Role of the Gut Microbiota in Osteoarthritis, Rheumatoid Arthritis, and Spondylarthritis: An Update on the Gut-Joint Axis.

Dysregulation of the gut microbiota and their metabolites is involved in the pathogenic process of intestinal diseases, and several pieces of evidence within the current literature have also highlighted a possible connection between the gut microbiota and the unfolding of inflammatory pathologies of the joints. This dysregulation is defined as the "gut-joint axis" and is based on the joint-gut interaction. It is widely recognized that the microbiota of the gut produce a variety of compounds, including enzymes, short-chain fatty acids, and metabolites. As a consequence, these proinflammatory compounds that bacteria produce, such as that of lipopolysaccharide, move from the "leaky gut" to the bloodstream, thereby leading to systemic inflammation which then reaches the joints, with consequences such as osteoarthritis, rheumatoid arthritis, and spondylarthritis. In this state-of-the-art research, the authors describe the connections between gut dysbiosis and osteoarthritis, rheumatoid arthritis, and spondylarthritis. Moreover, the diagnostic tools, outcome measures, and treatment options are elucidated. There is accumulating proof suggesting that the microbiota of the gut play an important part not only in immune-mediated, metabolic, and neurological illnesses but also in inflammatory joints. According to the authors, future studies should concentrate on developing innovative microbiota-targeted treatments and their effects on joint pathology as well as on organizing screening protocols to predict the onset of inflammatory joint disease based on gut dysbiosis.

Endoscopic Ultrasound and Gastric Sub-Epithelial Lesions: Ultrasonographic Features, Tissue Acquisition Strategies, and Therapeutic Management.

Background and objectives: Subepithelial lesions (SELs) of the gastrointestinal (GI) tract present a diagnostic challenge due to their heterogeneous nature and varied clinical manifestations. Usually, SELs are small and asymptomatic; generally discovered during routine endoscopy or radiological examinations. Currently, endoscopic ultrasound (EUS) is the best tool to characterize gastric SELs. Materials and methods: For this review, the research and the study selection were conducted using the PubMed database. Articles in English language were reviewed from August 2019 to July 2024. Results: This review aims to summarize the international literature to examine and illustrate the progress in the last five years of endosonographic diagnostics and treatment of gastric SELs. Conclusions: Endoscopic ultrasound is the preferred option for the diagnosis of sub-epithelial lesions. In most of the cases, EUS-guided tissue sampling is mandatory; however, ancillary techniques (elastography, CEH-EUS, AI) may help in both diagnosis and prognostic assessment.

Oral-Gut Microbiota, Periodontal Diseases, and Arthritis: Literature Overview on the Role of Probiotics.

Periodontal diseases are oral inflammatory diseases affecting the tissues supporting and surrounding the teeth and include gingivitis and periodontitis. Oral pathogens may lead to microbial products spreading into the systemic circulation and reaching distant organs, while periodontal diseases have been related to low-grade systemic inflammation. Gut and oral microbiota alterations might play a role in the pathogenesis of several autoimmune and inflammatory diseases including arthritis, considering the role of the gut-joint axis in the regulation of molecular pathways involved in the pathogenesis of these conditions. In this scenario, it is hypothesized that probiotics might contribute to the oral and intestinal micro-ecological balance and could reduce low-grade inflammation typical of periodontal diseases and arthritis. This literature overview aims to summarize state-of-the-art ideas about linkages among oral-gut microbiota, periodontal diseases, and arthritis, while investigating the role of probiotics as a potential therapeutic intervention for the management of both oral diseases and musculoskeletal disorders.

Saline-immersion peroral endoscopic septotomy: a case report.

Video 1Saline-immersion peroral endoscopic septotomy.

Per oral endoscopic myotomy for achalasia.

Achalasia, characterized by impaired lower esophageal sphincter (LES) relaxation and failed peristalsis, stands out as the most widely recognized primary esophageal motility disorder. It manifests with dysphagia to solid and liquid foods, chest pain, regurgitation, and weight loss, leading to significant morbidity and healthcare burden. Traditionally, surgical Heller myotomy and pneumatic dilation were the primary therapeutic approaches for achalasia. However, in 2009, Inoue and colleagues introduced a groundbreaking endoscopic technique called peroral endoscopic myotomy (POEM), revolutionizing the management of this condition. This review aims to comprehensively examine the recent advancements in the POEM technique for patients diagnosed with achalasia, delving into critical aspects, such as the tailoring of the myotomy, the prevention of intraprocedural adverse events (AEs), the evaluation of long-term outcomes, and the feasibility of retreatment in cases of therapeutic failure.

"The crackers challenge": A reassuring low-dose gluten challenge in adults on gluten-free diet without proper diagnosis of coeliac disease.

BACKGROUND: Gluten-free diet (GFD) is the one therapy in coeliac disease (CeD). Unfortunately, some patients adopt GFD before the diagnostic work-up. The guidelines suggest a 14-day gluten intake > 3 gr to get CeD diagnosis, although many subjects refuse this approach. Other evidence showed that the intake of 50 mg/day of gluten for 3 months could be useful for CeD diagnosis. AIMS: We performed a dietary study, administering a low dose of gluten in form of "crackers" (about 60-120 mg of gluten/day) for 3 months, to get a final diagnosis of CeD in subjects already on GFD. METHODS: We enrolled adult patients with a suspicion of CeD on self-prescribed GFD. All subjects performed the crackers challenge for 3 months. At the end, all patients were analysed for CeD serology and if positive underwent endoscopy/histology. Also, we recorded the grade of satisfaction for the gluten challenge and the onset of adverse events. RESULTS: We enrolled 120 patients. All patients concluded the challenge without relevant adverse events. Serological positivity was detected in 54 patients (45%). Histology showed atrophy in 87% and Marsh 1-2 grade in 13% of patients. Ninety-nine patients (83%) were satisfied by this challenge. CONCLUSIONS: The "crackers challenge" is a useful and safe diagnostic approach in people on self-administered GFD.

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.

Updates on the Management of Ampullary Neoplastic Lesions.

Ampullary neoplastic lesions (ANLs) represent a rare cancer, accounting for about 0.6-0.8% of all gastrointestinal malignancies, and about 6-17% of periampullary tumors. They can be sporadic or occur in the setting of a hereditary predisposition syndrome, mainly familial adenomatous polyposis (FAP). Usually, noninvasive ANLs are asymptomatic and detected accidentally during esophagogastroduodenoscopy (EGD). When symptomatic, ANLs can manifest differently with jaundice, pain, pancreatitis, cholangitis, and melaena. Endoscopy with a side-viewing duodenoscopy, endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP) play a crucial role in the ANL evaluation, providing an accurate assessment of the size, location, and characteristics of the lesions, including the staging of the depth of tumor invasion into the surrounding tissues and the involvement of local lymph nodes. Endoscopic papillectomy (EP) has been recognized as an effective treatment for ANLs in selected patients, providing an alternative to traditional surgical methods. Originally, EP was recommended for benign lesions and patients unfit for surgery. However, advancements in endoscopic techniques have broadened its indications to comprise early ampullary carcinoma, giant laterally spreading lesions, and ANLs with intraductal extension. In this paper, we review the existing evidence on endoscopic diagnosis and treatment of ampullary neoplastic lesions.

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.

Advancements in Endoscopic Resection for Colitis-Associated Colorectal Neoplasia in Inflammatory Bowel Disease: Turning Visible into Resectable.

Patients suffering from inflammatory bowel disease (IBD) face a two to three-fold higher risk of developing colorectal cancer (CRC) compared to the general population. In recent years, significant progress has been made in comprehending the natural history of IBD-associated CRC (IBD-CRC) and refining its treatment strategies. The decreased incidence of IBD-CRC can be attributed to improved therapeutic management of inflammation, advancements in endoscopy, and early detection of precancerous lesions via surveillance programs. Advanced imaging technologies have made previously undetectable dysplasia visible in most cases, allowing for a much more precise and detailed examination of the mucosa. Additionally, new tools have facilitated the endoscopic resection (ER) of visible lesions in IBD. Particularly, the key to effectively manage colitis-associated colorectal neoplasia (CAN) is to first identify it and subsequently guarantee a complete ER in order to avoid surgery and opt for continuing surveillance. Advanced ER techniques for CAN include endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and hybrid ESD-EMR (h-ESD). This narrative review aims to consolidate the current literature on IBD-CRC, providing an overview of advanced techniques for ER of CAN in IBD, with a particular emphasis on the impact of ESD on the long-term outcomes of IBD patients.

Peroral Endoscopic Myotomy for Achalasia after Bariatric Surgery: A Case Report and Review of the Literature.

INTRODUCTION: Achalasia following bariatric surgery is a rare phenomenon with diverse potential physiopathological origins. AIMS: This article aims to explore the hypothetical physiopathological connection between bariatric surgery and the subsequent onset of achalasia. MATERIAL AND METHODS: A review was conducted to identify studies reporting cases of peroral endoscopic myotomy (POEM) after bariatric procedures and detailing the outcomes in terms of the technical and clinical success. Additionally, a case of a successful POEM performed on a patient two years after undergoing laparoscopic sleeve gastrectomy (LSG) is presented. RESULTS: The selection criteria yielded eight studies encompassing 40 patients treated with POEM for achalasia after bariatric surgery: 34 after Roux-en-Y gastric bypass (RYGB) and 6 after LSG. The studies reported an overall technical success rate of 97.5%, with clinical success achieved in 85% of cases. Adverse events were minimal, with only one case of esophageal leak treated endoscopically. However, a postprocedural symptomatic evaluation was notably lacking in most of the included studies. CONCLUSIONS: Achalasia poses a considerable challenge within the bariatric surgery population. POEM has emerged as a technically viable and safe intervention for this patient demographic, providing an effective treatment option where surgical alternatives for achalasia are limited. Our findings highlight the promising outcomes of POEM in these patients, but the existing data remain limited. Hence, prospective studies are needed to elucidate the optimal pre-surgical assessment and timing of endoscopic procedures for optimizing outcomes.

Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis.

Osteoporosis is characterized by an alteration of bone microstructure with a decreased bone mineral density, leading to the incidence of fragility fractures. Around 200 million people are affected by osteoporosis, representing a major health burden worldwide. Several factors are involved in the pathogenesis of osteoporosis. Today, altered intestinal homeostasis is being investigated as a potential additional risk factor for reduced bone health and, therefore, as a novel potential therapeutic target. The intestinal microflora influences osteoclasts' activity by regulating the serum levels of IGF-1, while also acting on the intestinal absorption of calcium. It is therefore not surprising that gut dysbiosis impacts bone health. Microbiota alterations affect the OPG/RANKL pathway in osteoclasts, and are correlated with reduced bone strength and quality. In this context, it has been hypothesized that dietary supplements, prebiotics, and probiotics contribute to the intestinal microecological balance that is important for bone health. The aim of the present comprehensive review is to describe the state of the art on the role of dietary supplements and probiotics as therapeutic agents for bone health regulation and osteoporosis, through gut microbiota modulation.

Exploring the concept of deep remission in Crohn's disease: correlation between transmural healing and biomarkers.

Background: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn's disease (CD), little is known about the real significance and clinical impact of deep remission (DR). Objectives: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. Design: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. Methods: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. Results: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 µg/g to 260 ± 354.9 µg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 µg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 µg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). Conclusion: An FC < 94 µg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics.

Impact of Sarcopenia on Clinical Outcomes in a Cohort of Caucasian Active Crohn's Disease Patients Undergoing Multidetector CT-Enterography.

(1) Background: Sarcopenia has a high incidence in Crohn's disease (CD) with considerable heterogeneity among ethnicities and variable impact on clinical outcomes. Aim: to assess the impact of sarcopenia on clinical outcomes in a cohort of Caucasian patients with active CD undergoing CT-enterography (CTE) for clinical assessment. We further investigated the prevalence of sarcopenia and its predictors. (2) Methods: Caucasian CD patients with moderate−severe clinical activity, who underwent CTE in an emergency setting, were retrospectively recruited. The skeletal muscle index (SMI) at the third lumbar vertebra was used to detect sarcopenia in the early stages. Clinical malnutrition was defined according to global clinical nutrition criteria. Clinical outcomes included the rate of surgery and infections within one year. (3) Results: A total of 63 CD patients (34 M; aged 44 ± 17 years) were recruited, and 48 patients (68.3%) were sarcopenic. Malnutrition occurred in 28 patients (44.4%) with a significant correlation between body mass index (BMI) and sarcopenia (r = 0.5, p < 0.001). The overall rate of surgery was 33%, without a significant difference between sarcopenic and non-sarcopenic (p = 0.41). The rate of infection in patients with sarcopenia was significantly higher than in non-sarcopenic (42%vs15%, p = 0.03). BMI (OR 0.73,95%, CI 0.57−0.93) and extraintestinal manifestations (EIM) (OR 19.2 95%, CI 1.05−349.1) were predictive of sarcopenia (p < 0.05). (4) Conclusions: Sarcopenia was associated with an increased rate of infections, and it was observed in 68.3% of the Caucasian cohort with active CD.

Sarcopenic Dysphagia, Malnutrition, and Oral Frailty in Elderly: A Comprehensive Review.

Frailty is a highly prevalent condition in the elderly that has been increasingly considered as a crucial public health issue, due to the strict correlation with a higher risk of fragility fractures, hospitalization, and mortality. Among the age-related diseases, sarcopenia and dysphagia are two common pathological conditions in frail older people and could coexist leading to dehydration and malnutrition in these subjects. "Sarcopenic dysphagia" is a complex condition characterized by deglutition impairment due to the loss of mass and strength of swallowing muscles and might be also related to poor oral health status. Moreover, the aging process is strictly related to poor oral health status due to direct impairment of the immune system and wound healing and physical and cognitive impairment might indirectly influence older people's ability to carry out adequate oral hygiene. Therefore, poor oral health might affect nutrient intake, leading to malnutrition and, consequently, to frailty. In this scenario, sarcopenia, dysphagia, and oral health are closely linked sharing common pathophysiological pathways, disabling sequelae, and frailty. Thus, the aim of the present comprehensive review is to describe the correlation among sarcopenic dysphagia, malnutrition, and oral frailty, characterizing their phenotypically overlapping features, to propose a comprehensive and effective management of elderly frail subjects.

Endoscopic Postoperative Recurrence in Crohn's Disease After Curative Ileocecal Resection with Early Prophylaxis by Anti-TNF, Vedolizumab or Ustekinumab: A Real-World Multicentre European Study.

BACKGROUND: Endoscopic-post-operative-recurrence [ePOR] in Crohn's disease [CD] after ileocecal resection [ICR] is a major concern. We aimed to evaluate the effectiveness of early prophylaxis with biologics and to compare anti-tumour necrosis factor [anti-TNF] therapy to vedolizumab [VDZ] and ustekinumab [UST] in a real-world setting. METHODS: A retrospective multicentre study of CD-adults after curative ICR on early prophylaxis was undertaken. ePOR was defined as a Rutgeerts score [RS] ≥ i2 or colonic-segmental-SES-CD ≥ 6. Multivariable logistic regression was used to evaluate risk factors, and inverse probability treatment weighting [IPTW] was applied to compare the effectiveness between agents. RESULTS: The study included 297 patients (53.9% males, age at diagnosis 24 years [19-32], age at ICR 34 years [26-43], 18.5% smokers, 27.6% biologic-naïve, 65.7% anti-TNF experienced, 28.6% two or more biologics and 17.2% previous surgery). Overall, 224, 39 and 34 patients received anti-TNF, VDZ or UST, respectively. Patients treated with VDZ and UST were more biologic experienced with higher rates of previous surgery. ePOR rates within 1 year were 41.8%. ePOR rates by treatment groups were: anti-TNF 40.2%, VDZ 33% and UST 61.8%. Risk factors for ePOR at 1 year were: past-infliximab (adjusted odds ratio [adj.OR] = 1.73 [95% confidence interval, CI: 1.01-2.97]), past-adalimumab [adj.OR = 2.32 [95% CI: 1.35-4.01] and surgical aspects. After IPTW, the risk of ePOR within 1 year of VDZ vs anti-TNF or UST vs anti-TNF was comparable (OR = 0.55 [95% CI: 0.25-1.19], OR = 1.86 [95% CI: 0.79-4.38]), respectively. CONCLUSION: Prevention of ePOR within 1 year after surgery was successful in ~60% of patients. Patients treated with VDZ or UST consisted of a more refractory group. After controlling for confounders, no differences in ePOR risk were seen between anti-TNF prophylaxis and other groups.