Safety, Effectiveness, and Treatment Persistence of Subcutaneous Vedolizumab in IBD: A Multicenter Study From the United Kingdom.

BACKGROUND AND AIMS: Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking. METHODS: IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52. RESULTS: Data from 563 patients (187 [33.2%] Crohn's disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups. CONCLUSIONS: Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks.

Do screening tools assess palliative care needs and 12-month mortality in patients admitted to hepatology in-patient wards?

Background: Many liver patients have unmet palliative care needs, but liver clinicians are unclear whom to refer to specialist palliative care (SPC). The Supportive and Palliative Care Indicator Tool (SPICT) and the Bristol Prognostic Screening Tool (BPST) could help identify suitable patients, but neither has been tested for this role. This study evaluated their role as screening tools for palliative care needs and for predicting 12-month mortality. Methods: A case note review of hepatology in-patients, who were not peritransplant and post-transplant status, was conducted in one tertiary unit. Main outcomes were clinical judgement of need for SPC referral, BPST scores, SPICT attribution of caseness and 12-month survival status. Discriminatory ability of tools was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic (AUROC) curve. Results: 117 medical notes were reviewed for survival analysis, 47 of which were additionally assessed for suitability for SPC referral, using clinical judgement. SPICT (sensitivity=93%; PPV=93%; AUROC=0.933) and BPST (sensitivity=59%, PPV=79%, AUROC=0.693) demonstrated excellent and good performance, respectively, in predicting patients' need for SPC referral. SPICT and BPST only had moderate ability at predicting death at 12 months (PPV: 54% and 56%, respectively). Conclusion: SPICT and BPST show potential as screening tools for identifying patients for referral to SPC. Further work is needed to determine how to implement these tools in a clinical setting.

The fate of indeterminate liver lesions: What proportion are precursors of hepatocellular carcinoma?

BACKGROUND: The natural history and incidence of hepatocellular carcinoma (HCC) arising from indeterminate liver lesions are not well described. We aimed to define the incidence of HCC in a cohort of patients undergoing surveillance by magnetic resonance imaging (MRI) and estimate any associations with incident HCC. METHODS: We performed a retrospective follow-up study, identifying MRI scans in which indeterminate lesions had been reported between January 2006 and January 2017. Subsequent MRI scan reports were reviewed for incident HCC arising from indeterminate lesions, data were extracted from electronic patient records and survival analysis performed to estimate associations with baseline factors. RESULTS: One hundred and nine patients with indeterminate lesions on MRI were identified. HCC developed in 19 (17%) patients over mean follow up of 4.6 years. Univariate Cox proportional hazards analysis found incident HCC to be significantly associated with baseline low platelet count (hazard ratio (HR) = 7.3 (95% confidence intervals (CI) 2.1-24.9), high serum alpha-fetoprotein level (HR = 2.7 (95% CI 1.0-7.1)) and alcohol consumption above fourteen units weekly (HR = 3.1 (95% CI 1.1-8.7)). Multivariate analysis, however, found that only low platelet count was independently associated with HCC (HR = 5.5 (95% CI 0.6-5.1)). CONCLUSIONS: HCC arises in approximately one fifth of indeterminate liver lesions over 4.6 years and is associated with a low platelet count at the time of first diagnosis of an indeterminate lesion. Incidence of HCC was more common in people with viral hepatitis and in those consuming > 14 units of alcohol per week. Our data may be used to support a strategy of enhanced surveillance in patients with indeterminate lesions.

Multidimensional Prognostic Index Predicts Clinical Outcome and Mortality in Hospitalised Older Patients with Diverticular Disease.

INTRODUCTION: The Multidimensional Prognostic Index (MPI) is a validated tool for assessing mortality risk in hospitalised patients. We aimed to evaluate whether the MPI predicted mortality and the risk of developing diverticular disease (DD) complications in older patients. METHODS: This is a multicentre study conducted in January 2016-March 2018. All patients with DD aged 65 years and older were included. Patients were stratified into three groups according to MPI groups (1, low risk; 2, moderate risk; 3, high risk). Risk of developing DD complications and mortality rate were assessed. Bivariate models were fitted. RESULTS: One hundred hospitalised patients with DD (mean age 77.9 ± 10.6 years, 53 female patients) were included. Patients with higher MPI groups were more likely to develop DD complications. In particular, 12 (46.2%), 21 (52.5%), and 28 (82.4%) patients with complicated DD were distributed to the MPI 1, MPI 2, and MPI 3 groups (p = 0.0063), respectively. Two patients died in the MPI 1, 4 in the MPI 2, and 29 in the MPI 3 group, with mortality rates of 4.0 per 100 person-year (95% confidence interval [CI] 1.0-15.9), 5.6 (95% CI 2.1-15.0), and 89.2 (95% CI 62-130), respectively (log-rank test p < 0.001). In bivariate analysis, after adjustment for age >80 years, Charlson Comorbidity Index >4, DD complications, and the presence of thromboembolism, higher MPI group was independently associated with higher mortality. Those in the MPI 3 group experienced a greater risk of 1-year hospital readmission (p < 0.001). CONCLUSION: MPI predicted mortality in patients with DD and also correlated with the risk of developing DD complications. Studies focussing on possible pathophysiological mechanisms between DD complications and MPI are needed.

Validation of the Italian translation of the perceived stigma scale and resilience assessment in inflammatory bowel disease patients.

BACKGROUND: Stigmatization is the separation of an individual from a group due to aspects that make them different. Resilience may in turn influence the perception of stigma. Patients with inflammatory bowel disease (IBD) are susceptible to stigma, although data are very limited. AIM: To validate an Italian translation of the IBD perceived stigma scale (PSS) in relation to patients' resilience. METHODS: Consecutive IBD outpatients were prospectively enrolled (December 2018-September 2019) in an Italian, tertiary referral, IBD center. Clinical and demographic data were collected. Stigma and resilience were evaluated through the IBD-PSS and the 25-item Connor-Davidson Resilience Scale, respectively. The International Quality of Life Assessment Project approach was followed to translate the IBD-PSS into Italian and to establish data quality. Higher scores represent greater perceived stigma and resilience. Multivariable analysis for factors associated with greater stigma was computed. RESULTS: Overall, 126 IBD patients (mean age 46.1 ± 16.9) were enrolled. The International Quality of Life Assessment criteria for acceptable psychometric properties of the scale were satisfied, with optimal data completeness. There was no ceiling effect, whilst floor effect was present (7.1%). The discriminant validity and the internal consistency reliability were good (Cronbach alpha = 0.87). The overall internal consistency was 95%, and the test-retest reliability was excellent 0.996. The median PSS score was 0.45 (0.20-0.85). Resilience negatively correlated with perceived stigma (Spearman's correlation = -0.18, 95% confidence intervals: -0.42-0.08, P = 0.03). CONCLUSION: We herein validated the Italian translation of the PSS scale, also demonstrating that resilience negatively impacts perceived stigma.

Liver-spleen axis dysfunction in COVID-19.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an acute infectious disease that spreads mainly through the respiratory route. Besides interstitial pneumonia, a number of other clinical manifestations were noticed in COVID-19 patients. In particular, liver and spleen dysfunctions have been described both as complications of COVID-19 and as potential predisposing factors for severe COVID-19. Liver damage is rather common in COVID-19 patients, and it is most likely multifactorial, caused by the direct insult of SARS-CoV-2 to the liver by the cytokine storm triggered by the virus, by the use of hepatotoxic drugs, and as a consequence of hypoxia. Although generally mild, liver impairment has been found to be associated with a higher rate of intensive care unit admission. A higher mortality rate was reported among chronic liver disease patients. Instead, spleen impairment in patients with COVID-19 has been poorly described. The main anatomical changes are the architectural derangement of the B cell compartment, white pulp atrophy, and reduction or absence of lymphoid follicles, while, from a functional point of view, the IgM memory B cell pool is markedly depleted. The outcome of COVID-19 in asplenic or hyposplenic patients is yet to be defined. In this review, we will summarise the current knowledge regarding the impact of SARS-CoV-2 on the liver and spleen function, as well as the outcome of patients with a pre-existent liver disease or defective spleen function.

Is there scope to improve the selection of patients with alcohol-related liver disease for referral to secondary care? A retrospective analysis of primary care referrals to a UK liver centre, incorporating simple blood tests.

OBJECTIVES: Twenty per cent of people with alcohol use disorders develop advanced fibrosis and warrant referral to secondary care. Improving outcomes in alcohol-related liver disease (ArLD) relies on its earlier detection in primary care with non-invasive tests (NIT). We aimed to determine the proportion of alcohol-related referrals who were diagnosed with advanced fibrosis in secondary care, the prevalence of both alcohol and fatty liver disease ('BAFLD') and the potential impact of NIT on referral stratification. DESIGN/SETTING: Retrospective analysis of all general practitioner-referrals with suspected ArLD/non-alcoholic fatty liver disease (NAFLD) to a UK hepatology-centre between January 2015 and January 2018. PARTICIPANTS: Of 2944 new referrals, 762 (mean age 55.5±13.53 years) met inclusion criteria: 531 NAFLD and 231 ArLD, of which 147 (64%) could be reclassified as 'BAFLD'. PRIMARY OUTCOME MEASURE: Proportion of referrals with suspected ArLD/NAFLD with advanced fibrosis as assessed by tertiary centre hepatologists using combinations of FibroScan, imaging, examination and blood tests and liver histology, where indicated. SECONDARY OUTCOME MEASURES: Included impact of body mass index/alcohol consumption on the odds of a diagnosis of advanced fibrosis, and performance of NIT in predicting advanced fibrosis in planned post-hoc analysis of referrals. RESULTS: Among ArLD referrals 147/229 (64.2%) had no evidence of advanced fibrosis and were judged 'unnecessary'. Advanced fibrosis was observed in men drinking ≥50 units per week (U/w) (OR 2.74, 95% CI 1.51 to 5, p=0.001) and ≥35 U/w in women (OR 5.11, 95% CI 1.31 to 20.03, p=0.019). Drinking >14 U/w doubled the likelihood of advanced fibrosis in overweight/obesity (OR 2.11; 95% CI 1.44 to 3.09; p<0.001). Use of fibrosis 4 score could halve unnecessary referrals (OR 0.50; 95% CI 0.32 to 0.79, p=0.003) with false-negative rate of 22%, but was rarely used. CONCLUSIONS: The majority of referrals with suspected ArLD were deemed unnecessary. NIT could improve identification of liver damage in ArLD, BAFLD and NAFLD in primary care. Anecdotal thresholds for harmful drinking (35 U/w in women and 50 U/w in men) were validated. The impact of alcohol on NAFLD highlights the importance of multi-causality in chronic liver disease.

Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse specialists using the ELF test.

BACKGROUND AND AIMS: Alcohol use disorders (AUD) cause 7.2% of UK hospital admissions/year. Most are not managed by hepatologists and liver disease may be missed. We used the Enhanced Liver Fibrosis (ELF) test to investigate prevalence and associations of occult advanced liver fibrosis in AUD patients not known to have liver fibrosis. METHODS: Liver fibrosis was assessed using ELF in prospective patients referred to the Royal Free Hospital Alcohol Specialist Nurse (November 2018-December 2019). Known cases of liver disease were excluded. Patient demographics, blood tests, imaging data and alcohol histories recorded. Advanced fibrosis was categorised as ELF ≥ 10.5. RESULTS: The study included 99 patients (69% male, mean age 53.1 ± 14.4) with median alcohol intake 140 units/week (IQR 80.9-280), and a mean duration of harmful drinking of 15 years (IQR 10-27.5). The commonest reason for admission was symptomatic alcohol withdrawal (36%). The median ELF score was 9.62, range 6.87-13.78. An ELF score ≥ 10.5 was recorded in 28/99 (29%) patients, of whom 28.6% had normal liver tests. Within previous 5-years, 76% had attended A&E without assessment of liver disease. The ELF score was not associated with recent alcohol intake (p = 0.081), or inflammation (p = 0.574). CONCLUSION: Over a quarter of patients with AUD had previously undetected advanced liver fibrosis assessed by ELF testing. ELF was not associated with liver inflammation or recent alcohol intake. The majority had recent missed opportunities for investigating liver disease. We recommend clinicians use non-invasive tests to assess liver fibrosis in patients admitted to hospital with AUD.

Systematic review: Accuracy of the enhanced liver fibrosis test for diagnosing advanced liver fibrosis and cirrhosis.

BACKGROUND AND AIMS: The rising incidence of chronic liver disease (CLD) has increased the need for early recognition. This systematic review assesses the diagnostic accuracy of the enhanced liver fibrosis (ELF) test in cases of advanced fibrosis and cirrhosis due to multiple etiologies in at-risk populations. METHODS: Studies evaluating the ELF accuracy in identifying advanced fibrosis or cirrhosis, defined as METAVIR stage F ≥ 3 and F = 4 or equivalent, in patients with non-alcoholic fatty liver disease (NAFLD), alcohol liver disease (ALD), or viral hepatitis were included. Liver biopsy was used as the reference standard. Medline and Embase databases were searched. The QUADAS-2 tool was used as a framework to assess risk of bias and applicability. The area under the receiver operator curve (AUROC) was extracted as a summary measure of diagnostic accuracy. RESULTS: Thirty-six studies were included: 11 hepatitis C, 4 hepatitis B, 9 NAFLD, 2 ALD, and 10 mixed. The ELF test showed good diagnostic performance in detecting advanced fibrosis in patients with viral hepatitis (AUROC 0.69 to 0.98) and excellent performance in NAFLD (AUROC 0.78 to 0.97) and ALD (AUROC from 0.92 to 0.94). There is also evidence of good diagnostic performance for detecting cirrhosis in patients with viral hepatitis (AUROC 0.63 to 0.99), good performance in NAFLD (AUROC 0.85 to 0.92), and excellent performance in patients with ALD (AUROC 0.93 to 0.94). CONCLUSION: This systematic review supports the use of the ELF test across a range of CLD as a possible alternative to liver biopsy in selected cases.

Safety and durability of PEG-J: a single-centre experience.

INTRODUCTION: Although percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is currently indicated in a variety of conditions, limited data are available regarding its safety and the best timing for its replacement. We herein describe a single-centre cohort of patients who underwent PEG-J placement or replacement to assess the short- and long-term safety of the procedure. METHODS: Demographic and procedure-related data regarding all patients undergoing a PEG-J procedure between March 2010 and 2020, either first placement or any replacement, at the Endoscopy Unit of a University Hospital in Northern Italy (IRCCS Policlinico San Matteo, Pavia, Italy), were retrospectively collected. Data were collected until last available follow-up. RESULTS: We included 73 patients (mean age 70 ± 9.7, 60.3% female) who underwent a PEG-J procedure. Data on a total of 215 procedures were gathered with a median follow up time of 21 months (IQR 9.3-39.5). No immediate adverse events (AEs) were reported. Short-term (within 30 days) AEs, including jejunal extension dislocations, accidental removal, obstruction and kinking occurred in 12 patients (5.6% of the total procedures), whilst long-term AEs (obstruction, tube malfunctions, inner tube dislocation, pyloric ulcer, hypergranulation tissue, wear, buried bumper syndrome and accidental removal) were reported in 40 patients. The risk of developing an AE was not reduced if tube replacement was performed electively. The median duration of the PEG-J before replacement was 12 months (IQR 6-16 months). CONCLUSION: PEG-J placement and replacement are safe procedures. Although PEG-J durability is variable an elective procedure might be indicated to reduce urgent replacements.

Impact of COVID-19 on liver function: results from an internal medicine unit in Northern Italy.

Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25-97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO2/FiO2 < 200 was associated with greater mortality and need for intensive care (HR 2.34, 95% CI 1.07-5.11, p = 0.033). To conclude, a high prevalence of altered liver function tests was noticed in Italian patients with COVID-19, and this was associated with worse outcomes when developing severe acute respiratory distress syndrome.

Preventing Infections by Encapsulated Bacteria Through Vaccine Prophylaxis in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which comprises ulcerative colitis and Crohn's disease, is an immune-mediated, chronic-relapsing, disabling disorder which is associated with increased mortality and poor patients' quality of life. Patients with IBD are at increased risk of infections for many reasons. In fact, IBD often requires a lifelong immunosuppressive and/or biologic therapy, both commonly associated with respiratory and opportunistic infections, but also gastrointestinal, urinary tract infections, and sepsis. Moreover, impaired spleen function has been found in a considerable proportion of IBD patients, further increasing the risk of developing infections sustained by encapsulated bacteria, such as S. pneumoniae, H. influenzae, and N. meningitidis. Finally, comorbidities and surgery represent additional risk factors for these patients. Despite the availability of vaccinations against the most common serotypes of encapsulated bacteria, uncertainties still exist regarding a proper vaccination strategy and the actual effectiveness of vaccinations in this particular setting. Aim of this narrative review is to focus on the broad topic of vaccinations against encapsulated bacteria in IBD patients, discussing the clinical impact of infections, predisposing factors, vaccinations strategies, and unmet research and clinical needs.

Stigmatisation and resilience in inflammatory bowel disease.

Inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis, is an immune-mediated, chronic relapsing disorder characterised by severe gastrointestinal symptoms that dramatically impair patients' quality of life, affecting psychological, physical, sexual, and social functions. As a consequence, patients suffering from this condition may perceive social stigmatisation, which is the identification of negative attributes that distinguish a person as different and worthy of separation from the group. Stigmatisation has been widely studied in different chronic conditions, especially in mental illnesses and HIV-infected patients. There is a growing interest also for patients with inflammatory bowel disease, in which the possibility of disease flare and surgery-related issues seem to be the most important factors determining stigmatisation. Conversely, resilience represents the quality that allows one to adopt a positive attitude and good adjustments despite adverse life events. Likewise, resilience has been studied in different populations, age groups, and chronic conditions, especially mental illnesses and cancer, but little is known about this issue in patients with inflammatory bowel disease, even if this could be an interesting area of research. Resilience can be strengthened through dedicated interventions that could potentially improve the ability to cope with the disease. In this paper, we focus on the current knowledge of stigmatisation and resilience in patients with inflammatory bowel disease.

Defective spleen function in autoimmune gastrointestinal disorders.

Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria.

Cell Blood Count Alterations and Patterns of Anaemia in Autoimmune Atrophic Gastritis at Diagnosis: A Multicentre Study.

BACKGROUND: Autoimmune atrophic gastritis (AAG) leads to iron and/or vitamin B12 malabsorption, with subsequent haematological alterations which could represent the sole clinical manifestation. We aimed to assess patterns of anaemia and micronutrient deficiencies in patients with AAG at the time of diagnosis. METHODS: Observational, multicentre, cross-sectional study including consecutive adult patients diagnosed with AAG within the last ten years. Cell blood count, red cell distribution width, serum vitamin B12, and ferritin were collected. Multivariate analysis for predictive factors of anaemia was computed. RESULTS: 654 AAG patients (mean age 59.2 ± 13.8 years, female (F): male (M) ratio = 2.3:1) were included. Anaemia was present in 316 patients (48.3%; mean age 60.1 ± 15.8 years, F:M ratio = 2.3:1). Pernicious anaemia (132/316 cases, 41.7%) was more common in males (27.1% versus 12.4%; p = 0.001) and in older patients (63.0 ± 14.6 versus 58.9 ± 14.9 years; p = 0.014), while iron deficiency anaemia (112/316 cases, 35.4%) was more common in females (16.9% versus 10.0%; p = 0.039) and in younger patients (56.8 ± 16.6 versus 60.2 ± 14.6 years; p = 0.043). The prevalence of iron deficiency was equally distributed between anaemic and non-anaemic patients (p = 0.9). Anisocytosis (odds ratio: 10.65, 95% confidence interval: 6.13-18.50, p < 0.0001) was independently associated with anaemia. CONCLUSIONS: Anaemia is a common manifestation in AAG patients, mostly due to micronutrient deficiencies. Scant haematologic alterations and micronutrient deficiencies may precede overt anaemia.

Determinants of diagnostic delay in autoimmune atrophic gastritis.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is characterised by a wide clinical spectrum that could delay its diagnosis. AIMS: To quantify the diagnostic delay in patients suffering from AAG and to explore possible risk factors for longer diagnostic delay. METHODS: Consecutive patients with AAG evaluated at our gastroenterological outpatient clinic between 2009 and 2018 were included. Diagnostic delay was estimated as the time lapse occurring between the appearance of the first likely symptoms, laboratory alterations, and other clues indicative of AAG and the final diagnosis. Patient-dependent and physician-dependent diagnostic delays were also assessed. Multivariable regression models were fitted. RESULTS: 291 patients with AAG (mean age at diagnosis 61 ± 15 years; F:M ratio = 2.3:1) were included. The median overall diagnostic delay was 14 months (interquartile range [IQR] 4-41). Factors associated with longer median overall diagnostic delay were female sex (17 months, IQR 5-48), having a previous misdiagnosis (36 months, IQR 17-125) and a history of infertility/miscarriages (33 months, IQR 8-120), whereas a higher level of education was associated with longer patient-dependent diagnostic delay (4 months, IQR 1-12). First evaluation by a gastroenterologist was associated with a median longer diagnostic delay (6 months, IQR 2-15) compared to an internist (3 months, IQR 3-31) and a haematologist (1 month, IQR 0-2). Age, socioeconomic or marital status did not affect the diagnostic delay. CONCLUSIONS: AAG is burdened by substantial diagnostic delay, especially in female patients, and due to lack of awareness, particularly among gastroenterologists. Uncommon vitamin B12 deficiency-related manifestations are overlooked and may prolong the diagnostic delay.

Controlling Gut Inflammation by Restoring Anti-Inflammatory Pathways in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is caused by a dysregulated immune response against normal components of the intestinal microflora combined with defective functioning of anti-inflammatory pathways. Currently, all therapies approved for IBD manipulate the immune system by inhibiting pro-inflammatory mechanisms, such as tumor necrosis factor-α, gut-homing α4ß7 integrin, interleukin-12/interleukin-23, and Janus kinases. However, some IBD patients are non-responders to these drugs, which are also associated with serious side effects. Thus, it has been hypothesized that therapies aimed at restoring anti-inflammatory signals, by exploiting the tolerogenic potential of cytokines (interleukin-10, transforming growth factor-ß, granulocyte macrophage colony-stimulating factor), immune cells (regulatory T cells, tolerogenic dendritic cells), or mesenchymal stem cells, might offer promising results in terms of clinical efficacy with fewer side effects. In this review, we provide new insights into putative novel treatments aimed at restoring anti-inflammatory signaling pathways in IBD.

Mortality rate and risk factors for gastrointestinal bleeding in elderly patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is burdened by high mortality rate that increases with aging. Elderly patients may be exposed to multiple risk factors for GIB. We aimed at defining the impact of GIB in elderly patients. METHODS: Since 2008, samples of elderly patients (age ≥ 65 years) with multimorbidity admitted to 101 internal medicine wards across Italy have been prospectively enrolled and followed-up (REPOSI registry). Diagnoses of GIB, length of stay (LOS), mortality rate, and possible risk factors, including drugs, index of comorbidity (Cumulative Illness Rating Scale [CIRS]), polypharmacy, and chronic diseases were assessed. Adjusted multivariate logistic regression models were computed. RESULTS: 3872 patients were included (mean age 79 ±â€¯7.5 years, F:M ratio 1.1:1). GIB was reported in 120 patients (mean age 79.6 ±â€¯7.3 years, F:M 0.9:1), with a crude prevalence of 3.1%. Upper GIB occurred in 72 patients (mean age 79.3 ±â€¯7.6 years, F:M 0.8:1), lower GIB in 51 patients (mean age 79.4 ±â€¯7.1 years, F:M 0.9:1), and both upper/lower GIB in 3 patients. Hemorrhagic gastritis/duodenitis and colonic diverticular disease were the most common causes. The LOS of patients with GIB was 11.7 ±â€¯8.1 days, with a 3.3% in-hospital and a 9.4% 3-month mortality rates. Liver cirrhosis (OR 5.64; CI 2.51-12.65), non-ASA antiplatelet agents (OR 2.70; CI 1.23-5.90), and CIRS index of comorbidity >3 (OR 2.41; CI 1.16-4.98) were associated with GIB (p < 0.05). CONCLUSIONS: A high index of comorbidity is associated with high odds of GIB in elderly patients. The use of non-ASA antiplatelet agents should be discussed in patients with multimorbidity.