The efficacy of bismuth quadruple therapy, sequential therapy, and hybrid therapy as a first-line regimen for Helicobacter pylori infection compared with standard triple therapy.

Background and Aim: To compare the effectiveness of first-line Helicobacter pylori eradication treatments as standard triple therapy (sTT), bismuth-containing quadruple therapy (BQT), sequential therapy (ST), and hybrid therapy (HT). Patients and Methods: 303 patients treated between July 2018 and June 2021 were studied. In this study, 76 patients in the sTT group, 78 patients in the BQT group, 75 patients in the ST group, and 74 patients in the HT group were randomly allocated. The diagnosis of H. pylori was made endoscopically. H. pylori stool antigen test was performed 4 weeks after finishing the treatment. Results: The mean age was 48.53 (13.48) in sTT, 49.04 (13.02) in BQT, 48.47 (14.54) in ST, and 47.45 (13.4) in HT. There was no significant age difference among the groups (P = 0.909). H. pylori eradication rate in intention-to-treat (ITT) analysis was 68.4% in sTT, 79.5% in BQT, 78.7% in ST, and 83.8% in HT. There was no significant difference between sTT, BQT, and ST regarding of eradication rate. The difference between HT and sTT was significant (P = 0.028). In the per-protocol (PP) analysis, the eradication rate was 74.3% in sTT, 88.6% in BQT, 86.8% in ST, and 92.5% in HT. There was a significant difference between sTT and BQT (P = 0.030) and sTT and HT (P = 0.004), whereas there was borderline significant difference between sTT and ST (P = 0.065). Conclusion: In terms of eradication, HT had the best rate, whereas the lowest rate was in the sTT treatment group. This study does not recommend using sTT because of the low eradication rates. This study recommends HT for overcoming antibiotic resistance and better results.

Parotid elastography: a potential alternative to replace labial biopsy in classification of patients with primary Sjögren's syndrome?

BACKGROUND: There has been a substantial improvement in classifying patients with primary Sjögren's syndrome (pSS), with the new 2016 ACR/EULAR classification criteria. It was aimed to investigate the potential role of parotid elastography in the classification of patients with pSS, as well as the clinical diagnosis of those who do not otherwise fulfil the criteria. METHOD: This is a cross-sectional analysis of patients with pSS followed up in tertiary out-patient rheumatology clinic. Patients' medical records were retrospectively investigated whether or not clinically diagnosed pSS patients fulfil 2016 ACR/EULAR criteria sets. Elastographic evaluation of parotid and submandibular glands bilaterally was performed when presented for follow-up. Strain ratio, shear wave velocity and Pascal values of the glands were obtained. RESULTS: Clinical data on 179 patients with Sjögren's syndrome were investigated. Ninety-six patients with pSS and 30 gender and age-matched healthy controls were included in the study. Eighty-six percent of the clinically diagnosed patients satisfied the 2016 ACR /EULAR criteria and were considered 'criteria patients', and the remaining were considered 'non-criteria patients'. Both criteria and non-criteria patients had significantly higher parotid strain ratio and submandibular velocity compared with healthy controls (p < 0.001 and p < 0.001 for parotid strain ratio and p < 0.001 and p = 0.016 for submandibular velocity, respectively). Replacing labial gland biopsy findings with parotid strain ratio in the new classification criteria resulted in similar sensitivity and lower specificity, 91.6% and 80%, respectively. CONCLUSION: Parotid shear elastography is an easy and noninvasive method and might be a useful tool for the classification of patients with pSS, especially when labial gland biopsy is not feasible. Key Points • Salivary gland elastography (SGE) is a useful tool for the classification of patients with pSS. • SGE could be performed instead of labial biopsy without changing the diagnostic power of classification criteria.

Frequency, characteristics, and clinical determinants of 'prodrome' in familial Mediterranean fever patients.

Objective: Prodrome is defined by manifestations that precede a familial Mediterranean fever (FMF) attack and predict its emergence. We aimed to determine the frequency, characteristics, and clinical determinants of prodrome in patients with FMF.Method: This cross-sectional study was conducted in a tertiary rheumatology clinic. During the clinical interview, all patients completed a standardized questionnaire about the pre-attack period. Prodrome was defined as the presence of any recurrent pre-attack manifestation occurring at least 4 h before an attack. Patients were classified according to whether they had prodrome of any kind of attack.Results: The study enrolled 401 patients aged 37.7 ± 11.0 years (mean ± sd). Male gender, M694V/M694V, homozygous MEFV mutation, peritonitis, pleuritis, and arthritis were more frequent in prodrome-positive patients. Altogether, 141 patients (35.2%) had prodrome. Male gender and ever having attack types of peritonitis or arthritis were independent clinical determinants of prodrome [relative risk (95% confidence interval): 1.72 (1.07-2.76), p = 0.02; 4.27 (1.80-10.1), p = 0.001; 1.77 (1.04-3.04), p = 0.04, respectively]. Age, MEFV mutations, pleuritis, and erysipelas-like erythema were not clinical determinants.Conclusions: All FMF patients, particularly males and patients who had peritonitis or arthritis at any time, should be questioned about prodrome. Prodrome should be analysed in terms of elucidating the pathogenesis of FMF and as an opportunity for a secondary prevention strategy for impending attacks. This study may shed light on prodrome for future cytokine or drug studies with the purpose of developing new cost-effective treatment protocols irrespective of colchicine resistance.

The Pan-Cancer Landscape of Coamplification of the Tyrosine Kinases KIT, KDR, and PDGFRA.

PURPOSE: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable. The presence of 4q12amp has been sporadically reported in small tumor specific series but a large-scale analysis is lacking. We assess the pan-cancer landscape of 4q12amp and provide early clinical support for the feasibility of targeting this amplicon. EXPERIMENTAL DESIGN: Tumor specimens from 132,872 patients with advanced cancer were assayed with hybrid capture based comprehensive genomic profiling which assays 186-315 genes for all classes of genomic alterations, including amplifications. Baseline demographic data were abstracted, and presence of 4q12amp was defined as 6 or more copies of KIT/KDR/PDGFRA. Concurrent alterations and treatment outcomes with matched therapies were explored in a subset of cases. RESULTS: Overall 0.65% of cases harbored 4q12amp at a median copy number of 10 (range 6-344). Among cancers with >100 cases in this series, glioblastomas, angiosarcomas, and osteosarcomas were enriched for 4q12amp at 4.7%, 4.8%, and 6.4%, respectively (all p < 0.001), giving an overall sarcoma (n = 6,885) incidence of 1.9%. Among 99 pulmonary adenocarcinoma cases harboring 4q12amp, 50 (50%) lacked any other known driver of NSLCC. Four index cases plus a previously reported case on treatment with empirical TKIs monotherapy had stable disease on average exceeding 20 months. CONCLUSION: We define 4q12amp as a significant event across the pan-cancer landscape, comparable to known pan-cancer targets such as NTRK and microsatellite instability, with notable enrichment in several cancers such as osteosarcoma where standard treatment is limited. The responses to available TKIs observed in index cases strongly suggest 4q12amp is a druggable oncogenic target across cancers that warrants a focused drug development strategy. IMPLICATIONS FOR PRACTICE: Coamplification of the receptor tyrosine kinases (rtks) KIT/KDR/PDGFRA (4q12amp) is present broadly across cancers (0.65%), with enrichment in osteosarcoma and gliomas. Evidence for this amplicon having an oncogenic role is the mutual exclusivity of 4q12amp to other known drivers in 50% of pulmonary adenocarcinoma cases. Furthermore, preliminary clinical evidence for driver status comes from four index cases of patients empirically treated with commercially available tyrosine kinase inhibitors with activity against KIT/KDR/PDGFRA who had stable disease for 20 months on average. The sum of these lines of evidence suggests further clinical and preclinical investigation of 4q12amp is warranted as the possible basis for a pan-cancer drug development strategy.

Chronic inflammation in adult familial Mediterranean fever patients: underlying causes and association with amyloidosis.

Background: Chronic inflammation, as determined by persistently elevated acute-phase reactants in attack-free periods, can occasionally be observed in patients with familial Mediterranean fever (FMF) and is suggested to be a risk factor for the development of amyloidosis. We aimed to investigate the underlying causes of chronic inflammation in FMF patients and its association with amyloidosis in long-term follow-up. Method: Electronic medical records of FMF patients who had regular follow-up for ≥ 5 years in our cohort were utilized. As part of routine evaluation, detailed history, physical examination, and pertinent laboratory and radiographic investigations were performed in all patients to determine potential causes of elevated C-reactive protein (CRP) levels. Results: The study included 146 FMF patients who had no evidence of amyloidosis at baseline and had regular follow-up for ≥ 5 years. Thirty-seven patients (25.3%) were found to have chronic inflammation in the disease course. Twenty-five (67.5%) of them had either very frequent attacks or chronic manifestations of disease. In the entire study group, amyloidosis developed in five patients (3.42%) during the 5 year follow-up, four in the FMF with chronic inflammation group (10.8%), and only one of the 109 patients without chronic inflammation (odds ratio 13.09, 95% confidence interval 1.41-121.2). Conclusions: The results suggest that persistently high CRP levels during the attack-free periods may be a strong risk factor for the development of amyloidosis in patients with FMF. The vast majority of FMF patients with chronic inflammation had active FMF.

Increased incidence of spondyloarthropathies in patients with Takayasu arteritis: a systematic clinical survey.

OBJECTIVES: Takayasu arteritis and Spondyloarthritis are two distinct inflammatory diseases that affect the same age periods. Increasing number of reports on co-incident Takayasu arteritis-spondyloarthritis cases in literature raised the hypotheses about their association. The purpose of this study is to evaluate the incidence of spondyloarthropathy spectrum diseases in Takayasu arteritis patients. METHODS: Detailed clinical and demographic features of Takayasu arteritis patients were recorded and all were screened meticulously for the presence of spondyloarthropathy features following recommendations of Assessment of SpondyloArthritis international Society. Patients were questioned for inflammatory back pain, enthesitis, uveitis, inflammatory bowel disease, peripheral arthritis, and investigated accordingly with HLA-B27, plain X-rays and sacroiliac magnetic resonance imaging. RESULTS: A total of 69 Takayasu arteritis patients (65 female, 94.2%) were enrolled. After detailed investigation, 14 (20.3%) Takayasu arteritis patients fulfilled the Assessment of SpondyloArthritis international Society criteria for Spondyloarthropathy. Two of 14 (14.2%) spondyloarthropathy patients were positive for HLA-B27. Type 1 and type 2 Takayasu arteritis were more common in patients with diagnosis of both Takayasu arteritis and spondyloarthropathy than those without spondyloarthropathy. Most of patients with diagnosis of both these diseases required biologic therapies than patients with diagnosis of Takayasu arteritis alone (64.3% vs 29.1%, P = 0.014) due to refractory Takayasu arteritis. CONCLUSION: Our results suggest a significant association between Takayasu arteritis and spondyloarthropathy. Possible shared genetic or immunopathogenic processes may explain this association, which merits further investigations.

Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.

BACKGROUND: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists ≤40 (YOs). METHODS: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. RESULTS: Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P < 0.0001). Burnout was highest in central European (84%) and lowest in Northern Europe (52%). Depersonalization scores were higher in men compared with women (60% versus 45% P = 0.0001) and low accomplishment was highest in the 26-30 age group (P < 0.01). In multivariable linear regression analyses, European region, work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P < 0.05). CONCLUSIONS: This is the largest burnout survey in European Young Oncologists. Burnout is common amongst YOs and rates vary across Europe. Achieving a good work/life balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed.

A case of chronic lymphocytic leukemia still taking etanercept for ankylosing spondylitis.

The possible risk of hematologic malignancies in anti TNF users is a matter of debate. Whether associated with the drug or not, how to behave when a hematologic malignancy is discovered in the course of anti TNF treatment remains unanswered. Here we present a 66 year old male patient who had AS for 30 years and had been on etanercept for the last two years and who is diagnosed with B cell chronic lymphocytic leukemia (CLL) stage 1. The patient is still on etanercept for 5 years after the diagnosis without any progression in CLL.

A rare association: Sirenomelia with adrenalomegaly in an infant of diabetic mother.

Sirenomelia or the Mermaid syndrome is a rare congenital anomaly with an incidence of one in 60,000 to 70,000 pregnancies. Sirenomelia is characterized by complete fusion of the lower limbs, commonly associated with renal agenesis, absent external genitalia and other gastrointestinal defects. A 37-week, 3040-g infant was born to a 35-year-old multigravida mother with type 2 diabetes mellitus and hyperlipidemia. To our knowledge, this is the first case of sirenomelia with adrenalomegaly.

Endothelial dysfunction in primary Sjögren syndrome.

OBJECTIVE: In this study, we aimed to investigate endothelial functions in primary Sjögren syndrome. METHODS: Thirty-five patients with primary Sjögren syndrome and 20 age and sex-matched healthy volunteers were recruited to the present study. Flow mediated dilatation of brachial artery and carotid intima-media thickness were measured in the study population. RESULTS: Carotid intima-media thickness values were similar between groups (0.50 +/- 0.10, 0.53 +/- 0.08, p > 0.05). Flow mediated dilatation of the brachial artery was disrupted in the primary Sjögren syndrome group (7% vs 12%, p = 0.002). CONCLUSION: There is endothelial dysfunction in patients with primary Sjögren syndrome, although they had comparable carotid intima-media thickness with the healthy control group.

Serum heart-type fatty acid binding protein levels in acromegaly patients.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a major cytoplasmic low molecular weight protein and released into the circulation when the myocardium is injured. Previous studies have demonstrated that H-FABP is closely associated with acute coronary syndrome, hypertrophic and dilated cardiomyopathy, heart failure, stroke, obstructive sleep apnea syndrome, and pulmonary embolism. The aim of this study was to investigate serum H-FABP value in patients with acromegaly. METHODS AND RESULTS: We measured serum H-FABP levels in 30 consecutive patients with acromegaly, and 55 age-matched control subjects by using a sandwich enzymelinked immunosorbent assay. Serum H-FABP levels were significantly higher in patients with acromegaly than in control subjects (17.40 ± 10.70, and 8.30 ± 7.20, respectively) (p<0.001). A significant positive correlation was found by Spearman's correlation test between serum H-FABP levels and left ventricular end-systolic diameter (r=0.483, p=0.004). CONCLUSION: Patients with acromegaly have increased levels of H-FABP. Serum H-FABP levels might be a marker of myocardial performance in patients with acromegaly.

Synchronous renal cell carcinoma and multiple myeloma: report of two cases and review of the literature.

Coexistence of renal cell carcinoma (RCC) and multiple myeloma (MM) is an extremely rare condition. Appearance of synchronous RCC and MM was not reported independently so far. In this brief communication, we report 2 cases of synchronous RCC and MM, discuss common risk factors or pathogenetic mechanisms seen in either RCC or MM, point out the importance of IL-6 in this coexistence and provide some descriptive properties of all reported synchronous RCC and MM cases.

A case of Kikuchi-Fujimoto disease misdiagnosed as Hodgkin's lymphoma: the importance of second opinion.

Kikuchi-Fujimoto disease (KFD), a rare clinicopathological entity, is a benign and self-limiting disease. It was first described in 1972 by Kikuchi and Fujimoto in Japan independently. KFD is prevalent in Asia, although it may be seen in wide geographical areas, including Turkey. It mainly affects young women. Cervical lymphadenopathy is the most prominent sign and should be differentiated from lymphoproliferative, autoimmune, and infectious diseases. We report on a 30-year-old female patient who was referred to our medical oncology unit for chemotherapy and/or radiotherapy with diagnosis of Hodgkin's lymphoma. Ultimately her diagnosis was corrected as KFD after second opinion of the pathology specimens. We herein provide a brief review about KFD and the importance of second opinion of the pathology specimens.

Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far-East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey.

PTPN22 gene polymorphism in Takayasu's arteritis.

OBJECTIVE: Takayasu's arteritis (TA) is a chronic, rare granulomatous panarteritis of unknown aetiology involving mainly the aorta and its major branches. In this study, genetic susceptibility to TA has been investigated by screening the functional single nucleotide polymorphism (SNP) of PTPN22 gene encoding the lymphoid-specific protein tyrosine phosphatase. METHODS: Totally, 181 patients with TA and 177 healthy controls are genotyped by PCR-RFLP method for the SNP rs2476601 (A/G) of PTPN22 gene. Polymorphic region was amplified by PCR and digested with Xcm I enzyme. RESULTS: Detected frequencies of heterozygous genotype (AG) were 5.1% (9/177) in control group and 3.8% (7/181) in TA group (P = 0.61, odds ratio: 0.75, 95% CI: 0.3, 2.0). No association with angiographic type, vascular involvement or prognosis of TA was observed either. CONCLUSION: The distribution of PTPN22 polymorphism did not reveal any association with TA in Turkey.

Plasma and platelet serotonin levels in familial Mediterranean fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is the most common auto-inflammatory syndrome with exaggerated acute phase and inflammatory response. After revealing the MEFV gene mutation with the finally disturbed end product pyrin, some of the mechanisms were explained. However it is still unknown what triggers or ends these periodical attacks. Moreover, the treatment of up to 30% of the patients, that are resistant to colchicine is still a problem. In this study we investigated the role of serotonin in colchicine-resistant FMF patients. METHODS: Twenty-four FMF patients (male/female: 15/9) and 32 age- and sex-matched healthy controls (male/female: 17/15) were included into the study. Patients were subdivided into two groups. Thirteen had FMF attacks despite regular colchicine (colchicine-resistant group), other 11 had disease under control with colchicine for at least 6-months. Sampling was done both during the attack and ten days after its cessation. Plasma and platelet serotonin levels and acute phase reactants were studied in patients and controls. RESULTS: Colchicine-resistant patients had plasma serotonin (5-HT) levels of 7.85 +/- 1.0 nmol/l during acute attacks which significantly reduced to the levels of 6.3 +/- 0.6 nmol/l (p < 0.001), after 10 days of acute attacks and these levels were significantly lower than those of attack-free patients' and controls' (10.7 +/- 0.2 nmol/l and 10.1 +/- 0.3 nmol/l, respectively). Platelet 5-HT level was 6.4 +/- 0.3 nmol/10(9) platelets during acute attack, and this level was increased to 9.8 +/- 0.5 nmol/10(9) platelets on the 2(nd) sampling, 10 days after the cessation of the acute attack (p < 0.001). They were both significantly higher than those of attack-free FMF patients (5.9 +/- 0.1 nmol/10(9) platelets) and healthy controls (5.7 +/- 0.3 nmol/10(9) platelets). There was a negative correlation between plasma and platelet 5-HT levels (r=-0.77, p < 0.001). CONCLUSION: Changes in plasma and platelet 5-HT levels may be related to the disturbances in 5-HT transport mechanisms or may also be attributed to the potential role of serotonin in the inflammatory cascade. Last but not least, serotonin may have a role in the pathogenesis of FMF.

The relationship between hip joint space width, center edge angle and acetabular depth.

OBJECTIVE: Radiographic parameters used to define acetabular dysplasia may be related to anthropological characteristics independent of dysplasia. The goal of the present study was to investigate the relationship between the minimal joint space width (JSW) of the hip and the parameters that define acetabular dysplasia, in clinically normal subjects. DESIGN: One hundred and eighteen patients who underwent supine abdominal radiography for non-rheumatological indications and had no hip pain or history of hip arthritis were evaluated. JSW was quantified manually using dial calipers, and center edge (CE) angle and acetabular depth were measured for each hip. RESULTS: CE angle, but not acetabular depth, correlated (inversely) with the minimal hip JSW (r=-0.26 and -0.20, P=0.005 and 0.038, R (right) and L (left) hips, respectively). CE angle inversely correlated with the pelvic width (r=-0.27 and 0.27, P=0.003 and 0.004, R and L hips, respectively) and acetabular depth correlated with subject's height (r=0.27 and 0.42, P=0.008 and <0.001 R and L hips, respectively) and leg length (r=0.27 and 0.45, P=0.008 and <0.001, R and L hips, respectively). Also, pelvic width correlated significantly with the JSW (r=0.27 and 0.20, P=0.003 and 0.033, for R and L hips, respectively). CONCLUSIONS: The radiographic parameters used to define acetabular dysplasia, CE angle and acetabular depth, are strongly associated with anthropological variables and CE angle is associated with minimal JSW of the hip. It is important to recognize that height and limb length variability may affect radiographic parameters of acetabular dysplasia, and thus may falsely suggest the presence of anatomic abnormalities in some patients.