Cancer risk-reducing surgery: Brazilian society of surgical oncology guideline part 1 (gynecology and breast).

BACKGROUND: Risk-reducing operations are an important part of the management of hereditary predisposition to cancer. In selected cases, they can considerably reduce the morbidity and mortality associated with cancer in this population. OBJECTIVES: The Brazilian Society of Surgical Oncology (BSSO) developed this guideline to establish national benchmarks for cancer risk-reducing operations. METHODS: The guideline was prepared from May to December 2021 by a multidisciplinary team of experts to discuss the surgical management of cancer predisposition syndromes. Fourteen questions were defined and assigned to expert groups that reviewed the literature and drafted preliminary recommendations. Following a review by the coordinators and a second review by all participants, the groups made final adjustments, classified the level of evidence, and voted on the recommendations. RESULTS: For all questions including risk-reduction bilateral salpingo-oophorectomy, hysterectomy, and mastectomy, major agreement was achieved by the participants, always using accessible alternatives. CONCLUSION: This and its accompanying article represent the first guideline in cancer risk reduction surgery developed by the BSSO, and it should serve as an important reference for the management of families with cancer predisposition.

Combined evaluation of fecal calprotectin and C-reactive protein as a therapeutic target in the management of patients with Crohn's disease.

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 155µg/g showed high sensitivity (96%) and accuracy (78%) for the diagnosis of endoscopic activity. For CRP, the value of 6.7mg/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.

Faecal calprotectin is the biomarker that best distinguishes remission from different degrees of endoscopic activity in Crohn's disease.

BACKGROUND: Effective control of the inflammatory process in Crohn's disease (CD) is reflected in intestinal mucosal healing. The performances of faecal calprotectin (fcal), clinical and serologic parameters in the inflammatory activity evaluation and their correlation to the simple endoscopic score (SES-CD) are the goals of this study. METHODS: Patients with CD referred for ileocolonoscopy were prospectively included and distributed according to the degree of endoscopic inflammatory activity into remission, mild activity, and moderate to severe activity groups. The different degrees of endoscopic activity were correlated with the following indexes: Crohn's disease activity index (CDAI), fCal, serum C-reactive protein (CRP), and haemogram. The control group comprised individuals without known intestinal disease who were referred for colorectal cancer screening. RESULTS: Eighty colonoscopies were performed in patients with CD and 21 in the control group. The control group had a lower median fCal (59.7 mcg/g) than patients with CD (683 mcg/g, p < 0.001). A moderate Spearman correlation occurred between SES-CD and CRP (r = 0.525), fCal (r = 0.450), and CDAI (r = 0.407), while a weak correlation was found with the platelet count (r = 0.257). Only fCal distinguished patients in remission from those with mild activity (236.6 mcg/g × 654.9 mcg/g, p = 0.014) or moderate to severe activity (236.6 mcg/g × 1128 mcg/g, p < 0.001). An fCal cut-off of 155 mcg/g was sensitive (96%) and accurate (78%) for the diagnosis of endoscopic activity. CONCLUSIONS: fCal provides greater diagnostic accuracy than the other activity markers for endoscopic activity of patients with CD, moderate correlation to SES-CD, and a capacity to discriminate patients in remission from those with mild or moderate to severe activity.

Δ-FeOOH as Support for Immobilization Peroxidase: Optimization via a Chemometric Approach.

Owing to their high surface area, stability, and functional groups on the surface, iron oxide hydroxide nanoparticles have attracted attention as enzymatic support. In this work, a chemometric approach was performed, aiming at the optimization of the horseradish peroxidase (HRP) immobilization process on Δ-FeOOH nanoparticles (NPs). The enzyme/NPs ratio (X1), pH (X2), temperature (X3), and time (X4) were the independent variables analyzed, and immobilized enzyme activity was the response variable (Y). The effects of the factors were studied using a factorial design at two levels (-1 and 1). The biocatalyst obtained was evaluated for the ferulic acid (FA) removal, a pollutant model. The materials were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The SEM images indicated changes in material morphology. The independent variables X1 (-0.57), X2 (0.71), and X4 (0.42) presented the significance effects estimate. The variable combinations resulted in two significance effects estimates, X1*X2 (-0.57) and X2*X4 (0.39). The immobilized HRP by optimized conditions (X1 = 1/63 (enzyme/NPs ratio, X2 = pH 8, X4 = 60 °C, and 30 min) showed high efficiency for FA oxidation (82%).

Predominant role of DNA polymerase eta and p53-dependent translesion synthesis in the survival of ultraviolet-irradiated human cells.

Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells. Viability increase was associated with improved elongation of nascent DNA, indicating the protective effect was due to more efficient lesion bypass by pol eta. This protection was observed in cells proficient or deficient in nucleotide excision repair, suggesting that, from a cell survival perspective, proper bypass of DNA damage can be as relevant as removal. These results indicate p53 controls the induction of pol eta in DNA damaged human cells, resulting in improved TLS and enhancing cell tolerance to DNA damage, which parallels SOS responses in bacteria.

Soybean peroxidase immobilized on δ-FeOOH as new magnetically recyclable biocatalyst for removal of ferulic acid.

A significant enhancement in the catalytic performance due to enzymes immobilization is a great way to enhance the economics of biocatalytic processes. The soybean peroxidase (SP) immobilization under ferroxyte and the ferulic acid removal by the enzyme free and immobilized were investigated. The immobilization via silica-coated ferroxyte nanoparticles was effective, and immobilization yield of 39%. The scanning electron microscopy (SEM) images showed significant changes in the materials morphology. Substantial differences were observed in the particles' Fourier Transform Infrared (FTIR) spectra. The magnetic catalyst revealed a better performance than the free enzyme in the ferulic acid conversion, presenting a good V max/K m ratio when compared with the free enzyme. The reuse evaluated by ten cycles exhibited excellent recycling, remaining constant between the sixth and seventh cycles. The use of magnetic nanocatalyst becomes possible to eliminate the high operational costs, and complicated steps of the conventional enzymatic processes. Thus, a viable industrial route for the use of the enzyme as catalyst is possible.

Psychometric Properties of the Personality Inventory for DSM-5 faceted Brief Form in a Brazilian Community Sample.

OBJECTIVE: The aim of the present study was to verify the psychometric qualities of the PID-5-FBF in a community sample of Brazilian adults. The internal consistency of the facets and the internal structure of the dimensions were checked. In addition, we verified the correlations between the PID-5-FBF facets and domains with a five-factor model measure. METHODS: The sample of this study consists of the 774 Brazilian adults aged 18 to 73 years (mean 28.9±11.58) who answered the PID-5-FBF and BFI-2S. RESULTS: The alpha values were adequate. The internal structure was similar to the PID-5 original form. All the factors and dimensions of the PID-5-FBF have a negative association with agreeableness, while, on the other hand, all correlations with neuroticism were positive. Neuroticism was the factor with the highest correlation with the PID-5-FBF, and openness was the one with the lowest number of correlations. CONCLUSIONS: This research contributes to adding evidence of validity to the PID-5-FBF in the Brazilian community sample. Our results are important because it is the first study with the PID-FBF in a Brazilian sample.

PROXIMAL HUMERAL LOCKING PLATE: A VIABLE ALTERNATIVE FOR FIXATION OF DISTAL FEMORAL FRACTURES IN CHILDREN.

Distal femoral metaphyseal fractures are rare in children, and the proximity of the fracture to the growth plate makes their approach challenging. Objective: Evaluate outcomes and complications of treatment of distal femoral metaphyseal fractures in children with proximal humeral locking plates. Method: Retrospective study between 2018 and 2021, including seven patients. The analysis included general characteristics, trauma mechanism, classification, clinical and radiographic outcomes, and complications. Results: The mean follow-up was 20 months, the average age was nine years, five patients were boys, and six fractured on the right side. Five fractures were caused by car accidents, one by falling from their own height and one by playing soccer. Five fractures were classified as 33-M/3.2 and two as 33-M/3.1. Three fractures were open, Gustilo IIIA. All seven patients recovered mobility and resumed their pre-trauma activities. All seven healed, and one fracture was reduced to 5 degrees valgus, without any other complications. Six patients had the implant removed and did not present refracture. Conclusion: Treatment of distal femoral metaphyseal fractures with proximal humeral locking plates is a viable option that offers good results and fewer complications, saving the epiphyseal cartilage. Level of Evidence II; Controlled study without randomization.

As fraturas metafisárias distais do fêmur são raras em crianças, a proximidade da fratura com a placa de crescimento torna a sua abordagem desafiadora. Objetivo: Avaliar resultados e complicações do tratamento das fraturas da metáfise distal do fêmur em crianças com placas de úmero proximal. Método: Estudo retrospectivo entre 2018 e 2021 incluindo sete pacientes. A análise incluiu características gerais, mecanismo do trauma, classificação, resultados clínicos, radiográficos e complicações. Resultados: A média do acompanhamento foi de 20 meses, a idade média foi de nove anos, cinco pacientes eram meninos e seis fraturas do lado direito. Cinco fraturas por acidentes automobilísticos, uma por queda da própria altura e uma jogando futebol. Cinco fraturas classificadas como 33-M/3,2 e duas como 33-M/3,1. Três fraturas foram expostas, Gustilo IIIA. Todos os sete pacientes recuperaram a mobilidade e retomaram às atividades anteriores ao trauma. Todas as sete fraturas consolidaram, uma fratura foi reduzida com valgo de 5 graus, e não houveram outras complicações. Seis pacientes tiveram o implante removido e não apresentaram refratura. Conclusão: O tratamento das fraturas da metáfise distal do fêmur com placas de úmero proximal é uma opção viável que oferece bons resultados com poucas complicações, poupando a cartilagem epifisária. Nível de Evidência II; Estudo controlado sem randomização.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Implementation of a patient blood management program based on a low-income country-adapted clinical decision support system.

INTRODUCTION: Patient blood management (PBM) programs are associated with better patient outcomes, a reduced number of transfusions and cost-savings The Clinical Decision Support (CDS) systems are valuable tools in this process, but their availability is limited in developing countries This study assesses the feasibility and effectiveness of an adapted CDS system for low-income countries. METHODS: This was a prospective study of the PBM program implementation, in a 200-bed tertiary hospital, between February 2019 and May 2020. Outcome measures were red blood cell (RBC), fresh frozen plasma (FFP) and platelet unit transfusions, the transfusion of a single unit of red blood cells and an RBC adequacy index (RAI). RESULTS: Comparing the post-PBM program era with the pre-PBM system era, there was a decrease in red blood cell transfusions (p=0.05), with an increase in single unit red blood cell transfusions (p=0.005) and RAI (p<0.001). CONCLUSIONS: The PBM programs, including electronic transfusion guidelines with pre-transfusion medical auditing, was associated with improved transfusion practices and reduced product acquisition-related costs.

Evaluation of key parameters for developing a Metarhizium rileyi-based biopesticide against Spodoptera frugiperda (Lepidoptera: Noctuidae) in maize: laboratory, greenhouse, and field trials.

BACKGROUND: The entomopathogenic fungus Metarhizium rileyi is known to cause natural infections in some caterpillars. In this multiyear study, we carried out laboratory, greenhouse and three field trials with the aim of developing a sustainable option for control of the fall armyworm (FAW) in maize. Association of M. rileyi with Spodoptera frugiperda baculovirus (SfMNPV) and delivery strategies were also investigated. RESULTS: The selected isolate (CG381) was effective in the laboratory at a low concentration (~ 4 × 103 conidia cm-2 ), killing >95% of FAW larvae within 8 days. In the greenhouse assay, applications of conidia suspended in water or as dry powder in maize whorls (~ 6.3 × 106 conidia per plant) produced similar larval mortalities (88%-96%). In the field trials, conventional spraying of unformulated conidia (0.6 and 1.2 × 1012 conidia ha-1 ) caused low larval mortalities (27-31%). Simultaneous application of either unformulated or oil-based formulations of M. rileyi conidia and S. frugiperda baculovirus (SfMNPV) to plant rows caused larval mortalities comparable with each of the pathogens applied alone. However, when a formulation containing both pathogens was sprayed directly into the whorls, the overall mortality of S. frugiperda larvae due to pathogens (mostly to M. rileyi infections) reached ~ 59%, twofold higher than the other treatments with conventional spraying, whereas in the control, the overall mortality was only 1%. CONCLUSION: Optimizing exposure of S. frugiperda larvae to an inoculum of virulent entomopathogens through directed applications to maize whorls is critical to produce satisfactory mortality levels and is promising for integrated pest management.

COLONOSCOPY FINDINGS IN LIVER TRANSPLANTATION CANDIDATES.

BACKGROUND: Mandatory colonoscopy in liver transplantation (LT) candidates is recommended but still controversial. OBJECTIVE: To investigate the frequency of colonoscopy lesions in order to support colorectal cancer (CRC) screening in a real-world pre-LT cohort. METHODS: Retrospective study conducted at a single-center included 632 subjects who underwent pre-transplantation colonoscopy. RESULTS: Median age was 56.9 years (yr.) old (82.3% were ≥50 yr.). Primary sclerosing cholangitis (PSC) occurred in 4.6%. Colonoscopy was abnormal in 438 (69.3%) by detection of polyps (37.7%), vascular changes (29.9%), diverticulosis (18.4%), inflammatory bowel disease features (5.2%) and CRC (0.6%). Histology was available in 66.8% of polyps: hyperplastic (47.8%), low-grade dysplasia (56.6%) and high-grade dysplasia (3.8%). High-risk adenomas occurred in 8.2% of the 594 subjects evaluated. Individuals ≥50 yr. were more likely to present abnormal colonoscopy and polyps. High-grade dysplasia and CRC were only found in individuals ≥50 yr. Patients with high-risk adenomas were more likely to be ≥50 yr.: there was no association between high-risk adenomas detection and liver disease etiology or PSC diagnosis. CONCLUSION: Most LT candidates presented abnormal colonoscopy examination, especially by polyps presence. All cases of high-grade dysplasia and CRC occurred in patients ≥50 yr., regardless of disease etiology.

Different combinations of the GLIM criteria for patients awaiting a liver transplant: Poor performance for malnutrition diagnosis but a potentially useful prognostic tool.

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-phase angle + 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.

Bioelectrical impedance vector analysis in patients on the waiting list for liver transplant: Associated factors and prognostic effects.

OBJECTIVES: The aim of this study was to assess patients on the waiting list for liver transplant (LTx) according to bioelectrical impedance vector analysis (BIVA), as well as to verify the association between the placement of the vectors on the graph with clinical outcomes and identify the predictors to vector placement in quadrant 4 (Q4; indicating more hydration and less cellularity). METHODS: This was a retrospective observational study including 129 patients ≥20 y of age awaiting LTx. Patients' nutritional status was assessed by using different tools, including single-frequency bioelectrical impedance analysis and the Subjective Global Assessment (SGA). Clinical data were registered. The BIVA was evaluated by comparing the individual vectors plotted for all patients to the tolerance ellipses of 50%, 75%, and 95% of the reference healthy population. The quadrant of the vector for each patient was registered. RESULTS: The majority of the vectors were placed in Q1 (n = 54; 41.9%) and Q4 (n = 39; 30.2%). The presence of ascites or edema (hazard ratio [HR], 2.43; 95% confidence interval [CI], 1.15-5.12; P = 0.019) and the BIVA vector placed in Q4 in any ellipse (HR, 2.10; 95% CI, 1.07-4.09; P = 0.029) were independent predictors for mortality on the waiting list or ≤1 y after LTx. BIVA was not associated with longer hospital length of stay. The predictors of vector placement in Q4 were higher age, malnutrition according to SGA, and presence of ascites or edema. CONCLUSION: Patients on the waiting list for LTx with BIVA vectors placed in Q4, in the 50%, 75%, or 95% tolerance ellipses, presented a worse prognosis.

Risk factors for acute kidney injury after liver transplantation in intensive care unit: a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a frequent complication during the postoperative period following liver transplantation. Occurrence of AKI in intensive care unit (ICU) patients is associated with increased mortality and higher costs. OBJECTIVE: To evaluate occurrences of moderate or severe AKI among patients admitted to the ICU after liver transplantation and investigate characteristics associated with this complication. DESIGN AND SETTING: Single-center retrospective cohort study in a public hospital, Belo Horizonte, Brazil. METHODS: Forty-nine patients admitted to the ICU between January 2015 and April 2017 were included. AKI was defined from a modified Kidney Disease Improving Global Outcomes (KDIGO) score (i.e. based exclusively on serum creatinine levels). RESULTS: Eighteen patients (36.7%) developed AKI KDIGO 2 or 3; mostly KDIGO 3 (16 out of the 18 patients). Lactate level within the first six hours after ICU admission (odds ratio, OR: 1.3; 95% confidence interval, CI: 1.021-1.717; P = 0.034) and blood transfusion requirement within the first week following transplantation (OR: 8.4; 95% CI: 1.687-41.824; P = 0.009) were independently associated with development of AKI. Patients with AKI KDIGO 2 or 3 underwent more renal replacement therapy (72.2% versus 3.2%; P < 0.01), had longer hospital stay (20 days versus 15 days; P = 0.001), higher in-hospital mortality (44.4% versus 6.5%; P < 0.01) and higher mortality rate after one year (44.4% versus 9.7%; P = 0.01). CONCLUSION: Need for blood transfusion during ICU stay and hyperlactatemia within the first six postoperative hours after liver transplantation are independently associated with moderate or severe AKI. Developing AKI is apparently associated with poor outcomes.

Arg72Pro TP53 polymorphism and cancer susceptibility: a comprehensive meta-analysis of 302 case-control studies.

Arg72Pro is a common polymorphism in TP53, showing differences in its biological functions. Case-control studies have been performed to elucidate the role of Arg72Pro in cancer, although the results are conflicting and heterogeneous. Here, we analyzed pooled data from case-control studies to determine the role of Arg72Pro in different cancer sites. We performed a systematic review and meta-analysis of 302 case-control studies that analyzed Arg72Pro in cancer susceptibility. Odds ratios were estimated for different tumor sites using distinct genetic models, and the heterogeneity between studies was explored using I(2) values and meta-regression. We adopted quality criteria to classify the studies. Subgroup analyses were done for tumor sites according to ethnicity, histological, and anatomical sites. Results indicated that Arg72Pro is associated with higher susceptibility to cancer in some tumor sites, mainly hepatocarcinoma. For some tumor sites, quality of studies was associated with the size of genetic association, mainly in cervical, head and neck, gastric, and lung cancer. However, study quality did not explain the observed heterogeneity substantially. Meta-regression showed that ethnicity, allelic frequency and genotyping method were responsible for a substantial part of the heterogeneity observed. Our results suggest ethnicity and histological and anatomical sites may modulate the penetrance of Arg72Pro in cancer susceptibility. This meta-analysis denotes the importance for more studies with good quality and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of Arg72Pro in cancer.

Real-world disease activity and sociodemographic, clinical and treatment characteristics of moderate-to-severe inflammatory bowel disease in Brazil.

BACKGROUND: Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce. AIM: To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions. METHODS: Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 µg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables. RESULTS: In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%). CONCLUSION: In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment.

Effect of Oral Nutrition Supplements and TGF-ß2 on Nutrition and Inflammatory Patterns in Patients With Active Crohn's Disease.

BACKGROUND: Crohn's disease (CD) is often associated with nutrition disorders. Many nutrition therapeutic alternatives have been studied. Nevertheless, the actual role of nutrition therapy is still controversial. The objective of this study was to assess the effects of nutrition supplementation with and without transforming growth factor-beta 2 (TGF-ß2) on inflammatory, endoscopic, histopathologic, and nutrition parameters in active CD. MATERIALS AND METHODS: Thirty-eight patients were allocated into 3 groups: group 1 (patients who received only nutrition orientation), group 2 (nutrition orientation and a normoproteic, normocaloric nutrition supplement), and group 3 (nutrition orientation and the nutritional supplement with TGF-ß2). Clinical and nutrition evaluation, C-reactive protein (CRP) levels, and assessment of endoscopic and histologic parameters in the intestinal mucosa were performed before and after nutrition intervention. RESULTS: The mean follow-up period was 3 months. In the beginning of the study, groups were homogeneous regarding age, gender, CD behavior and localization, and medication in use. In the end of the study, the Clinical Disease Activity Index score was reduced in groups 2 and 3; in group 3, a reduction in CRP levels and an improvement in histologic findings were observed. Among patients who received nutritional supplement, some anthropometric patterns were improved. CONCLUSION: The results of the study indicate that nutritional supplementation improved nutrition and inflammatory patterns in patients with active CD. However, only patients receiving TGF-ß2-enriched formula showed improvement in histologic parameters and significant reduction in CRP levels.

DISCONTINUATION RATES FOLLOWING A SWITCH FROM A REFERENCE TO A BIOSIMILAR BIOLOGIC IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.