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.

The Natural History of Patients With Pre-Existing and De Novo Inflammatory Bowel Disease After Solid Organ Transplantation: EITOS Study of GETECCU.

BACKGROUND: Limited data are available on the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). We describe the natural history of pre-existing IBD and de novo IBD after SOT. METHODS: This was a retrospective, multicenter study that included patients with pre-existing IBD at the time of SOT and patients with de novo IBD after SOT. The primary outcome was IBD progression, defined by escalation of medical treatment, surgical therapy, or hospitalization due to refractory IBD. Risk factors were identified using multivariate Cox proportional hazard analysis. RESULTS: A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) were included. Most patients with pre-existing IBD (92.5%) were in remission before SOT. During follow-up, 32% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 (interquartile range, 1.3-4.6) years. In the de novo cohort, 55% of patients had disease progression with a median time to flare of 1.9 (interquartile range, 0.8-3.9) years after diagnosis. In the pre-existing IBD cohort, active IBD at the time of SOT (hazard ratio, 1.80; 95% confidence interval, 1.14-2.84; P = .012) and the presence of extraintestinal manifestations (hazard ratio, 3.10; 95% confidence interval, 1.47-6.54; P = .003) were predictive factors for IBD progression. CONCLUSIONS: One-third of patients with pre-existing IBD and about half of patients with de novo IBD have disease progression after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for IBD progression.

Increased prevalence of migraine in women with inflammatory bowel disease: A cross-sectional study.

BACKGROUND: Some studies have suggested an association between migraine and inflammatory bowel disease. We determined migraine prevalence in a cohort of patients with inflammatory bowel disease. METHODS: Patients with inflammatory bowel disease aged 18-65 years were interviewed using an ad hoc headache questionnaire. Those who admitted a history of headache in the last year answered the three questions of the ID-Migraine questionnaire. Those who answered "yes" to the three of them were classified as "definite" and those who answered "yes" to two were classified as "probable" migraine. RESULTS: We interviewed 283 patients with inflammatory bowel disease. Of these, 176 (62.2%) had headache. Fifty-nine (20.8%; 95% CI 16.3-26.0%) met migraine criteria either definite (n = 33; 11.7%; 95% CI 8.2-16.0%) or probable (n = 26; 9.2%; 95% CI 6.1-13.2). When divided by gender, 12 men (9.6%; 95% CI 5.1-16.2%) and 47 women (29.8%; 95% CI 22.8-37.5%) met migraine criteria. The prevalence of migraine was increased in inflammatory bowel disease patients from the current cohort (20.8%) versus that reported for our general population for the same age group (12.6%; p < 0.0001). These differences remained significant in female inflammatory bowel disease patients (29.8% versus 17.2% in our general population; p < 0.0001), but not in males (9.6% in inflammatory bowel disease vs 8.0%; p = 0.30). Seventeen patients with inflammatory bowel disease (6.0%; 95% CI 3.54-9.44%) fulfilled chronic migraine criteria. There were no differences in migraine prevalence by inflammatory bowel disease subtypes. CONCLUSION: Migraine prevalence, including chronic migraine, seems to be increased in patients with inflammatory bowel disease. The fact that this association was stronger for women suggests an influence of sex-related factors.

Deficiências visuais: incidência e sua relação regional e escolar em um município no noroeste paulista / Visual disabilities: incidence and its regional and school relationship in a municipality in northwest paulista

Introdução: Baixa acuidade visual é um problema de alta prevalência, podendo atingir até 25% das crianças em idade escolar e dentre os principais problemas estão a miopia, a hipermetropia, o astigmatismo, a ambliopia, o estrabismo e o daltonismo. Objetivo: O estudo visa determinar a prevalência de deficiências visuais não diagnosticadas em crianças de quatro e cinco anos que frequentam escolas em um município no noroeste paulista, relacionando-a ao sexo e a característica de escola (pública ou privada). Material e Método: Estudo observacional transversal prospectivo quantitativo, realizado em duas escolas públicas e duas privadas, localizadas no munícipio de Catanduva, São Paulo, Brasil, onde se aplicaram testes realizados para possíveis diagnósticos de distúrbios de acuidade visual (Teste de Snellen), Daltonismo (Teste de Ishihara) e Estrabismo (Teste de Hirschberg). Resultados: Foram avaliadas 245 crianças. Para a análise estatística, foram utilizados os testes qui-quadrado de Pearson e exato de Fisher. A prevalência de baixa acuidade visual foi de 29,73% nas escolas particulares, 43,27% nas públicas (p=0,046); no que se refere a sexo, 20,57% dos meninos apresentaram baixa acuidade visual, contra 17,31% das meninas (p=0,52). O Teste de Hirschberg apresentouse alterado em 24,32% dos alunos de escola particular, 17,54% dos de escola pública (p=0,22), 18,44% dos meninos e 21,15% das meninas (p=0,6). Já, alterações no teste de Ishihara manifestaram-se em 5,41% dos alunos das escolas privadas e 4,09% dos de escola pública (p=0,65); 6,38% e 1,92% dos meninos e meninas, respectivamente, apresentaram alterações (p=0,1). Destaca-se a importância do acompanhamento com um oftalmologista desde a infância, visto que a prevalência de deficiências visuais não diagnosticadas permanece significativa, principalmente quanto aos distúrbios de acuidade visual nas escolas públicas. Conclusão: O diagnóstico precoce de deficiência visual é primordial, pois muitas alterações são reversíveis por apenas um curto período

Introduction: Low visual acuity is a highly prevalent problem, affecting up to 25% of school-age children and the main problems include myopia, hyperopia, astigmatism, amblyopia, strabismus and color blindness. Objective: The study aims to determine the prevalence of undiagnosed visual impairments in children aged four and five who attend schools in a city in the northwest of São Paulo, relating it to gender and the characteristics of the school (public or private). Material and Method: Quantitative prospective cross-sectional observational study, carried out in two public and two private schools, located in the municipality of Catanduva, São Paulo, Brazil, where tests were applied, carried out for possible diagnoses of visual acuity disorders (Snellen Test), Color blindness (Ishihara Test) and Strabismus (Hirschberg Test). Results: 245 children were evaluated. For statistical analysis, Pearson's chi-square and Fisher's exact tests were used. The prevalence of low visual acuity was 29.73% in private schools, 43.27% in public schools (p=0.046); Regarding gender, 20.57% of boys had low visual acuity, compared to 17.31% of girls (p=0.52). The Hirschberg Test was altered in 24.32% of private school students, 17.54% of public school students (p=0.22), 18.44% of boys and 21.15% of girls (p =0.6). Changes in the Ishihara test were manifested in 5.41% of students in private schools and 4.09% of those in public schools (p=0.65); 6.38% and 1.92% of boys and girls, respectively, showed changes (p=0.1). The importance of monitoring with an ophthalmologist since childhood is highlighted, as the prevalence of undiagnosed visual impairments remains significant, especially regarding visual acuity disorders in public schools. Conclusion: Early diagnosis of visual impairment is essential, as many changes are reversible for only a short period

Introducción: La baja agudeza visual es un problema altamente prevalente, afecta hasta al 25% de los niños en edad escolar y los principales problemas incluyen miopía, hipermetropía, astigmatismo, ambliopía, estrabismo y daltonismo. Objetivo: El estudio tiene como objetivo determinar la prevalencia de discapacidad visual no diagnosticada en niños de cuatro y cinco años que asisten a escuelas de una ciudad del noroeste de São Paulo, relacionándola con el género y las características de la escuela (pública o privada). Material y Método: Estudio observacional cuantitativo, prospectivo, transversal, realizado en dos escuelas públicas y dos privadas, ubicadas en el municipio de Catanduva, São Paulo, Brasil, donde se aplicaron pruebas realizadas para posibles diagnósticos de trastornos de la agudeza visual (Snellen Test), daltonismo (test de Ishihara) y estrabismo (test de Hirschberg). Resultados: Se evaluaron 245 niños. Para el análisis estadístico se utilizaron las pruebas de chi-cuadrado de Pearson y exacta de Fisher. La prevalencia de baja agudeza visual fue de 29,73% en colegios privados, 43,27% en públicos (p=0,046); En cuanto al género, el 20,57% de los niños presentó baja agudeza visual, frente al 17,31% de las niñas (p=0,52). El Test de Hirschberg se vio alterado en el 24,32% de los estudiantes de escuelas privadas, el 17,54% de los estudiantes de escuelas públicas (p=0,22), el 18,44% de los niños y el 21,15% de las niñas (p =0,6). Los cambios en la prueba de Ishihara se manifestaron en el 5,41% de los estudiantes de escuelas privadas y el 4,09% de los de escuelas públicas (p=0,65); El 6,38% y el 1,92% de niños y niñas, respectivamente, presentaron cambios (p=0,1). Se destaca la importancia del seguimiento con un oftalmólogo desde la infancia, ya que la prevalencia de deficiencias visuales no diagnosticadas sigue siendo significativa, especialmente en lo que respecta a los trastornos de la agudeza visual en las escuelas públicas. Conclusión: El diagnóstico temprano de la discapacidad visual es esencial, ya que muchos cambios son reversibles sólo durante un período corto

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.

Real-world outcomes of switching from adalimumab originator to adalimumab biosimilar in patients with inflammatory bowel disease: The ADA-SWITCH study.

BACKGROUND AND AIMS: Data on the outcomes after switching from adalimumab (ADA) originator to ADA biosimilar are limited. The aim was to compare the treatment persistence, clinical efficacy, and safety outcomes in inflammatory bowel disease patients who maintained ADA originator vs. those who switched to ADA biosimilar. METHODS: Patients receiving ADA originator who were in clinical remission at standard dose of ADA originator were included. Patients who maintained ADA originator formed the non-switch cohort (NSC), and those who switched to different ADA biosimilars constituted the switch cohort (SC). Clinical remission was defined as a Harvey-Bradshaw index ≤4 in Crohn's disease and a partial Mayo score ≤2 in ulcerative colitis. To control possible confounding effects on treatment discontinuation, an inverse probability treatment weighted proportional hazard Cox regression was performed. RESULTS: Five hundred and twenty-four patients were included: 211 in the SC and 313 in the NSC. The median follow-up was 13 months in the SC and 24 months in the NSC (p < 0.001). The incidence rate of ADA discontinuation was 8% and 7% per patient-year in the SC and in the NSC, respectively (p > 0.05). In the multivariate analysis, switching from ADA originator to ADA biosimilar was not associated with therapy discontinuation. The incidence rate of relapse was 8% per patient-year in the SC and 6% per patient-year in the NSC (p > 0.05). Six percent of the patients had adverse events in the SC vs. 5% in the NSC (p > 0.05). CONCLUSION: Switching to ADA biosimilar did not impair patients' outcomes in comparison with maintaining on the originator.

Should Inflammatory Bowel Disease Clinicians Provide Their Patients with e-Health Resources? Patients' and Professionals' Perspectives.

Introduction: The internet is emerging as a source of information for patients with inflammatory bowel disease (IBD). However, it is not always reliable and may cause anxiety. We aim to assess patients' information habits and patients' and professionals' perceptions of a national website integrated as an educational resource for the IBD unit. Methods: Patients aged 18-65 years, comfortable with the internet, and attending follow-ups at participating IBD units (March-June 2019) and their professionals were invited to evaluate a recommended website through an online survey. Results: Three hundred eighty-nine patients and 95 professionals completed the survey. The internet (n = 109; 27.4%) was the second preferred source of information after the health care team (n = 229; 57.5%). Eighty percent of patients searched the internet for information on their disease and 28.6% did so at least once a week (n = 114), especially newly diagnosed ones (<2 years). Patients valued a website recommended by their professional (n = 379; 95.2%) and endorsed by the National Working Group (n = 377; 94.7%). They would attend online educational initiatives on the website (n = 279; 70.1%) and complete periodical surveys to improve its usefulness (n = 338; 84.9%). According to IBD professionals, this type of website is the best patient source of supplementary information (n = 76; 80%) and they "prescribe" it to most patients (67.0 ± 25.2%), especially the newly diagnosed patients (52.7 ± 26.5%). It effectively integrates routine face-to-face education (n = 95; 100%). Conclusions: Patients of IBD units, especially newly diagnosed ones, appreciate a trusted e-Health resource to back up professional information. The favorable opinion of patients and professionals will allow its use in training interventions.

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.

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.

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.

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.

Prevalence of antinuclear antibodies in inflammatory bowel disease and seroconversion after biological therapy.

BACKGROUND: Estimates of detectable antinuclear antibodies (ANA) prevalence vary widely, from 6% in healthy populations to 50-80% in patients with autoimmune disease. However, there is a lack of evidence about the overall prevalence in inflammatory bowel disease (IBD) and ANA seroconversion after the beginning of biological therapy. OBJECTIVES: The aim of the study was to investigate the overall prevalence of ANA in IBD patients, their relationship with different treatments, clinical outcomes and the seroconversion rate of ANA in patients treated with biological therapy. METHODS: Ambispective observational study including all consecutive IBD patients was carried out. Information about the presence of ANA, disease phenotype, duration, activity, complications, and past and current treatments were transversally collected. Retrospectively, in patients with detectable ANA, data regarding previous ANA detection and the diagnosis of lupus-like syndrome (LLS) was gathered. RESULTS: A total of 879 IBD patients were included. We observed a detectable ANA prevalence of 13.6%. The presence of ANA was frequently associated with biological therapy (36/118) and decreased when immunomodulators were combined to this therapy (7/32). Of 78 patients with ANA prior to the beginning of biological therapy, a seroconversion rate of 28.8% was observed after a mean of 3.14 years. Only 1 patient suffered LLS. CONCLUSION: Our study showed a prevalence of detectable ANA higher than the expected in healthy population. The presence of ANA was lower when immunomodulator therapy is associated. The ANA seroconversion rate is relevant after the initiation of biological treatment nevertheless, the risk of LLS appeared to be marginal.

Mutational profile confers increased stability of SARS-CoV-2 spike protein in Brazilian isolates.

Spike (S) protein has been recognized as a promising molecular target for diagnostic, vaccines and antiviral drugs development for COVID-19. In this study, we analyzed the most predominant mutations in the S protein of Brazilian isolates and predicted the effect of these amino acid alterations to protein conformation. A total of 25,924 sequences were obtained from GISAID for five regions of Brazilian territory (Midwest, North, Northeast, South, and Southeast), according to exclusion criteria. Most of the SARS-CoV-2 isolates belongs to the G clade and showed a large occurrence of D614G, N501Y and L18F substitutions. Prediction effects of these amino acid substitutions on the structure dynamics of the spike protein indicated a positive ΔΔG values and negative ΔΔSVib in most cases which is associated to structural stabilization and flexibility reduction of the S protein. Mutations E484K, N501Y and K417N belong to several SARS-CoV-2 variants of concern such as Alpha, Beta, Gamma and Delta, and showed high incidence among Brazilian isolates. These mutations have been described to increase RBD affinity to ACE-2 host and abolishment of RBD affinity to potent neutralizing ant-RBD. The increase in rates of infection and reinfection requires continuous genomic surveillance studies in order to characterize emerging mutations and monitor vaccine efficacy, and thus consideration structural data and dynamics in the observed phenotypes.Communicated by Ramaswamy H. Sarma.

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.