Unravelling the role of beta-CGRP in inflammatory bowel disease and its potential role in gastrointestinal homeostasis.

BACKGROUND: The role of beta calcitonin gene-related peptide (beta-CGRP) in gastrointestinal tract is obscure, but experimental models suggest an effect on the homeostasis of the intestinal mucosa. We measured beta-CGRP circulating levels in a large series of subjects with a recent diagnosis of inflammatory bowel disease (IBD), in order to assess the potential role of this neuropeptide in IBD pathogenesis. METHODS: Morning serum beta-CGRP levels were measured by ELISA (CUSABIO, China) in 96 patients recently diagnosed of IBD and compared with those belonging from 50 matched healthy controls (HC) and 50 chronic migraine (CM) patients. RESULTS: Beta-CGRP levels were lower in patients with IBD (3.1 ± 1.9 pg/mL; 2.9 [2.4-3.4] pg/mL) as compared to HC (4.7 ± 2.6; 4.9 [4.0-5.8] pg/mL; p < 0.001) and to CM patients (4.6 ± 2.6; 4.7 [3.3-6.2] pg/mL; p < 0.001). Beta-CGRP levels in CM were not significantly different to those of HC (p = 0.92). Regarding IBD diagnostic subtypes, beta-CGRP levels for ulcerative colitis (3.0 ± 1.9pg/mL; 2.5 [2.1-3.4] pg/mL) and Crohn's disease (3.3 ± 2.0 pg/mL; 3.2 [2.4-3.9] pg/mL) were significantly lower to those of HC (p < 0.01 and p < 0.05, respectively) and CM (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: We have found a significant reduction in serum beta-CGRP levels in patients with a recent diagnosis of all kinds of IBD as compared to two control groups without active intestinal disease, HC and CM, which may suggest a role for this neuropeptide in the pathophysiology of IBD. Our data indicate a protective role of beta-CGRP in the homeostasis of the alimentary tract.

Improving quality of care by standardising patient data collection in electronic medical records in an oncology department in Spain.

BACKGROUND: Evaluation of quality of care in oncology is key in ensuring patients receive adequate treatment. American Society of Clinical Oncology's (ASCO) Quality Oncology Practice Initiative (QOPI) Certification Program (QCP) is an international initiative that evaluates quality of care in outpatient oncology practices. METHODS: We retrospectively reviewed free-text electronic medical records from patients with breast cancer (BR), colorectal cancer (CRC) or non-small cell lung cancer (NSCLC). In a baseline measurement, high scores were obtained for the nine disease-specific measures of QCP Track (2021 version had 26 measures); thus, they were not further analysed. We evaluated two sets of measures: the remaining 17 QCP Track measures, as well as these plus other 17 measures selected by us (combined measures). Review of data from 58 patients (26 BR; 18 CRC; 14 NSCLC) seen in June 2021 revealed low overall quality scores (OQS)-below ASCO's 75% threshold-for QCP Track measures (46%) and combined measures (58%). We developed a plan to improve OQS and monitored the impact of the intervention by abstracting data at subsequent time points. RESULTS: We evaluated potential causes for the low OQS and developed a plan to improve it over time by educating oncologists at our hospital on the importance of improving collection of measures and highlighting the goal of applying for QOPI certification. We conducted seven plan-do-study-act cycles and evaluated the scores at seven subsequent data abstraction time points from November 2021 to December 2022, reviewing 404 patients (199 BR; 114 CRC; 91 NSCLC). All measures were improved. Four months after the intervention, OQS surpassed the quality threshold and was maintained for 10 months until the end of the study (range, 78-87% for QCP Track measures; 78-86% for combined measures). CONCLUSIONS: We developed an easy-to-implement intervention that achieved a fast improvement in OQS, enabling our Medical Oncology Department to aim for QOPI certification.

Impact of Clonal Hematopoiesis-Associated Mutations in Phase I Patients Treated for Solid Tumors: An Analysis of the STING Trial.

PURPOSE: With liquid biopsy's widespread adoption in oncology, an increased number of clonal hematopoiesis-associated mutations (CHm) have been identified in patients with solid tumors. However, its impact on patient outcomes remains unclear. This study aimed to analyze and describe CHm in a cohort of phase I patients. METHODS: Retrospective data collection from medical records and molecular profiles (Foundation One Liquid CDx Assay) was performed before first study drug administration at the Drug Development Department of Gustave Roussy (France) within the STING trial (ClinicalTrials.gov identifier: NCT04932525). CHm prevalence was assessed using any and ≥1% variant allele frequency (VAF) in epigenetic modifier genes (DNMT3A, TET2, and ASXL1). RESULTS: From January 2021 to December 2022, 255 patients were enrolled in a phase I clinical trial. A total of 55% were male, with a median age of 62 years (24-86). Principal tumor locations were GI (27%) and genitourinary (21%). Overall, 104 patients (41%) had at least one CHm in liquid biopsy, with 55 patients (22%) having a VAF of ≥ 1%. The most frequent mutation was DNMT3A 73% at any VAF (n = 76) and 22% at 1% VAF (n = 23). Median progression-free survival (PFS) and overall survival were 3.8 months (m) for the CHm group versus 3.2 m for nonclonal hematopoiesis (CH; P = .08) and 18.26 m CHm versus 15.8 m non-CH (P = .9), respectively. PFS increased in the CHm population treated with targeted therapy (hazard ratio, 0.6 [95% CI, 0.42 to 0.84]; P = .004). CONCLUSION: CHm was commonly found in patients with solid tumors treated in phase I trials, with a prevalence of 41% in our cohort. The most frequently mutated gene was DNMT3A. The presence of CHm had no impact on the population of patients treated in the phase I trials.

Relato de caso: persistência da artéria isquiática completa bilateral associada à degeneração aneurismática / Case report: persistent bilateral complete sciatic artery associated with aneurysmal degeneration

Resumo A persistência da artéria isquiática é uma anomalia congênita rara, com poucos casos descritos na literatura. Este estudo tem como objetivo apresentar a variação embriológica observada no sistema circulatório de membros inferiores da paciente observada. A descrição anatômica foi realizada a partir da revisão de prontuário e exames de imagem. O presente caso relata uma paciente feminina, de 63 anos de idade, admitida em serviço de pronto atendimento com queixa de dor importante em membro inferior direito, com extremidade fria e pálida e presença de equimose em dorso do pé. Realizou-se duplex scan que evidenciou ausência de fluxo detectável nas artérias tibial anterior e fibular, e padrão tardus parvus na artéria tibial posterior. A paciente evoluiu com perda de movimentação e cianose fixa no pé direito e foi encaminhada para tromboembolectomia de urgência, entretanto, após o procedimento, não foi visualizado reperfusão adequada. No primeiro pós-operatório, foi realizada angiotomografia, que evidenciou persistência da artéria isquiática bilateralmente, com degeneração aneurismática parcialmente trombosada e ausência de opacificação do sistema arterial à jusante do aneurisma. No terceiro dia pós-operatório, a paciente apresentava áreas de necrose seca em membro, sem perfusão até tornozelo, e foi submetida à amputação transfemoral. Apesar de ser uma condição rara, apresenta grande importância clínica devido a suas altas taxas de complicações.

Abstract Persistent sciatic artery is a rare congenital anomaly, with few cases described in the literature. This study presents a case of this embryological variation observed in a patient's lower limb circulatory system. The anatomical description is based on a review of medical records and imaging exams. This case report describes a 63-year-old female patient admitted to the emergency department complaining of severe pain in the right lower limb, with a cold, pale extremity and ecchymosis on the dorsum of the foot. Duplex ultrasound showed no detectable flow in the anterior tibial and fibular arteries and a tardus parvus pattern in the posterior tibial artery. The patient developed loss of movement and fixed cyanosis in the right foot and was referred for urgent thromboembolectomy. However, adequate reperfusion was not seen after the procedure. Angiotomography was performed on the first postoperative day, showing bilateral persistence of the sciatic artery, with aneurysmal degeneration, partially thrombosed, and no opacification of the arterial system downstream of the aneurysm. By the third postoperative day, the patient had developed areas of dry necrosis in the limb, with no perfusion to the ankle, and underwent transfemoral amputation. Despite being a rare condition, it is of great clinical importance because of the high complication rates.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors.

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.

Efficacy, safety and prognostic factors in patients with refractory metastatic colorectal cancer treated with trifluridine/tipiracil plus bevacizumab in a real-world setting.

We evaluated the efficacy and safety of trifluridine/tipiracil (TAS-102) plus bevacizumab in treating refractory metastatic colorectal cancer (mCRC) in a retrospective, observational study. Patients refractory or intolerant to standard therapies received TAS-102 (30-35 mg/m2 twice daily on days 1-5 and days 8-12 every 28 days) plus bevacizumab 5 mg/kg on days 1 and 15. Clinical and pathological characteristics, overall response rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) data were collected and analysed. Thirty-five patients were treated from July 2019 to October 2021 (median age 64 years). The majority of patients (68.6%) were receiving TAS-102 plus bevacizumab as third-line treatment. Patients received a median of 4 (range 2-15) cycles of treatment. Among 31 patients evaluable for response (88.6%), ORR and DCR were 3.2% and 51.6%, respectively. After a median 11.6 months' follow-up, median PFS was 4.3 (95% confidence interval [CI] 3.4-5.1) months and median OS was 9.3 (95% CI 6.6-12.1) months. The most common grade 3-4 toxicities were neutropenia, asthenia and nausea/vomiting, and there were no treatment-related deaths. This real-world study confirms the efficacy and safety of TAS-102 plus bevacizumab in patients with refractory mCRC.

Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen.

BACKGROUND: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. MATERIALS AND METHODS: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. RESULTS: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). CONCLUSIONS: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.

Impact of chronic exposure of rats to bisphenol A from perinatal period to adulthood on intraprostatic levels of 5α-reductase isozymes, aromatase, and genes implicated in prostate cancer development.

The synergetic effect of estrogens and androgens is known to play a crucial role in the physiopathology of the prostate gland. Bisphenol A (BPA) is an endocrine disrupting compound that can interfere with endocrine hormone functioning and thereby influence prostate development. The objective of this study was to examine the impact on prostate expression of aromatase, 5α-R isozymes, and prostate cancer-related genes of exposure to low doses of BPA from perinatal period to adulthood. Vehicle or BPA (2.5 µg/kg b.w./day) was administered to gestating Wistar rats from gestational day 12 (GD12) to parturition and then to their male pups from postnatal day 1 (PND1) until euthanization on PND90. Their prostate glands were examined by qRT-PCR, Western blot, PCR array, and morphological study. mRNA and protein levels of 5α-R2 were significantly reduced and mRNA and protein levels of aromatase were significantly increased in BPA-treated animals, which also showed modifications of 8 out of the 84 key genes implicated in the development of prostate cancer. Because BPA interferes with genes involved in intraprostatic androgen and estrogen production and others implicated in prostate cancer, research is warranted into the prostate disease risk associated with chronic low-dose BPA exposure throughout life.

Surgery due to Inflammatory Bowel Disease During Pregnancy: Mothers and Offspring Outcomes From an ECCO Confer Multicentre Case Series [Scar Study].

AIMS: i] To evaluate the evolution of pregnancies and offspring after inflammatory bowel disease [IBD] surgery during pregnancy; and ii] to describe the indications, the surgical techniques, and the frequency of caesarean section concomitant with surgery. METHODS: Patients operated on due to IBD during pregnancy after 1998 were included. Participating clinicians were asked to review their databases to identify cases. Data on patients' demographics, IBD characteristics, medical treatments, IBD activity, pregnancy outcomes, surgery, delivery, and foetal and maternal outcomes, were recorded. RESULTS: In all, 44 IBD patients were included, of whom 75% had Crohn's disease; 18% of the surgeries were performed in the first trimester, 55% in the second, and 27% in the third trimester. One patient had complications during surgery, and 27% had postsurgical complications. No patient died. Of deliveries, 70% were carried out by caesarean section. There were 40 newborns alive. There were four miscarriages/stillbirths [one in the first, two in the second, and one in the third trimester]; two occurred during surgery, and another two occurred 2 weeks after surgery; 14% of the surgeries during the second trimester and 64% of those in the third trimester ended up with a simultaneous caesarean section or vaginal delivery. Of the 40 newborns, 61% were premature and 47% had low birth weight; 42% of newborns needed hospitalisation [25% in the intensive care unit]. CONCLUSIONS: IBD surgery during pregnancy remains an extremely serious situation. Therefore, surgical management should be performed in a multidisciplinary team, involving gastroenterologists, colorectal surgeons, obstetricians, and neonatal specialists.

Disposição a pagar e Método de Valoração Contingente na avaliação econômica de serviços farmacêuticos / Willingness to pay and Contingent Valuation Method in the economic evaluation of pharmacy services

Objetivo: Sintetizar os principais pontos abordados em investigações de Disposição a Pagar (DAP) por serviços farmacêuticos, com foco no Método de Valoração Contingente (MVC). Métodos: Foi realizada uma revisão não sistemática com recuperação e análise de manuscritos publicados até novembro de 2020. A busca por estudos ocorreu nas bases MEDLINE, LILACS e SciELO. Resultados: Foram discutidos os fundamentos teóricos e processos metodológicos da análise, apresentando o MVC como principal perspectiva de abordagem. Enquanto delineamento do questionário, é sugerida uma estrutura que apresente, sequencialmente, os elementos: "conhecimento do participante sobre a intervenção", "apresentação da intervenção", "cenário hipotético", "pergunta DAP", "estado de saúde percebido" e "informações socioeconômicas". No mais, é enfatizada a importância da execução de etapas de validação, tanto do instrumento quanto da avaliação. Conclusão: Avaliar a preferência declarada da população por serviços farmacêuticos é uma estratégia ainda limitada. Se realizado adequadamente, esse tipo de investigação pode auxiliar gestores e tomadores de decisão no processo de implementação de novas tecnologias de cuidado.

Objective: To synthesize key points addressed in investigations of Willingness to Pay (WTP) for pharmaceutical care services, focusing on the Contingent Valuation Method (CVM). Methods: We performed a non-systematic review with recovery and analysis of manuscript published until November 2020. Three databases were majorly searched, including MEDLINE, LILACS and SciELO. Results: The theoretical foundations and methodological process were discussed, presenting the CVM as the main perspective. For questionnaire design, is suggested a structure that sequentially presents the elements: "participant knowledge on intervention", "intervention presentation", "hypothetical scenario", "WTP question", "perceived health status", and "socioeconomic information". In addition, we emphasize the importance of executing validation steps for the instrument of measurement as well as the evaluation process. Conclusion: Assessing the population's declared preference for pharmaceutical services is still a limited strategy. If carried out properly, this type of investigation can help managers and decision makers in the process of implementing technologies of care.

Experienciando a gravidez em idade materna avançada em hospital privado / Experiencing pregnancy at an advanced maternal age in a private hospital

Objetivo: descrever as experiências de gestantes em idade materna avançada atendidas em hospital privado. Métodos:estudo qualitativo, realizado com 17 mulheres, por meio de entrevistas semiestruturadas via telefone. Os dados foram submetidos à Análise de Conteúdo Temática. Resultados: as participantes tinham idades entre 35 e 40 anos. Emergiram duas categorias: Experienciando a gestação como casal e família: o preparo do casal para a gestação e o parto (Gesta-ção a partir dos 35 anos como elemento de potencialidade; Mudança na rotina da família para a chegada do bebê) e Vi-venciando a gestação e suas alterações: percebendo a gesta-ção como uma vivência saudável e tranquila (Alteração dos padrões emocionais relacionados ao processo gestacional). Conclusão: vivenciar a gestação tardiamente não foi uma preocupação para as mulheres. A maturidade e as condições socioeconômicas favoráveis podem ter influência proteti-va para o transcorrer de gestações saudáveis em mulheres atendidas no serviço privado de saúde. (AU)

Impact of Biological Agents on Postsurgical Complications in Inflammatory Bowel Disease: A Multicentre Study of Geteccu.

BACKGROUND: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. AIMS: To evaluate the impact of biologics on the risk of PC. METHODS: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered "exposed". The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. RESULTS: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5; 95% CI: 1.2-2.0), urgent surgery (OR: 1.6; 95% CI: 1.2-2.2), laparotomy approach (OR: 1.5; 95% CI: 1.1-1.9) and severe anaemia (OR: 1.8; 95% CI: 1.3-2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2; 95% CI: 0.97-1.58), although it could be a risk factor for postoperative infections (OR 1.5; 95% CI: 1.03-2.27). CONCLUSIONS: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

COVID-19 e organizações: estratégias de enfrentamento para redução de impactos / COVID-19 and organizations: coping strategies to reduce impacts / COVID-19 y organizaciones: estrategias de afrontamiento para reducción de los impactos

As organizações sofrem com os impactos socioeconômicos do cenário de crise global provocados pela pandemia de COVID-19. Nesse contexto é primordial adotar medidas objetivas para minimizar os reflexos nocivos dentro da gestão organizacional. Este estudo buscou identificar as principais estratégias para redução de impactos da COVID-19 nas organizações brasileiras. Trata-se de um ensaio teórico baseado em uma revisão de literatura, através de análise de artigos de bases a partir de dados nacionais e internacionais sobre a COVID-19, bem como investigação relacionada às experiências em pandemias anteriores, assim como a legislação brasileira vigente no período pandêmico. Considerando esse cenário de incertezas, sugere-se a adoção de estratégias para minimizar impactos desfavoráveis às atividades corporativas, tais como: comunicação eficiente; planejamento do trabalho; aprimoramento digital; tele-trabalho; adoção de medidas visando o bem-estar dos trabalhadores. Identificou-se a necessidade de planejamentos emergenciais para o enfrentamento da pandemia, incluindo: políticas empáticas, fornecimento de suporte para tele-trabalho e ações para adaptação e manutenção organizacional durante a crise.

Organizations have suffered from the socioeconomic impacts of the global crisis scenario caused by the COVID-19 pandemic. In this context, it is essential to adopt objective measures to minimize harmful effects on organizational management. This study sought to identify the main strategies for reducing the impacts of COVID-19 on Brazilian organizations. It is a theoretical essay based on a literature review of articles from national and international databases, covering COVID-19, experiences in previous pandemics, as well as Brazilian legislation in force during the pandemic period. Considering this scenario of uncertainties, it is suggested to adopt strategies to minimize unfavorable impacts on corporate activities, such as efficient communication, work planning, digital enhancement, teleworking, and adoption of measures aimed at the welfare of workers. The need for emergency planning to face the pandemic was identified, with measures including empathic policies, provision of support for telework, and actions for adaptation and organizational maintenance during the crisis.

Las organizaciones sufren los impactos socioeconómicos del escenario de crisis global causado por la pandemia de COVID-19. En este contexto es esencial adoptar medidas objetivas para minimizar los efectos nocivos dentro de la gestión organizacional. Este estudio buscó identificar las principales estrategias para reducir los impactos de la COVID-19 en las organizaciones brasileñas. Es un ensayo teórico basado en una revisión de literatura, a través del análisis en artículos de bases a partir de datos nacionales e internacionales sobre COVID-19, bien como investigación relacionada a las experiencias en pandemias anteriores, así como la legislación brasileña vigente en el período de la pandemia. Considerando este escenario de incertidumbres, se sugiere la adopción de estrategias para minimizar los impactos desfavorables en las actividades corporativas, tales como: comunicación eficiente; planificación del trabajo; mejora digital; teletrabajo; adopción de medidas destinadas al bienestar de los trabajadores. Se identificó la necesidad de una planificación de emergencia para enfrentar la pandemia, que incluye: políticas empáticas, provisión de apoyo para el teletrabajo y acciones para la adaptación y el mantenimiento de la organización durante la crisis.

Early removal of indwelling urinary catheter after radical surgery for early-stage cervical cancer-A cohort study.

OBJECTIVE: To evaluate the difference between early and delayed removal of indwelling urinary catheter after radical hysterectomy (RH) or radical trachelectomy (RT). METHODS: An ambispective study was conducted in early-stage cervical cancer patients who underwent RH or RT. Delayed indwelling urinary catheter removal occurred on a postoperative day (POD) 7 in the retrospective group (January 2012-November 2013), and early removal occurred on POD 1 in the prospective group (May 2014-June 2017). The postvoid residual (PVR) test was performed after indwelling catheter removal in both groups. RESULTS: Our sample included 47 patients in the delayed group and 48 in the early one. There was no difference in age, body mass index, tumor size, histology, stage, surgical approach, and intraoperative and postoperative complications. Indwelling urinary catheter reinsertion was needed in 16 (34%) patients in the delayed group and 12 (25%) in the early group (P = .37), with no statistical difference between the median PVR volumes -82.5 and 45 mL (P = .06), respectively. Seven (14.9%) patients in the delayed group presented with 30-day urinary tract infection vs two (4.2%) in the early group (P = .09). CONCLUSIONS: Early indwelling urinary catheter removal, in regard to the rate of catheter reinsertion and PVR volume, does not differ from delayed removal.

Effect of Nitrosative Stress on the S-Nitroso-Proteome of Paracoccidioides brasiliensis.

The fungi Paracoccidioides brasiliensis and Paracoccidioides lutzii are the causative agents of paracoccidioidomycosis (PCM), a systemic mycosis endemic to Latin America. This fungus is considered a facultative intracellular pathogen that is able to survive and replicate inside macrophages. The survival of the fungus during infection depends on its adaptability to various conditions, such as nitrosative/oxidative stress produced by the host immune cells, particularly alveolar macrophages. Currently, there is little knowledge about the Paracoccidioides spp. signaling pathways involved in the fungus evasion mechanism of the host defense response. However, it is known that some of these pathways are triggered by reactive oxygen species and reactive nitrogen species (ROS/RNS) produced by host cells. Considering that the effects of NO (nitric oxide) on pathogens are concentration dependent, such effects could alter the redox state of cysteine residues by influencing (activating or inhibiting) a variety of protein functions, notably S-nitrosylation, a highly important NO-dependent posttranslational modification that regulates cellular functions and signaling pathways. It has been demonstrated by our group that P. brasiliensis yeast cells proliferate when exposed to low NO concentrations. Thus, this work investigated the modulation profile of S-nitrosylated proteins of P. brasiliensis, as well as identifying S-nitrosylation sites after treatment with RNS. Through mass spectrometry analysis (LC-MS/MS) and label-free quantification, it was possible to identify 474 proteins in the S-nitrosylated proteome study. With this approach, we observed that proteins treated with NO at low concentrations presented a proliferative response pattern, with several proteins involved in cellular cycle regulation and growth being activated. These proteins appear to play important roles in fungal virulence. On the other hand, fungus stimulated by high NO concentrations exhibited a survival response pattern. Among these S-nitrosylated proteins we identified several potential molecular targets for fungal disease therapy, including cell wall integrity (CWI) pathway, amino acid and folic acid metabolisms. In addition, we detected that the transnitrosylation/denitrosylation redox signaling are preserved in this fungus. Finally, this work may help to uncover the beneficial and antifungal properties of NO in the P. brasiliensis and point to useful targets for the development of antifungal drugs.

The Harvey-Bradshaw Index Adapted to a Mobile Application Compared with In-Clinic Assessment: The MediCrohn Study.

Objectives: Mobile apps are useful tools in e-health and self-management strategies in disease monitoring. We evaluated the Harvey-Bradshaw index (HBI) mobile app self-administered by the patient to see if its results agreed with HBI in-clinic assessed by a physician. Methods: Patients were enrolled in a 4-month prospective study with clinical assessments at months 1 and 4. Patients completed mobile app HBI and within 48 h, HBI was performed by a physician (gold standard). HBI scores characterized Crohn's disease (CD) as remission <5 or active ≥5. We determined agreement per item and total HBI score and intraclass correlation coefficients (ICCs). Bland-Altman plot was performed. HBI changes in disease activity from month 1 to month 4 were determined. Results: A total of 219 patients were enrolled. All scheduled assessments (385 pairs of the HBI questionnaire) showed a high percentage of agreement for remission/activity (92.4%, κ = 0.796), positive predictive value (PPV) for remission of 98.2%, and negative predictive value of 76.7%. High agreement was also found at month 1 (93.15%, κ = 0.82) and month 4 (91.5%, κ = 0.75). Bland-Altman plot was more uniform when the HBI mean values were <5 (remission). ICC values were 0.82, 0.897, and 0.879 in all scheduled assessments, 1 and 4 months, respectively. Conclusions: We found a high percentage of agreement between patients' self-administered mobile app HBI and in-clinic physician assessment to detect CD activity with a remarkably high PPV for remission. The mobile app HBI might allow a strict control of inflammation by remote monitoring and flexible follow-up of CD patients. Reduction of sanitary costs could be possible.

Ovarian Sertoli-Leydig Cell Tumors: Epidemiological, Clinical and Prognostic Factors.

OBJECTIVE: To describe a series of cases of ovarian Sertoli-Leydig cell tumors (SLCTs). METHODS: Retrospective review of 12 cases of SLCT treated at the Hospital do Câncer de Barretos, Barretos, state of São Paulo, Brazil, between October 2009 and August 2017. RESULTS: The median age of the patients was 31 years old (15-71 years old). A total of 9 patients (75.0%) presented symptoms: 8 (66.7%) presented with abdominal pain, 5 (41.7%) presented with abdominal enlargement, 2 (16.7%) presented with virilizing signs, 2 (16.7%) presented with abnormal uterine bleeding, 1 (8.3%) presented with dyspareunia, and 1 (8.3%) presented with weight loss. The median preoperative lactate dehydrogenase (LDH) was 504.5 U/L (138-569 U/L), alpha-fetoprotein (AFP) was 2.0 ng/ml (1.1-11.3 ng/ml), human chorionic gonadotropin (ß-hCG) was 0.6 mUI/ml (0.0-2.3 mUI/ml), carcinoembryonic antigen (CEA) was 0.9 ng/ml (0.7-3.4 ng/ml), and cancer antigen 125 (CA-125) was 26.0 U/ml (19.1-147.0 U/ml). All of the tumors were unilateral and surgically treated. Lymphadenectomy was performed in 3 (25.0%) patients, but none of the three patients submitted to lymphadenectomy presented lymph node involvement. In the anatomopathological exam, 1 (8.3%) tumor was well-differentiated, 8 (66.7%) were moderately differentiated, and 3 (25.0%) were poorly differentiated. A total of 5 (55.6%) tumors were solid-cystic, 2 (22.2%) were purely cystic, 1 (11.1%) was cystic with vegetations, and 1 (11.1%) was purely solid, but for 3 patients this information was not available. The median lesion size was 14.2 cm (3.2-23.5 cm). All of the tumors were at stage IA of the 2014 classification of the International Federation of Gynecology and Obstetrics (FIGO). A total of 2 (16.7%) patients received adjuvant treatment; 1 of them underwent 3 cycles of paclitaxel and carboplatin every 21 days, and the other underwent 4 cycles of ifosfamide, cisplatin and etoposide every 21 days. None of all of the patients had recurrence, and one death related to complications after surgical staging occurred. CONCLUSION: Abdominal pain was the most frequent presentation. There was no ultrasonographic pattern. All of the SLCTs were at stage IA, and most of them were moderately differentiated. Relapses did not occur, but one death related to the surgical staging occurred.

OBJETIVO: Descrever uma série de casos de tumores de células de Sertoli-Leydig (TCSLs) ovarianos. MéTODOS: Revisão retrospectiva de 12 casos de TCSL tratados no Hospital de Câncer de Barretos entre outubro de 2009 e agosto de 2017. RESULTADOS: A mediana de idade foi 31 anos (15­71 anos). Um total de 9 pacientes (75,0%) apresentaram sintomas: 8 (66,7%) apresentaram dor abdominal, 5 (41,7%) apresentaram aumento abdominal, 2 (16,7%) apresentaram virilização, 2 (16,7%) apresentaram sangramento uterino anormal, 1 (8,3%) apresentou dispareunia, e 1 (8,3%) apresentou emagrecimento. A mediana de desidrogenase láctica (DHL) foi 504,5 U/L (138­569 U/L), alfafetoproteína (AFP) foi 2,0 ng/ml (1,1­11,3 ng/ml), gonadotrofina coriônica humana (ß-hCG) foi 0,6 mUI/ml (0,0­2,3 mUI/ml), antígeno carcinoembrionário (CEA) foi 0,9 ng/ml (0,7­3,4) ng/ml, e antígeno cancerígeno 125 (CA-125) foi 26,0 U/ml (19,1­147,0 U/ml), todos pré-operatórios. Todos os tumores foram unilaterais e tratados cirurgicamente. Realizou-se linfadenectomia em 3 (25,0%) pacientes, porém, nenhuma das três apresentou acometimento linfonodal. No exame anatomopatológico, 1 tumor (8,3%) era bem diferenciado, 8 (66,7%) eram moderadamente diferenciados, e 3 (25,0%) eram pouco diferenciados. Um total de 5 (55,6%) tumores eram sólido-císticos, 2 (22,2%) eram puramente císticos, 1 (11,1%) era cístico com vegetações, e 1 (11,1%) era puramente sólido, mas para 3 pacientes estas informações não estavam disponíveis. A mediana da dimensão da lesão foi 14,2 cm (3,2­23,5 cm). Todos os tumores eram estádio IA de acordo com a classificação de 2014 da Federação Internacional de Ginecologia e Obstetrícia (FIGO, na sigla em inglês). Duas (16,7%) pacientes receberam adjuvância; uma realizou 3 ciclos de paclitaxel e carboplatina a cada 21 dias, e a outra 4 ciclos de ifosfamida, cisplatina e etoposide a cada 21 dias. Dentre todas as pacientes, nenhuma apresentou recidiva e houve um óbito relacionado a complicações após estadiamento cirúrgico. CONCLUSãO: Dor abdominal foi a apresentação mais frequente. Todos os TCSLs eram estádio IA e a maioria era moderadamente diferenciada. Não ocorreram recidivas, mas ocorreu um óbito relacionado ao estadiamento cirúrgico.