Previous epidemiologic data demonstrate that cardiovascular (CV) morbidity and mortality may occur decades after ionizing radiation exposure. With increased use of proton and carbon ion radiotherapy and concerns about space radiation exposures to astronauts on future long-duration exploration-type missions, the long-term effects and risks of low-dose charged particle irradiation on the CV system must be better appreciated. Here we report on the long-term effects of whole-body proton (1H; 0.5 Gy, 1 GeV) and iron ion (56Fe; 0.15 Gy, 1GeV/nucleon) irradiation with and without an acute myocardial ischemia (AMI) event in mice. We show that cardiac function of proton-irradiated mice initially improves at 1 month but declines by 10 months post-irradiation. In AMI-induced mice, prior proton irradiation improved cardiac function restoration and enhanced cardiac remodeling. This was associated with increased pro-survival gene expression in cardiac tissues. In contrast, cardiac function was significantly declined in 56Fe ion-irradiated mice at 1 and 3 months but recovered at 10 months. In addition, 56Fe ion-irradiation led to poorer cardiac function and more adverse remodeling in AMI-induced mice, and was associated with decreased angiogenesis and pro-survival factors in cardiac tissues at any time point examined up to 10 months. This is the first study reporting CV effects following low dose proton and iron ion irradiation during normal aging and post-AMI. Understanding the biological effects of charged particle radiation qualities on the CV system is necessary both for the mitigation of space exploration CV risks and for understanding of long-term CV effects following charged particle radiotherapy.

Deep-space travel presents risks of exposure to ionizing radiation composed of a spectrum of low-fluence protons (H) and high-charge and energy (HZE) iron nuclei (e.g., Fe). When exposed to galactic cosmic rays, each cell in the body may be traversed byH every 3-4 days and HZE nuclei every 3-4 months. The effects of low-dose sequential fractionated H or HZE on the heart are unknown. In this animal model of simulated ionizing radiation, middle-aged (8-9 months old) male C57BL/6NT mice were exposed to radiation as follows: group 1, nonirradiated controls; group 2, three fractionated doses of 17 cGyH every other day (H × 3); group 3, three fractionated doses of 17 cGy H every other day followed by a single low dose of 15 cGyFe two days after the final H dose (H × 3 + Fe); and group 4, a single low dose of 15 cGyFe followed (after 2 days) by three fractionated doses of 17 cGy H every other day (Fe + H × 3). A subgroup of mice from each group underwent myocardial infarction (MI) surgery at 28 days postirradiation. Cardiac structure and function were assessed in all animals at days 7, 14 and 28 after MI surgery was performed. Compared to the control animals, the treatments that groups 2 and 3 received did not induce negative effects on cardiac function or structure. However, compared to all other groups, the animals in group 4, showed depressed left ventricular (LV) functions at 1 month with concomitant enhancement in cardiac fibrosis and induction of cardiac hypertrophy signaling at 3 months. In the irradiated and MI surgery groups compared to the control group, the treatments received by groups 2 and 4 did not induce negative effects at 1 month postirradiation and MI surgery. However, in group 3 after MI surgery, there was a 24% increase in mortality, significant decreases in LV function and a 35% increase in post-infarction size. These changes were associated with significant decreases in the angiogenic and cell survival signaling pathways. These data suggest that fractionated doses of radiation induces cellular and molecular changes that result in depressed heart functions both under basal conditions and particularly after myocardial infarction.

Our understanding of the left atrium is growing, although there are many aspects that are still poorly understood. The left atrium size as an imaging biomarker has been consistently shown to be a powerful predictor of outcomes and of different cardiovascular disorders, such as, but not limited to, atrial fibrillation, congestive heart failure, mitral regurgitation and stroke. Left atrial function has been conventionally divided into three integrated phases: reservoir, conduit and booster-pump. The highly dynamic left atrium and its response to the stretch and secretion of atrial neuropeptides leaves the left atrium far from being a simple transport chamber. The aim of this review is to provide an understanding of the left atrial physiology and its relation to disorders within the heart.

Background One third of patients with eosinophilic esophagitis (EoE) do not achieve histological remission with standard medical or dietary treatment. The outcome of these patients undergoing various rescue treatments is not known and whether these patients constitute a distinct subset remains unclear. Objective To analyze EoE treatment outcomes in a predominantly pediatric population, including after initial treatment failure (rescue treatment) for differences in outcomes and clinical presentation. Methods We identified 100 serial cases of confirmed EoE from our REDCap® database established at Massachusetts General Hospital starting from January 2007. Demographic data, clinical symptoms, treatment regimens, endoscopic findings, skin testing results, food triggers and clinical outcome of various rescue treatment strategies were presented. We defined clinical response as histological remission with peak eosinophil count of at least 6 biopsies less than 10 per high power field. RESULTS Ninety-seven EoE patients underwent initial treatments. Eighty-one elected dietary treatment (7 elemental diet, 54 multiple food elimination diet, and 20 milk-free diet and 16 elected medical treatment (15 swallowed fluticasone and 1 budesonide). Initial response rate to dietary and medical treatment was 67% (54/81) and 56% (9/16) respectively. Of the 34 who failed initial treatment, 24 of them elected various second treatment regimens (3 medical therapy, 2 milk-free diet, 14 multiple food elimination diet and 5 elemental diet) and 54% (13/24) achieved histological remission. Eight of the remaining 11 who failed second treatment underwent additional treatments and 2 ultimately achieved histological remission. The overall response rate by intention-to-treat analysis increased from 65% (63/97) with initial treatment to 78% (76/97) with rescue treatment, and further to 80% (78/97) with multiple rescue treatments. On a per-protocol basis, the overall response rate was 93% (78/84); however, patients who failed the first two rounds of therapy had only a 20% response rate. Patients who responded to initial treatment were found to have more symptoms and endoscopic abnormalities. In contrast, comparison of patients who failed both initial and rescue therapy to those who responded to rescue therapy did not identify any differentiating clinical features. CONCLUSION More than half of the patients who failed initial EoE treatment could still achieve histological remission with rescue treatments. Elemental diet is the most effective initial and rescue therapy in achieving histological remission. No clinical features could not identified to reliably predict response to rescue treatment.

No abstract

Our data suggest that treatment of unstable distal radius fractures with a volar bearing variable angle plate fixation is safe and effective. In our series, there was a significant reduction in the rate of hardware-related complications with the polyaxial locking plate as compared with a fixed angle plate.Therapeutic, Level III, retrospective comparative study.

Purpose Flexor tendon lacerations are a common and debilitating injury for thousands of Americans annually. Despite this, no study has attempted to estimate the economic impact of these injuries. The objective of this study was to estimate the economic impact of flexor tendon lacerations in America. Methods The cost of flexor tendon lacerations to society was estimated using a validated prevalence-based cost of illness model. The primary cohort was defined as all patients in the United States presenting with complete flexor tendon lacerations who underwent surgical repair. The secondary cohort was defined by all patients who required reoperation within 1 year of their initial operation. For these groups, both direct and indirect costs (lost income, missed workdays, and disability payments) were measured. Results Flexor tendon lacerations incur an estimated cost of between US $240.8 and US $409.1 million annually to the American medical system. The total direct cost per injury is estimated to be US $13,725, whereas estimates to the indirect costs range from US $60,786 to US $112,888. Conclusions Flexor tendon lacerations represent an important economic burden to our health care system, even when compared with other common hand conditions. Specifically, indirect costs, such as missed workdays, are the major contributor toward the total cost these injuries incur on society, accounting for upward of 89% of the total cost. This suggests that we should focus our efforts to improve treatments and rehabilitation protocols which decrease these indirect costs.

A rare side effect of fluoroquinolone (FQ) antibiotics is QT prolongation, which may result in serious arrhythmias. Most published comparative trials describe the relative risks among the drug class but do not focus on the incidence of serious arrhythmias. It is important for the prescriber to have a sense not only of relative risk but also of incidence to balance the risks against the other attributes of the individual members of the drug class. A review of English-language literature was performed to identify trials that provide data on the relative risk and, when able to be calculated, the incidence of adverse cardiac events among the commonly used FQs. Moxifloxacin had a several-fold higher risk of cardiac arrhythmias than levofloxacin or ciprofloxacin in randomized trials. However, the actual event rate was low in 2 of 3 studies. Given inconsistencies among the studies and the relative rarity of the events, the clinician need not base the choice of drug primarily on concern for a cardiac arrhythmia except in patients at the highest risk of such an event.