COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.

Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited.

Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.

Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease.

During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.

SpA plus IBD or IBD plus SpA: Does commutative property apply?

The term spondyloarthritis (SpA) encompasses a group of interrelated disorders characterised by the involvement of the musculoskeletal system as well as extra-articular manifestations like acute anterior uveitis, psoriasis and inflammatory bowel diseases (IBD). Likewise, IBD may present with various extra-intestinal manifestations among which those involving the musculoskeletal system, namely peripheral and axial SpA are the most common. The identification of patients with both SpA and IBD is of paramount importance in clinical practice since the coexistence of these two entities has been associated with great disability and decreased quality of life. In order to achieve an early diagnosis of IBD-SpA it is instrumental that rheumatologists seek for gastrointestinal symptoms in SpA patients and likewise that gastroenterologists seek for inflammatory musculoskeletal symptoms in patients with IBD. This narrative review aims at critically appraising the available evidence about SpA occurring in IBD patients versus IBD occurring in patients with SpA and at highlighting similarities and differences between the two scenarios.

Prophylactic Treatment with Vedolizumab in the Prevention of Postoperative Recurrence (POR) in High-Risk Crohn's Patients.

About 50% of Crohn's Disease (CD) patients undergo an intestinal resection during their lifetime. Although the patients experience a fairly long period of well-being after the intestinal resection, they presented a postoperative recurrence (POR) in 40% of cases within 5 years. In this case series, we aimed to evaluate the incidence of POR in CD patients with high risk for early POR, prophylactically treated with Vedolizumab. All consecutive CD patients (followed from 2017 to 2020) who underwent ileocolonic resection after the loss of response at anti-Tumor Necrosis Factor α (anti-TNFα) and with one or more risk factors for early POR were included. POR was defined as a Rutgeerts score (Ri) > 1 at the colonoscopic evaluation. All the included patients underwent a Magnetic resonance enterography (MRE) at least one year after the surgical resection. Six patients (4 Female; 2 Males) were included. At the first endoscopic evaluation, all patients were in endoscopic remission (5 patients Ri 0; 1 patient Ri 1). No stenosis nor other intestinal wall changes or complications were observed at MRE. Five patients underwent colonoscopy over two years of follow-up (median: 32 months; range 25-33). The Ri score was 0 in four patients, while the fifth patient showed severe endoscopic relapse. The same patient presented a clinical relapse (Harvey-Bradshaw index = 10) with a flare of disease in the colonic mucosa. These data suggest that early post-operative treatment with Vedolizumab could be a valuable strategy to be submitted to a prospective controlled trial for preventing POR.

Immunoglobulin G4-Related Disease of the Intestine: A Clinicopathological Entity to Be Considered.

Background and Objectives: Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated, systemic condition of unknown etiology, associated with fibroinflammatory lesions. Diagnosis is set in the presence of IgG4-positive plasma cell infiltration of the involved tissue and elevated serum IgG4 levels. However, approximately 30% of patients have normal serum IgG4 levels. IgG4-RD may affect several organs, including the pancreas, bile ducts, mesentery, retroperitoneum, and salivary glands, but the involvement of the gastrointestinal tract is uncommon. Materials and Methods: The case series of 4 patients with IgG4-RD involving the intestinal tract was observed in the period of 2017-2022. Colorectal and ileal biopsy specimens were stained with hematoxylin and eosin and immunohistochemical techniques using monoclonal antihuman IgG4 primary antibody. Diagnosis of IgG4-RD was based on the presence of >50 cells/ HPF and IgG4/IgG ratio >40 confirmed by two pathologists. Results: IgG4-RD was set in patients previously diagnosed as affected by Crohn's disease. Conclusions: Systematic IgG4 immunohistochemical staining should be considered in the diagnostic workup of patients with gastrointestinal strictures, mimicking Crohn's disease. The exact prevalence of the condition is likely more frequent than reported and should be defined by a large series of consecutive patients.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

BACKGROUND: The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). METHOD: We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. RESULTS: Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. CONCLUSIONS: This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

This article is a systematic review with meta-analysis of randomized clinical trials involving inflammatory bowel disease patients treated with vitamin D supplementation, compared with placebo. We aim to assess the risk of clinical relapse or disease activity among these patients.

Immune-mediated inflammatory diseases after anti-SARS-CoV-2 vaccines: new diagnoses and disease flares.

OBJECTIVE: New-onset immune-mediated inflammatory diseases (IMIDs) and flares of pre-existing IMIDs have been reported following anti- SARS-CoV2 vaccination. Our study aimed at describing a retrospective cohort of patients developing new-onset IMIDs or flares of known IMIDs within 30 days after any anti-SARS-CoV2 vaccine dose. METHODS: We evaluated clinical records of all inpatients and outpatients referring to our institution between February 2021 and February 2022 with any clinical manifestations. We then selected those having received any anti-SARS-CoV2 vaccine dose within the prior 30 days and classified them as having or not a previous IMID according to predefined criteria. We recorded new-onset IMIDs or flares of known IMIDs and investigated any relationship with demographic, clinical and serological variables. RESULTS: 153 patients that received any anti-SARS-CoV2 vaccine dose within the previous 30 days were included of which 45 (29%) already had a diagnosis of IMID while 108 (71%) had no previously diagnosed IMID. 33 (30%) of the 108 patients, were diagnosed with a new-onset IMID. Pericarditis, polymyalgia rheumatica and vasculitis were the most frequent conditions. Among the 45 patients that already had an IMID, disease flare was the reason for referral in 69% of patients. Patients with an IMID flare had a lower number of comorbidities and tended to be younger compared with those who developed other conditions after anti-SARS-CoV2 vaccination. CONCLUSION: We provided a retrospective overview of a cohort of patients who developed new-onset IMIDs or flares of known IMIDs within 30 days after any dose of anti-SARS-CoV2 vaccine. While vaccination campaigns proceed, postvaccination surveillance programmes are ongoing and hopefully will soon clarify whether a causal relationship between vaccines and new-onset/flares of IMIDs exists.

Systematic review and meta-analysis: the advantage of endoscopic Mayo score 0 over 1 in patients with ulcerative colitis.

BACKGROUND: Mucosal healing (MH) evaluated by endoscopy is a novel target of therapy in UC as it is associated with improved long-term outcomes. It is defined based on the Mayo endoscopic score (MES), but it is still to define whether a value of MES 0 or 1 should be the target. The purpose of this paper is to present the results of a systematic review with meta-analysis which compares long-term outcomes of patients in steroid-free clinical remission with MES 0 with those with MES 1. METHODS: A systematic electronic search of the literature was performed using Medline, Scopus, and CENTRAL through December 2020 (PROSPERO n:CRD42020179333). The studies concerned UC patients, in steroid-free clinical remission, with MES of 0 or 1, and with at least 12-months of follow-up. RESULTS: Out of 4611 citations, 15 eligible studies were identified. Increases in clinical relapse among patients with MES 1 were observed in all the studies included in this review, suggesting that MES of 1 have a higher risk of relapse than a score of 0. MES 0 patients displayed a lower risk of clinical relapse (OR 0.33; 95% CI 0.26-0.43; I2 13%) irrespective of the follow-up time (12-months or longer). On the other hand, no differences were found comparing MES 0 versus MES 1 about the risk of hospitalization or colectomy. CONCLUSIONS: MES 0 is associated with a lower rate of clinical relapse than is MES 1. For this reason, MES 0, rather than MES 0-1, should be considered the therapeutic target for patients with UC.

Non-steroidal anti-inflammatory drugs and acetylsalicylic acid increase the risk of complications of diverticular disease: a meta-analysis of case-control and cohort studies.

BACKGROUND: The role of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid in the occurrence of diverticular bleeding (DB), complicated diverticulitis (CD), and acute diverticulitis (AD) is not yet defined. AIM: Update a systematic review and meta-analyses of case-control and cohort studies to evaluate the association between NSAIDs or acetylsalicylic acid with DB, CD, or AD. METHODS: The study included were identified through MEDLINE, Scopus, Web of Science, and Cochrane Library databases. Sizes were pooled across studies to obtain the overall effect size. A random-effects model was used to account for different sources of variation among studies. Odds ratio (OR) with 95% confidence interval (CI) was used as a measure of effect size. RESULTS: Thirteen studies were included in the systematic review and meta-analysis. NSAIDs and acetylsalicylic acid use were associated with an increased risk of DB (OR: 6.90, 95% CI 3.86 to 12.35, P ˂ 0.00001, and OR 2.84, 95% CI 2.19 to 3.67, P < 0.00001, respectively). NSAIDs and acetylsalicylic acid use were also associated with increased risk of CD occurrence (OR 3.13, 95% CI 1.73 to 5.68, P = 0.0002, and OR 1.49, 95% CI 1.02 to 2.17, P = 0.04, respectively). The only study found about AD occurrence showed that NSAIDs use was not associated with AD and acetylsalicylic acid use had a low risk of AD. CONCLUSION: NSAIDs and acetylsalicylic acid significantly increase the risk of DB and CD. Further studies are needed to clarify the role of NSAIDs and acetylsalicylic acid in AD. However, increasing evidence suggests caution in the use of such medications in patients with colonic diverticula.

Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications.

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged.

Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis.

BACKGROUND: It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. METHODS: A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. RESULTS: Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37-3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40-14.00) and delayed PPB (OR 10.80; CI 4.63-25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. CONCLUSIONS: Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

Pericarditis after SARS-CoV-2 Infection: Another Pebble in the Mosaic of Long COVID?

With the emerging success of the COVID-19 vaccination programs, the incidence of acute COVID-19 will decrease. However, given the high number of people who contracted SARS-CoV-2 infection and recovered, we will be faced with a significant number of patients with persistent symptoms even months after their COVID-19 infection. In this setting, long COVID and its cardiovascular manifestations, including pericarditis, need to become a top priority for healthcare systems as a new chronic disease process. Concerning the relationship between COVID-19 and pericardial diseases, pericarditis appears to be common in the acute infection but rare in the postacute period, while small pericardial effusions may be relatively common in the postacute period of COVID-19. Here, we reported a series of 7 patients developing pericarditis after a median of 20 days from clinical and virological recovery from SARS-CoV-2 infection. We excluded specific identifiable causes of pericarditis, hence we speculate that these cases can be contextualized within the clinical spectrum of long COVID. All our patients were treated with a combination of colchicine and either ASA or NSAIDs, but four of them did not achieve a clinical response. When switched to glucocorticoids, these four patients recovered with no recurrence during drug tapering. Based on this observation and on the latency of pericarditis occurrence (a median of 20 days after a negative nasopharyngeal swab), could be suggested that post-COVID pericarditis may be linked to ongoing inflammation sustained by the persistence of viral nucleic acid without virus replication in the pericardium. Therefore, glucocorticoids may be a suitable treatment option in patients not responding or intolerant to conventional therapy and who require to counteract the pericardial inflammatory component rather than direct an acute viral injury to the pericardial tissue.

Fecal Lactoferrin and Other Putative Fecal Biomarkers in Crohn's Disease: Do They Still Have a Potential Clinical Role?

INTRODUCTION: The need for noninvasive markers of disease activity is mandatory in the assessment of Crohn's disease (CD). The most widely fecal biomarker in CD, despite several limits, is fecal calprotectin. This review aims to elucidate the role, if any, of all other fecal biomarkers, as alternative tools for assessing clinical and endoscopic disease activity, and predict capsule endoscopy findings, response to therapy, disease relapse, and postoperative recurrence. These fecal biomarkers included lactoferrin, S100A12, high mobility group box 1, neopterin, polymorphonuclear neutrophil elastase, fecal hemoglobin, alpha1-antitrypsin, lysozyme, human beta-defensin-2, neutrophil gelatinase-associated lipocalin, matrix metalloproteinase-9, chitinase 3-like-1, M2-pyruvate kinase, myeloperoxidase, and eosinophil proteins. METHODS: A systematic electronic search in the medical literature was performed up to April 2020. Seventy eligible studies were identified out of 859 citations. Data were grouped according to the assessment of clinical and endoscopic disease activity, capsule endoscopy findings, response to therapy, prediction of relapse, and postoperative recurrence. RESULTS: The overall correlation between lactoferrin and clinical indexes is poor, while performance is good with endoscopic scores. Lactoferrin seems to represent a reasonably good surrogate marker of response to therapy and to be potentially useful in identifying patients at high risk for endoscopic relapse or postoperative recurrence. The evaluation of the performance of all other fecal markers is limited by the lack of adequate data. CONCLUSIONS: None of the fecal markers so far represents an acceptable alternative to calprotectin in clinical practice. Fecal lactoferrin is the only possible exception, but a more extensive investigation is still required.

Are Volatile Organic Compounds Accurate Markers in the Assessment of Colorectal Cancer and Inflammatory Bowel Diseases? A Review.

Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the Western world. Early detection decreases incidence and mortality. Screening programs based on fecal occult blood testing help identify patients requiring endoscopic examination, but accuracy is far from optimal. Among the alternative strategies, volatile organic compounds (VOCs) represent novel potentially useful biomarkers of colorectal cancer. They also represent a promising tool for the screening of both intestinal inflammation and related CRC. The review is focused on the diagnostic potential of VOCs in sporadic CRC and in inflammatory bowel diseases (IBD), which increase the risk of CRC, analyzing future clinical applications. Despite limitations related to inadequate strength of evidence, differing analytical platforms identify different VOCs, and this unconventional approach for diagnosing colorectal cancer is promising. Some VOC profiles, besides identifying inflammation, seem disease-specific in inflammatory bowel diseases. Thus, breath, urine, and fecal VOCs provide a new and promising clinical approach to differential diagnosis, evaluation of the inflammatory status, and possibly the assessment of treatment efficacy in IBD. Conversely, specific VOC patterns correlating inflammatory bowel disease and cancer risk are still lacking, and studies focused on this issue are strongly encouraged. No prospective studies have assessed the risk of CRC development by using VOCs in samples collected before the onset of disease, both in the general population and in patients with IBD.

Lymphocytic gastritis and celiac disease.

We read with great interest the review article "Lymphocytic gastritis" by Puderecki et al., which was recently published in your journal [1]. The article describes the features of lymphocytic gastritis (LG), a rare form of gastritis with unclear pathogenesis. The diagnosis of LG is based on histology which reveals intraepithelial lymphocytosis (> 25 intraepithelial lymphocytes per 100 gastric surface and foveolar epithelial cells). The endoscopic appearance of LG can vary from normal mucosa to aphthous erosions, nodularity, local spots, polyps, and ulcers. The most common locations of the lesions are the body and the antrum. With regard to etiology, Celiac disease (CD) is the main reported cause of LG, followed by Helicobacter pylori infection. After a careful review of the argument, Puderecki et al. conclude that there is no one exact cause of LG, and rather than being a separate disease, LG is more likely a sign of the disease with which it is associated [1]. We wrote to remark on the strong connection between LG and CD. Such a connection may allow some etiopathogenetic and clinical speculations.

What are the challenges in selecting pharmacotherapy for pregnant women with inflammatory bowel disease?

The peak of incidence of inflammatory bowel disease (IBD) overlaps with the peak of reproductive age. Moreover, women affected by IBD are often concerned with the possible negative effects of their disease and medications on pregnancy and birth outcomes. From a physician point of view, managing IBD in pregnancy is challenging. Disease activity is the major cause of poor pregnancy outcomes and, therefore, achieving and maintaining IBD remission for the whole duration of pregnancy is the main therapeutic goal. The challenges in selecting therapy lie in balancing the proven efficacy of each drug with the level of safety uncertainty. Except for methotrexate and thalidomide, for which it exits an absolute contraindication in pregnancy, the evidence actually available suggest that most medications can be safely used during pregnancy if appropriately prescribed. The risks associated with drug withdrawal may be higher than the known risks of the medications themselves on pregnancy outcomes. However, all the decisions should be shared with the patient, all available information should be discussed and any therapeutic strategy must be tailored according to patient's context, including disease pattern, activity, severity and acceptance of risk.

Serum transglutaminase antibodies do not always detect the persistent villous atrophy in patients with celiac disease on a gluten-free diet.

BACKGROUND AND AIM: Serum transglutaminase antibodies (tTGs) are used for celiac disease screening and to monitor celiac disease patients on a gluten-free diet (GFD). The need for histology of duodenal biopsies to assess mucosal healing after a GFD is still a matter of debate. We evaluated whether tTGs are adequate to detect the persistence of histological lesions of duodenal mucosa in celiac patients after a GFD. METHODS: In total 253 patients with histological diagnosis of celiac disease according to Marsh criteria, both at the time of diagnosis (T0) and 18-24 months after starting a GFD (T2), were included. tTGs were evaluated both at T0 and T2; endomysial antibodies (EMAs) only at T0. RESULTS: At T0, 9.2% of patients had both tTG and EMA negative values, despite the evidence of duodenal lesions: 33.3% of Marsh 1, 14.3% of Marsh 2 and 5.2% of Marsh 3. At T2, tTGs were negative in 77.6% of patients: 82.2% of Marsh 0, 79.8% of Marsh 1, 70.0% of Marsh 2 and 59.1% of Marsh 3. At T2, approximately 60% of patients with the persistence of mucosal atrophy had negative tTGs. At T0, tTG median values were lower in patients with Marsh 1 and Marsh 2 than patients with Marsh 3 (P < 0.001), whereas no difference was found at T2 regardless of Marsh's grade (P = 0.4). CONCLUSIONS: The results of our study highlight how histologic evaluation of duodenal biopsies remains the gold standard for both celiac disease diagnosis and the evaluation of mucosal recovery after 18-24 months of a GFD.

Secondary hemophagocytic lymphohistiocytosis: a case report.

Hemophagocytic lymphohistiocytosis (HLH) is a rare hematologic syndrome presenting either as an inherited life-threatening inflammatory disorder in children or as a secondary disease in adults. Inherited HLH involves inborn defects in lymphocytes and includes autosomal recessive and X-linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines. Secondary or acquired HLH occurs in the settings of infections, systemic connective tissue disease and lymphoid malignancies, possibly due to underlying genetic predisposition to develop HLH. The mechanisms leading to secondary HLH have yet to be fully determined and the disease remains frequently undiagnosed and thereby untreated. Herewith we report the case of an 83-year old Caucasian male who referred to our Division of Internal Medicine and Nephrology due to marked asthenia associated with fever, mental confusion, drowsiness and hyporexia, who was ultimately diagnosed with HLH secondary to anaplastic B cell lymphoma. This case report illustrates the difficulties in the diagnostic workup of HLH, mainly related to early identification of the underlying disease and rapid instauration of appropriate therapy.

Inflammatory Bowel Disease: New Insights into the Interplay between Environmental Factors and PPARγ.

The pathophysiological processes of inflammatory bowel diseases (IBDs), i.e., Crohn's disease (CD) and ulcerative colitis (UC), are still not completely understood. The exact etiology remains unknown, but it is well established that the pathogenesis of the inflammatory lesions is due to a dysregulation of the gut immune system resulting in over-production of pro-inflammatory cytokines. Increasing evidence underlines the involvement of both environmental and genetic factors. Regarding the environment, the microbiota seems to play a crucial role. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that exert pleiotropic effects on glucose homeostasis, lipid metabolism, inflammatory/immune processes, cell proliferation, and fibrosis. Furthermore, PPARs modulate interactions with several environmental factors, including microbiota. A significantly impaired PPARγ expression was observed in UC patients' colonic epithelial cells, suggesting that the disruption of PPARγ signaling may represent a critical step of the IBD pathogenesis. This paper will focus on the role of PPARγ in the interaction between environmental factors and IBD, and it will analyze the most suitable in vitro and in vivo models available to better study these relationships.