• Rebound incidence of anterior cruciate ligament reconstructions in the peripandemic coronavirus disease era: An audit of centers experience.
    1 month ago
    The coronavirus disease (COVID)-19 pandemic led to shutdowns of organized sporting activity. Prolonged periods of inactivity lead to deconditioning and may increase one's risk for injury. The purpose of this study was to quantify the incidence of anterior cruciate ligament (ACL) injuries requiring reconstruction during the peripandemic period.

    The electronic medical record of a single university teaching hospital was queried for current procedural terminology codes for ACL reconstructions (ACLR; 29,888) from January 2017 to December 2022. Date of injury was collected from clinic notes if it could be estimated within 2 weeks. The years 2017-2019 were used as a proxy for "pre-COVID," the year 2020 for "COVID," and the years 2021-2022 for "post-COVID."

    In total, 2178 patients had an ACL injury and underwent reconstruction from 2017 to 2022. Date of injury could be estimated for 1,617 patients (51.3% male, average age 30.9 ± 11.0 years). There was a decrease in the number of ACL surgeries observed during the COVID era, followed by a post-COVID rebound. The proportion of female patients who underwent ACLR increased from the pre-COVID to the post-COVID period (42.7% vs. 49.4%, P < .001). The proportion of patients with American Society of Anesthesiologists (ASA) score 2 increased from the COVID to the post-COVID period in relation to the proportion of patients with ASA score 1 (P = .007).

    ACLRs decreased at our institution during the COVID-19 pandemic, followed by an increase in ACLRs from 2021 to 2022. The proportion of female patients and patients with higher ASA scores increased in the post-COVID era.
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  • Family health coverage and care reorganization during the COVID-19 pandemic.
    1 month ago
    to evaluate the reorganization of Primary Health Care services for individuals with suspected and/or confirmed COVID-19 during the critical phase of the pandemic, considering family health team coverage. analytical cross-sectional study conducted with 1,474 managers of Primary Health Care services. Data were collected using Google Forms and analyzed by prevalence ratios, employing a Poisson regression model with random effects. municipalities with coverage below 25% showed a 10% higher prevalence of patient distancing, a 33% higher prevalence of attending patients with suspected/confirmed COVID-19 in a separate sector, a 60% higher prevalence of using Telehealth for monitoring mild cases, and a 7% higher prevalence of providing guidance on home isolation, compared to municipalities with coverage between 25% and 49.99. the reorganization of Primary Health Care occurred differently among Family Health Strategy, with municipalities with lower coverage more frequently implementing prevention and monitoring measures. This finding underscores the need to establish and standardize protocols to guide the reorganization of health services in public health emergencies.
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  • Functional capacity and quality of life after telerehabilitation in post-tuberculosis lung disease: a randomized controlled trial.
    1 month ago
    Despite advances in diagnosis and treatment, approximately 50% of individuals affected by tuberculosis develop post-tuberculosis lung disease (PTLD), leading to functional limitations and reduced quality of life (QoL). Pulmonary rehabilitation programs have demonstrated benefits in patients with PTLD; however, access remains limited, and telerehabilitation may offer a cost-effective solution. This study sought to compare physical capacity and QoL in patients with PTLD following an eight-week telerehabilitation program.

    This was a randomized controlled trial including 30 participants with confirmed PTLD. They were recruited and randomly assigned to an intervention group that received weekly telerehabilitation or a control group that received standard care. The interventions included aerobic training, breathing exercises, strength training, and stretching exercises. Physical capacity and QoL were assessed before and after the interventions by means of isokinetic dynamometry, the six-minute walk test, the five-repetition sit-to-stand test, spirometry, handgrip strength, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Saint George's Respiratory Questionnaire.

    After eight weeks, the intervention group showed significant improvements in all physical capacity parameters and QoL. Quadriceps strength correlated significantly with the physical functioning and mental health domains of the SF-36.

    Our findings suggest that telerehabilitation is an effective approach for enhancing physical function and QoL in patients with PTLD.
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  • SARS-CoV-2 lineage-specific disease symptoms and disease severity in a city in southeastern Brazil.
    1 month ago
    In 2020, Sao Caetano do Sul city, located in the metropolitan region of Sao Paulo State, Brazil, established a web-based platform to provide primary care to suspected COVID-19 patients, integrating clinical and demographic data and sample metadata. Here we describe lineage-specific spatiotemporal dynamics of infections, clinical symptoms, and disease severity during the first year of the epidemic, which included circulation of the poorly characterised Gamma variant of concern. From April 6, 2020, to April 30, 2021, we gathered clinical, demographic, spatial and epidemiological data from the city's platform. We selected and sequenced 879 PCR+ swab samples (8% of all reported cases), obtaining a spatially and temporally representative set of sequences. Daily lineage-specific prevalence was estimated with a moving-window approach, allowing inference of cumulative cases and symptom probability stratified by lineage using integrated data from the platform. Most infections were caused by B.1.1.28 (41.3%), followed by Gamma (31.7%), Zeta (9.6%), and B1.1.33 (9.0%). Gamma and Zeta correlated with larger prevalence of dyspnoea (respectively, 81.3% and 78.5%) and persistent fever (84.7% and 61.1%) compared with B.1.1.28 and B.1.1.33. Ageusia, anosmia, and coryza were respectively 18.9%, 20.3%, and 17.8% less commonly caused by Gamma, whereas altered mental status was 108.9% more common in Zeta. Case incidence was spatially heterogeneous and larger in poorer and younger districts. Our study reveals that Gamma was associated with more severe presentation of the disease, emphasising its role in the heightened mortality levels in Brazil.
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  • Circulating cell-free mitochondrial DNA as a candidate marker of hyperinflammation and immune activation in pre-adolescents, adolescents and young adults with COVID-19 and comorbidities.
    1 month ago
    Youth encompasses pre-adolescence (10-14 years), adolescence (15-17 years), and young adulthood (18-24 years). Adolescents in general, particularly those with comorbidities, appear more susceptible to severe COVID-19, a vulnerability also observed in newborns and young infants. The mechanisms underlying this increased risk remain unclear, highlighting the need for early disease biomarkers. Circulating cell-free mitochondrial DNA (ccf-mtDNA), a damage-associated molecular pattern (DAMP), has been linked to systemic inflammation and immune activation during viral infections. This study evaluated plasma ccf-mtDNA levels in pre-adolescents, adolescents, and young adults with and without COVID-19, all presenting respiratory symptoms and predominantly harboring comorbidities, some with coinfections by other respiratory viruses. In this prospective study of 88 participants aged 12-21 years, half tested positive and half negative for SARS-CoV-2 by Reverse-Transcribed Polymerase Chain Reaction (RT-PCR). Comorbidities were present in 75% of COVID-19-positive and 54.5% of COVID-19-negative participants. Coinfections were detected in 52.3% and 25% of tested participants, respectively. Plasma ccf-mtDNA was quantified by a quantitative Real Time PCR (qPCR) targeting the mitochondrial NADH dehydrogenase 2 (ND2) gene or MT-ND2. COVID-19-positive participants exhibited significantly higher ccf-mtDNA levels than both symptomatic COVID-19-negative individuals and healthy controls (p<0.001). Although median levels were numerically higher in severe/critical compared with mild/moderate cases (7,769 vs. 4,649 ccf-mtDNA/mL), the difference was not statistically significant, likely due to limited sample size. In conclusion, elevated ccf-mtDNA distinguishes young individuals with COVID-19 and comorbidities from non-COVID-19 symptomatic participants and healthy controls. Although not linked to disease severity in this preliminary study, ccf-mtDNA may serve as an early biomarker of SARS-CoV-2-induced hyperinflammation and immune activation, supporting further targeted clinical investigations.
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  • Contribution of artificial intelligence to the imaging diagnosis of pediatric pulmonary tuberculosis.
    1 month ago
    Pediatric tuberculosis (TB) remains a diagnostic challenge in Brazil and worldwide. The Brazilian Ministry of Health recommends a clinical scoring system (S-MoH) for children and adolescents with suspected TB. Interpretation of radiographs within this scoring system may require specialist input. AI-based systems, such as CAD4TB (Delft Imaging Systems B.V.), approved by the WHO for adults, are not yet recommended for standalone use in children under 15 years of age. A retrospective study was conducted at a pediatric institute from January 31, 2017, to January 29, 2025, including 179 patients aged 0-14 years with pulmonary TB or other diseases. CAD4TBv7.1 analyzed chest radiographs using two cutoff points established by Youden's index: 53.48 for analyses against the S-MoH score and 53.89 for analyses against microbiological confirmation. Results were compared with both microbiological confirmation and S-MoH score. Among the 179 participants, 61 (34.1%) had TB, 25 of which were microbiologically confirmed. CAD4TBv7.1 showed an area under the ROC curve (AUROC) of 0.71, with a sensitivity of 52% and a specificity of 86.3% compared with microbiological diagnosis. Against S-MoH, AUROC was 0.59, with a sensitivity of 34.43% and a specificity of 86.44%. CAD4TBv7.1 demonstrated low sensitivity and high specificity, particularly regarding its overall discriminative capacity. Thus, CAD4TBv7.1 emerges as a promising complementary screening tool for pediatric TB. Although its standalone use is not yet recommended, it may complement S-MoH in settings lacking radiologists. Investments in AI must be accompanied by consistent pediatric validation and strategies that combine technological innovation with traditional and cost-effective clinical approach.
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  • IL-6 and TGF-β1 as biomarkers of schistosomiasis-associated pulmonary hypertension in a murine model.
    1 month ago
    Schistosomiasis can lead to vascular damage resulting in pulmonary arterial hypertension (PAH). Although its pathophysiology remains unclear, cytokine imbalance is known to play a key role. This study aimed to evaluate serum mediators in association with hemodynamic, echocardiographic, and histological parameters in a murine model of Schistosoma mansoni-induced pulmonary hypertension (Sch-PH). Twenty male C57BL/6 mice were randomized into infected group and non-infected control group. Sch-PH was induced by intraperitoneal inoculation of S. mansoni eggs (240 eggs/g body weight), followed by intravenous administration (175 eggs/g). After 21 days, systolic pulmonary artery pressure was measured by right ventricular catheterization (RHC), and cardiac function was assessed by transthoracic echocardiography. Animals were then euthanized for collection of lungs and heart for histopathology, and blood samples were obtained for quantification of interleukin (IL)-6, IL-10, and tumor necrosis factor (TGF)-β1 by ELISA. The Sch-PH group had significantly lower tricuspid annular plane systolic excursion and pulmonary artery acceleration time/pulmonary ejection time ratio (P<0.05), and increased pulmonary artery peak flow, tricuspid and pulmonary regurgitation, IL-6, and TGF-β1 levels (P<0.05). IL-10 was undetectable. Lung tissue showed inflammatory infiltrates, alveolar and perivascular granulomas, and S. mansoni eggs. Pulmonary arteries exhibited intimal thickening, medial hypertrophy, and fibrosis. Cardiac tissue presented inflammatory foci, fibroblast proliferation, and thickening of connective septa. IL-6 and TGF-β1 were elevated in Sch-PH and correlated with echocardiographic and hemodynamic alterations. These findings suggest a role for these mediators in Sch-PH pathogenesis and highlight the potential for targeting inflammatory pathways in this condition.
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  • Spatial and epidemiological mapping of tuberculosis on an Amazon island: effect of the COVID-19 pandemic.
    1 month ago
    With the emergence and rise of the COVID-19 pandemic in 2020, many health services were interrupted and reallocated due to system overload. Tuberculosis (TB) care was one of the affected services during this period, especially in regions with greater social vulnerabilities. Thus, this study aimed to describe the distribution of TB cases before and during the COVID-19 pandemic on an island in the Brazilian Amazon. This quantitative descriptive retrospective study evaluated the distribution of 797 new confirmed and notified cases of TB in residents of the sixteen municipalities in the region of Marajó Island (Pará, Brazil), from 2017 to 2022. The data were obtained from the Development and Administration Company of the Metropolitan Area of Belém and Google Earth, using the ArcGIS and TerraView software for georeferencing notification points in each municipality of the archipelago. The Kernel density estimator and scan statistics were used to analyze the point patterns. Almost all municipalities in the archipelago showed variations during the study years. The scan statistics showed a greater number of cases in the pre-pandemic years of 2017-2019. These data indicated that the factors related to the increase and decrease in the number of cases must be analyzed, as the decrease may be related to the underreporting of patients due to the lack of access to health resources in more isolated areas.
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  • Mechanistic insights into the noncovalent inhibition of SARS-CoV-2 PLpro: a multiscale computational study.
    1 month ago
    The papain-like protease of SARS-CoV-2 (PLpro2) is integral to viral polyprotein cleavage and the modulation of host immune responses, positioning it as a critical target for antiviral drug development. Here, we elucidate the molecular mechanisms governing the noncovalent inhibition of PLpro2 through a comprehensive computational approach, including molecular docking, extensive molecular dynamics (MD) simulations, binding free energy calculations (MM/GBSA and SIE), principal component and free energy landscape (PCA/FEL) analyses, and protein-ligand interaction fingerprinting (ProLIF). We assessed a structurally diverse set of noncovalent inhibitors for their capacity to induce conformational rearrangements and stabilize key structural motifs of PLpro2, with particular emphasis on the BL2 loop. Notably, XR3 and A19 exhibited superior experimental and predicted binding affinities, which can be attributed to favorable contacts with essential residues Tyr268 and Gln269, the attenuation of loop dynamics, and the stabilization of energetically favorable conformational states. By contrast, less potent inhibitors were associated with increased conformational heterogeneity, fragmented free energy landscapes, and diminished interactions with critical loop residues. Therefore, our integrative analysis delineates the structural and energetic determinants underpinning noncovalent PLpro2 inhibition, underscoring the central roles of loop immobilization and π-stacking interactions in the rational design of next-generation PLpro2 inhibitors.
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  • Subclinical pulmonary abnormalities on chest CT in patients with eosinophilic chronic rhinosinusitis.
    1 month ago
    Chronic rhinosinusitis (CRS) often coexists with lower respiratory tract diseases, and such cases tend to be more refractory. However, few studies have specifically investigated chest computed tomography (CT) findings in patients with CRS. This study analyzed chest CT findings in patients with CRS and investigated their associations with CRS phenotypes and clinical characteristics.

    We retrospectively analyzed 278 patients with CRS who underwent preoperative chest CT prior to endoscopic sinus surgery. Patients were stratified based on the presence or absence of abnormal chest CT findings. Clinical parameters related to upper and lower airway inflammation, including CRS phenotypes, were compared between the groups. The prognosis for ECRS was evaluated using the systemic steroid dose as a longitudinal outcome variable in a linear mixed-effects model.

    Among the 278 patients, 174 were diagnosed with eosinophilic CRS (ECRS) and 104 with non-eosinophilic CRS (NECRS). Ground-glass attenuation (GGA) and bronchial wall thickening (BWT) were observed in 35 and 27 patients (12.6 %, 9.7 %), respectively. The frequencies of GGA and BWT were significantly higher in the ECRS group than in the NECRS group. Among patients with ECRS, those with GGA had significantly higher tissue eosinophil counts and Lund-Mackay CT scores, as well as significantly lower olfactory function. Steroid dose reduction was significantly slower in the GGA group.

    The presence of GGA on chest CT in patients with CRS is associated with the CRS phenotype and greater disease severity, suggesting that chest imaging findings could serve as potential indicators of systemic disease burden in CRS.
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