Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation

Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.ObjectiveThe aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation.Methods46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio – USA) and CMV-(Roche – USA). A frozen whole blood sample collected weekly (from the 1^st to the 6^th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen – Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest – Germany) from the 4^th to the 12^th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched.ResultsPre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p = 0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p = 0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p = 0.441), neither concerning DCMV (p = 0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or ? (p = 0.206 and p = 0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p = 0.009) and fungal (p = 0.001) infections, and higher number (p = 0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p = 0.033 and p = 0.001).ConclusionLatent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.     

Therapeutic strategies in male breast cancer: Clinical implications of chromosome 17 gene alterations and molecular subtypes

Male breast cancer (MBC) is a rare disease. To date, therapy is mainly based on studies and clinical experiences with breast cancer in women. Only little is known about molecular typing of MBC, particularly with regard to potential biological predictors for adjuvant therapy. In female breast cancer tumors with chromosome 17 centromere (CEP17) duplication, HER2 and/or Topoisomerase II alpha (Topo II-α) gene alterations have been suggested to be associated with poor prognosis and increased sensitivity to anthracycline-containing regimens.In a well characterized cohort of 96 primary invasive MBC, we studied CEP17, HER2 and Topo II-α alterations by fluorescence in-situ hybridization (FISH), and expression of hormone receptors (HR), HER2 and Ki67 by immunohistochemistry to define molecular subtypes. Tumor characteristics and follow-up data were available and correlated with molecular findings.HER2 amplification and Topo II-α amplification/deletion were exceptionally rare in MBC (6.3% and 3.1%, respectively). CEP17 polysomy were found in 9.4% of tumors. HER2, Topo II-α and CEP17 gene alterations were not correlated to patients outcome. 96.9% of our cases were HR positive. Triple negative tumors were found in only 3.1% of the cases. In nodal negative tumors luminal A subtypes were significantly associated with better overall survival.Our results provide evidence for a predominant male breast cancer phenotype, characterized by HR expression and a lack of HER2/Topo II-α alterations and CEP17 duplicates. Therefore, the impact of anthracycline sensitivity linked to HER2/Topo II-α alterations as found in female breast cancer has low clinical significance for this specific male breast cancer phenotype.     

The value of perfusion computed tomography in predicting clinically relevant vasospasm in patients with aneurysmal subarachnoid hemorrhage

Delayed cerebral ischemia remains a severe potential complication of aneurysmal subarachnoid hemorrhage (SAH) possibly leading to death and disability. We evaluated a semiquantitative and visual analysis of perfusion computed tomography (PCT) as a predictor of clinically relevant vasospasm (CRV) in patients with aneurysmal SAH. Thirty-eight patients with aneurysmal SAH were analyzed yielding 145 PCT scans. PCT, clinical examination, and transcranial Doppler ultrasound (TCD) were performed on days 3, 7, 10, and 14 after hemorrhage. Cerebral blood flow, cerebral blood volume, and time to peak (TTP) were analyzed semiquantitatively using six regions of interest, and visually for signs of cerebral hypoperfusion. CRV was defined as secondary cerebral infarction (CI) seen on cranial computed tomography scans and/or delayed neurological deterioration (DND). CI occurred in 13 (34.2 %) and DND in 11 patients (28.9 %). With TCD as pretest, TTP had a sensitivity of 90 % and a specificity of 72 % (cutoff value, 0.963) as predictor for CI. TTP’s sensitivity as predictor for DND was 90 % with a specificity of 61.1 % (cutoff value, 0.983). Visual analysis of TTP showed a negative predictive value of 100 % with a positive predictive value of 52 %. TTP is a sensitive and specific perfusion parameter in predicting CI in patients with SAH. Its use in the clinical setting may optimize the early treatment of patients at risk for vasospasm before the onset of clinical deterioration, especially when applying TCD as pretest. Further investigation in a larger patient population is required.     

Percutaneous Transluminal Coronary Angioplasty versus Thrombolysis in Acute Myocardial Infarction: A Prospective,Matched, Controlled Study

The aim of this study was to evaluate the outcome of primary percutaneous transluminal coronary angiography (PTCA) in the treatment of acute myocardial infarction (AMI) The study included patients with electrocardiographic signs of transmural AMI, symptom duration of less than 12 h, and with no contraindications to thrombolytic therapy. Patients who had undergone primary PTCA were matched consecutively, for age, gender, infarct localization and duration of symptoms, to patients who had received thrombolytic therapy (82 patients to each group). Patients who were admitted to hospital during daytime had a primary PTCA, whereas those admitted outside daytime were given thrombolytic therapy. In the primary PTCA group, 9 patients had a combined endpoint compared with 22 patients in the thrombolysis group (p < 0.02 ). In-hospital mortality was 3.7% in the PTCA group and 4.9% in the thrombolysis group (ns). At six months, a combined endpoint occurred in 23 patients in the primary PTCA group and in 50 patients in the thrombolysis group (p < 0.00005). Six months' mortality was 4.9% in the PTCA group and 7.3% in the thrombolysis group (ns). Among patients in the PTCA group, left ventricular ejection fraction was significantly higher, stay in hospital was shorter and there were significantly fewer incidences of heart failure and severe arrhythmias than among patients in the thrombolysis group. The results of primary PTCA implemented in our departments are comparable with those reported in randomized trials from experienced centres. Our study indicates that patients treated with primary PTCA have fewer complications, a better left ventricular systolic function and a shorter hospital stay compared with patients treated with thrombolysis.