Expanding the mutation spectrum in ICF syndrome: Evidence for a gender bias in ICF2.

BACKGROUND: Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations). AIM: To study the mutation spectrum in ICF syndrome. MATERIALS AND METHODS: Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members. RESULTS: We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta-analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients. DISCUSSION: The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort. CONCLUSION: Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes.

Community-acquired hypokalemia in elderly patients: related factors and clinical outcomes.

PURPOSE: Electrolyte imbalance is a common problem affecting the elderly. Increased number of comorbidities and frequent use of drugs may contribute to increased risk of hypokalemia in the elderly. This study was performed to investigate the prevalence of community-acquired hypokalemia (CAH), risk factors for its development, related factors with hypokalemia, and morbidities and all-cause mortality rates (MR) of CAH in the elderly patients. METHODS: Total of 36,361 patients aged above 65 years were screened retrospectively. Group 1 consisted of 269 elderly patients with potassium level ≤3.5 mmol/L, and group 2 (control group) consisted of 182 subjects with potassium level between 3.6 and 5.5 mmol/L. Etiologic factors of CAH, presence of comorbidities, duration of hospital stay, hospital cost, and clinical outcomes were recorded. RESULTS: Prevalence of hypokalemia was found 3.24% in patients aged above 65 years. Duration of hospital stay, presence of ≥2 comorbid diseases, hospital cost, and MR were significantly higher in group 1 compared to group 2 (p < 0.001 for all). Loop diuretics, hydrochlorothiazides, beta agonists, inadequate oral intake, and female gender were all independent risk factors for CAH in elderly patients. Patients with ≥2 comorbid diseases were found to have greater risk of hypokalemia than the patients with <2 comorbidities. CONCLUSIONS: Length of hospital stay, hospital cost, and MR were higher in elderly with CAH. Female gender, hydrochlorothiazides, loop diuretics, and ≥2 comorbid diseases are the leading risk factors associated with CAH in elderly.

Clinical outcomes of acute kidney injury developing outside the hospital in elderly.

PURPOSE: Although various studies have improved our knowledge about the clinical features and outcomes of acute kidney injury developing in the hospital (AKI-DI) in elderly subjects, data about acute kidney injury developing outside the hospital (AKI-DO) in elderly patients (age ≥ 65 years) are still extremely limited. This study was performed to investigate prevalence, clinical outcomes, hospital cost and related factors of AKI-DO in elderly and very elderly patients. METHODS: We conducted a prospective, observational study in patients (aged ≥ 65 years) who were admitted to our center between May 01, 2012, and May 01, 2013. Subjects with AKI-DO were divided into two groups as "elderly" (group 1, 65-75 years old) and "very elderly" (group 2, >75 years old). Control group (group 3) consisted of the hospitalized patients aged 65 years and older with normal serum creatinine level. In-hospital outcomes and 6-month outcomes were recorded. Rehospitalization rate within 6 months of discharge was noted. Hospital costs and mortality rates of each group were investigated. Risk factors for AKI-DO were determined. RESULTS: The incidence of AKI-DO that required hospitalization in elderly and very elderly patients was 5.8 % (136/2324) and 11 % (100/905), respectively (p < 0.001), with an overall incidence of 7.3 % (236/3229). Chronic kidney disease (CKD) was developed in 43.4 % of group 1 and 67 % of group 2 within the 6 months of discharge (p < 0.001). Progression to CKD was significantly lower in the control group than in groups 1 and 2 (p < 0.001). Mortality rates for groups 1, 2 and 3 were 23.5 % (n = 32), 31 % (n = 31) and 4.2 % (n = 8), respectively (p < 0.05). Rehospitalization rate within the 6 months of discharge for the groups with AKI-DO was higher than for the control group (p < 0.001). Hospital cost of groups 1 and 2 was significantly higher than that of the control group (p < 0.001). Nonsteroidal anti-inflammatory drugs (NSAIDs) (OR: 6.839, 95 % CI = 4.392-10.648), angiotensin-converting enzyme inhibitors (ACEI) (OR: 7.846, 95 % CI = 5.161-11.928), angiotensin receptor blockers (ARB) (OR: 6.466, 95 % CI = 4.813-8.917), radiocontrast agents (OR: 8.850, 95 % CI = 5.857-13.372), hypertension (OR: 4.244, 95 % CI = 2.729-6.600), diabetes mellitus (OR: 2.303, 95 % CI = 1.411-3.761), heart failure (OR: 3.647, 95 % CI = 2.276-5.844) and presence of infection (OR: 3.149, 95 % CI = 1.696-5.845) were found as the risk factors for AKI-DO in elderly patients (p < 0.001 for all). Patients with AKI-DO had higher 6-month mortality rate (HR 1.721, 95 % CI: 1.451-2.043, p < 0.001). Mortality risk increased 0.519 times at 20th day. CONCLUSIONS: The incidence of AKI-DO requiring hospitalization is higher in very elderly patients than elderly ones, especially in male gender. Use of ACEI, ARB, NSAID and radiocontrast agents is the main risk factors for the development of AKI-DO in the elderly.

Recurrent Acute Kidney Injury in Renal Transplant Patients: A Single-Center Study.

OBJECTIVE: Renal transplant patients may have recurrent episodes of acute kidney injury (AKI) during the posttransplant period. Determination and management of risk factors may help to prevent recurrence of AKI and allograft loss. In this study, we investigated the clinical features of renal transplant patients with recurrent AKI and evaluated etiologies and risk factors. MATERIALS AND METHODS: A total of 19 patients with 79 AKI episodes were examined retrospectively. AKI classes, etiologies, and risk factors were investigated. Their features were compared with 38 renal transplant patients without AKI. RESULTS: Distribution of AKI episodes according to the type of injury was as follows: 15 prerenal, 43 renal, 6 postrenal, and 15 mixed. Renal transplant patients with recurrent AKI had a greater duration of dialysis before transplantation (P < .05). Logistic regression analysis revealed no predictor for recurrent AKI after renal transplantation. Infections participated in the development of 45 AKI episodes. Chronic kidney disease developed in 16 patients. CONCLUSION: Infections are the leading condition associated with recurrent AKI in renal transplant patients. Recurrent AKI may contribute to the development and progression of chronic kidney injury.

JAGN1 Deficient Severe Congenital Neutropenia: Two Cases from the Same Family.

Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN) JAGN1-mutant neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in JAGN1 gene, exhibiting multisystemic involvement.

How do we measure blood pressure at home?

BACKGROUND: Home blood pressure monitoring (HBPM) is one of the measures that increases compliance with antihypertensive therapy. HBPM requires a proper measurement technique as well as an accurate sphygmomanometer. The aim of this study was to assess the characteristics of home sphygmomanometers (HS) in a big city in Turkey. SUBJECTS AND METHOD: We assessed the HS of hypertensive patients (n = 452; male: 253, female: 199) who were examined for the first time in our outpatient center. General evaluation of HS included trademark, model, device's age, cuff size, validation and calibration status. RESULTS: We interviewed 452 patients and 452 HS were identified. The most common factors affecting the patients' choice for the type and model of the HS were its simplicity and ease of use (28.2%), followed by advertisements (44%), physician's advice (19.3%) and the belief in accurate measurement (< 1%). All patients were unaware of validation and calibration of their devices. CONCLUSION: Awareness of both patients and physicians about the validation status of HS is not enough. Some complaints from patients may be associated with using non-validated HS. There is a need for a policy or standard criteria for HS.

Vitamin D as an adjunct to subcutaneous allergen immunotherapy in asthmatic children sensitized to house dust mite.

BACKGROUND: We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen-specific immunotherapy (IT). METHODS: Fifty children with asthma and receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1-specific IgG4. In addition, D. pteronyssinus-induced CD4(+) CD25(+) FOXP3(+) T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL-10 and TGF-ß responses were assessed. RESULTS: In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month - baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1-specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1-induced IL-10 and TGF-ß were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02). CONCLUSION: Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.

Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients: a single-center experience in Turkey.

PURPOSE: Hyponatremia is a common electrolyte disorder in hospitalized patients. Clinical features, outcome and cost of hyponatremia-associated admission and hospitalization in elderly and very elderly patients are not well known. METHODS: Elderly (>64 years) patients admitted to the emergency department (ED) and hospitalized between January 1, 2010, and December 31, 2010, were evaluated. Hyponatremia was defined as serum sodium level below 135 mmol/L. Hyponatremic patients were divided into two groups: group 1 (n = 150, 65-74 years old) and group 2 (n = 103, >74 years old). RESULTS: A total of 4,960 patients above 65 years of age admitted to ED and hospitalized were included. Prevalence of ED in group 1 and group 2 was 4.1 % (150/3,651) and 7.8 % (103/1,309), respectively (p < 0.001). Vomiting and diarrhea were the most important complaints. A total of 111 (43.8 %) patients were being treated with renin-angiotensin system (RAS) blockers. Mortality, morbidity and hospital cost increased in parallel to decrease in serum Na(+) level and increase in age. Group 2 subjects had not only higher intensive care need (p < 0.01) and mortality rates (p < 0.01), but also higher hospital cost burden (p < 0.05) compared to group 1. Alzheimer's disease was one of the most common co-morbidity in patients, particularly in group 2 (5.3 % vs. 21.3 %, p < 0.001). CONCLUSION: Hyponatremia-associated hospitalization is an important and potentially lethal condition in elderly and very elderly patients. Clinicians should be careful when prescribing RAS blockers and diuretics in elderly patients.

Serum retinol binding protein 4 level is related with renal functions in Type 2 diabetes.

AIM: We aimed to evaluate the metabolic parameters and diabetes complications which would probably affect the serum retinol-binding protein 4 (RBP4) levels in Type 2 diabetic individuals. In addition to serum RBP4 concentration, the levels of its ligands, serum retinol and transthyretin (TTR) were also considered in this evaluation. SUBJECTS AND METHODS: Serum RBP4, retinol, and TTR levels were measured in 53 Type 2 diabetic subjects and 30 body mass index (BMI)- matched controls. The molar ratios of RBP4 to retinol and RBP4 to TTR were compared. RESULTS: While the RBP4 values were similar to those in the control group in Type 2 diabetic patients, the molar ratio of RBP4 to TTR was found to be higher than that of the control group. The serum RBP4 levels in patients who had retinopathy and macrovascular disease were similar to those in patients who did not. However, the RBP4 levels, molar ratios of RBP4 to retinol and RBP4 to TTR in micro- macroalbuminuric patients were found to be significantly higher than in normoalbuminuric subjects and controls. There was no correlation between the RBP4 levels and the patients' age, BMI, duration of diabetes, LDL, triglyceride, serum creatinine, and glycated hemoglobin values. Micro-macroalbuminuria and estimated glomerular filtration rate were independent determinants for increased serum RBP4 levels. CONCLUSION: According to the data obtained from this study, diabetic retinopathy and cardiovascular complications do not affect the serum RBP4 level in Type 2 diabetes. Renal functions rather than the metabolic factors of diabetes determine the RBP4 level and its relation with its ligands.

Pure red cell aplasia preceding malignant lymphoma in a renal transplant patient.

Malignant disorders are one of the major causes of morbidity and mortality in transplant patients. We present herein a renal transplant recipient with malignant lymphoma which preceded by pure red cell aplasia (PRCA). Acquired PRCA is a rare hematologic disorder in renal transplant recipients. It has been associated with a variety of disorders of immunologic dysfunction and neoplasms, exposure to drugs and toxins, infectious diseases, pregnancy and severe nutritional deficiency. This is the first case with PRCA preceding the malign lymphoma in a renal transplant patient. Treatment of lymphoma and lymphoma-related humoral and cellular changes or other undefined effects that may be related to therapy may be responsible of the resolving of PRCA in this patient. In this regard, renal transplant patients with acquired PRCA, must be closely followed for an underlying neoplastic disorder.