Clinical features,exercise hemodynamics,and determinants of left ventricular elevated filling pressure in heart‐transplanted patients

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart‐transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi‐supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV‐FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty‐one patients (54%) had normal LV‐FP and 26 patients (46%) had elevated LV‐FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left‐ and right‐sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV‐FP than in patients with normal LV‐FP. No between‐group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV‐FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV‐FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).     

Cognitive impairment and associations with structural brain networks,endocrine status,and risk genotypes in newly orchiectomized testicular cancer patients

Brain Imaging and Behavior - A higher incidence of cognitive impairment (CI) has previously been reported among orchiectomized testicular cancer patients (TCPs), but little is known about the...     

Cancer risk in fathers and brothers of testicular cancer patients in Denmark. A population-based study

There are several reports of familial testicular cancer in the literature but few systematic attempts have been made to estimate the risk of testicular cancer in first-degree relatives of patients with this neoplasm, and the risk remains to be fully assessed in population-based studies. By means of data from the Danish Cancer Registry, we identified all testicular cancer patients (index cases) born and diagnosed during 1950–1993 in Denmark. Their fathers were identified from national registries, as were the brothers of a subcohort of these patients. Familial cancer occurrence was determined through linkage with the cancer registry and compared with the cancer incidence in the general male population in Denmark. The ratio of observed to expected cancers generated the measure used for the relative risk. Fathers of 2,113 index cases with testicular cancer experienced an almost 2-fold risk of developing testicular cancer themselves (RR = 1.96; 95% CI: 1.01–3.43). Overall, the fathers had a decreased relative cancer risk (RR = 0.84; 95% CI: 0.74–0.95) with a significantly decreased risk of cancers of the lung and digestive organs. Brothers of a subcohort of 702 index cases showed a markedly increased risk of testicular cancer (RR = 12.3; 95% CI: 3.37ndash;31.5). In conclusion, we documented a significantly increased familial risk of testicular cancer which was relatively more pronounced between brothers than between fathers and sons. These findings support the possible involvement of a genetic component in the aetiology of testicular cancer, but also leave room for a hypothesized influence of in-utero exposures, such as specific maternal hormone levels, that might be shared by brothers. © 1996 Wiley-Liss, Inc.     

Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?

Nicotinamide adenine dinucleotide (NAD⁺) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD⁺-dependent enzymes. In the early 2000s, reports that NAD⁺ declines with aging introduced the notion that NAD⁺ metabolism is globally and progressively impaired with age. Since then, NAD⁺ became an attractive target for potential pharmacological therapies aiming to increase NAD⁺ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD⁺ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human), to determine whether the notion that overall NAD⁺ levels decrease with aging stands true. We find that, despite systematic claims of overall changes in NAD⁺ levels with aging, the evidence to support such claims is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD⁺ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies to assess how NAD⁺ levels develop with aging in various tissues. This will strengthen our conclusions on NAD metabolism during aging and should provide a foundation for better pharmacological targeting of relevant tissues.     

Epstein-Barr virus immune response in high-risk nasopharyngeal carcinoma families in Greenland

Undifferentiated nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection. Presence of EBV IgA antibodies is rare among healthy individuals and is used as a marker of nasopharyngeal carcinoma in high-incidence populations. Reasons for EBV IgA seropositivity are unknown, but high EBV IgA levels have been found among unaffected close family members and spouses to nasopharyngeal carcinoma patients in Chinese populations. In Greenland, a nasopharyngeal carcinoma-high-incidence area, we compared EBV serology and viral load in high-risk nasopharyngeal carcinoma family members (N = 20) and controls without nasopharyngeal carcinoma-affected relatives (N = 90). There was no significant difference in EBV viral loads between relatives and controls, and EBV was detected in plasma in 5.0% of relatives and 11.4% of controls. There was no significant difference in EBV serology, but the seroprevalence of EBV viral capsid antigen (VCA) IgA was high in both relatives (25.0%) and controls (20.5%). Compared with anti-VCA IgA-negative, anti-VCA IgA-positive individuals had significantly higher EBV viral loads in peripheral blood mononuclear cells (PBMCs) (P < 0.01). The very high prevalence of anti-VCA IgA indicates that this antibody is unsuitable for nasopharyngeal carcinoma screening among Inuits.