Citations

Abstract Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging is associated with an increased prevalence of coronary artery disease and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate in tissues, including the heart, and contribute to age‐related pathologies. However, the role of senescence in recovery following MI has not been investigated. In this study, we demonstrate that treatment of aged mice with the senolytic drug, navitoclax, eliminates senescent cardiomyocytes and attenuates profibrotic protein expression in aged mice. Importantly, clearance of senescent cells improved myocardial remodelling and diastolic function as well as overall survival following MI. These data provide proof‐of‐concept evidence that senescent cells are major contributors to impaired function and increased mortality following MI and that senolytics are a potential new therapeutic avenue for MI.

Background: Achilles tendon tears are potentially career-ending injuries for professional athletes. For players in the National Football League (NFL), return requires not only surgery and extensive rehabilitation but also the ability to compete in a market with limited positions that annually introduces new recruits. Purpose/Hypothesis: We authors sought to evaluate factors related to return to play (RTP) and changes in performance following a primary Achilles tear. Our hypothesis was that “skilled” position players and those drafted in later rounds would return at a lower rate as compared with “unskilled” position players and higher draft-round players. Study Design: Case-control study; Level of evidence, 3. Methods: From a previously established database, 80 NFL players were identified as having primary Achilles tendon tears between the 2009 and 2014 seasons. RTP was defined as playing in a regular season or postseason game following injury. Probability of RTP was modeled as a function of time after injury in Kaplan-Meier analysis with demographic variables assessed via generalized linear models. Twelve players (15%) experienced a subsequent Achilles tendon tear during or after the study period and were included in the overall RTP rate but were excluded from performance analyses owing to the confounding effects of an ipsilateral retear or contralateral tear. Results: The overall RTP rate was 61.3%. Age, number of prior seasons, position type, or draft round status did not significantly affect RTP when evaluated with Kaplan-Meier analysis. In the season before their injury, players who did RTP played in a significantly greater number of regular season games (13.7) compared with players who did not RTP (8.71) ( P = .011). Players who did not RTP exhibited a significant decrease in performance in the season preceding injury (12.7 regular season games played 2 seasons preinjury vs 8.71 regular season games played 1 season prior preinjury;, P = .019). Players who returned did not display a significant change in the number of games played or started in seasons following injury when >1 season after return was evaluated. Conclusion: Rate of RTP following primary Achilles tendon tears may be lower than previously published. However, for those able to return, performance only in the season immediately following injury appears to be affected; players return to preinjury levels if given the opportunity to play >1 season after injury.

Background: Neuropsychological assessment can add essential information to the characterization of individuals presenting with the logopenic variant of primary progressive aphasia (lvPPA). Objective: This study examined the neuropsychological characteristics of lvPPA patients. We also examined differences in regional and whole brain atrophy based on neuropsychological profiles. Methods: We conducted a hierarchical cluster analysis on memory, executive functioning, and visuospatial neuropsychological test data for 56 individuals with lvPPA. We then compared resultant clusters to left middle temporal, inferior parietal, and superior parietal regions-of-interest using multivariate analysis of covariance. We also performed voxel-level analyses. Results: We identified three clusters characterized as lvPPA with no neurocognitive impairment ( n = 5), lvPPA with mild neurocognitive deficits ( n = 23), and lvPPA with marked cognitive deficits ( n = 28). WAB-AQ was associated with left middle temporal volume. Superior parietal volumes were smaller for the lvPPA group with marked cognitive symptoms compared to the less severe groups. Voxel-level analyses showed greater atrophy in temporal, parietal, lateral occipital, and frontal regions, left worse than right. Age, disease duration, gender, WAB-AQ, and PiB-PET did not account for differences between groups. Conclusions: LvPPA patients without cognitive deficits in other domains were relatively uncommon while 50% of our sample exhibited pronounced neurocognitive deficits outside the language domain. Pronounced cognitive deficits in lvPPA are associated with widespread atrophy, left worse than right. Our study underscores the importance of examining neuropsychological function in addition to language in patients with lvPPA.

An autoantibody target on brain microvascular endothelial cells in patients with neuromyelitis optica may be exploited to manipulate blood-brain barrier permeability.

Objectives: Noise pollution in pediatric intensive care units (PICU) contributes to poor sleep and may increase risk of developing delirium. The Environmental Protection Agency (EPA) recommends <45 decibels (dB) in hospital environments. The objectives are to assess the degree of PICU noise pollution, to develop a delirium bundle targeted at reducing noise, and to assess the effect of the bundle on nocturnal noise pollution. Methods: This is a QI initiative at an academic PICU. Thirty-five sound sensors were installed in patient bed spaces, hallways, and common areas. The pediatric delirium bundle was implemented in 8 pilot patients (40 patient ICU days) while 108 non-pilot patients received usual care over a 28-day period. Results: A total of 20,609 hourly dB readings were collected. Hourly minimum, average, and maximum dB of all occupied bed spaces demonstrated medians [interquartile range] of 48.0 [39.0-53.0], 52.8 [48.1-56.2] and 67.0 [63.5-70.5] dB, respectively. Bed spaces were louder during the day (10AM to 4PM) than at night (11PM to 5AM) (53.5 [49.0-56.8] vs. 51.3 [46.0-55.3] dB, P < 0.01). Pilot patient rooms were significantly quieter than non-pilot patient rooms at night (n=210, 45.3 [39.7-55.9]) vs. n=1841, 51.2 [46.9-54.8] dB, P < 0.01). The pilot rooms compliant with the bundle had the lowest hourly nighttime average dB (44.1 [38.5-55.5]). Conclusions: Substantial noise pollution exists in our PICU, and utilizing the pediatric delirium bundle led to a significant noise reduction that can be perceived as half the loudness with hourly nighttime average dB meeting the EPA standards when compliant with the bundle.

Background: Cutaneous calciphylaxis is a rare disorder that occurs most frequently in patients with end-stage renal disease (ESRD), those on hemodialysis, and renal transplant recipients. It is frequently associated with hyperparathyroidism and a markedly elevated calcium–phosphate product, and it carries a high mortality rate. The usual clinical presentation is of painful, stellate necrosis of the thighs or buttocks, often in the setting of livedo reticularis. Death usually results from septicemia. Objective: This report documents an unusual case of recurrent, self-limiting calciphylaxis in the setting of a patient with ESRD and discusses the clinical and pathologic features of this potentially very fatal disorder. Methods and Remits: A 52-year-old woman presented with a greater than one-year history of relapsing and remitting, exquisitely painful, necrotic, numular plaques on the abdomen, breast, and arm. This patient had a markedly elevated calcium–phosphate product and parathyroid hormone level. The diagnosis of calciphylaxis was made by wedge biopsy of the most recent plaque, revealing calcification of medium-sized subcutaneous vessels and lobular capillaries with associated epidermal necrosis. Conclusions: This case demonstrates an unusual clinical variant of calciphylaxis that presented without the characteristic stellate necrosis or livedo reticularis that normally marks this condition and spontaneous resolution without incurring septicemia. Regardless of morphology, calciphylaxis should be considered in the differential diagnosis of painful, necrotic lesions occurring in the setting of ESRD.