搜索结果：Open medicine (Warsaw, Poland)

More effective therapies are required for advanced breast cancer. We report results from 58 women with locally advanced unresectable or metastatic hormone-receptor (HR)-negative, human epidermal growth factor receptor 2 (HER2)-low breast cancer enrolled in arm 6 of the multicenter, open-label phase 1b/2 BEGONIA platform trial, who received durvalumab (1,120 mg) plus trastuzumab deruxtecan (T-DXd; 5.4 mg kg-1) intravenously every 3 weeks as first-line treatment. Objective response rate (ORR) and safety were primary endpoints; duration of response (DoR), progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Median follow-up was 20.6 months (range: 1-37). ORR was 62.1% (95% confidence interval (CI): 48.4-74.5), which did not meet the protocol-specified objective of 38/57 (66.6%) responses. Median DoR was 15.2 months (95% CI: 8.44-not calculable), PFS was 12.6 months (95% CI: 8.4-16.3) and OS was 30.3 months (95% CI: 18.8-not calculable). The safety profile of the combination treatment was consistent with those of the individual therapies. Adjudicated, drug-related interstitial lung disease or pneumonitis occurred in 20.7% of participants (grades 1 and 2, 19.0%; grade 5, 1.7%). Durvalumab plus T-DXd demonstrated clinically relevant efficacy for first-line treatment of metastatic HR-negative, HER2-low breast cancer, with no unexpected toxicities observed. ClinicalTrials.gov identifier: NCT03742102 .

Iatrogenic urethral strictures represent a relevant complication following endoscopic surgical treatment for benign prostatic hyperplasia, potentially leading to significant morbidity and impaired quality of life. Despite advances in endoscopic technologies, urethral trauma related to prolonged operative time and large-caliber instruments remains a concern. The optimal management of urethral strictures secondary to surgery is still debated, and high-quality evidence comparing endoscopic and open reconstructive approaches is lacking. This systematic review aimed to evaluate the efficacy and safety of contemporary treatments for iatrogenic urethral strictures following endoscopic management of benign prostatic hyperplasia. A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD42024604611). MEDLINE, Embase, and the Cochrane Library were searched from 2000 to June 2025. Studies reporting outcomes of endoscopic or open surgical treatments for urethral strictures following benign prostatic hyperplasia surgery were included. Data extraction focused on patient characteristics, stricture features, treatment modality, success rates, complications, and follow-up. Due to substantial heterogeneity, a meta-analysis was not performed. Eleven studies comprising a total of 610 patients were included. Of these, 443 (73%) patients underwent primary treatment for urethral stricture, while 167 (27%) were treated for recurrent disease. The bulbar and membranous urethra were the most commonly involved sites. Overall, 58 patients (9%) underwent endoscopic management, whereas 552 patients (91%) were treated with open reconstructive surgery. The overall recurrence rate was 8 and 10% for both endoscopic and open approaches. However, follow-up duration differed substantially between groups, ranging from 12 to 24 months in endoscopic series and extending up to 54 months in open reconstructive cohorts. Complication rates were generally low. No perioperative or functional complications were reported following endoscopic treatments. Among open procedures, urinary incontinence was the most frequent complication, with rates varying from 4% after ventral onlay graft urethroplasty to 15% following intrasphincteric bulbo-prostatic anastomosis. Flap-related complications were rare. Management of urethral strictures following endoscopic prostatic surgery remains challenging. While endoscopic treatments offer acceptable short-term outcomes with minimal morbidity, open reconstructive surgery provides more durable long-term results at the cost of a higher, yet acceptable, risk of functional complications. Treatment choice should be individualized based on stricture characteristics, patient factors, and surgical expertise. Prospective, multicenter studies with standardized outcome reporting and longer follow-up are warranted to optimize treatment algorithms for this complex condition.

Major vascular injury during laparoscopic surgery is rare but potentially catastrophic. Existing literature is largely limited to case series and registry-based analyses without reliable denominators or validated measures of disease severity. Procedure-specific risk and overall population burden remain incompletely defined. This study aimed to determine the statewide incidence, severity profile, and procedure-specific risk of iatrogenic major vascular injury during inpatient laparoscopic surgery. We conducted a retrospective population-based cohort study using the 2024 Texas Inpatient and Outpatient Public Use Data File (PUDF). Adult patients (≥ 18 years) undergoing inpatient laparoscopic procedures were identified using ICD-10-PCS approach codes. Iatrogenic major vascular injury was defined using ICD-10-CM diagnosis codes T81.71* and/or I97.5*. The primary outcome was statewide incidence per 10,000 inpatient laparoscopic procedures. Secondary outcomes included markers of clinical severity, including mortality, ICU admission, conversion to open surgery, transfusion, organ failure, and length of stay. Among 119,652 inpatient laparoscopic procedures, 84 cases of iatrogenic major vascular injury were identified, yielding an incidence of 7.02 per 10,000 procedures. (R3C3) These injuries were associated with high clinical severity, including an in-hospital mortality rate of 7.2% and ICU admission in 66.3% of cases. Surgical management often required escalation, with 55.4% of cases undergoing conversion to open surgery and 30.1% requiring blood transfusion. Acute kidney injury (26.5%) and respiratory failure (24.1%) were common. The median length of stay was 6 days (IQR 3-11), compared with 3 days (IQR 1-5) without injury. Diagnostic laparoscopy demonstrated the highest incidence (20.59 per 10,000), whereas colorectal resection had the lowest (0.89 per 10,000). Iatrogenic major vascular injury during inpatient laparoscopic surgery was rare but associated with substantial morbidity and mortality. The elevated incidence observed during diagnostic laparoscopy may suggest abdominal access as an important contributing mechanism of injury, reinforcing the need for continued emphasis on safe-entry techniques and heightened specialty-specific risk awareness. (R2C1).

Inflammatory rheumatic diseases (IRDs) present substantial risks of infection-related comorbidities during pregnancy. This study evaluates the knowledge, experience, and perceptions of healthcare professionals concerning the prevention of these risks. An international, cross-sectional survey was administered using the SurveyMonkey platform. The survey was disseminated to healthcare professionals specializing in rheumatology, obstetrics, infectious diseases, internal medicine, general practice, and related disciplines through social media channels. Developed in accordance with European Alliance of Associations for Rheumatology (EULAR) recommendations, this survey comprised 30 questions, including multiple-choice, Likert-type, and open-ended formats. A total of 201 healthcare professionals from thirty-six countries participated in the study, with rheumatologists comprising the majority (n = 145, 72.1%). Systemic lupus erythematosus (n = 183), systemic vasculitis (n = 141), and rheumatoid arthritis (n = 86) were identified as the diseases associated with the highest risk of infection-related comorbidities. The most frequently recommended infectious conditions for screening included Hepatitis B (n = 142), urinary tract infections (n = 141), and Hepatitis C (n = 129). The primary risk factors were uncontrolled disease activity (n = 176), high-dose corticosteroid use (n = 164), and high disease severity (n = 162). The most significant systemic barriers were insufficient number of specialists (n = 156), and absence of multidisciplinary teams (n = 155). This study identifies structural and educational deficiencies in the management of infection-related comorbidities among pregnant patients with IRD. The results underscore the need for targeted clinical guidelines, enhanced multidisciplinary care models, and expanded pre-pregnancy counseling.

Diabetic foot ulcers (DFUs) are associated with substantial clinical and economic burden and impaired health-related quality of life (HRQoL). Although wound healing remains a core endpoint, recent consensus work identifies HRQoL as an essential outcome in DFU studies. This study describes wound healing, patient-reported outcomes, function, and safety in adults with DFU treated with silicone superabsorbent polymer (SAP) dressings. This exploratory prospective, multicenter, nonrandomized cohort study reports the DFU subgroup from a broader single-arm investigation conducted at eight specialist centers in Poland. Adults with superficial, noninfected DFUs received silicone SAP dressings for up to 6&#xa0;weeks with standard offloading. Prespecified patient-reported outcome measures were the Patient Benefit Index for wounds (PBI-W) and the Wound Quality of Life questionnaire (Wound-QoL-17). Additional endpoints included wound area reduction (centralized digital planimetry), complete epithelialization, accelerometry-based activity, offloading adherence, and safety. Twenty-eight participants were included (75.0% male; mean age, 63.4 years), with a median wound duration of 166 days. By the final visit, 21 (77.8%) achieved at least 20% wound area reduction before cleansing/debridement and 24 (85.7%) after cleansing/debridement; 6 (22.2%) achieved complete epithelialization. Mean global Wound-QoL improved from 2.4 &#xb1; 0.6 to 1.5 &#xb1; 1.0 (mean change, -1.0 &#xb1; 0.8; P < 0.001), with greatest improvements in psyche and everyday-life domains. Mean PBI-W increased from 2.44 &#xb1; 0.94 to 2.94 &#xb1; 0.87 (mean change, 0.45 &#xb1; 1.10; P = 0.043). Activity intensity remained stable, offloading adherence exceeded 95%, and no device-related adverse events were reported. In this prospective DFU cohort, use of silicone SAP dressings within a structured care setting was associated with improvements in wound area reduction and wound-related quality of life over 6&#xa0;weeks. These results highlight the feasibility of integrating patient-reported outcomes in DFU studies and provide a clinically relevant platform for future comparative and health-economic evaluations. Diabetic foot ulcers are open wounds on the foot that can last for months and can affect far more than the skin. They can make walking harder, limit daily activities, increase anxiety, and require repeated clinic visits and dressing changes. Because of this, it is important to measure not only whether a wound becomes smaller, but also whether people feel and function better during treatment. We followed 28 adults with diabetic foot ulcers who were treated with 2 silicone dressings designed to absorb wound fluid and protect the surrounding skin. Patients were observed for up to 6&#xa0;weeks and were also asked to complete questionnaires about quality of life and perceived treatment benefit. Most wounds improved during follow-up. Around 78% to 86% of patients achieved at least a 20% reduction in wound area, depending on whether the wound was measured before or after cleansing and debridement, and about 1 in 5 ulcers healed completely. Patients also reported meaningful improvements in wound-related quality of life, especially in emotional well-being and everyday life. Perceived treatment benefit also improved. Physical activity remained broadly stable, patients followed offloading recommendations closely, and no dressing-related safety concerns were identified. These findings suggest that silicone superabsorbent polymer dressings may support both wound improvement and patient well-being. Future studies should test these results against comparator dressings and should also measure costs and resource use so that the full value of treatment can be evaluated.

Concizumab is a novel non-factor-replacement therapy intended for once-daily subcutaneous prophylactic treatment of hemophilia A/B with and without inhibitors. Superiority was confirmed for concizumab compared with on-demand treatment in patients with hemophilia A/B without inhibitors (HA/HB) in the prospective, multicenter, open-label phase 3 explorer8 study. Here, longer&#x2011;term efficacy and safety results from the start of the study up to the 56-week cut-off are presented. Males aged &#x2265;12 years with HA/HB were randomized 1:2 to no prophylaxis (group 1) or concizumab (group 2), or allocated to concizumab (groups 3/4). Assessments at the 56-week cut-off included measures of efficacy, pharmacokinetics/pharmacodynamics, and safety. The 56-week cut-off was defined as when all patients in group 2-4 had completed the visit at 56 weeks or permanently discontinued treatment. Of 148 patients in the full analysis set, 21 were randomized to no prophylaxis (group 1: HA, n=9; HB, n=12), 42 to concizumab (group 2: HA, n=18; HB, n=24) and 85 were assigned to the non-randomized concizumab groups 3/4 (HA, n=55; HB, n=30). After &#x2265;24 weeks of treatment, 17 patients in group 1 switched to concizumab. Low median annualized bleeding rates for treated spontaneous and traumatic bleeding episodes were maintained at the 56-week cut-off in patients receiving concizumab (HA: 1.7 [interquartile range, 0.0; 4.5]; HB: 2.8 [0.0; 6.4]), consistent with 32&#x2011;week cut&#x2011;off results. Concizumab plasma concentration remained stable over time and no new safety concerns were reported. Concizumab showed longer-term efficacy in patients with HA/HB at the 56-week cut-off and was considered safe and well tolerated. ClinicalTrials.gov; NCT04082429.

Social media platforms such as X (formerly Twitter) are increasingly used by journals, authors, and institutions to promote newly published research. Well-designed posts can enhance visibility, accelerate knowledge translation, and increase altmetric attention. However, creating accurate and policy-compliant content is time-intensive. Large language models (LLMs) offer a potential solution, yet systematic evaluations of their performance in post-publication promotion remain limited. We conducted a blinded, crossed, offline evaluation of four LLMs: GPT-5 (OpenAI), Gemini 2.5 Pro (Google DeepMind), Grok-3 (xAI), and Perplexity Pro (Perplexity AI), tasked with generating X-style posts (&#x2264; 260 characters) for 36 open access articles from The Lancet Public Health, The Lancet Planetary Health, and Annual Review of Public Health. Posts were generated using a standardized system and user prompt. A single blinded rater scored outputs using a five-domain rubric (factual accuracy, clarity, policy compliance, call-to-action quality, structure/metadata; maximum score 10). Secondary measures included character count, hashtag use, and readability (Flesch-Kincaid Grade Level). General linear models with Bonferroni-adjusted post hoc tests and non-parametric analyses were applied. All four models achieved perfect factual accuracy and no policy violations. Mean total quality scores differed significantly by model, P < 0.001. GPT-5 (9.60) and Perplexity Pro (9.60) performed best, followed by Gemini 2.5 Pro (9.47), while Grok-3 scored lower (8.80). Domain analyses showed Grok-3 underperformed in call-to-action quality (1.40 vs. &#x2265;1.97 in other models, P < 0.001) and produced significantly shorter posts (median 194 characters, P < 0.001). Perplexity Pro scored highest for policy compliance, while GPT-5 and Gemini 2.5 Pro achieved superior structural scores. Readability varied: GPT-5 8.9 (7.3-9.2) and Perplexity Pro 7.3 (6.5-8.8) generated more complex outputs, whereas Gemini 2.5 Pro 5.1 (4.8-6.5) and Grok-3 4.5 (3.6-6.3) produced more accessible posts. LLMs can reliably generate accurate and policy-compliant social media posts for research promotion, with differences in style and readability that may inform audience targeting. GPT-5, Gemini 2.5 Pro, and Perplexity Pro produced high-quality outputs, while Grok-3 underperformed across several domains. These findings highlight the potential of LLMs as scalable first-draft tools for post-publication promotion, capable of improving the reach and accessibility of scientific research. Careful model selection, tailored to audience and communication goals, together with human oversight, remains essential.

The implantable shock absorber (ISA) addresses patients within the knee osteoarthritis treatment gap between failure of nonsurgical care and arthroplasty. This follow-up of a prospective, open-label, comparative cohort study reports effectiveness and safety outcomes at 5 years. Eighty-one participants received the ISA. Participants had statistically significant improvement in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain (mean 43.4 point improvement, p < 0.0001) and function (mean 42.1 point improvement, p < 0.0001) versus baseline, beginning 6 weeks postsurgery, and remaining statistically significant and clinically meaningful through the 5-year follow-up. The study was designed to satisfy regulatory requirements, and survival was defined, a priori, in the study protocol with US Food and Drug Administration to be freedom from conversion to arthroplasty or high tibial osteotomy. At 5 years, 73/81 (90.1%) participants reported conversion-free survival. ISA provided benefits that were statistically significant and clinically meaningful for at least 5 years. Based on these 5-year data of durable, conversion-free survivorship, the ISA has proven to be a treatment option for medial knee osteoarthritis patients.

Cardio-oncology has traditionally focused on treatment-related cardiovascular toxicity and conventional cardiovascular risk factors. However, increasing evidence suggests that environmental exposures may contribute to both cancer development and cardiovascular disease through shared biological mechanisms. Endocrine-disrupting chemicals (EDCs) are ubiquitous environmental contaminants capable of interfering with hormonal signaling, metabolic homeostasis, vascular function, and inflammatory pathways. Despite growing evidence linking EDCs to cardiometabolic disorders and hormone-sensitive malignancies, their potential role within the cardio-oncology continuum remains largely unexplored. This narrative review summarizes and critically discusses current experimental, translational, and epidemiological evidence regarding the potential contribution of environmental endocrine disruptors to cardiovascular risk and cancer biology. Particular attention is given to molecular pathways relevant to cancer therapy-related cardiovascular toxicity, breast cancer biology, adipose tissue dysfunction, and emerging exposomic determinants of long-term cardiovascular outcomes in patients with cancer. Major classes of EDCs, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), persistent organic pollutants (POPs), parabens, pesticides, and other environmental contaminants, are continuously encountered through food systems, plastics, consumer products, contaminated water, and healthcare materials. These compounds influence multiple biological processes that are central to both oncogenesis and cardiovascular disease, including oxidative stress, mitochondrial dysfunction, endothelial injury, chronic inflammation, metabolic reprogramming, thrombosis, and epigenetic remodeling. In breast cancer, EDCs may modulate subtype-specific signaling pathways involving estrogen receptor activation, HER2 crosstalk, aryl hydrocarbon receptor signaling, and homologous recombination networks. In parallel, growing evidence supports associations between EDC exposure and hypertension, accelerated atherosclerosis, heart failure, metabolic syndrome, and major adverse cardiovascular events. We further discuss the hypothesis that lipophilic EDCs may accumulate within adipose depots and that dysfunctional epicardial adipose tissue could represent a local toxicological niche capable of amplifying cardiovascular vulnerability in cancer survivors, although direct evidence remains unavailable. EDCs should not yet be considered established cardio-oncology risk factors; however, they represent biologically plausible exposomic modifiers operating at the intersection of cancer, metabolism, and cardiovascular disease. Incorporating environmental exposures into cardio-oncology research may improve understanding of interindividual variability in cardiovascular outcomes and open new avenues for risk stratification, prevention, and survivorship care. Future prospective studies integrating exposure biomarkers, adipose tissue biology, and cardiovascular phenotyping are warranted to define the clinical relevance of EDCs in patients with cancer.

Tasty&Healthy is an exclusive whole food diet designed to reduce inflammation in Crohn's disease (CD) without the need for formula. This TASTI-E randomized-controlled trial compared the effect of Tasty&Healthy versus habitual diet on subclinical inflammation in CD (NCT#04239248). Clinically quiescent patients with CD, 6-40 years of age, with Mucosal Inflammation Non-invasive (MINI) index >8 reflecting bowel inflammation, were randomized to an 8-week Tasty&Healthy intervention or to continue their regular diet. Thereafter, the habitual group was offered an 8-week open-label Tasty&Healthy intervention. The primary outcome was >50% decline in calprotectin. The study was terminated early due to COVID-19-related challenges. Of the 46 randomized patients (mean age, 18.2&#xb1;7.6 years; median disease duration, 9.01 months [IQR 2.9-17.1]), 19 were allocated to Tasty&Healthy and 27 to habitual diet. Calprotectin response was greater in the Tasty&Healthy (53%) versus habitual arm (7%, relative risk=3.23 [95%CI 1.15-9.01], p=0.028). Among 15 patients who crossed-over to Tasty&Healthy, the rates of calprotectin<250 &#x3bc;g/g (53% vs. 7%, respectively, p=0.045) and MINI <8 (93% versus 20%, p=0.002) were higher at week 16 versus week 8. Adherence to Tasty&Healthy was 77% based on self-reported questionnaires and 71% by fecal gluten. Micronutrient and macronutrient consumption was similar between the groups, except for higher fiber intake with Tasty&Healthy. The Tasty&Healthy intervention resulted in a unique serum metabolic signature. The Tasty&Healthy diet may reduce calprotectin levels in patients with CD with subclinical inflammation. Its flexible structure, free of formula, likely explains the high adherence among asymptomatic individuals.

To investigate the neuroprotective effects of adalimumab against cisplatin-induced cognitive impairment (CICI) and to evaluate its potential to ameliorate anxiety- and depression-like behaviors as well as learning and memory deficits through modulation of Tumor necrosis factor-&#x3b1; (TNF-&#x3b1;)-mediated neuroinflammation, cholinergic homeostasis, and apoptosis. Adult male Wistar rats were divided into four groups (n=6/group): Control, Cisplatin (2&#x202f;mg/kg/day, i.p., 10 days), ADA (10&#x202f;mg/kg, i.p., three doses), and Cisplatin + ADA. Anxiety-, depression-like behaviors and memory performance were assessed using the open field test, elevated plus maze, forced swim test, and novel object recognition test. Serum and hippocampal TNF-&#x3b1;, nitric oxide (NO), acetylcholinesterase (AChE), acetylcholine (ACh), and p53 levels were measured by ELISA. Cisplatin induced anxiety- and depression-like behaviors and impaired recognition memory without affecting locomotor activity. These behavioral alterations were accompanied by increased TNF-&#x3b1;, NO, AChE, and p53 levels in the hippocampus. ADA treatment significantly reversed behavioral deficits and normalized inflammatory, cholinergic, and stress-related markers. Adalimumab attenuates cisplatin-induced cognitive and mood disturbances, likely through modulation of TNF-&#x3b1;-mediated neuroinflammation, cholinergic imbalance, and stress-related signaling pathways.

The purpose of this study was to create a risk score for loss of aorto-bifemoral artery bypass (ABF) patency utilizing preoperative, perioperative, and long term follow up variables in the Vascular Quality Initiative (VQI) database. The VQI supra-inguinal arterial bypass module was queried from 2009-2025 and 4971 patients undergoing ABF had long term follow patency data and thus met inclusion. These patients were then divided into a 2/3 testing cohort (N=3364) and a 1/3 validation cohort (N=1607) on whom the risk score would be trialed. The first step was univariable analysis for the outcome of loss of patency of either or both ABF limbs after elective ABF with Chi-squared testing for categorical variables. The 67% testing cohort was used for this initial analysis. Demographics, socioeconomics, and co-morbidities that were hypothesized to have any potential association with bypass occlusion were selected for the initial univariable analysis. Next, multivariable Cox regression time dependent analysis was performed for the outcome of thrombosis of either ABF limb utilizing factors which had a univariable P value of 0.05 or less. Variables with a multivariable P-value < .05 from the above-mentioned regression were included in the risk score and weighted based on their respective regression beta-coefficient in a point scale. Variables with a beta-coefficient of less than .25 were assigned 1 point, and then a point was added for each rise in beta-coefficient at .25 intervals. Machine learning (ML) supplemental analysis with IBM modeler software was also performed. Multivariable Cox regression analysis for the development of ABF thrombosis after index operative hospitalization utilizing significant univariable factors found multivariable significance (P<.05) and ultimate inclusion in the risk score for : operative site infection after discharge (hazard ratio [HR] 1.84, P=.038); revision to achieve primary assisted patency (open or endovascular) in follow up (HR 7.14, P<.001); ischemic tissue loss at initial operation (HR 2.29, P<.001); and either femoral outflow target artery being less than 8mm in diameter (HR 1.59, P<.001). End to end proximal aortic anastomosis was protective (HR .568, P=.003) as was patient not being selected for anticoagulation medication at the time of most recent long-term follow-up (LTFU; HR .731, P<.001). Patients who fell into risk score bundle #1 (raw scores <0) experienced the primary event in 2.1% of cases. Patients in risk score bundle #2 (raw scores 0 - 5) had a 5% event rate and patients in risk score bundle #3 (raw score >5) experienced graft thrombosis at a 44.8% risk. There was thus statistically significant escalation in event rate with rising risk score (P<.001). Receiver operator characteristics for the risk score revealed an area under the curve (AUC) value of .733. There was no significant difference in primary event rate between the testing and validation cohorts at any of the risk score bundles. The top ML methodology achieved an AUC of .914 and confirmed all the Cox regression significant multivariable factors (including end to end anastomosis) to be of high importance. A validated risk score for the event of ABF occlusion after index operative hospitalization has been developed. Performing an end-to-end proximal aortic anastomosis when not anatomically contra-indicated should be considered to enhance long term patency. Anatomic and disease pattern variables weigh most heavily on patency.

Leptospirosis is a zoonotic disease caused by Leptospira spirochetes. It is widespread worldwide, but remains uncommon in European countries. People who come into contact with water, soil, and animals, especially wild rodents, are at risk of infection. The course of the disease is usually mild, but severe cases presenting with multiorgan dysfunction are potentially fatal. When leptospirosis is suspected, rapid treatment is essential for avoiding life-threatening complications. This report discusses the case of a 51-year-old man who was admitted to the hospital with a history of several days of fever, weakness, vomiting, abdominal pain, and jaundice. His condition quickly deteriorated. Initial test results indicated acute liver and kidney injury and thrombocytopenia. Leptospirosis was considered when, upon further questioning, the patient reported the presence of rats in the kitchen where he worked. Serological tests supported the diagnosis of probable leptospirosis. Empirical treatment with ceftriaxone was effective as the patient's condition improved significantly. This case describes the dynamic course of severe leptospirosis, a disease that is very rare in Poland.

BEGONIA (NCT03742102) is a phase Ib/II, Simon's 2-stage, open-label, platform study evaluating the safety and efficacy of durvalumab, an anti-programmed death ligand-1 (PD-L1) antibody, combined with novel therapies, as first-line treatment for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Arms 7 and 8 of BEGONIA assessed the combination of datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate, with durvalumab. Arm 7 included patients regardless of tumor PD-L1 expression level. Arm 8 then enrolled patients with PD-L1-high tumors, as determined by local immunohistochemistry-based testing. In Arms 7 and 8, patients received Dato-DXd 6 mg/kg intravenously plus durvalumab 1120 mg intravenously every 3 weeks. Primary endpoints were safety and tolerability, and investigator-assessed confirmed objective response rate (cORR). Secondary endpoints included cORR (Part 1), duration of response (DoR), progression-free survival (PFS) per RECIST 1.1 and overall survival (OS). Overall, 62 and 33 patients had received Dato-DXd and durvalumab in Arms 7 and 8, respectively. At data cutoff (29 November 2024), median study follow-up was 35.0 and 10.7 months in Arms 7 and 8, respectively. In Arm 7, cORR was 79.0% [95% confidence interval (CI) 66.8-88.3], median DoR was 17.6 months (95% CI 10.5-27.3), median PFS was 14.0 months (11.0-21.1) and median OS was not reached. In Arm 8, cORR was 81.8% (95% CI 64.5-93.0). The median DoR and median PFS for Arm 8 were immature given the short median follow-up (8.3 months in censored patients). The safety profile of the combination was manageable, with no new safety signals versus prior studies. First-line Dato-DXd plus durvalumab demonstrated substantial and durable antitumor activity in locally advanced unresectable or metastatic TNBC, regardless of PD-L1 status.

Shoulder rehabilitation is prolonged, feedback-dependent, and frequently limited by adherence, particularly after surgery. Virtual reality (VR) and related immersive or semi-immersive technologies may support rehabilitation by combining motion tracking, visual feedback, graded repetition, and gamified engagement. This narrative review summarizes current evidence on VR and digitally assisted shoulder and upper-limb rehabilitation and critically evaluates the extent to which these data can inform post-arthroplasty pathways. A narrative review was performed using PubMed/MEDLINE, PubMed Central, and targeted cross-checking in Scopus, Web of Science, and the Directory of Open Access Journals up to May 2026. Search domains combined shoulder and upper-limb terms, virtual reality, augmented reality, mixed reality, extended reality, and exergaming terms, rehabilitation and telerehabilitation terms, and postoperative shoulder surgery or arthroplasty terms. Priority was given to systematic reviews, randomized or controlled studies, validation studies, feasibility studies, and clinician-perspective studies relevant to shoulder biomechanics and rehabilitation implementation. The available literature supports three main conclusions. First, consumer-grade immersive systems can provide reliable within-system shoulder motion monitoring, although absolute agreement across devices remains imperfect. Second, VR, exergaming, and digitally assisted rehabilitation have shown feasibility, high acceptability, and potential benefits for adherence, pain, range of motion, and patient-reported function in rotator cuff repair, adhesive capsulitis, subacromial impingement, and other shoulder disorders. Third, evidence directly specific to anatomic or reverse shoulder arthroplasty rehabilitation remains limited; therefore, extrapolation from rotator cuff repair, conservative shoulder disorders, and digital home-based arthroplasty rehabilitation should be made cautiously. Rehabilitation clinicians support supervised or hybrid use rather than autonomous unsupervised replacement of conventional care. VR should be interpreted as an adjunct to clinician-led rehabilitation, not as a stand-alone substitute. Its most plausible current roles are improving engagement, enabling structured repetition, supporting within-system range-of-motion monitoring, and extending supervised practice into home settings. Future studies should test procedure-specific, phase-based VR protocols for anatomic and reverse shoulder arthroplasty, with explicit attention to compensation control, safety limits, long-term outcomes, cost-effectiveness, and multidisciplinary oversight.

Yellow fever virus (YFV) is a mosquito-borne pathogen causing severe hemorrhagic fever in tropical and subtropical regions. This study aimed to design and evaluated a multi-epitope subunit vaccine against yellow fever virus using immunoinformatics and computational approaches. The yellow fever virus envelope glycoprotein was selected as the target antigen. Antigenic, non-allergenic, and non-toxic B-cell, MHC-I, and MHC-II epitopes were predicted and assembled into a vaccine construct using linkers and &#x3b2;-defensin-3 as an adjuvant. Structural modeling and validation were performed using AlphaFold3 and quality assessment tools. Molecular docking with TLR2 and TLR8 was conducted using ClusPro, followed by molecular dynamics simulations to assess structural stability. Disulfide engineering was applied to enhance rigidity, immune simulation was performed to predict host immune responses, and in silico cloning was carried out using the pBR322 vector. Six conserved epitopes with strong antigenic potential were identified. The vaccine construct showed favorable docking interactions with TLR2 and TLR8, yielding ClusPro weighted interaction scores of&#xa0;-1105.52 and&#xa0;-1152.9, respectively. Molecular dynamics simulations revealed structural stability, supported by stable RMSD and compact radius of gyration profiles. Immune simulation indicated robust humoral and cellular immune responses. The designed multi-epitope vaccine showed promising immunogenic and structural properties, supporting its potential as a potential vaccine candidate against yellow fever virus. However, experimental validation through in&#xa0;vitro and in&#xa0;vivo studies is required.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100&#x2008;000 population, and age-standardised rates per 100&#x2008;000 population. We estimated 1&#xb7;17 billion (95% uncertainty interval 1&#xb7;06-1&#xb7;31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14&#x2008;210&#xb7;7 cases (12&#x2008;849&#xb7;5-15&#x2008;940&#xb7;1) per 100&#x2008;000 population. These estimates represented a 95&#xb7;5% (75&#xb7;0-121&#xb7;2) increase in prevalent cases and 24&#xb7;2% (11&#xb7;4-41&#xb7;4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070&#xb7;5 DALYs (1519&#xb7;1-2750&#xb7;5) per 100&#x2008;000 population. Mental disorders contributed to 6&#xb7;1% (4&#xb7;8-7&#xb7;6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17&#xb7;3% (14&#xb7;8-20&#xb7;6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239&#xb7;6 [1643&#xb7;7-3014&#xb7;1] per 100&#x2008;000) than among males (1900&#xb7;2 [1399&#xb7;8-2510&#xb7;8] per 100&#x2008;000), and peaked in the 15-19 years age group (2617&#xb7;3 [1850&#xb7;6-3696&#xb7;8] per 100&#x2008;000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302&#xb7;4 (952&#xb7;7-1683&#xb7;7) per 100&#x2008;000 in Viet Nam to 3555&#xb7;8 (2661&#xb7;9-4715&#xb7;0) per 100&#x2008;000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853&#xb7;0 (1352&#xb7;1-2469&#xb7;3) per 100&#x2008;000 for middle SDI to 2184&#xb7;1 (1606&#xb7;1-2890&#xb7;3) per 100&#x2008;000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Dexamethasone, a synthetic analogue of betamethasone, exerts vast actions to mediate anti-inflammatory and immunosuppressive effects. Despite failing to exhibit obvious adverse involvements during its protective therapy, the unique role of dexamethasone affects an array of organs implicated in preliminary histopathological findings. This prospective study aimed to verify the alterations in the liver, brain, kidney, and spleen of pregnant rats treated with low-versus high-dexamethasone doses. Overall, 72 Wistar rats weighing 250 &#xb1; 20 g were divided into the control pregnant group, which was subdivided into two subgroups (14 and 21 days); the pregnant group, which was ultimately subdivided into two groups and then orally administered diluted concentrations of dexamethasone at 625 and 125 &#xd7; 10 &#xb5;g/kg body weight (BW); each of these concentrations was subdivided into two subgroups (14 and 21 days); the control non-pregnant group, which was subdivided into two subgroups (14 and 21 days); and the non-pregnant group, which was sub grouped into two groups, was orally administered the same mentioned concentrations of dexamethasone. Histological sections from the liver, brain, kidney, and spleen were further stained with hematoxylin and eosin and then examined under a microscope to evaluate tissue integrity and histopathological lesions. Dexamethasone exhibited significant adverse effects on total organ weights. Significant histopathological variations in dexamethasone-treated tissues. Therefore, liver changes included hepatocyte necrosis and interstitial inflammation. Structural brain changes involving neuronal necrosis and perineuronal vacuolations. Despite kidney lesions, which included dilated tubules and necrosis with sloughing of the renal epithelium, the spleen exhibited lymphoid follicle depletion and hemorrhage of red pulp. Strong, unlimited alterations (+++) of the tissues were observed in the group that received 125 &#xd7; 10 &#xb5;g/kg BW dexamethasone. Additionally, the lowest concentration group, which received 625 &#xb5;g/kg BW dexamethasone, showed non-negligible changes (++) compared with the controls. These findings suggest that the harmful effects of dexamethasone on organ architecture are dose-dependent. Therefore, dexamethasone is not decidedly contraindicated during pregnancy, but strict consideration and incessant monitoring are required during application, irrespective of the healthcare supplier.

Diabetic foot ulcers (DFU) are a common and severe complication of diabetes, associated with high morbidity, infection risk, and amputation rates. Various dressings have been applied in clinical practice, yet their comparative safety and efficacy remain unclear. This study aimed to systematically evaluate different dressings for DFU treatment through meta-analysis. Relevant studies from Chinese and English databases were retrieved and analyzed. A total of 25 studies involving 2,421 patients were included. Dichotomous data analysis showed that the experimental group had a significantly higher complete wound healing rate than the control group (OR=4.62, 95 % CI: 3.10-6.90, p<0.01), a significantly lower incidence of wound infection (OR=0.63, 95 % CI: 0.43-0.93, p=0.02), and no significant difference in amputation rate (OR=0.62, 95 % CI: 0.34-1.14, p=0.12). Continuous data analysis indicated that the experimental group had higher wound healing scores (MD=25.77, 95 % CI: 2.33-49.20, p=0.03), greater ulcer area reduction (MD=27.96, 95 % CI: 21.93-34.00, p<0.01), and shorter healing time (MD=-11.41, 95 % CI: -14.35 to -8.47, p<0.01). Meta-regression analysis suggested that publication year, blinding, and outcome indicators contributed to heterogeneity (p<0.05). Activated carbon cloth (ACC), negative pressure wound therapy (NPWT), and olive oil dressings demonstrated favorable safety and efficacy, although each has distinct advantages. Clinical selection should therefore be individualized according to patient conditions and wound characteristics. Future studies with larger sample sizes and higher methodological quality are needed to further validate these findings and reduce heterogeneity, thereby providing more robust evidence for clinical decision-making.