Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.     

Prolidase deficiency

A 32‐year‐old mentally retarded woman was admitted to hospital with recurrent ulcers on her legs, which appeared for the first time at 8 years of age. Apart from recurrent lower respiratory tract infections and chronic otitis media, her personal history was unremarkable. Her parents were second‐degree relatives. The family history showed no similar disease or mental retardation. Physical examination revealed that the patient had an unusual facial appearance, with a high‐arched palate; she had multiple tooth caries ( Fig. 1 ).

Figure Figure 1  Open in figure viewer PowerPoint Facial appearance of the patient     

Life's Simple 7 and Nonalcoholic Fatty Liver Disease: The Multiethnic Study of Atherosclerosis

BackgroundThe American Heart Association (AHA) has defined Life's Simple 7 (LS7) as a measure of overall cardiovascular health . Nonalcoholic fatty liver disease (NAFLD) has been involved as a risk factor for cardiovascular disease. We evaluated the association between LS7 and NAFLD.MethodsWe evaluated participants form the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Cardiovascular health score was calculated from the Life's Simple 7 metrics. A score of 0-8 was considered inadequate, 9-10 average, and 11-14 optimal. NAFLD was defined using noncontrast cardiac computed tomography (CT) and a liver/spleen attenuation ratio (L/S) < 1. Multivariable regression were performed to evaluate the association.ResultsOur cross-sectional analysis of 3901 participants showed 19% (n = 747) had optimal cardiovascular health, 33% (n = 1270) had average, and 48% (n = 1884) had inadequate. White participants were most likely to have an optimal score (51%, n = 378), whereas African American participants had the lowest proportion with optimal scores (16%, n = 120; P < 0.001). The overall prevalence of NAFLD was 18% with a distribution of 7%, 14%, and 25% in the optimal, average, and inadequate score categories, respectively (P < 0.001). Adjusted for risk factors, average and optimal health categories had lower odds of NAFLD compared to those with inadequate scores: odds ratio for average, 0.44 (95% confidence interval 0.36-0.54); optimal, odds ratio 0.19 (95% confidence interval 0.14-0.26). This association was similar across gender, race and age groups.ConclusionA more favorable cardiovascular health score was associated with a lower prevalence of NAFLD. This study may suggest a potential of Life's Simple 7 in the prevention of liver disease.     

Sildenafil Citrate Does Not Alter Ventricular Repolarization Properties: Novel Evidence from Dynamic QT Analysis

Background: Sildenafil citrate may have direct cardiac electrophysiological effects, and is possibly responsible for some cardiac events. The aim of our study was to investigate the effects of sildenafil citrate on QT dynamicity properties with a new QT analysis program showing even small changes in ventricular repolarization. Methods: Twenty‐four‐hour Holter electrocardiographic recordings were used to obtain the data in the predrug phase (1‐hour rest position before drug administration), and in the postdrug phase (1‐hour rest position, which began 60 minutes after 50 mg oral sildenafil citrate administration). With the special QT analysis program (Verda, Reynolds Medical Ltd., UK); mean values of RR, QT, QT_o (corrected QT), J (the exponent of correction formula) and S (QT/RR plots slope) parameters together with QT variability indexes (QTVI) were calculated for study phases. Results: Mean ± SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR: 845 ± 42 ms vs 816 ± 46 ms, P < 0.05; QT: 371 ± 8 ms vs 361 ± 9 ms, P < 0.05). However, sildenafil did not induce any significant change in mean ± SEM values for QT_o, J, and S in postdrug phase compared with predrug phase (408 ± 10 ms vs 406 ± 8 ms, 0.474 ± 0.030 vs 0.433 ± 0.025, 0221 ± 0.020 vs 0.198 ± 0.017, respectively; P > 0.05). QTVIs were also not different in each phase (predrug: ?0.874 ± 0.071 vs postdrug: ?0.997 ± 0.067, P = 0.109). Conclusions: Fifty milligrams sildenafil does not affect QT dynamicity properties. The cardiac events associated with sildenafil could not be explained with ventricular arrhythmias.     

Diagnostic value of screening tests in subgroups of women with recurrent pregnancy loss

Objective: To evaluate the diagnostic value of screening laboratory tests in women who had recurrent pregnancy loss (RPL).

Methods: A total of 252 women with RPL managed in our tertiary referral research and education hospital were included in the study. Risk factors recorded involved age, gravidity, parity, number of prior live births, number of pregnancy losses, and thrombophlia tests. The cases were divided into three different groups and each group was analyzed separately.

Results: There was no statistically significant difference between the first and second groups in terms of clinical and laboratory parameters (p?>?0.05). In the third group, there was a statistically significant difference among cases in terms of parity, gravidity, number of pregnancy losses, serum AT III levels, APCR, and age of the women. According to the logistic regression model, odds ratios (95% CI) were 6.116 (3.797–9.852), 5.665 (2.657–12.079), 4.763 (3.099–7.321), 4.729 (3.080–7.260), 2.820 (1.836–4.333), and 1.911 (1.232–2.965), respectively.

Conclusions: We do not recommend the screening of all women with RPL, but in women with high parity and those who had prior live birth pregnancies, increased AT III, and APCR may be diagnostic markers for subsequent pregnancy loss.     

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.     

Rheumatoid arthritis and anti-thyroid antibodies

The aim of this study was to evaluate the quality of B cell responses in patients with Inflammatory Bowel Disease (IBD) and healthy individuals of different ages, vaccinated with the pandemic (p)2009 influenza vaccine. The in vivo response was measured by the hemagglutination inhibition (HAI) assay, which represents the most established correlate with vaccine protectiveness. The in vitro response was measured by activation-induced cytidine deaminase (AID) in cultures of vaccine-stimulated PBMC. Both responses are somewhat impaired in IBD patients undergoing anti-TNF-α treatment but these are much more decreased in IBD patients undergoing treatment with anti-TNF-α and immunosuppressive (IS) drugs. These latter patients had in vivo and in vitro B cell responses similar to those of elderly individuals. Moreover, as we have previously demonstrated in healthy subjects, the in vitro response to the polyclonal stimulus CpG may be used as a biomarker for subsequent vaccine response and AID activation is correlated with the serum response in IBD patients, as it is in healthy individuals. These results altogether indicate that IBD patients on anti-TNF-α and IS have significantly impaired in vivo and in vitro B cell responses, as compared to those on monotherapy. This is the first report to demonstrate that B cell defects, as measured by the autonomous AID reporter, in IBD patients contribute to reduced humoral responses to the influenza vaccine, as we have previously shown for elderly individuals.     

Is There a Role for On-Site Evaluation of Thyroid Fine Needle Aspiration to Reduce the Nondiagnostic Rate?

The use of immediate on-site evaluation of fine-needle aspiration biopsy (FNAB) specimens can determine the adequacy of specimens and provides a specific preliminary diagnosis. In this prospective study, we evaluated the impact of on-site assessment of thyroid FNAB performed under ultrasound guidance. Totally, 204 (170 female, 34 male) patients (102 on site, 102 control group) were included. The patients were randomized on site and regular cytologic examination groups. Quick May-Grünwald Giemsa stain was used for on-site examination and FNA was continued until adequate aspirate for optimal cytological examination. Two (2.0 %) of the 102 patients evaluated with on-site examination had a nondiagnostic result. However, 16 (15.7 %) of the 102 patients examined by regular cytologic examination method, had nondiagnostic result. The difference between these two groups was statistically significant (p?<?0.0001). The major cause of a nondiagnostic thyroid FNAB specimen is the failure to aspirate a sufficient number of cells necessary for diagnosis cystic lesions. Immediate on-site evaluation can significantly decrease the nondiagnostic rate of thyroid FNAB specimens.