Citations

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher ( P <0.001), and there were fewer women ( P =0.046) in the AF than in the non‐AF group. Left ventricular ejection fraction was significantly lower ( P =0.001), and cardiogenic shock was more often observed ( P <0.001) in the AF group. Both in‐hospital ( P <0.001) and long‐term mortality ( P <0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long‐term mortality (hazard ratio, 2.31; 95% CI, 1.50–3.55; P <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in‐hospital and long‐term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in‐hospital and long‐term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01947621.

Background: Stroke symptoms in the general population are common (≈18% of adults 45+) and are associated with future stroke. These symptoms may also identify a broad spectrum of clinically-undetected vascular conditions. Methods: Stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, and loss of ability to communicate or understand) and time to self-reported hospitalization for any cardiovascular (CVD) reason (heart, stroke, or TIA) or stroke were assessed in the REGARDS Study (a national, population-based, longitudinal study of 30,239 African-American and white adults > 45 years enrolled 2003-2007). The symptom-hospitalization association was assessed by proportional hazards analysis in persons stroke/TIA-free at baseline, with adjustment for demographics (age, race and sex), further adjustment for SES (income and education), CVD risk factors (smoking, hypertension, diabetes, dyslipidemia, atrial fibrillation and heart disease), and “perceived health status.” Results: Over an average follow-up of 5.6 years, presence of any stroke symptom was associated with greater risk of hospitalization for stroke (11% versus 6%; HR = 1.68; 95% CI: 1.52 - 1.85), a risk only modestly attenuated by adjustment for SES (HR = 1.59; 95% CI: 1.44 - 1.76), risk factors (HR = 1.44; 95% CI: 1.29 - 1.60), and perceived health (HR = 1.37; 95% CI: 1.23 - 1.53). However, presence of any stroke symptom was more strongly related to hospitalization for CVD (42% vs. 24%; HR = 1.92; 95 CI: 1.82 - 2.03), only modestly mediated by adjustment for SES (HR = 1.82; 95% CI: 1.73 - 1.93), risk factors (HR = 1.66; 95% CI: 1.57 - 1.76), and perceived health (HR = 1.57; 95% CI: 1.48 - 1.66). Conclusions: Stroke symptoms appear to be a marker not only for stroke risk, but also for general CVD. Simple questions can identify 18% of the general population that have over a 40% chance of hospitalization for CVD over a 5-year horizon. Implications for potential intervention to reduce risk are profound.

Introduction: Morbidity and mortality attributable to hypertension are higher in African American (AAEH) compared to Caucasian essential hypertensive (EH) patients, possibly related to a differential effect on vascular injury and repair. While circulating endothelial progenitor cells (EPC) preserve endothelial integrity IEC detach from sites of injury and represent markers of vascular damage. We hypothesized that plasma levels of IEC and inflammatory markers would be higher in AAEH compared to EH patients. METHODS: Inferior vena cava levels of CD34+/KDR+ (EPC) and VAP-1+ (IEC) cells were measured by FACS in EH and AAEH under fixed sodium intake (150 mEq/d) and blockade of the renin-angiotensin-system, and compared to systemic levels in normotensive control subjects (n=19 each). Systemic levels of inflammatory cytokines and EPC homing factors were measured by Luminex. Results: Blood pressure, serum creatinine, lipids, antihypertensive medications, and EPC levels did not differ between EH and AAEH patients. Circulating IEC were higher in AAEH, and inversely correlated with EPC levels (Figure). Systemic levels of inflammatory cytokines and EPC homing factors were higher in AAEH compared to EH patients (Table), and correlated directly with IEC. Conclusion: Despite preserved kidney function and controlled BP, circulating inflammatory markers were elevated in AAEH and correlated with increased IEC and decreased EPC levels. Increased release of cytokines and IEC in AAEH may impair EPC reparative capacity and predispose to hypertensive vascular injury. This process may aggravate vascular damage and accelerate hypertension-related morbidity/mortality rates in AAEH.

Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.

5017 Background: HDCT/ASCT represents a curative salvage treatment for patients with GCT but is rarely used for other solid tumors. Patients undergoing HDCT/ASCT for hematologic neoplasms require revaccination for their childhood immunizations. Whether this is necessary in patients with GCT is unknown. Methods: In this prospective longitudinal study, patients with GCT undergoing HDCT-ASCT from 11/2010 to 5/2018 had serologies for Measles, Mumps, Rubella, Diphtheria, Tetanus, Polio, and Varicella Zoster measured before HDCT and at 3, 6, and in a subset, 12+ months after the last HDCT with results at these timepoints compared using descriptive statistics. In addition, titer levels at ≥6 months post-transplant were matched 1:1 for age and gender with HL patients who underwent HDCT/ASCT during the same time period. Immunity was compared between cohorts using the Cochran-Mantel-Haenszel test. Results: Of 80 patients with GCT (median age 30, 84% nonseminoma), 91% received 3 sequential transplants and 68 had repeat titers at ≥6 months. Immunity at baseline was >95% for Diphtheria, Tetanus and Polio and 89% for Varicella Zoster but lower for Measles (74%), Mumps (85%), and Rubella (83%) (Table). Compared to baseline, proportional immunity for all infections was similar at 3, 6, and 12 months post-transplant in the GCT population (≥6 months shown in Table). Matching resulted in 58 GCT-HL pairs. One-year immunity was numerically lower for most infections in the HL vs. GCT patients and significantly decreased for Measles and Rubella (Table). Conclusions: To our knowledge, this is the first study to assess vaccine titers following HDCT/ASCT for GCT. We demonstrate that HDCT/ASCT does not result in loss of immunity to childhood vaccines and that GCT patients retain protective titers more frequently than those with HL. However, 15-31% of GCT patients lack MMR immunity at baseline and at 1-year post-ASCT. Therefore, we recommend checking MMR titers at 1-year post-ASCT with revaccination of those lacking immunity. Titer evaluation and revaccination is not necessary for other childhood immunizations.[Table: see text]

The efficacy and safety of a fluid‐filled intragastric balloon (IGB) for weight loss in patients with cirrhosis on the liver transplantation (LT) waiting list is unknown. We enrolled stable compensated patients with body mass index >35 kg/m2 and on the waiting list for IGB placement endoscopically for a maximum of 6 months. A total of 8 patients (7 men) aged mean ± SD, 56 ± 4.6 years with Model for End‐Stage Liver Disease–sodium (MELD‐Na) scores 14.1 ± 3.4 experienced weight reduction (146 ± 22.2 kg versus 127 ± 21.6 kg [P = 0.005] with IGB in place and 130 ± 24.6 kg [P = 0.014] at 6 months), with a total body weight loss of 12.2% ± 8.8% with IGBs in place and 10.9% ± 8.9% at 6 months. Body fat decreased from 48.6% ± 5.8% to 40.6% ± 6.4% (P = 0.001) and lean mass increased from 51.3% ± 6% to 59.4% ± 6.4% (P = 0.001). No change in MELD‐Na scores occurred (P = 0.770). Early balloon retrieval was attributed to accommodative symptoms (n = 2) and liver decompensation (n = 1). Mallory Weiss tears (n = 3), but no portal hypertensive bleeding, occurred. Liver decompensation and/or hepatocellular carcinoma (HCC) developed in 3 patients. A total of 4 patients with LT ± sleeve gastrectomy maintained overall weight loss. Of 4 patients who did not receive transplants, 2 experienced weight regain. IGB results in short‐term weight loss in patients with cirrhosis awaiting LT, with body fat loss without lean mass loss. Adverse effects were common. Decompensation and HCC did occur, with uncertainty of the relation to weight loss, and thus careful patient selection and close follow‐up are required.

AbstractBackgroundA plethora of age‐related changes contribute to hollowing of the temples, as bone remodeling, atrophy of the temporalis muscle, thinning of the skin, and deflation of the subcutaneous and deep temporal fat create the appearance of a skeletonized face. In addition, previous studies have established a relationship between facial skeletonization, temporal hollowing, and postmenopausal sarcopenia.ObjectiveTo compare the volume change, adverse events, and patient satisfaction of soft‐tissue filler injections in the temple between young (<51) and old (>51) females.Material and MethodsA total of 30 women with a mean age of 53.1 ± 12.1 years underwent bilateral temporal volumization. Adverse events and satisfaction were assessed after 3 and 6 months. 3‐Dimensional surface imaging was performed at baseline and after 2 weeks, 3 and 6 months to assess volumetric changes.ResultsA mean volume of 5.55 ± 1.9 cc was injected into the temples. A total of 31 adverse events were observed in 13 patients. The overall satisfaction of the procedure was very high after 3 and 6 months in both patient groups, and raters showed a significant agreement in their assessment of the aesthetic improvement, while the self‐reported patient satisfaction was also substantially high. The surface‐volume coefficient differed significantly between 14 days and 3 months post‐injection only in pre‐menopausal patients, while no significant difference was detected between 3 and 6 months.ConclusionTemporal soft‐tissue filler injections are safe and provide long‐lasting aesthetic improvement both in pre‐ and postmenopausal women.

Parkinson’s disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world’s aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.