Impact of Kaposi sarcoma-associated herpesvirus (KSHV) burden and HIV coinfection on the detection of T cell responses to KSHV ORF73 and ORF65 proteins

Cellular immune responses to Kaposi sarcoma-associated herpesvirus (KSHV), the etiological agent of KS and several other malignancies, are incompletely characterized. We assessed KSHV-specific interferon- gamma enzyme-linked immunospot responses in a cohort of 154 individuals, using overlapping peptide sets spanning the KSHV-encoded latency-associated nuclear antigen (ORF73) and the minor capsid glycoprotein (ORF65). Among KSHV-seropositive subjects, ORF73-specific responses dominated over responses to ORF65 and were preferentially detected in human immunodeficiency virus-coinfected individuals who had elevated levels of cell-associated KSHV DNA, indicating that the viral antigen burden may have been driving these responses. Responses to both ORF73 and ORF65 were also detected in several KSHV-seronegative subjects who were at increased risk for KSHV infection, which demonstrates that cellular immunity can be found in the absence of detectable humoral responses. These data have implications for the reliable identification of KSHV infection and may help guide the design of immune-based therapeutic and prophylactic interventions.     

Thrombophilic polymorphisms in Israel

Three thrombophilic polymorphisms, FV G1691A, FII G20210A and MTHFR C677T were investigated in Israeli populations by FRET, (fluorescence resonance energy transfer) real-time PCR. We observe extensive variability in the frequencies of each of the polymorphisms, as has been observed in the study of other polymorphisms in these populations. Very high allele frequencies for FV G1691A (the highest 0.087 in Turkish and Greek Jews) and FII G20210A (the highest 0.061 in Georgian Jews) in some of the Israeli populations justify a clinical investigation to assess their risk for venous thrombosis. Principal Coordinates Analysis demonstrates that the Jewish populations are interspersed among the non-Jewish populations. The resemblance of some Jewish populations to certain non-Jewish populations coincides with findings based on classical markers.     

Association between a prolonged corrected QT interval and outcomes in patients in a medical Intensive Care Unit

Introduction:

Patients admitted into a medical Intensive Care Unit (ICU) have varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool to assess the cardiac status. The aim of the study was to determine the prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular events, and duration of ICU stay.

Materials and Methods:

Prospective observational study, 6 months duration, assessing the prevalence of prolonged corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by Bazett''s formula, of >440 ms for males and >460 ms for females was considered prolonged. Details of illness, clinical and lab parameters were monitored.

Results:

The total number of patients screened was 182. There was a high prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse outcome from ICU was 3.17 (confidence interval [CI]: 1.52–6.63) (P = 0.001) and of adverse outcome for hospital stay was 2.27 (CI: 1.11–4.66) (P = 0.014). In the study, 35% of all patients received drugs with QT prolonging action. Of patients with a prolonged QTc at admission 18 (35%) received a QT prolonging drug.

Conclusions:

We found that prolonged QTc is common (30%) in our medical ICU at admission and a large proportion (35%) received drugs capable of prolonging QT interval. These patients with QTc prolongation have a higher odds ratio for adverse outcomes.     

Association with right atrial strain with right atrial pressure: an invasive validation study

Echocardiographic assessment of right atrial pressure (RAP) from inferior vena cava (RAP_IVC) dimension may underestimate catheter-derived (RAP_C). As right atrial (RA) deformation, measured by speckle tracking, is preload-dependent, we hypothesized that RA strain may improve estimation of RAP_C. Right atrial strain components [RA reservoir function (?R), peak RA contraction (?CT) and RA conduit function (?CD)] were measured in 125 of 175 patients who had echocardiography and invasive measures of RAP (median difference 1 day). To determine whether RA strain measures differentiated patients with correct vs incorrect RAP_IVC assessment, categories with RAP_IVC values?<?3, 8 and >?15 mmHg were compared with RAP_C groups?<?3, 4–7, 8–10, 11–14 and >?15 mmHg. Non-invasively determined RAP was significantly lower (p?=?0.001) than invasively determined RAP_C, with a weak correlation (r?=?0.35, p?<?0.001). RA strain components were associated with RA size, RV function and IVC size. In those with RAP_IVC?>?15 mmHg, half of patients were categorized into RAP?<?10 mmHg. There were no significant differences in RA characteristics that differentiated patients in whom echocardiographic estimation of RAP was inaccurate. Right atrial strain measures were feasible, and had associations with RA size, RV systolic function and IVC size. Right atrial strain was significantly different between those with normal vs raised pressure, but it did not identify those with incorrect echocardiographic assessment of RAP.