To evaluate whether extending the American College of Rheumatology (ACR)-recommended monitoring interval for complete blood count and liver function tests in patients receiving methotrexate (MTX) affects timely detection of medication-related toxicity. We conducted an observational cohort analysis of 14,199 laboratory encounters from 2,439 patients receiving MTX with at least two measurements of alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cell (WBC) count, hematocrit (HCT), mean corpuscular volume (MCV), and/or platelet (PLT) count. Fibrosis-4 (FIB-4) scores were calculated when possible. Changes between consecutive measurements were plotted against time between encounters. Monitoring intervals of 3 months (45-135 days) and 6 months (135-225 days) were compared. After propensity score matching, we assessed incident clinically relevant abnormalities. Testing frequency showed no meaningful correlation with changes in ALT, AST, WBC, HCT, MCV, PLT, or FIB-4 (all R2 < 0.01). Mean laboratory changes did not differ meaningfully between monitoring intervals. Patients monitored every 135-225 days were equally or less likely to develop incident abnormal results than those monitored every 45-135 days; most odds ratios were not statistically significant (p > 0.05). Patients in the 6-month group were less likely to develop ALT >1×ULN (OR 0.72 [0.52-0.99]) or MCV >100 fL (OR 0.67 [0.46-0.96]). Extending routine MTX monitoring from every 3 months to every 6 months was not associated with more severe abnormalities or delayed detection of toxicity, suggesting quarterly testing may be more frequent than necessary and could be reconsidered to reduce cost and patient burden.
The EyeMate-SC (G-Metrics GmbH, Hanover, Germany) is a permanently implantable microsensor positioned in the suprachoroidal space for telemetric, high-frequency self-measurement of intraocular pressure (IOP), with measurements transmitted to the treating ophthalmologist via an external reading device. The aim of this review is to summarize the evidence regarding the safety of the implant, agreement of measurements with Goldmann applanation tonometry (GAT), patient adherence and acceptance, and the potential for capturing IOP fluctuations. This review includes 24 patients with open-angle glaucoma who received an EyeMate-SC sensor as part of a nonpenetrating glaucoma surgery and were followed for 3 years within the ARGOS-SC01 study and its follow-up study, ARGOS-SC01_FU. Implantation was successfully performed in all cases without complications. Over the observation period 15 moderate adverse events occurred beyond the early postoperative phase, of which one case was possibly related to the sensor. The device demonstrated long-term positional stability without dislocation and remained astigmatically neutral despite its superficial location. Agreement with GAT remained consistently good. Patients reported high acceptance and adherence and stated they would recommend the system to other glaucoma patients. In addition, the sensor enabled the assessment of both short-term and long-term IOP fluctuations. The EyeMate-SC enables, for the first time, high-frequency telemetric self-monitoring of IOP independent of lens status and supports therapeutic decisions based on comprehensive pressure profiles rather than single measurements. Newer system generations further extend this concept by enabling automated, continuous data acquisition with higher temporal resolution. In combination with artificial intelligence, this could enable early detection of progression-associated patterns; however, the impact on disease progression, quality of life and social participation requires further investigation. HINTERGRUND: Der EyeMate-SC (G-Metrics GmbH, Hannover, Deutschland) ist ein dauerhaft im suprachoroidalen Raum implantierbarer Mikrosensor zur telemetrischen, hochfrequenten Selbstmessung des intraokularen Drucks (IOD), dessen Messwerte über ein externes Lesegerät an den behandelnden Augenarzt übermittelt werden. Ziel dieser Arbeit ist die Zusammenfassung der Evidenz zur Sicherheit des Implantats, zur Übereinstimmung der Messwerte mit der Goldmann-Applanationstonometrie (GAT), zur Patientenadhärenz und -akzeptanz sowie zum Potenzial der Erfassung von IOD-Fluktuationen. In diese Übersichtsarbeit wurden 24 Patienten mit Offenwinkelglaukom eingeschlossen, die im Rahmen einer nicht penetrierenden Glaukomoperation mit einem EyeMate-SC-Sensor versorgt und über 3 Jahre im Rahmen der ARGOS-SC01-Studie und der Follow-up-Studie ARGOS-SC01_FU nachverfolgt wurden. Die Implantation verlief in allen Fällen komplikationslos. Über den Beobachtungszeitraum traten jenseits des frühen postoperativen Intervalls 15 moderate unerwünschte Ereignisse auf, von denen ein Fall möglicherweise sensorassoziiert war. Der Sensor zeigte eine hohe langfristige Lagestabilität ohne Dislokationen und blieb trotz seiner oberflächlichen Position astigmatismusneutral. Die Übereinstimmung mit der GAT war dauerhaft gut. Zudem berichteten Patienten eine hohe Akzeptanz und Adhärenz und würden das System weiterempfehlen. Darüber hinaus ermöglichte der Sensor die Erfassung sowohl kurzfristiger als auch langfristiger IOD-Fluktuationen. Der EyeMate-SC ermöglicht erstmals eine hochfrequente telemetrische Selbstmessung des IOD unabhängig vom Linsenstatus und erlaubt eine Therapieentscheidung auf Basis umfassender Druckprofile statt Einzelmessungen. Neuere Systemgenerationen erweitern dieses Konzept um eine automatisierte, kontinuierliche Datenerfassung mit höherer zeitlicher Auflösung. In Kombination mit künstlicher Intelligenz könnten so progredienzassoziierte Muster frühzeitig erkannt werden. Der Nutzen hinsichtlich Krankheitsprogression, Lebensqualität und gesellschaftlicher Teilhabe bedarf weiterer Studien.
We report a simple and general strategy to monitor sulfur oxidation states using 19F NMR by incorporating a 4-fluorophenyl tag on sulfur-containing molecules. A series of structurally related compounds spanning various sulfur oxidation states were compiled, and their 19F NMR chemical shifts were recorded to establish a diagnostic fingerprint tool. This approach enables rapid characterization of products and byproducts in sulfur-based transformations, particularly those involving redox changes such as disproportionation. To demonstrate the utility of the method, we applied it to study reactions involving sulfur oxidation state changes, establishing a proof-of-concept for this diagnostic platform. This technique offers a valuable tool for mechanistic analysis and product profiling in diverse areas of sulfur chemistry.
Hemorrhagic transformation (HT) remains a life-threatening complication after acute ischemic stroke (AIS), yet no active predictive tool is available for early risk assessment. Herein, we develop an integrated triplex electrochemical aptasensing platform for the parallel and simultaneous quantification of three HT-associated biomarkers-matrix metalloproteinase-9 (MMP-9), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1). The system enables parallel detection by inserting three independent screen-printed carbon electrodes (SPCEs) into a multi-channel electrochemical workstation, each functionalized with a distinct aptamer, allowing simultaneous quantification of MMP-9, FN, and PAI-1 within 30 min. Each SPCE is modified with a conductive polypyrrole/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate/polyvinyl alcohol hydrogel and gold nanoparticles, followed by immobilization of specific thiolated aptamers via Au-S bonds. Upon target binding, aptamer conformational changes induce a concentration-dependent decrease in differential pulse voltammetry current. The sensor achieves ultralow detection limits of 4.04 fg/mL, 0.30 fg/mL, and 2.79 fg/mL for MMP-9, FN, and PAI-1, respectively, with a total assay time of 30 min. Clinical validation using plasma from 12 AIS patients demonstrates excellent agreement with enzyme-linked immunosorbent assay (mean bias <10%) and high reproducibility (RSD <5%). This work presents the first electrochemical aptasensor for FN and PAI-1 detection and provides a clinically validated, point-of-care-compatible platform for personalized HT risk prediction in thrombolytic therapy.
Real-time temperature monitoring of edible oil is crucial for cooking safety and quality. Conventional contact and infrared methods suffer from slow response, high cost, or low accuracy. Herein, a series of La3+-modulated Yb0.2Zr0.8O1.9: Ho3+ upconversion (UC) phosphors was synthesized via a high-temperature solid-state reaction. La3+ doping up to 30% preserves the cubic fluorite phase and significantly enhances UC luminescence by lowering the local crystal field symmetry around Ho3+ ions, achieving an 8.29-fold green emission enhancement with a color purity exceeding 85% under 980 nm excitation. Temperature-dependent luminescence measurements over 303-723 K reveal that the visible emissions undergo conventional thermal quenching, whereas the near-infrared (NIR) emission exhibits negative thermal quenching attributed to the enhanced non-radiative relaxation and phonon-assisted energy transfer. Based on the fluorescence intensity ratio (FIR) of non-thermally coupled levels of Ho3+, the thermometric performance was found to be strongly dependent on La3+ concentration, with the optimal relative sensitivity of 1.92% K-1 achieved at 7% La3+. A flexible film sensor was further fabricated from this material, which enables precise, non-invasive real-time temperature detection of edible oil with a relative error below 1%. This work provides a La3+-modulation strategy for high-performance UC thermometry and a practical platform for non-contact food temperature monitoring.
Hydrogen sulfide (H2S) is a crucial endogenous gas transmitter for the evaluation of food spoilage and disease diagnosis. Thus, we have effectively prepared a novel Aggregation-Induced Emission (AIE) probe EHAT, which displayed a obvious fluorescence color change after the addition of H2S (from orangered to green), suggesting that probe EHAT can identify H2S with the naked eye and the detection limit was calculated to be 1.5 × 10-7 M for H2S. The probe EHAT-based test strip was also developed to conveniently detect H2S gas generated during food spoilage. Moreover, the probe EHAT were successfully utilized to image endogenous and exogenous H2S in live cells.
Leptomeningeal Metastasis (LM) is a catastrophic complication of systemic malignancies with poor prognosis and significant diagnostic challenges. Extracellular vesicle (EV)-based liquid biopsy is an emerging technology that may improve the detection, prognosis, and therapeutic monitoring for LM. This systematic review aims to critically appraise and synthesize existing evidence on the use of EV-derived biomarkers from cerebrospinal fluid (CSF) or serum for the diagnosis, prognosis, and therapeutic monitoring of LM. A systematic search of PubMed, ScienceDirect, Semantic Scholar, and Google Scholar was conducted up to January 2025. Eligible studies evaluated EV-associated molecular biomarkers (microRNAs or proteins) in LM patients using CSF or serum samples. Data extraction included study design, sample source, EV isolation method, biomarker type, validation method, and diagnostic/prognostic relevance. Risk of bias was assessed using QUADAS-2. Ten studies met inclusion criteria, encompassing EV miRNA and proteomic profiling in LM, primarily from non-small cell lung cancer (NSCLC) and medulloblastoma. miR-21 consistently correlated with poor prognosis and therapy resistance. Novel candidates such as miR-183-5p demonstrated high diagnostic accuracy (AUC 1.0 in a discovery cohort), targeting PTEN pathways. EV-derived proteins including fibronectin-1 (FN1), transketolase (TKT), and complement C2 also showed strong discriminative potential. Heterogeneity in EV isolation techniques and small sample sizes limited meta-analysis feasibility. EV-based liquid biopsy holds cautious promise as a minimally invasive tool for LM diagnosis, prognosis, and therapeutic monitoring. Larger, multicenter studies with standardized protocols are required to validate these findings and facilitate clinical translation.
In today's demanding environment, the need for advanced fluorosensors capable of detecting various metal ions, especially aluminum (Al³⁺), which is common in industrial processes and environmental monitoring, is growing. To address this need, we have engineered a highly sensitive fluorescent probe, MSS, which exhibits distinctive greenish-yellow fluorescence specifically in the presence of Al³⁺ ions when illuminated with a 365 nm UV lamp in aqueous medium and has been employed for the detection of picric acid. The Job's plot analysis confirmed a 1:1 stoichiometric relationship between MSS and Al³⁺ ions. The limits of detection (LOD) and quantification (LOQ) are in the µM range. Moreover, we have developed a practical paper-strip-based test kit for on-site cascade detection of Al³⁺ ions and picric acid, enabling quick, efficient monitoring of aluminum levels across diverse environments. The successful detection of Al³⁺ in soil samples further validates MSS as a promising tool for environmental analysis and monitoring.
The integration of novel systemic therapies including antibody-drug conjugates (ADCs), immune checkpoint inhibitors (ICIs), and cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors with radiotherapy (RT) presents new opportunities in breast cancer (BC) management. However, clinical guidance on concurrent administration remains limited, particularly for advanced techniques. A multidisciplinary panel of radiation and medical oncologists from AROME and the Moroccan Medical Oncology Association conducted a literature review and established expert consensus recommendations during the fourth Moroccan Congress of Medical Oncology Private Practice. An evidence-informed, structured consensus process was used to achieve agreement on safety profiles across six RT modalities. Trastuzumab deruxtecan has shown a favorable safety profile with whole-breast irradiation and palliative RT, while trastuzumab emtansine combined with stereotactic radiosurgery shows elevated radionecrosis risk. ICIs are generally feasible with most RT modalities and toxicity monitoring applied; however, risk is context dependent, and evidence supporting stereotactic body radiotherapy-ICI benefit in oligometastatic BC remains limited. The use of CDK4/6 inhibitors concurrently with conventional and stereotactic RT seems feasible, although caution is advised for visceral metastases. These experts' agreements are supported by retrospective data and preclinical evidence, highlighting the need for prospective validation. This expert consensus statement provides pragmatic, modality-specific guidance on combining contemporary RT techniques with selected novel systemic agents in BC, complementing existing European Society for Medical Oncology /European Society for Radiotherapy and Oncology‑oriented frameworks and highlighting areas where prospective data are still needed. The findings underscore the importance of toxicity monitoring, particularly for ADCs in CNS-directed therapies, and call for biomarker-driven studies to optimize combination strategies. These recommendations aim to guide safe integration of novel agents with RT across resource-variable settings, including low- and middle-income countries.
Hydrogen sulfide (H2S) serves as a critical gasotransmitter that participates in diverse physiological and pathological processes. Developing dual-mode sensing approaches with high specifity, increased accuracy and portable testing for monitoring H2S level is highly demanded. Herein, a novel Cu2+ and nitro co-functionalized nanozyme (Cu@UiO-66-NO2) has been constructed for colorimetric/ratiometric fluorescence dual-mode sensing H2S. The Cu2+ modification endows the inert UiO-66-NO2 with oxidase-like activity to dissociate O2 into •OH and 1O2 radicals, that oxidize the substrate o-phenylenediamine (OPD), whereas the nitro group in the skeleton serves as reactive site for H2S. When H2S is present, the fluorescence of Cu@UiO-66-NO2 boosts at 435 nm owing to the reduction of NO2 into NH2 but its oxidase-like activity is inhibited, weakening the OPD oxidation. Accordingly, both the colorimetric (λ = 416 nm) and fluorescence (λem = 570 nm) signal originated from oxidized OPD decrease remarkably. The absorbance at 416 nm and fluorescence intensity ratio F435/F570 display good linear responses toward H2S between 1-20 μM and 2-100 μM, respectively. Moreover, H2S induces an obvious color transition from yellow to blue under UV light. A smartphone-integrated sensing platform was further established for visual and portable monitoring H2S. The MTT assay demonstrates the excellent biocompatibility of this nanoprobe and confocal laser scanning microscopy studies imply its efficiency for imaging endogenous and exogenous H2S in living cells.
Cancer therapy-related cardiac dysfunction (CTRCD) remains a significant risk of contemporary cancer treatment. Despite advances in oncologic therapies, cardiac surveillance strategies have largely relied on uniform, intensive monitoring, often without consideration of individual cardiotoxicity risk. This review evaluates the rationale for transitioning from blanket surveillance to risk-based, personalized cardiac monitoring strategies, especially for HER2-targeted therapy. Evolving definitions of CTRCD and improved risk stratification tools, have highlighted substantial heterogeneity in cardiotoxicity risk. Prospective studies in low-risk patients receiving non-anthracycline HER2-targeted therapies demonstrate that reduced-frequency echocardiographic surveillance appears safe and does not compromise cardiovascular or oncologic outcomes. Similar paradigms need to be studied for other cardiotoxic therapies, including BRAF/MEK inhibitors and VEGF inhibitors, with a need for prospective validation before clinical application. Risk-adapted cardiac surveillance offers a pragmatic, evidence-based approach to optimize resource utilization while maintaining patient safety. Future research should focus on prospective validation and guideline harmonization to enable personalized cardio-oncology care.
Influenza A viruses (IAVs) remain a persistent global threat because of rapid antigenic change, frequent genetic reassortment, and cross-species transmission. Swine act as key "mixing vessels," permitting co-infection with avian and human strains and accelerating viral diversification and zoonotic risk. Effective veterinary surveillance is therefore critical for detecting viral evolution within swine populations and for providing early warning at the animal-human interface. Taiwan, home to approximately 5.5 million pigs and 23.4 million people, offers a representative case for examining how swine influenza surveillance has evolved in response to these challenges. This review describes the development of veterinary surveillance strategies from fragmented, event-driven monitoring to a coordinated One Health governance framework incorporating routine whole-genome sequencing, targeted serological surveillance, and coordinated data exchange across sectors. Key historical milestones include mass vaccination and culling programs, the 2009 pandemic response and recent zoonotic detections of H1N2v in humans (2021-2023), collectively evidencing ongoing bidirectional viral exchange. Episodes of severe human seasonal influenza activity, including H3N2-associated outbreaks, further highlighted the importance of coordinated surveillance across human and animal health sectors. By focusing on surveillance practices applied to animals, this review highlights the practical value of integrating molecular epidemiology, veterinary field monitoring, artificial intelligence (AI)-enabled technologies and cross-sector communication under a One Health framework. The Taiwanese experience demonstrates how strengthened veterinary surveillance can improve the sensitivity for detecting reassortment events, enhance traceability of viral spread, and support timely risk assessment in intensive livestock systems. These lessons offer a practical, replicable pathway for other countries aiming to overcome swine influenza surveillance fragmentation and strengthen pandemic preparedness under a One Health framework.
Cervical cancer is the fourth leading cause of cancer mortality in women worldwide. PD-L1 is expressed in 34.4% to 96% of cervical cancers. Camrelizumab is an anti-PD-1 IgG4 antibody with antitumor activity. This study evaluates the efficacy and safety of camrelizumab in cervical cancer. A systematic search of PubMed, Embase, Web of Science, Cochrane Library, Ovid MEDLINE, and Scopus was performed to identify studies of pathologically confirmed cervical cancer treated with camrelizumab alone or in combination with chemotherapy or VEGFR-TKIs, including apatinib or famitinib. Eligible studies included randomized trials, single-arm trials, cohort studies, and case-control studies. Pooled proportions with 95% CIs were calculated using R version 4.4.1. Heterogeneity was assessed using I2, and evidence certainty was evaluated using GRADE. Eight studies comprising 382 patients were included. Camrelizumab was evaluated as monotherapy, with chemotherapy, or with VEGFR-TKIs. The pooled objective response rate (ORR) was 0.62 (95% CI: 0.32-0.85). The disease control rate (DCR), assessed in 7 studies including 297 patients, was 0.83 (95% CI: 0.60-0.94). The pooled partial response (PR) rate was 0.45 (95% CI: 0.29-0.62), while the complete response (CR) rate was 0.15 (95% CI: 0.10-0.23). Progressive disease (PD) outcomes were reported in a cohort of 297 patients, corresponding to a proportion of 0.16 (95% CI: 0.06-0.36), and stable disease (SD) demonstrated a pooled proportion of 0.30 (95% CI: 0.19-0.44). Commonly reported adverse events included neutropenia, anemia, leukopenia, hypertension, lymphopenia, and myelosuppression. Camrelizumab demonstrates clinically meaningful antitumor activity in cervical cancer, particularly in combination regimens, though toxicity requires careful monitoring.
Aeromonas spp. are extensively distributed across diverse aquatic environments and recognized as pathogens capable of causing diseases in aquatic animals. Pathogenic Aeromonas causes foodborne gastroenteritis in humans and can also lead to extra-intestinal infections. However, accurate identification of Aeromonas species remains challenging. This study aimed to accurately identify Aeromonas spp. and compare their virulence gene profiles, antimicrobial resistance patterns, and molecular evolutionary relationships. A total of 42 Aeromonas isolates were obtained from retail food and foodborne disease outbreaks. They were initially identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and further confirmed by genomic methods. Average nucleotide identity (ANI) can accurately identify Aeromonas species. However, a higher ANI threshold is required to distinguish closely related species. The genus Aeromonas was found to possess an open pan-genome, enabling the acquisition of new genetic elements and enhancing environmental adaptability. All isolates encoded β-lactamase resistance genes, and 90.5% (38/42) of these were conferred resistance to ampicillin and amoxicillin-sulbactam, with the 95% confidence interval (CI) of 77.9%-96.2%. Some strains harbored antimicrobial resistance genes, such as mcr, tetE, sul, qnr, and so forth, and conferred resistance to the corresponding antibiotics. Some strains contained mobile elements carrying antimicrobial resistance gene clusters, such as transposon Tn5393 and antibiotic-resistant plasmids, providing mechanistic insights into their potential for horizontal antimicrobial gene transfer and adaptive evolution. Certain Aeromonas species possessed numerous virulence genes, including ast, hlyA, rtx, aerA, and hutX, and genes encoding flagellar, pili, and secretion systems. A. dhakensis, A. salmonicida, A. hydrophila, A. veronii, and A. enteropelogenes were predicted to have higher virulence potential. In contrast, A. caviae, the main Aeromonas species associated with foodborne disease outbreaks, exhibited relatively fewer virulence genes. This study emphasized the pathogenic potential and antimicrobial resistance profiles of Aeromonas species. Continuous monitoring of resistance patterns and contamination levels in food products is crucial for minimizing infection risks and preventing disease outbreaks caused by Aeromonas spp.
To compare the adverse event reporting profiles of tacrolimus combined with everolimus versus tacrolimus combined with sirolimus for immunosuppressive therapy after organ transplantation using the FDA Adverse Event Reporting System (FAERS) database and to generate hypotheses to inform the individualized selection of mTOR inhibitors. As FAERS does not record drug dose, the two combinations are compared without reference to tacrolimus dosing. Adverse event reports from the FAERS database spanning the first quarter of 2004 to the fourth quarter of 2025 were extracted. Disproportionality analysis was performed using four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). Analyses were conducted at the system organ class (SOC) and preferred term (PT) levels, as well as age-stratified (< 60 years vs. ≥ 60 years), sex-stratified, and time-to-onset analyses. A total of 3101 reports for tacrolimus combined with everolimus (ta_ev) involving 13,237 adverse events, and 3093 reports for tacrolimus combined with sirolimus (ta_si) involving 13,356 adverse events were retrieved. The ta_ev regimen generated 459 PT signals covering 25 SOCs, with the three strongest SOCs being renal and urinary disorders (ROR = 4.85), infections and infestations (ROR = 3.55), and blood and lymphatic system disorders (ROR = 3.48). The ta_si regimen generated 413 PT signals also covering 25 SOCs, with the three strongest SOCs being immune system disorders (ROR = 5.22), renal and urinary disorders (ROR = 3.52), and blood and lymphatic system disorders (ROR = 2.98). Both regimens generated strong renal/urinary and haematological disproportionality signals, but the reporting patterns diverged in several respects: the ta_ev regimen had a significantly stronger signal for hepatobiliary disorders (ROR = 3.12 vs. 1.89), whereas the ta_si regimen showed a stronger signal for cardiac disorders (ROR = 1.14 vs. 0.81) and a stronger association with wound healing complications. A formal between-regimen comparison (ratio of reporting odds ratios (rROR), with 95% CIs) indicated that these differences in reporting were statistically distinguishable (Table 5), although the magnitudes were modest for the cardiac and several other classes. Age-stratified analysis indicated that patients under 60 years of age had a higher frequency and greater variety of adverse events; male patients accounted for a higher proportion of reports in both groups. The median time to adverse event onset was approximately 3-3.5 months, but more than 10% of events occurred after one year of treatment. Tacrolimus combined with everolimus and with sirolimus show distinct adverse event reporting profiles in FAERS: the everolimus-based combination was relatively enriched for hepatobiliary, BK-related renal and infectious events, and the sirolimus-based combination for cardiac, immune system, and wound healing events. These disproportionality signals describe reporting rather than measured risk and are hypothesis-generating; they require confirmation in controlled studies before they can guide the individualized choice of an mTOR inhibitor, with closer monitoring suggested for recipients under 60 years of age and for male patients.
Hospital ward strain occurs when care demands exceed available staffing, beds, and resources, posing a significant threat to safe inpatient care. While emergency department and intensive care settings have been extensively studied, ward-level pressures have received less attention, particularly from the perspectives of patients and frontline staff. This review aimed to synthesise current evidence on how hospital ward strain is experienced by staff and patients, and its implications for care quality, safety, and workforce sustainability. A mixed-methods systematic review was conducted on patient and staff perspectives on hospital ward strain. MEDLINE, CINAHL, PsycINFO, and HMIC were searched for empirical studies published from January 2000 to March 2025. Three reviewers screened titles and abstracts in pairs; full-text assessment was conducted by one reviewer with independent verification of a random 20% sample. The Mixed-Methods Appraisal Tool was used to assess methodological quality. Findings were analysed using Donabedian's Structure-Process-Outcome (SPO) model and Hollnagel's Resilience framework. Of 9,943 studies identified, 16 observational and non-randomised studies met the inclusion criteria, representing diverse healthcare settings across multiple countries. Most studies (87.5%) focused exclusively on staff perspectives; only two included patient experiences. Structural pressures (inadequate staffing, bed capacity constraints) consistently led to process failures (care delays, missed care, coordination breakdowns), resulting in burnout, turnover, quality and safety trade-offs, and compromised patient safety. Ward resilience was mainly reactive: respond and monitor were evident, but anticipate and learn were mostly absent. Patient acuity was inconsistently reported, limiting cross-study comparison. Ward strain is a systemic patient safety issue requiring structural solutions beyond staff resilience. Patient perspectives remain underrepresented and must be prioritised in future research. Policymakers should invest in anticipatory and learning resilience capacities, through workforce planning, real-time monitoring, and formal learning mechanisms, to ensure sustainable, safe ward care.
Survivorship of critical illness has increased, shifting attention toward recovery and long-term outcomes. Post-ICU nutrition is emerging as a clinically relevant, yet underperforming contributor to functional recovery and quality of life. Persistent nutritional inadequacy reflects insufficiently defined physiological requirements and limited implementable evidence-based guidance during ICU recovery. Energy and protein delivery sharply decline after ICU discharge, despite persistent metabolic demands. Underfeeding can result from the absence of recovery-specific targets, patient-level barriers (e.g. appetite loss, dysphagia, fatigue), and fragmented care transitions, including premature feeding-tube removal and suboptimal monitoring of oral intake. Structured patient and family engagement can help operationalize individualized nutritional strategies and improve feasibility without substantial resource burden, acting as continuity agents. Post-ICU nutritional failure reflects combined physiological and implementation challenges. Clinicians should recognize the post-ICU hospitalization period as a potential 'metabolic danger zone', requiring a shift from acute-phase restrictive feeding toward strategies prioritizing functional recovery and lean mass preservation. Improving outcomes requires standardized, yet adaptable, care pathways that bridge ICU-to-ward transitions, operationalize individualization, and integrate patient and family input as clinical instruments. Future research should prioritize multicenter implementation studies centered on 'disability-free survival' to inform adaptive, evidence-based nutritional protocols.
Renal and urological manifestations are understudied extraintestinal features of inflammatory bowel disease (IBD). Our aim was to estimate their prevalence and identify associated clinical parameters. This retrospective, single-center, observational study, included IBD patients with at least 1 year of follow-up and documented renal function monitoring. Demographic, clinical, and laboratory data were collected. The primary outcome was renal injury defined as acute kidney injury (AKI), chronic kidney disease (CKD), or both during follow-up. Secondary outcomes were AKI, CKD, and urolithiasis. Associations were assessed using univariate and multivariable logistic regression analyses. A total of 660 patients were included [379 (57.4%) male; 368 (56%) had Crohn's disease and 292 (44%) ulcerative colitis]. The primary outcome occurred in 54 patients (8.2%), AKI in 23 (3.5%), CKD in 35 (5.3%), and urolithiasis in 48 (7.3%). Independent risk factors for renal injury included IBD-related surgery [adjusted odds ratio (aOR): 2.69, 95% confidence interval (CI): 1.25-5.80, P = 0.012], extensive ulcerative colitis (aOR: 2.81, 95% CI: 1.11-7.73, P = 0.035), arterial hypertension (aOR: 2.43, 95% CI: 1.20-4.94, P = 0.014), male sex, and Charlson Comorbidity Index. AKI was associated with older age at IBD diagnosis and a higher frequency of disease flares. In a multivariable model, IBD-related surgery was independently associated with urolithiasis (aOR: 2.20, 95% CI: 1.03-4.70, P = 0.042). Renal and urological complications are relatively common in IBD. IBD-related surgery, extensive ulcerative colitis, and cardiometabolic comorbidities are associated with renal injury, while IBD-related surgery is also independently associated with urolithiasis.
The incidence of atypical femoral fractures in breast cancer patients is theoretically expected to be significantly higher than in those with primary osteoporosis. This is due to the prolonged and higher dosages of bisphosphonates used for post-operative bone protection and secondary osteoporosis. However, there is a notable lack of literature addressing this issue. Diagnosing and managing atypical femoral fractures in breast cancer patients presents unique challenges that differ substantially from those encountered in osteoporosis patients. We present a 58-year-old postmenopausal woman with a history of breast cancer who reported bilateral mid-thigh pain. From June 2015 to January 2017, she received zoledronic acid (4 mg) intravenously every 3 months, totaling seven doses. From 2017 to 2021, her regimen changed to a 4 mg infusion every 6 months, resulting in ten doses during this period. Overall, she underwent 17 zoledronic acid infusions over approximately 5.5 years. After minor trauma, she suffered sequential bilateral femoral shaft fractures. Bone metastases were initially suspected but ruled out through histopathological examination of both fracture sites, which showed no malignancy. Following her last infusion in June 2024, a multidisciplinary team (MDT) discussion was held. Considering her prolonged bisphosphonate exposure, the fracture sites, and imaging consistent with the 2013 American Society for Bone and Mineral Research (ASBMR) criteria, she was diagnosed with bisphosphonate-related atypical bilateral femoral fractures. Zoledronic acid was discontinued, and teriparatide treatment began, leading to significant pain relief, improved mobility, and radiological evidence of fracture healing after 9 months. However, due to mildly elevated tumor markers (CA19-9 and neuron-specific enolase [NSE]), teriparatide was switched to denosumab, which led to a prompt recurrence of bilateral thigh pain. This case underscores the critical importance of early and differential diagnosis of atypical femoral fractures in this patient population. The findings suggest that teriparatide can be effective in promoting atypical femoral fracture healing; however, its use in patients with a history of cancer remains controversial and requires individualized risk-benefit assessment under multidisciplinary guidance. Furthermore, switching to denosumab during active fracture healing may lead to symptomatic recurrence. This approach might also be relevant for patients with primary osteoporosis. Multidisciplinary management and long-term monitoring are crucial for managing such complex cases.
Following the 2021 policy change that opened Medicare Advantage enrollment to all Medicare beneficiaries with kidney failure, Medicare Advantage enrollment among this population has risen sharply. However, little is known about the financial and organizational consequences of this expansion for dialysis providers. Administrative leadership and clinical staff from two large national and four small regional dialysis organizations were recruited to participate in semi-structured, in-depth interviews. Interviews were conducted with executive, financial, and clinical staff from January 2022 to May 2024. This descriptive qualitative study analyzed interview transcripts using a modified grounded theory and content analysis approach. Interviews were conducted with thirty-seven leadership and staff from six dialysis organizations. Three main themes were identified reflecting their experiences managing the fiscal repercussions of Medicare Advantage expansion: 1) contract negotiations with Medicare Advantage plans were described as complicated, with large dialysis organizations securing more favorable rates and profit margins than small dialysis organizations; 2) although Medicare Advantage out-of-pocket caps were a cost-savings for patients with kidney failure, the expenses prior to reaching maximums were described by dialysis leadership and staff as a significant financial burden for their patients often leading to medical debt - a cost that small dialysis organizations reported absorbing as bad debt, and 3) dialysis organizations expressed concerns around the long-term financial impacts of Medicare Advantage expansion noting high health care costs, Medicare Advantage enrollment trends by their patients with kidney failure, and financial instability amidst market consolidation for small dialysis providers. Medicare Advantage expansion created uneven financial consequences for large and small dialysis organizations, raising concerns about consolidation, sustainability, and care quality. Ongoing monitoring is needed to ensure that the rapid growth of Medicare Advantage does not compromise the financial stability of dialysis providers or access and quality of care for individuals with kidney failure.