Response to Ustekinumab Therapy Is Associated with an Improvement of Nutritional Status in Patients with Crohn's Disease.

The presence of sarcopenia has been associated with the worst outcome of Crohn's disease (CD). At present, no studies have evaluated the impact of ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition as assessed by bioelectrical impedance assay (BIA) in patients with CD. We prospectively enrolled consecutive patients with CD treated with UST, evaluating the therapeutic outcome at week 48 in terms of clinical remission and mucosal healing. BIA was performed at baseline and at week 48, assessing body cellular mass, total body water, phase angle, and body mass index. Out of 44 patients enrolled, 26 (59%) were in clinical remission and 22 (50%) achieved mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value = 0.009 and 0.007 for clinical remission and mucosal healing, respectively). The same differential increase was observed for body cellular mass (test for the interaction between time and outcome, p-value = 0.03 and 0.05 for clinical remission and mucosal healing, respectively). Total body water and BMI increased homogenously over time regardless of the outcomes (tests for the association with time, p-values of 0.01). To conclude, responsiveness to UST therapy seems to be associated with body composition modifications in patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients.

Serum oncostatin M predicts mucosal healing in patients with inflammatory bowel diseases treated with anti-TNF, but not vedolizumab.

BACKGROUND: Oncostatin M was recently highlighted as a promising biomarker for therapeutic effectiveness in inflammatory bowel diseases (IBD), with particular regard for infliximab. The primary aim was to evaluate the ability of serum oncostatin M to predict endoscopic response to different drugs in IBD. METHODS: We selected two different cohorts of patients with IBD, treated with anti-TNF (infliximab and adalimumab) or with vedolizumab. Therapeutic response was evaluated at week 54 in terms of mucosal healing. Serum oncostatin M and C-reactive protein were measured at baseline; fecal calprotectin was measured at baseline and after 14 weeks of treatment. We evaluated the association of these biomarkers with mucosal healing at week 54. RESULTS: Among 66 patients treated with anti-TNFs and 68 treated with vedolizumab, 35 and 31 attained mucosal healing, respectively. Mucosal healing at 54 weeks was significantly associated with low oncostatin M levels at baseline in the anti-TNF cohort; the diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing was 0.91 (95% CI 0.84 to 0.99) in the anti-TNF cohort and 0.56 (95% CI 0.43 to 0.70, P < 0.001) in the vedolizumab cohort. Mucosal healing was also associated with low fecal calprotectin levels at week 14 in both cohorts. CONCLUSION: Our study suggests that serum oncostatin M is a drug-specific biomarker, since it could be used to predict therapeutic effectiveness to anti-TNFs but not to vedolizumab. Moreover, these results emphasize the utility of serum oncostatin M measurement in patients treated with anti-TNF.

Evidence-based efficacy of methotrexate in adult Crohn's disease in different intestinal and extraintestinal indications.

Introduction: Methotrexate (MTX) is included in the therapeutic armamentarium of Crohn's disease (CD), although its positioning is currently uncertain in an era in which many effective biological drugs are available. No systematic reviews or meta-analysis have stratified the clinical outcomes of MTX according to the specific clinical scenarios of its use. Methods: Medline, PubMed and Scopus were used to extract eligible studies, from database inception to May 2021. A total of 163 studies were included. A systematic review was performed by stratifying the outcomes of MTX according to formulation, clinical indication and criteria of efficacy. Results: The use of MTX is supported by randomized clinical trials only in steroid-dependent CD, with similar outcomes to thiopurines. The use of MTX in patients with steroid-refractoriness, failure of thiopurines or in combination with biologics is not supported by high levels of evidence. Combination therapy with biologics can optimize the immunogenic profile of the biological drug, but the impact on long-term clinical outcomes is described only in small series with anti-TNFα. Other off-label uses, such as fistulizing disease, mucosal healing, postoperative prevention and extraintestinal manifestations, are described in small uncontrolled series. The best performance in most indications was shown by parenteral MTX, favouring higher doses (25 mg/week) in the induction phase. Discussion: Evidence from high-quality studies in favour of MTX is scarce and limited to the steroid-dependent disease, in which other drugs are the leading players today. Many limitations on study design have been found, such as the prevalence of retrospective underpowered studies and the lack of stratification of outcomes according to specific types of patients and formulations of MTX. Conclusion: MTX is a valid option as steroid-sparing agent in steroid-dependent CD. Numerous other clinical scenarios require well-designed clinical studies in terms of patient profile, drug formulation and dosage, and criteria of efficacy.

Vitamin D-Related Genetics as Predictive Biomarker of Clinical Remission in Adalimumab-Treated Patients Affected by Crohn's Disease: A Pilot Study.

Adalimumab (ADA) is a human anti-tumor necrosis factor (TNF-α) monoclonal antibody used in inflammatory bowel diseases, such as Crohn's disease (CD). Vitamin-D (VD) is important for biological functions, such as the modulation of expression of genes encoding enzymes and transporters involved in drug metabolism and transport. ADA trough levels were associated with VD concentrations in patients with IBD, but no data are present in the literature concerning VD pathway-related gene single-nucleotide polymorphisms (SNPs) in affecting clinical outcomes. For this reason, the aim of this study was to evaluate the ability of VD-related genetics to predict clinical remission at 3 and 12 months in patients affected by CD treated with ADA. Patients affected by CD were included in this study. SNPs in CYP27B1, CYP24A1, GC, and VDR genes were analyzed through real-time PCR. A total of 63 patients were enrolled. Calprotectin, hemoglobin, and C-reactive protein levels were influenced by SNPs in VDR, CYP27B1, and GC genes. After 3 months of therapy, clinical remission was predicted by smoke, systemic steroids, and VDR BsmI, whereas at 12 months by GC 1296AA/AC and VD supplementation. This study reports the association between VD pathway-related genetics and ADA treatment. Further studies are needed to confirm these promising data.

Hospitalisation for Drug Infusion Did Not Increase Levels of Anxiety and the Risk of Disease Relapse in Patients with Inflammatory Bowel Disease during COVID-19 Outbreak.

During the coronavirus disease 2019 (COVID-19) pandemic, immunomodulatory therapies and hospital admission were suspected to increase the risk of infection. Nevertheless, patients with inflammatory bowel diseases (IBD) treated with intravenous (i.v.) biologics had to move to hospitals for drug infusion. We investigated the impact of hospitalisation in patients with IBD. We conducted a survey including consecutive IBD patients initially in clinical and biochemical remission treated with biologics at the end of the first lockdown period. Patients underwent the normally scheduled clinical visits, performed at hospital for i.v.-treated patients or at home for patients treated with s.c. drugs. We administered to all patients the Hospital Anxiety and Depression Scale (HADS) questionnaire and other 12 questions, specifically related to COVID-19 and its implications. A total of 189 IBD patients were recruited, 112 (59.3%) treated with i.v. drugs and 77 (40.7%) with s.c. ones. No relapses were recorded in either group (hospitalized vs. non-hospitalized, p = ns), as well as which, COVID-19 infections were not demonstrated in patients in contact with people with suspected symptoms or directly experiencing them. The total HADS score obtained by the sum of all items was also almost identical between groups (37.1 ± 2.8 vs. 37.2 ± 2.8; p = 0.98). In patients treated with i.v. drugs receiving a televisit (n = 17), the rate of satisfaction with telemedicine (58.8%) was significantly lower compared with those treated with s.c. drugs (94.8%; p < 0.0005). Our results suggest that hospitalisation during the COVID-19 outbreak does not increase the risk of COVID-19 infection as well as the risk of IBD relapse; moreover, the similar levels of anxiety in both groups could confirm that there is no need to convert patients from i.v. to s.c. therapy.

Ig Glycosylation in Ulcerative Colitis: It's Time for New Biomarkers.

Background: Ulcerative colitis (UC) is a chronic relapsing disease, which needs a continue monitoring, especially during biological therapies. An increasing number of patients is treated with anti-Tumor Necrosis factor (TNF) drugs, and current research is focalized to identify biomarkers able to monitor the disease and to predict therapeutic outcome. Methods: We enrolled consecutive UC patients treated with anti-TNF, naïve to biologic drugs. Therapeutic outcome was evaluated after 54 weeks of treatment in terms of clinical remission (Partial Mayo Score -PMS- <2) and mucosal healing (Mayo Endoscopic Score <2). On serum samples collected at baseline and after 54 weeks of treatment, a Lectin-based ELISA assay was performed, and specific glycosylation patterns were evaluated by biotin-labelled lectins. We have also collected 21 healthy controls (NHS) samples, age and sex-matched. Results: Out of 44 UC patients enrolled, 22 achieved clinical remission and mucosal healing after 54 weeks. At baseline, when Protein A was used as coating, UC patients non-responders showed a reduced reactivity to Jacalin (JAC) in comparison with NHS (p = 0.04). After one year of treatment, a decrease in JAC binding was seen only in responders, in comparison with baseline (p = 0.04). When JAC binding was tested selecting IgG by means of Fab anti-IgG Fab, UC patients displayed an increased reactivity after anti-TNF therapy (p < 0,0001 vs controls). At baseline, PMS inversely correlates with JAC binding when Fab anti-IgG Fab was used in solid phase (r 2 = 0,2211; p = 0,0033). Patients with higher PMS at baseline (PMS ≥5) presented lower binding capacity for JAC in comparison with NHS and with lower PMS patients (p = 0,0135 and p = 0,0089, respectively). Conclusion: Ig glycosylation was correlated with clinical and endoscopic activity in patients with UC. JAC protein A-selected Ig showed a possible role in predicting therapeutic effectiveness. If these data would be confirmed, Ig glycosylation could be used as biomarker in UC.

Oral Sucrosomial Iron Is as Effective as Intravenous Ferric Carboxy-Maltose in Treating Anemia in Patients with Ulcerative Colitis.

Anemia is a frequent complication of ulcerative colitis, and is frequently caused by iron deficiency. Oral iron supplementation displays high rates of gastrointestinal adverse effects. However, the formulation of sucrosomial iron (SI) has shown higher tolerability. We performed a prospective study to compare the effectiveness and tolerability of oral SI and intravenous ferric carboxy-maltose (FCM) in patients with ulcerative colitis in remission and mild-to-moderate anemia. Patients were randomized 1:1 to receive 60 mg/day for 8 weeks and then 30 mg/day for 4 weeks of oral SI or intravenous 1000 mg of FCM at baseline. Hemoglobin and serum levels of iron and ferritin were assessed after 4, 8, and 12 weeks from baseline. Hemoglobin and serum iron increased in both groups after 4 weeks of therapy, and remained stable during follow up, without significant treatment or treatment-by-time interactions (p = 0.25 and p = 0.46 for hemoglobin, respectively; p = 0.25 and p = 0.26 for iron, respectively). Serum ferritin did not increase over time during SI supplementation, while it increased in patients treated with FCM (treatment effect, p = 0.0004; treatment-by-time interaction effect, p = 0.0002). Overall, this study showed that SI and FCM displayed similar effectiveness and tolerability for treatment of mild-to-moderate anemia in patients with ulcerative colitis under remission.

Urgent and emergency surgery for secondary peritonitis during the COVID-19 outbreak: an unseen burden of a healthcare crisis.

The COVID-19 pandemic has raised concerns about the negative impact of the fear of contagion on people's willingness to seek medical care and the subsequent effects on patients' prognosis. To date, not much is known about the outcomes of acute surgical diseases in this scenario. The aim of this multicenter observational study is to explore the effects of COVID-19 outbreak on the outcomes of patients who underwent surgery for peritonitis. Patients undergoing surgery for secondary peritonitis during the first COVID-19 surge in Italy (March 23-May 4, 2020-COVID period group) were compared with patients who underwent surgery during the same time interval of year 2019 (no-COVID period group). The primary endpoint was the development of postoperative complications. Logistic regression analysis was conducted to identify predictors of complications. Of the 332 patients studied, 149 were in the COVID period group and 183 were in the no-COVID period group. Patients in the COVID period group had an increased frequency of late presentations to the emergency departments (43% vs. 31.1%; P = 0.026) and a higher rate of postoperative complications (35.6% vs. 18%; P < 0.001). The same results were found in the subset analysis of patients with severe peritonitis at surgical exploration. The ASA score, severity of peritonitis, qSOFA score, diagnosis other than appendicitis, and COVID period resulted independent predictors of complications. During the COVID-19 pandemic patients with peritonitis had a higher rate of complicated postoperative courses, weighing on hospital costs and assistance efforts already pressured by the ongoing sanitary crisis.

Serum triiodothyronine-to-thyroxine (T3/T4) ratio predicts therapeutic outcome to biological therapies in elderly IBD patients.

INTRODUCTION: Rates of elderly patients with inflammatory bowel diseases (IBDs) are increasing, and biomarkers are needed to optimise their therapies. Serum triiodothyronine-to-thyroxine (T3/T4) ratio has been correlated with geriatric patient frailty. AIM: To assess the suitability of T3/T4 ratio as a response marker to biologics in elderly patients with IBD. METHODS: Patients with IBD over 60 years old were enrolled, when starting biological therapy. Therapeutic outcome was assessed after 54 weeks of treatment as mucosal healing (Mayo endoscopic score < 2 for ulcerative colitis; ulcer disappearance for Crohn's disease) and clinical remission (Partial Mayo Score < 2 for ulcerative colitis; Harvey-Bradshaw Index < 5 for Crohn's disease). T3/T4 ratio was evaluated at baseline, and its association with therapeutic outcomes was tested by multivariable logistic regression and receiver operating characteristic (ROC). RESULTS: We enrolled 80 patients; 44 achieved clinical remission and 36 mucosal healing. Baseline T3/T4 ratio was higher in patients with mucosal healing, as compared with those without mucosal healing (P < 0.0001), regardless of the disease type or biological drug (OR 6.4 [2.9-14.3] for each T3/T4 unit increase, P < 0.0001). A cut point of 3.3 was identified as the optimal threshold of baseline T3/T4 ratio for predicting mucosal healing, providing 78% sensitivity and 89% specificity (area under the ROC curve 0.88 [0.79-0.94]; positive and negative likelihood ratios 6.8 [2.9-15.9] and 0.3 [0.1-0.5] respectively). CONCLUSIONS: T3/T4 ratio seems a reliable tool for predicting therapeutic outcome of biological therapy in elderly patients with IBD. If validated, the assessment of this parameter before starting biological treatment might be suggested.

An unusual clinical presentation of colonic lipomatosis: A case report.

INTRODUCTION: Colonic lipomatosis is defined as a poorly circumscribed, non-capsulated fat accumulation in the submucosal layer of the colonic wall. Clinical presentation varies from asymptomatic to acute surgical complications. PRESENTATION OF CASE: We report the case of a 79-year old male who arrived at the Emergency Department complaining of worsening abdominal pain, fever and nausea. A CT scan revealed a periappendicular abscess extended to the ileocecal valve and also the presence of diffuse intramural fatty tissue of the ascending colon. The patient underwent surgery and a right hemicolectomy was performed. The final histological exam confirmed the diagnosis of gangrenous appendicitis with diffuse abscessualization of the ileocecal valve and the presence of submucosal lipomatosis of the ICV extending to the ascending colon. Patient was discharged at 11th-POD. DISCUSSION: Acute appendicitis can represent a complication, although rare, of colonic lipomatosis. The underlying mechanism can be explained by the obstruction of the stool discharge from the appendix caused by the thickened colonic wall due to lipomatosis. Despite the lack of established guidelines on the management of colonic lipomatosis, surgery remains the preferred treatment in case of acute complications. CONCLUSION: Acute appendicitis is a rare clinical manifestation of colonic lipomatosis. As in the case of other acute complications, such as intussesception, surgery remains the preferred therapeutic approach.

Fecal Calprotectin Predicts Mucosal Healing in Patients With Ulcerative Colitis Treated With Biological Therapies: A Prospective Study.

INTRODUCTION: Biological therapies are widely used for the treatment of ulcerative colitis. However, only a low proportion of patients achieve clinical remission and even less mucosal healing. There is currently scarce knowledge about the early markers of therapeutic response, with particular regard to mucosal healing. The aim of this prospective study was to evaluate the role of fecal calprotectin (FC) as early predictor of mucosal healing. METHODS: A prospective observational study was conducted on patients with ulcerative colitis, who started biological therapy with infliximab, adalimumab, golimumab, or vedolizumab at our center. All patients underwent colonoscopy, performed by 2 blinded operators, at baseline and week 54 or in case of therapy discontinuation because of loss of response. FC was assessed at baseline and week 8 and evaluated as putative predictor of mucosal healing at week 54. RESULTS: We enrolled 109 patients, and 97 were included in the analysis. Twenty-six patients (27%) experienced loss of response. Over 71 patients (73%) with clinical response at week 54, clinical remission was obtained in 60 patients (61.9%) and mucosal healing in 45 patients (46.4%). After 8 weeks of treatment, FC predicted mucosal healing at week 54 (P < 0.0001). Sensitivity, specificity, positive predictive value, and negative predictive value were estimated to be 75%, 88.9%, 86.6%, and 75.5%, respectively, based on a cutoff of 157.5 mg/kg. DISCUSSION: The present study suggests that FC assessment after 8 weeks of treatment with all the biological drugs could represent a promising early marker of response to therapy in terms of mucosal healing.

Clinical outcomes and quality of life associated with the use of a biosynthetic mesh for complex ventral hernia repair: analysis of the "Italian Hernia Club" registry.

With the development of newer meshes and approaches to hernia repair, it is currently difficult to evaluate their performances while considering the patients' perspective. The aim of the study was to assess the clinical outcomes and quality of life consequences of abdominal hernia repairs performed in Italy using Phasix and Phasix ST meshes through the analysis of real-world data to support the choice of new generation biosynthetic meshes. An observational, prospective, multicentre study was conducted in 10 Italian clinical centres from May 2015 to February 2018 and in 15 Italian clinical centres from March 2018 to May 2019. The evaluation focused on patients with VHWG grade II-III who underwent primary ventral hernia repair or incisional hernia intervention with a follow-up of at least 18 months. Primary endpoints included complications' rates, and secondary outcomes focused on patient quality of life as measured by the EuroQol questionnaire. Seventy-five patients were analysed. The main complications were: 1.3% infected mesh removal, 4.0% superficial infection requiring procedural intervention, 0% deep/organ infection, 8.0% recurrence, 5.3% reintervention, and 6.7% drained seroma. The mean quality of life utility values ranged from 0.768 (baseline) to 0.967 (36 months). To date, Phasix meshes have proven to be suitable prostheses in preventing recurrence, with promising outcomes in terms of early and late complications and in improving patient quality of life.

Fecal calprotectin: current and future perspectives for inflammatory bowel disease treatment.

Fecal calprotectin has been widely studied in inflammatory bowel disease (IBD) under clinical and therapeutic settings. It showed a good correlation with clinical, endoscopic, and histologic findings. For these reasons, fecal calprotectin is currently one of the most useful tools in IBD care, both in diagnosis and in clinical management. The development of biologic drugs allowed a deeper control of disease, which sometimes reaches histological healing; this is associated with a reduced risk of relapses and complications. The management of IBD treatment is currently carried out with a treat-to-target approach, and mucosal healing is considered at present to be the optimal therapeutic target, but the future is going through histologic remission. Fecal calprotectin is probably the best marker of mucosal healing, but it is correlated also with histologic remission: moreover, it has been recently studied as a possible therapeutic target in the CALM study. We carried out a comprehensive literature review in order to evaluate the role of fecal calprotectin at present and in the future in the management of IBD therapies.

Abdominal wall desmoid tumors: A proposal for US-guided resection.

BACKGROUND: Desmoid tumors (DTs) is a benign tumor with high tendency to infiltrative evolution and recurrence. Nowadays, in abdominal localization, the standard approach is surgery with R0 condition. The need to repair post-surgical wide wall defect requires conservative technique to decrease the incidence of incisional hernia and to obtain better quality of life (QoL). METHODS: We perform an abdominal wall desmoid resection using ultrasound guide. This technique ensures to spare a wide wall area and to obtain a multilayer reconstruction minimizing postoperative risk. This approach allows good oncological results and better managing abdominal wall post-resection defect. RESULTS: We use US guided surgery to get radical approach and wall tissue spare that allows us a multilayer reconstruction minimizing post-operative complications. No recurrences were observed in one year follow up period. CONCLUSION: Our experience represents first step to consider ultrasound mediated technique usefull to optimize wall resection surgery and to minimize following complications.

Gastrointestinal stromal tumours. Our experience ten years later.

AIM: To analyze GISTs behaviour observing their clinical evolution and outline the best approach to this neoplasia. MATERIAL OF STUDY: In a period between December 1999 and October 2009 came to our observation, at the Institute of General Surgery, 37 patients with GIST. We conducted a retrospective study evaluating the anatomo-pathological aspects, the clinical situation and the tumour characteristics of the 37 patients with GIST. RESULTS: The 37 patients included 21 women (57%) and 16 men (43%), the mean age was 67 years. GISTs originated from the stomach (27), jejunum (5), ileum (3), anus (1) and transverse mesocolon (1), the symptom most frequently found was acute anaemia and in 5 cases the diagnosis was occasional; 36 patients underwent surgical treatment. Based on tumor size, mitotic count, presence of areas of necrosis and/or haemorrhage, GISTs were classified according to the categories of potential high-grade malignancy (13 pts), intermediate grade (8 pts), low grade (16 pts). DISCUSSION: According to international literature, surgery remains the cornerstone of treatment for patients with primary resectable GIST without evidence of metastasis and should also be utilized when surgery has minimal risk of morbidity for the patient. The goal of surgery is complete surgical resection with negative margins (R0). The follow-up for some patients is still ongoing; only 10 patients underwent to adjuvant therapy with Imatinib. CONCLUSIONS: In the last decade, GISTs have become an emblematic example of the possibility of pharmacologically interfering with the molecular mechanisms of carcinogenesis.

Jejuno-jejunal invagination due to intestinal melanoma.

Cutaneous melanoma is one of the most studied neoplastic lesions in biology and clinical oncology. It has been well documented that this type of neoplasm presents a high metastatic rate, and is able to involve nearly every tissue. Non-cutaneous melanoma represents an unusual pattern of melanoma, and the small intestine is an uncommon anatomic localization. Herein we report an extremely rare clinical case of a young woman affected by a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination.