Moderate Disease Group Research Articles

Examination of cardiac functions during acute attack and remission period in children with familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disease characterized by recurring serosal inflammation. Cardiac involvement in FMF commonly manifests as pericarditis and pericardial effusion; however, there is limited research on myocardial function. This study aimed to assess cardiac functions during active inflammation and remission periods of FMF patients and investigate the cardiac effects of inflammation during the attack period. Thirty-eight FMF patients without additional cardiac diseases were included in the study. Demographic characteristics, clinical symptoms, family history, and MEFV gene analysis results were obtained retrospectively. Blood tests, blood pressure measurements, electrocardiogram evaluations, conventional echocardiography, and speckle tracking echocardiography were performed during the attack and remission periods. Disease severity was assessed using the Pras scoring system. During the attack period, FMF patients exhibited significantly higher leukocyte count, neutrophil count, C-reactive protein, and erythrocyte sedimentation rate compared to the remission period (p < 0.005). Speckle tracking echocardiography revealed decreased function in the inferior segments of the left ventricle during the attack period (p < 0.005). Right ventricular function was more affected in the moderate disease group. FMF patients with lymphopenia during the attack demonstrated more impaired right ventricular function compared to those with normal lymphocyte count. Conclusions: FMF patients experience cardiac abnormalities during active inflammation, highlighting the importance of monitoring cardiac functions in these patients. Speckle tracking echocardiography can provide valuable insights into cardiac involvement in FMF. These findings emphasize the cardiac impact of FMF inflammation and the significance of long-term cardiac function monitoring in the management of FMF patients.What is Known:• The current literature lacks studies investigating myocardial function in the pediatric population during the attack period of this particular disease.• Our objective was to assess the alterations in cardiac function during the attack and remission periods, considering clinical manifestations, disease severity, acute phase reactant levels, and mutation type. We also evaluated the pattern of cardiac involvement and the affected cardiac areas by comparing remission and attack periods.What is New:• Several studies have demonstrated a rise in the prevalence of ischemic cardiac disease and mortality among individuals with FMF.• Investigating cardiac involvement during the attack period in FMF patients can provide valuable insights for the prevention of long-term complications.

A STUDY TO ESTABLISH THE RELATIONSHIP BETWEEN DEPRESSION AND OSTEOARTHRITIS ACCORDING TO THE SEVERITY OF PAIN AND LOSS OF FUNCTION

Objective: To establish a relationship between depression and osteoarthritis according to the severity of pain and loss of function. &#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of study: Orthopedic and Rheumatology department of Combined Military Hospital, Lahore from October 2022 to March 2023&#x0D; Patients and Methods: All the patients reporting to the outpatient department of either gender aged more than 45 years with a diagnosis of OA based on X-ray findings and a consultant review were included in our study. Severity of OA was studied using the WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index. Depression was measured using the Personal Health Questionnaire (PHQ-9) scale in these patients simultaneously. (12) It was translated in Urdu for the ease of our participants.&#x0D; Results: Out of the 196 participants of our study, 71 (36.2%) were males while 125 (63.8%) were females. Mean age of the participants of our study was 55.49 Years + 8.98. Mean WOMAC index score was 61.02 + 19.11. 3 (1.5%) patients of OA had mild disease in our study and no depression was found in them. In the moderate disease group, 34 (17.3%) had no symptoms of depression, 62 (31.6%) had minimal depression, none had mild, moderate or severe depression while only 1 (0.5%) had moderately severe depression. Out of 96 (48.9%) of the OA patients with severe disease as per the WOMAC index, 3 (1.5%) had minimal depression, 47 (23.9%) had mild depression, 15 (7.6%) had moderate depression, 27 (13.8%) had moderately severe depression and 4 (2.0%) had severe depression.&#x0D; Conclusion: OA is a debilitating disease. Quality of life of patients is severely affected as the duration increases due to pain, stiffness and loss of function of joints. Long term disease leads to depression of variable degrees. . Thus early diagnosis and timely intervention in such patients with an individualized management plan can improve the outcome and quality of life of patients.&#x0D; &#x0D; Keywords: Osteoarthritis, Depression, Morbidity

Can Fetuin-A Deficiency Predict the Severity of COVID-19 Disease in Kidney Transplant Recipients?

BackgroundThis study aims to investigate whether fetuin A deficiency predicts the prognosis of COVID-19 disease in kidney transplant recipients (KTRs). MethodThe study was conducted on 35 hospitalized KTRs with COVID-19 pneumonia between November 2020 and June 2021. Serums were collected for fetuin-A measurement at admission and after six months of follow-up. The demographic and laboratory data of the patients were recorded and analyzed with the appropriate statistical method. ResultsA total of 35 KTRs, 23 of which (65.7%) were men, were included in the study. The mean age of the patients was 51.6 ± 14.0 years. Seventeen (48.6%) patients had severe disease criteria and required intensive care (ICU) support. Biopsy-proven acute rejection developed in 6 (17.1%) patients in the follow-up. At admission, the median fetuin-A value was 173.5 mcg/mL (143.5-199.25) in the moderate disease group and 126.0 mcg/mL (89.4-165.5) in the severe patient group (p = 0.005). While the Median fetuin-A value at the time of diagnosis was 173.5 mcg/mL (143.5-199.25), and in the 6th month was 208 mcg/mL [184-229] (p<0.001). By ROC analysis, the effect of serum fetuin-A level in predicting the severity of COVID-19 disease was significant (AUC: 0.771, p = 0.006, 95% CI: 0.615-0.927). When serum fetuin-A cut-off value was taken as 138 mcg/mL to determine disease severity, it was shown to have 83.3% sensitivity and 64.7% specificity. ConclusionsSerum fetuin-A level can predict disease severity in kidney transplant recipients in the presence of active COVID-19 disease.

Galectin-3 as a Potential Prognostic Biomarker for COVID-19 Disease: A Case-Control Study.

BackgroundRecent studies have investigated the importance of Galetin-3 in inflammation, fibrosis, cell proliferation, cardiac disease, diabetes, and tumor formation.AimsThis study aims to investigate the role of the Galectin-3 level in the diagnosis of COVID-19 pneumonia and the value of the Galectin-3 level in predicting the clinical course of the patient.MethodsThis study employed a prospective, case-control study design and was conducted at Bakircay University Ciğli Training and Research Hospital. A total of 100 patients (40 had moderate and 60 had severe/critical COVID-19 disease according to World Health Organisation guidelines) and 50 non-symptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, Galectin-3 levels were evaluated using the enzyme-linked immunosorbent assay (ELISA) method. ResultsThe serum Galectin-3 level was measured as 13.57 (10.9-16.4) ng/mL in the control group, 13.52 (10.69-16.6) ng/mL in the moderate disease group, and 11.65 (6.09-14.33) ng/mL in the severe/critical disease group. Serum Galectin-3 levels were significantly lower in the severe/critical disease group compared to the control and moderate disease groups (p=0.001 and p=0.019, respectively).Using ROC analysis, a larger area under the curve (AUC) for the serum Galectin-3 levels of the control group (AUC=0.622, 95% CI =0.529-0.714; p=0.015) was calculated compared to the COVID-19 patient group for the diagnosis of COVID-19 disease. The Galectin-3 level was found to be 75% sensitive and 50% specific at a cut-off level of 11.3 ng/mL in predicting the need for ICU treatment.ConclusionGalectin-3 levels may be a beneficial biomarker in predicting the clinical severity of COVID-19 disease when used in conjunction with other known biomarkers, at the time of admission to the emergency department (ED).

Decreased fetal cardiac output in pregnant women with severe SARS-Cov-2 infection.

AimWe aimed to examine fetal cardiac output (CO) in patients who recovered from severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV‐2) infection.MaterialsThis prospective study included 48 pregnant women recovered from SARS‐CoV‐2 infection and 50 control cases. SARS‐CoV‐2 infection was diagnosed by polymerase chain reaction (PCR) test in patients. Fetal echocardiographic evaluations were performed at 24–37 weeks of gestation in pregnant women who recovered from the infection and control group.ResultsThe median value of ultrasound evaluation was 34 (2.6) weeks of gestation in the recovery from the SARS‐CoV‐2 infection (RSI) group, and 32 (7.6) weeks in the control group (p = .565). Left cardiac output (LCO) z score was significantly lower in the RSI group than the control group (p = .041). LCO and combine cardiac output (CCO) z score were significantly lower in the severe disease group than mild, moderate disease groups, and controls (p = .019 and p = .013). CCO (ml/min/kg) was decreased in the severe disease group when compared with control and mild disease groups (p = .044).ConclusionIn the present study, fetal cardiac output in pregnant women who recovered from SARS‐CoV‐2 infection was found to be significantly reduced in those with severe disease, while there was no significant difference in mild and moderate cases. Placental dysfunction and inflammatory cytokines might cause fetal cardiac changes. Further studies could be clarified on the impact of SARS‐CoV‐2 infection on fetal cardiac function.

Annexin A1 as a potential prognostic biomarker for COVID-19 disease: Case-control study.

BackgroundAnnexin A1 (AnxA1) is an important endogenous glucocoticoid protein that contributes to the suppression of inflammation by limiting the production of neutrophil and pro‐inflammatory cytokines. This study aims to determine the clinical predictivity value of blood AnxA1 levels in patients with mild and severe–critical pneumonia induced by COVID‐19.MethodsThis study employed a prospective, case–control study design and was conducted at Ankara Training and Research hospital between 10 February 2021 and 15 March 2021. A total of 74 patients (42 of whom had moderate and 32 of whom had severe/critical cases of COVID‐19 disease according to World Health Organization guidelines) and 50 nonsymptomatic healthy volunteers participated in the study. Blood samples were taken from patients at the time of hospital admission, after which serum was isolated. Following the isolation of serum, AnxA1 levels were evaluated using the enzyme‐linked immunosorbent assay method.ResultsThe serum AnxA1 levels were measured as 25.5 (18.6‐38.6) ng/ml in the control group, 21.2 (14.7‐32) ng/ml in the moderate disease group, and 14.8 (9.7‐26.8) ng/ml in the severe/critical disease group. Serum AnxA1 levels were significantly lower in the severe/critical disease group compared with the control and moderate disease groups (P = .01 and P = .0001, respectively). Using receiver operating characteristic analysis, a larger area under the curve (AUC) for the serum AnxA1 levels of the control group (AUC = 0.715, 95% CI = 0.626‐0.803; P = .0001) was calculated compared with the COVID‐19 patient group for the diagnosis of COVID‐19 disease. The AnxA1 level was found to be 80% sensitive and 54.1% specific at a cut‐off level of 18.5 ng/ml for the diagnosis of COVID‐19 disease. Moreover, the AnxA1 level was found to be 69.8% sensitive and 58.1% specific at a cut‐off level of 17.2 ng/ml in predicting the need for intensive care unit (ICU) treatment.ConclusionAnxA1 levels may be a beneficial biomarker in the diagnosis of COVID‐19 pneumonia and in predicting the need for ICU treatment in patients with COVID‐19 pneumonia at the time of admission to the emergency department.

Single-cell analysis reveals cell communication triggered by macrophages associated with the reduction and exhaustion of CD8+ T cells in COVID-19

BackgroundThe coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has become an ongoing pandemic. Understanding the respiratory immune microenvironment which is composed of multiple cell types, together with cell communication based on ligand–receptor interactions is important for developing vaccines, probing COVID-19 pathogenesis, and improving pandemic control measures.MethodsA total of 102 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study. Clinical information, routine laboratory tests, and flow cytometry analysis data with different conditions were collected and assessed for predictive value in COVID-19 patients. Next, we analyzed public single-cell RNA-sequencing (scRNA-seq) data from bronchoalveolar lavage fluid, which offers the closest available view of immune cell heterogeneity as encountered in patients with varying severity of COVID-19. A weighting algorithm was used to calculate ligand–receptor interactions, revealing the communication potentially associated with outcomes across cell types. Finally, serum cytokines including IL6, IL1β, IL10, CXCL10, TNFα, GALECTIN-1, and IGF1 derived from patients were measured.ResultsOf the 102 COVID-19 patients, 42 cases (41.2%) were categorized as severe. Multivariate logistic regression analysis demonstrated that AST, D-dimer, BUN, and WBC were considered as independent risk factors for the severity of COVID-19. T cell numbers including total T cells, CD4+ and CD8+ T cells in the severe disease group were significantly lower than those in the moderate disease group. The risk model containing the above mentioned inflammatory damage parameters, and the counts of T cells, with AUROCs ranged from 0.78 to 0.87. To investigate the molecular mechanism at the cellular level, we analyzed the published scRNA-seq data and found that macrophages displayed specific functional diversity after SARS-Cov-2 infection, and the metabolic pathway activities in the identified macrophage subtypes were influenced by hypoxia status. Importantly, we described ligand–receptor interactions that are related to COVID-19 serverity involving macrophages and T cell subsets by communication analysis.ConclusionsOur study showed that macrophages driving ligand–receptor crosstalk contributed to the reduction and exhaustion of CD8+ T cells. The identified crucial cytokine panel, including IL6, IL1β, IL10, CXCL10, IGF1, and GALECTIN-1, may offer the selective targets to improve the efficacy of COVID-19 therapy.Trial registration: This is a retrospective observational study without a trial registration number.8NBAGhie3qFBk1N_iCrR49Video

Analysis of the Correlation between the Level of Serum Inflammatory Factors and the Degree and Diagnosis of Coronary Artery Disease

To observe the changes of neutrophil gelatinase associated apolipoprotein (neutrophil gelatinase associated lipocalin), lipoprotein associated phospholipase A2 and inflammatory cytokine hypersensitive C-reactive protein in patients with coronary heart disease and to explore the correlation between serum lipoproteinassociated phospholipase A2, neutrophil gelatinase associated lipocalin, hypersensitive C-reactive protein and the degree of coronary artery disease in patients with coronary heart disease. 200 inpatients in cardiovascular department of our hospital were divided into coronary heart disease group (n=153) and control group (n=47) according to coronary angiography. The serum levels of lipoprotein-associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein were measured. According to the Gensini score, the patients in the CHD group were divided into mild, moderate, severe and extremely severe groups. The changes of serum lipoprotein associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein was analyzed. At the same time, the relationship between the levels of serum lipoprotein associated phospholipase A2, neutrophil gelatinase associated lipocalin, hypersensitive C-reactive protein and the degree of coronary artery disease was discussed from the three aspects of coronary artery stenosis and Gensini score and the value of combined detection in the diagnosis of coronary heart disease. The serum levels of lipoprotein associated phospholipase A2 lipoprotein associated phospholipase A2 , neutrophil gelatinase-associated lipocalin, hypersensitive C-reactive protein and Gensini score in the coronary heart disease group were significantly higher than those in the control group (p<0.01). The serum levels of lipoprotein-associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein in extremely severe coronary artery disease group were significantly higher than those in moderate to severe disease group, mild disease group and control group (p<0.05) and those in severe disease group were significantly higher than those in mild and moderate disease group and control group (p<0.05). The area under the curve of combined detection of lipoprotein-associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein in the diagnosis of coronary heart disease reached 0.859. The serum levels of lipoprotein associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein are significantly increased in patients with coronary heart disease and are closely related to the severity of coronary artery disease, which can be used to evaluate the severity of coronary artery disease. The diagnostic rate of combined detection of serum lipoprotein associated phospholipase A2, neutrophil gelatinase associated lipocalin and hypersensitive C-reactive protein for coronary heart disease can reach 0.859, which can provide important clinical guidance value.

Novel serological biomarkers for inflammation in predicting disease severity in patients with COVID-19

BackgroundPatients with severe coronavirus disease 2019 (COVID-19) develop acute respiratory distress and multi-system organ failure and are associated with poor prognosis and high mortality. Thus, there is an urgent need to identify early diagnostic and prognostic biomarkers to determine the risk of developing serious illness. MethodsWe retrospectively analyzed 114 patients with COVID-19 at the Jinyintan Hospital, Wuhan based on their clinical and laboratory data. Patients were categorized into severe and mild to moderate disease groups. We analyzed the potential of serological inflammation indicators in predicting the severity of COVID-19 in patients using univariate and multivariate logistic regression, receiver operating characteristic curves, and nomogram analysis. The Spearman method was used to understand the correlation between the serological biomarkers and duration of hospital stay. ResultsPatients with severe disease had reduced neutrophils and lymphocytes; severe coagulation dysfunction; altered content of biochemical factors (such as urea, lactate dehydrogenase); elevated high sensitivity C-reactive protein levels, neutrophil–lymphocyte, platelet-lymphocyte, and derived neutrophil–lymphocyte ratios, high sensitivity C-reactive protein-prealbumin ratio (HsCPAR), systemic immune-inflammation index, and high sensitivity C-reactive protein-albumin ratio (HsCAR); and low lymphocyte-monocyte ratio, prognostic nutritional index (PNI), and albumin-to-fibrinogen ratio. PNI, HsCAR, and HsCPAR correlated with the risk of severe disease. The nomogram combining the three parameters showed good discrimination with a C-index of 0.873 and reliable calibration. Moreover, HsCAR and HsCPAR correlated with duration of hospital stay. ConclusionTaken together, PNI, HsCAR, and HsCPAR may serve as accurate biomarkers for the prediction of disease severity in patients with COVID-19 upon admission/hospitalization.

Analysis of Influencing Factors and Pharmaceutical Care of Patients with COVID-19 in Fangcang Shelter Hospital.

PurposeIn December 2019, coronavirus disease 2019 (COVID-19) was first identified in Wuhan, and rapidly spread throughout China. Patients with mild symptoms were admitted to Fangcang shelter hospitals for centralized quarantine. We aimed to clarify the medication usage, related adverse reactions, and pharmaceutical interventions in patients with mild COVID-19.Patients and MethodsWe innovatively carried out targeted pharmacy services. We provided online and off-line pharmaceutical services to patients in the Fangcang shelter hospital. The use of medication, related adverse reactions, and the effects of pharmaceutical intervention were analyzed.ResultsLower blood lymphocyte count was proposed as the most significant risk factor in patients with mild illness. All patients received antiviral treatment (arbidol, oseltamivir, and ribavirin); 78.4% of patients received antibiotic therapy (moxifloxacin, levofloxacin, and cefdinir); patients in the moderate disease group received more antibiotic therapy than those in the mild disease group. Most of the patients were treated with traditional Chinese medicine. Patients with moderate disease preferred to receive sedative hypnotic therapy. Diarrhea, nausea and vomiting, insomnia, arrhythmia, and constipation were the most common adverse reactions. The rate of mild-to-moderate illness in the pharmaceutical intervention and non-intervention groups was 20.6% and 31.7%, respectively.ConclusionMost patients with mild illness were treated with antiviral, antibiotic, and Chinese medicine therapy. However, attention should be paid to patients with mild illness presenting with hypertension and low lymphocyte count at the onset; these patients are more likely to develop moderate or severe disease. Moreover, there were many drug-related problems in Fangcang shelter hospital; pharmaceutical care might contribute to alleviate the progress of the patient’s condition. Pharmacists should be prepared to provide skilled and effective services to patients, with the aim to ensure medication safety and promote the overall control of the COVID-19 pandemic.

Sustained Klotho delivery reduces serum phosphate in a model of diabetic nephropathy.

Diabetic nephropathy (DN) is a primary cause of end-stage renal disease and is becoming more prevalent because of the global rise in type 2 diabetes. A model of DN, the db/db uninephrectomized ( db/db-uni) mouse, is characterized by obesity, as well as compromised renal function. This model also manifests defects in mineral metabolism common in DN, including hyperphosphatemia, which leads to severe endocrine disease. The FGF23 coreceptor, α-Klotho, circulates as a soluble, cleaved form (cKL) and may directly influence phosphate handling. Our study sought to test the effects of cKL on mineral metabolism in db/db-uni mice. Mice were placed into either mild or moderate disease groups on the basis of the albumin-to-creatinine ratio (ACR). Body weights of db/db-uni mice were significantly greater across the study compared with lean controls regardless of disease severity. Adeno-associated cKL administration was associated with increased serum Klotho, intact, bioactive FGF23 (iFGF23), and COOH-terminal fragments of FGF23 ( P < 0.05). Blood urea nitrogen was improved after cKL administration, and cKL corrected hyperphosphatemia in the high- and low-ACR db/db-uni groups. Interestingly, 2 wk after cKL delivery, blood glucose levels were significantly reduced in db/db-uni mice with high ACR ( P < 0.05). Interestingly, several genes associated with stabilizing active iFGF23 were also increased in the osteoblastic UMR-106 cell line with cKL treatment. In summary, delivery of cKL to a model of DN normalized blood phosphate levels regardless of disease severity, supporting the concept that targeting cKL-affected pathways could provide future therapeutic avenues in DN. NEW & NOTEWORTHY In this work, systemic and continuous delivery of the "soluble" or "cleaved" form of the FGF23 coreceptor α-Klotho (cKL) via adeno-associated virus to a rodent model of diabetic nephropathy (DN), the db/db uninephrectomized mouse, normalized blood phosphate levels regardless of disease severity. This work supports the concept that targeting cKL-affected pathways could provide future therapeutic avenues for the severe mineral metabolism defects associated with DN.

Evaluation of serum chitinase-3-like protein 1, pentraxin-3, and neutrophil gelatinase-associated lipocalin levels in diabetic foot cases

Introduction: Diabetic foot is a chronic metabolic disease requiring a long duration of treatment and hospitalization in advanced stages. It requires a multidisciplinary approach to the different clinical presentations of the disease that complicate the process. In this study, the effects of serum chitinase-3-like protein 1 (YKL-40), pentraxin-3 (PTX-3), and neutrophil gelatinase-associated lipocalin (NGAL) levels on the prognosis of diabetic foot in different stages were evaluated. Subjects and Methods: A total of 65 patients with diabetes, and 13 healthy controls were included in the study. Wagner stage 0–1 patients were classified as mild disease (n = 26), Wagner stage 2–3 patients were classified as moderate disease (n = 26), and Wagner Stage 4 patients were classified as severe disease (n = 13). Venous blood was taken from the patients, and serum C-reactive protein, erythrocyte sedimentation rate, hemoglobin A1c, YKL-40, PTX-3, and NGAL levels were evaluated. In addition, the relationship between lower extremity vascular status and the markers was investigated. Results: YKL-40 was significantly higher in the severe disease group, PTX-3 was significantly higher in the moderate disease group, and NGAL was significantly higher in the mild disease group. In addition, YKL-40 and PTX-3 levels were found to be high in patients with arterial and venous insufficiency, but this was not observed for NGAL. Conclusions: High levels of serum YKL-40 are associated with advanced stage disease with atherosclerotic process at the forefront, high PTX-3 levels are associated with moderate stage disease with a high level of infection findings, and high NGAL levels are associated with the mild stage of diabetic foot.

Studying of B-cell differentiation and macrophage colony-stimulating factors as new players in the diagnosis of rheumatoid arthritis

Background/aim There is an imperative, yet unmet need for the development of a biomarker panel for progression of rheumatoid arthritis (RA). This study aimed to investigate the reliability of B-cell differentiation factor (BCDF) and macrophage colony-stimulating factor (MCSF) as diagnostic and prognostic biomarkers of RA. Patients and methods A total of 25 RA patients were enrolled and divided into three subgroups according to the disease activity score, remission/minimal, moderate, and severe, in addition to 20 healthy controls. Enzyme-linked immunosorbent assay was used to measure serum BCDF, MCSF, and interleukin (IL)-2, and the calorimetric method was used to measure immunoglobulin G (IgG). In addition, the erythrocyte sedimentation rate was measured at 1 h in the RA patients. Results BCDF, MCSF, and IgG were significantly higher in the RA patients compared with the controls. BCDF was significantly higher in the severe disease group compared with the remission/mild and the moderate disease groups, whereas IgG was significantly higher among the moderate disease group compared with the remission/mild disease group, and among the severe disease group compared with the remission/mild disease group, whereas the erythrocyte sedimentation rate did not show any significant difference between the three subgroups of the disease group. BCDF delineates RA from controls at a cut-off value of 102 pg/ml, whereas at a cut-off value of 37.5 ng/l MCSF delineates RA from controls. Conclusion Serum BCDF and MCSF can be used as RA diagnostic biomarkers, whereas BCDF can be used additionally as a prognostic biomarker.

Three Different Classifications, B Lymphocyte Subpopulations, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) Gene Mutations, CTLA-4 and ICOS Gene Polymorphisms in Turkish Patients with Common Variable Immunodeficiency

B lymphocyte subpopulations, previously defined classification schemes (Freiburg, Paris, EuroClass), TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF13 (APRIL) gene mutations, CTLA-4 and ICOS gene polymorphisms were analyzed in 25 common variable immunodeficiency (CVID) patients and 25 healthy controls. Patients were also divided into two subgroups due to some disease severity criteria. SG (severe disease group) (n:11) included patients who have splenomegaly and/or granulomatous diseases and/or bronchiectasis and/or lower baseline IgG values (<270 mg/dl). MG (moderate disease group) (n:14) patients diagnosed as having ESID/PAGID criteria but does not fulfill SG inclusion criteria. The onset of infectious symptoms and age at diagnosis were 50.0 ± 45.7 and 78.5 ± 54.5 months, respectively. Parental consanguinity rate was 54.5% in SG and 7.1% in MG. Switched-memory B cells (CD19 + 27 + IgD-IgM-) showed significant decrease in CVID patients and these cells were also significantly lower in SG compared to MG. CVID patients had significantly higher percentages of CD19 + κ + B cells and CD19 + λ + B cells than healthy controls. Freiburg classification: 87.5% of patients (n:21) were in group I and 12.5% were in Group II. Eighteen (75%) CVID patients with a low percentage of CD21(low) B cells were in Group Ib while three patients classified as Group Ia. The significantly lower levels of IgG and IgA in Group Ia is a novel finding. The percentages of patients for Paris Classification groups MB0, MB1, MB2 were 88%, 4% and 8%, respectively. There was a significant increase of splenomegaly, lymphadenopathy and autoimmune cytopenia in Group MB0. EuroClass: 45.8% of patients were smB+ and 54.2% were smB-. Splenomegaly and lymphadenopathy were significantly higher in smB- group. TACI: One patient carried heterozygous C104R mutation which was known as disease causing. APRIL: G67R and N96S SNPs were detected in most of the patients and healthy controls. BAFF-R: P21R/H159Y compound heterozygous mutation (n:1) and P21R heterozygous mutations (n:3) were detected. +49 A > G changes in exon 1 of CTLA-4 gene: GG and AG genotypes increase the risk of CVID development 1.32 and 2.18 fold, respectively. 1564 T > C polymorphisms on 3'UTR region in exon 2 of ICOS gene was not found to be significantly different in CVID patients. CVID classifications were not helpful in determining the genetic etiology of CVID.

Prevalence and characteristics of restless legs syndrome (RLS) in the elderly and the relation of serum ferritin levels with disease severity: Hospital-based study from Istanbul, Turkey

The RLS is an underdiagnosed condition, characterized by unpleasant sensations in the legs. Pathophysiological mechanisms may include iron deficiency as reflected by low serum ferritin levels and dopaminergic system dysfunction. The purpose of our study was to investigate the prevalence and characteristics of RLS in the elderly and the relation of serum ferritin levels with disease severity. Ambulatory 1012 (621 women, 391 men, mean age: 73.51±7.12 years) consecutive patients above 65 years who admitted to our clinic for any reason were evaluated according to the International RLS Study Group (IRLSSG) criteria: 103 patients (74 women, 29 men, mean age: 72.43±6.31) (10.18%) had RLS diagnosis. Only 9 of them had known RLS. The duration of symptoms was 4.80±4.65 years and 27 patients (26.2%) had positive family history. The average of serum ferritin levels was 39.13±23.74ng/ml and 71 patients (68.9%) had serum ferritin levels ≤50ng/ml. The disease severity was evaluated with IRLSSG rating scale. Patients were classified as severe–very severe group (n=49) and mild–moderate group (n=54). The ferritin levels of severe–very severe disease group were lower than those of mild–moderate disease group (26.01±15.82ng/ml versus 49.87±23.24ng/ml, p<0.001). Our data show that RLS is very common in the elderly and the disease is more severe in patients with lower ferritin levels.

Lymphatic malformations of the head and neck: Introduction of a disease score for children, Cologne Disease Score (CDS)

A clinical staging system for children with lymphatic malformations that would allow for a standardized comparison of disease and treatment outcomes. We developed an examination sheet for the determination of a disease score ranging from 0 (worst) points to 10 (best) points, Cologne Disease Score (CDS). Disfigurement, dysphagia, dysphonia, dyspnea and an observer statement towards progression were contributing to CDS. Each parameter yielded two, one or zero points. Two points were given when no limitation was seen in the patient concerning the respective item. One point was given at mild limitation and zero points were given when considerable limitation in the respective item could be observed. We evaluated 26 patients with lymphatic malformations of the head and neck retrospectively by completing one examination sheet for each patient-visit. Four patients had an initial CDS value of three or less points (severe disease-group). After therapy the mean value of their score increased only slightly to 3.9+/-2.6 points. Six patients had an initial CDS value of four, five or six points (advanced disease-group). After treatment their mean score value increased dramatically to 9.0+/-1.5 points (P<0.001). Sixteen patients initially had seven points or higher (moderate disease-group), they had 9.8+/-0.4 points after treatment. The evaluation of the CDS was easy and expeditious. The score itself was a good predictor in view of the outcome. This new disease score for paediatric patients might be appropriate to evaluate therapeutic trials in paediatric patients.

Safety of Bronchoscopy, Biopsy, and BAL in Research Patients with COPD

Bronchoscopy with biopsy and BAL is being performed increasingly in patients with COPD as a research tool. Previous reports have shown these procedures to be safe in asthmatic patients, but there is little safety data specific to COPD. We studied 57 patients with COPD (11 women and 46 men; median FEV(1), 1.2 L [range, 0.64 to 2.69 L]; percent predicted FEV(1), 44.5% [range, 25 to 74.8%]). Eleven patients had mild disease, 28 patients had moderate disease, and 18 patients had severe disease according to British Thoracic Society classification. Ninety-eight bronchoscopies were performed according to American Thoracic Society guidelines: 68 procedures with endobronchial biopsy and BAL and 30 procedures with biopsy alone. Controlled oxygen was administered via nasal cannula, and pulse oximetry and vital signs were monitored. Five adverse events occurred. One patient in the moderate-disease group had severe bronchospasm requiring 4 days of inpatient treatment. One patient in the severe-disease group had a pneumothorax requiring 7 days of inpatient treatment. There were three episodes of hemoptysis, two with pleuritic pain (in the BAL group) that settled without intervention. No deaths or prolonged morbidity were observed. We found a 2.0% incidence of adverse events requiring hospital treatment and a 3.1% incidence of minor hemoptysis requiring no intervention. Bronchoscopy, biopsy, and BAL can be performed safely in patients with COPD, including those with severe disease, provided careful assessment is performed and guidelines are adhered to.

Bone Mineral Density and Bone Turnover Markers in a Group of Male Ankylosing Spondylitis Patients: Relationship to Disease Activity

Conflicting data have been published about osteoporosis and bone turnover markers in patients with ankylosing spondylitis (AS). The aim of this study was to determine bone mineral density (BMD) of the lateral lumbar spine in a group of male patients with AS and to investigate the relationship between clinical parameters and markers of bone turnover. Thirty-two consecutive AS patients with a mean disease duration of 14.8 years and 32 control subjects were included. Demographic and clinical characteristics were recorded. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to determine the activity of disease. BMD was determined for the lateral lumbar spine in both patients and control groups. Serum osteocalcin and urinary N-telopeptide were measured as bone turnover markers in patient and control groups. Although the mean values of lumbar BMD in AS patients tended to be lower than in the control group, the difference was not statistically significant. Osteoporosis was observed in 11 (34.3%) of AS patients and in 2 (6.2%) of the control group. Osteocalcin levels were significantly higher in AS patients in comparison with control subjects (p < 0.05). In the subgroup analysis according to the activity of the disease, erythrocyte sedimentation rate and N-telopeptide levels were significantly higher in the severely active group when compared with that in mild or moderate disease groups. Active AS patients compared with the control group had significantly lower BMD and significantly higher N-Telopeptide levels (p < 0.05). The levels of BASDAI scores and N-telopeptide values correlated significantly with each other. The incidence of osteoporosis is high in AS patients, and patients with active disease are especially at risk for developing osteoporosis. The monitoring of bone turnover markers and disease activity indices may help to predict patients at risk. Prophylactic and therapeutic strategies are needed to struggle against bone loss in patients with this disabling condition.

Complement activation by titin and ryanodine receptor autoantibodies in myasthenia gravis: A study of IgG subclasses and clinical correlations

To elucidate the mechanism of immune damage caused by titin and ryanodine receptor (RyR) autoantibodies in myasthenia gravis (MG), we studied the complement-activating capacity and the IgG subclass distribution of these autoantibodies in sera from 49 MG patients. Complement activation occurred in 38 out of 49 titin antibody positive sera, and in 14 out of 21 RyR antibody positive sera. The titin antibodies occurred only in the IgG 1 and IgG 4 subclasses, whereas the RyR antibodies occurred in all four IgG subclasses but with IgG 1 predominance. Complement-activating RyR antibodies occurred with higher frequency in sera of thymoma MG than of late-onset MG. RyR IgG 1 antibodies occurred more often in severe MG than in mild and moderate disease groups. Mean total IgG and IgG 1 titin and RyR antibody titers fell during long-time patient observation together with an improvement of the MG symptoms.