Clinical, imaging and genotypical features of three deceased and five surviving cases with ADA2 deficiency

Deficiency of adenosine deaminase type 2 (DADA2) is a rare form of autoinflammatory disorder with limited reported cases. In this paper, we have presented the clinico-immunological, radiological and genetic characteristics of five surviving and three deceased childhood-onset DADA2 patients. We aimed to compare surviving and deceased patients in terms of clinical features and treatment modalities. Moreover, we have evaluated the causes of death in our DADA2 subjects together with the previously reported cases. Demographic features, clinical characteristics, imaging findings, mutations and pharmacological treatments of DADA2 subjects were noted from patient records of pediatric and adult rheumatology clinics in a retrospective and longitudinal nature. Eight patients from seven families were enrolled. While five of them were surviving, three of them had died due to various reasons. Median age of the patients at disease onset and diagnosis was 7 years (range 0.5-13 years) and 14 years (range 5-27 years), respectively. The main clinical manifestations were cutaneous findings (7/8), recurrent low-grade fever (6/8), neurological involvement (6/8) and gastrointestinal involvement (5/8). All patients had increased acute phase reactants at presentation and also during the disease flares. Until the diagnosis of DADA2 was confirmed, five patients have been followed-up with the diagnosis of PAN: two patients both with PAN and FMF, and one patient with CAPS and vasculitis. Demographic, clinical, neurological features and genetic mutations did not differ in surviving and deceased DADA2 patients. Deceased and surviving subjects differed in terms of treatment modalities after the diagnosis of DADA2. Anti-TNF alpha treatment has been initiated in five surviving patients as soon as the diagnosis of DADA2 was established. However, three patients who have died were not able to use sufficient doses of anti-TNF alpha treatment; in one case due to reluctance of patient and in two cases due to establishment of the definite diagnosis by genetic analysis at the same time with the last fatal DADA2 episode. Despite limited number of patients, this case series for the first time compares the phenotypic, genotypic and medication differences between surviving and deceased DADA2 patients. Anti-TNF alpha treatment seems to be efficient and lifesaving in DADA2 patients

Evaluation of factors affecting early and late complications after elective splenectomy

We aimed to investigate the factors affecting early and late complications following splenectomy. The potential factors expected to affect postsplenectomy complications included age (≥60 vs. [Med-Science 2022; 11(2.000): 844-8

Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study

Systemic autoinflammatory diseases (sAIDs) are a heterogeneous group of disorders, having monogenic inherited forms with overlapping clinical manifestations. More than half of patients do not carry any pathogenic variant in formerly associated disease genes. Here, we report a cross-sectional study on targeted Next-Generation Sequencing (NGS) screening in patients with suspected sAIDs to determine the diagnostic utility of genetic screening. Fifteen autoinflammation/immune-related genes (ADA2-CARD14-IL10RA-LPIN2-MEFV-MVK-NLRC4-NLRP12-NLRP3-NOD2-PLCG2-PSTPIP1-SLC29A3-TMEM173-TNFRSF1A) were used to screen 196 subjects from adult/pediatric clinics, each with an initial clinical suspicion of one or more sAID diagnosis with the exclusion of typical familial Mediterranean fever (FMF) patients. Following the genetic screening, 140 patients (71.4%) were clinically followed-up and re-evaluated. Fifty rare variants in 41 patients (20.9%) were classified as pathogenic or likely pathogenic and 32 of those variants were located on the MEFV gene. We detected pathogenic or likely pathogenic variants compatible with the final diagnoses and inheritance patterns in 14/140 (10%) of patients for the following sAIDs: familial Mediterranean fever (n=7), deficiency of adenosine deaminase 2 (n=2), mevalonate kinase deficiency (n=2), Muckle-Wells syndrome (n=1), Majeed syndrome (n=1), and STING-associated vasculopathy with onset in infancy (n=1). Targeted NGS panels have impact on diagnosing rare monogenic sAIDs for a group of patients. We suggest that MEFV gene screening should be first-tier genetic testing especially in regions with high carrier rates. Clinical utility of multi-gene testing in sAIDs was as low as expected, but extensive genome-wide familial analyses in combination with exome screening would enlighten additional genetic factors causing disease

Factors Affecting Inadequate Empirical Antimicrobial Therapy and the Clinical Course of Upper Urinary Tract Infections in Elderly Patients: A Multicenter Study

Introduction: In this study, we aimed to determine the risk factors associated with inadequate empirical antibiotherapy (IEAT) and hospital-related mortality in elderly patients being treated for upper urinary tract infections (UTI)