Persistent BK Viremia Does Not Increase Intermediate-Term Graft Loss but Is Associated with De Novo Donor-Specific Antibodies

There are limited data regarding intermediate-term outcomes in patients with persistent BK viremia. Other viral infections have been implicated in the development of allosensitization through heterologous immunity, but the relationship between BK viremia and donor-specific antibodies (DSAs) is unexplored. In 2008, we initiated routine post-transplant BK viremia and DSA screening at our center; 785 kidney or kidney–pancreas transplant recipients were included in our study. Of these recipients, 132 (17%) recipients developed BK viremia during the study period. The median duration of BK viremia was 140 days (interquartile range=40–393 days), and persistent BK viremia was defined as lasting ≥140 days. Kaplan–Meier curves were generated to assess differences in patient and allograft survival on the basis of BK viremia status; survival was modeled using Cox proportional hazard regression. After a median follow-up of 3 years, there was no significant difference in terms of patient (hazard ratio [HR], 0.83; 95% confidence interval [95% CI], 0.28 to 2.49) or allograft survival (HR, 0.80; 95% CI, 0.37 to 1.73) between patients with and without BK viremia, which was confirmed in a time-varying analysis. In our logistic regression model, persistent BK viremia was strongly associated with the development of class II (HR, 2.55; 95% CI, 1.30 to 4.98) but not class I (HR, 1.13; 95% CI, 0.46 to 2.77) DSAs. These data suggest that persistent BK viremia does not negatively affect intermediate-term patient or allograft survival but is associated with increased risk for de novo DSA, although the exact mechanism is unclear.     

Dabigatran and Warfarin for Secondary Prevention of Stroke in Atrial Fibrillation Patients: A Nationwide Cohort Study

Background

This register-based observational study compares dabigatran to warfarin for secondary stroke prevention in atrial fibrillation patients among both “new starters” on dabigatran and “switchers” to dabigatran from warfarin.

Methods

We identified, in nationwide Danish registries, 2398 patients with atrial fibrillation and a history of stroke/transient ischemic attack, making a first-time purchase of dabigatran 110 mg twice a day (bid; D110) and 150 mg bid (D150). Patients were categorized as either vitamin K antagonist (VKA) naive or experienced. Warfarin controls were identified using a complete (for VKA-naive dabigatran patients) or matched sampling approach (for VKA-experienced dabigatran patients). Subjects were followed for an average of 12.6 months for stroke and transient ischemic attacks. Confounder-adjusted Cox regression models were used to compare event rates between treatments.

Results

Among patients with a history of stroke/transient ischemic attack and prior VKA experience, switching to dabigatran was associated with an increased stroke/transient ischemic attack rate for both dabigatran doses compared with continuing on warfarin (D110 hazard ratio [HR] 1.99; 95% confidence interval [CI], 1.42-2.78; D150 HR 2.34; 95% CI, 1.60-3.41). Among prior stroke/transient ischemic attack patients who were new starters on dabigatran or warfarin, the rate of stroke/transient ischemic attack for both doses of dabigatran was similar to or lower than warfarin (D110 HR 0.64; 95% CI, 0.50-0.80; D150 HR 0.92l; 95% CI, 0.73-1.15).

Conclusions

In this register-based study, VKA-experienced patients with a history of stroke or transient ischemic attack who switched to dabigatran therapy had an increased rate of stroke compared with patients persisting with warfarin therapy.     

Safety and immunogenicity of two doses of quadrivalent meningococcal conjugate vaccine or one dose of meningococcal group C conjugate vaccine,both administered concomitantly with routine immunization to 12- to 18-month-old children

OBJECTIVES:

To describe the immunogenicity and safety of a two-dose series of a quadrivalent meningococcal (serogroups A, C, Y and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) administered to toddlers.

METHODS:

Children were randomly assigned (1:1) at study entry to receive MenACYW-D at 12 and 18 months of age (group 1; n=61) or meningococcal serogroup C conjugate vaccine (MCC) at 12 months of age (group 2; n=62). All received routine childhood immunizations. A, C, Y and W antibody titres were measured in group 1 before and one month after the 18-month MenACYW-D vaccination and were measured in group 2 at one and seven months post-MCC vaccination. Antibodies elicited by diphtheria and tetanus toxoids, and acellular pertussis vaccine adsorbed combined with inactivated poliomyelitis vaccine and Haemophilus influenzae b conjugate (DTaP-IPV-Hib) vaccine coadministered at the 18-month vaccination were measured one month later. Safety data were collected.

RESULTS:

At 19 months of age, ≥96% in group 1 achieved protective titres for the four meningococcal serogroups after dose 2; 67% in group 2 exhibited protective titres against serogroup C 28 days after MCC vaccination at 12 months of age, declining to 27% seven months later. DTaP-IPV-Hib elicited high antibody concentrations/titres in groups 1 and 2, consistent with historical values. The safety profiles after each dose generated no unexpected safety signals; no serious adverse events were related to vaccination.

DISCUSSION:

A two-dose series of MenACYW-D given concomitantly with a DTaP-IPV-Hib booster dose at 18 months of age demonstrated a good immunogenicity and safety profile. A two-dose series of MenACYW-D can be used as an alternative to one dose of MCC and provides protection against additional serogroups (NCT ID: {"type":"clinical-trial","attrs":{"text":"NCT01359449","term_id":"NCT01359449"}}NCT01359449).     

Atrial fibrillation

The management of atrial fibrillation has evolved greatly in the past few years, and many areas have had substantial advances or developments. Recognition of the limitations of aspirin and the availability of new oral anticoagulant drugs that overcome the inherent drawbacks associated with warfarin will enable widespread application of effective thromboprophylaxis with oral anticoagulants. The emphasis on stroke risk stratification has shifted towards identification of so-called truly low-risk patients with atrial fibrillation who do not need antithrombotic therapy, whereas oral anticoagulation therapy should be considered in patients with one or more risk factors for stroke. New antiarrhythmic drugs, such as dronedarone and vernakalant, have provided some additional opportunities for rhythm control in atrial fibrillation. However, the management of the disorder is increasingly driven by symptoms. The availability of non-pharmacological approaches, such as ablation, has allowed additional options for the management of atrial fibrillation in patients who are unsuitable for or intolerant of drug approaches.     

Brachial blood pressure-independent relations between radial late systolic shoulder-derived aortic pressures and target organ changes

Central aortic blood pressure (BP; BPc) predicts outcomes beyond brachial BP. In this regard, the application of a generalized transfer function (GTF) to radial pulse waves for the derivation of BPc is an easy and reproducible measurement technique. However, the use of the GTF may not be appropriate in all circumstances. Although the peak of the second shoulder of the radial waveform (P2) is closely associated with BPc, and, hence, BPc may be assessed without the need for a GTF, whether P2-derived BPc is associated with adverse cardiovascular changes independent of brachial BP is uncertain. Thus, P2- and GTF-derived aortic BPs were assessed using applanation tonometry and SphygmoCor software. Left ventricular mass was indexed for height(1.7) (n=678) and carotid intima-media thickness (IMT; n=462) was determined using echocardiography and vascular ultrasound. With adjustments for nurse-derived brachial pulse pressure (PP), P2-derived central PP was independently associated with left ventricular mass indexed for height(1.7) (partial r=0.18; P<0.0001) and IMT (partial r=0.40; P<0.0001). These relations were similar to nurse-derived brachial PP-independent relations between GTF-derived central PP and target organ changes (left ventricular mass indexed for height(1.7): partial r=0.17, P<0.0001; IMT: partial r=0.37, P<0.0001). In contrast, with adjustments for central PP, nurse-derived brachial PP-target organ relations were eliminated (partial r=-0.21 to 0.05). Twenty-four-hour, day, and night PP-target organ relations did not survive adjustments for nurse-derived brachial BP. In conclusion, central PP derived from P2, which does not require a GTF, is associated with cardiovascular target organ changes independent of brachial BP. Thus, when assessing adverse cardiovascular effects of aortic BP independent of brachial BP, P2-derived measures may complement GTF-derived measures of aortic BP.     

Prediction of Oncotype DX and TAILORx risk categories using histopathological and immunohistochemical markers by classification and regression tree (CART) analysis

Oncotype DX is an RT-PCR assay used to predict which patients with ER-positive node-negative (NN) disease will benefit from chemotherapy. Each patient is stratified into a risk category based on a recurrence score (RS) and the TAILORx trial is determining the benefit of chemotherapy for patients with mid-range RSs.We tested if Oncotype DX and TAILORx risk categories could be predicted by standard pathological features and protein markers corresponding to 10 genes in the assay (ER, PR, Ki67, HER2, BCL2, CD68, Aurora A kinase, survivin, cyclin B1 and BAG1) on 52 patients who enrolled on TAILORx. Immunohistochemistry for the protein markers was performed on whole tissue sections.Classification and regression tree (CART) analysis correctly classified 69% of cases into Oncotype DX risk categories based on the expression of PR, survivin and nuclear pleomorphism. All tumours with PR staining (Allred score ≥2) and marked nuclear pleomorphism were in the high-risk category. No case with PR <2, low survivin (≤15.5%) and nuclear pleomorphism <3 was high-risk. Similarly, 77% of cases were correctly classified into TAILORx categories based on nuclear pleomorphism, survivin, BAG1 and cyclin B1. Ki67 was the only variable that predicted the absolute RS with a cut-off for positivity of 15% (p = 0.003).In conclusion, CART revealed key predictors including proliferation markers, PR and nuclear pleomorphism that correctly classified over two thirds of ER-positive NN cancers into Oncotype DX and TAILORx risk categories. These variables could be used as an alternative to the RT-PCR assay to reduce the number of patients requiring Oncotype DX testing.     

Glioblastoma Metastasis to Parotid Gland and Neck Lymph Nodes: Fine-Needle Aspiration Cytology with Histopathologic Correlation

Glioblastoma (GBM) is one of the most highly aggressive neoplasms of the central nervous system. Extra-cranial metastases in GBM are rare. Here we present the case of a 26-year-old man with extra-cranial metastasis of a frontal lobe GBM to the parotid gland, cervical lymph nodes, and bones, with initial diagnosis made by fine needle aspiration cytology (FNAC) of the parotid gland. FNAC is a reliable technique in the study of primary and secondary parotid gland neoplasms, allowing a presumptive diagnosis in difficult cases. We correlate the cytologic, histopathologic, and immunohistochemical findings in this case and discuss previous literature reports.