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Atrial fibrillation (AF) and stroke are prevalent conditions worldwide, and the AF burden is expected to concentrate in low- and middle-income countries like Brazil. The National Institute for Health and Care Excellence–funded Global Health Research Group on Atrial Fibrillation Management (GHRG-AF) had a Brazilian arm that addressed AF epidemiology and care in Brazil. GHRG-AF analyzed data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a long-term cohort of 15,105 middle-aged adults in Brazil, focused on cardiovascular disease and diabetes. Additionally, the GHRG-AF used data from the Brazilian Study of Stroke Mortality and Morbidity (EMMA) study to understand AF impact on this cohort of 1863 stroke survivors, all admitted to a community hospital. The GHRG-AF also surveyed healthcare practices and the pathways of individuals who live with AF, interviewing health professionals and patients treated in different healthcare units in São Paulo. Despite these multiple approaches, those data were restricted to individuals living in large urban centers. Approximately 70% of the Brazilian territory comprises sparsely populated cities (

Background. Healthcare-associated infections (HAIs) are preventable complications that overwhelm the healthcare system. The implementation of multifaceted control intervention actions in the intensive care setting modifies clinical outcomes, but its effectiveness has not been specifically investigated for high-risk patients, such as kidney transplant recipients (KTRs). Methods. This observational retrospective natural experiment evaluated the effectiveness of multifaceted control interventions (bundles) in reducing HAIs in a KTR intensive care unit. We also measured the bundle adherence rate during 16 mo in the after era. Results. We included 1257 KTRs, 684 before and 573 in the postintervention period. After the bundle implementation, the incidence density of device-associated HAIs decreased from 8.5 to 3.9 per 1000 patient-days (relative risk [RR] = 0.46; 95% confidence interval [CI], 0.25-0.85; P = 0.01), primarily because of the reduction in central line-associated bloodstream infection from 8.0 to 3.4 events per 1000 catheter-days (RR = 0.43; 95% CI, 0.22-0.83; P = 0.012). Reductions in catheter-associated urinary tract infection (2.5 versus 0.6 per 1000 catheter-days; RR = 0.22; 95% CI, 0.03-1.92; P = 0.17) and ventilator-associated pneumonia (3.4 versus 1.0 per 1000 ventilator-days; RR = 0.29; 95% CI, 0.03-2.63; P = 0.27) were not significant. Central venous (P = 0.53) and urinary catheter (P = 0.47) insertion adherence were stable during 16 mo, whereas central venous (P

Introduction: The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs. Methods: A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers. We sought to characterize the frequency and location of oligoprogression and determine the overall survival (OS) after radiotherapy in this population. Results: A total of 159 patients were included in the study. At first progression, 62 (39.0%) were classified as undergoing oligoprogression. Multivariate analysis confirmed the presence of brain metastases was associated with an increased likelihood of oligoprogression (OR = 2.44, p = 0.04) with most (63.2%) of these patients experiencing progression intracranially. The presence of liver metastases was associated with a decreased likelihood of oligoprogression (OR = 0.17, p < 0.01). For patients with oligoprogression, those who received radiotherapy had a longer median progression-free survival-2 (PFS2) (17 versus 11.5 mo, HR = 0.51, p = 0.02) and a longer median OS (23 versus 13 mo, HR = 0.40, p < 0.001) compared with those who did not receive radiotherapy. No difference in PFS2 or OS outcomes was observed between patients who received radiotherapy versus those who did not for systemic progression. Conclusions: In patients with oligoprogressive metastatic NSCLC after treatment with first-line ICIs, radiotherapy significantly improves OS and PFS2 outcomes. Patients with baseline brain metastases are more likely to experience oligoprogression. Further prospective studies in directed, less heterogeneous populations of patients with metastatic NSCLC will be fundamental to optimize management.

Background. Dialysis vintage is associated with worse outcomes after kidney transplantation. The reasons behind this observation include immunological and nonimmunological risk factors. To mitigate the influence of immunological factors, we examined the association between time on dialysis and clinical outcomes in a cohort of HLA-identical kidney transplant recipients. Methods. This retrospective study included 13 321 kidney transplant recipients between 1999 and 2016, of whom 589 were HLA identical followed for at least 5 y. Patient and graft survivals were compared according to dialysis time (12 mo) using the log-rank test and Cox regression analysis. We compared surgical complications, cytomegalovirus infection, acute rejection, disease recurrence, and the trajectories of estimated glomerular filtration rate (eGFR). Results. Median time on dialysis was 15 mo; 9.2% of patients received preemptive transplants, and 55.3% of patients were on dialysis for >12 mo. After a median follow-up time of 154 mo, there were no differences in unadjusted and adjusted patient and graft survivals (1, 5, 10, and 15 y) between the 2 groups. There were no differences in the incidence of surgical complications (6.2% versus 3.1%), acute rejection (6.1% versus 7.7%), cytomegalovirus infection (7.6% versus 4.0%), and disease recurrence (4.2% versus 4.0%), respectively. There were no differences in mean eGFR during 5 y or in the proportion of patients with an eGFR

Background. There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. Methods. This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Results. Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. Conclusions. In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.

Background. The urinary microbiome, also known as the urobiome, was traditionally considered sterile. However, emerging evidence suggests its presence in the urinary tract. Urobiome dysbiosis has been associated with various urologic conditions, making it a topic of interest also in kidney transplantation. This systematic review examines the evidence of urobiome changes in kidney transplant recipients (KTRs). Methods. Systematic literature searches in the PubMed and SCOPUS databases. Results. Of the 770 articles identified, 8 met the inclusion criteria. The urobiome showed reduced diversity in KTRs compared with healthy controls and patients on dialysis. Proteobacteria enrichment was associated with graft stability or spontaneous tolerance in KTRs without immunological events. Kidney interstitial fibrosis and tubular atrophy were associated with changes in resident urinary microbes and increased pathogenic bacteria. Additionally, KTRs with chronic allograft dysfunction had a higher prevalence of Corynebacterium. Conclusions. The review highlights the importance of studying the urobiome in KTRs and its potential impact on transplant outcomes. The field remains largely unexplored, and further research is needed to establish consistent study designs and objectives. Future studies could lead to biomarker discovery, personalized therapies, and improved outcomes and graft survival in KTRs.

Purpose: To evaluate mydriatic handheld retinal imaging performance assessed by point-of-care (POC) artificial intelligence (AI) as compared with retinal image graders at a centralized reading center (RC) in identifying diabetic retinopathy (DR) and diabetic macular edema (DME). Design: Prospective, comparative study. Subjects: Five thousand five hundred eighty-five eyes from 2793 adult patients with diabetes. Methods: Point-of-care AI assessment of disc and macular handheld retinal images was compared with RC evaluation of validated 5-field handheld retinal images (disc, macula, superior, inferior, and temporal) in identifying referable DR (refDR; defined as moderate nonproliferative DR [NPDR], or worse, or any level of DME) and vision-threatening DR (vtDR; defined as severe NPDR or worse, or any level of center-involving DME [ciDME]). Reading center evaluation of the 5-field images followed the international DR/DME classification. Sensitivity (SN) and specificity (SP) for ungradable images, refDR, and vtDR were calculated. Main Outcome Measures: Agreement for DR and DME; SN and SP for refDR, vtDR, and ungradable images. Results: Diabetic retinopathy severity by RC evaluation: no DR, 67.3%; mild NPDR, 9.7%; moderate NPDR, 8.6%; severe NPDR, 4.8%; proliferative DR, 3.8%; and ungradable, 5.8%. Diabetic macular edema severity by RC evaluation was as follows: no DME (80.4%), non–ciDME (7.7%), ciDME (4.4%), and ungradable (7.5%). Referable DR was present in 25.3% and vtDR was present in 17.5% of eyes. Images were ungradable for DR or DME in 7.5% by RC evaluation and 15.4% by AI. There was substantial agreement between AI and RC for refDR (κ = 0.66) and moderate agreement for vtDR (κ = 0.54). The SN/SP of AI grading compared with RC evaluation was 0.86/0.86 for refDR and 0.92/0.80 for vtDR. Conclusions: This study demonstrates that POC AI following a defined handheld retinal imaging protocol at the time of imaging has SN and SP for refDR that meets the current United States Food and Drug Administration thresholds of 85% and 82.5%, but not for vtDR. Integrating AI at the POC could substantially reduce centralized RC burden and speed information delivery to the patient, allowing more prompt eye care referral. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), represents a substantial healthcare challenge. Provoked and unprovoked DVT cases carry distinct risks and treatment considerations. Recognizing the limitations of this classification, molecular markers may enhance diagnostic precision and guide anticoagulation therapy duration relying on patient history and risk factors. This preliminary, open-label, prospective cohort study was conducted including 15 patients (10 provoked DVT and 5 unprovoked DVT) and a control group of healthy plasmatic subjects. Plasma levels of 9 biomarkers were measured at diagnosis (baseline, day 0, and D0) and after 30 days (day 30-D30). Patient demographics, clinical data, and biomarker concentrations were analyzed. Serum concentrations of D-dimer, von Willebrand factor, C-reactive protein, and Anti-Xa were elevated in DVT groups at D0 compared to controls. No significant differences were observed between the provoked and unprovoked groups on the day of diagnosis and 30 days later. Over 30 days, the provoked group exhibited significant biomarker changes related to temporal assessment. No significant differences were noted in the biomarker profile between provoked and unprovoked DVT groups. This study is indicative of the concept of individualized thrombosis assessment and subsequent treatment for VTE. Larger cohorts are warranted to validate these findings and further define the most appropriate use of the molecular markers.

Introduction: Stage III NSCLC is a heterogeneous disease, representing approximately one-third of newly diagnosed lung cancers. Brazil lacks detailed information regarding stage distribution, treatment patterns, survival, and prognostic variables in locally advanced NSCLC. Methods: RELANCE/LACOG 0118 is an observational, retrospective cohort study assessing sociodemographic and clinical data of patients diagnosed with having stage III NSCLC from January 2015 to June 2019, regardless of treatment received. The study was conducted across 13 cancer centers in Brazil. Disease status and survival data were collected up to June 2021. Descriptive statistics, survival analyses, and a multivariable Cox regression model were performed. p values less than 0.05 were considered significant. Results: We recruited 403 patients with stage III NSCLC. Most were male (64.0%), White (31.5%), and smokers or former smokers (86.1%). Most patients had public health insurance (67.5%), had stage IIIA disease (63.2%), and were treated with concurrent chemoradiation (53.1%). The median follow-up time was 33.83 months (95% confidence interval [CI]: 30.43–37.50). Median overall survival (OS) was 27.97 months (95% CI: 21.57–31.73), and median progression-free survival was 11.23 months (95% CI: 10.70–12.77). The type of treatment was independently associated with OS and progression-free survival, whereas the types of health insurance and histology were independent predictors of OS only. Conclusions: Brazilian patients with stage III NSCLC with public health insurance are diagnosed later and have poorer OS. Nevertheless, patients with access to adequate treatment have outcomes similar to those reported in the pivotal trials. Health policy should be improved to make lung cancer diagnosis faster and guarantee prompt access to adequate treatment in Brazil.

Background: Anterior cruciate ligament (ACL) injury in children is an increasingly common occurrence. Historically, nonsurgical treatment has been the main treatment option; however, the indication for surgical reconstruction is increasing, as the histological characteristics of the immature skeleton are better known. Indications: The extra-articular surgical technique for ACL reconstruction is a good option for Tanner I patients, aged up to 8 years, with knee instability and recurrent pain. Its advantage in skeletally immature patients is due to the fact that it avoids the bone growth plates. Technique Description: After skin incision and subcutaneous dissection, we isolated the iliotibial band and released the proximal portion of the band. We proceeded with the tubularization of the graft, suturing its edges, and with the aid of radioscopy we marked the top of the lateral femoral condyle. Thus, we transported the graft, in an over-the-top position, to the intercondylar portion of the femur. Femoral fixation is performed by placing the graft close to the lateral femoral condyle. For fixation on the tibia, a second incision is made, preserving the physis, and the graft is fixed to the tibia using an absorbable Swivelock anchor. Results: Six months after the surgery, when his physical rehabilitation was completed, the patient was asymptomatic and able to perform his daily activities, and also returned to sports. Clinical evaluation showed a knee with almost the same functional parameters as the uninjured one. Furthermore, radiographic studies showed no bone abnormalities and magnetic resonance image showed a newly reconstructed ligament with good positioning. Discussion/Conclusion: According to the literature, surgical treatment seems to be better than conservative treatment in skeletally immature patients. However, there is a continuous discussion about the most appropriate surgical technique. The decision is relative to many specific characteristics for these patients: age, bone age, graft choice, sports modality, and surgeon expertise. In this case, we decide to do an ACL extra-articular reconstruction technique with the iliotibial band over the top in the femoral condyle and fixed in the anterior cortical bone of the tibia. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: There are several techniques for the combined reconstruction of the anterior cruciate ligament (ACL) and the anterolateral ligament (ALL), but none have shown superiority. This study aims to present a surgical technique that theoretically reduces some of the risks reported in these procedures. Indications: The main indications for the ALL reconstruction include chronic ACL injuries, revision ACL reconstruction, acute ACL injuries in patients with high-grade pivot-shift (grades 2 or 3), patients involved in pivoting sports, and generalized ligament hyperlaxity or knee hyperextension. Technique Description: Hamstring tendon autografts are used for the ACL and ALL reconstruction; a common femoral ACL and ALL tunnel is made outside-in, making a short socket. A continuous looped hamstring tendon autograft attached to one button is used. The ACL is fixed with an adjustable-loop button. Through small incisions, the tibial fixation of both grafts is performed with bioabsorbable screws. Results: We present a 19-year-old professional soccer player with an acute ACL tear, with no associated meniscal or chondral lesions. Owing to his young age and high-risk sports practice, a combined ACL and ALL reconstruction was performed. The combined ACL and ALL reconstruction with a single femoral tunnel using the hamstrings tendons graft is a well-established procedure for ACL augmentation, reducing failure rates for certain risk groups, with excellent outcomes reported. The use of an adjustable-loop button on the femur is a viable option for this kind of reconstruction with postoperative stability comparable to the interference screw, classically used for this kind of reconstruction. Discussion/Conclusion: This technique has some advantages, such as the use of a short outside-in femoral socket, thus theoretically improving healing. In addition, this lowers the risk of lateral collateral ligament injury, and since the ileotibial band graft is not used, the risk of injuring the lateral inferior genicular vessels and the peroneal nerve is theoretically reduced. Besides, using an adjustable-loop cortical button in the femur can theoretically reduce potential complications such as screw migration, soft-tissue impingement, femoral-site pain, and implant removal. Finally, the reconstruction is done with small incisions, improving the aesthetic result and postoperative pain. Considering all the aforementioned factors, this technique theoretically offers some benefits. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Purpose: The most widely used classifications of age-related macular degeneration (AMD) and its severity stages still rely on color fundus photographs (CFPs). However, AMD has a wide phenotypic variability that remains poorly understood and is better characterized by OCT. We and others have shown that patients with AMD have a distinct plasma metabolomic profile compared with controls. However, all studies to date have been performed solely based on CFP classifications. This study aimed to assess if plasma metabolomic profiles are associated with OCT features commonly seen in AMD. Design: Prospectively designed, cross-sectional study. Participants: Subjects with a diagnosis of AMD and a control group (> 50 years old) from Boston, United States, and Coimbra, Portugal. Methods: All participants were imaged with CFP, used for AMD staging (Age-Related Eye Disease Study 2 classification scheme), and with spectral domain OCT (Spectralis, Heidelberg). OCT images were graded by 2 independent graders for the presence of characteristic AMD features, according to a predefined protocol. Fasting blood samples were collected for metabolomic profiling (using nontargeted high-resolution mass spectrometry by Metabolon Inc). Analyses were conducted using logistic regression models including the worst eye of each patient (AREDS2 classification) and adjusting for confounding factors. Each cohort (United States and Portugal) was analyzed separately and then results were combined by meta-analyses. False discovery rate (FDR) was used to account for multiple comparisons. Main Outcome Measures: Plasma metabolite levels associated with OCT features. Results: We included data on 468 patients, 374 with AMD and 94 controls, and on 725 named endogenous metabolites. Meta-analysis identified significant associations (FDR < 0.05) between plasma metabolites and 3 OCT features: hyperreflective foci (6), atrophy (6), and ellipsoid zone disruption (3). Most associations were seen with amino acids, and all but 1 metabolite presented specific associations with the OCT features assessed. Conclusions: To our knowledge, we show for the first time that plasma metabolites have associations with specific OCT features seen in AMD. Our results support that the wide spectrum of presentations of AMD likely include different pathophysiologic mechanisms by identifying specific pathways associated with each OCT feature. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Category: Ankle Introduction/Purpose: The measurement of the ankle's range of motion is now considered of great importance for the diagnosis, therapeutic choice, and follow-up of the evolution of the treatment in patients with pathologies, both of the ankle and the whole hindfoot. However, there is no established method of choice for the safety assessment of talocrural mobility. Therefore, to evaluate the methods of measuring leg-foot movement in normal ankles and feet by comparing the results of clinical measurements with those of radiographic measurement and to determine the range of leg-foot movement considered normal. Methods: The leg-foot movement was measured in 44 patients (60 feet) using a traditional goniometer, digital goniometer, inclinometer, smartphone application, and radiographic measurement (considered gold standard). Maximum dorsiflexion was achieved by asking the patient to take a step forward with the contralateral foot and perform as much dorsiflexion as possible in the ankle studied without removing the heel from the ground. For maximum plantar flexion, the patient was asked to take a step back with the contralateral foot and make as much plantar flexion as possible without removing the studied forefoot from the ground. Results: The values obtained in radiographic measurement were higher than those obtained with clinical measurement. When we compared only the results of clinical measurement, the traditional goniometer was inaccurate. According to the radiographic method, the mean leg-foot range of motion was 65.6 degrees. The mean maximum plantar flexion was 34.9 degrees, and the mean maximum dorsiflexion was 30.7 degrees. Conclusion: The most appropriate method for evaluating the leg-foot range of motion is the radiographic one. The traditional goniometer proved to be the most imprecise clinical method. The mean leg-foot range of motion in healthy young adults was 65 degrees.

Background: Synovial hemangioma is a rare neoplastic lesion, which can result in recurrent hemarthrosis and pain. It can affect any joint, tendon, or bursa, withal those around the knee. The intra-articular lesion is more prevalent and is more frequently diagnosed in female children or young adults. Indications: Surgery is indicated when patients present with recurrent painful hemarthrosis that affect daily living and functionality. Technique Description: Diagnostic knee arthroscopy, initially without tourniquet inflation, was performed to detect and study the extent of the lesion. Afterwards, the tourniquet was inflated to proceed with the surgical excision. Medial parapatellar approach was performed, and limits of the hemangioma were identified. Wide resection was performed taking care to not damage the medial meniscus and medial condyle cartilage. Neoplastic lesion was sent to pathology analysis. The tourniquet was deflated and hemostasis checked because these lesions can present extensive bleeding. Results: Localized, well-circumscribed, and encapsulated lesions have been reported to usually present low recurrence rate when completely excised. Discussion/Conclusion: It is a rare disease, and around 200 cases have been reported; therefore, conclusions about treatment and outcomes rely mostly on case series and case reports. Early diagnosis and treatment are paramount to prevent degenerative changes secondary to recurrent hemarthrosis. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Lesions of the medial collateral ligament (MCL) are the most common knee ligament injuries and, when they occur in isolation, they often progress with satisfactory outcomes using conservative treatment. However, MCL lesions associated with anterior cruciate ligament or posterior cruciate ligament (PCL) injuries in knee dislocations should be reconstructed to prevent failure of the central pivot. In knees with combined injuries involving the PCL and the MCL, the confluence of tunnels in the medial femoral condyle can be a potential problem during reconstruction surgery. Indications: The indication of this technique is the combined injury of the PCL and the MCL. Technique Description: The technique consists in the reconstruction of the PCL and the MCL with an Achilles tendon allograft. The bone plug of the graft is fixed on the tibial bed with the inlay technique. The graft passes through a single femoral tunnel drilled in the medial femoral condyle, with entrance point on the footprint of the PCL on the inner wall of the condyle and exit on the origin of the native MCL, near to the medial epicondyle. The graft is fixed in the femoral tunnel with an interference screw and continues to the isometric point of the anatomic insertion of the MCL in the tibia, where an interference screw is used to fix it. Results: Results from our group using this technique have shown good clinical outcomes, with complications and failure rates similar to other series in the literature. Discussion/Conclusion: This technique is an excellent option for surgeons, when an Achilles tendon allograft is available, to avoid confluence of tunnels in the medial femoral condyle. It presents good results and acceptable complication rates, compatible with the severity of this lesion. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Background: Posterolateral knee injuries can occur in 16% of patients with acute ligament injuries, and up to 70% have a combined anterior cruciate ligament (ACL) tear. Studies have shown that, in different populations, the distance between the insertion of the popliteus tendon and the lateral collateral ligament (LCL) may be smaller than the 18.5 mm previously reported in the literature. When we have an associated injury of the ACL and the posterolateral corner (PLC), the confluence of tunnels in the lateral femoral condyle can be a potential problem during reconstruction surgery. Indications: The indication of this technique is the combined injury of the ACL and the PLC. Technique Description: The reconstruction is performed with 2 semitendinosus tendons and 1 gracilis tendon. The technique consists of making a tunnel in the lateral wall of the femur, from the outside-in, at the isometric point between the origin of the LCL and insertion of the popliteus tendon, and emerging in the inner wall of the lateral femoral condyle at the anatomic point of the ACL. The graft is passed from the tibia to the femur with the doubled gracilis tendon and the 2 simple semitendinosus tendons for the ACL graft. The remaining portions of the semitendinosus tendons are left for reconstruction of the PLC structures, with one of them going straight to the posterolateral tibial tunnel (reconstructing the popliteus tendon), and the other passing through the fibular head tunnel (reconstructing the LCL) and continuing from the fibular head to the posterolateral tibial tunnel (reconstructing the popliteofibular ligament). Results: Patients undergoing this technique achieved good functional outcomes and a failure rate similar to that reported in the literature for combined ACL and PLC reconstruction. Discussion/Conclusion: This technique is an excellent option for patients with the combined injury of the ACL and the PLC, avoiding the confluence of tunnels in the lateral femoral condyle. It presents good results and acceptable complication rates, compatible with the severity of this lesion. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Graphical Abstract This is a visual representation of the abstract.

ABSTRACT: Intermediate- to high-grade non-muscle invasive bladder cancer is preferably treated with transurethral resection followed by adjuvant intravesical immunotherapy with Bacillus Calmette-Guérin (BCG). BCG acts as an immune stimulator, inducing a complex inflammatory response that selectively targets tumoral cells. Mild side effects of BCG instillation, such as fever, malaise, and bladder irritation are frequent, while severe treatment-associated complications of the genito-urinary tract are rare. “Distant” complications are even rarer and, since BCG is able to disseminate hematogenously, virtually all organs and systems can be involved, with the lungs, liver and musculoskeletal system being most commonly affected. Vascular complications of BCG immunotherapy are exceedingly rare and difficult to diagnose, because they can mimic other vascular infections and may occur several years after treatment. Knowledge of previous BCG immunotherapy and awareness about treatment-related complications is essential to avoid misdiagnosis, and to guide appropriate treatment.

Background: Use of ultrasound (US) to facilitate vascular access has increased compared to landmark-based procedures despite ergonomic challenges and need for extrapolation of 2-dimensional images to understand needle position. The MantUS™ system (Sentiar, Inc.,) uses a mixed reality (MxR) interface to display US images and integrate real-time needle tracking. Objective: The purpose of this prospective preclinical study was to evaluate the feasibility and usability of MantUS in a simulated environment. Methods: Participants were recruited from pediatric cardiology and critical care. Access was obtained in 2 vascular access training models: a femoral access model and a head and neck model for a total of 4 vascular access sites under 2 conditions—conventional US and MantUS. Participants were randomized for order of completion. Videos were obtained, and quality of access including time required, repositions, number of attempts, and angle of approach were quantified. Results: Use of MantUS resulted in an overall reduction in number of needle repositions (P = .03) and improvement in quality of access as measured by distance (P

Background: Pancreaticoduodenectomy is a highly invasive procedure associated with high morbidity. Several preoperative variables are associated with postoperative complications. The role of perioperative factors is uncertain. The use of perioperative epidural analgesia is potentially associated with fewer postoperative surgical complications. We hypothesize that perioperative epidural analgesia might be associated with fewer surgical complications. Methods: We reviewed data from 288 cases performed at our institution between 2012 and 2019, classifying patients into 2 groups: perioperative use of epidural analgesia and non-perioperative use of epidural analgesia. The decision to use epidural as an adjunct to general anesthesia was based on the judgment of the attending anesthesiologist. Uni- and multivariate analyses were then performed to determine factors associated with postoperative surgical complications, ie, postoperative pancreatic fistula, delayed gastric emptying, among others, after adjusting for confounders. Results: Baseline and intraoperative factors were similar between the groups, except for sex and postoperative surgical complications. In the univariate analyses, factors associated with fewer postoperative surgical complications were the diameter of the pancreatic duct ≥6 mm, hard pancreatic gland parenchyma texture, younger age (

Background:. In primary craniosynostosis, the premature fusion of one or more sutures prevents the perpendicular expansion of brain tissue (primary defect). Providing space for the brain to expand, the compensatory growth of unaffected sutures causes progressive skull deformation (secondary defect). Understanding the need to treat the osteogenic matrix responsible for the cranial vault’s shape was essential to develop a novel surgical concept known as dynamic osteotomy. It uses springs to activate stenotic sutures and trigger dura-mater distension while flexibilizing compensatory osseous defects via helicoid osteotomy (nautilus technique), allowing for efficient bone expansion and remodeling in craniosynostosis. Method:. This case series describes patients with craniosynostosis treated with dynamic osteotomy utilizing structural transformation inductors such as springs and helicoid osteotomy (nautilus technique), operated on between July 2004 and January 2020 at a single center in Brazil. Result:. Dynamic osteotomy longitudinally achieved stable osseous remodeling during growth period while maintaining good vitality and continuity of the osteotomized cranial vault. Conclusion:. Dynamic osteotomy utilizing springs and nautilus technique, alone or in combination, is a successful treatment of craniosynostosis regardless of patient’s age.

Background:. Self-fulfilling prophecy bias occurs when a perceived prognosis leads to treatment decisions that inherently modify outcomes of a patient, and thus, overinflate the prediction performance of prognostic methods. The goal of this series of systematic reviews is to characterize the extent to which neuroprognostic studies account for the potential impact of self-fulfilling prophecy bias in their methodology by assessing their adequacy of disclosing factors relevant to this bias. Methods:. Studies evaluating the prediction performance of neuroprognostic tools in cardiac arrest, malignant ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and spontaneous intracerebral hemorrhage will be identified through PubMed, Cochrane, and Embase database searches. Two reviewers blinded to each other’s assessment will perform screening and data extraction of included studies using Distiller SR and following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will abstract data pertinent to the methodology of the studies relevant to self-fulfilling prophecy bias. Results:. We will conduct a descriptive analysis of the data. We will summarize the reporting of mortality according to timing and mode of death, rates of exposure to withdrawal of life-sustaining therapy, reasoning behind limitations of supportive care, systematic use of standardized neuroprognostication algorithms and whether the tool being investigated is part of such assessments, and blinding of treatment team to results of neuroprognostic test being evaluated. CONCLUSIONS:. We will identify if neuroprognostic studies have been transparent in their methodology to factors that affect the self-fulfilling prophecy bias. Our results will serve as the foundation for standardization of neuroprognostic study methodologies by refining the quality of the data derived from such studies.

Summary:. Lipedema is a chronic and progressive disease that may compromise lymphatic function. Although suction-assisted lipectomy (SAL) is considered a safe treatment for lipedema patients, the lymphatic repercussions of this surgical procedure are not fully understood. There is not enough evidence to support the role of SAL in lymphatic function treatment in lipedema. Here, we report a case of lymphatic drainage improvement after lipedema treatment with SAL. Tumescent SAL was performed in the deep subcutaneous layer, preserving the superficial and muscular lymphatic vessels. Pre- and postsurgical lymphoscintigraphy was equally documented under the Genoa protocol. A 34-year-old female patient presented with painful enlargement of the arms and lower limbs caused by lipedema. The patient had undergone conservative treatment with mild improvement in pain and heaviness. Lymphoscintigraphy showed slowed radiotracer progression on the left lower limb, collateral and tortuous lymphatic vessels on the right lower limb, and exuberant radiopharmaceutical concentration on the inguinal chain. Nine months after SAL was performed, the patient underwent another lymphoscintigraphy, which exhibited normalized radiopharmaceutical progression time and normal and symmetrical lymphatic vessel patterns. Collateral lymphatic paths and tortuosity vessels were no longer identified. Furthermore, the patient reported significant improvement in pain and the limb’s appearance. Tumescent SAL is not only efficient and safe in treating lipedema, but may also be responsible for improvement in lymphatic drainage in lipedema patients. Additional prospective studies are fundamental to reinforce the current evidence and possibly yield predicting information about the tumescent liposuction eligibility in the improvement of lymphatic drainage.

Background: Hereditary angioedema (HAE) is an autosomal dominant disease characterized by recurrent episodes of subcutaneous or mucosal edema caused by excess bradykinin. The aim of the present study was to assess the knowledge of pediatricians about hereditary angioedema. Methods: An online survey with 12 HAE-related and 14 demographics-related questions was e-mailed to all pediatricians who were members of the Brazilian Society of Pediatrics (n = 17 145) once a week during the months of June and July 2021. The electronic questionnaire assessed clinical manifestations, diagnosis, and treatment of hereditary angioedema in children and adolescents. Results: Four hundred and fifty-five pediatricians responded to the questionnaire (2.6%), of whom 55 (12.1%) were board certified in Allergy and Immunology (A/I), while 400 (87.9%) were not (N-A/I). Three hundred and sixty-eight (80.9%) were female, 289 (55.7%) were under 50 years of age, 286 (62.9%) graduated from Medical School more than 10 years previously, 83 (18.2%) held an MSc/PhD degree, and 253 (55.6%) were living in the Southeast Region of Brazil. The median number of correct answers to the questions related to HAE among A/I was 7 out of 12 (58.3%), with median ranging from 4.5 to 8 correct answers, while for N-A/I it was 3 (25%), with median ranging from 2.5 to 4 correct answers (p

Previous studies have used cardiopulmonary exercise test (CPET) data to objectively assess physiological changes in patients undergoing percutaneous pulmonary valve implantation. A retrospective review was performed to assess pre- and post-CPET data among patients undergoing Alterra Adaptive Prestent and SAPIEN 3 transcatheter heart valve (Alterra) placement. Of the 7 patients eligible for the study, 5 (71%) were male. The mean age was 22 years (range: 12-49 years). CPET data showed significant (P = 0.03) improvement in ventilatory efficiency (VE/VCO2) while only 2 (29%) patients had an improvement of percent predicted peak oxygen consumption (VO2). These findings suggest favourable haemodynamic changes though further investigation is needed. Résumé: Des résultats aux épreuves d’effort cardiorespiratoire ont été utilisés lors d’études antérieures pour mesurer de manière objective les changements physiologiques chez les patients ayant subi l’implantation percutanée d’une valvule pulmonaire. Nous présentons une étude rétrospective des résultats à ces épreuves avant et après l’intervention dans des cas d’implantation transcathéther d’une prothèse Alterra Adaptive Prestent et d’une valve cardiaque SAPIEN 3 (Alterra). Parmi les sept patients admissibles à l’étude, cinq (71 %) étaient de sexe masculin. L’âge moyen des sujets était de 22 ans (plage de 12 à 49 ans). Les résultats obtenus à l’épreuve d’effort cardiorespiratoire ont démontré une amélioration significative (P = 0,03) de l’efficacité respiratoire (VE/VCO2), mais seulement deux patients (29 %) ont présenté une amélioration du pourcentage prévu de la consommation maximale d’oxygène (VO2). Bien que ces observations semblent indiquer des changements hémodynamiques favorables, d’autres études sont nécessaires pour élucider la question.

Objectives: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. Methods: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March–July, 2020. The model was validated in the 1054 patients admitted during August–September, as well as in an external cohort of 474 Spanish patients. Results: Median (25–75th percentile) age of the model-derivation cohort was 60 (48–72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829–0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833–0.885]) and Spanish (0.894 [95% CI 0.870–0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). Conclusions: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.

Background: There are no data on lung function reference values for Portuguese children, and the contribution from the Portuguese data set in the Global Lung Function Initiative (GLI) is scant. Objectives: We aimed to estimate new up-to-date reference values for Portuguese children by fitting a multivariable regression model to a general population sample. Further, we intended to assess the external validity of the obtained reference values and to compare them to the GLI reference values. Methods: A random sample of 858 children from 20 primary schools were screened by health questionnaire, physical examination, and spirometry. Spirometric parameters recorded were FVC, FEV1, and FEF25-75. Multiple regression models were used to derive reference equations. Results: Overall, 481 children, aged between 7 and 12 years, 267 boys (55.5%), were included. Boys had higher values for FVC and FEV1 than girls (P < .05). The strongest correlation was found for FVC with height (r = 0.71 for boys and 0.70 for girls), while the lowest correlation was observed in both sexes for FEF25-75 with age (r = 0.23). Height was the most significant predictor of FVC, FEV1, and FEF25-75 in our models. Weight and body mass index were not significant predictors for boys but had a significant effect on girls’ equations for all spirometry parameters. Compared to obtained reference equations with GLI, they performed better for FVC in boys, FEV1 in girls, and FEF25-75 in both boys and girls. Conclusion: We offer up-to-date reference values of spirometry for Portuguese children that can be used in clinical practice and research.

Background. The association between Kidney Donor Profile Index (KDPI) and 1-y estimated glomerular filtration rate (eGFR) with long-term kidney graft survival is well known. Yet, the association between KDPI and 1-y eGFR remains uncertain considering the several concurrent competing risk factors. Methods. This single-center, retrospective cohort study analyzed data from 3059 consecutive deceased donor kidney transplant recipients with a 1-y follow-up from January 2013 to December 2017. The aim was to determine the association between the KDPI strata (0%–35%, 36%–50%, 51%–85%, 86%–100%) and 1-y eGFR estimated by the CKD-EPI equation. Results. The incidence of delayed graft function (50.6% versus 59.3% versus 62.7% versus 62.0%; P < 0.001) and cytomegalovirus infection (36.7% versus 36.6% versus 43.3% versus 57.8%; P < 0.001) increased with increasing KDPI strata but not biopsy-proven acute rejection (9.1% versus 9.8% versus 8.4% versus 9.1%; P = 0.736). The median 1-y eGFR decreased with increasing KDPI strata (64.8 versus 53.5 versus 46.9 versus 39.1 mL/min/1.73 m2; P < 0.001). In the Cox regression, the higher the KDPI was, the lower the probability of a lower 1-y eGFR was. Assuming the 0%–35% strata as the reference, the likelihood of eGFR 35%–50% (HR = 2.239, 95% CI = 1.862–2.691), and >51%–85% (HR = 2.871, 95% CI = 2.361–3.491), respectively. Other variables associated with a lower graft function were donor sex (HR male versus female = 0.896, 95% CI = 0.813–0.989) and cold ischemia time (HR for each hour = 1.011, 95% CI = 1.004–1.019). This association was sustained after the Poisson mediation analysis, including delayed graft function, cytomegalovirus, and acute rejection as mediators. Conclusions. In this cohort of deceased donor kidney recipients, KDPI, and cold ischemia time were the major independent risk factors associated with lower 1-y kidney function.

Introduction and Objectives: Liver transplantation (LT) selection models for hepatocellular carcinoma (HCC) have not been proposed to predict waitlist dropout due to tumor progression. This study aimed to compare the alfa-fetoprotein (AFP) model and other pre-LT models in their prediction of HCC dropout. Materials and Methods: A multicenter cohort study was conducted in 20 Latin American transplant centers, including 994 listed patients for LT with HCC from 2012 to 2018. Longitudinal tumor characteristics and patterns of progression were recorded at the time of listing, after treatments and at last follow-up over the waitlist period. Competing risk regression models were performed, and the model's discrimination was compared by estimating Harrell's adapted c-statistics. Results: HCC dropout rate was significantly higher in patients beyond [24% (95% CI 16-28)] compared to those within Milan criteria [8% (95% IC 5-12%); P2 [adjusted SHR of 3.17 (CI 2.13-4.71)], c-index of 0.71 (95% CI 0.65-0.77; P=0.09 vs. Milan). Similar discrimination power for HCC dropout was observed between the AFP score and the Metroticket 2.0 model. In patients within Milan, an AFP score >2 points discriminated two populations with a higher risk of HCC dropout [SHR 1.68 (95% CI 1.08-2.61)]. Conclusions: Pre-transplant selection models similarly predicted HCC dropout. However, the AFP model can discriminate a higher risk of dropout among patients within Milan criteria.

The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.