Background: Unprovoked venous thromboembolism (VTE) can be the first clinical manifestation of an undiagnosed cancer. A cancer diagnosis at an earlier stage could reduce the risk of cancer progression and contribute to improvements in cancer‐related mortality. Aim: This review analyzes whether extensive screening for undiagnosed cancer in patients with a first episode of unprovoked VTE is effective in reducing cancer-related mortality. Methods: Prospective studies in which patients with an unprovoked VTE were allocated to receive specific tests for identifying cancer were eligible for inclusion. To identify studies, PubMed, Web of Science, Cochrane Library, Scopus, EMBASE, Clinical Trials, the International Clinical Trials Registry Platform, and the Cochrane Central Register of Controlled Trials were searched. Results: Four randomized clinical trials (RCTs) and six prospective observational studies were included. Rates of cancer diagnosis at initial screening and during the follow-up in RCTs differed statistically between the two groups (odds ratio [OR]: 2.28 [95% confidence interval (CI): 1.37 ‒ 3.82; p<0.001] vs. OR: 0.35 [95% CI: 0.16 ‒ 0.77; p<0.001], respectively). The analysis of the RTCs indicated early-stage cancer at diagnosis in an extensive screening group, with results statistically significant (OR: 8.5; 95% CI: 2.57 ‒ 28.17; p<0.001). No differences were observed in cancer-related mortality (OR: 1.07; 95% CI: 0.57 ‒ 2.00; p=0.143) and overall mortality (OR: 0.80; 95% CI: 0.44 ‒ 1.45; p=0.567) at the end of follow-up. Conclusion: Extensive testing for undiagnosed cancer in people with a first episode of unprovoked VTE does not reduce cancer-related mortality. Relevance for Patients: This study supports tailored cancer screening in VTE patients, potentially reducing harm from overtesting and improving clinical outcomes.

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the key risk determinants for hepatocellular carcinoma (HCC), which is a significant public health issue worldwide. Molecular mechanisms of HBV- and HCV-related hepatocarcinogenesis are reviewed here, together with the therapeutic potential of propranolol against HCC. HBV and HCV promote HCC development through chronic inflammation, oxidative stress, and dysregulation of signaling pathways involved in proliferation, apoptosis, and immunity. Propranolol demonstrates promise in inhibiting tumor growth, angiogenesis, and metastasis in HCC by modulating adrenergic receptors and the immune response. Evidence suggests propranolol reduces inflammatory cytokines, enhances natural killer cell activity, and decreases the expression of immune checkpoint proteins such as programmed cell death protein 1 and T cell immunoglobulin and mucin domain-containing protein-3 in HCC cells. Clinical studies indicate that propranolol may lower HCC incidence and improve survival in cirrhotic patients. However, optimal dosing, long-term safety, and efficacy require further research through large randomized controlled trials. Aim: This paper aims to review the potential of propranolol as an adjuvant therapy for HBV/HCV-induced HCC by examining its antitumor, anti-angiogenic, and immunomodulatory effects. Conclusion: Propranolol represents a prospective adjuvant therapy for HBV/HCV-induced HCC that warrants continued investigation to fully elucidate its therapeutic potential against this disease. Relevance for patients: Propranolol may improve outcomes in HBV/HCV-related HCC by reducing tumor growth, angiogenesis, and immune evasion, offering a potential adjunct therapy to enhance patient survival and prognosis.

Introduction: Functional capacity is significantly impaired in patients with chronic obstructive pulmonary disease (COPD), as they tend to lead a less active lifestyle compared to healthy controls. Physical activity offers several benefits for COPD patients, including a reduction in mortality risk, fewer hospitalizations due to illness, and improved functional capacity. Objective: To review the effects of physical exercise on the functional capacity of COPD patients. Methods: The databases PubMed, Web of Science, OVID, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Health Sciences Literature, and Scientific Electronic Library Online were searched without language restrictions. Randomized controlled trials investigating the effects of physical exercise on COPD patients were included. Study selection, data extraction, and risk of bias assessment were conducted independently. RevMan software (version 5.3) was used for the meta-analysis. Results: Five studies were identified from the database search. Compared to the control group, the 6-min walking distance improved in the experimental group (mean difference [MD]: 43.12 m; 95% confidence interval [CI]: −0.70 - 86.94). Notably, Borg scale scores (MD: −0.24 points; 95% CI: −0.72 - 0.25) did not differ significantly between groups. Conclusion: Exercise may improve the functional capacity of patients with COPD. Relevance for patients: Exercise interventions may enhance walking ability in COPD patients, potentially improving daily function and quality of life.

Background: Evoked otoacoustic emissions are one of the most widely employed techniques in assessing neonatal hearing. However, several factors may influence the outcomes of this test. One such factor is gender, as previous research has shown that females tend to exhibit a greater otoacoustic response than males. Aim: This study evaluates whether gender influences the pass rate of the otoacoustic emissions test in neonatal hearing screening, using data from both the general population and twin pairs. Methods: Data from the Newborn Hearing Screening (NHS) program and infant gender were collected between 2002 and 2023 from 22,825 healthy newborns in the maternity or neonatal ward. Of these, 586 cases were from twin pregnancies. A separate analysis was conducted for twins, distinguishing between same-sex and opposite-sex pairs. Results: A highly significant difference (p<0.0001) in NHS pass rates was observed in favor of females, who demonstrated better responses to the test. In the twin subgroup, analysis of the 112 discordant-sex pairs with differing test outcomes revealed a statistically significant result (p<0.023), further supporting the positive effect of female sex on successfully passing the hearing screening test. Conclusion: Female newborns exhibit stronger otoacoustic emission responses and higher pass rates in the NHS test compared to male newborns. These gender-based variations in otoacoustic emission responses may have important implications for the NHS, as otoacoustic emissions are a commonly used screening tool in neonatal hearing assessment. Relevance for patients: Recognizing and accounting for these gender-based differences in otoacoustic emission responses may inform modifications to screening program protocols, potentially improving the identification of hearing impairment in newborns.

Background: Transcatheter aortic valve replacement (TAVR) using the J-Valve system provides a solution for patients with aortic regurgitation (AR). However, it remains unclear whether its coaxiality performance is related to procedural complications. Aim: Our goal was to improve the efficacy and accuracy of TAVR in patients with AR by adjusting J-Valve coaxiality using three-dimensional printing (3DP). Methods: This multicenter, prospective study included 612 patients with AR who underwent transapical TAVR. Of these, 228 patients were assigned to the 3DP group, in which the insertion angle and implantation depth were pre-determined. The coaxiality index was calculated using the distances from the bottom of the bioprosthesis to the base of the three cusps. Results: Compared to the non-3DP group, the 3DP group demonstrated better coaxiality performance (coaxiality index: 3.4 ± 1.7 vs. 4.0 ± 2.1; coaxiality angle: 10.5 ± 3.7° vs. 12 ± 4.2°; both p<0.001). Post-operative coaxiality index showed a strong correlation with the coaxiality angle (correlation coefficients: 0.85 in the 3DP group and 0.88 in the non-3DP group). The procedural success rate was higher in the 3DP group (100% vs. 96.4%; p=0.008). Paravalvular leakage (PVL) occurred less frequently in the 3DP group (mild PVL: 3.51% vs. 18.2%; p<0.001; moderate PVL: 0% vs. 1.04%; p<0.001). Multivariable analysis identified the coaxiality index, coaxiality angle, and horizocardia as independent predictors of PVL. Conclusion: PVL incidence after TAVR can be reduced through pre-operative simulations that adjust coaxiality using 3DP. Relevance for patients: The high incidence of PVL in transapical TAVR with the J-Valve is associated with coaxiality after bioprosthesis implantation. This study suggests that adjusting coaxiality using pre-procedural 3DP simulations may effectively reduce PVL incidence and other procedural complications during transapical TAVR. In the future, randomized clinical trials will be needed to evaluate the efficacy and accuracy of pre-procedural 3DP simulations and the coaxiality index in treating patients with pure AR undergoing transapical TAVR.

Background: Psoriasis is a chronic, non-contagious inflammatory skin disease with significant physical and quality-of-life impacts. In Brazil, its estimated incidence is 1.3%. Due to the complexity of the disease, effective management requires addressing multiple factors, with treatment adherence and persistence being critical challenges. Aim: To evaluate the correlation between psoriasis severity and treatment adherence and persistence among patients in Paraná, Brazil. Methods: This cross-sectional study included 133 psoriasis patients treated at the three primary specialized care centers in the state, between January 28, 2022, and December 9, 2022. Results: A negative correlation (−0.102, rs² = 1.04%) was observed between psoriasis severity and treatment adherence. Conversely, there was a positive correlation (0.2444, rs² = 5.97%) between psoriasis severity and treatment discontinuation history. Conclusion: Treatment interruptions were correlated with increased psoriasis severity, whereas higher adherence was associated with milder clinical manifestations. Relevance for patients: These findings underscore the critical role of consistent treatment adherence in managing psoriasis. Interruptions in treatment are linked to more severe forms of psoriasis, highlighting the detrimental effects of non-adherence. In contrast, patients who maintained high levels of adherence experienced less severe symptoms, emphasizing that consistent treatment is key to improved disease control. Strengthening patient-provider collaboration and adherence strategies can improve clinical outcomes and enhance quality of life.

Background: Ischaemic stroke, a leading cause of mortality and disability, induces oxidative stress (OS), largely driven by overactive nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Targeting this enzyme system may offer therapeutic benefits by mitigating cerebrovascular damage. Aim: This study investigated whether suppressing NADPH oxidase through VAS2870 reduces ischaemic brain injury and functional deficits in a rodent stroke model. Methods: Male Sprague Dawley rats underwent 45-min middle cerebral artery occlusion (MCAO), followed by intravenous VAS2870 or vehicle administration 30 min post-reperfusion. Infarct volume was measured at 48 h and day 11 post-MCAO using magnetic resonance imaging or Nissl staining. At day 11 post-MCAO, brains and blood samples were collected to analyse OS, inflammation and cellular changes. Behavioural tests were used to evaluate cognitive and functional outcomes. Results: VAS2870 significantly improved survival outcome following MCAO. However, no significant differences in infarct volume were observed between the control and VAS2870-treated groups. In addition, no significant alterations were detected in total antioxidant capacity, interleukin-1 beta, tissue inhibitor of metalloproteinases-1, or vascular endothelial growth factor levels. Assessment of post-MCAO functional and cognitive deficits revealed a significant worsening of neurological function following VAS2870 treatment on day 2, whereas no significant effect of NADPH oxidase inhibition was found at day 11 post-MCAO. In addition, cellular analysis showed no effect of NADPH oxidase inhibition on neuronal counts, neurogenesis, or angiogenesis in MCAO-affected brain regions. Conclusion: Although post-MCAO targeting of NADPH oxidase significantly improved acute survival, it did not significantly reduce ischaemic injury or improve functional outcome. These findings suggest that although NADPH oxidase inhibition holds promise as a therapeutic strategy, its effectiveness may be limited, particularly when administered during early phases of cerebral reperfusion. Relevance for patients: Although inhibition of NADPH oxidase alone did not improve cognition and neurovascular recovery, it may be beneficial in post-stroke recanalisation therapy.

Background: The COVID-19 crisis significantly affected school-based dental sealant programs (SBDSPs). Nationwide mitigation efforts, including school closures, led to the de-implementation of SBDSPs by default. Aims: We examined how COVID-19 crisis management planning by SBDSPs, or lack thereof, influenced: (i) de-implementation-related adaptations, (ii) re-implementation processes, (iii) workforce capacity required for re-implementation, (iv) the role of organizational resources in early re-implementation, and (v) overall school reach. Methods: We conducted an embedded multiple case study using a stratified random sample of organizations delivering SBDSPs in Oregon. Semi-structured interviews were conducted with program personnel (n = 10) from the six organizations. We performed quantitative (e.g., counts and percentages) and qualitative (i.e., directed content analysis, within, and across case study analysis) analyses to identify crisis management efforts, de-implementation adaptations, re-implementation timelines, and related challenges. Results: A universal absence of proactive crisis management during SBDSP de-implementation was observed and resulted in challenges for re-implementation. SBDSPs initiated different adaptations (e.g., mobile dental vans) to reach their targeted population. Re-implementation timeline varied (i.e., partial, intermediate, and full) and followed different rates (i.e., full rapid, full gradual, and intermediate slow). Challenges with workforce capacity, organizational resources, program policies, schools’ response, and inter-organizational communication influenced re-implementation. Re-implementation occurred more rapidly for SBDSPs that: (i) formed “crisis management teams” and quickly rebuilt their workforce and (ii) operated within well-sourced organizations that retained staff during de-implementation. However, school responses and COVID-19-related policies often created complex approval systems that limited re-implementation and overall school reach. Results suggested that COVID-19 crisis management planning largely overlooked dental public health programs (i.e., SBDSPs). Conclusion: Public health and school-related organizations must develop proactive crisis management plans that support the continuity of dental public health programs during the crises. Relevance for patients: School reach is foundational to SBDSPs’ implementation processes. Addressing barriers to re-implementation during crises is essential to ensure continued dental care access for the target population.