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Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte balance, systemic cancer therapies, tumour lysis syndrome and anatomical alterations after urinary diversion or nephrectomy. Moreover, urolithiasis itself has been linked to increased rates of renal cell carcinoma, urothelial carcinoma and bladder cancer, potentially mediated by chronic inflammation, recurrent infections and shared metabolic or environmental factors. Management in this setting is complex and must be individualized. Percutaneous nephrolithotomy achieves the highest stone-free rates in patients with altered urinary tract anatomy, whereas retrograde intrarenal surgery and shock wave lithotripsy have more selective roles. Preventive strategies focus on thorough metabolic evaluation, hydration optimization and addressing cancer-specific risk factors such as hypercalcaemia, acidosis and chronic urinary stasis. Despite these insights, data on the epidemiology, mechanistic underpinnings and optimal management of urolithiasis in patients with cancer remain limited. Prospective studies are needed to clarify causal relationships, refine preventive strategies and develop evidence-based treatment algorithms for this growing and complex population.
We previously established an interpretable combinatorial data-mining framework to identify combinations of clinical factors predictive of heart failure. Because hypertension (HT) is a major contributor to heart failure, accurate prediction of new-onset HT is critically important for prevention. To identify combinations of clinical factors predictive of HT onset using a novel limitless-arity multiple-testing procedure (LAMP) and to estimate the probability of developing HT. We analyzed 2,610,286 individuals without HT who underwent annual health check-ups starting in 2005-2015 and were followed for 5 consecutive years without missing data. Using the LAMP method, we systematically identified statistically significant combinations of fewer than four clinical factors associated with HT onset. Among 28,618 subjects used for rule discovery, 4802 combinations predictive of HT onset were identified. The remaining 2,581,668 individuals were classified into one group with no predictive combinations (G0) and 20 groups (G1-G20) according to increasing numbers of predictive combinations. The incidence of HT increased stepwise with the number of predictive combinations, as confirmed by Kaplan-Meier analyses (p < 0.001). Receiver-operating characteristic analysis demonstrated a moderate discriminative performance (area under the curve = 0.69). We identified combinations of routine clinical parameters that predict new-onset HT in the general population. A greater number of matching predictive combinations was associated with a proportionally higher probability of developing HT. This interpretable combinatorial data-mining framework may enable risk stratification for HT and support early preventive strategies.
Percutaneous endoscopic lumbar discectomy (PELD) is a preferred minimally invasive surgery for lumbar disc herniation (LDH); however, postoperative recurrence, nerve root damage, and hyperesthesia continue to present key clinical challenges. Chitosan represents a novel preventive approach against postoperative complications. This study aimed to assess the clinical efficacy of ultrasound-guided percutaneous endoscopic interlaminar discectomy (PEID) plus medical chitosan in treating lumbar 4-5 disc herniation (L4-5 LDH). Totally, 200 L4-5 LDH patients were prospectively recruited and randomly divided into the control group (ultrasound-guided PEID) and observation group (ultrasound-guided PEID plus medical chitosan). Low back and leg pain and lumbar dysfunction were assessed preoperatively and postoperatively using Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association (JOA). Efficacy and postoperative complications were evaluated according to the modified MacNab criteria. Logistic regression analyses identified the risk factors. Mann-Whitney U test was used for inter-group comparisons, and the Kruskal-Wallis test for timepoint comparisons. The two groups showed significant differences in pre-treatment Pfirrmann classification and operation time. As time progressed, patients exhibited reduced VAS and ODI scores and increased JOA scores postoperatively. Significant differences were observed in VAS, JOA, and ODI scores in the observation group at 2 weeks postoperatively. The observation group demonstrated superior treatment efficacy and a lower complication incidence than the control group. Age, disease course, and postoperative bleeding were independent risk factors affecting clinical efficacy of ultrasound-guided PEID plus chitosan. Ultrasound-guided PEID plus medical chitosan reduces postoperative pain and perioperative complications, demonstrating superior clinical efficacy.
The popularity of domestic cats (Felis catus) as companion animals is undisputed. However, the human-feline proximity poses potential health risks due to zoonotic disease transmission as well as physical injuries from bites and scratches. It is alarming to note that epidemiological data supports the prevalence and colonisation of Staphylococcus spp., including methicillin resistant Staphylococcus aureus (MRSA) in the oral cavity of cats. Considering the problem of antibiotic resistance globally, this review collates recent findings on the role of cats as reservoirs of antibiotic resistant pathogenic Staphylococcus spp. and examines the clinical implications of staphylococcal infections in cats. It provides an in-depth study into the link between pathogenesis and antibiotic resistance. In the context of "one health" the pathogenesis mechanisms enabling persistence and virulence such as colonisation, invasion, toxin and enzyme production, and immune evasion are also discussed. A mechanistic overview of promotion of antibiotic resistance in bacteria is provided, focusing on genetic adaptations such as target modification, efflux pumps, and gene acquisition. Patterns of antimicrobial resistance (AMR) among cat-derived isolates are critically assessed, outlining emerging trends and their implications for therapeutic strategies. Zoonotic concerns, vis-a-vis the impact of resistant Staphylococcus spp. on human health are addressed. The threats posed by rising antibiotic resistance, such as compromised treatment outcomes and the heightened risk of transmission across species are reviewed and strategies for mitigation, including preventive methods, ongoing surveillance, and the adoption of alternative non-antibiotic measures such as probiotics, bacteriophage therapy, and antimicrobial peptides, are suggested herein.
Individuals who engage in illicit or nonmedical opioid use may have elevated risk of health and social consequences, including progression to opioid use disorder (OUD). Preventive interventions to reduce this risk are lacking. This trial tested the impact of a primary care-integrated collaborative care approach for reducing risky opioid use, defined as nonmedical use of prescription opioids or any use of illicit opioids. Cluster-randomized controlled trial randomized primary care providers (PCPs) and their patients into the Subthreshold Opioid Use Disorder Prevention (STOP) intervention or enhanced usual care (EUC). Primary care clinics at 5 U.S. sites. PCPs and their patients were recruited January 2021-May 2023. A total of 119 PCP clusters (STOP = 48, EUC = 51) and 202 patients (STOP = 88, EUC = 114) enrolled. Eligible patients were adults (≥18 years) having current risky opioid use, without moderate-severe OUD. Patient participants were majority female (63.4%), white (70.8%) and non-Hispanic (96.5%), with a mean age of 55.7 [standard deviation (SD) = 12.7] years. At baseline, 63.4% of participants had moderate-severe pain (Brief Pain Inventory) and below average physical (79.2%) and mental (62.4%) health (SF-12). The STOP collaborative care intervention consisted of brief advice from the PCP about reducing risky opioid use, meetings with a clinic-embedded nurse care manager over 12 months and remote health coaching (2-6 sessions). Both groups received primary care treatment as usual and overdose risk reduction materials. The primary outcome was total days of risky opioid use, recorded from 6 monthly electronic surveys. A key secondary outcome was moderate-severe OUD at 6 and 12 months. A total of 77 (87.5%) STOP and 107 (93.9%) EUC participants completed the 6-month assessment period. The primary outcome analysis used the Intention-to-Treat sample with multiple imputations of missing data. Mean days of risky opioid use at 180 days were lower in STOP than EUC [12.2 (SD = 27.73) vs. 15.5 (SD = 32.64)]; the difference between groups adjusted for baseline risky opioid use was not statistically significant (rate ratio 0.95, 95% confidence interval = 0.52-1.74). One STOP participant (1.1%) and 13 EUC participants (11.4%) developed moderate-severe OUD at 6 months, and 3 (3.4%) STOP and 6 (5.3%) EUC participants had moderate-severe OUD at 12 months (P < 0.001). This cluster-randomized controlled trial did not find evidence that the STOP intervention for reducing risky opioid use produced greater reductions over 6 months compared with enhanced usual care, though fewer intervention participants progressed to moderate-severe opioid use disorder. Patients had a high burden of pain and comorbidities that may present challenges to reducing opioid use.
Type 2 diabetes exhibits substantial heterogeneity prior to disease onset, posing challenges for early prevention. This study aimed to identify pre-disease subgroups with distinct risk profiles and develop subgroup-specific prediction models to facilitate early detection and precision intervention. Proteomic data from 41 030 participants without diabetes at baseline in the UK Biobank were analysed. Proteins associated with incident type 2 diabetes were identified using multivariable-adjusted Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression. Finite Gaussian mixture model-based clustering was applied to define risk subgroups. Heterogeneity among subgroups was characterised according to proteomic patterns, clinical traits and disease risk. Subgroup-specific prediction models were subsequently developed using Cox regression. A total of 113 protein markers were identified, stratifying the population into three subgroups: metabolically healthy group (MHG), mild inflammation group (MIG) and Dyslipidemia with inflammation group (DLIG). Compared with MHG, DLIG showed the highest risk of type 2 diabetes (HR = 2.58, 95% CI: 2.34-2.84), followed by MIG (HR = 1.71, 95% CI: 1.49-1.98). Enrichment analysis indicated dysregulation of immune-inflammatory and lipid metabolism pathways in DLIG and MIG. Clinically, DLIG exhibited higher BMI, waist circumference, triglycerides, and C-reactive protein levels, whereas MIG showed moderately elevated C-reactive protein. Subgroup-specific proteomic models outperformed traditional clinical models in predicting diabetes risk (AUC 0.820-0.889 vs. 0.709-0.784; C-index 0.787-0.847 vs. 0.687-0.747). Proteomics-based clustering identified three pre-disease subtypes of type 2 diabetes characterized by inflammation-lipid profiles, improving risk prediction and supporting precision prevention.
The seismic design response spectrum is a vital parameter for determining the potential seismic load of the engineering structure. Differential evolution algorithm (DE) with a novel hybrid mutation operator is utilized to calibrate the spectral parameters in order to enhance iteration efficiency. This study calibrates the seismic design response spectrum for China based on the Chinese seismic intensity scale and compares the results with the Code for Seismic Design of Buildings (CSDB2010).The calibration spectra are based on strong ground motion records with destructive power exceeding the Chinese seismic intensity 7 and above. The characteristics of the calibration spectral parameters are analyzed and subsequently compared with the design spectra of the Code for Seismic Design of Buildings (CSDB2010). It is found that: Increasing the number of iterations can enhance the fitting goodness of DE between the calibration spectrum and the record response spectrum. The average site characteristic period (Tg) for rock and hard soil site conditions (Class I and II) is greater than the Tg specified in CSDB2010. The average Tg for intensity 10 + is greater than the average Tg for intensity 7, 8, and 9. Tg increases with the seismic intensity. The average spectra platform value (βmax) from this study gradually approaches the βmax in CSDB2010 as the intensity increases. The average attenuation index (γ) at different intensities of this study is greater than γ in CSDB2010.
Yacon concentrate, which is rich in fructan, phenolic compounds, and flavonoids, exhibits notable nutritional and antioxidant properties. This study explored the potential of New Zealand yacon concentrate to modulate the gut microbiota and host metabolism, alleviate inflammation, and enhance antitumor immunity. The anti-inflammatory and antitumor effects of yacon concentrate were evaluated in mouse models of dextran sulfate sodium (DSS)-induced colitis and colorectal cancer (CRC). Ex vivo gut chemostat model experiments were performed to assess the impact of yacon concentrate on human gut microbiota remodeling. The gut microbiota composition was then analyzed via metagenomic sequencing, and metabolomic profiling was conducted to identify the key bioactive metabolites. Yacon concentrate significantly ameliorated DSS-induced colitis by reducing weight loss, lowering the disease activity index scores, and alleviating colonic shortening in mice. In CRC models, yacon concentrate markedly suppressed tumor growth, reduced tumor incidence, and decreased tumor burden. Microbiota derived from the chemostat after yacon supplementation not only enriched beneficial bacteria and inhibited the growth of immunotherapy-resistant bacteria but also enhanced energy and short-chain fatty acid metabolism. Moreover, transplantation of this microbiota into mice significantly improved the tumor microenvironment and inhibited tumor growth. Collectively, these findings indicate that yacon concentrate is associated with changes in the gut microbiota and metabolomic profiles, supporting a potential link between yacon intake and modulation of the gut microbiota-metabolome axis. These observations provide a rationale for further mechanistic and interventional studies evaluating yacon concentrate as a dietary strategy for colitis prevention and CRC prevention, and as an adjunctive treatment.
Evidence regarding the outcomes of intravenous thrombolysis (IVT) in patients taking direct oral anticoagulants (DOACs) within 1 day before acute ischemic stroke remains limited. In this study, we aimed to evaluate the bleeding risk after IVT in patients with and without recent DOAC exposure. This retrospective cohort study analyzed TriNetX global network data (January 2010-September 2024) in adults aged ≥ 20 years receiving IVT for acute ischemic stroke. Groups with DOAC and no anticoagulant (no-OAC) exposure within 1 day before stroke were compared. The primary outcome was intracranial hemorrhage (ICH) within 2 days after IVT. Secondary outcomes included major bleeding, blood transfusion within 2 days, and 30-day and 90-day mortality rates. Subgroup analyses examined individual DOACs (apixaban, rivaroxaban, edoxaban, and dabigatran). Propensity score matching controlled for confounders with risk differences (RDs) and odds ratios (ORs) to estimate outcome events. Among 64,667 patients (mean age 65.1 ± 16.1 years; 50.1% women), 1183 (1.8%) received DOACs, and 63,462 (98.1%) received no anticoagulants. After propensity score matching, the DOAC cohort had lower risks of ICH (RD, - 2.88% [95% CI, - 4.28% to - 1.48%]; OR, 0.36 [95% CI, 0.21-0.60]) and major bleeding (RD, - 2.54% [95% CI, - 4.53% to - 0.55%]; OR, 0.66 [95% CI, 0.47-0.91]) than the no-OAC cohort. Mortality rates were similar at 30 (OR, 0.87 [95% CI, 0.69-1.08]) and 90 (OR, 1.04 [95% CI, 0.85-1.26]) days. In subgroup analyses, apixaban showed lower ICH and mortality risks than no-OAC. DOAC exposure within 1 day before stroke does not result in higher bleeding or mortality risk in patients receiving IVT for acute ischemic stroke.
To evaluate whether a 3D-printed shoe sole can passively replicate toe-out gait biomechanics and reduce the knee adduction moment (KAM) and knee adduction angular impulse (KAAI), addressing limitations of traditional gait retraining. Custom shoe soles were 3D-printed using gyroid infill structures to create a rotational hind-sole and a variable stiffness fore-sole ('RVS' shoes). Twenty-one healthy adults completed three baseline gait trials in control shoes, followed by randomised biofeedback-based gait retraining at toe-out angles of 5°, 10° and 15°. After each retraining session, motion capture was used during overground walking. Participants then walked wearing RVS shoes for three trials. Gait biomechanics were analysed using repeated measures ANOVA and multiple linear regression. Compared to baseline, KAM's second peak was significantly reduced after toe-out retraining: 5° (13.6%, p = 0.002), 10° (20.2%, p < 0.001) and 15° (31.7%, p < 0.001). RVS shoes alone reduced it by 16.3% (p < 0.001), and KAAI by 8.6% (p < 0.001)-a reduction not achieved by retraining. Regression analysis showed that changes in KAM were strongly predicted (95%) by knee centre-of-pressure offset and mediolateral ground reaction force. 3D-printed RVS shoes passively replicated or exceeded the biomechanical effects of active toe-out gait retraining, offering a promising, low-effort intervention for managing knee osteoarthritis.
Geobacter bacteria use conductive pili and redox-active outer membrane vesicles to mediate metal transformations critical to the effectiveness of bioremediation and energy technologies. Mechanistic knowledge into these processes primarily comes from studies with Geobacter sulfurreducens grown in media closely formulated to mirror the mineral chemistry of contaminated sites. Here we show that, although subtle differences in the media's cationic strength did not measurably change permeability, they reprogrammed outer membrane-peptidoglycan crosslinks to modulate vesiculation and envelope functions impacting growth efficiency and mineralization. Cations that strongly bind and neutralize peptidoglycan carboxylates to prevent cell wall distortions, such as sodium and uranyl ions, controlled the extent of envelope remodeling and cell bias toward pili-driven uranium mineralization or membrane adsorption and release in vesicles. These findings identify cation chemistry as a key regulator of outer membrane vesiculation and the reprogramming of envelope functions ultimately determining the reproducibility of laboratory studies and effectiveness of bioremediation and energy-harvesting applications.
Klebsiella spp. are pathobionts associated with acute infections, including pneumonia and infections in the urinary tract and bloodstream, often acquired in health-care settings. They represent a global threat owing to the prevalence of multidrug-resistant strains. Moreover, Klebsiella spp., similarly to other members of the human gut microbiota, can contribute to the pathogenesis of non-communicable disorders. In this Review, we describe the taxonomical and molecular characteristics of the Klebsiella genus, as well as its epidemiology and impact as an infectious agent. We also review current evidence that associates Klebsiella spp. with different non-communicable disorders, including chronic inflammatory and metabolic disorders and cancer. We discuss different approaches to target Klebsiella spp., including tailored antibiotics, faecal microbiota transplantation, live biotherapeutic products and bacteriophages. Finally, we discuss the importance of preventative measures, such as epidemiological surveillance, infection control practices and lifestyle interventions, to reduce the spread of Klebsiella spp. in health-care settings and the broader community.
Carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) transmission studies incorporating clinical and genomic data from hospitals in India are lacking. We prospectively enrolled surgical intensive care unit (SICU) patients in a tertiary-care hospital in India (July 29 to November 30, 2023) and collected peri-rectal swabs at SICU admission, SICU discharge, and hospital discharge, alongside SICU environmental sampling. CP-CRE isolates were whole-genome sequenced to investigate differences between community-acquired (CA), healthcare-associated (HCA), hospital-acquired (HA), and environmental isolates. Twenty-seven percent of participants were CP-CRE-colonized on SICU admission, with risk factors of previous hospitalization and exposure to ≥2 antimicrobials. Among 148 admission-negative patients, 115 had repeat PRS; 42 (36.5%) acquired CP-CRE (27 upon SICU discharge, 15 upon hospital discharge). blaNDM (84%, n = 103) and blaOXA (29%, n = 36) carbapenemase genes were present in the sequenced isolates; 20 isolates (16%) carried both. Highly similar E. coli and K. pneumoniae clusters suggest hospital transmission, although the sample size limited network inference.
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The Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) randomised trial found that a restrictive intravenous fluid regimen increased the risk of acute kidney injury (AKI) after major abdominal surgery. We examined whether AKI after restrictive fluid therapy increased the risk for chronic kidney disease (CKD). We conducted long-term follow-up between 90 days and 48 months after surgery in RELIEF participants randomly assigned to a restrictive vs liberal fluid regimen, from May 2013 through September 2016. The primary outcome was incident or progressive CKD (stage ≥3), including worsening by ≥1 CKD stage in participants with preoperative CKD stage ≥3. Secondary outcomes included lowest recorded estimated glomerular filtration rate (eGFR) and maximal change in eGFR from baseline. Long-term follow-up data were obtained for 1670/2983 participants (mean age 69 (range: 58-75)yr; 47% females) included in the modified intention-to-treat analysis of the original RELIEF trial. The primary analysis was performed for 754 (49.6%) assigned to a restrictive fluid regimen and 766 (50.4%) assigned to a liberal fluid regimen. The incidence of new or worse CKD ≥ stage 3 did not differ between 422/754 (56%) participants assigned to restrictive fluid therapy, compared with 409/766 (53.4%) participants who received liberal fluid therapy (adjusted odds ratio 1.13 [95% CI 0.91-1.41]). These findings remained unaltered in sensitivity analyses. There were also no differences for eGFR secondary outcomes. Within the limits of this post hoc analysis, no difference was found in the incidence of new or progressive CKD was not related to a restrictive perioperative fluid regimen. ClinicalTrials.gov (NCT01424150).
While post-exposure prophylaxis (PEP) is considered a gate way to pre-exposure prophylaxis (PrEP), prospective evidence remains limited. This study aimed to investigate the association between PEP experience and subsequent PrEP initiation. A nested case-control study was conducted within a prospective cohort of men who have sex with men (MSM) in Qingdao, China. Cases were participants newly initiating PrEP, matched to four controls selected from participants who were at risk of initiating PrEP at the exact time the case occurred. The primary exposure was self-reported baseline PEP use, classified as never, ever, or recent use. Supplementary analyses examined PEP use at the visit immediately preceding PrEP initiation. A dichotomous exposure categorization grouping strategy was also applied across the above analysis (combining ever and recent users). Conditional Logistic regression estimated associations between PEP and PrEP initiation. Subgroup analyses were performed to assess the potential effect modification. A total of 59 cases and 234 matched controls were included. Baseline PEP experience was not significantly associated with subsequent PrEP initiation (ever use: aOR = 1.79, 95%CI: 0.86-3.69, P = 0.117; recent use: aOR = 1.52, 95%CI: 0.46-4.99, P = 0.488). This lack of a significant association persisted when ever and recent PEP users were combined into a single "prior use" category (aOR = 1.72, 95%CI: 0.88-3.35, P = 0.110). However, subgroup analyses showed that among participants who report recent recreational drug use, those with a history of PEP use were more likely to initiate PrEP (aOR = 2.25, 95%CI: 1.09-4.64, P = 0.029). These findings suggest that to effectively leverage PEP encounters as a gateway to sustained prevention, health systems should prioritize and intensify linkage interventions for high-risk groups identified during the PEP consultation, particularly individuals who use substances. Transforming PEP encounters into opportunities for tailored intervention can strengthen the HIV prevention cascade for those most in need.
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Sexual and gender minority youth (SGMY) experience a heightened risk of HIV acquisition due to barriers to HIV prevention, specifically connected to a lack of comfort in discussing sexual identity and practices with healthcare providers (HCPs). Decision-aid tools that support communication and shared decision-making may improve both access to and uptake of numerous HIV prevention modalities among SGMY. The study aimed to inform the decision-making process of HIV prevention modalities for HCPs and SGMY, providing key information about HIV prevention modalities with PrEPChoices, a web-based decision aid tool. Our study recruited two participant groups, HCPs (N = 15) and SGMY (N = 18). Eligible HCPs held a Doctor of Medicine (MD), Doctor of Osteopathic Medicine (DO), Nurse Practitioner (NP), or Physician Assistant/Associate (PA) degree, were licensed to prescribe medications in at least one United States state, had provided care to patients aged 15 to 24 within the past month, and were 18 years of age or older. Eligible SGMY were assigned male sex at birth, reported sexual attraction to and/or sexual behavior with cisgender men or transgender women in the past six months, and were 15 to 24 years of age. Participants completed a semi-structured Webex interview focused on the clarity and relevance, presentation and usability, and application of PrEPChoices, a web-based decision aid tool to support HIV prevention modalities selection among HCPs and SGMY. Interview transcripts were coded using an iteratively developed codebook. Findings were thematically analyzed within a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis framework. Thirty-three participants enrolled (N = 33), including 15 HCPs and 18 SGMY. Strengths included: (1) support for HIV prevention-based decision making; (2) utilization of the filtering tool to select preferred HIV prevention modalities; and (3) intuitive website design. Weaknesses included: (1) gaps in needs and literacy levels between HCPs and SGMY; (2) limited visual design appeal and inclusive representation; and (3) limited in-tool features for comparing HIV prevention modalities. Opportunities included: (1) potential for multimodal dissemination; and (2) expanding external resources provided. Threats included: (1) challenge of integrating PrEPChoices into clinical practices; and (2) ability to stand out compared to other online HIV prevention education resources. HCPs and SGMY highlight the value of PrEPChoices as a web-based decision aid tool to enhance HIV prevention modality selection among SGMY. Our results emphasize the critical role PrEPChoices can play in reducing barriers to sexual health education among SGMY, improving the patient-provider relationship with the PrEP landscape, and strengthening HIV prevention among SGMY.