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Background: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. Objective: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. Design: RCT with parallel and balanced large groups. Setting: Academic university hospital and Olympic gyms. Subjects: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. Methods: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of “life movements”, strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. Results: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). Conclusion: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes. Clinical Trials Registration No: NCT03858114

To determine risk factors for coronavirus disease (COVID-19) among US healthcare personnel (HCP), we conducted a case–control analysis. We collected data about activities outside the workplace and COVID-19 patient care activities from HCP with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results (cases) and from HCP with negative test results (controls) in healthcare facilities in 5 US states. We used conditional logistic regression to calculate adjusted matched odds ratios and 95% CIs for exposures. Among 345 cases and 622 controls, factors associated with risk were having close contact with persons with COVID-19 outside the workplace, having close contact with COVID-19 patients in the workplace, and assisting COVID-19 patients with activities of daily living. Protecting HCP from COVID-19 may require interventions that reduce their exposures outside the workplace and improve their ability to more safely assist COVID-19 patients with activities of daily living.

Resume La prise en charge dun cancer de penis est complexe, une collaboration entre radiologue, pathologiste et urologue est necessaire pour etablir un staging correct. Dans cette revue nous essayons de montrer comment on peut obtenir un compte–rendu complet (imagerie, biopsie, examen extemporane) et comment prendre en charge le malade (traitement chirurgicaux et autres).

Summary Background & aims Studies using the Global Leadership Initiative on Malnutrition (GLIM) criteria for patients with liver cirrhosis are limited. This study aimed to assess the impact of malnutrition according to the GLIM criteria on the outcomes of patients awaiting a liver transplant (LTx) and compare these criteria with Subjective Global Assessment (SGA). Methods This retrospective observational study included adult patients awaiting LTx. Patient clinical data, nutritional status according to various tools including SGA, and resting energy expenditure were assessed. The distinct phenotypic and etiologic criteria provided 36 different GLIM combinations. The GLIM criteria and SGA were compared using the kappa coefficient. The variables associated with mortality before and after the LTx and with a longer length of stay (LOS) after LTx (≥18 days) were assessed by Cox regression and logistic regression analyses, respectively. Results A total of 152 patients were included [median age 52.0 (interquartile range: 46.5–59.5) years; 66.4% men; 63.2% malnourished according to SGA]. The prevalence of malnutrition according to the GLIM criteria ranged from 0.7% to 30.9%. The majority of the GLIM combinations exhibited poor agreement with SGA. Independent predictors of mortality before and after LTx were presence of ascites or edema (p = 0.011; HR:2.58; CI95%:1.24–5.36), GLIM 32 (PA + MELD) (p = 0.026; HR:2.08; CI95%:1.09–3.97), GLIM 33 (PA + MELD-Na ≥ 12) (p = 0.018; HR:2.17; CI95%:1.14–4.13), and GLIM 34 (PA + Child–Pugh) (p = 0.043; HR:1.96; CI95%:1.02–3.77). Malnutrition according to GLIM 28 (handgrip strength + Child-Pugh) was independently associated with a longer LOS (p = 0.029; OR:7.21; CI95%:1.22–42.50). Conclusion The majority of GLIM combinations had poor agreement with SGA, and 4 of the 36 GLIM combinations were independently associated with adverse outcomes.

Background and Aims: Several studies have found Golimumab (GOL) effective and safe in the short-term treatment of ulcerative colitis (UC), but few long-term data are currently available from real world. Our aim was to assess the long-term real-life efficacy and safety of GOL in managing UC outpatients in Italy. Methods: A retrospective multicenter study assessing consecutive UC outpatients treated with GOL for at least 3-month of follow-up was made. Primary endpoints were the induction and maintenance of remission in UC, defined as Mayo score ≤2. Several secondary endpoints, including clinical response, colectomy rate, steroid free remission and mucosal healing, were also assessed during the follow-up. Results: One hundred and seventy-eight patients were enrolled and followed up for a median (IQR) time of 9 (3-18) months (mean time follow-up: 33.1±13 months). Clinical remission was achieved in 57 (32.1%) patients: these patients continued with GOL, but only 6 patients (3.4%) were still under clinical remission with GOL at the 42nd month of follow-up. Clinical response occurred in 64 (36.4%) patients; colectomy was performed in 8 (7.8%) patients, all of them having primary failure. Steroid-free remission occurred in 23 (12.9%) patients, and mucosal healing was achieved in 29/89 (32.6%) patients. Adverse events occurred in 14 (7.9%) patients. Conclusions: Golimumab does not seem able to maintain long-term remission in UC in real life. The safety profile was good.

The most widely practiced (standard) treatment of non-metastatic rectal cancer is based on proctectomy with mesorectal excision (partial or total according to the location of the tumor and commonly called TME). Surgery is preceded by CAP50-type chemoradiotherapy (capecitabineand 50 Grays radiation) and performed 6-8 weeks after the end of chemoradiotherapy. The development of new endoscopic, surgical, radiation-based and chemotherapeutic modalities leads surgeons to envisage customized treatment to find the best compromise between functional and oncologic results according to the locoregional extension of the tumor. Superficial lesions are amenable to transanal excision. T2-3 tumors4cm are amenable to rectal preservation when neoadjuvant treatment obtains a complete response, allowing local excision or close surveillance. Intensification endocavitary radiotherapy and induction and consolidation chemotherapy regimens to avoid recourse to salvage abdomino-perineal resection (APR) are under investigation. For locally advanced rectal cancers (T3-4 and all N+ irrespective of T), the following scenarios can be envisaged: for initially resectable tumors (T3N0, T1-T3N+, circumferential resection margin2mm), neoadjuvant chemotherapy alone aims to minimize the risk of local recurrence while avoiding the sequelae of radiotherapy. In case of initially non-resectable tumors (T4, circumferential resection margin1mm), induction chemotherapy before chemoradiotherapy and consolidation chemotherapy after short course radiotherapy provide better results than standard treatment in terms of complete response and recurrence-free survival, and should be routinely proposed in this indication.

International audience; Objective Annual countrywide data are scarce when comparing surgical approaches in terms of hospital stay outcomes and costs for radical prostatectomy (RP). We aimed to assess the impact of surgical approach on post-operative outcomes and costs after RP by comparing open (ORP), laparoscopic (LRP), and robot-assisted (RARP) RP in the French healthcare system. Patients and methods Data from all patients undergoing RP in France in 2020 were extracted from the central database of the national healthcare system. Primary endpoints were length of hospital stay (LOS including intensive care unit (ICU) stay if present), complications (estimated by severity index), hospital readmission rates (at 30 and 90 days), and direct costs of initial stay. Results and limitations A total of 19,018 RPs were performed consisting in ORP in 21.1%, LRP in 27.6%, and RARP in 51.3% of cases. RARP was associated with higher center volume (p < 0.001), lower complication rates (p < 0.001), shorter LOS (p < 0.001), and lower readmission rates (p = 0.004). RARP was associated with reduced direct stay costs (2286 euros) compared with ORP (4298 euros) and LRP (3101 euros). The main cost driver was length of stay. The main limitations were the lack of mid-term data, readmission details, and cost variations due to surgery system. Conclusions This nationwide analysis demonstrates the benefits of RARP in terms of post-operative short-term outcomes. Higher costs related to the robotic system appear to be balanced by patient care improvements and reduced direct costs due to shorter LOS.

Pain after total knee arthroplasty (TKA) is not infrequent and may be indicative of a broad spectrum of prosthesis-related, intra-articular, or extra-articular pathologies. To diagnose and treat the underlying cause of a painful TKA, systematic evaluation of the patient is critical to ensure that they are managed appropriately and expeditiously. This evidence-based review presents current concepts regarding the pathophysiology, etiology, and diagnosis of painful TKA and our recommended approach for management. [ Orthopedics . 2021;44(6):341–352.]

A ultrassonografia transvaginal (USTV) e um exame muito utilizado na propedeutica ginecologica. Um achado de espessamento endometrial a USTV, por exemplo, requer maior investigacao, geralmente realizada pela histeroscopia diagnostica, o metodo mais apropriado para avaliar a cavidade uterina. Estabelecer o perfil epidemiologico da mulher com achados de espessamento endometrial a USTV e investigar a correlacao entre os achados desse exame e os provenientes da histeroscopia. Estudo transversal e prospectivo com delineamento observacional, baseado na analise histeroscopica de 79 pacientes cuja USTV constata espessamento endometrial. Das pacientes que apresentavam espessamento endometrial, foi obtida uma media de idade de 55,9 ± 11,4 anos. Dentre essas, 52 (65,8%) estavam na pos-menopausa. 31 mulheres (39,24%) eram assintomaticas e 48 (60,75%) relataram queixas de sangramento uterino anormal e dor pelvica 31 (39,24%). A histeroscopia, apenas 18 pacientes (22,8%) apresentavam de fato espessamento endometrial, sendo que 46 (58,2%) apresentavam polipo endometrial, 9 (11,4%) apresentavam mioma submucoso e 10 (12,7%) nao possuiam alteracoes na cavidade uterina. Apenas 3 (3,8%) das pacientes apresentaram lesoes sugestivas de neoplasia maligna. As pacientes abordadas no estudo eram mulheres pos-menopausa, multiparas, com IMC acima da faixa considerada adequada e alta prevalencia de comorbidades, em especial a hipertensao arterial sistemica. Alem de espessamento endometrial a USTV, queixavam de sangramento uterino anormal e/ou dor pelvica. Devido a esses fatores, essas mulheres possuiam um maior risco para neoplasias endometriais, o que justifica o acompanhamento e investigacao por meio da histeroscopia.

Background: Stroke is among the leading causes of death and disability worldwide. Interventions for stroke rehabilitation aim to minimize sequelae, promote individuals’ independence and potentially recover functional damage. The role of aerobic exercise as a facilitator of post-stroke neuroplasticity in humans is still questionable. Objective: To investigate the impact of aerobic exercise on neuroplasticity in patients with stroke sequelae. Methods: A systematic review of randomized clinical trials and crossover studies was performed, with searches for human studies in the following databases: PUBMED, EMBASE, LILACS and PeDRO, only in English, following the PRISMA protocol. The keywords used for selecting articles were defined based on the PICO strategy. Results: This systematic review evaluated the impacts of aerobic exercise on neuroplasticity through assessment of neural networks and neuronal excitability, neurotrophic factors, or cognitive and functional assessment. Studies that evaluated the effects of aerobic exercise on neuroplasticity after stroke measured through functional resonance (fMRI) or cortical excitability have shown divergent results, but aerobic exercise potentially can modify the neural network, as measured through fMRI. Additionally, aerobic exercise combined with cognitive training improves certain cognitive domains linked to motor learning. Studies that involved analysis of neurotrophic factors to assess neuroplasticity had conflicting results. Conclusions: Physical exercise is a therapeutic intervention in rehabilitation programs that, beyond the known benefits relating to physical conditioning, functionality, mood and cardiovascular health, may also potentiate the neuroplasticity process. Neuroplasticity responses seem more robust in moderate to high-intensity exercise training programs, but dose-response heterogeneity and non-uniform neuroplasticity assessments limit generalizability. RESUMO Antecedentes: O acidente vascular cerebral (AVC) é a segunda causa principal de morte no mundo. Intervenções para reabilitação dos pacientes com AVC visam minimizar sequelas, promover sua independência e potencialmente recuperar danos funcionais. O papel do exercício aeróbico como facilitador da neuroplasticidade pós-AVC em humanos ainda é questionável. Objetivo: Investigar o impacto do exercício aeróbico na neuroplasticidade em pacientes com sequelas de AVC. Métodos: Foi realizada revisão sistemática de literatura, pesquisando nas seguintes bases de dados: PUBMED, EMBASE, LILACS e PeDRO. Foram selecionados trabalhos em língua inglesa, realizados apenas com humanos, seguindo o protocolo PRISMA. As palavras-chave utilizadas para a seleção de artigos foram definidas com base na estratégia PICO. Resultados: Esta revisão sistemática avaliou os impactos do exercício aeróbico na neuroplasticidade através da avaliação das redes neurais e da excitabilidade neuronal, por meio de fatores neurotróficos, por meio da avaliação cognitiva e funcional. Estudos que avaliaram os efeitos do exercício aeróbico sobre neuroplasticidade após o AVC medido através de ressonância funcional ou excitabilidade cortical, são controversos, mas há dados sugerindo uma modificação da rede neural na ressonância funcional após o exercício aeróbico. Há evidências de que, associar exercício aeróbico com treinamento cognitivo melhora certos domínios cognitivos ligados à aprendizagem motora. Estudos que envolveram a análise de fatores neurotróficos, como avaliação da neuroplasticidade, tiveram resultados conflitantes. Conclusões: Exercício aeróbico é uma intervenção terapêutica em programas de reabilitação, pois, além de proporcionar os benefícios no condicionamento físico, funcionalidade, humor e saúde cardiovascular, pode potencializar a neuroplasticidade.

Distal radius fractures (DRFs) are associated with a high economic burden and an impact on quality of life on these patients. Its high prevalence demonstrates the importance of registering functional results, with emphasis on vulnerable population such as elderly females.Thirty-six patients were admitted to a multimodal rehabilitation program. Exercise progressions combined with manual therapy and electrophysical agents were provided, taking into account bone and soft tissues healing stages, protection of surgical intervention and symptoms of each patient. The primary outcome was the Patient Rated Wrist Evaluation (PRWE) questionnaire. The secondary outcomes were wrist and forearm range of motion (ROM), grip strength and lateral and tripod pinch strength. The paired t-test was used to compare mean PRWE, ROM, and strength between 6 and 12 weeks.An improvement of functionality was observed with a decreased of -20.9 (CI 95%: 25.9 to -15.9) points in the PRWE questionnaire (p 0.001) between 6 and 12 weeks after DRF surgery. In addition, an increase in the ROM of the wrist (p 0.001), grip strength (p 0.001), lateral pinch (p 0.001) and tripod pinch (p 0.001) were observed between 6 and 12 weeks after surgery.These findings showed a clinically and statistically significant improvement in function, ROM, and strength assessed at weeks 6 and 12 after surgery. However, this study design cannot establish a cause-and-effect relationship. Future randomized controlled clinical trials should investigate the effectivity of similar rehabilitation programs.

Purpose Hepatic steatosis is a common incidental finding on abdominal imaging that is not always reported or recognized as having clinical significance. Because of its association with liver disease, cirrhosis, and diabetes, the aim of this study was to bring attention to this finding and provide clinical guidance to referring clinicians by inserting standardized text into radiology reports of patients with incidentally detected hepatic steatosis. Methods Patients with incidentally discovered hepatic steatosis on abdominal ultrasound or CT had standard text inserted into the impression sections of their diagnostic imaging reports. A total of 1,256 patients whose reports were tagged between April 2016 and September 2017 were retrospectively identified and their electronic medical records reviewed to determine subsequent acknowledgment in the medical record or clinical action in response to the tagged report. Information regarding patient demographics, the type of provider who ordered the examination, and the acuity of the examination results was also recorded. Results Acknowledgment and subsequent clinical action were more likely in patients whose examinations was ordered by primary care providers, whose examination results were not urgent, and who were in the ultrasound group. The overall diagnostic yield in patients who underwent clinical evaluation was nonalcoholic fatty liver disease in 70%, nonalcoholic steatohepatitis in 6%, and alcoholic hepatitis in 17%. Conclusions Opportunistic screening for incidental hepatic steatosis on abdominal CT and ultrasound is feasible, with substantial yield for patients with clinically important entities including nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

Los Schwannomas vestibulares (SV) son tumores benignos del ángulo pontocerebeloso. Su tratamiento clásico es la microcirugía, sin embargo, con la aparición de la radiocirugía y la mejor comprensión de la historia natural de la enfermedad, la terapia quirúrgica ha disminuido en frecuencia quedando reservada para los casos mas complejos. En este artículo se realiza un análisis prospectivo de los SV operados en el Hospital Clínico de la Universidad de Chile (HCUCh) entre los años 2015 y 2019 con el objetivo de describir sus resultados quirúrgicos y funcionales. Se operaron 7 pacientes, todos por via retrosigmoidea transmeatal con ayuda de monitoreo neurofisiológico intraoperatorio. El 86% correspondieron a tumores T4b y el 14% a tumores T3b de la clasificación de Hannover. La función facial ipsilateral al año de evolución postoperatoria fue de HB1 28,5%, HB2 43% y HB3 28,5%. El 86% obtuvo buen resultado de la función facial y el 14% resultado intermedio al año de evolución según los parámetros establecidos en este articulo. No se logro preservar la audición en ningún paciente. Todos los pacientes se encuentran en mRS 1 al año de cirugía. Se presenta esta serie con resultados comparables a series internacionales en un centro de bajo volumen.

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease 2019 (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behavior and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not-admitted cohort, n = 388) or required hospitalization (n = 468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95% confidence interval (CI), 11% to 15%) and 23% (95% CI, 20% to 27%), respectively. Antilymphoma treatment, including anti-CD20 containing regimens, did not impact survival. Patients with Hodgkin’s lymphoma had the more favorable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate- and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment of their underlying disease and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

Several Mendelian disorders follow an autosomal recessive inheritance pattern. Epidemiological information on many inherited disorders may be useful to guide health policies for rare diseases, but it is often inadequate, particularly in developing countries. We aimed to calculate the carrier frequencies of rare autosomal recessive Mendelian diseases in a cohort of Brazilian patients using whole exome sequencing (WES). We reviewed the molecular findings of WES from 320 symptomatic patients who had carrier status for recessive diseases. Using the Hardy-Weinberg equation, we estimated recessive disease frequencies (q2 ) considering the respective carrier frequencies (2pq) observed in our study. We calculated the sensitivity of carrier screening tests based on lists of genes from five different clinical laboratories that offer them in Brazil. A total of 425 occurrences of 351 rare variants were reported in 278 different genes from 230 patients (71.9%). Almost half (48.8%) were carriers of at least one heterozygous pathogenic/likely pathogenic variant for rare metabolic disorders, while 25.9% of epilepsy, 18.1% of intellectual disabilities, 15.6% of skeletal disorders, 10.9% immune disorders, and 9.1% of hearing loss. We estimated that an average of 67% of the variants would not have been detected by carrier screening panels. The combined frequencies of autosomal recessive diseases were estimated to be 26.39/10,000 (or ~0.26%). This study shows the potential research utility of WES to determine carrier status, which may be a possible strategy to evaluate the clinical and social burden of recessive diseases at the population level and guide the optimization of carrier screening panels.

International audience; Objective: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients.Methods: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses.Results: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications.Conclusions: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.

Healthcare personnel with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection were interviewed to describe activities and practices in and outside the workplace. Among 2,625 healthcare personnel, workplace-related factors that may increase infection risk were more common among nursing-home personnel than hospital personnel, whereas selected factors outside the workplace were more common among hospital personnel.

Objective/Background: Hematopoietic stem cell transplantation (HSCT) is a treatment for benign and malignant hematological diseases. These aggressive treatments cause reduced levels of physical activity, decreased lung function, and worse quality of life. Alterations in pulmonary function tests before HSCT are associated with the risk of respiratory failure and early mortality. The objective of this study was to evaluate functional capacity and lung function before and after HSCT and identify the predictors of mortality after 2 years. Methods: A prospective cohort study was carried out with individuals with oncohematological diseases. The evaluations were carried out in two moments during hospitalization and at hospital discharge. Follow-up was carried out after 48 months. Assessments were carried out on 34 adults, using spirometry, manovacuometry, 6-Minute Walk Test (6MWT), Handgrip Strength Test, and 30-Second Chair Stand Test (30-s CST). Results: There was a statistically significant reduction for the variables in forced vital capacity, forced expiratory volume predicted in the 1st second, Tiffeneau index, handgrip strength, and distance covered (% predicted) on the 6MWT (p < .05). There was a significant difference in the 30-s CST when individuals were compared according to the type of transplant. We found that a 10% reduction in the values of maximum inspiratory pressure (MIP) can predict an increased risk for mortality. Conclusions: Individuals undergoing HSCT have reduced functional capacity, lung function, and muscle strength during the hospitalization phase. Reduction in the values of MIP increases the risk of nonrelapse mortality.

Phonotactic female and vocal male responses of frogs to advertisement calls have been shown to encompass broader ranges than those of variation of natural mate-attracting signals. Anuran aggressive calls contribute to expand the range of sound features significant for communication. Evoked vocal responses (EVRs) of males of Batrachyla leptopus to synthetic advertisement calls and variants with different temporal features altered parametrically were studied to assess their correspondence with features of natural signals. Frogs responded to stimuli differing in note rate with vocal patterns that depended on the design of the synthetic sounds: lower call rates were obtained with stimuli composed of notes with linear rise-fall times deviating from the average of this parameter for natural calls. However, opposite results were obtained with stimuli composed of sinusoidally amplitude-modulated notes. Calls of longer duration resembling aggressive calls were emitted in response to low note rate sinusoidal stimuli. Stimuli with note durations above and below the natural average, stimuli having low pulse rates and a continuous tone also elicited longer calls of aggressive type. These patterns relate the vocal responses recorded to recognition of conspecific and heterospecific advertisement and aggressive calls, as well as to novel signal features.

INTRODUCTION Predictors of financial costs related to total joint arthroplasty (TJA) have become increasingly important becuase payment methods have shifted from fee for service to bundled payments. The purpose of this study was to assess the relationship between preoperative opioid use and cost of care in primary TJA. METHODS A retrospective study was conducted in Medicare patients who underwent elective unilateral primary total knee or hip arthroplasty between 2015 and 2018. Preoperative opioid usage, comorbidities, length of stay, and demographic information were obtained from chart review. The total episode-of-care (EOC) cost data was obtained from the Centers of Medicare and Medicaid Services based on Bundled Payments for Care Improvement Initiative Model 2, including index hospital and 90-day postacute care costs. Patients were grouped based on preoperative opioid usage. Costs were compared between groups, and multivariate linear regression analyses were performed to analyze whether preoperative opioid usage influenced the cost of TJA care. Analyses were risk-adjusted for patient risk factors, including comorbidities and demographics. RESULTS A total of 3,211 patients were included in the study. Of the 3,211 TJAs, 569 of 3,211 patients (17.7%) used preoperative opioids, of which 242 (42.5%) only used tramadol. EOC costs were significantly higher for opioid and tramadol users than nonopioid users ($19,229 versus $19,403 versus $17,572, P < 0.001). Multivariate regression predicted that the use of preoperative opioids in TJA was associated with increased EOC costs by $789 for opioid users (95% confidence interval [CI] $559 to $1,019, P < 0.001) and $430 for tramadol users (95% CI $167 to $694, P = 0.001). Total postacute care costs were also increased by 70% for opioid users (95% CI 44% to 102%, P < 0.001) and 48% for tramadol users (95% CI 22% to 80%, P < 0.001). DISCUSSION This study demonstrated that preoperative opioid usage was associated with higher cost of care in TJA. Limiting preoperative opioid use for pain management before TJA could contribute to cost savings within a bundled model.

Background Infliximab and adalimumab are widely used for the treatment of Crohn's disease and ulcerative colitis. Aim To compare the long-term efficacy and safety of infliximab and adalimumab in a large cohort of Crohn's disease and ulcerative colitis patients reflecting real-life clinical practice. Methods Seven hundred twelve patients were retrospectively reviewed, 410 with Crohn's disease (268 treated with adalimumab and 142 with infliximab; median follow-up 60 months, range, 36-72) and 302 with ulcerative colitis (118 treated with adalimumab and 184 with infliximab; median follow-up 48 months, range, 36-84). Results In Crohn's disease, clinical remission was maintained in 75.0% of adalimumab vs. in 72.5% of infliximab patients (P = 0.699); mucosal healing and steroid-free remission were maintained in 49.5% of adalimumab vs. 63.9% of infliximab patients (P = 0.077) and in 77.7% of adalimumab vs. 77.3% in infliximab group (P = 0.957), respectively. In ulcerative colitis, clinical remission was maintained in 50.0% of adalimumab vs. 65.8% of infliximab patients (P 10 were predictors of failure in Crohn's disease; treatment with adalimumab, BMI ≥30 and Mayo score >10 were predictors of failure in ulcerative colitis. infliximab was more likely to cause adverse events than adalimumab (16.6 vs. 6.2%, P Conclusion Both adalimumab and infliximab are effective in long-term outpatients management of inflammatory bowel diseases. Adalimumab had a lower rate of adverse events.

We conducted a retrospective study on the long-term effect of mitotane treatment on testicular adrenal rest tumors (TARTs) in five adult patients with classic 21-hydroxylase deficiency. After 60 months of mitotane treatment, a decrease in adrenal steroids was observed in four patients. Testicular ultrasonography showed complete disappearance of TART in two patients, stabilization in two patients and a halving of TART volume in the remaining patient. Sperm count improved notably in two patients who had normal baseline inhibin B levels and small inclusions, thus enabling cryopreservation of the subjects’ semen. Four years of follow-up of these two patients after the withdrawal of mitotane showed no recurrence of TART and persistent normal testicular function. In conclusion, mitotane could be used as a last resort in CAH patients in the cases of azoospermia associated with TARTs but normal inhibin B levels, as it can improve long-term endocrine and exocrine testicular function.

Objective While vitamin D regulates immune cells, little is known about it in autoimmune Addison’s disease (AAD). We investigated the vitamin D status in AAD patients from five European populations to assess its deficiency. In addition, we studied two case-control cohorts for vitamin D metabolism and pathway genes. Design Cross-sectional study. Methods A total of 1028 patients with AAD from Germany (n = 239), Italy (n = 328), Norway (n = 378), UK (n = 44) and Poland (n = 39) and 679 controls from Germany (n = 301) and Norway (n = 378) were studied for 25(OH)D3 (primary objective). Secondary objectives (1,25(OH)2D3 and pathway genes) were examined in case-controls from Germany and Norway correlating 25(OH)D3 and single nucleotide polymorphisms within genes encoding the vitamin D receptor (VDR), 1-α-hydroxylase (CYP27B1), 25-hydroxylase (CYP2R1), 24-hydroxylase (CYP24A1) and vitamin D binding protein (GC/DBP). Results Vitamin D deficiency (25(OH)D3 10–20 ng/mL) was highly prevalent in AAD patients (34–57%), 5–22% were severely deficient (30 ng/mL). Lower 25(OH)D3 and 1,25(OH)2D3 levels were observed both in Norwegian and German AAD (P = 0.03/0.003 and P = 1 × 10-5/< 1 × 10-7, respectively) the former was associated with CYP2R1 (rs1553006) genotype G. Whereas controls achieved sufficient median 25(OH)D3 in summers (21.4 to 21.9 ng/mL), AAD patients remained largely deficient (18.0 to 21.2 ng/mL) and synthesize less 1,25(OH)2D3. Conclusion Vitamin D deficiency and insufficiency are highly prevalent in AAD patients. The vitamin D status of AAD may be influenced by genetic factors and suggests individual vitamin D requirements throughout the year.

Introduction: The current COVID-19 pandemic has involved developing vaccines to control the virulence of SARS-CoV-2. More than 4.1 million people have died from COVID-19.1 In response to this public health emergency, several vaccines against COVID-19 have been developed, with more than 3.7 billion doses administered worldwide. After the introduction of the adenovirus vector vaccine ChAdOx1, several cases of severe venous thrombosis with thrombocytopenia were reported worldwide. Objective: It was to present a case report of a 25-year-old female patient who presented extensive left intraparenchymal hematoma and rapid progression to brain death followed by death. Case report: A 25-year-old woman, CSS, was vaccinated against COVID-19 with the adenovirus ChAdOx1, 14 days after admission, evolved with a fever that started about 13 days ago, associated with holocranial, tight, moderate-intensity headache. On the day of admission, she was found by the torporous, unresponsive, and vomiting family, referred to the hospital emergency room. The patient was admitted to Glasgow 4 with evidence of anisocoria, with the left pupils larger than the right, rapidly progressing to mydriasis. Cranial computed tomography (CT) showed extensive left intraparenchymal hematoma, performing urgent decompressive craniectomy and placement of an intracranial pressure monitoring catheter. The cerebrospinal fluid exam did not show bacteria or fungi. CT angiography showed extensive thrombosis of the anterior portions of the superior sagittal sinus and probable thrombosis of the superficial drainage veins of the frontal regions. Skull CT revealed diffuse and bilateral ischemia. Laboratory tests showed mild thrombocytopenia and no change in the coagulogram. After one day, the patient evolved with worsening neurological status. Sedation was turned off to start the brain death protocol, which was confirmed twice. Finally, an electroencephalogram was performed with evidence of a straight-line tracing, without evidence of electrical brain activity. Final considerations: Several studies have been published regarding cerebral thrombosis, stroke, and thrombotic thrombocytopenic events. Thus, safe and effective vaccines against COVID-19 are an urgent need, as they can leave pathophysiological responses of hypercoagulability and thrombo inflammation associated with acute infection.

Objectives Proper management of the inflammatory process in Crohn's disease (CD) results in lower rates of complications. The objective of this study was to investigate the performance of isolated and combined use of fecal calprotectin (FC) and serum levels of C-reactive protein (CRP) as markers of inflammatory activity in CD and the possibility of their use as a therapeutic target. Patients and methods Patients with CD and indication for colonoscopy were prospectively enrolled in the study and allocated according to the presence or absence of endoscopic inflammatory activity. The correlation between FC and CRP levels and the Simplified Endoscopic Score of Crohn's Disease (SES-CD) was performed, and the accuracy of these markers was evaluated for the diagnosis of inflammatory activity, when used alone or in series. Results Eighty colonoscopies were performed in patients with CD. The FC cut-off value of 155 μg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7 mg/L demonstrated sensitivity of 75% and specificity of 67%. The sequential usage of these markers (FC + CRP) showed greater specificity (82%) when compared to the use of these markers alone. Depending on the probability of inflammatory activity, different scenarios were used to evaluate the performance of these markers and an algorithm is proposed. Discussion Combined analysis of FC and CRP, when performed consecutively, allows decisions to be made with a high degree of certainty and even eliminates the need for colonoscopy in many situations.

Colorectal cancer (CRC) is a multifactorial disease commonly diagnosed worldwide, with high mortality rates. Several studies demonstrate important associations between differential expression of micro-RNAs (miRs) and the prognosis of CRC. However, only a few systematic reviews emphasize the most relevant miRs able to contribute to the establishment of new prognostic biomarkers in CRC patients. The present study aimed to identify differentially expressed tissue miRs associated with prognostic factors in CRC patients, through a systematic review of the Literature. Using the PubMed database, Cochrane Library and Web of Science, studies published in English evaluating miRs differentially expressed in tumor tissue and significantly associated with the prognostic aspects of CRC were selected. All the included studies used RT-PCR (Taqman or SYBR Green) for miR expression analysis and the period of publication was from 2009 to 2018. A total of 115 articles accomplished the inclusion criteria and were included in the review. The studies investigated the expression of 102 different miRs associated with prognostic aspects in colorectal cancer patients. The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). Specific tissue miRs are shown to be promising prognostic biomarkers in patients with CRC, given their strong association with the prognostic aspects of these tumors, however, new studies are necessary to establish the sensibility and specificity of the miRs in order to use them in clinical practice.

Objectives To compare topical granulocyte and macrophage colony-stimulating factor (GM-CSF) and miltefosine (G + M) versus placebo and miltefosine (P + M) or parenteral meglumine antimoniate (MA) in the treatment of 150 patients with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis in the Amazon. Design A randomized and double-blinded clinical trial. Results At 90 days after the initiation of therapy, the cure rates were 66%, 58%, and 52% for the groups P + M, G + M, and MA, respectively (p > 0.05). Cure rates at 180 days did not differ. Healing time was similar in the 3 groups, but faster in the MA group as compared to the G + M group (p = 0.04). Mild and transitory systemic adverse events were frequent in all groups (above 85%). Nausea (85%) and vomiting (39%) predominated in the miltefosine groups and arthralgia (51%) and myalgia (48%) in the MA group. One patient (group MA) stopped treatment after presenting with fever, exanthema, and severe arthralgia. Conclusions Miltefosine did not present a higher cure rate than MA, and the association of GM-CSF did not improve the therapeutic response. Nevertheless, because of its less toxicity, easier administration, and a similar cure rate when compared with MA, miltefosine should remain as one of the main drugs for treating CL due to L. guyanensis. (Clinicaltrials.gov Identifier NCT03023111).

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified. OBJECTIVES The study sought to assess COVID-19`s impact on global cardiovascular diagnostic procedural volumes and safety practices. METHODS The International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained. RESULTS Surveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoradc echocardiography decreased by 59%, transesophageat echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). hi multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower-middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and teteheatth. CONCLUSIONS COVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world's economically challenged. Further study of cardiovascular outcomes and COVID-19-related changes in care delivery is warranted. (C) 2021 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

PI-RADS version 2.1 updates the technical parameters for multiparametric MRI (mpMRI) of the prostate and revises the imaging interpretation criteria while maintaining the framework introduced in version 2. These changes have been considered an improvement, although some issues remain unresolved, and new issues have emerged. Areas for improvement discussed in this review include the need for more detailed mpMRI protocols with optimization for 1.5-T and 3-T systems; lack of validation of revised transition zone interpretation criteria and need for clarifications of the revised DWI and dynamic contrast-enhanced imaging criteria and central zone (CZ) assessment; the need for systematic evaluation and reporting of background changes in signal intensity in the prostate that can negatively affect cancer detection; creation of a new category for lesions that do not fit into the PI-RADS assessment categories (i.e., PI-RADS M category); inclusion of quantitative parameters beyond size to evaluate lesion aggressiveness; adjustments to the structured report template, including standardized assessment of the risk of extraprostatic extension; development of parameters for image quality and performance control; and suggestions for expansion of the system to other indications (e.g., active surveillance and recurrence).

To investigate the relationship between phase angle (PA) and objective and subjective indicators of nutritional status in cancer patients, as well as to identify cutoff points for PA, to detect malnutrition in these patients. The study was a systematic review, carried out following the guidelines of the Preferred Reporting Items for Systematic Reviews and meta-analyses (PRISMA). Literature search was performed for two authors, in indexed databases, including the National Library of Medicine, Bethesda, MD (PubMed), Latin American and Caribbean Literature in Health Sciences (LILACS), and Scopus (Elsevier). We used the checklist from the Joanna Briggs Institute for assessing the risk of bias. The review was registered with the Systematic Review Registration (PROSPERO), number CRD42020134324. In total, nine papers were eligible. PA was correlated with several objective and subjective indicators of nutritional status in most cases. Cutoff point values for the PA, capable of detecting malnutrition, varied from 4.73° to 6°, despite the modest diagnostic accuracy. We assume that PA may be considered an indicator of nutritional status, when complementing additional data and assisting health practitioners in evaluating individuals with malignant neoplasms. However, a single cutoff point with fair and concomitant sensitivity and specificity was not identified.

To report the current clinical practice of French physicians for metachronous resectable liver metastasis (LM) occurring after a FOLFOX adjuvant chemotherapy for primary cancer. Twenty four clinical situations were proposed to a panel of experts via 4 learned societies. Clinical situations varied according time of recurrence (early between 6 and 12 month or > 12 month), extension of LM (limited ≤ 2 or extended > 2 lesions), presence of a neuropathy or not, and of a RAS or BRAF mutation. A total of 157 physicians participated in this study. A consensus was reached in 17 (71%) clinical situations. For an early limited recurrence, whatever presence of neuropathy, the preferred therapeutic approach (45%) was upfront surgery. For an early extended recurrence, whatever presence of neuropathy, there was a consensus (64%) for a preoperative chemotherapy by FOLFIRI + biologic agent. For a late recurrence without neuropathy, there was a consensus (50%) for a preoperative FOLFOX chemotherapy, whatever the extension of LM. For a late recurrence with neuropathy, upfront surgery was chosen (52%) for limited LM, and preoperative chemotherapy by FOLFIRI + biologic agent (73%) for extended LM. No response was influenced by the RAS mutation status. There was a strong consensus for intensified preoperative chemotherapy in all clinical situations for BRAF-mutated LM. This national survey provides an overview of the practice patterns in the treatment of LM occurring after adjuvant FOLFOX for primary. It could be a basis to establish expert’s recommendations for the clinical practice.

Resume Objectif. Le but du Comite de cancerologie de l’Association francaise d’urologie est de proposer une mise a jour des recommandations dans la prise en charge du cancer de la prostate. Methodes. Une revue systematique (Medline) de la litterature de 2018 a 2020 a ete conduite par le CCAFU concernant les elements du diagnostic, les options de traitement et la surveillance du cancer de la prostate, en evaluant les references avec leur niveau de preuve. Resultats. Les recommandations precisent la genetique, l’epidemiologie et les moyens diagnostiques du cancer de la prostate, les notions de depistage et de detection precoce. L’imagerie par resonance magnetique (IRM), examen d’imagerie de reference du cancer localise, est recommandee avant la realisation de biopsies prostatiques. Les moyens therapeutiques sont detailles et recommandes en fonction des situations cliniques. La surveillance active est une option therapeutique de reference pour les tumeurs de faible risque evolutif. La radiotherapie de rattrapage precoce est recommandee en cas de recidive biologique postprostatectomie totale. La suppression androgenique (SAd) reste le traitement de fond au stade metastatique. Le docetaxel associe a la SAd ameliore la survie globale en premiere ligne du cancer de la prostate metastatique synchrone. Dans cette situation, l’association de la SAd a l’abiraterone est egalement un standard therapeutique quel que soit le volume tumoral. Les donnees recentes amenent a recommander la SAd a une hormonotherapie de nouvelle generation (apalutamide ou enzalutamide) chez les patients metastatiques synchrones ou metachrones, quel que soit le volume tumoral. Le traitement local du cancer de la prostate par radiotherapie ameliore la survie des patients oligometastatiques synchrones. Le traitement cible des metastases est en cours d’evaluation. Chez les patients presentant un cancer de la prostate resistant a la castration (CPRC), l’apport des nouvelles therapies qui ont emerge ces dernieres annees aide a mieux controler la progression tumorale et a ameliorer la survie. Conclusion. Cette actualisation des recommandations francaises doit contribuer a ameliorer la prise en charge des patients porteurs d’un cancer de la prostate.

Objective: To understand the perception of quality of life, functionality, and psychological aspects of adults with lower limb sarcoma who underwent conservative surgery or amputation. Methods: Sociodemographic data were collected, and the following questionnaires were used: EORTC QLQ - C30 for quality of life, the Functional Assessment System (MSTS) for functionality and the Beck Depression Inventory (BDI) for depression symptoms. Results: The sample consisted of 45 young adults with sarcoma, divided into two groups: amputation (29) and conservative surgery (16). Most were male, single and students. Average family income before and after the disease did not differ, but those that were employed had a better perception of general quality of life, as well as those with higher family income after the disease. Regarding the type of surgery, there was a predominance of amputation; osteosarcoma was the most common histological type and the most affected region was the femur. All participants participated in social, cultural, sporting or religious activities. MSTS and Beck scale values did not differ between procedures. Conclusion: Given the scarcity of studies on the subject at the national level, further investigations are suggested to explore aspects related to quality of life for patients with sarcomas. Level of Evidence III, Retrospective comparative study. RESUMO Objetivo: Conhecer a percepção da qualidade de vida, funcionalidade e aspectos psicológicos de adultos com sarcoma de membros inferiores, submetidos à cirurgia conservadora ou amputação. Métodos: Foram coletados dados sociodemográficos, e utilizados os questionários: EORTC QLQ-C30 para a qualidade de vida; o Sistema de Avaliação Funcional (MSTS) para a funcionalidade; e o Inventário de Depressão de Beck (BDI) para sintomas de depressão. Resultados: A amostra foi constituída por 45 adultos jovens com sarcoma, divididos em dois grupos: amputação (29) e cirurgia conservadora (16). Predominaram jovens do sexo masculino, solteiros e estudantes. A média da renda familiar antes e após a doença não diferiu, porém os que estavam trabalhando apresentaram melhor percepção de qualidade de vida global, assim como os com maior renda familiar após a doença. Quanto ao tipo de cirurgia, houve predomínio da amputação, o osteossarcoma foi o tipo histológico mais comum e a região do fêmur a mais acometida. Todos os participantes participavam de atividades sociais, culturais, esportivas ou religiosas. Os valores do MSTS e da escala de Beck não diferiram entre os procedimentos. Conclusão: Visto a escassez de estudos sobre o tema em nível nacional, sugerem-se novas investigações, a fim de explorar aspectos relacionados com a qualidade de vida para pacientes com sarcomas. Nível de Evidência III, Estudo retrospectivo comparativo.

Objetivo: analisar as praticas de cuidado com a saude sexual de estudantes universitarias e a vulnerabilidade as infeccoes sexualmente transmissiveis e agravos de saude. Metodo: trata-se de estudo descritivo, quantitativo, realizado com uma amostra de 123 universitarias do Rio de Janeiro. Aplicou-se um questionario e os dados foram organizados em planilha do software Excel. Os achados foram analisados com aplicacao da estatistica descritiva. Resultados: As jovens iniciaram a vida sexual entre 16 e 18 anos; praticavam sempre sexo seguro, apenas 5,6% ja usou preservativo feminino; tinham parceiros fixos; faziam uso de preservativo com esses parceiros e fizeram o exame ginecologico recentemente. Conclusao: No grupo investigado existe um quantitativo expressivo de jovens assumindo um comportamento de risco. Os profissionais de saude e a enfermagem tem um importante papel na educacao em saude dos jovens, com estimulo para o autocuidado e cuidado com a saude sexual e reprodutiva.

Introduction: Histopathological analysis of the foreskin has become more common in the last two decades. Objectives: This study aims to analyze the morphology of the foreskin and determine the effects of topical corticosteroid therapy on this tissue. Materials and Methods: We retrospectively evaluated forty foreskin samples from children aged from 2 years to 15 years with phimosis undergoing circumcision at our institution over a 2-year period. In the foreskin samples, we analyzed the elastic fibers (Verhoeff), epidermal thickness (hematoxylin and eosin), and Annexin 1 and Langerhans cells (LCs) (immunohistochemistry). Results: In the present study, 18 (45%) patients made use of topical corticosteroids, and 22 (55%) did not, while 4 (10%) had a history of balanoposthitis as previous complication. Forty patients were divided according to the parameter analyzed: with or without previous complication and with or without previous topical corticotherapy. Annexin 1 expression was significantly higher in group with a history of complications when compared with group without complications (P = 0.024) and lower in the group of those who used corticosteroids when compared with those who did not used corticosteroids (P = 0.364). In the analysis of all samples, the density of mature LCs was significantly higher when compared with immature LCs (P < 0.0001). The density of immature LCs was significantly higher in patients without previous complications when compared with group with complications (P = 0.028). Conclusions: These findings contribute to a better understanding of the histopathological aspects of previous complications and of treatment with corticosteroids in children with phimosis.

Background The treatment of cutaneous leishmaniasis (CL) in Brazil using pentavalent antimony (Sbv) is associated with a high rate of failure. Miltefosine has proven efficacy for CL caused by L. braziliensis, with a cure rate (CR) of 75%. A combined treatment with granulocyte macrophage colony-stimulating factor (GM-CSF) and miltefosine could increase CR and decrease healing time. Methods A randomized, double-blind clinical trial to evaluate the efficacy of miltefosine combined with topical GM-CSF (M + GM) vs miltefosine and placebo (M + P) vs Sbv in 133 patients with CL caused by L. braziliensis in Bahia, Brazil. Results The final CR at 180 days after the initiation of treatment was 44.4% in the Sbv group, 76.6% in the M + P group (P = .003 vs Sbv), and 75.6% in the M + GM group (P = .004 vs Sbv). The median healing time for cure was 102 days for the Sbv group and 60 days for both miltefosine groups (P = .0009). During the 6-month follow-up period, 4 relapses were documented: 1 in the Sbv group, 1 in the M + P group, and 2 in the M + GM group. Mild adverse events occurred in 65% of patients from the Sbv group, 76% and 79% from the M + P and M + GM groups respectively. Conclusions Miltefosine is more effective than Sbv for the treatment of CL caused by L. braziliensis in Brazil and accelerates the healing time. Association with GM-CSF does not improve therapeutic outcome. Clinical Trials Registration NCT03023111., This was a randomized, double-blind trial to evaluate the efficacy of oral miltefosine combined with topical granulocyte macrophage colony-stimulating factor compared with monotherapy with miltefosine and standard pentavalent antimony in treating cutaneous leishmaniasis caused by Leishmania braziliensis in Brazil.

Resumo O Ministério da Saúde declarou em 03 de fevereiro de 2020 estado de emergência em saúde pública de importância nacional em decorrência da pandemia pelo novo coronavírus SARS-CoV-2. Com isso, o IBGE adiou a realização do Censo Demográfico de 2020 e passou a formular uma PNAD COVID-19. O inquérito contou com uma amostra total de 349 mil pessoas em cerca de 200 mil domicílios. Do total da população-residente brasileira, o IBGE estimou em maio/2020 que 24,0 milhões (11,4%) tiveram pelo menos um dos sintomas de síndrome gripal (SG). Desse contingente, 20,2 milhões (84,3% do total dos sintomáticos) não procuraram unidade de saúde. As inovações trazidas para a vigilância em saúde e o pioneirismo do IBGE demonstram ser possível, em um país continental e que vem experimentando diversas epidemias locais em momentos diferentes em seu território, que outros países também desenvolvam inquéritos domiciliares semelhantes, com coleta de dados semanal (referida às semanas epidemiológicas) por telefone de forma inovadora e tempestiva. A PNAD COVID-19 trouxe ainda uma nova tecnologia para o Instituto, resgatando o papel de avaliador externo do Sistema Único de Saúde (SUS).

Background Major postoperative morbidity after laparoscopic sleeve gastrectomy (LSG) is often related to staple line leaks (SLL). Of note, a recent study suggested a central role of the absolute numbers of stapler firings as a predictive factor for postoperative morbidity due to SLL. In addition, a larger gastric remnant volume could be responsible for lower weight loss after LSG, and nevertheless, the gastric resection volume (GRV) is strictly related to the residual volume. Methods Prospectively, collected data of 384 consecutive patients with complete follow-up at 12 months after LSG at our institution were retrospectively analyzed. Patients were stratified according to three different variables (i.e., number of stapler firings, GRV, and GRV/stapler firings-ratio), and respective impact on postoperative complications and weight loss was analyzed. Results High absolute number of stapler firings was linked to increased intraoperative and postoperative bleeding and prolonged hospitalization, but was not associated with SLL, transfusion rate or revisional procedures. Absolute GRV showed no impact on both complications and outcome after LSG. Interestingly, higher ratio of GRV/stapler firings was not only linked to decreased intraoperative bleeding and shorter hospital stay but also to higher Excess Body Mass Index Loss (EBMIL) at 12 months after LSG. Conclusions Here, we introduce GRV/stapler firings-ratio as a simple predictive factor for identifying patients at risk for postoperative complications and impaired weight loss that is superior compared with absolute number of stapler firings or GRV alone.

Aim To provide dynamic guidance from a rigorous and up-to-date consensus on the safe implementation and application of transanal total mesorectal excision (TaTME) from an international panel of expert surgeons and educationalists supported by 14 international surgical societies. Method An adapted Delphi method and focus group discussion approach was implemented for this consensus process, with expert advice from a guidelines methodologist. Statements were generated focusing on three main topics relating to the safe implementation of TaTME: (1) indications, (2) quality and outcome measures, (3) training and implementation of TaTME. Results Five rounds of the Delphi consensus process were completed over a 13-month period. A total of 56 surgeons experienced in TaTME and surgical education participated in this project. By Delphi round four, 80.0% or greater agreement was reached for all statements except for two, which were further reviewed during a fifth round. More complex cases that are likely to benefit from TaTME were identified, with the recommendation that they should be referred to TaTME expert centres. The most agreed upon definition of expert centres is outlined. Conclusion We have provided a current framework of best practice related to implementation of TaTME. The statements are not indefinite and will continue to be 'dynamic' and updated as new evidence emerges.

Resume Objectif Le but du Comite de Cancerologie de l’Association francaise d’urologie (CCAFU) est de proposer une mise a jour des recommandations dans la prise en charge du cancer de la prostate metastatique hormonosensible, a partir d’une revue systematique. Methodes Une revue systematique (Medline) de la litterature de 2018 a 2020 a ete conduite par le CCAFU en evaluant les references par leur niveau de preuve. Resultats Plusieurs formes peuvent etre definies a ce stade de la maladie en fonction du risque evolutif, du volume metastatique, et du caractere synchrone ou metachrone des metastases. La suppression androgenique (SAd) reste le traitement de fond au stade metastatique. Le docetaxel associe a la SAd ameliore la survie globale en premiere ligne du cancer de la prostate metastatique synchrone. Dans cette situation, l’association de la SAd a l’abiraterone est egalement un standard therapeutique quel que soit le volume tumoral. Les donnees recentes amenent a recommander une hormonotherapie de nouvelle generation (apalutamide ou enzalutamide) en association a la SAd chez les patients metastatiques synchrones ou metachrones, quel que soit le volume. Le traitement local du cancer de la prostate par radiotherapie ameliore la survie des patients oligometastatiques synchrones. Le traitement cible des metastases est en cours d’evaluation. Conclusion Cette actualisation des recommandations francaises doit contribuer a ameliorer la prise en charge des patients porteurs d’un cancer de la prostate.

This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.

Care for patients with cardiac arrest in the context of the coronavirus disease 2019 (COVID-19) pandemic has several unique aspects that warrant particular attention. This joint position statement by the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Society of Cardiology (SBC), Brazilian Association of Intensive Care Medicine (AMIB), and Brazilian Society of Anesthesiology (SBA), all official societies representing the corresponding medical specialties affiliated with the Brazilian Medical Association (AMB), provides recommendations to guide health care workers in the current context of limited robust evidence, aiming to maximize the protection of staff and patients alike. It is essential that full aerosol precautions, which include wearing appropriate personal protective equipment, be followed during resuscitation. It is also imperative that potential causes of cardiac arrest of particular interest in this patient population, especially hypoxia, cardiac arrhythmias associated with QT prolongation, and myocarditis, be considered and addressed. An advanced invasive airway device should be placed early. Use of HEPA filters at the bag-valve interface is mandatory. Management of cardiac arrest occurring during mechanical ventilation or during prone positioning demands particular ventilator settings and rescuer positioning for chest compressions which deviate from standard cardiopulmonary resuscitation techniques. Apart from these logistical issues, care should otherwise follow national and international protocols and guidelines, namely the 2015 International Liaison Committee on Resuscitation (ILCOR) and 2019 American Heart Association (AHA) guidelines and the 2019 Update to the Brazilian Society of Cardiology Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Guideline.

Variants of vitamin D metabolism-genes may predispose to type 2 diabetes (T2D). This study investigated the impact of these variants on disease susceptibility, Vitamin D, parathyroid hormone, C-peptide and HbA1c levels before and after cholecalciferol supplementation in patients with T2D.Twelve polymorphisms within CYP2R1, CYP27B1, DBP, VDR and CYP24A1 were genotyped in 553 T2D patients and 916 controls. In addition 65 patients receiving either cholecalciferol or placebo were analyzed during 6 months intervention and 6 months follow-up.T2D risk alleles are VDR rs7975232 “G” (pc=0.031), rs1544410 “G” (pc=0.027) and CYP2R1 rs10741657 “A” (pc=0.016). Patients with genotypes CYP27B1 rs10877012 “CC” (pc=4x10-5), DBP rs7041 “GG” (pc=0.003), rs4588 “CC” (pc = 3x10-4), CYP24A1 rs2585426 “CG” (pc=0.006) and rs2248137 “CG” (pc=0.001) showed lower 25(OH)D3 and DBP rs4588 “CC” lower 1,25(OH)2D3 levels (pc=0.005). Whereas DBP rs4588 “CC” (pc=0.009), CYP27B1 rs10877012 “AC” (pc=0.059), VDR rs7975323 “AG” (pc=0.033) and rs1544410 “GG” (pc=0.013) are associated with higher 25(OH)D3 levels at 6 months’ follow-up. Significant PTH suppression was detected for CYP2R1 “AG“ (pc=0.002), DBP rs4588 “CC” (pcGenetic variants of the vitamin D system predispose to type 2 diabetes and regulate – partially - vitamin D metabolism, concentrations and the vitamin D status. Vitamin D insufficiency is a T2D risk factor. The response to cholecalciferol supplementation can be measured as 25(OH)D3 increment and PTH suppression. This process is regulated by genes of the vitamin D system conferring modest T2D risk.

Significance: Regular exercise training can reduce myocardial damage caused by acute ischemia/reperfusion (I/R). Exercise can reproduce the phenomenon of ischemic preconditioning, due to the capacity of brief periods of ischemia to reduce myocardial damage caused by acute I/R. In addition, exercise may also activate the multiple kinase cascade responsible for cardioprotection even in the absence of ischemia. Recent Advances: Animal and human studies highlighted the fact that, besides to reduce risk factors related to cardiovascular disease, the beneficial effects of exercise are also due to its ability to induce conditioning of the heart. Exercise behaves as a physiological stress that triggers beneficial adaptive cellular responses, inducing a protective phenotype in the heart. The factors contributing to the exercise-induced heart preconditioning include stimulation of the anti-radical defense system and nitric oxide production, opioids, myokines, and adenosine-5'-triphosphate (ATP) dependent potassium channels. They appear to be also involved in the protective effect exerted by exercise against cardiotoxicity related to chemotherapy. Critical Issues and Future Directions: Although several experimental evidences on the protective effect of exercise have been obtained, the mechanisms underlying this phenomenon have not yet been fully clarified. Further studies are warranted to define precise exercise prescriptions in patients at risk of myocardial infarction or undergoing chemotherapy.

Highlights • There are 170 cases of post colonoscopy splenic injury reported in the literature. • Management should be dictated by the patient’s clinical status and adhere to traumatic blunt splenic injury guidelines. • Awareness of risk factors and post-procedure vigilance leads to prompt detection and intervention for this rare complication., Introduction Splenic trauma is quite rare after colonoscopy and can be overlooked as a complication when a patient presents with severe abdominal pain. It can be difficult to diagnose without appropriate imaging, but it should be considered as part of the differential in a patient arriving for evaluation of left upper quadrant abdominal pain. Presentation of case In this case series, we discuss four patients who presented to our institution with splenic trauma specifically after colonoscopy. These patients were diagnosed with splenic trauma utilizing computed tomography (CT) scans of the abdomen and pelvis. They were all immediately transferred to our surgical intensive care unit (SICU) for close monitoring and serial hemoglobin checks. Two of the four patients had decreasing hemoglobin levels and were monitored until they underwent interventional radiology (IR) angiography and angioembolization. The other two patients had significant transfusion requirements and ultimately went to the operating room for an open splenectomy. All four of these patients did well after their interventions, although one of them required longer hospitalization while on the ventilator secondary to Haemophilus infection. Discussion This case series recognizes that there is potential for quite severe splenic trauma after colonoscopy. While one of the four patients did have a history of prior splenic trauma, the other three had no history of trauma. Conclusion These cases demonstrate that this complication should be managed similarly to traumatic splenic injury unrelated to colonoscopy, and that non-operative treatment remain a possibility. Certainly, non-operative management requires a SICU and IR capabilities to be successful. If the patient becomes unstable, they should undergo the appropriate operative intervention.

espanolObjetivo: Examinar los efectos del entrenamiento en intervalico de alta intensidad (HIIT) sobre los indicadores de grasa corporal en adultos con sobrepeso u obesidad. Metodos: Se incluyeron ensayos aleatorios en la revision sistematica. Se examinaron medidas directas (p. Ej., Grasa corporal total) e indirectas (p. Ej., Circunferencia de la cintura). Resultados: De 1156 articulos encontrados inicialmente, se incluyeron 24. La mayoria de los estudios se realizaron, al menos, durante 10 semanas. El entrenamiento en intervalico de alta intensidad provoco reducciones en todos los indicadores de grasa corporal. Los modelos metaanaliticos mostraron diferencias significativas despues de la intervencion com entrenamiento en intervalico de alta intensidad en el peso corporal, la masa grasa y el porcentaje de grasa. Por otro lado, el indice de masa corporal y la circunferencia de la cintura no presentaron cambios significativos. Conclusiones: El entrenamiento fisico de alta intensidad puede inducir mejoras en la composicion corporal en personas con sobrepeso y obesidad. El entrenamiento en intervalico de alta intensidad puede ser un componente tempo-eficiente en los programas de control de peso. EnglishObjective: To examine the effects of high-intensity interval training on body fat indicators in overweight and obese adults. Methods: Randomized trials were included in the systematic review. Direct measures (e.g. whole-body fat) and indirect measures (e.g. waist circumference) were examined. Results: From 1156 articles initially screened, 24 were included. The majority of studies were conducted, at least, for 10 weeks. High-intensity interval training elicited reductions in whole- body fat indicators. The meta-analytic models showed significant differences after high-intensity interval training intervention among body weight, fat mass and fat percentage. On the other hand, body mass index and waist circumference did not present significant results. Conclusions: High-intensity exercise training can induce body composition improvements in overweight and obese individuals. High-intensity interval training may be a time-efficient component of weight management programs. portuguesObjetivo: Examinar os efeitos do treinamento intervalado de alta intensidade (HIIT) nos indicadores de gordura corporal em adultos com sobrepeso ou obesidade. Metodos: Ensaios randomizados foram incluidos na revisao sistematica. Medidas diretas (por exemplo, gordura corporal) e medidas indiretas (por exemplo, circunferencia da cintura) foram examinadas. Resultados: Dos 1156 artigos selecionados inicialmente, 24 foram incluidos. A maioria dos estudos foi realizada, pelo menos, por 10 semanas. O treinamento intervalado de alta intensidade provocou reducoes nos indicadores de gordura corporal. Os modelos meta-analiticos mostraram diferencas significativas apos a intervencao com treinamento intervalado de alta intensidade entre peso corporal, massa gorda e porcentagem de gordura. Por outro lado, o indice de massa corporal e a circunferencia da cintura nao apresentaram resultados significativos. Conclusoes: O treinamento fisico de alta intensidade pode induzir melhorias na composicao corporal em individuos com sobrepeso e obesidade. O treinamento intervalado de alta intensidade pode ser um componente eficiente em termos de tempo dos programas de controle de peso.