HFE Gene Mutations, Serum Ferritin Level, Transferrin Saturation, and Their Clinical Correlates in a Korean Population

The aim of this study was to investigate HFE gene mutations, blood iron indices, and their clinical correlates in a Korean population. In 484 prospectively enrolled health-check examinees, HFE gene mutations and iron indices with clinical and laboratory variables were analyzed. Although neither the C282Y nor S65C gene mutation were found, the H63D heterozygote was detected in 41 subjects (8.5%). The mean serum ferritin and transferrin saturation (TS) were 136.2 ± 129.8 μg/dl and 39.2 ± 15.7%, respectively. The H63D genotype was not significantly associated with iron indices. High serum ferritin was associated with old age, the male gender, high body mass index (BMI), and the presence of nonalcoholic fatty liver disease (NAFLD). High TS was associated with the male gender and alcohol drinking. HFE gene mutation is rare; however, TS seems to be higher in Koreans compared to Caucasians or other ethnic groups. Serum ferritin reflects iron store as well as the presence of NAFLD.     

Extrinsic factors modifying expressivity of the HFE variant C282Y, H63D, S65C phenotypes in 1,294 Danish men

This study analysed the influence of extrinsic factors on the phenotypic expression of HFE gene variants in ethnic Danish men. A cohort of 6,020 men aged 30-53 years was screened for HFE C282Y, H63D and S65C variants. Serum iron, serum transferrin, transferrin saturation, and serum ferritin were analysed in 1,452 men and 1,294 men completed a questionnaire on factors, which could influence iron balance. The C282Y allele was present in 5.6%, H63D in 12.8% and S65C in 1.8% of the men. In the entire series, 3% had elevated iron status markers (transferrin saturation ≥50%, ferritin ≥300 μg/L). Self-reported liver disease had an elevating effect and peptic ulcer a lowering effect on iron status markers. Age increased the fraction of men with elevated ferritin from 8.3% at 32-38 years to 16.2% at 46-53 years of age (p = 0.002). Blood donation had a lowering effect on iron status markers (p = 0.0001). Alcohol consumption elevated serum iron and serum ferritin (p = 0.001). Meat consumption had an elevating effect (p = 0.02) and milk consumption a lowering effect (p = 0.03) on serum ferritin. There was no influence of vitamin-mineral tablets on iron status markers. In adjusted logistic regression analysis, the HFE genotype had the highest impact on iron status markers; high alcohol consumption was significantly associated with elevated transferrin saturation. High age and high alcohol consumption were significantly associated with elevated ferritin and high egg consumption and blood donation was significantly associated with normal ferritin levels. In conclusion, the expressivity of HFE variant phenotypes in Danish men was enhanced by alcohol and meat consumption and decreased by milk and egg consumption and blood donation.     

Genetic screening for HFE hemochromatosis in 6,020 Danish men: penetrance of C282Y, H63D, and S65C variants

The aim of this epidemiologic population survey was to assess the penetrance of the most frequent hemochromatosis (HFE) gene variants in ethnic Danish men. A cohort of 6,020 men aged 30–53 years was screened for HFE C282Y, H63D, and S65C variants by restriction fragment length polymorphism analysis. Subsequently, iron status markers (serum transferrin saturation, serum ferritin) were analyzed in 1,452 men. The C282Y allele was present in 5.6%, H63D in 12.8%, and S65C in 1.8% of the men. We found 23 out of 6,020 (0.38%) C282Y homozygotes, of whom two had been treated with phlebotomy. Among untreated C282Y homozygotes (n = 21) with available iron status markers (transferrin saturation n = 18, ferritin n = 16), 89% had elevated transferrin saturation ≥50%, 94% had elevated ferritin ≥300 μg/L, and 88% had elevation of both iron status markers; seven out of 16 (44%) had ferritin values >800 μg/L. One C282Y homozygote had normal iron status markers possibly due to nonexpressivity. Among C282Y/H63D compound heterozygotes (n = 66), 23% had elevated transferrin saturation, 27% elevated ferritin, and 9% elevation of both iron status markers. Among H63D/H63D homozygotes (n = 74), 15% had elevated transferrin saturation, 19% elevated ferritin, and 5.4% elevation of both iron status markers. Among C282Y/wild type (wt) heterozygotes (n = 255), 9% had elevated transferrin saturation, 9% elevated ferritin, and 1.2% elevation of both iron status markers. Among H63D/wt heterozygotes (n = 600), 8% had elevated transferrin saturation, 12% elevated ferritin, and 2% elevation of both iron status markers. None of the men with the S65C variant displayed elevation of both iron status markers. In conclusion, this study demonstrates a high penetrance of the C282Y variant in Danish men followed by the H63D variant while the S65D variant had no significant impact on iron status markers.     

Human Cytomegalovirus DNA Is Not Detectable with Nested Double Polymerase Chain Reaction in Healthy Blood Donors

The PCR method was introduced to detect cytomegalovirus (CMV) DNA from 189 peripheral blood samples of volunteer donors. We adopted the nested double PCR method with primers specific for immediate early gene 1 followed by electrophoresis and ethidium bromide staining. This nested double PCR method was sensitive enough to detect approximately a single copy of CMV DNA. However, we failed to obtain positive amplification of CMV DNA from any of these donor samples. In contrast, CMV DNA could be detected in all 3 tested immunocompromised patients who had undergone bone marrow transplantation. These results support our previous report that the frequency of CMV DNA is of an order lower than 1 copy/10⁵ leucocytes in the peripheral blood of healthy seropositive individuals.     

Presence of Anomalous Coronary Seen on Angiogram Is Not Associated with Increased Risk of Significant Coronary Artery Disease

It is unclear if anomalous coronary arteries are at higher risk for atherosclerosis. The link between anomalous coronary artery and early coronary artery disease has been suggested. The aim of this study is to determine whether the coronary artery anomaly predisposes to development of significant coronary disease. Using retrospective chart review, patients with documented anomalous coronary arteries recognized during coronary angiography between years 2000 to 2007 were analyzed. Prevalence of significant atherosclerotic coronary artery disease (defined as more than 50% luminal narrowing) was compared between normal and anomalous coronaries. A total of 147 patients with anomalous coronary arteries were found. Right coronary artery was the most common anomalous artery 128 of 148 (86.5%) in our dataset. There was no difference in the occurrence of atherosclerosis between anomalous and nonanomalous coronaries. Significant atherosclerosis was present in 59 of the 148 anomalous coronary arteries (37.8%), and 112 of the 293 nonanomalous coronary arteries (38.2%, p = 0.9). On the basis of our study, there is no evidence that anomalous coronary arteries predispose to significant coronary artery disease in comparison to normal coronary arteries.     

Exaggerated Blood Pressure Response to Exercise Is Not Associated With Masked Hypertension in Patients With High Normal Blood Pressure Levels

The association between exaggerated blood pressure (BP) response to exercise (ExBPR) and “masked hypertension” is unclear. Medical records of patients with high‐normal BP who were evaluated in the Chaim Sheba Screening Institute Ramat Gan, Israel, during the years 2002–2007 and referred for 24‐hour ambulatory BP monitoring (ABPM) and exercise test were reviewed. Data on exercise tests performed in the preceding 5 years were retrieved. Reproducible ExBPR was defined when it was recorded at least twice. BP levels on 24‐hour ABPM were compared between patients with a normal BP response and those with an ExBPR (systolic BP ≥200 mm Hg). Sixty‐nine normotensive patients with high normal BP levels were identified. ExBPR was recorded in 43 patients and was reproducible in 28. BP levels on 24‐hour ABPM were similar in patients with and without ExBPR. In patients with high‐normal BP levels, ExBPR is not associated with masked hypertension.     

Trauma of Hospitalization Is Common in Medical Inpatients But Is Not Associated with Post-Discharge Outcomes

BackgroundTrauma of hospitalization is characterized by patient-reported disturbances in sleep, mobility, nutrition, and/or mood and one study suggested it was associated with more 30-day readmissions.ObjectiveTo define the trauma of hospitalization in medical inpatients and determine whether higher rates of disturbance correlate with adverse post-discharge outcomes.DesignA prospective cohort study was conducted between June 2018 and August 2019 with patients reporting disturbances in sleep, mobility, nutrition, and/or mood. High trauma of hospitalization was defined as disturbance in 3 or 4 domains.ParticipantsGeneral medicine inpatients at an academic hospital in Edmonton, Canada.Main Measures7-day, 30-day, and 90-day rates of death, unplanned hospital readmission, or emergency department (ED) visit.Key ResultsOf 299 patients (mean age 65.9 years, 47.8% female, mean Charlson score 3.6, and mean length of stay 8.2 days), 260 (87.0%) reported disturbance in at least one domain (most commonly nutrition or mobility) during their hospitalization, 179 (59.9%) reported disturbances in multiple domains, and 87 (29.1%) met the criteria for high trauma of hospitalization. Patients who reported a high trauma of hospitalization did not differ from those reporting less hospitalization disturbances in terms of demographics, burden of comorbidities, or length of stay, but did report higher rates of pre-hospital disturbances in sleep (32.3% vs. 14.4%, p = 0.03), nutrition (77.4% vs. 54.4%, p = 0.02), and mood (41.9% vs. 13.3%, p = 0.0007). High trauma of hospitalization was not significantly associated with death, readmission, or ED visit at 7 days (12.6% vs. 11.3%, aOR 1.13 [95% CI 0.52–2.46]), 30 days (31.0% vs. 32.1%, aOR 1.03 [95% CI 0.59–1.79]), or 90 days (52.9% vs. 50.9%, aOR 1.16 [95% CI 0.69–1.94]) after discharge.ConclusionsIn-hospital disturbances in sleep, mobility, nutrition, and mood are common in medical inpatients but were not associated with post-discharge outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06427-4.KEY WORDS: hospitalization, patient experiences, post-discharge outcomes

While it has long been known that hospitalization exposes patients to risk of iatrogenic illnesses, nosocomial infections, and deconditioning, there is emerging evidence that patient subjective experiences during their hospitalization may also influence their post-discharge outcomes.^1–3 Detsky and Krumholz described the stressful and depersonalizing effects of the hospital environment as the “trauma of hospitalization” and hypothesized that the cumulative effect of hospital-related disturbances in sleep, mobility, nutrition, and mood (even when not recognized by their care team) may cause physiologic disruptions that worsen patient outcomes, potentially increasing their probability of unplanned readmissions or emergency department (ED) visits.^4–6A recently published prospective cohort study used a 10-item patient-reported “in-hospital disturbance survey” (see Box 1) to examine the trauma of hospitalization in medical inpatients and post-discharge outcomes.⁷ The survey evaluated the 4 domains of sleep, nutrition, mobility, and mood: the 29.5% of patients who reported disturbance in 3 or 4 domains in hospital were considered to have high trauma of hospitalization and they exhibited a substantial and statistically significant increase in risk of 30-day readmission or ED visit (37.7% vs. 21.9% in those patients who reported lower trauma of hospitalization, adjusted Odds Ratio 2.52, 95% CI 1.24 to 5.17).⁷ While this result highlighted a potentially important novel opportunity for future interventions to improve both patient experience and clinical outcomes, their findings must be validated in other settings. Thus, we designed this study to examine the trauma of hospitalization in medical inpatients and to explore whether high scores on the in-hospital disturbance survey are associated with higher rates of readmissions or repeat ED visits or death at 7 days (our primary outcome), 30 days, and 3 months in a different geographic setting.Box 1 Disturbance survey (adapted from Rawal et al.⁷)     

Inter‐Arm Blood Pressure Difference in Hospitalized Elderly Patients Is Not Associated With Excess Mortality

Inter‐arm blood pressure difference (IAD) has been found to be associated with cardiovascular mortality. Its clinical significance and association with mortality in the elderly is not well defined. This study evaluated the association of IAD with mortality in a cohort of hospitalized elderly individuals. Blood pressure (BP) was measured simultaneously in both arms in elderly individuals (older than 65 years) hospitalized in a geriatric ward from October 2012 to July 2014. During the study period, 445 patients, mostly women (54.8%) with a mean age of 85±5 years, were recruited. Systolic and diastolic IAD were >10 mm Hg in 102 (22.9%) and 76 (17.1%) patients, respectively. Patients were followed for an average of 342±201 days. During follow‐up, 102 patients (22.9%) died. Mortality was not associated with systolic or diastolic IAD. It is therefore questionable whether BP should be routinely measured in both arms in the elderly.     

HCV-Positive Allograft Use in Heart Transplantation Is Associated With Increased Access to Overdose Donors and Reduced Waitlist Mortality Without Compromising Outcomes

BackgroundBecause of ongoing shortages of donors for heart transplantation, the use of donor candidates whose availabilities are the result of drug overdoses (ODs) has become increasingly prevalent, even though these donors carry a high preponderance of the now curable hepatitis C virus (HCV). This study investigated temporal trends and regional variabilities in HVC-positive (HCV+) allograft use in heart transplantation and assessed the relationship between the use of HCV+ graft donors and the use of OD donors as well as assessing waitlist and post-transplant outcomes.Methods and ResultsA retrospective review of the United Network for Organ Sharing database assessed adults listed for heart transplantation. Patients were stratified both temporally into pre-HCV and HCV eras related to HCV+ graft use trends and regionally by degree of HCV+ allograft use. Regions of high HCV+ donor use were associated with an increase in OD donor access by 7.8% across eras compared to 0.4% in low HCV+ donor-use regions. One-year waitlist mortality decreased from 4.7% to 2.5% across eras in high HCV+ donor-use regions (P= 0.001) and remained roughly the same as before in low HCV+ donor-use regions (3.0% vs 2.4%; P= 0.244.). Post-transplant survival at 1 year remained similar across eras.ConclusionsHCV+ donor allograft use can help to optimize donor use, decreasing waitlist mortality without compromising early survival. Ongoing assessment is essential to ensure long-term safety and efficacy of using HCV+ donors.