Behçet disease, familial Mediterranean fever and MEFV variations: More than just an association.

Behçet disease (BD) and familial Mediterranean fever (FMF) are two inflammatory disorders that share many features including historical background, ethnical distribution and inflammatory characteristics. Several studies suggested that BD and FMF might occur in the same individual more commonly than expected. Additionally, the pathogenic MEFV gene variants, especially p.Met694Val, activating the inflammasome complex have been shown to increase the risk for BD in regions where both FMF and BD are prevalent. Whether these variants are associated with certain disease subtypes and whether they may help in the planning of treatment need to be explored. This review provides a recent overview of the plausible association between FMF and BD and the role of MEFV variants in the pathogenesis of BD.

Efficacy of rituximab on disease activity, severity, and disease-related damage in patients with immunosuppressive-resistant systemic sclerosis.

Background/aim: B-cell depletion with rituximab (RTX) is widely used as a rescue therapy in patients with systemic sclerosis (SSc). The aim herein was to analyze the progress of disease-related outcomes after RTX therapy in severe SSc patients. Materials and methods: Included in this study were 27 SSc patients who were followed-up between 2012 and 2020 and received at least 1 cycle of RTX for active disease, despite receiving standard immunosuppressives (ISs). In addition to the European Scleroderma Study Group and European Scleroderma Trials and Research Group activity scores, Medsger's severity, and the recently developed Scleroderma Clinical Trials Consortium Damage Index values were evaluated initially and at 1 year after the first infusion. The progress of individual organ damage was also assessed at the end of the follow-up period (at least 6 months after the last infusion) using the data extracted from the medical records. Results: Disease activity and severity-improved and disease-related overall damage worsened after the first year of RTX therapy (p < 0.001, p = 0.008, and p = 0.005). Some of the disease-related organ damage had improved at the end of the follow-up period, indicating its reversibility. Overall damage scores ≥11 after the first year of RTX therapy were found to be associated with mortality (p = 0.035). Conclusion: RTX contributed to reducing the activity and severity in SSc patients with severe disease, nonetheless the efficacy related to the damage was limited. High damage scores in the first year were found to be associated with mortality. Spontaneous progress of manifestations requiring a longer period to improve and irregular consecutive RTX courses might lead to difficulties in differentiation between activity and damage.

Tocilizumab treatment in severe COVID-19: a multicenter retrospective study with matched controls.

Coronavirus disease-2019 (COVID-19) associated pneumonia may progress into acute respiratory distress syndrome (ARDS). Some patients develop features of macrophage activation syndrome (MAS). Elevated levels of IL-6 were reported to be associated with severe disease, and anti-IL-6R tocilizumab has been shown to be effective in some patients. This retrospective multicenter case-control study aimed to evaluate the efficacy of tocilizumab in hospitalized COVID-19 patients, who received standard of care with or without tocilizumab. Primary outcome was the progression to intubation or death. PSMATCH (SAS) procedure was used to achieve exact propensity score (PS) matching. Data from 1289 patients were collected, and study population was reduced to 1073 based on inclusion-exclusion criteria. The composite outcome was observed more frequently in tocilizumab-users, but there was a significant imbalance between arms in all critical parameters. Primary analyses were carried out in 348 patients (174 in each arm) after exact PS matching according to gender, ferritin, and procalcitonin. Logistic regression models revealed that tocilizumab significantly reduced the intubation or death (OR 0.40, p = 0.0017). When intubation is considered alone, tocilizumab-users had > 60% reduction in odds of intubation. Multiple imputation approach, which increased the size of the matched patients up to 506, provided no significant difference between arms despite a similar trend for intubation alone group. Analysis of this retrospective cohort showed more frequent intubation or death in tocilizumab-users, but PS-matched analyses revealed significant results for supporting tocilizumab use overall in a subset of patients matched according to gender, ferritin and procalcitonin levels.

Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome.

BACKGROUND: In individuals with atherosclerotic risk factors, endothelial dysfunction (ED) appears as an early phase in the development of clinical symptoms. Recent studies indicate that adropin, a newly identified peptide, participates in cardiovascular health through the regulation of several metabolic events including angiogenesis and blood flow. In this study, we aimed to determine the relation of adropin with biochemical and radiologic parameters which reflect ED such as endothelial nitric oxide synthase (eNOS), endothelin 1 (ET-1), nitric oxide (NO) and flow-mediated dilatation (FMD) along with the routine biochemical measurements in patients recently diagnosed with metabolic syndrome (MetS). METHODS: Fasting blood samples from 110 patients with MetS diagnosed according to the NCEP ATP III-2005 criteria were collected to measure the concentrations of adropin and other parameters including the lipid profile, insulin and glucose. Serum NOx concentrations were determined by measuring NO2 plus NO3. FMD test was performed by ultrasonography, and patients were stratified as FMD (+) or (-). Data were compared between these two subgroups and also with matching healthy controls (n=50). Biochemical data were evaluated using Student's t or Mann-Whitney U tests. RESULTS: Fifty-nine subjects had ED (+) and the remaining 101 subjects were ED (-). In the first group, adropin levels were significantly lower than the latter (2.13±1.05 vs. 3.41±1.63 ng/mL, respectively; p<0.001) and independently associated with FMD positivity as assessed by the logistic regression analysis. CONCLUSIONS: Low adropin level in circulation is related to ED and has a close association with FMD. Any alterations in its level may be of help in order to assess the development of ED before the occurrence of clinical symptoms in patients with metabolic syndrome.

Acquired FVIII and FIX Inhibitors after Pregnancy: A Case Report.

Acquired hemophilia is a relatively rare clinical presentation, and most cases present with acquired FVIII inhibitor. The co-occurrence of inhibitors to multiple coagulation factors is uncommon. These autoantibodies may induce spontaneous life-threatening bleeding in patients who have had no previous bleeding disorder. Herein, we present a patient with postpartum acquired FVIII and FIX inhibitors who developed intramuscular hematoma and hemothorax during follow-up. She was then treated with activated prothrombin complex concentrate and methylprednisolone.

Criteria for Hyperinflammation Developing in COVID-19: Analysis of 2 Cohorts From Different Periods of the Pandemic.

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.

Malnutrition treatment and follow-up in clinical nutrition outpatient clinics associated with increased muscle mass.

OBJECTIVE: Clinical nutrition outpatient clinics (CNOCs) are the mainstay of the nutrition bundle in hospitals. They are important for the diagnosis, treatment, and follow-up of outpatients with malnutrition (MN) and sarcopenia. The aim of this study was to evaluate changes in muscle mass during the treatment of MN in patients admitted to CNOCs. METHODS: A total number of 1118 patients were included in this retrospective cohort descriptive study. Data including medical history, weight loss, anthropometric measurements, MN diagnosis (according to ESPEN definition), nutrition treatment, bioelectrical impedance analysis and laboratory examinations were noted for the first admission and the follow-up. RESULTS: This retrospective, cohort descriptive study included 1118 patients. The mean age of the participants was 54 ± 22 y (18-101 y) and half of the patients were men. Of the 1118 patients, 37,7% were ≥65 y of age. Cancer (32.2%) was the most frequent diagnosis followed by diabetes (16.7%) and dementia (11.3%). MN prevalence was 51.6%. Protein- and energy-enriched diet, oral enteral nutrition supplementation, tube enteral feeding, and parenteral nutrition were used in 42.7%, 69.6%, 11%, and 2.7% of the patients with MN, respectively. Skeletal muscle mass was significantly increased in MN, cancer, neuromuscular diseases (NMD) and patients ≥65 y of age in the first 6 mo, and could be maintained during the next 6 mo of follow-up. Patients with cancer, chronic kidney disease, and NMD and those ≥65 y of age were able to increase their body mass index. CONCLUSIONS: MN treatment and follow-up can restore muscle mass especially in patients ≥65 y of age and in those with chronic diseases. CNOCs are beneficial in the treatment and follow-up of MN.

Hypovitaminosis D is Associated with Endothelial Dysfunction in Patients with Metabolic Syndrome.

OBJECTIVES: Recent research has shown that hypovitaminosis D may increase the risk of hypertension, vascular disease, diabetes mellitus, obesity and Metabolic Syndrome (MetS). Endothelial Dysfunction (ED) is one of the key components of MetS which is associated with an imbalance between vasoactive substances such as Nitric Oxide (NO) and Endothelins (ET). In this study, we assessed the association of 25(OH) D3 level with endothelial dysfunction and subclinical atherosclerosis in MetS patients. DESIGN AND METHODS: 105 MetS patients and 48 controls were included. 25(OH) D3 levels were measured using Ultra-High Performance Liquid Chromatography (UHPLC). NOx (NO2 plus NO3) and Endothelin- 1(ET-1) concentrations were determined along with routine biochemical tests. Flow-Mediated Dilatation (FMD) and carotid Intima-Media Thickness (cIMT) were measured by ultrasonography. RESULTS: In MetS patients, vitamin D and NOx levels were significantly lower (p<0.001), while ET-1 levels were higher than controls (p<0.005). MetS patients with ED exhibited significantly lower vitamin D levels than their counterparts free of ED. Vitamin D levels were correlated positively with FMD and NOx, and negatively with systolic blood pressure and body mass index. Subclinical atherosclerosis as assessed by the cIMT did not associate with low vitamin D levels. CONCLUSION: Vitamin D deficiency seen in MetS patients is more prominent in the presence of ED. Hypovitaminosis D may affect endothelial cells, and participate in the development of hypertension.