Hospital de Clínicas de Porto Alegre is a large teaching hospital located in Porto Alegre, Brazil. Affiliated with Federal University of Rio Grande do Sul, it was inaugurated in 1970, gradually becoming a reference for the state of Rio Grande do Sul and southern Brazil. It currently has 125,000 square meters of floor space, distributed on 13 floors, and 741 beds. There is an emergency room with capacity for 50 patients, which contains a vascular unit, an operating theatre with 15 rooms, an outpatient surgery center, and an Interventional Neuro/Cardiovascular center with 3 rooms. It takes care of in about 60 specialties, since the simplest procedures until most complex, with priority, for patients of the SUS.
PURPOSE:To report interim results from the ongoing, open-label, phase 3 APHENITY Extension Study (NCT05166161), evaluating long-term treatment with sepiapterin in patients with phenylketonuria. METHODS:Participants received an age-based dose of oral sepiapterin daily; those with mean blood phenylalanine (Phe) levels <360 μmol/L (<5.95 mg/dL) after 2 weeks underwent a 26-week dietary Phe tolerance assessment, wherein dietary Phe intake was adjusted and blood Phe levels monitored. Other participants continued treatment with optional diet liberalization. Primary endpoints included change from baseline to week 26 in dietary Phe intake and treatment-emergent adverse events (TEAEs). RESULTS:As of September 2, 2024, 169 participants received sepiapterin (median [minimum, maximum] age: 14.0 [0.2, 55.0] years, median exposure: 72.9 weeks); 102 participants underwent dietary Phe tolerance assessments. Mean (SD) dietary Phe intake increased from 27.6 (18.0) mg/kg/day at baseline to 62.5 (41.5) mg/kg/day at week 26 (least-squares mean change [SE]: 36.4 [2.8] mg/kg/day from baseline) (P < .0001 from post hoc analysis). The incidence of treatment-related TEAEs was 29.0%; 3 participants (1.8%) discontinued treatment owing to treatment-related TEAEs. There were no treatment-related serious TEAEs or deaths. CONCLUSION:Interim results support the long-term safety of sepiapterin and demonstrate the potential for diet liberalization in adults and children with phenylketonuria. CLINICALTRIALS: GOV IDENTIFIER:NCT05166161 (https://www. CLINICALTRIALS:gov/study/NCT05166161; date of registration, December 8, 2021).
BACKGROUND AND OBJECTIVE:Multiparametric magnetic resonance imaging (mpMRI) is the reference modality for detecting clinically significant prostate cancer (csPC). Biparametric MRI (bpMRI), which omits contrast, has emerged as a streamlined alternative. Recent studies have demonstrated the noninferiority of bpMRI to mpMRI for csPC detection in biopsy-naïve men. We performed an updated systematic review and meta-analysis of head-to-head studies comparing bpMRI and mpMRI for csPC detection, and conducted a noninferiority analysis. METHODS:Literature databases were searched up to September 2025 for head-to-head studies. Eligible studies enrolled men with suspected PC and used biopsy or prostatectomy as the reference standard. The primary outcome was diagnostic accuracy for csPC at per-patient and per-lesion levels; detection of any PC was a secondary outcome. Noninferiority was assessed using a margin of -5% applied to paired absolute differences (bpMRI - mpMRI) in sensitivity and specificity via a random-effects model. KEY FINDINGS AND LIMITATIONS:A total of 40 studies (9403 patients) were analyzed. For csPC, the paired absolute differences were -2.3% (95% confidence interval [CI] -4.1% to -0.5%) for sensitivity, and +1.8% (95% CI -0.4% to +4.0%) for specificity, which confirm noninferiority at the patient level. At the lesion level, bpMRI was noninferior for specificity but not sensitivity, probably because of fewer studies and greater heterogeneity. CONCLUSIONS AND CLINICAL IMPLICATIONS:bpMRI is noninferior to mpMRI for csPC detection at the patient level. At the per-lesion level, noninferiority was demonstrated for specificity but not for sensitivity. Broader implementation should occur in settings with assured image quality, and further work is needed to define minimum quality-control standards required for adoption.
Importance:Geriatric syndromes are common in hospitalized older adults and complicate acute care; however, their overall prevalence and cumulative burden remain poorly understood, especially in resource-limited settings. Objectives:To measure the prevalence of geriatric syndromes upon hospital admission and examine the independent association between the number of geriatric syndromes and 90-day mortality. Design, Setting, and Participants:This cohort study used data from the Creating a Hospital Assessment Network in Geriatrics (CHANGE) study, a multicenter, prospective cohort of 43 hospitals, including 38 in Brazil, 1 in Angola, 1 in Chile, 2 in Colombia, and 1 in Portugal. Consecutive patients aged 65 years or older admitted under geriatric teams between June 1, 2022, and December 31, 2023, were enrolled within 48 hours; patients with terminally illness were excluded. Data were analyzed from February 1 to November 23, 2025. Exposure:A standardized comprehensive geriatric assessment captured 14 geriatric syndromes: loneliness, dementia, depressive symptoms, sensory impairment, disability, immobility, incontinence, falls, frailty, malnutrition, pressure ulcers, polypharmacy, potentially inappropriate medications, and delirium. The exposure of interest was the within-patient count of syndromes. Main Outcomes and Measures:The primary outcome was 90-day all-cause mortality, ascertained by masked telephone follow-up with verification in medical records or public registries. Prespecified mixed-effects Cox proportional hazards regression were performed. Results:The study included 2556 participants (mean [SD] age, 79 [9] years, 1437 female [56.2%]). The median number of geriatric syndromes was 5 (IQR, 3-8). The highest prevalence rates for syndromes were 70.8% (95% CI, 69.1%-72.6%) for disability, 61.7% (95% CI, 59.8%-63.6%) for polypharmacy, 58.2% (95% CI, 56.3%-60.1%) for frailty, and 54.7% (95% CI, 52.8%-56.7%) for sensory impairment. Across categories, the mortality rate rose from 8.4% (95% CI, 6.2%-11.4%) for 0 to 2 syndromes to 12.7% (95% CI, 10.1%-15.7%) for 3 to 4 syndromes, 25.4% (95% CI, 22.2%-29.1%) for 5 to 6 syndromes, 30.4% (95% CI, 26.7%-34.5%) for 7 to 8 syndromes, 39.5% (95% CI, 34.4%-44.8%) for 9 to 10 syndromes, and 47.0% (95% CI, 36.4%-57.9%) for 11 or more syndromes. After adjusting for confounders, each additional geriatric syndrome was associated with an increased risk of mortality (hazard ratio, 1.22 [95% CI, 1.15-1.30), which became increasingly pronounced in older age groups. Conclusions and Relevance:This cohort study found that hospitalized older adults had a median of 5 geriatric syndromes, which were independently and incrementally associated with 90-day mortality. Multidomain assessments should be integrated into standard hospital care to identify and address vulnerabilities that commonly affect older adults with acute illness.
BACKGROUND:There is a lack of contemporary studies addressing the prevalence rates and antifungal susceptibility of bloodstream infections (BSI) caused by rare yeasts (RY) from the Saccharomycotina subphylum. OBJECTIVES:This 16-year multicentre study (2007-2023) aimed to assess the prevalence and antifungal susceptibility of rare yeasts isolated from BSIs in 28 Brazilian tertiary care hospitals. METHODS:Yeasts from the Saccharomycotina subphylum, excluding common Candida species and Basidiomycota, were selected from BSI episodes. Species were identified using proteomics and molecular methods. Antifungal susceptibility testing was performed by EUCAST broth microdilution. RESULTS:Among 2655 BSI episodes, 100 (3.76%) involved rare yeasts. Prevalence showed a slight, non-significant increase from 3.16% (2007-2015) to 4.17% (2016-2023; p = 0.183). A total of 11 genera and 20 species were identified, with Clavispora lusitaniae (20%), Wickerhamomyces anomalus (16%), Candida haemulonii (14%) and Candida duobushaemulonii (12%) being the most frequent species. Eight species, including Pichia kluyveri and Kodamaea ohmeri, appeared only in the latter period. Most rare yeasts showed low MICs to amphotericin B and anidulafungin, except for Clavispora lusitaniae, Candida haemulonii and Candida duobushaemulonii, which were less susceptible to amphotericin B. Wickerhamomyces anomalus and Candida duobushaemulonii also showed reduced susceptibility to fluconazole. CONCLUSIONS:This study provides valuable insights into the prevalence rates, species distribution and antifungal susceptibility of rare yeasts causing BSIs in tertiary care hospitals. Our findings highlight the need for continuous surveillance, incorporation of new diagnostic and tailored therapeutic strategies to mitigate morbidity and mortality due to invasive infections caused by emerging fungal pathogens.
Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, a burden further exacerbated by HIV co-infection and the increasing prevalence of drug-resistant strains. Although a wide range of laboratory diagnostic methods are currently available, their applicability, implementation, and clinical impact vary substantially across healthcare settings with different levels of complexity and resources. This review provides a comprehensive overview of the main laboratory diagnostic methods for active and latent TB, emphasizing their clinical applicability, implementation challenges, and role within integrated diagnostic strategies. Conventional approaches, such as smear microscopy and culture, are discussed alongside modern diagnostic technologies, including automated nucleic acid amplification tests (NAATs), loop-mediated isothermal amplification (LAMP), line probe assays (LPAs), next-generation sequencing (NGS), and lateral flow assays, highlighting their strengths and limitations in distinct epidemiological and operational contexts. Unlike existing WHO guidelines and prior reviews that predominantly focus on test performance and recommendation status, this review adopts an implementation-oriented perspective, critically examining diagnostic methods in light of real-world constraints, regional disparities, and evidence gaps. Particular attention is given to limitations related to laboratory infrastructure, biosafety, workforce capacity, and sustainability, as well as to under-addressed areas such as latent TB, metagenomic approaches, and the investigation of co-pathogens. By integrating WHO guidance with contextual and operational considerations, this review aims to support rational test selection and the development of flexible, integrated diagnostic workflows tailored to local health system capacity, patient populations, and clinical scenarios, thereby strengthening the effectiveness and equity of TB diagnostic strategies.
