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

Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy

Background: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. Aims: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. Methods: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. Results: A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. Conclusion: We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding

Serum markers of refractoriness and enteropathy-associated t-cell lymphoma in coeliac disease

The persistence or recurrence of symptoms in patients with coeliac disease (CD), despite a gluten-free diet (GFD), must prompt further work-up for excluding refractory CD (RCD). The aim of this study was to assess the accuracy of serum markers in predicting refractoriness in CD patients. This study included 72 patients affected by CD followed-up at our center, namely 49 uncomplicated CD before and after GFD and 23 RCD. Serum levels of chromogranin A (CgA) and β2-microglobuline were measured at baseline and at follow-up (median time of 13 months) in each group of patients. Cut-off points for each marker were estimated to differentiate RCD from uncomplicated CD patients. Serum levels of CgA and β2-microglobuline were significantly higher in patients with RCD compared to uncomplicated CD (p < 0.001), both at baseline and at follow-up, with no significant difference between RCD type 1 and type 2. The estimated cut-off point for CgA was 90.2 ng/mL (sensitivity 83%, specificity 100%), while for β2-microglobuline it was 696 mcg/L (sensitivity 100%, specificity of 100%). To conclude, CgA and β2-microglobuline could be useful serological markers of refractoriness in CD, with the ability to discriminate those patients who should undergo upper gastrointestinal endoscopy for making a definite diagnosis

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

Comprehensive nutritional assessment in short bowel syndrome with chronic renal failure on teduglutide therapy: A case report

We report the case of a 62-y-old woman with short bowel syndrome (SBS) and chronic renal failure, successfully treated with teduglutide, who underwent comprehensive systematic nutritional assessment including bioelectrical impedance vectorial analysis (BIVA). The patient did not tolerate the attempt of gradual suspension of parenteral nutrition (PN), bumping into the worsening of nutritional status and renal function. She was declared eligible for teduglutide, a glucagonlike peptide 2 analog that stimulates structural and functional intestinal adaptation and increases nutrient and fluid absorption. To date, there is no standardized nutritional management protocol for PN-dependent SBS patients treated with teduglutide. We here report our first 1-y follow-up data. The patient underwent comprehensive systematic nutritional assessment initially every 2 wk, then monthly. It included handgrip strength (HGS), blood tests (particularly serum creatinine, estimated glomerular filtration rate, urea, electrolytes, micronutrients, serum albumin), fluid intake, urine output, quality-of-life (QoL) evaluation, and BIVA, which estimates fat-free mass (FFM) and measures phase angle (PhA) and hydration status. At treatment initiation, the patient was on PN 3 d/wk. After 3 mo, she was weaned off PN. At 1 y, weight and serum albumin were reduced (–7.5 kg and –0.6 g/dL, respectively); FFM, PhA, and HGS slightly decreased; hydration status and renal function were preserved; and QoL subtly improved. No relevant clinical complications or metabolic imbalances occurred. The inclusion of BIVA in the comprehensive systematic nutritional assessment of SBS patients treated with teduglutide could be proposed for appropriate and safe management, particularly in the presence of renal impairment

Impact of in-hospital intravenous iron supplementation on red blood cell transfusions: experience from an Internal Medicine Unit

BACKGROUND: Pharmacological treatment of iron deficiency anaemia can reduce red blood cell (RBC) transfusions. Intravenous iron provides a more effective and quicker correction of iron deficiency anaemia than oral iron, and third-generation high-dose intravenous iron formulations allow the complete correction of iron deficiency with just one or two drug infusions, thus facilitating iron supplementation therapy and reducing transfusion requirement. MATERIAL AND METHODS: In an observational, retrospective study we compared RBC transfusion requirement during hospitalisation and within 3 months of hospital discharge in 88 patients with iron deficiency anaemia treated with high-dose ferric carboxymaltose and in 85 patients treated with ferric gluconate while hospitalised in the Internal Medicine unit of our Institution. RESULTS: Ferric carboxymaltose reduced the number of RBC units given to each transfused patient during hospitalisation (1.81±0.84 vs 2.39±1.49, p=0.011). At hospital discharge, fewer ferric carboxymaltose patients were prescribed home therapy with iron. No differences between treatment groups were observed in the proportion of patients or the number of RBC units transfused within 3 months of discharge. At one month from discharge, however, only 2 ferric carboxymaltose patients had been transfused compared with 7 ferric gluconate patients (p=0.078). Patients transfused post-discharge were more likely to have an underlying malignancy and/or higher serum creatinine concentrations. DISCUSSION: Treatment with ferric carboxymaltose reduced the number of RBC units per transfused patient. Larger studies are required to define risk factors associated with post-discharge transfusion requirement and to establish if home therapy with iron will reduce subsequent transfusions in patients treated with ferric carboxymaltose

Oxidative stress and thromboxane-dependent platelet activation in inflammatory bowel disease : effects of anti-TNF&#945; treatment

Patients with inflammatory bowel disease (IBD) are at higher risk of venous thromboembolism and coronary artery disease despite having a lower burden of traditional risk factors. Platelets from IBD patients release more soluble CD40 ligand (CD40L), and this has been implicated in IBD platelet hyper-activation. We here measured the urinary F2-isoprostane 8-iso-prostaglandin (PG)2\u3b1 (8-iso-PGF2\u3b1), urinary 11\u2013dehydro\u2013thromboxane (TX) B2 (11-dehydro\u2013TXB2) and plasma CD40L in IBD patients, and explored the in vitro action of anti-tumour necrosis factor (TNF)\u2013 \u3b1 antibody infliximab on IBD differentiating megakaryocytes. Urinary and blood samples were collected from 124 IBD patients and 37 healthy subjects. Thirteen IBD patients were also evaluated before and after 6\u2013week infliximab treatment. The in vitro effect of infliximab on patient-derived megakaryocytes was evaluated by immunoflorescence microscopy and by flow cytometry. IBD patients had significantly (p<0.0001) higher urinary 8\u2013iso\u2013PGF2\u3b1 and 11\u2013dehydro\u2013TXB2 as well as plasma CD40L levels than controls, with active IBD patients displaying higher urinary and plasma values when compared to inactive patients in remission. A 6-week treatment with infliximab was associated with a significant reduction of the urinary excretion of 8\u2013iso\u2013PGF2\u3b1 and 11\u2013dehydro\u2013TXB2 (p=0.008) and plasma CD40L (p=0.001). Infliximab induced significantly rescued pro-platelet formation by megakaryocytes derived from IBD patients but not from healthy controls. Our findings provide evidence for enhanced in vivo TX\u2013dependent platelet activation and lipid peroxidation in IBD patients. Anti-TNF\u2013 \u3b1 therapy with infliximab down-regulates in vivo isoprostane generation and TX biosynthesis in responder IBD patients. Further studies are needed to clarify the implication of infliximab induced-proplatelet formation from IBD megakaryocytes

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 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