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Competing Interests: MFPP has received honoraria for speaking engagements and consulting from Eurofarma, Ache, Libbs, Teva, Abbvie, Pfizer, Lundbeck, Lilly, and Viatris; participates on data safety monitoring boards or advisory boards for Abbvie, Pfizer, Lundbeck, and Teva; has patents planned, issued, or pending for US 17/196,611 and BR202017023353; and has roles in Abraces and the Brazilian Headache Society

Should we care about the biomechanics of the foot or the full locomotor system? Anatomic changes are the main concerns of an orthopedic surgeon; however, the main objectives of treatment for lesser toe dysfunctions are to relieve the patient's symptoms to preserve or improve function. It is imperative to understand that the foot is part a three-dimensional biokinetic system that needs to function combined so that loads are harmoniously distributed throughout the body without harmful effects, especially for one of the most frequent voluntary neuromotor tasks in humans: walking., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Objective: Male sex has inconsistently been associated with the development of postoperative pulmonary complications (PPCs). These studies were different in size, design, population and preoperative risk. We reanalysed the database of 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery study' (LAS VEGAS) to evaluate differences between females and males with respect to PPCs., Design, Setting and Patients: Post hoc unmatched and matched analysis of LAS VEGAS, an international observational study in patients undergoing intraoperative ventilation under general anaesthesia for surgery in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs in the first 5 postoperative days. Individual PPCs, hospital length of stay and mortality were secondary endpoints. Propensity score matching was used to create a similar cohort regarding type of surgery and epidemiological factors with a known association with development of PPCs., Main Results: The unmatched cohort consisted of 9697 patients; 5342 (55.1%) females and 4355 (44.9%) males. The matched cohort consisted of 6154 patients; 3077 (50.0%) females and 3077 (50.0%) males. The incidence in PPCs was neither significant between females and males in the unmatched cohort (10.0 vs 10.7%; odds ratio (OR) 0.93 [0.81-1.06]; P = 0.255), nor in the matched cohort (10.5 vs 10.0%; OR 1.05 [0.89-1.25]; P = 0.556). New invasive ventilation occurred less often in females in the unmatched cohort. Hospital length of stay and mortality were similar between females and males in both cohorts., Conclusions: In this conveniently-sized worldwide cohort of patients receiving intraoperative ventilation under general anaesthesia for surgery, the PPC incidence was not significantly different between sexes., Registration: LAS VEGAS was registered at clinicaltrial.gov (study identifier NCT01601223)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: The features and outcomes of sepsis-associated acute kidney injury (SA-AKI) may be affected by chronic kidney disease (CKD). Accordingly, we aimed to compare SA-AKI in patients with or without CKD., Methods: Retrospective cohort study in 12 intensive care units (ICU). We studied the prevalence, patient characteristics, timing, trajectory, treatment and outcomes of SA-AKI with and without CKD., Results: Of 84 240 admissions, 7255 (8.6%) involved patients with CKD. SA-AKI was more common in patients with CKD (21% vs 14%; p < .001). CKD patients were older (70 vs. 60 years; p < .001), had a higher median Charlson co-morbidity index (5 vs. 3; p < .001) and acute physiology and chronic health evaluation (APACHE) III score (78 vs. 60; p < .001) and were more likely to receive renal replacement therapy (RRT) (25% vs. 17%; p < .001). They had less complete return to baseline function at ICU discharge (48% vs. 60%; p < .001), higher major adverse kidney events at day 30 (MAKE-30) (38% vs. 27%; p < .001), and higher hospital and 90-day mortality (21% vs. 13%; p < .001, and 27% vs. 16%; p < .001, respectively). After adjustment for patient characteristics and severity of illness, however, CKD was not an independent risk factor for increased 90-day mortality (OR 0.88; 95% CI 0.76-1.02; p = .08) or MAKE-30 (OR 0.98; 95% CI 0.80-1.09; p = .4)., Conclusion: SA-AKI is more common in patients with CKD. Such patients are older, more co-morbid, have higher disease severity, receive different ICU therapies and have different trajectories of renal recovery and greater unadjusted mortality. However, after adjustment day-90 mortality and MAKE-30 risk were not increased by CKD., (© 2024 The Author(s). Nephrology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Nephrology.)

Objectives: To evaluate the role of salvage local treatment in managing recurrent PCa following FT, focusing on oncological and functional outcomes., Methods: A systematic review and meta-analysis were performed following the PRISMA framework. A comprehensive literature search using the PubMed/MEDLINE and EMBASE databases was performed until July 2023. Eligible studies included patients with clinically localised PCa initially treated with FT, who experienced relapse during surveillance and subsequently underwent salvage radical prostatectomy (sRP), salvage external beam radiation therapy (sEBRT) or salvage focal therapy (sFT). The primary endpoint was the biochemical recurrence rate post-salvage treatment. The secondary endpoints were functional outcomes, including urinary incontinence and erectile dysfunction rates., Results: In 26 retrospective studies including 990 patients, the overall pooled biochemical recurrence rate postsalvage treatment was 26%. The subgroup analysis revealed a biochemical recurrence rate of 20%, 22%, and 42% after sRP, sEBRT, and sFT, respectively. The overall pooled rate of urinary incontinence was 20%. Salvage FT had the lowest prevalence of urinary incontinence, followed by sRP and sEBRT. The overall pooled rate of erectile dysfunction was 43%. Salvage RP had the highest prevalence of erectile dysfunction, followed by sFT and sEBRT. Substantial heterogeneity was observed among the studies, primarily due to different sample sizes. Meta-regression analysis revealed no to low contributions of salvage treatment modalities, extent of ablation, age, prostatic specific antigen level before salvage treatment, proportion of patients with Gleason score ≥7 at recurrence, and time between the primary and salvage therapies to heterogeneity., Conclusion: Salvage local treatment for recurrent PCa after FT is feasible, and it provides acceptable oncological and functional outcomes. Among all treatment modalities, sRP and sEBRT appeared to have the lowest biochemical recurrence rates, whereas sFT was associated with improved functional outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To analyze the self-reported perception of obstetric medical teams regarding the practice of delivering bad news in public and private hospitals., Methods: Cross-sectional study considering physicians delivering obstetric care at the Municipal Hospital Vila Santa Catarina, Municipal Hospital Dr. Moysés Deutsch, and Albert Einstein Israelite Hospital, in São Paulo, Brazil. The applied questionnaire reflected the steps of the SPIKES protocol for delivering difficult news, with the questions adapted to obstetric and fetal medicine practice context., Results: Specialists self-reported higher levels of knowledge, better emotional management, and superior strategy planning and summarization skills than residents. Participants with more than five years of experience reported higher knowledge levels, better emotional management, and superior strategy development skills. When comparing professionals from private and public hospitals, no significant differences emerged in self-reported communication aspects., Conclusions: Experience duration significantly influences professionals' impressions in their ability to provide information, manage emotions, and plan post-diagnosis. Specialists and those with more years of experience self-report enhanced readiness in executing communication steps effectively., Practice Implications: Our findings underscore the importance of tailored training and experience in navigating sensitive medical conversations in the field of Obstetrics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To assess the effect of antisense therapy to block kallikrein-kinin pathway in COVID-19 patients., Material and Methods: Randomized, placebo-controlled, double blind, controlled trial enrolling hospitalized COVID-19 patients that required supplementary oxygen to sustain peripheral oxygen saturation. Key exclusion criteria included use of mechanical ventilation or vasopressors, and patients with more than 10 days since symptom onset or more than 48 h of oxygen use. Patients were randomized to either one subcutaneous dose of ISIS721744, an antisense that blocks prekallikrein, or placebo. The primary outcome was the number of days alive and free of oxygen support up to 15 days (DAFOR15). Secondary endpoints included organ failure score, need and duration of mechanical ventilation up to 15 days, and all-cause mortality at 30 days. Exploratory endpoints included physiological parameters, biomarkers, and quality of life., Results: From October 10, 2020, to December 09, 2020, 111 patients were randomized at thirteen sites in Brazil (56 to treatment and 55 to control group). Average age was 57.5 years, and most patients were male (68.5%). There were no significant differences in DAFOR15 between groups (5.9 ± 5.2 days for the intervention arm and 7.7 ± 5.1 for the control group; mean difference - 0.65, 95% confidence intervals from -2.95 to 1.36, p = 0.520)., Conclusion: Antisense therapy designed to block the kallikrein-kinin pathway did not demonstrate clinical benefits in increasing days-alive without respiratory support at 15 days in patients with COVID-19 during the first wave in 2020., Gov Identifier: NCT04549922., Competing Interests: Declaration of competing interest None. This study was funded by Ionis Pharmaceutical, US, through a grant provided to HCor. The sponsor reviewed and agreed with the protocol, but had no role in any other aspect of the trial execution. MJ and GB were Ionis employees at the time this study was designed and provided relevant feedback on design of the trial and reviewed the final manuscript for intellectually relevant content. FGZ has received consulting fees from Baxter, unrelated to the scope of this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Prostate magnetic resonance imaging (MRI) stands as the cornerstone in diagnosing prostate cancer (PCa), offering superior detection capabilities while minimizing unnecessary biopsies. Despite its critical role, global disparities in MRI diagnostic performance persist, stemming from variations in image quality and radiologist expertise. This manuscript reviews the challenges and strategies for enhancing image quality in prostate MRI, spanning patient preparation, MRI unit optimization, and radiology team engagement. Quality assurance (QA) and quality control (QC) processes are pivotal, emphasizing standardized protocols, meticulous patient evaluation, MRI unit workflow, and radiology team performance. Additionally, artificial intelligence (AI) advancements offer promising avenues for improving image quality and reducing acquisition times. The Prostate-Imaging Quality (PI-QUAL) scoring system emerges as a valuable tool for assessing MRI image quality. A comprehensive approach addressing technical, procedural, and interpretative aspects is essential to ensure consistent and reliable prostate MRI outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We describe a case of a 33-year-old male presented with fever, myalgia, nausea, and asthenia for six days. The patient lived in a rural area. Initial hypotheses included arbovirus infection, viral hepatitis, and Lyme disease. Reverse transcriptase polymerase chain reaction (RT-PCR) tests for Dengue, Zika, and Chikungunya resulted negative. We were able to recover complete S, L, and M segments of virus in the Orthohantavirus genome., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Telecardiology, the remote diagnosis and treatment of cardiac conditions, is experiencing a significant increase in developing nations. This article explores the driving forces behind this trend and its implications. Limited access to healthcare facilities, especially in rural, isolated, and underdeveloped regions, has propelled the adoption of telecardiology as a cost-effective solution to bridge the gap in cardiac care provision. Technological advancements, such as portable diagnostic devices and improvements in telecommunication infrastructure, have facilitated the expansion of telecardiology services. Moreover, the COVID-19 pandemic has accelerated the acceptance and deployment of telehealth solutions worldwide. Nevertheless, challenges persist, including regulatory hurdles, data privacy concerns, and disparities in digital literacy. Despite these obstacles, the rise of telecardiology in developing countries presents a promising opportunity to enhance access to cardiac care and improve health outcomes among underserved populations., Competing Interests: Declaration of competing interest The authors state that they have no known financial conflicts of interest or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Pneumonia remains a significant global health concern, particularly among those requiring admission to the intensive care unit (ICU). Despite the availability of international guidelines, there remains heterogeneity in clinical management. The D-PRISM study aimed to develop a global overview of how pneumonias (i.e., community-acquired (CAP), hospital-acquired (HAP), and Ventilator-associated pneumonia (VAP)) are diagnosed and treated in the ICU and compare differences in clinical practice worldwide., Methods: The D-PRISM study was a multinational, survey-based investigation to assess the diagnosis and treatment of pneumonia in the ICU. A self-administered online questionnaire was distributed to intensive care clinicians from 72 countries between September to November 2022. The questionnaire included sections on professional profiles, current clinical practice in diagnosing and managing CAP, HAP, and VAP, and the availability of microbiology diagnostic tests. Multivariable analysis using multiple regression analysis was used to assess the relationship between reported antibiotic duration and organisational variables collected in the study., Results: A total of 1296 valid responses were collected from ICU clinicians, spread between low-and-middle income (LMIC) and high-income countries (HIC), with LMIC respondents comprising 51% of respondents. There is heterogeneity across the diagnostic processes, including clinical assessment, where 30% (389) did not consider radiological evidence essential to diagnose pneumonia, variable collection of microbiological samples, and use and practice in bronchoscopy. Microbiological diagnostics were least frequently available in low and lower-middle-income nation settings. Modal intended antibiotic treatment duration was 5-7 days for all types of pneumonia. Shorter durations of antibiotic treatment were associated with antimicrobial stewardship (AMS) programs, high national income status, and formal intensive care training., Conclusions: This study highlighted variations in clinical practice and diagnostic capabilities for pneumonia, particularly issues with access to diagnostic tools in LMICs were identified. There is a clear need for improved adherence to existing guidelines and standardized approaches to diagnosing and treating pneumonia in the ICU. Trial registration As a survey of current practice, this study was not registered. It was reviewed and endorsed by the European Society of Intensive Care Medicine., Competing Interests: Declarations. Ethics approval and consent to participate: This multinational cross-sectional study conducted an online self-administered questionnaire to intensive care clinicians. As an anonymized survey of clinical practice without individual patient data, the requirement for research ethics approval and formal written consent was waived by the UK Health Research Authority. Consent for publication: Not applicable. Competing interests: Nathan D. Nielsen sits on the scientific advisory boards of Adrenomed AG and Inotrem. Jordi Rello received honoraria from the Speakers' Bureau and consultancies from ROCHE, Pfizer & MSD. Andrew Conway Morris reports speaking fees from Biomerieux, Thermo-Fisher, Fischer and Paykel and Boston Scientific, he sits on the scientific advisory board of Cambridge Infection Diagnostics. Pedro Póvoa reports honoraria for lectures and advisory boards from Merck Sharp & Dohme, Gilead, Mundipharma and Pfizer, and advisory boards from Merck Sharp & Dohme, Sanofi, Gilead and Biocodex. All other authors report no competing interests., (© 2024. The Author(s).)

Background: This systematic review aims to identify predictors of intradialytic hypotension (IDH) in critically ill patients undergoing kidney replacement therapy (KRT) for acute kidney injury (AKI)., Methods: A comprehensive search of PubMed was conducted from 2002 to April 2024. Studies included critically ill adults undergoing KRT for AKI, excluding pediatric patients, non-critically ill individuals, those with chronic kidney disease, and those not undergoing KRT. The primary outcome was identifying predictive tools for hypotensive episodes during KRT sessions., Results: The review analyzed data from 8 studies involving 2873 patients. Various machine learning models were assessed for their predictive accuracy. The Extreme Gradient Boosting Machine (XGB) model was the top performer with an area under the receiver operating characteristic curve (AUROC) of 0.828 (95% CI 0.796-0.861), closely followed by the deep neural network (DNN) with an AUROC of 0.822 (95% CI 0.789-0.856). All machine learning models outperformed other predictors. The SOCRATE score, which includes cardiovascular SOFA score, index capillary refill, and lactate level, had an AUROC of 0.79 (95% CI 0.69-0.89, p < 0.0001). Peripheral perfusion index (PPI) and heart rate variability (HRV) showed AUROCs of 0.721 (95% CI 0.547-0.857) and 0.761 (95% CI 0.59-0.887), respectively. Pulmonary vascular permeability index (PVPI) and mechanical ventilation also demonstrated significant diagnostic performance. A PVPI ≥ 1.6 at the onset of intermittent hemodialysis (IHD) sessions predicted IDH associated with preload dependence with a sensitivity of 91% (95% CI 59-100%) and specificity of 53% (95% CI 42-63%)., Conclusion: This systematic review shows how combining predictive models with clinical indicators can forecast IDH in critically ill AKI patients undergoing KRT, with validation in diverse settings needed to improve accuracy and patient care strategies., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

The MICA gene encodes a glycoprotein upregulated upon cellular stress, particularly in oxidative stress, intracellular infections, and tumorigenesis. This stress-signaling molecule interacts with the activating receptor NKG2D from Natural Killer (NK) and some T lymphocytes, stimulating their cytotoxic activity. MICA is encoded within the human Major Histocompatibility Complex next to the HLA-B locus and is highly polymorphic. MICA might be absent from chromosome 6 due to a large deletion of approximately 100 Kb between HLA-B and MICB. Therefore, some individuals may not produce any isoform of MICA. The distribution of this phenotype may vary among different populations. We evaluated the distribution of the MICA*del and other MICA null alleles in different biogeographic regions and the Linkage Disequilibrium (LD) pattern between this allele and HLA-B. We detected at least two different patterns of deletion, one with full deletion of MICA and surrounding sequences and one partial MICA deletion. The presence of different patterns of deletion suggests independent deletion events. We confirm that the previously described MICA*del allele is mainly associated with B*48 and MICB*009N in Asia and America, but other haplotypes also occur. While most samples with complete or partial MICA deletion are heterozygous and present one functional copy of both MICA and MICB genes, we detected two samples with no functional MICA and one with no functional MIC genes. Therefore, other mechanisms might be in place to compensate for the absence of MIC molecules., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

This study explores the challenges associated with nanoparticle-based drug delivery to the tumor parenchyma, focusing on the widely utilized enhanced permeability and retention effect (EPR). While EPR has been a key strategy, its inconsistent clinical success lacks clear mechanistic understanding and is hindered by limited tools for studying relevant phenomena. This work introduces an approach that employs multiparametric dynamic contrast-enhanced ultrasound (CEUS) with a nanoscale contrast agent for noninvasive, real-time examination of tumor microenvironment characteristics. We demonstrate that CEUS imaging can: (1) evaluate tumor microenvironment features, (2) be used to help predict the distribution of doxorubicin-loaded liposomes in the tumor parenchyma, and (3) be used to predict nanotherapeutic efficacy. CEUS using nanobubbles (NBs) was carried out in two tumor types of high (LS174T) and low (U87) vascular permeability. LS174T tumors consistently showed significantly different time intensity curve (TIC) parameters, including area under the rising curve (AUC R , 2.7×) and time to peak intensity (TTP, 1.9×) compared to U87 tumors. Crucially, a recently developed decorrelation time (DT) parameter specific to NB CEUS dynamics successfully predicted the distribution of doxorubicin-loaded liposomes within the tumor parenchyma ( r = 0.86 ± 0.13). AUC R , TTP, and DT were used to correlate imaging findings to nanotherapeutic response with 100% accuracy in SKOV-3 tumors. These findings suggest that NB-CEUS parameters can effectively discern tumor vascular permeability, serving as a biomarker for identifying tumor characteristics and predicting the responsiveness to nanoparticle-based therapies. The observed differences between LS174T and U87 tumors and the accurate prediction of nanotherapeutic efficacy in SKOV-3 tumors indicate the potential utility of this method in predicting treatment efficacy and evaluating EPR in diseases characterized by pathologically permeable vasculature. Ultimately, this research contributes valuable insights into refining drug delivery strategies and assessing the broader applicability of EPR-based approaches.

Objectives: To investigate the causes of failure in unicompartmental knee arthroplasty (UKA), types of implants used in the revision, evaluate the need to use tibial stems, metal block augmentations and bone grafts during conversion to total knee arthroplasty (TKA) METHODS: In a 10-year retrospective analysis, focusing on cases of UKA failure, our study aimed to categorize early and late failures, determine the primary failure modes, and assess the utilization of bone augmentations and grafts during conversion to TKA. We evaluated patient data, diagnoses, procedure intervals, and follow-up periods to provide a comprehensive understanding of the conversion process., Results: During the past decade, 301 UKA procedures were performed, with 36 knees (11.96%) requiring conversion to TKA. Patient ages averaged 64.3 years, with varied diagnoses, including osteoarthritis and avascular necrosis. The most common failure mode was component loosening or sinking (52.78%), followed by progression of arthritis (25%). Of the 31 cases with mobile-bearing UKA, 9 (29.03%) developed instability and displacement of the polyethylene. Of the 36 cases converted from UKA to TKA, in 31 (86.11%) a revision tibial component with a tibial stem was used. Metal block augmentation was performed in 19 knees (52,78%). All revised UKAs were converted to cemented TKA, with a focus on addressing tibial side issues, which constituted 72.22% of the revisions., Conclusion: This study highlights the challenges associated with UKA failure, particularly early failures linked to displaced bearings. Converting from UKA to TKA presents technical hurdles, including rod alignment and utilization. Management of proximal tibial defects with metal block augmentation proves to be a viable approach. The use of modular metal augmentation simplifies the reconstruction process. Although the study has limitations, it contributes valuable information about the complexities of knee arthroplasty conversion., Level of Evidence: Therapeutic study, level IV (case series)., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Vaccine hesitancy is a relevant driver of backslides in immunization rates globally. Myths and misinformation are key contributors to vaccine hesitancy. We aimed to investigate associations between beliefs in popular vaccine myths and vaccine incompleteness., Methods: In this survey, participants were asked questions on current vaccination status; barriers and motivations for vaccination; and beliefs regarding popular myths: the measles vaccine causes autism in children; acquiring the disease is preferable to facing vaccine side effects; and natural immunity developed from getting the disease is better than the immunity elicited by vaccination. We assessed the effect of failing to disagree with the myths on current vaccination status., Results: Of 4305 participants, 933 (22 %) were partially vaccinated and 61 (1 %) were fully unvaccinated; 403 (10 %) failed to disagree with the autism myth; 411 (10 %) failed to disagree with the side effects myth; and 904 (22 %) failed to disagree with the natural immunity myth. Failing to disagree with the myths was significantly associated with vaccine incompleteness., Conclusion: Vaccine-related myths are associated with both partial and total vaccine incompleteness in Brazil., Practice Implications: Strategies to improve adherence to vaccination recommendations should include interventions to limit the spread or elucidate vaccine-related myths and misconceptions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)