ADHERENCE AND PERSISTENCE TO TREATMENT WITH INFLIXIMAB: ANALYSIS OF A PATIENT SUPPORT PROGRAM COHORT IN BRAZIL.

BACKGROUND: Monoclonal antibodies have proven efficacy in the management of several conditions and infliximab (IFX) is one of the most important drugs of the class. Some recent data have shown low rates of both persistence and adherence to several available biologics. OBJECTIVE: The objective of this study was to describe adherence and persistence rate to IFX treatment and also persistence in the patient support program (PSP), among patients diagnosed with inflammatory bowel diseases (IBD) or rheumatic diseases (RD) enrolled in the program of a large pharmaceutical company in Brazil. METHODS: Retrospective observational analysis using the PSP database. IBD or RD patients using IFX enrolled on the PSP database between September 2015 and August 2019 were retrospectively evaluated to identify the persistence rate and adherence and followed up until March 1, 2020. Patients were excluded if treatment start date was prior to program entry; first infusion prior to September 1st, 2015 or after August 31st, 2019; the patients did not started treatment; and patients with "OTHERS" in "Indication" field. Persistence was assessed considering both persistence in the program ("PSP persistence") and persistence on IFX in the PSP ("IFX persistence in the PSP"). PSP persistence was defined as the proportion of patients remaining in the program at 6, 12, 24, 36 and 48 months after initiating IFX. To determine IFX persistence in the PSP, censoring was defined at the time the patient left the program, died, or was lost to follow-up. Adherence to treatment was measured by medication possession ratio ((MPR) - All days supply / elapsed days from first prescription to last day of medication possession)). Descriptive statistics were initially used. Kaplan-Meier curve, the median time estimated by the survival function, Cox regression model, and restricted mean survival time (RMST) were used to evaluate the treatment persistence time at 24 months and the logistic regression model was performed aiming to identify variables associated with adherence (MPR ≥80%). RESULTS: A total of 10,233 patients were analyzed, 5,826 (56.9%) with the diagnosis of RD and 4,407 (43.1%) of IBD. At the end of the follow-up (median 9.1 months from PSP entry to the last infusion), persistence in the PSP was 65.6%, 48.2%, 31.0%, 20.7% and 13.1% at 6, 12, 24, 36 and 48 months, respectively. Considering persistence on IFX in the PSP, estimates were 93.7%, 87.8%, 77.0%, 62.4% and 53.0% at 6, 12, 24, 36 and 48 months, respectively. Variables associated with the risk of non-persistence were gender, country region and diagnosis of rheumatoid arthritis and ankylosing spondylitis. Median MPR was 94.2%, while the percentage of patients with MPR ≥80% was 91.0%. Variables associated with MPR≥80% were country region and diagnosis of Crohn's disease. CONCLUSION: Many patients leave the program without discontinuing IFX, since the 12-month persistence were very different between program and medication estimates, while high adherence rates were observed among patients enrolled in the PSP. Data highlights the benefits of a PSP.

Is religiosity/spirituality in patients with Crohn's disease important to their quality of life?

The authors aim to study Religiosity/Spirituality (R/S) and Quality of Life (QoL) in patients with Crohn's disease and their correlation with the disease phenotypes. METHODS: Prospective cross-sectional cohort study with 151 consecutive patients enrolled from March 2021 to October 2021 at the Colorectal IBD Outpatient of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Sociodemographic, Religiosity/Spirituality (Duke University Religion Index - Durel) questionnaires and QoL (Inflammatory Bowel Disease Questionnaire - Short IBDQ-S) were applied. When necessary, qualitative variables were evaluated using the chi-square or Fisher's exact test. The Mann-Whitney and Kruskall-Wallis tests were used to analyze quantitative variables and compare more than two groups, both non-parametric statistical techniques. RESULTS: The most frequent location was Ileocolonic followed by Ileal and colonic (41.1 %, 27.2 %, and 25.2 %); only 6.6 % of subjects had a perianal presentation. Inflammatory, stenosing, and penetrating behaviors showed 36.4 %, 19.1 %, and 44.4 % respectively. The majority of the population is Catholic, Evangelical, or Spiritualist (92.4 %). QoL score showed no significant difference in the phenotypes. The scores for DUREL domains were 61.4 % for organizational religiosity, 75 % for non-organizational religiosity, 98.6 %, 93.6 % and 89.3 % for intrinsic spirituality, with high results in all disease phenotypes. CONCLUSIONS: The studied population presented homogeneous sociodemographic results and high religious and spiritual activity. R/S in a positive context were not associated with better QoL or phenotype. R/S is present in the patients' lives and could be seen as an important tool for adherence to treatment and the professional relationship between doctor and patient. The homogeneity of the sample difficult for an appropriate evaluation, which leads us to suggest new studies with more heterogeneous groups.

RISK FACTORS FOR EARLY POSTOPERATIVE COMPLICATIONS IN ACUTE COLITIS IN THE ERA OF BIOLOGIC THERAPY.

BACKGROUND: Despite major advances in the clinical treatment of inflammatory bowel disease, some patients still present with acute colitis and require emergency surgery. AIMS: To evaluate the risk factors for early postoperative complications in patients undergoing surgery for acute colitis in the era of biologic therapy. METHODS: Patients with inflammatory bowel disease admitted for acute colitis who underwent total colectomy at a single tertiary hospital from 2012 to 2022 were evaluated. Postoperative complications were graded according to Clavien-Dindo classification (CDC). Patients with more severe complications (CDC≥2) were compared with those with less severe complications (CDC<2). RESULTS: A total of 46 patients underwent surgery. The indications were: failure of clinical treatment (n=34), patients' or surgeon's preference (n=5), hemorrhage (n=3), toxic megacolon (n=2), and bowel perforation (n=2). There were eight reoperations, 60.9% of postoperative complications classified as CDC≥2, and three deaths. In univariate analyses, preoperative antibiotics use, ulcerative colitis diagnosis, lower albumin levels at admission, and preoperative hospital stay longer than seven days were associated with more severe postoperative complications. CONCLUSIONS: Emergency surgery for acute colitis was associated with a high incidence of postoperative complications. Preoperative use of antibiotics, ulcerative colitis, lower albumin levels at admission, and delaying surgery for more than seven days were associated with more severe early postoperative complications. The use of biologics was not associated with worse outcomes.

Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV in the anorectal fistula tract. A comparative study.

BACKGROUND & AIMS: Perianal fistulizing Crohn's disease is the main risk factor for anal cancer in patients with inflammatory bowel disease. Whether this occurs due to a higher frequency of human papillomavirus remains unclear. The authors aimed to evaluate the prevalence of HPV and high-risk HPV in patients with perianal Crohn's disease, compared with a control group. METHODS: The authors conducted a two-center cross-sectional study in which perianal fistulizing Crohn's disease patients were matched for age and sex with patients with anorectal fistula without Crohn's disease. Biopsy specimens were obtained from fistulous tracts during examination under anesthesia for both groups. The samples were sent for HPV detection and genotyping using the INNO-LiPA test. RESULTS: A total of 108 subjects (54 in each group) were recruited. The perianal fistulizing Crohn's disease group showed a statistically higher frequency of HPV in the fistulous tract than the control group (33.3% vs. 16.7%; p = 0.046). Separate analyses on high-risk types demonstrated that there was a numerically higher frequency of HPV in the perianal fistulizing Crohn's disease group. In multiple logistic regression, patients with perianal fistulizing Crohn's disease were found to have a chance of HPV 3.29 times higher than patients without Crohn's disease (OR = 3.29; 95% CI 1.20‒9.01), regardless of other variables. The types most frequently identified in the perianal fistulizing Crohn's disease group were HPV 11 (12.96%) and HPV 16 (9.26%). CONCLUSION: Perianal fistulizing Crohn's disease is associated with a higher prevalence of HPV than in patients with anorectal fistula without Crohn's disease.

STAPLED HEMORRHOIDOPEXY: RESULTS, LATE COMPLICATIONS, AND DEGREE OF SATISFACTION AFTER 16 YEARS OF FOLLOW-UP.

BACKGROUND: Stapled hemorrhoidopexy has been widely used for the treatment of hemorrhoids, but concerns about complications and recurrences after prolonged follow-up are still under debate. AIMS: The aim of this study was to evaluate the very long-term results of the stapled hemorrhoidopexy technique. METHODS: Stapled hemorrhoidopexy was performed on 155 patients between 2000 and 2003, and the early results have already been published. In this study, we evaluated the same patients after a very long follow-up. Data were collected with regard to late complications, rate and timing of recurrences, and patients' degree of satisfaction. RESULTS: From a total of 155 patients, 98 patients were evaluated: 59 (60.2%) were interviewed by telephone and 39 (39.8%) were evaluated by outpatient consultation. The mean follow-up was 193 months (range: 184-231), 52 were female, 52 were grade III hemorrhoids, and 46 were grade IV. Recurrence was higher in grade IV (26.1%) than in grade III (7.7%) (p=0.014). Recurrence after prolonged follow-up was seen in 16 patients (16.3%) and 11 (11.2%) required reoperations. The complications were skin tags (3.1%), anal sub-stenosis (2.1%), and fecal incontinence (2.1%). After a prolonged follow-up, 82.5% of patients were either very satisfied or satisfied with the surgery. CONCLUSIONS: Stapled hemorrhoidopexy is a safe and effective treatment for hemorrhoidal disease grades III and IV. Recurrence is higher for grade IV hemorrhoids and may occur up to 9 years of follow-up. Reoperations were infrequent and there is a high patient's degree of satisfaction associated with this technique.

Fournier's Gangrene During Pregnancy in a Patient with Crohn's Disease.

BACKGROUND Fournier's gangrene (FG) is a rapidly progressive necrotizing infection of the perineum. Risk factors include male sex and immunosuppression. Inflammatory bowel disease and pregnancy may alter immune response by complex mechanisms but have rarely been associated with necrotizing infections of the perineum. To the best of our knowledge, only 5 cases of FG in association with IBD have been reported in the literature, and none of them occurred during pregnancy. CASE REPORT We report the case of a young woman with long-standing Crohn's disease in clinical remission with Infliximab monotherapy who developed FG in the third trimester of pregnancy. A cesarean section was undertaken at 35 weeks due to fetal distress, followed by debridement, diverting stoma, and vacuum-assisted therapy. The perineal defect was closed following 4 debridements and vacuum-therapy exchanges with a unilateral medial thigh advancement flap, and a draining seton was placed in the suprasphincteric fistula. The patient was discharged after 28 days and her recovery was unremarkable. The neonate also recovered well. CONCLUSIONS The treatment of FG is multidisciplinary and includes early debridement and intestinal diversion. Perianal pain should not be disregarded, as it may be the initial symptom of severe perianal sepsis in the immunosuppressed. To the best of our knowledge, this is the first case report of FG during pregnancy in a patient with Crohn's disease.

A NEW APPROACH FOR HEMORRHOID DISEASE: SELECTIVE DEARTERIALIZATION AND MUCOPEXY WITHOUT DOPPLER GUIDANCE.

BACKGROUND: The surgical procedure: three dearterializations and three mucopexies.Transanal hemorrhoidal dearterialization (THD) is safe and effective minimally invasive treatment for hemorrhoidal disease, but reports regarding recurrence and postoperative complications (pain and tenesmus) vary significantly. AIM: To evaluate if selective dearterialization and mucopexy at the symptomatic hemorrhoid only, without Doppler guidance, achieves adequate control of the prolapse and bleeding and if postoperative morbidity is reduced with this technique. METHODS: Twenty consecutive patients with grade II and III hemorrhoids were treated with this new approach and were evaluated for postoperative complications and recurrence. RESULTS: Control of prolapse and bleeding was achieved in all patients (n=20). Postoperative complications were tenesmus (n=2), external hemorrhoidal thrombosis (n=2) and urinary retention (n=2). After a mean follow-up of 13 months no recurrences were diagnosed. CONCLUSION: Selective dearterialization and mucopexy is safe and achieves adequate control of prolapse and bleeding and, by minimizing sutures in the anal canal, postoperative morbidity is diminished. Doppler probe is unnecessary for this procedure, which makes it also more interesting from an economic perspective.

Spontaneous Knot Formation in a Central Venous Catheter.

BACKGROUND Central venous catheterization (CVC) is indispensable in the management of critically ill patients in the emergency room and intensive care units, either to avoid the various peripheral punctures and vasoactive drugs administration in decompensated patients, or even to administer parenteral nutrition. CVC is an invasive procedure with possible mechanical, infectious, and thrombotic complications. The complete knotting of a catheter is a rare complication. The aim of this study is to report a case of a simple tight knot 2 cm from the catheter tip. We provide insights for early identification of catheter knotting, as well as its management. CASE REPORT A 63-year-old man with a previous history of angioplasty and non-pharmacological coronary stent in a marginal branch of the circumflex coronary artery evolved to junctional bradycardia and cardiogenic shock and was transferred to the reference hospital. He had a CVC inserted in the right jugular vein; however, it did not have any blood flow. The hypothesis of catheter knotting was suggested and confirmed through a chest X-ray. Venotomy was performed and it was successfully removed. CONCLUSIONS Knotting in CVC obstruction is a rare complication. Recognition of this complication is essential to avoid major complications, such as catheter fragmentation and venous injury. Radiological follow-up after the procedure in patients with difficult anatomy is essential, and echo-guided catheterization should be encouraged when available. Despite the rarity of a knotted intravascular catheter, it is important to note this possible late complication that must be considered in the absence of catheter blood flow.

#Crohn's: Historical Cohort of Twitter Activity.

Background: Analysis of the Twitter activity on #Crohn's, identifying individuals with interest in Crohn's disease on Twitter. Methods: A historic cohort study was conducted about Twitter activity evaluation of #Crohn's analyzed over a period of 9 years. For the Twitter analysis, a health-care social media analytics tool, Symplur Signals, was adopted. Results: From 2011 until 2019, 627,000 tweets of #Crohn's were detected, with 276,380 retweets by 109,937 users; of these users, 32.4% were patient advocates and 12.6% were doctors. There was a pattern of annual peak activity of the #Crohn's, mainly in May and December, and less activity, usually in July. Of all tweets, 52.5% were categorized as positive and 47.5% as negative. Conclusions: Social media, especially Twitter, represents an important information tool, but it is still underutilized by gastroenterologists. This study suggests a significant interference of international awareness campaigns about inflammatory bowel disease in the activity of #Crohn's on Twitter, denoting an increase in debating this topic on the platform. Discussions on the subject by health professionals are still below expectations regarding the importance of the theme.

Anorectal Mucosal Melanoma: A Case Report and Literature Review.

BACKGROUND Anorectal mucosal melanoma (AMM) is a rare and aggressive neoplasm, with a 5-year survival rate of 10%. Due to its rarity and nonspecific symptoms, the diagnosis is often made late. Surgical resection remains the criterion standard for treatment of anorectal melanoma. CASE REPORT We present the case of an 81-year-old woman presenting with hematochezia, anal secretion, tenesmus, difficulty in defecation, and perianal pain. On physical examination, there was a prolapse of a 5-cm melanocytic nodule in the anal canal, hard on palpation. Biopsy confirmed anorectal melanoma. Staging revealed anal and metastatic disease, with adrenal, lymphatic, and hepatic involvement. As the patient continued to have bleeding, severe pain, and difficulty in defecation, she was submitted to a wide local excision. At 5-month follow-up, the anal lesion had relapsed, and the patient died 10 months after the procedure. CONCLUSIONS AMM is a rare and extremely aggressive tumor. Symptoms are nonspecific but early diagnosis should be pursued to allow curative treatment. Surgical resection with free margins is the goal of surgical treatment. New therapies are being studied, including immunotherapy, which can improve the dismal prognosis of this rare disease.

Abdominal Surgery in Crohn's Disease: Risk Factors for Complications.

INTRODUCTION: Abdominal surgery in patients with Crohn's disease (CD) is challenging, especially in the biologic era. The aim of this study was to evaluate factors associated with increased risk for postoperative complications in CD. METHODS: A retrospective study was conducted with consecutive patients who underwent abdominal surgery for CD from January 2012 to January 2018. RESULTS: Of 103 patients, 32% had postoperative complications. Gender, age, disease location and phenotype, hemoglobin and albumin levels, previous abdominal surgery, and preoperative optimization did not differ between the groups with or without complications. Thirty-five percent of the patients were under anti-TNF therapy, and this medication was not associated with increased risk for postoperative complications. Time since the onset of the disease was significantly higher in patients with complications (12.9 vs. 9.4, p = 0.04). In multivariate analysis, creation of ostomy and urgent surgery were the only variables independently associated with increased risk for complications (OR 3.2, 95% CI 1.12-9.46 and OR 2.94, 95% CI 0.98-9.09, respectively). CONCLUSION: Urgent surgery for CD should preferably be performed in specialized centers, and creation of stoma is not necessarily associated with lower rate of postoperative complications but rather less severe complications.

Coexistence of Takayasu's Arteritis in Patients with Inflammatory Bowel Diseases.

BACKGROUND: Takayasu's arteritis (TA) and inflammatory bowel disease (IBD) are chronic inflammatory granulomatous disorders that have rarely been concomitantly reported in case reports and small case series. OBJECTIVE: We report a series of seven cases of TA and IBD association in two referral centers with a comprehensive review of literature. METHODS: We analyzed retrospectively the electronic medical charts of TA-IBD patients at the University Hospital of São Paulo, Brazil, and at the Sheba Medical Center at Tel Aviv University, Israel. RESULTS: Overall, five patients had Crohn's disease (DC) and two had ulcerative colitis (UC), and they were mostly female and non-Asian. All patients developed IBD first and, subsequently, TA. Two underwent colectomy and one ileocecectomy due to IBD activity, while three required cardiovascular surgery due to TA activity. Most patients are currently in clinical remission of both diseases with conventional drug treatment. CONCLUSION: Although the coexistence of TA and IBD is uncommon, both seem to be strongly associated through pathophysiological pathways.

The novel BPRST classification for hemorrhoidal disease: A cohort study and an algorithm for treatment.

BACKGROUND: The classification for HD was developed by Goligher in 1980 and does not contemplate important aspects of this disease, which limits its use in guiding treatment. The aim of this study if to apply in clinical practice the new classification for hemorrhoids named BPRST (bleeding, prolapse, reduction, skin tags, thrombosis), to compare it with the original classification proposed by Goligher and to propose an algorithm for treatment. MATERIALS AND METHODS: This is a prospective study conducted at the University of São Paulo's teaching hospital and Hospital 9 de Julho. Patients with HD treated from March 2011 to July 2013 were included. Patients were classified according to BPRST and Goligher classifications and treated according to personal experience and most updated guidelines. The association between both classifications and the treatment adopted was compared and an algorithm for treatment was developed. RESULTS: 229 patients were included in this study and 28 patients were lost due to follow-up. According to Goligher, 29, 61, 85 and 26 were classified as grades I, II, III and IV, respectively. According to the BPRST, 23 were classified as stage I, 95 as stage II and 83 as stage III. Six patients classified as Goligher I were reclassified as BPRST stage III and required conventional hemorrhoidectomy, either due to thrombosis (n = 4) or intolerable skin tags (n = 2). The BPRST classification was more closely associated with the type of treatment employed and had few outliers than Goligher (p < 0.001). CONCLUSION: There are limitations to the use of Goligher's classification in clinical practice. The novel BPRST classification includes important aspects of HD that should be considered when deciding the best treatment option. Our algorithm for treatment contemplates the most commonly used techniques and can help to guide the treatment of this complex disease.

CRITICAL ANALYSIS OF ANTI-TNF USE IN THE ERA OF NEW BIOLOGICAL AGENTS IN INFLAMMATORY BOWEL DISEASE.

BACKGROUND: Inflammatory bowel diseases (IBD), both Crohn's disease and ulcerative colitis, are chronic immune-mediated diseases that present a relapsing and remitting course and requires long-term treatment. Anti-tumor necrosis factor (anti-TNF) therapy has changed the management of the disease by reducing the need for hospitalizations, surgeries and improving patient´s quality of life. OBJECTIVE: The aim of this review is to discuss the role of anti-TNF agents in IBD, highlighting the situations where its use as first-line therapy would be appropriate. METHODS: Narrative review summarizing the best available evidence on the topic based on searches in databases such as MedLine and PubMed up to April 2020 using the following keywords: "inflammatory bowel disease'', "anti-TNF agents" and ''biologic therapy''. CONCLUSION: Biological therapy remains the cornerstone in the treatment of IBD. In the absence of head-to-head comparisons, the choice of the biological agent may be challenging and should take into account several variables. Anti-TNF agents should be considered as first line therapy in specific scenarios such as acute severe ulcerative colitis, fistulizing Crohn's disease and extra-intestinal manifestations of IBD, given the strong body of evidence supporting its efficacy and safety in these situations.

Transanal hemorrhoidal dearterialization: Lessons learned from a personal series of 200 consecutive cases and a proposal for a tailor-made procedure.

BACKGROUND: Transanal hemorrhoidal dearterialization (THD) is an effective treatment for hemorrhoidal disease (HD). However, the surgical technique is not standardized and the results for advanced HD are controversial. The aim of this study was to assess surgical outcomes after a long follow-up and compare total and partial mucopexy. MATERIALS AND METHODS: Between March 2011 and July 2014, THD was offered to patients with symptomatic prolapsed hemorrhoids (Grades II, III and IV). Dearterialization was performed with the guidance of Ultrasound Doppler and mucopexy for prolapsed piles, and regarded as total or partial (if less than 6 mucopexies). Post-operative complications, long-term results and patients' satisfaction rates were analyzed. RESULTS: 200 consecutive patients were recruited with a mean follow-up of 43 months (range 29 - 57 months). HD distribution was GII (N = 35, 17.5%), GIII (N = 124, 62%), and GIV (N = 41, 20.5%). Postoperative complications included transient tenesmus (26,5%), pain (14%) and fecal impaction (2,5%). Recurrence rates were 0, 2,4% and 17,1% for prolapse (p < 0,01) and 2,9%, 4% and 9,8% for bleeding (p = 0,33) in grades II, III and IV, respectively. Total mucopexy resulted in more tenesmus (31,2%) than partial mucopexy (14,5%), (p < 0,01). After 12 weeks of follow-up, 85% of patients were either very satisfied or satisfied; 8,5% were dissatisfied. CONCLUSION: THD-mucopexy is safe with low overall recurrence. Grade IV HD is associated with more recurrence and postoperative complications. Total mucopexy is associated with more tenesmus, pain and fecal impaction. A tailor-made procedure with selective dearterialization and mucopexy may be the next step in this evolving technique.

TRANSANAL HAEMORRHOIDAL DEARTERIALIZATION WITH MUCOPEXY (THD-M) FOR TREATMENT OF HEMORRHOIDS: IS IT APPLICABLE IN ALL GRADES? BRAZILIAN MULTICENTER STUDY.

BACKGROUND: Transanal haemorrhoidal dearterialization with mucopexy (THD-M) is a valuable option for treating patients with haemorrhoidal disease. However, there is still controversy with regard to its efficacy for more advanced grades. AIM: To evaluate the effectiveness of THD-M technique for treating hemorrhoidal disease and to compare the immediate and late results in different grades. METHOD: Seven hundred and five consecutive patients with Goligher's grade II, III or IV symptomatic haemorrhoids underwent surgical treatment using the THD-M method in five participating centres. Six well-trained and experienced surgeons operated on the patients. Average follow-up was 21 months (12-48). RESULTS: Intraoperative complications were observed in 1.1% of cases, including four cases of haematoma, two of laceration of the mucosa, and two of bleeding. All of these were controlled by means of haemostatic suturing. In relation to postoperative complications, the most common of these were as follows: transitory tenesmus (21.4%); pain (7.2%); mucosal or haemorrhoidal prolapse (6.4%); residual skin tag (5.6%); faecal impaction (3.2%); haemorrhoidal thrombosis (2.8%); bleeding (2.1%); anal fissure (0.7%); and anal abscess (0.3%). Most of the complications were treated conservatively, and only 7.5% (53/705) required some type of surgical approach. There was no mortality or any severe complications. The recurrence of prolapse and bleeding was greater in patients with grade IV haemorrhoidal disease than in those with grade III and II (26.54% and 7.96% vs. 2.31% and 0.92% vs. 2.5% and 1.25%), respectively. CONCLUSION: The THD-M method is safe and effective for haemorrhoidal disease grades II and III with low rates of surgical complications. However, for grade IV hemorrhoids, it is associated with higher recurrence of prolapse and bleeding. So, THD-M method should not be considered as an effective option for the treatment of grade IV hemorrhoids.