Ultrasonography Tight Control and Monitoring in Crohn's Disease During Different Biological Therapies: A Multicenter Study.

BACKGROUND & AIMS: Bowel ultrasonography (BUS) is a noninvasive tool for evaluating bowel activity in Crohn's disease (CD) patients. Aim of our multicenter study was to assess whether BUS helps to monitor intestinal activity improvement/resolution following different biological therapies. METHODS: Adult CD patients were prospectively enrolled at 16 sites in Italy. Changes in BUS parameters [i.e. bowel wall thickening (BWT), lesion length, echo pattern, blood flow changes and transmural healing (TH: normalization of all BUS parameters)] were analyzed at baseline and after 3, 6 and 12 months of different biological therapies. RESULTS: One hundred eighty-eight out of 201 CD patients were enrolled and analyzed (116 males [62%]; median age 36 years). Fifty-five percent of patients were treated with adalimumab, 16% with infliximab, 13% with vedolizumab and 16% with ustekinumab. TH rates at 12 months were 27.5% with an NNT of 3.6. TH at 12 months after adalimumab was 26.8%, 37% after infliximab, 27.2% after vedolizumab and 20% after ustekinumab. Mean BWT improvement from baseline was statistically significant at 3 and 12 months (P < .0001). Median Harvey-Bradshaw index, C-reactive protein and fecal calprotectin decreased after 12 months from baseline (P < .0001). Logistic regression analysis showed colonic lesion was associated with a higher risk of TH at 3 months and a greater BWT at baseline was associated with a lower risk of TH at 3 months [P = .03 (OR 0.70, 95% CI 0.50-0.97)] and 12 months [P = .01 (OR 0.58, 95% CI 0.38-0.89)]. At 3 months therapy optimization during the study was the only independent factor associated with a higher risk of no ultrasonographic response [P = .02 (OR 3.34, 95% CI 1.18-9.47)] and at 12 months disease duration [P = .02 (OR 3.03, 95% CI 1.15-7.94)]. CONCLUSIONS: Data indicate that BUS is useful to monitor biologics-induced bowel activity improvement/resolution in CD.

Metabolic-associated fatty liver disease (MAFLD) in coeliac disease.

BACKGROUND AND AIMS: Coeliac disease (CD) is considered a high-risk condition for developing non-alcoholic fatty liver disease (NAFLD) and other related metabolic disorders, particularly after commencing gluten-free diet (GFD). Recently, a new concept of metabolic-associated fatty liver disease (MAFLD) has been proposed to overcome the limitations of NAFLD definition. This study aimed at exploring the prevalence of NAFLD and MAFLD in CD patients at the time of CD diagnosis and after 2 years of GFD. Furthermore, we evaluated the role of PNPLA3 rs738409 in the development of NAFLD and MAFLD in the same population. METHODS: We retrospectively enrolled all newly diagnosed CD patients who underwent clinical, laboratory and ultrasonography investigations both at diagnosis and after 2 years of follow-up. Moreover, a PNPLA3 rs738409 genotyping assay was performed. RESULTS: Of 221 newly diagnosed CD patients, 65 (29.4%) presented NAFLD at CD diagnosis, while 32 (14.5%) met the criteria for MAFLD (k = 0.57). There were no significant differences between NAFLD and MAFLD, except for the higher rate of insulin resistance (IR) of MAFLD patients (75% vs 33.8%, P < .001). At 2 years of follow-up, 46.6% of patients developed NAFLD while 32.6% had MAFLD (k = 0.71). MAFLD subjects had higher transaminases (P = .03), LDL-cholesterol (P = .04), BMI and waist circumference and higher IR than NAFLD patients. MAFLD patients showed higher non-invasive liver fibrosis scores than NAFLD subjects (APRI = 1.43 ± 0.56 vs 0.91 ± 0.62, P < .001; NFS=-1.72 ± 1.31 vs -2.18 ± 1.41, P = .03; FIB-4 = 1.27 ± 0.77 vs 1.04 ± 0.74, P = .04). About PNPLA3 polymorphisms, at 2 years follow-up, NAFLD subjects presented a higher rate of heterozygosis (40.8%) and homozygosis (18.4%) polymorphisms than non-NAFLD (26.3% and 7.6%, respectively, P = .03 and 0.02), while no correlation between PNPLA3 polymorphisms and MAFLD was seen. CONCLUSIONS: The new MAFLD definition better reflects the metabolic alterations following GFD in CD population. This new classification could be able to identify patients at higher risk of worse metabolic outcome, who need a close multidisciplinary approach for their multisystemic disease.

Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting.

BACKGROUND AND AIM: Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments. METHODS: All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included. RESULTS: Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P < 0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P < 0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P < 0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P = 0.32) and lower than corticosteroids (IR 0.05, P < 0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P = 0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P = 0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P = 0.02) or azathioprine (OR 2.6, P = 0.01) and a body mass index < 18.5 at time of infection (OR 2.2, P = 0.01). CONCLUSIONS: The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

Extracellular Vesicles: New Tools for Early Diagnosis of Breast and Genitourinary Cancers.

Breast cancers and cancers of the genitourinary tract are the most common malignancies among men and women and are still characterized by high mortality rates. In order to improve the outcomes, early diagnosis is crucial, ideally by applying non-invasive and specific biomarkers. A key role in this field is played by extracellular vesicles (EVs), lipid bilayer-delimited structures shed from the surface of almost all cell types, including cancer cells. Subcellular structures contained in EVs such as nucleic acids, proteins, and lipids can be isolated and exploited as biomarkers, since they directly stem from parental cells. Furthermore, it is becoming even more evident that different body fluids can also serve as sources of EVs for diagnostic purposes. In this review, EV isolation and characterization methods are described. Moreover, the potential contribution of EV cargo for diagnostic discovery purposes is described for each tumor.

Evaluation of nutritional adequacy in adult patients with Crohn's disease: a cross-sectional study.

PURPOSE: Inadequate oral intake may play an important role in the onset of malnutrition in patients with Crohn's disease (CD). The aims of this cross-sectional study were: (1) to compare dietary intake in clinically active and quiescent CD patients, and (2) to assess patients' nutritional adequacy relative to the dietary reference values (DRVs) for the Italian population using LARN (Livelli di Assunzione di Riferimento di Nutrienti ed energia per la popolazione italiana). METHODS: Patients aged between 18 and 65 years with a diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record. Disease activity was clinically defined using the Crohn's disease activity index (CDAI). RESULTS: Overall, 117 patients, 71 males and 46 females, with a mean age of 39.6 ± 13.8 years and a mean body weight of 65.4 ± 11.8 kg, were ultimately included. Our findings showed that the amount of nutrients was similar between patients with active and quiescent disease. The mean intake of macronutrients was adequate, except for fiber, while dietary micronutrients were insufficient. Median intakes of sodium, phosphorus, and fluorine met LARN recommendations in both sexes, and the DRVs were accomplished by many patients (53/117; 104/117 and 98/117, respectively). Interestingly, dietary amounts of iron and zinc were barely acceptable in males but not in females. However, a few of the patients (< 15) met the LARN for potassium, calcium, and magnesium, regardless of sex and CDAI. With respect to vitamins, no relevant difference was found between the active and quiescent groups, and none of them met recommended values in both sexes. CONCLUSIONS: This study showed that the assessment of dietary intake can be crucial for optimizing dietary intervention with focused nutrition counseling, to improve nutritional status in CD patients.

Beyond Irritable Bowel Syndrome: The Efficacy of the Low Fodmap Diet for Improving Symptoms in Inflammatory Bowel Diseases and Celiac Disease.

BACKGROUND AND AIM: To evaluate the usefulness of a low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet on patients with irritable bowel syndrome (IBS), non-active inflammatory bowel diseases (IBD), and celiac disease (CD) on a gluten-free diet (GFD). METHODS: Dietetic interventional prospective study. IBS, IBD, and CD subjects were evaluated to check if they fulfilled the Rome III criteria. Each subject was educated to follow a low FODMAP diet after being evaluated by filling out questionnaires that assessed the quality of life (QoL) and symptoms experienced (IBS-SSS and SF-36), and was reevaluated after 1 and 3 months. RESULTS: One hundred twenty-seven subjects were enrolled: 56 with IBS, 30 with IBD, and 41 with CD. IBS-SSS showed that abdominal symptoms improved after 1 and 3 months of diet in all subjects, with significant difference among the 3 groups at T0 (average scores IBS: 293 ± 137, IBD: 206 ± 86, CD: 222 ± 65, p < 0.001), but no difference at T3 (IBS: 88 ± 54, IBD: 73 ± 45, CD: 77 ± 49, p = ns). By analyzing the SF-36 questionnaire, we did not observe any difference between the 3 groups, in terms of response to diet (p = ns), we observed a clinical improvement from T0 to T3 for most of the questionnaire's domains. CONCLUSIONS: A low FODMAP diet could be a valid option to counter -abdominal symptoms in patients with IBS, non-active IBD, or CD on a GFD, and thus, improve their QoL and social -relations.

Insights into disability and psycho-social care of patients with inflammatory bowel disease.

In recent years, the concept of disability has increasingly garnered attention as a crucial long-term target of inflammatory bowel disease (IBD) management. The treatment paradigm has changed dramatically from full control of the disease (clinical and endoscopic remission) toward physical and emotional well-being with the goal of preventing disability and normalizing quality of life. However, in certain cases, despite achieving good disease control, patients may still experience symptoms associated with disability, and reduced emotional wellness. These symptoms can significantly impact various biopsychosocial factors, including interpersonal relationships, educational or work-related activities, body image, and sexual functioning. Nevertheless, they often remain overlooked in the context of IBD care. In this narrative review, we aim to shed light on the burden of certain disability-related symptoms such as bowel urgency, sexual dysfunction, impaired fertility and fatigue, emphasizing the importance of acknowledging and validating them in a clinical setting. There is a demanding need for comprehensive care for IBD patients, with IBD clinicians being mindful of the psychosocial challenges faced by their patients. Providing timely and appropriate management of these challenges alongside IBD treatment is key to achieving holistic remission and enhancing the overall quality of life while reducing disability.

Effectiveness of Partial Enteral Nutrition as Add-On to Biologics in Patients With Refractory and Difficult-to-Treat Crohn's Disease: A Pilot Study.

Background: Partial enteral nutrition (PEN) is a well-established treatment for children with Crohn's disease (CD). However, its efficacy in adults with CD remains uncertain. We aimed to assess the effectiveness of PEN as an add-on to escalated biological therapy in adults with CD who have lost response to biologics. Methods: We conducted a retrospective observational study including patients who had lost response to biologics and received PEN in combination with escalated treatment, compared to those treated only with escalated therapy. The primary endpoint was steroid-free clinical remission (CR) at 24 weeks. Secondary endpoints included transmural healing (TH) and response (TR) rates along with selected clinical outcomes. Results: Forty-two patients were screened; 12 (28.6%) were excluded for complicated disease and 30 (71.4%) were included in the final analysis. Fourteen (46.7%) patients completed PEN treatment at 8 weeks, while 16 patients (53.3%) discontinued treatment due to intolerance and continued with escalation of biologic (BT group). At 24 weeks, 9 patients (64.3%) in the PEN group achieved CR, compared to 4 patients (25%) in the BT group (P = .03). The TR rate was 64.9% in the PEN group and 25% in the BT group (P = .03). Patients receiving PEN exhibited an increase in albumin levels compared to those in the BT group (Δ = 0.5; P = .02). A higher rate of therapy changes (68.7%) was observed in the BT group compared to 14.2% in the PEN group (P = .004). Prior failure to 2 lines of biological therapy was associated with adherence to PEN (OR = 1.583; CI = 1.06-2.36; P = .01). Conclusions: In patients who had lost response to biologics, PEN in combination with escalated biologics was associated with CR and TR and improved nutritional status. Hence, the addition of PEN should be considered for patients with difficult-to-treat CD.

Time to grow up: readiness associated with improved clinical outcomes in pediatric inflammatory bowel disease patients undergoing transition.

Background: The transition from pediatric to adult healthcare in individuals with inflammatory bowel disease (IBD) poses significant challenges mainly due to the high burden of IBD during adolescence, a critical period of psychosocial development. So far, there are few longitudinal data linking transition readiness to long-term disease outcomes. Objective: We aimed to assess patients' readiness to transition and its impact on clinical outcomes, quality of life, and adherence to therapy. Design: An observational, prospective study was conducted in a tertiary adult and pediatric center, including adolescents aged ⩾17 years with a diagnosis of IBD, who underwent a 'structured transition' program including two joint adult-pediatric visits. Methods: Transition readiness skills were assessed with the Transition Readiness Assessment Questionnaire (TRAQ). All patients completed the TRAQ at the time of recruitment, which occurred during the initial joint adult-pediatric visit, to determine those deemed ready for transition versus those not ready. The Morisky Medication Adherence Scale and the 36-Item Short Form Health Survey Questionnaire (SF-36) were also completed at baseline and after 12 months. Clinical outcomes were collected at the 12-month follow-up. Results: In all, 80 patients were enrolled who had transitioned through a structured transition clinic and completed 12 months of follow-up. In total, 54 patients were ready for the transition, with a mean TRAQ = 3.2 ± 0.5. The number of clinical relapses and hospitalizations at 12 months was lower in ready compared to not-ready patients (p = 0.004 and p = 0.04, respectively). SF-36 did not differ between ready and not-ready patients and pre- and post-transition clinics (p > 0.05). Based on the receiver operating characteristic curve, a TRAQ cutoff ⩾3.16 could predict medication adherence with a sensibility of 77%, a specificity of 82%, and an AUC of 0.81 (0.71-0.91; p < 0.001). Conclusion: Patients ready for transition had better outcomes at 12 months compared to those who were not ready. Therefore, readiness assessment tools should be integrated into transition management to ensure that interventions are targeted, patient-centered, and responsive to individuals' changing needs.

Transition readiness associated with improved clinical outcomes The transition for individuals with inflammatory bowel disease (IBD) is a dynamic and complex process that must be planned and cannot simply be performed once the patient is 18 years old. Since it does not depend solely on the patient's age but also on developmental readiness, it requires preparation and education starting from early adolescence. In the current study, a 'joint-visit' including both pediatric and adult providers yields positive clinical outcomes over 12 months. Patients ready for transition reported fewer relapses, hospitalizations, and improved therapy adherence compared to those not ready. Readiness assessment tools should be integrated into transition clinics to facilitate targeted interventions for IBD patients based on the changing needs of individuals.

Neuroendocrine gene subsets are uniquely dysregulated in prostate adenocarcinoma.

Prostate cancer has heterogeneous growth patterns, and its prognosis is the poorest when it progresses to a neuroendocrine phenotype. Using bioinformatic analysis, we evaluated RNA expression of neuroendocrine genes in a panel of five different cancer types: prostate adenocarcinoma, breast cancer, kidney chromophobe, kidney renal clear cell carcinoma and kidney renal papillary cell carcinoma. Our results show that specific neuroendocrine genes are significantly dysregulated in these tumors, suggesting that they play an active role in cancer progression. Among others, synaptophysin (SYP), a conventional neuroendocrine marker, is upregulated in prostate adenocarcinoma (PRAD) and breast cancer (BRCA). Our analysis shows that SYP is enriched in small extracellular vesicles (sEVs) derived from plasma of PRAD patients, but it is absent in sEVs derived from plasma of healthy donors. Similarly, classical sEV markers are enriched in sEVs derived from plasma of prostate cancer patients, but weakly detectable in sEVs derived from plasma of healthy donors. Overall, our results pave the way to explore new strategies to diagnose these diseases based on the neuroendocrine gene expression in patient tumors or plasma sEVs.

Switching from VEDOlizumab intravenous to subcutaneous formulation in ulcerative colitis patients in clinical remission: The SVEDO Study, an IG-IBD study.

BACKGROUND: The administration of biological drugs in inflammatory bowel diseases (IBD) is increasingly moving from intravenous to subcutaneous formulations. AIMS: To evaluate the efficacy and safety of vedolizumab subcutaneous administration after switching from intravenous administration in ulcerative colitis (UC) patients in corticosteroid-free clinical remission. METHODS: An observational, multicentre, prospective study was conducted by the Italian Group for the study of IBD (IG-IBD). UC patients in clinical remission (pMAYO < 2) not receiving steroids for > 8 months before the switch, and with at least 6 months of follow-up were included. Switch from intravenous to subcutaneous vedolizumab was defined as successful in patients not experiencing a disease flare (pMAYO ≥ 2) or needing oral steroids or stopping subcutaneous vedolizumab during the 6 months of follow-up after the switch. RESULTS: Overall, 168 patients were included. The switch was a success in 134 patients (79.8%). Vedolizumab retention rate was 88.7% at month six. C-reactive protein and faecal calprotectin values did not change after the switch (p = 0.07 and p = 0.28, respectively). Ten of the 19 patients who stopped subcutaneous formulation switched back to intravenous formulation recapturing clinical remission in 80%. Side effects were observed in 22 patients (13.1%). CONCLUSION: Effectiveness of switching from intravenous to subcutaneous vedolizumab formulation in UC patients in steroid-free clinical remission is confirmed in a real-world setting.

Follow-up evaluation and management of anemia in inflammatory bowel disease: A study by the Italian Group for Inflammatory Bowel Diseases (IG-IBD).

BACKGROUND: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA). AIMS: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD. METHODS: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated. RESULTS: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL. CONCLUSIONS: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL.

David Against Goliath: Direct Comparison of Handheld Bowel Sonography and Magnetic Resonance Enterography for Diagnosis of Crohn's Disease.

BACKGROUND: Diagnosis of Crohn's disease (CD) requires ileo-colonoscopy (IC) and cross-sectional evaluation. Recently, "echoscopy" has been used effectively in several settings, although data about its use for CD diagnosis are still limited. Our aim was to evaluate the diagnostic accuracy of handheld bowel sonography (HHBS) in comparison with magnetic resonance enterography (MRE) for CD diagnosis. METHODS: From September 2019 to June 2021, we prospectively recruited consecutive subjects attending our third level IBD Unit for suspected CD. Patients underwent IC, HHBS, and MRE in random order with operators blinded about the result of the other procedures. Bivariate correlation between MRE and HHBS was calculated by Spearman coefficient (r). To test the consistency between MRE and HHBS for CD location and complications, the Cohen's k measure was applied. RESULTS: Crohn's disease diagnosis was made in 48 out of 85 subjects (56%). Sensitivity, specificity, positive predictive values, and negative predictive values for CD diagnosis were 87.50%, 91.89%, 93.33%, and 85% for HHBS; and 91.67%, 94.59%, 95.65%, and 89.74% for MRE, without significant differences in terms of diagnostic accuracy (89.41% for HHBS vs 92.94% for MRE, P = NS). Magnetic resonance enterography was superior to HHBS in defining CD extension (r = 0.67; P < .01) with a better diagnostic performance than HHBS for detecting location (k = 0.81; P < .01), strictures (k = 0.75; P < .01), abscesses (k = 0.68; P < .01), and fistulas (k = 0.65; P < .01). CONCLUSION: Handheld bowel sonography and MRE are 2 accurate and noninvasive procedures for diagnosis of CD, although MRE is more sensitive in defining extension, location, and complications. Handheld bowel sonography could be used as effective ambulatory (or out-of-office) screening tool for identifying patients to refer for MRE examination due to high probability of CD diagnosis.

Hocus Pocus: the Role of Hand-held Ultrasonography in Predicting Disease Extension and Endoscopic Activity in Ulcerative Colitis.

BACKGROUND: Ulcerative colitis [UC] assessment still requires ileocolonoscopy [IC]. Intestinal ultrasound [IUS] has emerged as a non-invasive assessment tool, and the Milan Ultrasound Criteria [MUC] score has been validated to estimate and grade UC disease activity. Recently, hand-held IUS [HHIUS] has been used in several clinical settings, but data about its use in UC are limited. We aimed to evaluate the diagnostic accuracy of HHIUS compared with conventional IUS in detecting UC extension and activity. PATIENTS AND METHODS: From November 2021 to September 2022, we prospectively enrolled UC patients afferent to our third-level IBD Unit for IC evaluation. Patients underwent IC, HHIUS, and IUS. Ultrasound activity was defined by MUC >6.2, and endoscopic activity was defined by a Mayo endoscopic score [MES] >1. Cohen's k test was applied to test the concordance between IUS-MUC and HHIUS-MUC after MUC dichotomisation [MUC >6.2, yes/no]. RESULTS: In all, 86 patients with UC were enrolled. No significant difference was recorded between IUS and HHIUS at the per-segment extension [p = N.S.], and both procedures were comparable in terms of results of bowel wall thickness [BWT] and bowel wall stratification [BWS] assessment [p = N.S.]. IUS and HHIUS displayed excellent agreement when the MUC score system was applied [k = 0.86, p <0.01]. CONCLUSION: Hand-held intestinal ultrasound and IUS are comparable in UC extension definition and MUC evaluation. HHIUS could be reliable for detecting disease activity and estimating its extension, providing close monitoring. It also represents a non-invasive, easily practicable investigation, allowing immediate medical decisions with significant time and cost advantages.

Serum Interleukin 6, Controlling Nutritional Status (CONUT) Score and Phase Angle in Patients with Crohn's Disease.

Crohn's disease (CD) is a chronic inflammatory disorder that may occur in any segment of the gastrointestinal tract. Asymptomatic or untreated inflammation along with malnutrition can often coexist in patients with CD, impairing clinical outcomes, therefore the aim of this study was to assess the relationship between inflammation, malnutrition risk and nutritional status in CD patients. Consecutive adult CD outpatients aged 18-65 years were recruited. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI), whilst anthropometry and phase angle (PhA) were measured. The Controlling Nutritional Status (CONUT) score was retrospectively calculated for screening malnutrition risk and blood samples were taken. A total of 140 CD patients with a mean age of 38.8 ± 13.9 years and an average weight of 64.9 ± 12.0 kg were included. Serum interleukin (IL)-6 concentration was increased in active-CD patients, unrelated to medical treatment, which was associated with CDAI and PhA. Based on the CONUT score, the prevalence of patients with moderate/severe malnutrition risk (score ≥ 5) was 10%, showing lower age, body mass index and fat mass, but higher IL-6 and IL-1ß levels than subjects classified as not at risk (score 0-1). Finally, increased IL-6 levels and reduced PhA values were identified as independent predictors of moderate/severe malnutrition risk (p < 0.05). In conclusion, IL-6 increased in active-CD patients, which was inversely correlated with PhA. Although the CONUT score might be helpful for identifying CD patients at moderate/severe risk of malnutrition, larger studies are needed to verify these results in different settings.

Amino acid profiles, disease activity, and protein intake in adult patients with Crohn's disease.

Introduction: Crohn's disease (CD) is an immune-mediated inflammatory disorder of the gastrointestinal tract with a relapsing-remitting course. Amino acids (AAs) may play critical roles in the intestinal manifestations of disease, due to their involvement in many metabolic and immune functions. The present study aimed to explore serum AA concentrations in adult patients with CD, looking into their variations due to disease activity, surgery and protein content of diet. Eventually, the link between AAs and inflammatory markers was also assessed. Methods: Consecutive adult patients aged 18-65 years with diagnosis of CD were recruited. All participants underwent anthropometry and were instructed to fill in a 3-day food record to assess protein intake. Disease activity was clinically defined using the Crohn's Disease Activity Index (CDAI), while blood samples were taken to analyze serum AA profile and inflammatory markers. Results: A total of 103 patients with CD (61 men and 42 women; age:39.9 ± 13.9 years, BMI: 23.4 ± 3.51 kg/m2) were included. Tryptophan levels were found to be remarkably decreased in most subjects, unrelated to disease activity. On the contrary, concentration of lysine, leucine, valine and glutamine decreased in active versus quiescent CD patients, while aspartic acid, glutamate and glycine increased. The latter AAs were also directly correlated with CDAI and serum interleukin (IL)- 1ß concentration. Considering the total protein intake, expressed as g/kg/body weight, we observed a reduction in some essential AAs in patients with unmet protein requirements compared to patients who met the recommendation. Discussion: In conclusion, specific AAs varied according to disease activity and protein intake, adjusted to body weight and disease status. Glu and Asp concentrations raised with increasing IL-1ß. However, extensive research is needed to understand the mechanisms underpinning the link between variation in serum AAs, disease activity and protein intake in patients with CD.

Cyclic Neutropenia Mimicking Crohn's Disease: Two Case Reports and a Narrative Review.

Cyclic neutropenia is a rare hematological condition characterized by periodic fluctuations in neutrophil counts, with a 21-day periodicity. Clinical presentation varies from mild to severe forms of the disease, with the onset of recurrent fever, painful oral ulcers, recurrent bacterial infections, peritonitis, and septic shock. The availability of granulocyte colony-stimulating factor (G-CSF) has revolutionized the management and natural history of this disease, regulating the proliferation, differentiation, and maturation of the progenitor cells, and reducing the duration of neutropenia. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic pathologies that affect the gastrointestinal tract. The onset of both diseases may be at a young age (even during childhood or adolescence), and clinical manifestations may lead to misdiagnosis, due to similar characteristics such as recurrent infections, oral ulcers, perianal abscesses, and infertility. Moreover, the two pathologies are rarely associated, with different management and therapeutic options. Here, we describe two case reports of patients who underwent surgery because of diagnosis of complicated CD. After surgery, due to persistent neutropenia, the hematologist consultant confirmed suspicions of cyclic neutropenia, and G-CSF therapy was started with benefits, underlining the crucial importance of proper differential diagnosis.

The Use of JAK/STAT Inhibitors in Chronic Inflammatory Disorders.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a critical role in orchestrating immune and inflammatory responses, and it is essential for a wide range of cellular processes, including differentiation, cell growth, and apoptosis. Over the years, this pathway has been heavily investigated due to its key role in the pathogeneses of several chronic inflammatory conditions, e.g., psoriasis, atopic dermatitis (AD), and inflammatory bowel diseases (IBDs). Nevertheless, the impact of this pathway on the pathogenesis of inflammatory conditions remains unclear. This review describes the role of the JAK/STAT signaling pathway in the pathogenesis of inflammatory diseases such as psoriasis (Pso), psoriatic arthritis (PsA), AD, and IBD with a focus on ulcerative colitis (UC) and briefly resumes the use of JAK inhibitors in their clinical management.

Comparison of two strategies for the management of postoperative recurrence in Crohn's disease patients with one clinical risk factor: A multicentre IG-IBD study.

BACKGROUND: The management of postoperative recurrence (POR) in Crohn's disease (CD) after ileo-colonic resection is a highly debated topic. Prophylactic immunosuppression after surgery is currently recommended in the presence of at least one clinical risk factor. OBJECTIVE: Our aim was to determine whether early immunosuppression can be avoided and guided by endoscopy in CD patients with only one risk factor. METHODS: CD patients with only one risk factor for POR, including previous intestinal resection, extensive small intestine resection (>50 cm), fistulising phenotype, history of perianal disease, and active smoking, were retrospectively included. Two groups were formed based on whether immunosuppression was started immediately after surgery ("prophylaxis group") or guided by endoscopy ("endoscopy-driven group"). Primary endpoints were rates of any endoscopic recurrence (Rutgeerts ≥ i2a) and severe endoscopic recurrence (i4) within 12 months after surgery. Secondary outcomes were clinical recurrence rates at 6, 12 and 24 months after surgery. RESULTS: A total of 195 patients were enroled, of whom 61 (31.3%) received immunoprophylaxis. No differences between immunoprophylaxis and the endoscopy-driven approach were found regarding any endoscopic recurrence (36.1% vs. 45.5%, respectively, p = 0.10) and severe endoscopic recurrence (9.8% vs. 15.7%, respectively, p = 0.15) at the first endoscopic evaluation. Clinical recurrence rates were also not statistically different (p = 0.43, p = 0.09, and p = 0.63 at 6, 12, and 24 months, respectively). CONCLUSIONS: In operated CD patients with only one risk factor for POR, immediate immunoprophylaxis does not decrease the rate of early clinical and endoscopic recurrence. Prospective studies are needed to confirm our results.

Targeting the αVß3/NgR2 pathway in neuroendocrine prostate cancer.

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVß3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVß3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVß3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in vitro functional assays, we here demonstrate that NgR2 is crucial in promoting cell adhesion to αVß3 ligands. Moreover, we describe for the first time co-fractionation of αVß3 integrin and NgR2 in small extracellular vesicles derived from metastatic prostate cancer patients' plasma. These prostate cancer patient-derived small extracellular vesicles have a functional impact on human monocytes, increasing their adhesion to fibronectin. The monocytes incubated with small extracellular vesicles do not show an associated change in conventional polarization marker expression and appear to be in an early stage that may be defined as "adhesion competent". Overall, these findings allow us to better understand integrin-directed signaling and cell-cell communication during cancer progression. Furthermore, our results pave the way for new diagnostic and therapeutic perspectives for patients affected by neuroendocrine prostate cancer.