Citations

Abstract Aims To investigate valve sizing and the haemodynamic relevance of the predicted left ventricular outflow tract (LVOT) in patients with mitral annular calcification (MAC) undergoing transatrial transcatheter valve implantation (THV). Methods and results In total, 21 patients undergoing transatrial THV, multiplanar reconstruction (MPR), maximum intensity projection (MIP), and cubic spline interpolation (CSI) were compared for MA sizing during diastole. In addition, predicted neo-LVOT areas were measured in 18 patients and correlated with the post-procedural haemodynamic dimensions. The procedure was successful in all patients (100%). Concomitant aortic valve replacement was performed in eight patients (43%) (AVR group). Sizing using MPR and MIP yielded comparable results in terms of area, perimeter, and diameter, whereas the dimensions obtained with CSI were systematically smaller. The simulated mean systolic neo-LVOT area was 133.4 ± 64.2 mm2 with an anticipated relative LVOT area reduction (neo-LVOT area/LVOT area × 100) of 59.3 ± 14.7%. The systolic relative LVOT area reduction, but not the absolute neo-LVOT area, was found to predict the peak (r = 0.69; P = 0.002) and mean (r = 0.65; P = 0.004) post-operative aortic gradient in the overall population as well as separately in the AVR (peak: r = 0.91; P = 0.002/mean: r = 0.85; P = 0.002) and no-AVR (peak: r = 0.89; P = 0.003/mean: r = 0.72; P = 0.008) groups. Conclusion In patients with severe MAC undergoing transatrial transcatheter valve implantation, MPR, and MIP yielded comparable annular dimensions, while values obtained with CSI tended to be systematically smaller. Mitral annular area and the average annular diameter appear to be reliable parameters for valve selection. Simulated relative LVOT reduction was found to predict the post-procedural aortic gradients.

Background: Although associations between hypertension in mid-life and the development of dementia and cognitive decline have been established, the impact of the new 2017 ACC/AHA guidelines on dementia risk at the population level has not been evaluated. Objectives: To assess the association of hypertension categories with the risk of incident dementia and to calculate the population attributable fraction (PAF) for dementia from hypertension categories according to the 2017 ACC/AHA guidelines, and compare these associations with hypertension defined according to JNC7. Methods: We studied dementia-free participants recruited to the Atherosclerosis Risk in Communities (ARIC) cohort in 1987-89. Hypertension was defined by 2003 JNC7 and 2017 ACC/AHA guidelines using blood pressure measured at baseline; participants using antihypertensive medication were included in hypertension stage 2 for both sets of guidelines. Dementia was defined using adjudicated consensus diagnoses at visit 5 (2011-13), informant telephone interviews, and ICD-9 codes from hospitalizations and death certificates through 2013. Cox proportional hazards regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) by hypertension categories, adjusting for potential confounders, including sociodemographic, lifestyle and clinical variables. PAF of dementia by hypertension category was calculated using rate ratios from Poisson regression and the prevalence of the risk factor in the population. Results: Among 13,971 participants followed for a median of 23.0 years, 1381 cases of dementia were identified. Prevalence of elevated BP (systolic BP [SBP] 120-129 and diastolic BP [DBP] <80), hypertension stage 1 (SBP 130-139 or DBP 80-89) and hypertension stage 2 (SBP ≥140 or DPB ≥90) according to 2017 ACC/AHA categories was 13%, 15% and 44%, respectively. Corresponding HR (95%CI) compared to normal BP were 1.35 (95%CI 1.12, 1.61), 1.28 (1.07, 1.52) and 1.36 (1.18, 1.57), respectively. PAF (95%CI) of dementia from hypertension categories were 3% (1%, 5%), 3% (1%, 5%) and 9% (4%, 14%). PAF using JNC7 categories were similar to 2017 ACC/AHA: 6% (3%, 9%) for prehypertension (SBP 120-129 or DBP 80-89), 0% (-2%, 2%) for hypertension stage 1 (SBP 140-159 or DBP 90-99), and 9% (5%, 13%) for hypertension stage 2 (SBP ≥160 or DBP ≥100). Conclusions: Risk of dementia was increased across categories defined by the new ACC/AHA hypertension guidelines. However, the population impact on dementia incidence using 2017 ACC/AHA was similar to the impact of JNC7. These results suggest that the new criteria for diagnosis of hypertension will not increase the number of persons in whom hypertension could be reasonably labeled as a risk for dementia.

Background: Dementia is increasingly appreciated to have important vascular disease contributions. Albuminuria and decreased estimated glomerular filtration rate (eGFR) define chronic kidney disease (CKD) and are related to the risk of its consequences as well as microvascular disease and endothelial damage across multiple vascular beds. We extend previous studies by examining albuminuria and eGFR measured at both mid-life and older age as risk factors for dementia. Methods: We studied 10,876 adult participants in the Atherosclerosis Risk in Communities (ARIC) Study excluding participants with end-stage renal disease, stroke and incident dementia at baseline. We analyzed the adjusted relative hazard of incident dementia as a function of eGFR (linear spine with a knot at 60 ml/min per 1.73m 2 ) and log urinary albumin-creatinine-ratio (UACR) adjusting for age, sex, race, education level, Apolipoprotein E4 level, smoking, alcohol consumption, body mass index, diabetes and hypertension. We used two different baseline visits: (1) Starting in 1996-1999 (Visit 4, age 54-74 years); (2) Starting 2011-2013 (Visit 5, age 70-90 years) with follow-up to 2017. Results: We observed 2,001 dementia cases over 16 years of follow-up (446 after Visit 5). Risk of dementia increased with higher levels of albuminuria with a stronger magnitude at older-age than in midlife ( see table ). Estimated GFR was more weakly associated with dementia (p>0.05 at both baselines). The albuminuria association was consistent across sex and race (p-interaction>0.05). Conclusion: Albuminuria, a marker of kidney disease and endothelial damage, is strongly related to dementia incidence. Albuminuria’s association with dementia is stronger in late-life unlike other vascular risk factors, where the association is weaker at older age.

Abstract Breast implants are typically placed for cosmetic or reconstructive purposes, and are recognized to have a substantial impact on aesthetics and quality of life. In addition, the presence of a breast implant on the chest wall has a potential benefit of force diffusion or force absorption in traumatic injury. This article reports a series of three patients with preexisting breast implants who suffered penetrating chest trauma. In each case, the presence of a breast implant was potentially lifesaving. We describe the cases in detail, provide a conceptual discussion, and discuss directions for future research. Level of Evidence: 5

Abstract There are currently no direct regulations and few guidelines regarding restraint design for commercial spaceflight vehicles. Operators designing vehicles intended solely for private commercial use, particularly short-duration suborbital flights, have questioned the need for 5-point restraints, instead considering the options of fewer restraints and less stringent application requirements. We sought to identify risks and benefits of alternative restraint designs for the commercial spaceflight industry, particularly for the diverse population of commercial spaceflight participants (SFPs). A systematic review was conducted on currently available information and published literature of human and animal studies as well as industry standards regarding restraint design, common injuries, and patterns of injuries in vehicular trauma, including automobile, aircraft, and spacecraft. Although data are lacking regarding commercial spacecraft or potential mishap forces, extensive studies are available in analogue environments, including motor vehicle crashes and aviation mishaps, which demonstrate variations of restraint design and relative risks and benefits of these systems. These studies demonstrate superiority of harnesses that include shoulder restraint and a negative-G (crotch) belt to limit torso movement. Injury patterns in anthropometrically varied populations, with factors including gender, obesity, and advanced age, demonstrate increased vulnerability to morbidity and mortality in obese and elderly populations and improved outcomes with more rigorous restraint designs. Given the varied population anticipated for commercial SFPs and significant reduction in morbidity and mortality associated with 5-point restraint designs, evidence suggests that the use of a 5-point restraint is most appropriate for commercial spacecraft.

AbstractDrug screening during pre-transplant evaluations can have major implications for patient care, particularly because drug abuse has been associated with poor transplant outcomes. Although urine drug screening is usually preferred, serum testing is available for situations such as anuria due to end stage renal disease. However, there are few studies evaluating serum drug screening in specific populations such as patients undergoing kidney transplant evaluation. All serum drug screens ordered between January 2015 and November 2017 on patients being evaluated for renal transplant were compared against a large population of serum drug screens ordered from other institutions. Cocaine screening and confirmation results were evaluated to determine false positives. Cocaine screens were positive in 23 of 537 (4.3%) pre-transplant samples, and 211 of 5,115 (4.1%) comparison samples. Confirmation testing demonstrated that 14 (60.9%) pre-transplant samples were false positives, which was significantly (P < 0.01) higher than the rate of false positives in the comparison group (47/211, 22.3%). No common medication or other cross-reacting substance could be identified in the pre-transplant cohort to explain the false-positive results. Although serum cocaine screening had a low overall false-positive rate, the proportion of false positives was significantly higher in pre-transplant patients. Given the poor transplant outcomes associated with drug abuse, failure to properly interpret screening results as being false positives could negatively affect patient care. All members of the transplant team should recognize the importance of confirmation testing in this setting, to avoid unintended consequences due to false-positive screening results.

ABSTRACT Normal vitamin D homeostasis is critical for optimal health; nevertheless, vitamin D deficiency is a worldwide public health problem. Vitamin D insufficiency is most commonly due to inadequate cutaneous synthesis of cholecalciferol and/or insufficient intake of vitamin D, but can also arise as a consequence of pathological states such as obesity. Serum concentrations of 25(OH)D (calcidiol) are low in obesity, and fail to increase appropriately after vitamin D supplementation. Although sequestration of vitamin D in adipose tissues or dilution of ingested or cutaneously synthesized vitamin D in the large fat mass of obese patients has been proposed to explain these findings, here we investigate the alternative mechanism that reduced capacity to convert parent vitamin D to 25(OH)D due to decreased expression of CYP2R1, the principal hepatic vitamin D 25-hydroxylase. To test this hypothesis, we isolated livers from female mice of 6 to 24 weeks of age, weaned onto either a normal chow diet or a high-fat diet, and determined the abundance of Cyp2r1 mRNA using digital droplet-quantitative PCR. We observed a significant (p &lt; 0.001) decrease in Cyp2r1 mRNA in the liver of high-fat diet–fed mice relative to lean-chow–fed female mice. Moreover, there was a significant (p &lt; 0.01) relationship between levels of Cyp2r1 mRNA and serum 25(OH)D concentrations as well as between Cyp2R1 mRNA and the ratio of circulating 25(OH)D3 to cholecalciferol (p &lt; 0.0001). Using linear regression we determined a curve with 25(OH)D3/cholecalciferol versus normalized Cyp2R1 mRNA abundance with an R2 value of 0.85. Finally, we performed ex vivo activity assays of isolated livers and found that obese mice generated significantly less 25(OH)D3 than lean mice (p &lt; 0.05). Our findings indicate that expression of CYP2R1 is reduced in obesity and accounts in part for the decreased circulating 25(OH)D. © 2019 American Society for Bone and Mineral Research.

AbstractImmune checkpoint inhibitors (ICPis) are a novel class of immunotherapeutic agents that have revolutionized the treatment of cancer; however, these drugs can also cause a unique spectrum of autoimmune toxicity. Autoimmune hemolytic anemia (AIHA) is a rare, but often severe, complication of ICPis. We identified 14 patients from nine institutions across the United States who developed ICPi‐AIHA. The median interval from ICPi initiation to development of AIHA was 55 days (interquartile range [IQR], 22‐110 days). Results from the direct antiglobulin test (DAT) were available for 13 of 14 patients: 8 patients (62%) had a positive DAT and 5 (38%) had a negative DAT. The median pretreatment and nadir hemoglobin concentrations were 11.8 g/dL (IQR, 10.2‐12.9 g/dL) and 6.3 g/dL (IQR, 6.1‐8.0 g/dL), respectively. Four patients (29%) had a preexisting lymphoproliferative disorder, and two (14%) had a positive DAT prior to initiation of ICPi therapy. All patients were treated with glucocorticoids, with three requiring additional immunosuppressive therapy. Complete and partial recoveries of hemoglobin were achieved in 12 (86%) and 2 (14%) patients, respectively. Seven patients (50%) were rechallenged with ICPis, and one (14%) developed recurrent AIHA. Clinical and laboratory features of ICPi‐AIHA were similar in DAT positive and negative patients. ICPi‐AIHA shares many clinical features with primary AIHA; however, a unique aspect of ICPi‐AIHA is a high incidence of DAT negativity. Glucocorticoids are an effective first‐line treatment in the majority of patients with ICPi‐AIHA, and most patients who are rechallenged with an ICPi do not appear to develop recurrence of AIHA.

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor–positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.