Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation.

PURPOSE: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). METHODS: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. RESULTS: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). CONCLUSIONS: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Leukocyte Dysfunction and reduced CTLA-4 Expression are Associated with Perianal Crohn's Disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for detection of plasma cytokines and LPS. PBMC were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma IL-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with history of PCD produced higher IL-6, IL-8 and IFN-γ, along with decreased TNF. CD patients had augmented FoxP3 and CTLA-4 regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4, as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact in the disease management.

Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB.

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.

Divergent androgenic modulation of SARS-CoV-2 infection cooperates with dysregulated immune response to dictate worse COVID-19 outcomes in men.

BACKGROUND: Sex-determined differences are rarely addressed in the management of diseases, despite well-known contrasting outcomes between female and male patients. In COVID-19 there is a remarkable disparity, with higher rates of mortality and more severe acute disease in men compared to women, who are mostly affected by long COVID-19. Furthermore, whether androgens play a protective or detrimental role in COVID-19 is still a matter of debate. Hence, the adequate management of the disease, especially regarding men presenting acute disease aggravation, still needs important data to elucidate the interplay between sex hormones and host immune responses that drive the worse evolution in male patients. METHODS: A cohort of 92 controls and 198 non-severe and severe COVID-19 patients, from both sexes, was assessed for clinical outcomes, plasma steroids, gonadotropins, sex hormone binding globulin (SHBG) and immune mediators, before vaccination. These data were correlated with the global gene expression of blood leukocytes. The androgen receptor (AR) signaling pathway was investigated by transcriptomics and tracheal aspirate was obtained from severe patients for SARS-COV-2 quantification in the respiratory tract. The interplay among clinical, endocrine and immunological data deciphered the sex differences in COVID-19. Importantly, statistical analyses, using 95% confidence interval, considered confounding factors such as age and comorbidities, to definitely parse the role of androgens in the disease outcome. RESULTS: There were notable contrasting levels of testosterone and dihydrotestosterone (DHT) throughout the disease course in male but not female patients. Inflammatory mediators presented significant negative correlations with testosterone, which was partially dependent on age and diabetes in men. Male subjects with severe COVID-19 had a significant up regulation of the AR signaling pathway, including modulation of TMPRSS2 and SRD5A1 genes, which are related to the viral infection and DHT production. Indeed, men had a higher viral load in the tracheal aspirate and levels of DHT were associated with increased relative risk of death. In contrast, the testosterone hormone, which was notably reduced in severe disease, was significantly related with susceptibility to COVID-19 worsening in male patients. Secondary hypogonadism was ruled out in the male severe COVID-19 subjects, as FSH, LH, and SHBG levels were not significantly altered. Instead, these subjects tended to have increased gonadotropin levels. Most interestingly, in this study we identified, for the first time, combined sets of clinical and immunoendocrine parameters that together predicted progression from non-severe to severe COVID-19 in men. One of the limitations of our study was the low or undetectable levels of DHT in many patients. Then, the evaluation of enzymes related to biosynthesis and signaling by androgens was mandatory and reiterated our findings. CONCLUSIONS: These original results unraveled the disease immunoendocrine regulation, despite vaccination or comorbidities and pointed to the fundamental divergent role of the androgens testosterone and DHT in the determination of COVID-19 outcomes in men. Therefore, sex-specific management of the dysregulated responses, treatments or public health measures should be considered for the control of COVID-19 pandemic.

Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Evaluation of the response rate to neoadjuvant chemoradiotherapy in patients with rectal adenocarcinoma: a retrospective long-term study in two terciary reference centers

Objectives: To evaluate the complete response (CR) rate and surgeries performed in patients with rectal adenocarcinoma who underwent neoadjuvant therapy (NT) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and at Hospital São Paulo, in Ribeirão Preto, from January 2007 to December 2017. Methods: We evaluated 166 medical records of patients with locally advanced rectal adenocarcinoma (T3, T4 or N+) who underwent NT. The regimen consisted of performing conventional (2D) or conformational (three-dimensional-3D/ radiotherapy with modulated intensity - IMRT) at a dose of 45-50.4Gy associated with capecitabine 1650mg/m2 or 5-fluorouracil (5FU) and leucovorin (LV). The following variables were analyzed: gender, age, pretreatment stage, radiotherapy, CR index, local and distant recurrence rates. Surgical treatment and complications were also evaluated. Results: The CR index was 28.3%. Patients treated with 3D/IMRT radiotherapy had a higher rate of CR (36.3% x 4.8%; p < 0.001), higher rates of clinical follow-up (21% x 0%; p < 0.001), lower surgery rates (79% x 100%; p < 0.001), higher rates of transanal resection (37.1% x 9.5%; p = 0.001), lower rates of abdominal rectosigmoidectomy (25.8% x 50%; p = 0.007) and lower rates of abdominoperineal resection of the rectum (16.1% x 40.5%; p = 0.002), when compared to patients treated with 2D radiotherapy. Conclusion Modern radiotherapy techniques such as 3D conformal and IMRT, by offering greater adequacy and precision of treatment, could result in better local control and less toxicity in organs at risk, enabling organ preservation strategies and less invasive approaches in selected cases. (AU)

Leukocytoclastic Vasculitis Secondary to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Diseases: A Multicenter Retrospective Cohort Study.

BACKGROUND: Vasculitis is an uncommon complication of biologics used to treat inflammatory bowel disease (IBD). This study describes a case series of vasculitis induced by anti-tumor necrosis factor (TNF) therapy in IBD patients. METHODS: Retrospective assessments were performed using the medical records of adult IBD patients who underwent outpatient clinical follow-ups between January 2010 and December 2019 in order to identify patients with vasculitis caused by anti-TNF therapy. RESULTS: There were 2442 patients altogether. Of these, 862 (35%) took anti-TNF medication. Five patients (0.6% of the overall patients; n = 3 (60%) Crohn's disease; n = 2 (40%), ulcerative colitis) were identified as having leukocytoclastic vasculitis (LCV) due to anti-TNF therapy; these patients were white, female, and non-smokers. The mean age of LCV diagnosis was 32.2 years, and the mean IBD duration was 7.2 years. The mean time between the start of biologic therapy and LCV onset was 30.8 months. Most of the patients were using adalimumab (80%; n = 4). All the patients were in remission at the time of the LCV diagnosis, and the vasculitis affected the skin in all cases. Anti-TNF therapy was discontinued in the five abovementioned patients, and the response of LCV to the oral steroids was significantly positive. Remarkably, all five patients experienced complete remission from LCV within 4-12 weeks after starting prednisone therapy, and none of them had LCV recurrence in the follow-up period (a mean duration of 28 months). CONCLUSIONS: LCV is an unusual complication of anti-TNF therapy in the IBD setting. In this context, clinicians should have a high degree of suspicion of LCV in patients who develop an unexplained cutaneous rash.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology.

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system. METHODS: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs. RESULTS: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD (n = 161, 78.5%), nearly half of them (n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab (n = 128, 62.5%) was the most used medication, followed by adalimumab (n = 39, 19.0%). Most patients (n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment. CONCLUSION: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn's Disease: A Cross-Sectional Multicentric Latin American Study.

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 µg/mL in patients with clinically active CD and 14.3 µg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 µg/mL as compared to 14.5 µg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.

The turning point of COVID-19 severity is associated with a unique circulating neutrophil gene signature.

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation.

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology / Análise retrospectiva dos resultados cirúrgicos e oncológicos em cirurgias videolaparoscópicas realizadas por residentes de coloproctologia

ABSTRACT Introduction: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. Purpose: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. Methods: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. Results: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. Conclusions: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

RESUMO Introdução: com o aperfeiçoamento e a ampla aceitação da laparoscopia nas operações colorretais, houve necessidade de treinamento específico dos cirurgiões em formação. Existem poucos estudos avaliando os resultados pós operatórios das colectomias videolaparoscópicas realizadas por médicos residentes e seu impacto na segurança do paciente. Objetivo: analisar os resultados cirúrgicos e oncológicos das colectomias videolaparoscópicas realizadas por residentes de coloproctologia e comparar com dados da literatura. Métodos: trata-se de uma análise retrospectiva de pacientes submetidos a cirurgias colorretais laparoscópicas, realizadas por médicos residentes do Hospital das Clínicas de Ribeirão Preto, entre 2014 e 2018. Foram estudadas as características clínicas dos pacientes bem como os principais aspectos cirúrgicos e oncológicos em um período de um ano. Resultados: analisou-se 191 operações, cuja principal indicação cirúrgica foi adenocarcinoma, a maioria estadio III. A duração média das cirurgias foi 210±58 minutos. Houve necessidade de estoma em 21,5% dos pacientes, principalmente colostomia em alça. A taxa de conversão foi 23%, sendo 79,5% por dificuldades técnicas, e os principais fatores preditores de conversão foram obesidade e acidentes intra-operatórios. A mediana do tempo de internação foi 6 dias. Anemia pré operatória associou-se a uma maior taxa de complicações (11,5%) e reoperações (12%). Houve comprometimento das margens de ressecção cirúrgica em 8,6% dos casos. A taxa de recidiva em um ano foi de 3,2%, e a taxa de mortalidade, 6,3%. Conclusões: a cirurgia colorretal videolaparoscópica realizada por residentes apresentou eficácia e segurança semelhante aos dados encontrados na literatura.

Postoperative Complications and Stoma Rates After Laparoscopic Resection of Deep Infiltrating Endometriosis with Bowel Involvement / Complicações pós-operatórias e taxas de estomia após ressecção laparoscópica de endometriose infiltrativa profunda com envolvimento intestinal

Abstract Objective The purpose was to assess the rates of postoperative complications and the need of temporary stoma of laparoscopic surgical treatment for bowel endometriosis in a referral center. Methods The surgical indication, type of operation, operative time, length of hospital stay, need for a temporary stoma, rate of conversion to open surgery, postoperative complications were evaluated. Results One-hundred and fifty patients were included. The average duration of surgery was significantly longer for segmental resection (151 minutes) than for disc excision (111.5 minutes, p < 0.001) and shaving (96.8 minutes, p < 0.001). Patients with segmental resection had longer postoperative lengths of hospital stay (1.87 days) compared with patients with disc excision (1.43 days, p < 0.001) and shaving (1.03 days, p < 0.001). A temporary stoma was performed in 2.7% of patients. Grade II and III postoperative complications occurred in 6.7% and 4.7% patients, respectively. Conclusion Laparoscopic intestinal resection has an acceptable postoperative complication rate and a low need for a temporary stoma.

Resumo Objetivo O objetivo foi avaliar as taxas de complicações pós-operatórias e a necessidade de estomia temporária do tratamento cirúrgico laparoscópico para endometriose intestinal em um centro de referência. Métodos Foram avaliados a indicação cirúrgica, tipo de operação, tempo operatório, tempo de internação, necessidade de estomia temporária, taxa de conversão para cirurgia aberta, complicações pós-operatórias. Resultados Cento e cinquenta pacientes foram incluídos. A duração média da cirurgia foi significativamente maior para a ressecção segmentar (151 minutos) do que para a excisão do disco (111,5 minutos, p < 0,001) e shaving (96,8 minutos, p < 0,001). Pacientes com ressecção segmentar tiveram maior tempo de internação pós-operatória (1,87 dias) em comparação com pacientes com excisão de disco (1,43 dias, p < 0,001) e shaving (1,03 dias, p < 0,001). Um estoma temporário foi realizado em 2,7% dos pacientes. Complicações pós-operatórias de grau II e III ocorreram em 6,7% e 4,7% dos pacientes, respectivamente. Conclusão A ressecção intestinal laparoscópica apresenta taxa aceitável de complicações pós-operatórias e baixa necessidade de estomia temporária.

Postoperative Complications and Stoma Rates After Laparoscopic Resection of Deep Infiltrating Endometriosis with Bowel Involvement.

OBJECTIVE: The purpose was to assess the rates of postoperative complications and the need of temporary stoma of laparoscopic surgical treatment for bowel endometriosis in a referral center. METHODS: The surgical indication, type of operation, operative time, length of hospital stay, need for a temporary stoma, rate of conversion to open surgery, postoperative complications were evaluated. RESULTS: One-hundred and fifty patients were included. The average duration of surgery was significantly longer for segmental resection (151 minutes) than for disc excision (111.5 minutes, p < 0.001) and shaving (96.8 minutes, p < 0.001). Patients with segmental resection had longer postoperative lengths of hospital stay (1.87 days) compared with patients with disc excision (1.43 days, p < 0.001) and shaving (1.03 days, p < 0.001). A temporary stoma was performed in 2.7% of patients. Grade II and III postoperative complications occurred in 6.7% and 4.7% patients, respectively. CONCLUSION: Laparoscopic intestinal resection has an acceptable postoperative complication rate and a low need for a temporary stoma.

OBJETIVO: O objetivo foi avaliar as taxas de complicações pós-operatórias e a necessidade de estomia temporária do tratamento cirúrgico laparoscópico para endometriose intestinal em um centro de referência. MéTODOS: Foram avaliados a indicação cirúrgica, tipo de operação, tempo operatório, tempo de internação, necessidade de estomia temporária, taxa de conversão para cirurgia aberta, complicações pós-operatórias. RESULTADOS: Cento e cinquenta pacientes foram incluídos. A duração média da cirurgia foi significativamente maior para a ressecção segmentar (151 minutos) do que para a excisão do disco (111,5 minutos, p < 0,001) e shaving (96,8 minutos, p < 0,001). Pacientes com ressecção segmentar tiveram maior tempo de internação pós-operatória (1,87 dias) em comparação com pacientes com excisão de disco (1,43 dias, p < 0,001) e shaving (1,03 dias, p < 0,001). Um estoma temporário foi realizado em 2,7% dos pacientes. Complicações pós-operatórias de grau II e III ocorreram em 6,7% e 4,7% dos pacientes, respectivamente. CONCLUSãO: A ressecção intestinal laparoscópica apresenta taxa aceitável de complicações pós-operatórias e baixa necessidade de estomia temporária.

PREVALENCE AND PREDICTIVE FACTORS ASSOCIATED WITH POSITIVITY OF SARS-COV-2 SEROLOGICAL MARKERS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE AT AN IBD REFERRAL CENTER.

BACKGROUND: Data related to SARS-CoV-2 exposure rates in patients with inflammatory bowel diseases (IBD) are scarce. Objective - Our aim was to determine the prevalence of serological markers of SARS-Cov-2 and the predictive factors for positivity in patients with IBD. METHODS: This is a cross-sectional, observational study carried out from May to September 2020. SARS-CoV-2 serological markers were determined using chemiluminescence immunoassay in 233 IBD patients without evidence of COVID-19 symptoms. Patient age was 36.6±11.1 years, 118 patients were male (50.6%), and 63.1% had Crohn's disease. Patient clinical data were extracted from individual electronic medical records and complemented by a structured interview. RESULTS: Twenty-six out of the 233 patients with IBD had positive serum markers for SARS-CoV-2 (11.2%). Female sex (P<0.003), extra-intestinal manifestations (P=0.004), use of corticosteroids (P=0.049), and previous contact with individuals with flu-like symptoms (P<0.001) or confirmed diagnosis of COVID-19 (P<0.001), were associated with a significant increased rate of positive SARS-Cov-2 serological markers. No significant difference was observed regarding to adherence to protection measures and positivity of SARS-Cov-2 serological markers (P>0.05). CONCLUSION: SARS-CoV-2 previous infection in IBD patients was not that uncommon, and its prevalence was 11.2% in our series. Positivity to SARS-CoV-2 serological markers was associated with female sex, extra-intestinal manifestations, use of corticosteroids, and contact with individuals with suspected or confirmed COVID-19. Studies with longer follow-up periods are needed to confirm these findings.

Acetylcholine, Fatty Acids, and Lipid Mediators Are Linked to COVID-19 Severity.

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4 Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1ß, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Prevalêncıa e fatores predıtıvos assocıados à posıtıvıdade dos marcadores serológıcos do SARS-COV-2 em pacıentes com doença ınflamatórıa ıntestınal em um centro de referêncıa em DII / Prevalence and predictive factors associated with positivity of sars-cov-2 serological markers in patients with inflammatory bowel disease at an ibd referral center

ABSTRACT Background: Data related to SARS-CoV-2 exposure rates in patients with inflammatory bowel diseases (IBD) are scarce. Objective - Our aim was to determine the prevalence of serological markers of SARS-Cov-2 and the predictive factors for positivity in patients with IBD. Methods: This is a cross-sectional, observational study carried out from May to September 2020. SARS-CoV-2 serological markers were determined using chemiluminescence immunoassay in 233 IBD patients without evidence of COVID-19 symptoms. Patient age was 36.6±11.1 years, 118 patients were male (50.6%), and 63.1% had Crohn's disease. Patient clinical data were extracted from individual electronic medical records and complemented by a structured interview. Results: Twenty-six out of the 233 patients with IBD had positive serum markers for SARS-CoV-2 (11.2%). Female sex (P<0.003), extra-intestinal manifestations (P=0.004), use of corticosteroids (P=0.049), and previous contact with individuals with flu-like symptoms (P<0.001) or confirmed diagnosis of COVID-19 (P<0.001), were associated with a significant increased rate of positive SARS-Cov-2 serological markers. No significant difference was observed regarding to adherence to protection measures and positivity of SARS-Cov-2 serological markers (P>0.05). Conclusion: SARS-CoV-2 previous infection in IBD patients was not that uncommon, and its prevalence was 11.2% in our series. Positivity to SARS-CoV-2 serological markers was associated with female sex, extra-intestinal manifestations, use of corticosteroids, and contact with individuals with suspected or confirmed COVID-19. Studies with longer follow-up periods are needed to confirm these findings.

RESUMO Contexto: Dados relacionados às taxas de exposição ao SARS-CoV-2 em pacientes com doenças inflamatórias intestinais (DII) são escassos. Objetivo Nosso objetivo foi determinar a prevalência de marcadores sorológicos do SARS-Cov-2 e os fatores preditivos de positividade em pacientes com DII. Métodos: Este foi um estudo transversal observacional realizado no período de maio a setembro de 2020. Os marcadores sorológicos SARS-CoV-2 foram determinados por imunoensaio de quimioluminescência em 233 pacientes com DII sem evidência de sintomas de COVID-19. A idade dos pacientes foi 36,6±11,1 anos, 118 pacientes eram do sexo masculino (50,6%) e 63,1% tinham doença de Crohn. Os dados clínicos dos pacientes foram extraídos de prontuários médicos eletrônicos individuais e complementados por meio de uma entrevista estruturada. Resultados: Vinte e seis dos 233 pacientes com DII apresentaram marcadores sorológicos positivos para SARS-CoV-2 (11,2%). Sexo feminino (P<0,003), manifestações extra-intestinais (P=0,004), uso de corticosteroides (P=0,049) e contato prévio com indivíduos com sintomas gripais (P<0,001) ou diagnóstico confirmado de COVID -19 (P<0,001), foram associados a um aumento significativo da taxa de positividade para marcadores sorológicos do SARS-Cov-2. Não foi observada diferença significativa em relação à adesão às medidas de proteção e positividade dos marcadores sorológicos para o SARS-Cov-2 (P>0,05). Conclusão: A infecção prévia pelo SARS-CoV-2 não é tão incomum em pacientes com DII e sua prevalência em nossa série foi de 11,2%. A positividade aos marcadores sorológicos SARS-CoV-2 foi associada ao sexo feminino, manifestações extra-intestinais, uso de corticosteroides e contato com indivíduos com suspeita ou diagnóstico confirmado de COVID-19. Estudos com períodos de acompanhamento mais longos são necessários para confirmar esses achados.

Factors Predictive of Proximal Disease Extension and Clinical Course of Patients Initially Diagnosed with Ulcerative Proctitis in an IBD Referral Center.

BACKGROUND: This study aims to determine whether risk factors at the time of diagnosis that are found to be predictive of proximal dis- ease extension in ulcerative proctitis (UP) occur in a cohort of Brazilian patients. METHODS: This is a retrospective analysis of data from 97 patients (67% female) with UP (Montreal classification: E1) with at least 12 months of follow-up who were admitted to the Ribeirão Preto Medical School IBD referral center between January 2001 and December 2018. Proximal disease extension, which was defined as E1 progressing to E3 (pancolitis), was evaluated endoscopically during follow-up. RESULTS: A total of 29 (29.9%) patients experienced proximal disease extension. The risk factors at diagnosis associated with proximal disease extension were younger age (<40 years; P = .012), higher Mayo endoscopic score (P < .0001), higher partial Mayo score (P = .0018), and use of oral corticosteroids (P = .0016). During the follow-up period, increased disease relapse rates (P < .0001), immuno- modulators (P = .00014) or the use of biological agents (P = .00037), and colectomy (P = .0002) were all significantly higher among UP patients with proximal disease extension. CONCLUSION: Similar to what has been demonstrated in other studies, Brazilian UP patients with increased clinical and endoscopic sever- ity at the time of diagnosis are likely to evolve with both proximal extension and a more adverse clinical course. Therefore, these patients should be followed-up more carefully.

Matrix Metalloproteinases on Severe COVID-19 Lung Disease Pathogenesis: Cooperative Actions of MMP-8/MMP-2 Axis on Immune Response through HLA-G Shedding and Oxidative Stress.

Patients with COVID-19 predominantly have a respiratory tract infection and acute lung failure is the most severe complication. While the molecular basis of SARS-CoV-2 immunopathology is still unknown, it is well established that lung infection is associated with hyper-inflammation and tissue damage. Matrix metalloproteinases (MMPs) contribute to tissue destruction in many pathological situations, and the activity of MMPs in the lung leads to the release of bioactive mediators with inflammatory properties. We sought to characterize a scenario in which MMPs could influence the lung pathogenesis of COVID-19. Although we observed high diversity of MMPs in lung tissue from COVID-19 patients by proteomics, we specified the expression and enzyme activity of MMP-2 in tracheal-aspirate fluid (TAF) samples from intubated COVID-19 and non-COVID-19 patients. Moreover, the expression of MMP-8 was positively correlated with MMP-2 levels and possible shedding of the immunosuppression mediator sHLA-G and sTREM-1. Together, overexpression of the MMP-2/MMP-8 axis, in addition to neutrophil infiltration and products, such as reactive oxygen species (ROS), increased lipid peroxidation that could promote intensive destruction of lung tissue in severe COVID-19. Thus, the inhibition of MMPs can be a novel target and promising treatment strategy in severe COVID-19.