) discontinued initial ICI due to disease progression. RESULTS: After rechallenge, median overall survival (OS) and progression-free survival (PFS) were 11.1 (95% CI, 8.6-13.7) and 5.6 (95% CI, 4.4-6.8) months, respectively; estimated OS and PFS rates at 12 months were 47.6% (95% CI, 36.8%-57.7%) and 21.4% (95% CI, 10.9%-34.2%), respectively. No complete response was reported and 21 (19.1%) patients attained partial response; the objective response rate was 19.1%. Fifty-five (50.0%) had stable disease for a disease control rate of 69.1%. Of the 21 responders, median duration of response was 6.4 months. Tendencies for longer OS were observed in patients with Eastern Cooperative Oncology Group Performance of 0 (P = .056). The incidence of grade 3 or higher treatment-related adverse events was 10.0%. CONCLUSION: Anlotinib plus ICI in the rechallenge setting was promising and resulted in encouraging benefits for patients with previously ICI-treated advanced ESCC. Our findings provided preliminary but unique evidence to help select ESCC patients benefiting from this strategy. TRIAL REGISTRATION: chictr.org.cn; number ChiCTR2300070777.

A flow cytometry method for safe detection of bacterial viability.

Flow cytometry is a relevant tool to meet the requirements of academic and industrial research projects aimed at estimating the features of a bacterial population (e.g., quantity, viability, activity). One of the remaining challenges is now the safe assessment of bacterial viability while minimizing the risks inherent to existing protocols. In our core facility at the Paris-Saclay University, we have addressed this issue with two objectives: measuring bacterial viability in biological samples and preventing bacterial contamination and chemical exposure of the staff and cytometers used on the platform. Here, we report the development of a protocol achieving these two objectives, including a viability labeling step before bacteria fixation, which removes the risk of biological exposure, and the decrease of the use of reagents such as propidium iodide (PI), which are dangerous for health (CMR: carcinogenic, mutagenic, and reprotoxic). For this purpose, we looked for a non-CMR viability dye that can irreversibly label dead bacteria before fixation procedures and maintain intense fluorescence after further staining. We decided to test on the bacteria, eFluor Fixable Viability dyes, which are usually used on eukaryotic cells. Since the bacteria had size and granularity characteristics very similar to those associated with flow cytometry background signals, a step of bacterial DNA labeling with SYTO or DRAQ5 was necessarily added to differentiate them from the background. Three marker combinations (viability-DNA) were tested on LSR Fortessa and validated on pure bacterial populations (Gram+ , Gram- ) and polybacterial cultures. Any of the three methods can be used and adapted to the needs of each project and allow users to adapt the combination according to the configuration of their cytometer. Having been tested on six bacterial populations, validated on two cytometers, and repeated at least two times in each evaluated condition, we consider this method reliable in the context of these conditions. The reliability of the results obtained in flow cytometry was successfully validated by applying this protocol to confocal microscopy, permeabilization, and also to follow cultures over time. This flow cytometry protocol for measuring bacterial viability under safer conditions also opens the prospect of its use for further bacterial characterization.

Smartphone-integrated visual inspection for enhancing agricultural product quality and safety: a review.

The increasing emphasis on the quality and safety of agricultural products, which are vital to global trade and consumer health, has driven the innovation of cost-effective, convenient, and rapid smart detection technologies. Smartphones, with their interdisciplinary functionalities, have become valuable tools in quantification and analysis research. Acting as portable, affordable, and user-friendly analytical devices, smartphones are equipped with high-resolution cameras, displays, memory, communication modules, sensors, and operating systems (Android or IOS), making them powerful, palm-sized remote computers. This review delves into how visual inspection technology and smartphones have enhanced the quality and safety of agricultural products over the past decade. It also evaluates the key features and limitations of existing smart rapid inspection methods for agricultural products and anticipates future advancements, offering insights into the application of smart rapid inspection technology in agriculture.

Extended long-term efficacy and safety of velmanase alfa treatment up to 12 years in patients with alpha-mannosidosis.

Enzyme replacement therapy (ERT) using velmanase alfa previously showed promising efficacy and safety outcomes for up to 4 years of therapy in patients with alpha-mannosidosis. This pooled analysis from two multicenter, open-label phase IIIb extension trials rhLAMAN-07 (N = 13; NCT01908712) and rhLAMAN-09 (N = 8; NCT01908725) evaluated the long-term effects of velmanase alfa. Sixteen patients who previously completed phase I-III rhLAMAN-02/-03/-04/-05/-08 trials and five ERT-naïve patients were enrolled. Patients received 1 mg/kg velmanase alfa once weekly. Endpoints included changes from treatment baseline (before initial dose of velmanase alfa in any trial) in serum oligosaccharides, 6-minute walk test (6MWT), 3-minute stair climb test (3MSCT), pulmonary function (forced vital capacity [FVC], % predicted), serum immunoglobulin G (IgG) levels, and adverse events. The overall cohort comprised 21 patients, divided by age at treatment baseline into pediatric (n = 14) and adult subgroups (n = 7). Distance walked according to 6MWT increased or stabilized in pediatric patients, while in adults either stabilization or slight decline was observed. Similarly, pediatric patients performed better in the 3MSCT. Changes in FVC, % predicted, were comparable in both subgroups up to ~6 years of observation, diverging thereafter. Overall, sustained serum oligosaccharide clearance and serum IgG level increase was observed upon treatment initiation and persisted until last common observation. Velmanase alfa treatment was generally well tolerated, with the majority of reported adverse events being of mild-to-moderate intensity. With follow-up of up to 12 years, long-term efficacy and safety outcomes indicate continued benefits of velmanase alfa in patients with alpha-mannosidosis.

National implementation trial of BeUpstanding™: an online initiative for workers to sit less and move more.

BACKGROUND: The online BeUpstanding™ program is an eight-week workplace-delivered intervention for desk-based workers to raise awareness of the benefits of sitting less and moving more and build a supportive culture for change. A workplace representative (the "champion") delivers the program, which includes a workshop where teams collectively choose their sit less/move more strategies. A toolkit provides the champion with a step-by-step guide and associated resources to support program uptake, delivery, and evaluation. Here we report on the main findings from the Australian national implementation trial of BeUpstanding. METHODS: Recruitment (12/06/2019 to 30/09/2021) was supported by five policy and practice partners, with desk-based work teams from across Australia targeted. Effectiveness was measured via a single arm, repeated-measures trial. Data were collected via online surveys, toolkit analytics, and telephone calls with champions. The RE-AIM framework guided evaluation, with adoption/reach (number and characteristics); effectiveness (primary: self-reported workplace sitting time); implementation (completion of core components; costs); and, maintenance intentions reported here. Linear mixed models, correcting for cluster, were used for effectiveness, with reach, adoption, implementation, and maintenance outcomes described. RESULTS: Of the 1640 website users who signed-up to BeUpstanding during the recruitment period, 233 were eligible, 198 (85%) provided preliminary consent, and 118 (50.6%) champions consented and started the trial, with 94% (n = 111 champions) completing. Trial participation was from across Australia and across industries, and reached 2,761 staff, with 2,248 participating in the staff survey(s): 65% female; 64% university educated; 17% from a non-English speaking background. The program effectively changed workplace sitting (-38.5 [95%CI -46.0 to -28.7] minutes/8-hour workday) and all outcomes targeted by BeUpstanding (behaviours and culture), with small-to-moderate statistically-significant effects observed. All participating teams (n = 94) completed at least 5/7 core steps; 72.4% completed all seven. Most champions spent $0 (72%) or >$0-$5 (10%) per team member; most (67/70 96%) intended to continue or repeat the program. CONCLUSIONS: BeUpstanding can be adopted and successfully implemented by a range of workplaces, reach a diversity of staff, and be effective at creating a supportive culture for teams of desk-based workers to sit less and move more. Learnings will inform optimisation of the program for longer-term sustainability. TRIAL REGISTRATION: ACTRN12617000682347.

Implications of potential clinically relevant interactions between COVID-19 vaccines and concomitant medications.

COVID-19 was announced as a global pandemic in 2020. Several types of COVID-19 vaccines are available such as mRNA vaccines, adenovirus vector vaccines, and protein subunit or inactivated virus vaccines. Vaccines are often administered in patients with chronic diseases who are likely to be treated with several drugs. A growing number of clinical observations indicated the possibility of interactions between COVID-19 vaccines and drugs. A hyperinflammatory state may spark significant imbalances in drug metabolism that may result in the alteration of drug pharmacokinetics and therapeutic response. Furthermore, interactions may result in additive or antagonistic or synergistic vaccine immune response. Information about COVID-19 vaccine-drug interactions is needed by physicians and pharmacists to make rational drug-use decisions. In this review, several individual and categorical evidence-based potential COVID-19 vaccine-drug interactions of clinical importance are described. Vigilance is needed to detect previously unreported COVID-19 drug interactions and to further assess known interactions. The clinical significance of which is not fully determined. Evidence suggests that adverse events to some drugs are rare after COVID-19 vaccination and their possibility should not affect vaccination of patients at risk. Clinicians prescribing medications should be aware of the likely risk of interaction with COVID-19 vaccines and may benefit from taking into account present recommendations of the best measures to avoid consequences of such interactions to preserve vaccine efficacy and patient safety.

Ten Years of Quality Monitoring of Abdominal Organ Procurement in the Netherlands and Its Impact on Transplant Outcome.

In this study, 10 years of procurement quality monitoring data were analyzed to identify potential risk factors associated with procurement-related injury and their association with long-term graft survival. All deceased kidney, liver, and pancreas donors from 2012 to 2022 and their corresponding recipients in the Netherlands were retrospectively included. The incidence of procurement-related injuries and potential risk factors were analyzed. Of all abdominal organs procured, 23% exhibited procurement-related injuries, with a discard rate of 4.0%. In kidneys and livers, 23% of the grafts had procurement-related injury, with 2.5% and 4% of organs with procurement-related injury being discarded, respectively. In pancreas procurement, this was 27%, with a discard rate of 24%. Male donor gender and donor BMI >25 were significant risk factors for procurement-related injury in all three abdominal organs, whereas aberrant vascularization was significant only for the kidney and liver. In the multivariable Cox regression analyses, procurement-related injury was not a significant predictor for graft failure (kidney; HR 0.99, 95% CI 0.75-1.33, p = 0.99, liver; HR 0.92, 95% CI 0.66-1.28, p = 0.61, pancreas: HR 1.16; 95% CI 0.16-8.68, p = 0.88). The findings of this study suggest that transplant surgeons exhibited good decision-making skills in determining the acceptability and repairability of procurement-related injuries.

Additive efficacy and safety of probiotics in the treatment of ulcerative colitis: a systematic review and meta-analysis.

BACKGROUND: We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC). METHODS: We systematically searched the relevant literature investigating the efficacy and/or safety of probiotics in patients with UC from PubMed, Embase and Web of Science up to January 2023. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Any discrepancies throughout these processes were solved by consensus. All statistical analyses were performed by Review Manager version 5.4 and Stata version 15.0. RESULTS: A total of 13 articles were included in the pooled analyses, and the studies were all randomized controlled trials with a total of 930 patients. There were no significant differences between the probiotics and placebo groups concerning demographic and baseline characteristics. For patients with active UC, the probiotic group boosted the remission rate by 87% compared to the placebo group, but failed to reach a statistical difference (OR: 1.87; 95% CI 0.98, 3.57; P = 0.06, I2 = 67%); furthermore, there were no statistical differences in maintenance of clinical remission, clinical response, change in UCDAI scores, or mucosal healing outcomes in the probiotic group compared to the placebo group. For patients in clinical remission, the clinical relapse rates were significantly lower in the probiotic group than in the placebo group (OR: 0.34; 95% CI 0.14, 0.79; P = 0.01). Moreover, this study did not observe a significant difference between the two groups for general adverse events rate (OR: 1.98; 95% CI 0.69, 5.68; P = 0.20). CONCLUSION: Probiotic-assisted therapy may be effective in inhibiting UC recurrence in patients in clinical remission without increasing the risk of treatment-related adverse events; furthermore, probiotics may increase the rate of clinical remission in patients with active UC. However, caution is needed when interpreting the clinical efficacy of probiotics in improving the clinical outcome of patients with active UC.

Efficacy and safety of adalimumab in pediatric patients with Crohn's disease: A systematic review and meta-analysis.

PURPOSE: There is currently no curative treatment for childhood Crohn's disease (CD). This meta-analysis aimed to validate the efficacy and safety of adalimumab (ADA) in pediatric patients with CD. MATERIALS AND METHODS: We searched all relevant studies in the PubMed, Web of Science, Embase, and Cochrane Library databases. The primary outcomes were induction (≤ 12 weeks) and maintenance (up to 48 weeks) of remission and response. Secondary outcomes were severe adverse events and opportunistic infections to ADA. The Cochrane bias assessment tool was used to assess the risk of bias in randomized controlled trials. The methodological quality of the single-arm studies was assessed using the methodological index for non-randomized studies tool. RESULTS: Ten clinical trials involving a total of 885 patients were included. Results indicated that 59% (95% confidence interval [CI] 39-80%) of the subjects treated with ADA achieved induction of remission, and 60% (95% CI 35-86%) of the subjects treated with ADA achieved induction of response, 57% (95% CI 44-70%) achieved maintenance of remission, and 63% (95% CI 26-69%) achieved maintenance of response. CONCLUSION: Current evidence indicates that ADA is effective in children and adolescents with CD and that adverse events vary but are usually not severe. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/ , identifier CRD42023402199.

Is precarious employment an occupational hazard? Evidence from Ontario, Canada.

OBJECTIVES: To examine the association between precarious employment and risk of occupational injury or illness in Ontario, Canada. METHODS: We combined accepted lost-time compensation claims from the Workplace Safety and Insurance Board with labour force statistics to estimate injury and illness rates between January 2016 and December 2019. Precarious employment was imputed using a job exposure matrix and operationalised in terms of temporary employment, low wages, irregular hours, involuntary part-time employment and a multidimensional measure of 'low', 'medium', 'high' and 'very high' probabilities of exposure to precarious employment. Negative binomial regression models examined exposure to precarious employment in relation to risk of occupational injury or illness. RESULTS: After adjusting for age, sex and year, all indicators of precarious employment were associated with increased risk of injury or illness. Workers with 'high' and 'very' high' exposure to precarious employment presented a nearly threefold risk of injury or illness (rate ratio (RR): 2.81, 95% CI 2.73 to 2.89; RR: 2.82, 95% CI 2.74 to 2.90). Further adjustment for physical demands and workplace hazards attenuated associations, though a statistically and substantively significant exposure-outcome relationship persisted for workers with 'high' and 'very high' exposures to precarious employment (RR: 1.65, 95% CI 1.58 to 1.72; RR: 2.00, 95% CI 1.92 to 2.08). CONCLUSIONS: Workers exposed to precarious employment are more likely to sustain a lost-time injury or illness in Ontario, Canada. Workplace health and safety strategies should consider the role of precarious employment as an occupational hazard and a marker of work injury risk.

Impact of carbon dioxide exposures on sleep latency among healthy volunteers: A randomized order, paired crossover study, evidence from the multiple sleep latency test.

BACKGROUND: Daytime sleepiness affects work efficiency, occupational safety, and public health. Although previous studies have reported an association between environmental carbon dioxide (eCO2) and daytime sleepiness, it has been challenging to draw a firm conclusion due to the lack of standardized sampling and profiling protocols. OBJECTIVE: We examined the effect of pure CO2 exposure at 5000 (ppm, parts per million) on daytime sleepiness. METHODS: Eleven healthy participants (males of 24 ± 3 years, mean ± SD) completed a four-nap multiple sleep latency test (MSLT) protocol in the environmentally controlled chamber under two conditions: the CO2 condition (4851 ± 229 ppm) and the Control condition (1102 ± 204 ppm). The subjective sleepiness level and cognitive performances were also evaluated using the Stanford Sleepiness Scale (SSS) questionnaire, Psychomotor Vigilance Test (PVT), and Stroop test after each nap session. RESULTS: A significant reduction in sleep latency was observed in the CO2 exposure condition (Control vs. CO2 = 13.1 ± 3.3 min vs. 9.7 ± 3.2 min). The subjective sleepiness scores were also significantly higher in the CO2 exposure condition than in the Control condition (Control vs. CO2 = 2.7 ± 0.5 vs. 4.7 ± 0.8). Cognitive responses after naps showed no significant difference across conditions. CONCLUSION: This study revealed that exposure to environmental CO2 at a concentration as high as the upper safety limit at work sites significantly shortened the sleep latency and enhanced subjective sleepiness during naps in the MSLT without affecting cognitive responses after each exposure. Our results demonstrated that exposure to high environmental CO2 induces daytime sleepiness that potentially compromises work efficiency and safety.

A system for developing reasonable adjustments to the application of the National Safety and Quality Health Service Standards for adult patients with intellectual disability in Australian hospital settings.

The Australian Commission of Safety and Quality in Health Care mandates the application of the eight National Safety and Quality Health Service Standards to minimise high-risk adverse events in hospital settings for all Australian patients. It acknowledges that adults with intellectual disability require reasonable adjustments to the application of the standards to optimise the impact of the quality and safety measures for this group. The paper proposes a system whereby reasonable adjustments can be developed for this population. First, particular criteria, items or actions of a standard are selected for the formulation of reasonable adjustments. Second, the adjustments are broken down into categories of alterations to usual knowledge, process, content and organisation involved in compliance with the chosen aspect of the standard. Third, the categories of reasonable adjustments are simultaneously influenced and shaped by aspects of living with intellectual disability, disability supports and a health-disability sectoral interface.

Efficacy of prophylactic antibiotics in the adjuvant treatment of alcohol-related liver disease (ALD): A systematic review and meta-analysisProphylactic antibiotics in ALD.

INTRODUCTION AND OBJECTIVES: This research aims to evaluate the efficacy and safety of prophylactic antibiotics in patients with alcohol-related liver disease (ALD). MATERIALS AND METHODS: We systematically searched databases including PubMed, Embase, Cochrane, and Web of Science up to October 2023. Our scope encompassed the influence of prophylactic antibiotics on all-cause mortality, infection, variceal bleeding, hepatic encephalopathy (HE), hepatorenal syndrome (HRS), adverse events (AE), fungal infection, clostridioides difficile infection (CDI), and multidrug-resistant (MDR) bacterial infection. Additionally, total bilirubin, creatinine, platelet counts, and plasma endotoxin levels were also analyzed. RESULTS: After comprehensive selection, 10 studies with 974 participants were included for further analysis. The study demonstrated that prophylactic antibiotic therapy was associated with reductions in infection rates, HE incidence, variceal bleeding, and all-cause mortality. The treatment did not increase the incidence of AE, fungal infection, and CDI, but it did raise the MDR bacteria infection rate. The analysis revealed no significant protective effect of antibiotic prophylaxis on total bilirubin and creatinine levels. Furthermore, the administration of antibiotics led to marginal increases in platelet counts, a minor reduction in endotoxin concentrations, and a subtle enhancement in HRS; however, these changes did not reach statistical significance. CONCLUSIONS: Prophylactic antibiotic therapy was an effective and safe treatment for advanced ALD. To mitigate the risk of MDR bacterial infections, a strategy of selective intestinal decontamination could be advisable. Future investigations should prioritize varied ALD patient populations with extended follow-up periods and assorted antibiotic regimens to solidify the efficacy and safety of ALD treatments.

Occupational health and safety among farmers: a comprehensive study in Central Anatolia, Turkey.

BACKGROUND: The agricultural sector is vital for food production, economic stability, and environmental sustainability. However, it also poses significant occupational health and safety challenges due to factors such as heavy machinery usage, exposure to chemicals, and challenging environmental conditions. METHOD: This cross-sectional study involved 366 farmers affiliated with the Yozgat Chamber of Agriculture in Turkey. Data on demographic characteristics, occupational factors, and work accidents were collected with interview technique between May and August 2023. While descriptive data were expressed as categories with numbers and percentages, chi-square analysis was used to compare the obtained answers with the status of having or not having a work accident. Binary logistic regression analysis was used to estimate the effect of independent variables on the probability of having a work accident. RESULTS: The study revealed that 33.0% of farmers experienced work accidents in the last year. Most accidents occurred during work shifts (28.8%) and in the fall season (34.8%). Factors contributing to accidents included lack of personal protective equipment (51.5%) and transportation-related issues (36.4%). Logistic regression analysis indicated that working more than 8 h daily, working 5 days or more per week, and using bus/minibus transportation significantly increased the likelihood of experiencing work accidents. CONCLUSION: Findings underscore the importance of implementing effective occupational health and safety measures, including proper training, provision of personal protective equipment, and improving transportation safety. Addressing these issues can enhance the well-being of agricultural workers and contribute to a safer working environment in the sector.

Physical work environment in an activity-based flex office: a longitudinal case study.

OBJECTIVE: This study aimed to investigate and explore Occupational Health and Safety (OHS) management, office ergonomics, and musculoskeletal symptoms in a group of office workers relocating from cell offices to activity-based flex offices (AFOs). METHODS: The analysis was based on qualitative interview data with 77 employees and longitudinal questionnaire data from 152 employees. RESULTS: Results indicate that there was a need to clarify roles and processes related to the management of OHS. Self-rated sit comfort, working posture, and availability of daylight deteriorated and symptoms in neck and shoulders increased after the relocation and seemed to be influenced by many factors, such as difficulties adjusting the workstations, the availability of suitable workplaces, and age, sex, and individual needs. CONCLUSION: Research on the long-term effects of physical work environments and management of (OHS) issues after implementing activity-based flex offices is sparse. This study demonstrates the importance of planning and organising OHS issue management when implementing an AFO, and to carefully implement office ergonomics among office workers.

The effectiveness and outcomes of epidural analgesia in patients undergoing open liver resection: a propensity score matching analysis.

BACKGROUND: Open liver resection necessitates a substantial upper abdominal inverted-L incision, resulting in severe pain and compromising patient recovery. Despite the efficacy of epidural analgesia in providing adequate postoperative analgesia, the potential epidural-related adverse effects should be carefully considered. This study aims to compare the efficacy and safety of continuous epidural analgesia and intravenous analgesia in open liver resection. METHODS: A retrospective study was conducted, collecting data from patients who underwent open liver resection between 2007 and 2017. Propensity score matching was implemented to mitigate confounding variables, with patients being matched in a 1:1 ratio based on propensity scores. The primary outcome was the comparison of postoperative morphine consumption at 24, 48, and 72 hours between the two groups. Secondary outcomes included pain scores, postoperative outcomes, and epidural-related adverse effects. RESULTS: A total of 612 patients were included, and after matching, there were 204 patients in each group. Opioid consumption at 24, 48, and 72 hours postoperatively was statistically lower in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). However, there was no significant difference in pain scores (p = 0.422). Additionally, perioperative hypotension requiring treatment, as well as nausea and vomiting, were significantly higher in the epidural analgesia group compared to the intravenous analgesia group (p < 0.001). CONCLUSIONS: Epidural analgesia is superior to intravenous morphine in terms of reducing postoperative opioid consumption within the initial 72 h after open liver resection. Nevertheless, perioperative hypotension, which necessitates management, should be approached with consideration and vigilance. TRIAL REGISTRATION: The study was registered in the Clinical Trials Registry at www. CLINICALTRIALS: gov/ , NCT number: NCT06301932.

Effectiveness and safety of pembrolizumab as first-line treatment for non-small cell lung cancer in real clinical practice.

INTRODUCTION: Pembrolizumab is currently the drug for the first-line treatment of stage-IV non-small cell lung cancer. The objective of this study is to measure the effectiveness of pembrolizumab as a first-line treatment and to analyze its safety in real clinical practice. METHODS: This was a retrospective study that included patients with metastatic non-small cell lung cancer who had received pembrolizumab as a first-line treatment between 1 June 2018 and 31 January 2021. Variables related to the patients, treatment, and drug's efficacy and safety were collected. RESULTS: A total of 50 patients were analyzed. The median real-world progression-free survival and real-world overall survival of those who received pembrolizumab in monotherapy were 10.5 months (95% CI: 2.3-18.6) and 18.9 months (95% CI: 16.9-20.8), respectively. The median real-world progression-free survival and real-world overall survival of those who received the drug with chemotherapy was 7.9 months (95% CI: 4.1-11.7) and 13.3 months (95% CI: 0.0-27), respectively. Mostly digestive (48.3%) and endocrine (41.4%) immune-related adverse events were detected among the patients who received pembrolizumab in monotherapy, whereas mostly digestive immune-related adverse events (85.7%) and hematological toxicities (71.5%) were observed in those treated with pembrolizumab plus chemotherapy. CONCLUSION: Pembrolizumab has proven its effectiveness in terms of increasing real-world progression-free survival and real-world overall survival in real clinical practice. The main adverse events were digestive toxicities with pembrolizumab in monotherapy and with chemotherapy.

The efficacy and safety of different does of intravenous tranexamic acid on blood loss in fresh foot and ankle fractures: a prospective, randomized controlled study.

BACKGROUND: There are a few studies on the effectiveness and safety of intravenous administration of tranexamic acid(TXA) in patients who underwent foot and ankle surgery, especially for preoperative hidden blood loss in patients with freshfoot and ankle fractures. Thus, the aim of this study was to investigate whether intravenous administration of different doses of TXA can effectively reduce perioperative blood loss and blood loss before surgery and to determine its safety. METHODS: A total of 150 patients with fresh closed foot and ankle fractures from July 2021 to July 2023 were randomly divided into a control group (placebo controlled [PC]), standard-dose group (low-dose group [LD], 1 g/24 h; medium-dose group [MD], 2 g/24 h), and high-dose group (HD, 3 g/24 h; ultrahigh-dose group [UD], 4 g/24 h). After admission, all patients completed hematological examinations as soon as possible and at multiple other time points postsurgery. RESULTS: There was a significant difference in the incidence of hidden blood loss before the operation between the TXA group and the control group, and the effect was greater in the overdose groups than in the standard-dose groups. There were significant differences in surgical blood loss (intraoperative and postoperative), postoperative HGB changes, and hidden blood loss among the groups. The TXA groups showed a significant decrease in blood loss compared to that of the control group, and the overdose groups had a more significant effect than the standard-dose groups. A total of 9 patients in the control group had early wound infection or poor healing, while only 1 patient in the other groups had this complication, and the difference among the groups was significant. No patients in any group suffered from late deep wound infection, cardiovascular or cerebrovascular events or symptomatic VTE. CONCLUSION: This is the first study on whether TXA can reduce preoperative hidden blood loss in patients with freshfoot and ankle fractures. In our study, on the one hand, intravenous application of TXA after foot and ankle fractures as soon as possible can reduce preoperative blood loss and postoperative blood loss. On the other hand, TXA can also lower wound complications, and over-doses of TXA are more effective than standard doses. Moreover, overdoses of TXA do not increase the incidence of DVT.

Sex exceptionalism and erasure in porn health protocols.

Porn production, like all forms of labour, entails certain occupational health and safety (OHS) risks. Porn production has generally not been subject to state occupational health oversight, and porn workers have instead implemented self-regulatory OHS systems. However, in California, where the industry is most established, governmental and non-governmental bodies have made several paternalist attempts to legislate standardised OHS protocols. Their proposed legislation exceptionalises sex work as uniquely dangerous while failing to tailor guidance to the specific needs of and practices associated with porn work. This is largely because: 1) regulators are ignorant of porn's self-regulatory processes; 2) industry self-regulation conceptualises the occupational hazard on porn sets as infectious bodily fluids, whereas external regulators perceive the hazard as sex itself; and 3) regulators devalue porn work and so do not take the viability of the labour into account when evaluating protocol effectiveness. Using critical-interpretive medical anthropology involving fieldwork and interviews with porn workers and a critical analysis of porn OHS texts, I argue that porn health protocols should be left to industry self-determination, to be developed by porn workers rather than for them.

Invited review: Role of Bacillus licheniformis in the dairy industry-Friends or foes?

Bacillus licheniformis is one of the major spore-forming bacteria with great genotypic diversity in raw milk, dairy ingredients, and final dairy products; it is found throughout the dairy-processing continuum. Although being widely used as a probiotic strain, this species also serves as a potential risk in the dairy industry based on its roles in foodborne illness and dairy spoilage. Biofilm formation of B. licheniformis, combined with the heat resistance of its spores, make it impossible to prevent the presence of B. licheniformis in final dairy products by using traditional cleaning and disinfection procedures. Despite the extensive efforts to identify B. licheniformis in various dairy samples, no reviews have been written on both hazards and benefits of this sporeformer. This review discusses the prevalence of B. licheniformis from raw milk to commercial dairy products, biofilm formation and spoilage potential of B. licheniformis, and possible prevention methods. In addition, the potential benefits of B. licheniformis in the dairy industry are also summarized.