Proactive physical activity programs in lung cancer surgical patients at short and mid-term: A systematic review and meta-analysis.

OBJECTIVE: To assess the effects of proactive physical activity (PA) programs on lung cancer patients undergoing lung resection at short and mid-term. METHODS: We conducted a literature search through MEDLINE, Science Direct, Web of Science, and the Cochrane Library (last search October 2023). The GRADE System and the Cochrane tool were applied to quality assessment. The included studies focused on the application of proactive PA interventions among lung cancer surgical patients compared to usual or standard care. We performed a meta-analysis addressing hospital stay, cancer-related symptoms, quality of life, and exercise capacity at short and mid-term. RESULTS: We selected 9 studies, which included 798 lung cancer patients. Proactive interventions were applied in combination with respiratory training and exercise in most of the studies. The treatment status was heterogeneous. Significant results in favour of proactive interventions were observed for hospital stay, cancer-related symptoms, quality of life, and short and mid-term exercise capacity. CONCLUSIONS: Proactive PA interventions showed positive effects for reducing length stay, enhancing exercise capacity at short and mid-term, alleviating cancer-related symptoms, and improving the quality of life for lung cancer surgical patients. PRACTICE IMPLICATIONS: Proactive interventions can optimize the timing and setting of PA results around lung surgical treatment.

Effectiveness of non-instrumental early mobilization to reduce the incidence of deep vein thrombosis in hospitalized patients: A systematic review and meta-analysis.

BACKGROUND: Deep vein thrombosis (DVT) poses a significant health risk, particularly in hospitalized patients with multiple risk factors (cigarette smoking, hypertension, diabetes and obesity). Despite advances in treatment, DVT remains a prevalent complication of hospitalization. OBJECTIVE: To assess the effectiveness of non-instrumental mobilization in hospitalized patients at high risk of DVT, exploring the challenges and variations in intervention protocols. DESIGN: Systematic review and meta-analysis. SETTING(S): Not applicable. PARTICIPANTS: Hospitalized patients at risk of deep vein thrombosis. METHODS: A systematic search of three databases was conducted from interception to September 2023 for randomized controlled trials. This study was registered in PROSPERO (CRD42023460485). This study was conducted according to PRISMA 2020 statement. Two authors independently screened the studies and extracted the data. The quality of the studies was evaluated using the Downs and Black checklist and GRADE system. The amount of evidence certainty was assessed using the Cochrane Risk of Bias Assessment tool. Meta-analysis was performed addressing the incidence of deep vein thrombosis during hospitalization. RESULTS: 7 studies were eligible for inclusion which included a total of 1774 participants. Interventions ranged from active and passive ankle exercises to walking. Meta-analysis demonstrated a significant overall effect in favor of non-instrumental early mobilization compared to usual care (RR = 0.55; 95 % CI = 0.41, 0.73; p < 0.0001). Subgroup analysis comparing type of mobilization revealed significant effects for global (RR = 0.54; 95 % CI = 0.38, 0.78; p = 0.001) and remote mobilization (RR = 0.25; 95 % CI = 0.07, 0.86; p = 0.03). CONCLUSIONS: Non-instrumental early mobilization is beneficial in reducing the incidence of deep vein thrombosis in hospitalized patients. REGISTRATION: PROSPERO, registration number: CRD42023460485.

Percutaneous Electrical Stimulation Improves Chronic Knee Pain and Function. A Systematic Review and Meta-analyses.

OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the effectiveness of the percutaneous electrical stimulation in the modulation of pain and its implication in the function of patients with a painful knee condition. METHODS: A search was conducted from database inception to September 2023 across PubMed, Web of Science and Scopus databases. Randomized controlled trials were included. Two reviewers performed independent data extraction and methodologic quality assessment of the studies. Study quality was assessed using the PEDro scale and the risk of bias was evaluated with the Cochrane Assessment tool. RESULTS: Eight studies were included. A significant statistical effect was found (P<0.001) for reducing pain and improving function after treatment. Additionally, a significant statistical effect was presented for reducing pain (P=0.009) and improving function (P<0.001) after follow-up. The risk of bias was low. CONCLUSION: This review showed a positive effect of applying the percutaneous electrical stimulation reducing pain and improving function in adults with a painful knee.

Association between cognitive reserve proxies and frailty phenotype: data from UK Biobank.

A potential protective role of cognitive reserve proxies against frailty has been suggested in older adults. We explored the cross-sectional association between cognitive reserve indicators and frailty phenotype. Data were obtained from the UK Biobank. We included 31,975 dementia-free participants aged ≥ 60 years (50.7% females, 2.2% frail) who completed a web-based cognitive assessment (fluid intelligence, working memory, visuospatial attention and processing speed, and executive functioning). Frailty was defined according to the Fried's phenotype (unintentional weight loss, exhaustion, low physical activity, slowness, and weakness). Participants meeting three or more criteria were classified as frail. Cognitive performance was compared between nonfrail and frail groups, and regression models were employed to analyze the associations between cognitive reserve proxies (education, skill level of occupation, social support, and multiple deprivation index (MDI)) and the likelihood of frailty. Frail and nonfrail groups significantly differed on cognitive function, with frail individuals demonstrating poorer performance on all cognitive functions (all p < .05) except fluid intelligence. Regression analysis showed that, after adjusting for age and sex, a lower educational level (odds ratio (OR) .797, 95% confidence interval (CI) .673-.944, p = .009), having maintained occupations with low cognitive requirements (OR .790, 95% CI .668-.936, p = .006), having less social support (OR .755, 95% CI .631-.903, p = .002), and living in a region with a high rate of multiple deprivation (OR 1.025, 95% CI 1.019-1.031, p < .001), significantly increased the probability of experiencing frailty. Our findings support the relationship between declined cognitive functions and frailty emphasizing the importance of implementing public health measures to enhance cognitive reserve.

Predictive Factors for Onset of Moderate-to-Severe Disability Following Hospital Discharge Due to Rib Fractures.

BACKGROUND: According to previous studies, a prolonged hospital stay, along with the patient's clinical features, can lead to the onset of disability. OBJECTIVES: This study aimed to identify predictive factors of moderate-to-severe disability following hospital discharge in rib fracture patients. METHODS: We conducted a retrospective study with hospitalized adult patients with rib fractures who received conservative treatment. Patients' clinical profiles and characteristics were collected from their clinical histories and healthcare professional records. RESULTS: Overall, patients exhibited a 44% rate of moderate-to-severe disability after a six-day hospital stay. The incidence of patients with a prolonged hospital stay who showed disabilities was associated with male sex (HR 0.73, p < 0.001), presence of first rib fracture (HR 1.78, p = 0.047), presence of flail chest (HR 1.29, p = 0.046), severity of lung injury (HR 1.65, p < 0.001), and functional status (HR 1.37, p < 0.001). CONCLUSIONS: Moderate-to-severe disability in patients with rib fractures may depend on factors such as sex, functionality, severity of lung injury, and presence of first rib fracture and flail chest during a prolonged hospital stay.

Short-Term Active Safety Surveillance of the Spikevax and Nuvaxovid Priming Doses in Australia.

Australia commenced administration of the Spikevax (Moderna mRNA-1273) COVID-19 vaccine in August 2021 and Nuvaxovid (Novavax NVX-CoV2373) in January 2022. This study describes the short-term safety profile of priming doses of the Spikevax and Nuvaxovid vaccines given between September 2021 and September 2023. Online surveys were sent via AusVaxSafety, Australia's active vaccine safety surveillance system, three and eight days after vaccination. A total of 131,775 day 3 surveys were sent, with a response rate of 38.5% (N = 50,721). A total of 43,875 day 8 surveys matched with day 3 survey responses were sent, with a response rate of 71.5% (N = 31,355). Half (50.7%) of respondents reported any adverse event following immunisation (AEFI) in the 0-3 days after vaccination and 24.6% reported any AEFI 4-7 days after vaccination. Fatigue, local pain, headache, and myalgia were the most frequently reported symptoms for both vaccines in both periods. After adjusting for respondent characteristics, vaccination clinic type, jurisdiction, and medical conditions, the odds for reporting AEFI increased with age from 16-19 years to highest odds at 30-39 years, after which it declined. Females had greater odd of reporting AEFI than males across most age groups, vaccine types, and doses. Respondents with a history of anaphylaxis had greater odds of reporting any AEFI (adjusted OR range: 1.50-2.86). A total of 3.1% of respondents reported seeking medical review 0-3 days after vaccination. This study affirms the short-term safety of Spikevax and Nuvaxovid COVID-19 vaccine priming doses in a large sample in Australia.

Nirsevimab and Acute Bronchiolitis Episodes in Pediatric Emergency Departments.

BACKGROUND AND OBJECTIVES: In the 2023-2024 respiratory syncytial virus (RSV) season, Spain became one of the first countries to introduce universal RSV prophylaxis, during which all infants born at this time were eligible to receive nirsevimab. Locally, most Spanish regions also immunized infants younger than age 6 months at the start of the season (extended catch-up). The aim of this study was to assess how RSV prophylaxis affected the number of infants presenting to pediatric emergency departments with acute respiratory infections. METHODS: A retrospective study was conducted in 15 Spanish pediatric emergency departments from 9 different regions between the 2018 and 2024 epidemic seasons (November-January). We compared the seasons occurring in 2018-2023 and the 2023-2024 season regarding the number of episodes of lower respiratory tract infection and acute bronchiolitis, acute bronchiolitis-related hospital admissions, and PICU admissions. RESULTS: A comparison with the average rates for the previous epidemic seasons revealed a 57.7% decrease in episodes of lower respiratory tract infection in 2023-2024 (95% CI, 56.5-58.8; P < .001; range among hospitals, 4.8-82.8), a 59.2% decrease in episodes of acute bronchiolitis (95% CI, 57.9-60.4; P < .001; range, 6.9-84.1), a 63.1% reduction in acute bronchiolitis-related hospital admissions (95% CI, 60.9-65.2; P < .001; range, 31.4-86.8), and a 63.1% reduction in PICU admissions (95% CI, 58.1-67.9; P < .001; range, 18.2-81.8). Hospitals in regions applying extended catch-up showed better results. CONCLUSIONS: Nirsevimab can protect a broad infant population against RSV infection with high effectiveness. Approaches including extended catch-up are the most effective, although cost- effectiveness must be considered.

Subclinical atherosclerosis burden in carotid and femoral territories in HIV subjects: relationships with HIV and non-HIV related factors.

BACKGROUND: Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. METHODS: We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0-47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 - 8.90) and age (OR 1.13, 95%CI 1.10 - 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques.

Cancer Predisposition Syndromes in Children: Who, How, and When Should Genetic Studies Be Considered?

Early detection of cancer predisposition syndromes (CPS) is crucial to determine optimal treatments and follow-up, and to provide appropriate genetic counseling. This study outlines an approach in a pediatric oncology unit, where 50 randomly selected patients underwent clinical assessment, leading to 44 eligible for genetic testing. We identified 2 pathogenic or likely pathogenic variants in genes associated with CPS and 6 variants of uncertain significance (VUS) potentially associated with cancer development. We emphasize the importance of a thorough and accurate collection of family history and physical examination data and the full coordination between pediatric oncologists and geneticists.

Nitrofurantoin as an Add-On to Conventional Prophylaxis for the Treatment of Urinary Tract Infections in Kidney Recipients: A Prospective Cohort Study.

Urinary tract infections (UTIs) constitute one of the main complications in kidney recipients, increasing both morbidity and mortality. Due to the resurgence of antimicrobial resistance, new prophylactic approaches are being investigated. Nitrofurantoin is an antibiotic from the nitrofuran group that is effective against several Gram-negative and Gram-positive organisms; hence, there has been a resurgence in its prescription for treating MDR pathogens. Objectives: This study aims to assess the effectiveness of nitrofurantoin as an add-on to conventional therapy (amikacin + ceftriaxone or cefotaxime) for the treatment of urinary tract infections in kidney recipients. Methods: In a prospective cohort study, we included patients who received a kidney in a tertiary-care hospital. According to the intensive care specialist, group 1 patients were treated with the conventional prophylactic treatment plus nitrofurantoin as an add-on. Group 2 patients were treated only with the conventional prophylactic treatment. They were followed-up for 3 months, and the incidence of urinary tract infections was reported. Results: The UTI incidence for group 1 at 3 months was 20.6%, and for group 2, it was 20.0%; no statistical difference between treatments was observed (p = 0.9). The most commonly isolated pathogens were E. coli (28.5) and K. pneumonie (28.5%). The factor most associated with developing a UTI was female gender (aHR: 7.0; 95% IC 2.3-20.9, p < 0.001). Conclusions: In our cohort study, nitrofurantoin as an add-on in conventional therapy did not prove to be effective in preventing UTI development; therefore, other treatment options should be considered as a part of prophylactic treatment.

The mechanics of the retina: Müller glia role on retinal extracellular matrix and modelling.

The retina is a highly heterogeneous tissue, both cell-wise but also regarding its extracellular matrix (ECM). The stiffness of the ECM is pivotal in retinal development and maturation and has also been associated with the onset and/or progression of numerous retinal pathologies, such as glaucoma, proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), epiretinal membrane (ERM) formation or uveitis. Nonetheless, much remains unknown about the biomechanical milieu of the retina, and specifically the role that Müller glia play as principal mechanosensors and major producers of ECM constituents. So far, new approaches need to be developed to further the knowledge in the field of retinal mechanobiology for ECM-target applications to arise. In this review, we focus on the involvement of Müller glia in shaping and altering the retinal ECM under both physiological and pathological conditions and look into various biomaterial options to more accurately replicate the impact of matrix stiffness in vitro.

Effect of exercise training in patients with chronotropic incompetence and heart failure with preserved ejection fraction: Training-HR study protocol.

BACKGROUND: Chronotropic incompetence (ChI) is linked with diminished exercise capacity in heart failure with preserved ejection fraction (HFpEF). Although exercise training has shown potential for improving functional capacity, the exercise modality associated with greater functional and chronotropic response (ChR) is not well-known. Additionally, how the ChR from different exercise modalities mediates functional improvement remains to be determined. This study aimed to evaluate the effect of three different exercise programs over current guideline recommendations on peak oxygen consumption (peakVO2) in patients with ChI HFpEF phenotype. METHODS AND RESULTS: In this randomized clinical trial, 80 stable symptomatic patients with HFpEF and ChI (NYHA class II-III/IV) are randomized (1:1:1:1) to receive: a) a 12-week program of supervised aerobic training (AT), b) AT and low to moderate-intensity strength training, c)AT and moderate to high-intensity strength training, or d) guideline-based physical activity and exercise recommendations. The primary endpoint is 12-week changes in peakVO2. The secondary endpoints are 12-week changes in ChR, 12-week changes in quality of life, and how ChR changes mediate changes in peakVO2. A mixed-effects model for repeated measures will be used to compare endpoint changes. The mean age is 75.1 ± 7.2 years, and most patients are women (57.5 %) in New York Heart Association functional class II (68.7 %). The mean peakVO2, percent of predicted peakVO2, and ChR are 11.8 ± 2.6 mL/kg/min, 67.2 ± 14.7 %, and 0.39 ± 0.16, respectively. No significant baseline clinical differences between arms are found. CONCLUSIONS: Training-HR will evaluate the effects of different exercise-based therapies on peakVO2, ChR, and quality of life in patients with ChI HFpEF phenotype. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT05649787).

Incriminating leishmaniases vectors in Colombia: An overview and roadmap for future research.

A major challenge in defining the vector status of phlebotomine sand flies is selecting the appropriate criteria. Vectors can be graded by importance, with successful transmission as the highest grade. Potential vectors are often identified based on high frequency in transmission foci, anthropophily, and more recently by identification of DNA in field samples. However, a species' ability to transmit a pathogen depends not only on its intrinsic biology of sand fly-Leishmania interactions but also on ecological parameters, which are rarely evaluated. This study aimed to analyze the literature data describing characteristics of Colombian sand flies related to their role as vectors of Leishmaniinae parasites. Based on information contained in scientific publications using combinations of five criteria, sand fly species were graded into five levels, and 26 species were considered as potential or proven leishmaniasis vectors in Colombia. Levels one to four refer to potential or suspected status, while level five denotes proven vectors. Studying vectors in a regional context is crucial because species' behaviors vary with environmental and ecological conditions, meaning a species may be a key vector in one area but not in another. A better understanding of vector-parasite interactions will aid in developing innovative control strategies and formulating significant epidemiological perspectives.

The GPI sidechain of Toxoplasma gondii inhibits parasite pathogenesis.

Glycosylphosphatidylinositols (GPIs) are highly conserved anchors for eukaryotic cell surface proteins. The apicomplexan parasite, Toxoplasma gondii, is a widespread intracellular parasite of warm-blooded animals whose plasma membrane is covered with GPI-anchored proteins, and free GPIs called GIPLs. While the glycan portion is conserved, species differ in sidechains added to the triple mannose core. The functional significance of the Glcα1,4GalNAcß1- sidechain reported in Toxoplasma gondii has remained largely unknown without understanding its biosynthesis. Here we identify and disrupt two glycosyltransferase genes and confirm their respective roles by serology and mass spectrometry. Parasites lacking the sidechain on account of deletion of the first glycosyltransferase, PIGJ, exhibit increased virulence during primary and secondary infections, suggesting it is an important pathogenesis factor. Cytokine responses, antibody recognition of GPI-anchored SAGs, and complement binding to PIGJ mutants are intact. By contrast, the scavenger receptor CD36 shows enhanced binding to PIGJ mutants, potentially explaining a subtle tropism for macrophages detected early in infection. Galectin-3, which binds GIPLs, exhibits an enhancement of binding to PIGJ mutants, and the protection of galectin-3 knockout mice from lethality suggests that Δpigj parasite virulence in this context is sidechain dependent. Parasite numbers are not affected by Δpigj early in the infection in wild-type mice, suggesting a breakdown of tolerance. However, increased tissue cysts in the brains of mice infected with Δpigj parasites indicate an advantage over wild-type strains. Thus, the GPI sidechain of T. gondii plays a crucial and diverse role in regulating disease outcomes in the infected host.IMPORTANCEThe functional significance of sidechain modifications to the glycosylphosphatidylinositol (GPI) anchor in parasites has yet to be determined because the glycosyltransferases responsible for these modifications have not been identified. Here we present identification and characterization of both Toxoplasmsa gondii GPI sidechain-modifying glycosyltransferases. Removal of the glycosyltransferase that adds the first GalNAc to the sidechain results in parasites without a sidechain on the GPI, and increased host susceptibility to infection. Loss of the second glycosyltransferase results in a sidechain with GalNAc alone, and no glucose added, and has negligible effect on disease outcomes. This indicates GPI sidechains are fundamental to host-parasite interactions.

A retrospective study describing the acetabular consequences of Legg- Calve-Perthes disease.

PURPOSE: Legg Calve Perthes disease (LCPD) is a paediatric hip disorder caused by ischemia of the femoral epiphysis, causing femoral head deformity when untreated. This study aims to determine if previously validated pelvic obliquity radiographic parameters, used for assessing acetabular retroversion in developmental dysplasia of the hip, are applicable to patients with LCPD and its prognostic value. METHOD: A retrospective study of patients with Legg Calve Perthes disease was carried out, analysing 4 pelvic parameters: Ilioischial Angle, Obturator Index, Sharp's Angle and Acetabular Depth-Width Ratio (ADR). The differences between healthy and affected hips were studied, and subsequently, it was assessed whether these parameters have prognostic value in the disease outcome. RESULTS: Statistically significant differences have been obtained in the ilioischial angle, obturator index and ADR, between the affected and healthy hip. However, only the Acetabular Depth-Width Ratio showed predictive value for the disease outcome. CONCLUSION: Although this study revealed differences in pelvic parameters between healthy and diseased hips, with only the ADR showing statistical significance in the disease's evolution and prognosis, further studies with larger sample sizes are necessary.

Applying causal inference and Bayesian statistics to understanding vaccine safety signals using a simulation study.

Community perception of vaccine safety influences vaccine uptake. Our objective was to assess current vaccine safety monitoring by examining factors that may influence the availability of post-vaccination survey data, and thereby the specificity and sensitivity of existing signal detection methods. We used causal directed acyclic graphs (DAGs) and a Bayesian posterior predictive analysis (PPA) signal detection method to understand biological and behavioural factors which may influence signal detection. The DAGs informed the data simulated for scenarios in which these factors were varied. The influence of biological factors such as severity of adverse reactions and behavioural factors such as healthcare-seeking behaviour upon survey participation was found to drive signal detection. Where there was a low prevalence of moderate to severe reactions, false signals were detected when there was a strong influence of reaction severity on both survey participation and seeking medical attention. These findings provide implications for future vaccine safety monitoring.

Molecular based confirmation of puma meat sausages implicated in trichinellosis outbreaks in Argentina.

Trichinellosis is a zoonotic disease caused by Trichinella, with the main source of infection being the consumption of pork and pork-derived products. However, it can also be acquired from eating the meat from wild animals targeted for sport hunting. The objectives of this study were: 1) to develop and implement a molecular method for the identification of Sus scrofa (pig and wild boar) and Puma concolor (Puma) meat in sausages eaten raw, which were linked to trichinellosis outbreaks occurring in Córdoba, Buenos Aires and La Pampa provinces, Argentina, in 2010, 2021, and 2022, respectively; and 2) to identify the Trichinella species present in the food. Specific primers were designed for PCR amplification and nucleotide sequencing of a region of the mitochondrial cytochrome b gene from both host species. Samples from the mentioned outbreaks were analysed, and the molecular identification of Trichinella spp. larvae was also performed. Results of the species identification system revealed that sausages from Córdoba and Buenos Aires had a mixed composition of pork and puma meat, while those from La Pampa contained puma meat only. Trichinella spiralis was implicated in all three outbreaks. The species identification system developed and implemented in this study revealed two host species of Trichinella related to human cases, and alerts about the risk of zoonotic transmission to humans through infected puma meat.