Severe community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality, requiring prompt empirical antibiotic therapy. The choice between amoxicillin/clavulanic acid (AMC) and third-generation cephalosporin (3GC) as first-line beta-lactam therapy in the ICU is still debated. To assess AMC and 3GC susceptibility in severe CAP or community-acquired aspiration pneumonia (CAAP) caused by Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and/or Staphylococcus aureus (SA), and to evaluate the appropriateness of empirical antibiotic therapy. We conducted a single-center retrospective study including patients admitted to the ICU between 01/01/2018 and 30/11/2022 for severe CAP/CAAP with microbiological documentation of at least one of the targeted pathogens. Clinical, microbiological, therapeutic, and outcome data were collected. The primary endpoint was AMC and 3GC susceptibility rates (expressed as percentage and [95% confidence intervals]). Among 104 included patients (median age 64 [48-71] years; 67% male), 60 (57.7%) had CAAP. AMC susceptibility rates were 81.5% [61.9-93.7], 78.0% [62.4-89.4], and 100% [92.6-100.0], while 3GC susceptibility rates were 96.3% [81.0-99.9], 95.1% [83.5-99.4], and 100% [92.6-100.0], for SP, HI, and SA, respectively. AMC was the empirical treatment in 59% of cases, and this choice was microbiologically appropriate in 86.9% of these prescriptions. Conversely, 3GC were prescribed empirically in 20% of cases, but this broad-spectrum choice was unjustified in 80% of those situations. Antibiotic de-escalation was performed in 28% of cases. In this single-center retrospective cohort, AMC appears to be a relevant empirical option for severe CAP/CAAP in the ICU, while 3GCs seem frequently overused. These findings required prospective multicenter validation before practice change can be recommended.
The tumor suppressor gene CDKN2/p16/MTS1, located on chromosome 9p21, is frequently inactivated in many human cancers through homozygous deletion. Recently, we have reported another pathway of inactivation that involves loss of transcription associated with de novo methylation of a 5' CpG island of CDKN2/p16 in lung cancers, gliomas, and head and neck squamous cell carcinomas. We now show that this aberrant CpG island methylation also occurs frequently in cell lines of breast cancer (33%), prostate cancer (60%), renal cancer (23%), and colon cancer (92%) and is associated with loss of transcription. Primary tumors of the breast (31%) and colon (40%) also displayed de novo methylation of this CpG island. This alteration of p16 in colon cancer was particularly striking, since inactivation does not occur through homozygous deletion in this tumor type. Our data show that in tumors, de novo methylation of the 5' CpG island is a frequent mode of inactivation of CDKN2/p16 and also firmly demonstrate that CDKN2/p16 is one of the most frequently altered genes in human neoplasia.
Lumbosacral spinal solitary fibrous tumors (SFTs) are rare, and their clinicopathological profile, surgical management, and recurrence behavior have not been systematically characterized as a dedicated anatomical subgroup. We assembled a lumbosacral-specific cohort to describe these tumors and identify factors associated with recurrence, with particular attention to dural compartment, extent of resection, and compartment-specific surgical constraints. We systematically reviewed reported lumbosacral spinal SFTs-both STAT6-confirmed and historically classified-together with the present case, extracting clinical, imaging, surgical, histopathological, and follow-up data. Associations with recurrence were assessed for tumor size (Mann-Whitney U test), resection extent, and dural compartment (Fisher's exact test, Kaplan-Meier estimation, log-rank), with Cox regression for recurrence-free survival. Sixty patients were included (17 STAT6-positive, 43 historically classified). Tumors were predominantly extradural (20 of 33 with a documented compartment). Locoregional recurrence or distant metastasis occurred in 21.7% (crude); the Kaplan-Meier estimated cumulative probability of an RFS event was approximately 26% at 3 years and 37% at 5 years. Recurrent tumors were larger than non-recurrent tumors (median 6.7 vs. 3.0 cm; p = 0.021). Local recurrence was substantially less frequent after complete than after subtotal resection (16.1% vs. 55.6%; p = 0.029). In this pooled cohort, larger tumor size was associated with recurrence, and local recurrence was less frequent after complete than after subtotal resection. The dural compartment appears to influence the surgical technique and margin that can realistically be achieved rather than whether complete removal is possible: extradural tumors more often permit en bloc, margin-negative excision, whereas intradural lesions involving the cauda equina, though frequently removable in full, generally require piecemeal function-preserving removal. Given the potential for delayed recurrence, long-term postoperative surveillance is warranted.
Incremental peritoneal dialysis (PD) is defined as prescribing a "less-than-standard" PD dose. High-certainty evidence to guide safe incremental PD prescription is lacking, resulting in substantial practice variability. We conducted a multi-national survey to evaluate current uptake, practice patterns and clinician perspectives on incremental PD. An online, unit-level survey, comprising 27 questions on incremental PD practice, was purposively disseminated to senior PD unit staff (physicians and/or nurses) from Australia, Canada and Thailand between June 2023 and September 2025. A total of 254 responses were received from 175 PD units (Australia: 55 (89%) of 62 units; Canada: 49 (60%) of 82 units; Thailand: 71 (34%) of 210 units). Incremental PD was reported as prescribed in fewer than 10% of patients in most units (56%, P=0.16). Incremental PD definitions varied substantially: CAPD with <4 daily exchanges (75%), APD or CAPD performed <7 days/week (65% and 61%), CAPD <8 L/day (50%), a single long overnight exchange (46%), or APD without a day dwell (44%), highlighting the absence of international consensus. Key reported advantages included increased patient satisfaction (81%), willingness to choose PD (75%) and preservation of residual kidney function (64%). Frequently cited disadvantages included patient or caregiver resistance to dose escalation (62%) and needing more frequent monitoring (31%). Quality of life was identified as the most important area for future research. Incremental PD is prescribed infrequently and variably. Concern about patient resistance to dose escalation is a barrier. High-quality data are needed to guide how incremental PD is defined, initiated and escalated.
The co-occurrence of species within the same area raises fundamental questions about how they can persist while sharing space and resources. One of the central aims of community ecology is to understand the processes that allow species to coexist over time. The sympatry between primates and ungulates has not received much specialized attention, despite long-term acknowledgment that the two groups frequently co-occur. In this contribution, we have reviewed and summarized empirical evidence from a set of published studies to determine the nature of primate and ungulate association in space and time, the ecological contexts within which such associations occur, and the types of interactions that have been reported. We particularly examined the trends in the study taxa, the geographic distribution of research, and the functional categories of interactions. Within the literature, interspecific interactions are frequently reported in Africa, between baboons (Papio sp.) and small to medium-sized ungulates. Foraging facilitation and antipredator benefits are among the most frequently documented interaction types, typically resulting in commensalistic or asymmetrical mutualistic outcomes favouring ungulate species. Nonetheless, mutualism and antagonistic interactions are also reported, which indicates the context-dependent nature of these relationships. The frequency and form of associations appear to further depend on seasonal variation and habitat structure, although these factors were not consistently taken into account in the studies considered in this review. This synthesis helps establish a set of research priorities to promote more systematic and focused studies of primate-ungulate sympatry.
This study aims to comparatively examine the readability, accuracy, and quality of responses provided by artificial intelligence (AI)-based chatbots such as Perplexity, ChatGPT-5, and Gemini to questions about knee osteoarthritis (KOA), which accounts for approximately four-fifths of the global osteoarthritis (OA) burden. In this study, 8 keywords were determined by excluding repetitive, irrelevant or synonymous ones from the 25 most frequently used English keywords associated with KOA based on Google Trends data, and these terms were asked as questions to three different artificial intelligence-based chatbots. The study measured readability using formulas like Coleman-Liau Index (CLI), Automated Readability Index (ARI), and Linsear Write (LW). Reliability of the information was assessed using the Journal of the American Medical Association (JAMA) benchmarks along with the modified DISCERN instrument. To determine overall content quality, the Global Quality Score (GQS) and the Ensuring Quality Information for Patients (EQIP) scale were applied. Together, these tools provided a comprehensive assessment of how understandable, reliable, and high-quality each chatbot's responses were. The most frequently searched keywords related to OA were "osteoarthritis of knee," "knee pain," and "osteoarthritis knee pain." A readability analysis of responses from three different AI-based chat systems revealed that all platforms had text levels above the Grade 6 threshold, and this difference was statistically significant (p < 0.05). Comparisons demonstrated that ChatGPT-5 produced the most readable content (FRES:45, GFOG:11.9, FKGL:9.24, CLI:14.03, SMOG:8.37, ARI:11.37, LW:7.2). However, Perplexity achieved significantly higher scores than ChatGPT-5 across all quality and reliability assessments, yielding superior median scores (DISCERN: 4, JAMA: 2, GQS: 4, EQIP: 92.8). Perplexity also outperformed Gemini in the mDISCERN reliability assessment (p = 0.001), while no significant difference in quality or reliability was found between Gemini and ChatGPT-5. No statistically significant difference was found between Gemini and ChatGPT in reliability and quality surveys. This analysis of KOA highlights significant challenges regarding the potential of popular AI chatbots for patient information. When examining readability levels, responses from these tools consistently exceed the recommended comprehensibility threshold, making it difficult for patients to absorb critical information. Furthermore, the relatively low scores recorded in reliability and content quality assessments raise significant concerns about the scientific validity and integrity of the medical information presented. Given these findings, the sufficient quality, robustness, and appropriate levels of understandability of future AI-based tools can only be ensured by the establishment and operation of an effective oversight mechanism.
Cushing's disease in pregnancy is rare and frequently underrecognized due to clinical overlap with physiologic gestational changes and hypertensive disorders of pregnancy, particularly preeclampsia. Delayed diagnosis may result in prolonged maternal morbidity and inappropriate management. A 30-year-old gravida 2, para 1 woman delivered at 37 weeks' gestation via induced vaginal delivery for preeclampsia without severe features. Her immediate postpartum course was unremarkable. At 12 weeks postpartum, she developed persistent proteinuria with associated hypercalciuria and hyperuricosuria despite preserved renal function. Over the following weeks, she developed hypokalemia, leukocytosis, and progressive cushingoid features including facial rounding, dorsocervical fat pad, central obesity, proximal muscle weakness, hypertension, easy bruising, hirsutism, and frequent falls. Endocrine evaluation revealed markedly elevated serum and urinary cortisol levels with concomitant hyperandrogenism. Magnetic resonance imaging demonstrated a 9-mm pituitary adenoma with evidence of hemorrhage. She was diagnosed with cyclic Cushing's disease with intermittent adrenal insufficiency and initiated on glucocorticoid replacement therapy. Transsphenoidal resection of the adenoma was performed at 26 weeks postpartum, resulting in improvement in blood pressure and clinical symptoms. At one year postpartum, she remained clinically stable on glucocorticoid replacement therapy. This case highlights the importance of maintaining a broad differential diagnosis in patients with hypertensive disorders of pregnancy. Persistent hypertension, proteinuria, and metabolic abnormalities should prompt evaluation for underlying endocrinopathies such as Cushing's disease. Early recognition and multidisciplinary management are critical to optimizing maternal outcomes and avoiding misattribution of symptoms to preeclampsia alone. Emerging biomarkers, including sFlt-1/PlGF ratios, may further aid in distinguishing preeclampsia from alternative pathologic processes.
Carbapenemase-producing Enterobacterales (CPE), particularly OXA-48-producing Enterobacterales, represent a major diagnostic and therapeutic challenge due to their frequent low-level carbapenem resistance and delayed microbiological detection. Rapid confirmation of carbapenemase production is essential to optimize antimicrobial therapy and infection control measures. This study evaluated the simplified carbapenem inactivation method (sCIM) for detection of OXA-48-producing Enterobacterales. Unlike the conventional mCIM, sCIM eliminates the preliminary carbapenem inactivation incubation step, simplifying the workflow and reducing turnaround time. A total of 150 OXA-48-producing Enterobacterales were analyzed, together with additional VIM-, KPC-producing, and non-carbapenemase-producing isolates collected from clinical specimens at the Hospital Central de la Defensa "Gómez-Ulla" in Spain. Carbapenemase production was confirmed using the Xpert® Carba-R molecular assay. The sCIM detected all OXA-48-producing Enterobacterales with 100% sensitivity (95% CI: 97.6-100%) and no indeterminate results, including isolates with low ertapenem MICs. Results were available after 16-18 h of incubation without previous 4-hour carbapenem inactivation step, simplifying laboratory workflow compared with the conventional mCIM. The rapid detection of OXA-48-producing Enterobacterales remains a major diagnostic challenge due to their frequently low carbapenem MICs and subtle phenotypic expression. This study demonstrates that sCIM provides a simple, reliable, and highly sensitive method for detecting these isolates, even in cases with borderline susceptibility profiles. Given its low cost and ease of implementation, sCIM represents a valuable tool for routine clinical laboratories, particularly in high-prevalence or resource-limited settings.
BACKGROUND Coronary artery embolism (CAE) is an infrequent but clinically significant non-atherosclerotic cause of ST-elevation myocardial infarction (STEMI). It presents unique diagnostic and therapeutic challenges due to its varied etiologies and the frequent absence of significant coronary artery disease. While atrial fibrillation is the most recognized cardiac arrhythmia associated with coronary embolism, atrial flutter as an embolic source remains underreported. This report highlights the complexities of diagnosing and managing CAE manifesting as an atypical STEMI and sudden cardiac arrest in a patient with previously undiagnosed atrial flutter, emphasizing the critical importance of identifying underlying embolic sources, particularly atrial flutter, to guide appropriate therapy. CASE REPORT An 82-year-old woman with non-ischemic cardiomyopathy presented after an out-of-hospital ventricular fibrillation cardiac arrest. Her post-resuscitation electrocardiogram revealed an inferior STEMI. Emergency coronary angiography demonstrated abrupt embolic occlusions in the distal right coronary artery, without evidence of significant underlying atherosclerosis. Percutaneous coronary intervention was performed to restore blood flow. After the procedure, telemetry revealed new-onset atrial flutter, the presumed embolic source. Her hospital course was complicated by severe global hypokinesis out of proportion to the infarct territory and progressive respiratory failure, ultimately leading to a family decision to transition to comfort care. CONCLUSIONS This case underscores the critical need to consider coronary artery embolism in the differential diagnosis for STEMI, particularly in patients lacking significant atherosclerotic disease burden. The presence of arrhythmias, such as atrial flutter, should raise strong clinical suspicion for an embolic etiology. While a good outcome was not achieved in this specific case, early recognition of CAE remains crucial for guiding appropriate revascularization strategies and initiating prompt anticoagulation to prevent recurrent thromboembolic events in surviving patients.
Internal state verbs and verb constructions (ISVs) play a central role in representing internal states, such as feelings or intentions, and are therefore frequently used when narrating fictional or personal narratives. This study aimed to compare the use of ISVs in German-speaking preschoolers across five ISV categories in two narrative genres: fictional and personal narratives. Twenty-one typically developing German-speaking preschoolers, ages 4;3 (years;months) to 7;0, produced two fictional narratives, consisting of three episodes each, elicited via the Multilingual Assessment Instrument of Narratives (MAIN), and six personal narratives using the Global TALES (Talking About Lived Experiences in Stories) protocol. The presentation of the tasks was counterbalanced. ISVs were classified into five categories of internal states (experiential, emotional, motivational, cognitive, and socio-relational). The relative use of ISV types and tokens per story was analyzed. Regression models were fitted as Bayesian multilevel binomial models. Preschoolers' use of ISVs was sparse but meaningfully patterned by ISV category and narrative genre. There was no effect of narrative genre on overall ISV use. However, ISV category revealed meaningful effects for experiential, socio-relational, and cognitive verbs. As predicted, experiential and motivational verbs were used more frequently in fictional narratives than personal narratives, while emotion and cognitive verbs showed the opposite pattern, with greater usage in personal narratives. For socio-relational verbs, no significant interaction was observed. This exploratory study is the first to investigate the impact of narrative genre and a classification into five ISV categories on the production of ISVs in the narratives of German-speaking preschoolers using globally accessible fictional and personal narrative elicitation tools. The results from this study may be of use to clinicians worldwide when selecting a narrative assessment tool to investigate children's production of ISVs.
Treatment goal limitations, such as "do not resuscitate", "do not escalate" and "comfort terminal care" are frequent in acute hospital care for patients with advanced illness, multimorbidity or impending death. Their ethical defensibility depends on transparent documentation of medical indications, proportionality and, where relevant, patient will. To examine whether documentation made medical rationale, patient will, advance directives, relatives' involvement or ethics consultation visible. We retrospectively analyzed documentation in an Austrian internal medicine department with intensive care over 12 months. Documents were identified in the hospital information system and descriptively analyzed. Deceased patients with documented limitations underwent manual review. Data were anonymized and analyzed using Microsoft Excel for Microsoft 365 (Microsoft Corporation, Redmond, WA, USA) and IBM SPSS Statistics, version 29 (IBM Corp., Armonk, NY, USA). Across 3998 inpatient stays involving 1829 patients, 277 patients had a documented treatment goal limitation (15.1%). Among 174 deceased patients, 111 had a documented limitation at death (63.8%). The most frequent order was combined do not resuscitate/do not escalate (75/111; 67.6%), followed by isolated do not resuscitate (23/111; 20.7%). Complete records were available for 101 cases; in 10 the rationale was not clearly traceable. Among the 101 manually reviewed cases, an explicit or presumed patient will was documented in 7 cases (6.9%), involvement of relatives in 13 cases (12.9%) and ethics consultation in 1 case (1.0%); medical rationale or physician decision was documented in 90 of 91 cases with traceable rationale (98.9%). Treatment goal limitations were common and usually medically justified in the records. The findings do not imply inappropriate decisions or lack of communication but show limited reconstruction of patient-centered reasoning. Documentation should make clearer how benefit, care, respect for autonomy and justice informed treatment limitation.
Disseminated gonococcal infection (DGI) is an uncommon but serious complication of untreated Neisseria gonorrhoeae infection, which typically presents as either the classic dermatitis-tenosynovitis-migratory polyarthralgia syndrome or as septic arthritis. Diagnosis is often challenging because blood and synovial cultures are frequently negative. A 35-year-old male with past medical history of recurrent diverticulitis and syphilis, presented with arthritis involving the left knee and ankle, followed by a progressive rash starting on the palms and soles and spreading towards his trunk during a diverticulitis flare. History was notable for multiple sexual partners. Physical examination was significant for multiple skin lesions with variable morphology involving the palms and soles. Left knee joint exam revealed swelling and reduced range of motion. Labs showed elevated inflammatory markers, and reactive RPR of 1:32 with positive treponemal antibodies. Infective workup, including blood cultures, urine Chlamydia/gonorrhea NAAT were negative. Subsequent arthrocentesis of the left knee and left ankle revealed elevated nucleated cells (73,500/µl ankle, 76,250/µl knee) with positive monosodium urate crystals. Notably, broad range synovial PCR was positive for N. gonorrhea but joint cultures negative. He was diagnosed with DGI, and started on IV Ceftriaxone, and received IM Benzathine penicillin G weekly for 3 weeks for concurrent secondary syphilis. This case underscores the diagnostic value of targeted molecular testing in DGI, when urine NAAT and cultures are often negative. Since mucosal gonococcal infections are frequently asymptomatic or may have cleared before dissemination, urogenital testing alone may be misleading. Concurrent rash with stable RPR titers and history of prior syphilis raised concern for active secondary infection. This reinforces the need for comprehensive STI screening in all patients with DGI. Lastly, presence of monosodium urate crystals does not exclude septic arthritis. Clinicians should maintain suspicion for DGI in sexually active patients presenting with fever, rash, and arthritis despite initially negative screening tests.
The continuity of essential medications is a fundamental component of clinical governance within custodial healthcare. National standards, including the Royal Pharmaceutical Society (RPS) Professional Guidance on the Safe and Secure Handling of Medicines1 and the College of Policing's 2024 Authorised Professional Practice (APP) for Custody,2 emphasise the importance of maintaining prescribed treatments to prevent avoidable clinical deterioration. Yet hormone replacement therapy (HRT) frequently remains excluded from rapid medicines continuity pathways, resulting in abrupt interruption for women entering police and prison custody despite risks highlighted in the UK National Preventive Mechanism (NPM) Menopause in Detention Toolkit.3 This article examines the immediate physiological and psychological consequences of abrupt iatrogenic oestrogen withdrawal, framing endocrine withdrawal as an acute patient safety issue rather than a lifestyle concern. It integrates emerging evidence, including the UK National Preventive Mechanism (NPM) Menopause in Detention Toolkit,3 the Independent Custody Visiting Association (ICVA) Menopause Impact Report,4 and the growing recognition that women and clinicians require clearer evidence to support decisions regarding the continuation or discontinuation of hormone replacement therapy(Hamoda and Panay, 2024).5 It also incorporates peer-reviewed neuroendocrine research demonstrating the destabilising effects of abrupt oestradiol withdrawal 6-8. The paper argues for a paradigm shift in custodial healthcare, recognising hormone replacement therapy as an essential endocrine treatment requiring timely continuity of care. It proposes practical approaches to medicines verification and rapid bridging protocols to reduce avoidable endocrine withdrawal, support accurate clinical assessment and improve patient safety.
Once-daily, single-tablet regimens have transformed care for persons living with human immunodeficiency virus type 1 (HIV-1); however, challenges to adherence continue to limit effective treatment. Long-acting oral-drug combinations could offer new options with less frequent dose administration. We conducted a phase 3, double-blind, randomized, active-controlled, noninferiority trial in 12 countries to evaluate the efficacy and safety of a switch to once-weekly oral islatravir-lenacapavir (ISL/LEN) from once-daily oral bictegravir-emtricitabine-tenofovir alafenamide (B/F/TAF) in adults in whom HIV-1 had been virologically suppressed for at least 6 months while they were receiving B/F/TAF. Participants were assigned in a 1:1 ratio to receive once-weekly ISL/LEN (2 mg/300 mg) or to continue once-daily B/F/TAF for 96 weeks; all received matched placebo for the alternative regimen. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, as determined by the Food and Drug Administration-defined snapshot algorithm. Noninferiority was determined at a margin of 4 percentage points. A total of 607 participants underwent randomization; 304 were assigned to the ISL/LEN group and 303 to the B/F/TAF group. A total of 21% of the participants were women, 31% were Black, 26% were Hispanic or Latine, and 15% were 65 years of age or older. At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was reported in no participants in the ISL/LEN group and 1 (0.3%) in the B/F/TAF group (difference, -0.3 percentage points; 95.002% confidence interval [CI], -1.4 to 0.8); an HIV-1 RNA level of less than 50 copies per milliliter was reported in 284 (93.4%) and 280 (92.4%), respectively (difference, 1.0 percentage point, 95% CI, -3.2 to 5.2). The mean change in the CD4+ T-cell count at week 48 was -10 cells per microliter with ISL/LEN and -18 cells per microliter with B/F/TAF (least-squares mean difference, 12 cells per microliter; 95% CI, -16 to 39). The trial regimen was discontinued owing to adverse events in 6 participants (2.0%) in the ISL/LEN group and 5 (1.7%) in the B/F/TAF group; serious adverse events occurred in 16 (5.3%) and 14 (4.6%), respectively. Among persons with virologically suppressed HIV-1, once-weekly oral ISL/LEN was noninferior to once-daily B/F/TAF in maintaining HIV viral load suppression. (Funded by Gilead Sciences and Merck Sharp and Dohme; ISLEND-1 ClinicalTrials.gov number, NCT06630286.).
Support persons are essential in cancer care, particularly during surgical consultations that involve complex decision-making and emotional stress. However, the COVID-19 pandemic introduced visitor restrictions that limited in-person companion access, raising concerns about patient-centered care. This study examined patterns of companion presence during breast reconstruction consultations in 2020 and compared findings to a pre-COVID cohort to assess shifting predictors of support-seeking behavior. A retrospective review was conducted of all breast reconstruction consultations (N = 59) at a regional plastic surgery center during the first year of the COVID-19 pandemic. Demographics, cancer status, travel distance, and companion presence were extracted from electronic medical records. Companion types and behaviors were qualitatively assessed from provider notes. Results were compared to a previously published pre-COVID cohort (N = 421). Statistical analyses included chi-squared tests and independent samples t-tests (α = 0.05). Despite pandemic restrictions, 51% of patients brought a companion. Companion presence was significantly associated with having an active cancer diagnosis (71.9% vs. 25.9%, p = .004), while marital status and travel distance were not significant predictors. In contrast, pre-COVID data showed marital status and travel burden as significant predictors of accompaniment. Provider notes revealed companions frequently offered emotional support, clarified medical details, and assisted in decision-making. Support persons remained integral to breast cancer care during COVID-19, particularly for patients facing active disease. These findings underscore the importance of flexible institutional policies that preserve the patient-companion relationship during emotionally charged consultations.
Several novel pharmacological therapies for chronic kidney disease (CKD) have been shown to reduce risks of disease progression, cardiovascular events, and mortality. However, their effects on health-related quality of life (HRQoL) remain scattered across trials and are difficult to interpret, owing to variability in instruments used and other design related factors. PubMed and Web of Science were searched for randomized clinical trials of pharmacological interventions aimed at slowing CKD progression in adults with non-dialysis CKD, published between January 2000 and January 2026. Two authors independently screened and extracted data. Data on study characteristics, HRQoL instruments used, and intervention effects were synthesized descriptively, and key methodological considerations were reviewed. Of 16,624 screened records, 13 trials collected HRQoL data. HRQoL was measured mainly using the EuroQol 5-Dimension questionnaire (EQ-5D; n=8), the 36-Item Short Form Health Survey (SF-36; n=4), or the Kidney Disease Quality of Life-36 questionnaire (KDQOL-36; n=5). Nine trials reported the effects of interventions on HRQoL. Three demonstrated statistically significant effects in at least one HRQoL domain, all involving interventions that also slowed CKD progression. Effects were generally greater for physical than for mental health domains and were detected more frequently using the disease-specific KDQOL-36, particularly in the symptoms and effects domains, than using the generic EQ-5D. Observed population average intervention effects generally were below conventional minimal clinically important difference thresholds at the population level, though individual-level benefits were evident. The impact of disease-modifying therapies on HRQoL in non-dialysis CKD is heterogeneous, instrument-dependent, and domain-specific. Consideration of the selected instrument, baseline HRQoL, duration of follow-up, missing data, and potential mediation through clinical events is important when interpreting HRQoL findings. Future trials should incorporate kidney-specific HRQoL instruments and report results for all domains using multiple effect measures.
Fluorescein compounds are diprotic acids prone to tautomeric transformations. Due to their valuable spectral properties, they are among the most commonly used dyes. However, nitro- and aminofluoresceins have been studied much less frequently than other fluorescein derivatives. At the same time, these compounds exhibit behavior that is different from that of other fluoresceins. Studying complex equilibria in organic solvents allows to identify molecular structures and equilibrium constant relationships that are impossible to observe in aqueous solutions. This study examines the acid-base equilibria of amino, nitro, and mixed aminonitro derivatives of fluorescein in DMSO. Basing on our previous results, we selected eight dyes, to clarify further the scheme of protolytic equilibria in this series. Among them are newly synthesized by us 3'-nitro-, 3'-amino-, 4,5-dinitro-4'-amino-, and 4,5-dinitro-5'-aminofluorescein. The pKa values were determined using the spectrophotometric method. Tautomerism is considered using the absorption spectra of molecular and anionic forms of the dyes and their esters and ethers that are used as model (auxiliary) compounds. All fractions of the tautomers, α, and the microscopic dissociation constants, pk, of the dyes are determined. For the neutral form, H2R, the colorless lactone predominates. Depending on the nature and position of the substituents, colorless tautomers were observed for the HR- and R2- anions, along with ordinary intensively colored species, which is atypical for aqueous solutions. This feature leads to very different ratios of stepwise dissociation constants: from resolution of pKa1 and pKa2 in the range from 1.5 to 4.1 to inversion, pKa1 > pKa2, for 4'-aminofluorescein. The results were compared with those obtained in water and an aqueous ethanol solution. A summary of all α and pk values of these and previously studied dyes, a total of 25 compounds, provides a quantitative description of the detailed protolytic equilibrium scheme of all amino-, nitro-, and aminonitrofluoresceins in solution.
Preterm (<37 weeks), early-term (37-38 weeks), or post-term (42 weeks) birth may elevate the risk of mental, neurodevelopmental, and cardiopulmonary disease in adulthood, potentially impacting work capacity. We examined the association between gestational age and early disability pension (DP) among 228 572 Finnish individuals born between 1 January 1987 and 30 September 1990. We identified the first DP decision from ages 16 to ∼32 years (2003-20) by using linked birth and DP records, including timing and diagnosis. Adjusted hazard ratios (HRs) with 95% confidence intervals were estimated by using Cox regression, with full-term birth (39-41 weeks) as the reference. A total of 9224 individuals (4.0%) received DPs. Adjusted for sex and birth year, the HRs for DP by gestational age groups of 23-31, 32-33, 34-36, 37-38, and 42 weeks were 5.20 (4.52-5.99), 2.47 (2.04-3.00), 1.55 (1.41-1.70), 1.22 (1.16-1.29), and 1.12 (1.01-1.25). Among preterm adults, the most common diagnoses included cerebral palsy, intellectual disability, depression, and schizophrenia. For early-term and post-term adults, depression and schizophrenia were the most frequent. Preterm, early-term, and post-term births were associated with early DPs, with slightly different diagnostic profiles. The risk was highest among those born very preterm (<32 weeks). High-quality perinatological care is crucial regarding future careers and societal costs.
Generative artificial intelligence (AI) tools are increasingly used by medical students and may influence clinical reasoning. These systems can assist with information retrieval, differential diagnosis generation, and clinical decision support. Studies demonstrate widespread student interest in AI despite limited formal training. However, concerns remain regarding overreliance, inaccurate outputs, and effects on diagnostic reasoning. This study evaluated how second-year medical students use AI during clinical reasoning and their primary concerns. We conducted a survey of second-year medical students at the USD Sanford School of Medicine. Students reported frequency of AI use for clinical reasoning tasks, including clarifying medical knowledge, generating differential diagnoses, prioritizing diagnoses, suggesting diagnostic tests, and recommending management strategies. Students also identified commonly used AI platforms and completed an open-ended question regarding concerns. Data were analyzed descriptively, with thematic review of qualitative responses. A total of 28 students completed the survey. AI use was widespread, with nearly all respondents reporting use. ChatGPT was the most commonly used platform (~90%), followed by OpenEvidence. Students most frequently used AI to suggest diagnostic tests, propose management strategies, and clarify medical knowledge, indicating early integration into clinical reasoning workflows. Common concerns included overreliance on AI, loss of independent diagnostic reasoning, and incorrect AI-generated information. AI is already integrated into clinical reasoning among medical students. Educational efforts should emphasize critical evaluation and calibrated use of AI to support, rather than replace, independent diagnostic reasoning.
Locally advanced gastroesophageal adenocarcinomas commonly relapse early with peritoneal disease, suggesting that a subset of patients harbor occult peritoneal micrometastases at diagnosis. These patients may benefit from peritoneal-directed therapy in the perioperative setting. To facilitate patient selection and evaluation of such therapies, we derived, validated, and compared prediction models for peritoneal recurrence after fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT)-based multimodality treatment using pre- and post-treatment clinicopathologic predictors. A total of 2,240 patients from the international Survival and Patterns of Care in the Era-FLOT registry were analyzed. Using Fine-Gray competing-risk regression, patients who developed peritoneal recurrence were compared with those with nonperitoneal recurrence, those who died without recurrence, and those who remained disease-free at follow-up. Pre- and post-treatment variables, obtained at staging and post-FLOT/surgery, respectively, were used to construct pre- and post-treatment predictive models of peritoneal recurrence, with internal validation using bootstrap optimism correction. Peritoneal recurrence was the most frequent (41% of all recurrences) and earliest site of disease relapse (median 9.8 v 11.4 months, P = .024) and was associated with poorer postrecurrence (median 4.4 v 9.8 months, P < .001) and overall (median 17.0 v 24.3 months, P < .001) survival compared with nonperitoneal recurrence. Six pretreatment and eight post-treatment variables independently predicted peritoneal recurrence and were incorporated into pre- and post-treatment models, respectively. At 12, 24, and 36 months postsurgery, both models demonstrated good discriminatory performance in predicting peritoneal relapse with comparable accuracy and risk calibration profiles. Decision curve analysis found that both models were superior to treat-none and treat-all approaches, highlighting their potential clinical utility. Peritoneal recurrence remains a common and important problem. We derived pre- and post-treatment prediction models for peritoneal recurrence, also available as web-based calculators. These tools can clinically prognosticate and may advance peritoneal-directed therapies for high-risk patients.