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Introduction: The risk of new or recurrent cancer in inflammatory bowel disease (IBD) patients with a history of cancer treated with immunomodulators (IMMs), including conventional immunosuppressors (ISSs), biologics or small molecules is undefined. The primary aim was to assess the frequency of new or recurrent cancer in IBD patients treated with IMMs after first cancer. The secondary aim was to evaluate risk factors for new/recurrent cancer in the same IBD population. Methods: In a retrospective multicenter study, all IBD patients using any IMM after first (index) cancer were enrolled. Inclusion criteria: Crohn’s disease (CD) or ulcerative colitis (UC), history of any cancer, detailed clinical history, and follow-up after cancer of ≥6 months. Exclusion criteria: IMM use for ≤3 months. Results: In total, 122 IBD patients (84 CD, 38 UC) treated with IMMs after first cancer were enrolled (age 59.5 [26–89] years). Index cancer included (n = [%]) genitourinary tract cancer (18 [14.8]), non-melanotic skin cancer (NMSC) (17 [13.9]), breast cancer (15 [12.3]), thyroid cancer (13 [10.7]), melanoma (14 [11.4]), colorectal cancer (CRC) (11 [9.0]), hematopoietic cancer (9 [7.4]), prostatic cancer (8 [6.6]), neuroendocrine cancer (4 [3.3]), head and neck cancer (3 [2.5]), liver cancer (3 [2.5]), endometrium cancer (2 [1.6]), lung cancer (1 [0.8]) and others (3 [2.5]). ISSs after cancer included (n = [%]) thiopurines (10 [37]), methotrexate (MTX) (14 [51.9]) and others (3 [11.1]) Biologics included (n = [%]) TNF-inhibitors (36 [32.4]), vedolizumab (60 [53.6]), ustekinumab (45 [40.2]), small molecules (9 [7.3]) and others (6 [5.4]). In a median follow-up of 8 [1–45] years after index cancer, 12/122 (9.8%) patients using IMMs after cancer developed new or recurrent cancer. No risk factors for new/recurrent cancer (i.e., age at diagnosis of cancer, smoke, gender, IBD type, IMM use, duration before or after cancer) were identified. Conclusions: In a multicenter study, ISSs or biologics after cancer were not identified as risk factors for new or recurrent cancer in IBD. However, IMMs were used after a long-term interval from index cancer.

Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: “Crohn’s Disease”, “Ulcerative Colitis”, “Endometriosis”, “Adenomyosis”, and “Inflammatory Bowel Disease”, individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.

Introduction: The frequency of obesity and possible correlations with characteristics and outcome of inflammatory bowel disease (IBD) are undefined. Primary aim was to assess the body mass index (BMI) distribution in IBD patients in follow-up. Secondary aim was to compare clinical characteristics and course of IBD in normal weight versus overweight or obese patients. Methods: Adult IBD patients in regular follow-up were prospectively enrolled and BMI was recorded during outpatient visits. Comparisons were assessed by the Student t-test, Mann-Whitney U test and Chi-square test, as appropriate. Results: In the 300 IBD patients enrolled (150 Crohn’s disease [CD], 150 ulcerative colitis [UC]), BMI distribution included: 16 (5.3%) underweight, 170 (56.7%) normal weight, 92 (30.7%) overweight, 22 (7.3%) obese patients. For the secondary aim, the 16 underweight patients were excluded, thus leaving 284 patients for the analysis (141 [49.6%] CD; 143 [50.4%] UC). Among these, 114 (40.2%) were overweight/obese and 170 (59.8%) normal weight. CD group included 89 (63.1%) normal weight and 52 (36.9%) overweight/obese patients. Perianal disease and refractoriness to biologics were more frequent in overweight/obese than normal weight CD patients (9 [10.1%] vs. 12 [23%], p = 0.03; 0 [0%] vs. 4 [23.4%], p = 0.01). In UC group, there were 81 (56.6%) normal weight and 62 (63.4%) overweight or obese patients. Conclusion: In IBD patients in follow-up, the proportion of underweight patients is low. Overweight and obese CD patients showed a higher frequency of perianal disease and refractoriness to biologics. BMI may influence phenotype and responsiveness to biologics in CD.

Patients with long-standing inflammatory bowel disease (IBD) involving the colon are at higher risk of developing colorectal dysplastic or neoplastic lesions. While from sporadic colorectal cancer follows an “adenoma-carcinoma” sequence, IBD colitis-associated carcinogenesis is mainly related to an “inflammation-dysplasia-carcinoma” sequence. Currently, specific endoscopic surveillance strategies involving dye spray and virtual chromoendoscopy have been standardized, aiming for early CRC diagnosis. When detected, colitis-associated dysplasia should be classified according to standard classification, thus allowing for better treatment. Indeed, most IBD-associated dysplastic lesions can be treated with endoscopic resection, even though available procedures are usually more challenging than those in the general population. The higher frequency of severe submucosal fibrosis and the difficulty in the definition of lesions’ margins account for this issue. Current endoscopic resection techniques include polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). Recent evidence suggests the relevance of en bloc resection, as this may be associated with lower rates of recurrence. Therefore, particularly for larger (>20 mm) lesions, ESD should be preferred, even though it is considered the most difficult technique due to frequent severe submucosal fibrosis. Considering the growing number of new endoscopic resective techniques, including underwater EMR or ESD, which in the general population have been suggested to lower procedure-related risks and may also allow a larger spread of advanced endoscopic resection in IBD. However, additional data are needed to assess the medium- and long-term efficacy of endoscopic resection of visible dysplasia in IBD patients, which are burdened by a high risk of local and, more importantly, metachronous recurrence.

Background: Janus kinase-inhibitors (JAK-i) have recently been approved for treating patients with Ulcerative Colitis (UC); therefore, further information is needed, particularly regarding efficacy and safety. Objectives: To provide a comprehensive review regarding the efficacy and safety of currently available JAK-i in UC. Methods: The PubMed and Scopus databases were considered, searching for ‘JAK’, ‘JAK-inhibitor’, ‘Janus Kinases’, ‘Tofacitinib’, ‘Filgotinib’, ‘Upadacitinib’, individually or in combination with ‘IBD’, ‘Ulcerative Colitis’, ‘safety’, ‘efficacy’, ‘study’ and ‘trial’. The search was focused on full-text papers published in English, with no publication date restrictions. Results: The efficacy and safety of JAK-i approved for treating patients with UC have been summarized. These included Tofacitinib, Filgotinib and Upadacitinib. Findings from both clinical trials and real-life studies in UC were reported, with particular regard to their efficacy in inducing clinical response and remission, steroid-free remission and endoscopic and histological healing. Overall, JAK-i proved to be effective and safe in selected subgroups of patients with UC. The rapid onset of action and the oral route of administration represent the most relevant characteristics of these drugs. Safety concerns using Tofacitinib in subgroups of patients (infections, hypercholesterolemia, venous thromboembolism and cardiovascular events) were initially raised. More recently, all JAK-i for UC showed an overall satisfactory safety profile. However, indication should be carefully given. Conclusions: The use of JAK-i UC is promising, although no predictive markers of response are currently available. Optimizing their use, as monotherapy or combined with other immunomodulators, may increase their efficacy in appropriately selected subgroups of patients with UC.

Background & Aim. Hepcidin, a key hormone in iron homeostasis, is synthesized by colorectal cancer (CRC) cells, particularly in the late stages of tumorigenesis. This study aimed to ascertain whether the serum levels of hepcidin could serve as a prognostic biomarker in microsatellite stable (MSS) metastatic CRC (mCRC). Specifically, we assessed the predictive value of baseline serum hepcidin levels for the overall survival (OS) of patients with MSS mCRC receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations). Methods. Serum samples were prospectively collected from 35 normal healthy volunteers (normal controls) and 55 patients with MSS mCRC and analyzed for their content of hepcidin by ELISA. Results. Serum hepcidin levels were significantly greater in patients with mCRC than in the normal controls. In the mCRC group, patients with baseline levels of hepcidin greater than 40 ng/mL had a significantly shorter 1-year OS rate (39%) than those with hepcidin levels lower than 40 ng/mL (80%) [hazard ratio (HR): 2.94; 95% CI: 1.27–6.84; p = 0.01]. A multivariate Cox regression analysis showed that the pre-treatment serum hepcidin levels were an independent prognostic factor for OS, not influenced by other well-known prognostic factors (i.e., CEA status, Karnofsky performance score, number of metastatic sites, RAS/BRAF mutations), and this was evident across all major patient subgroups. Conclusions. Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case–control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

The severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) global pandemic is a devastating event that is causing thousands of victims every day around the world. One of the main reasons of the great impact of coronavirus disease 2019 (COVID-19) on society is its unexpected spread, which has not allowed an adequate preparation. The scientific community is fighting against time for the production of a vaccine, but it is difficult to place a safe and effective product on the market as fast as the virus is spreading. Similarly, for drugs that can directly interfere with viral pathways, their production times are long, despite the great efforts made. For these reasons, we analyzed the possible role of non-pharmacological substances such as supplements, probiotics, and nutraceuticals in reducing the risk of Sars-CoV-2 infection or mitigating the symptoms of COVID-19. These substances could have numerous advantages in the current circumstances, are generally easily available, and have negligible side effects if administered at the already used and tested dosages. Large scientific evidence supports the benefits that some bacterial and molecular products may exert on the immune response to respiratory viruses. These could also have a regulatory role in systemic inflammation or endothelial damage, which are two crucial aspects of COVID-19. However, there are no specific data available, and rigorous clinical trials should be conducted to confirm the putative benefits of diet supplementation, probiotics, and nutraceuticals in the current pandemic.

The immunization of mice with the sterile culture medium supernatants of Mycobacterium tuberculosis (Mtb) H37Rv permitted the production of several monoclonal antibodies (mAbs) specific for secreted and/or released antigens. Two mAbs bound and immunoprecipitated an 80-kDa protein that was identified by mass spectrometry as Rv1133c, the methionine synthase MetE. The protein MetE is ubiquitous among prokaryota and shows a significant sequence homology in many bacteria. We produced both the full-length recombinant MetE and its N-terminal fragment, whose sequence is more conserved among mycobacteria, to select mAbs recognizing an Mtb-specific region of MetE. Finally, we produced and selected eight mAbs that specifically detect the MetE protein in the supernatant and cell lysate of Mtb and BCG, but not other bacteria such as non-tuberculous mycobacteria (NTM), Streptococcus pneumoniae, Staphylococcus aureus, Acinetobacter baumanii , or Escherichia coli . Taking advantage of our mAbs, we studied (i) the vitamin B12 dependence for the synthesis of MetE in Mtb and NTM and (ii) the kinetics of MetE production and secretion in supernatants during the in vitro reproduced replicative, dormant, and resuscitation cycle of Mtb. Our data demonstrate that dormant Mtb, which are assumed to be prevalent in latent infections, as well as NTM do not produce and secrete MetE. Results indicate an unexpected specificity for Mtb of our anti-MetE mAbs and encourage the use of rMetE and our mAbs as tools for the immunodiagnosis of TB and its stages.

Worsening heart failure (WHF) is a severe and dynamic condition characterized by significant clinical and hemodynamic deterioration. It is characterized by worsening HF signs, symptoms and biomarkers, despite the achievement of an optimized medical therapy. It remains a significant challenge in cardiology, as it evolves into advanced and end-stage HF. The hyperactivation of the neurohormonal, adrenergic and renin-angiotensin-aldosterone system are well known pathophysiological pathways involved in HF. Several drugs have been developed to inhibit the latter, resulting in an improvement in life expectancy. Nevertheless, patients are exposed to a residual risk of adverse events, and the exploration of new molecular pathways and therapeutic targets is required. This review explores the current landscape of WHF, highlighting the complexities and factors contributing to this critical condition. Most recent medical advances have introduced cutting-edge pharmacological agents, such as guanylate cyclase stimulators and myosin activators. Regarding device-based therapies, invasive pulmonary pressure measurement and cardiac contractility modulation have emerged as promising tools to increase the quality of life and reduce hospitalizations due to HF exacerbations. Recent innovations in terms of WHF management emphasize the need for a multifaceted and patient-centric approach to address the complex HF syndrome.