Clinical and Echocardiographic Characteristics of Bartonella Infective Endocarditis: An 8-Year Single-Centre Experience in the United States.

BACKGROUND: Infective endocarditis due to Bartonella species is rare. The clinical and echocardiographic characteristics are not well defined. We aimed to investigate the clinical and echocardiographic findings of Bartonella endocarditis in the contemporary era. METHODS: The infective endocarditis (IE) registry and echocardiographic database at our institution were retrospectively analysed to evaluate the clinical and echocardiographic features of Bartonella endocarditis. RESULTS: Between January 2008 and December 2015, there were 11 patients with Bartonella IE (0.84% among a total of 1,308 cases of definite IE): median age 54 (30-69) years, all male, 9 Caucasian, 10 had a history of cat exposure, 10 had a pre-existing valvulopathy including 6 patients with a prosthetic valve with prosthesis age range between 3 to 5 years and 1 patient with implantable cardioverter defibrillator (ICD). Bartonella henselae was responsible for all the cases. Echocardiographic evidence of IE was found in 6 of 11 patients on transthoracic echocardiography (TTE), and 6 of 8 on transoesophageal echocardiography (TEE). Bartonella IE was associated with significant valvular destruction and dysfunction on echocardiography. Nine (9) patients were managed surgically with excellent outcomes, including two patients who failed initial medical therapy. Two (2) patients who were managed medically had progression of valvular dysfunction. At a median follow-up of 6 months, there were no deaths attributable to IE or other cardiovascular causes. CONCLUSION: In a contemporary single-centre cohort in the United States, Bartonella IE remains rare, but should be considered when pathogen could not be identified in patients with suspected IE, especially those with prosthetic valves or bicuspid aortic valve (BAV). The vast majority of patients with Bartonella IE were managed surgically with excellent outcomes.

Regulation of RAGE splicing by hnRNP A1 and Tra2ß-1 and its potential role in AD pathogenesis.

The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, full-length membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis, either via interaction of mRAGE with ß-amyloid peptide (Aß) or inhibition of the mRAGE-activated signaling pathway. In the present study, we showed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and Transformer2ß-1 (Tra2ß-1) were involved in the alternative splicing of mRAGE and esRAGE. Functionally, two factors had an antagonistic effect on the regulation. Glucose deprivation induced an increased ratio of mRAGE/esRAGE via up-regulation of hnRNP A1 and down-regulation of Tra2ß-1. Moreover, the ratios of mRAGE/esRAGE and hnRNP A1/Tra2ß-1 were increased in peripheral blood mononuclear cells from AD patients. The results provide a molecular basis for altered splicing of mRAGE and esRAGE in AD pathogenesis. The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis. Mechanism for imbalanced expression of these two isoforms in AD brain remains elusive. We proposed here a hypothetic model to illustrate that impaired glucose metabolism in AD brain may increase the expression of splicing protein hnRNP A1 and reduce Tra2ß-1, which cause the imbalanced expression of mRAGE and esRAGE.

Role of a serum-based biomarker panel in the early diagnosis of lung cancer for a cohort of high-risk patients.

BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.

Polysomnographic validation of an under-mattress monitoring device in estimating sleep architecture and obstructive sleep apnea in adults.

OBJECTIVE: The objective of this study is to evaluate the validity of an under-mattress monitoring device (Fullpower Technologies) in estimating sleep continuity and architecture, as well as estimating obstructive sleep apnea in an adult population. METHODS: Adult volunteers (n=102, 55% male and 45% female, aged 40.6 ± 13.7 years with a mean body mass index of 26.8 ± 5.8 kg/m2) each participated in a one-night unattended in-lab study conducted by Fullpower Technologies. Each participant slept on a queen-sized bed with Sleeptracker-AI Monitor sensors placed underneath the mattress. Standard polysomnography (PSG) was simultaneously recorded on the same night. Researchers (FD and CK) were provided de-identified sleep studies and datasets by Fullpower Technologies for analysis. Sleep continuity measures, 30-s epoch-by-epoch sleep stages, and apnea and hypopnea events estimated by an automated algorithm from the Sleeptracker-AI Monitor were compared with the PSG recordings, with the PSG recordings serving as the reference. RESULTS: Overall, the Sleeptracker-AI Monitor estimated similar sleep continuity measures compared with PSG. The Sleeptracker-AI Monitor overestimated total sleep time (TST) by an average of 6.3 min and underestimated wake after sleep onset (WASO) by 10.2 min. Sleep efficiency (SE) was similar between the Sleeptracker-AI Monitor and PSG (87.6% and 86.3%, respectively). The epoch-by-epoch accuracy of Sleeptracker-AI Monitor to distinguish 4-stage sleep (wake, light, deep, and REM sleep) was 79.0% (95% CI: 77.8%, 80.2%) with a Cohen's kappa of 0.676 (95% CI: 0.656, 0.697). Thirty-five participants (34.3%) were diagnosed with obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥ 5 based on PSG. Accuracy, sensitivity, and specificity for the Sleeptracker-AI Monitor to estimate OSA (an AHI ≥5) were 87.3% (95% CI: 80.8%, 93.7%), 85.7% (95% CI: 74.1%, 97.3%), and 88.1% (95% CI: 80.3%, 95.8%) respectively. The positive likelihood ratio (LR+) for AHI ≥5 was 7.18 (95% CI: 3.69, 14.0), and the negative likelihood ratio (LR-) for AHI ≥5 was 0.16 (95% CI: 0.072, 0.368). CONCLUSION: The Sleeptracker-AI Monitor had high accuracy, sensitivity, and specificity in estimating sleep continuity measures and sleep architecture, as well as in estimating apnea and hypopnea events. These findings indicate that Sleeptracker-AI Monitor is a valid device to monitor sleep quantity and quality among adults. Sleeptracker-AI Monitor may also be a reliable complementary tool to PSG for OSA screening in clinical practice.

A case of hypereosinophilic syndrome with STAT5b N642H mutation.

Hypereosinophilia is defined as persistent eosinophilia (>1.5 × 109/L). Hypereosinophilic syndrome (HES) is a term used to describe a group of disorders characterized by sustained hypereosinophilia associated with end-organ damage. Based on underlying molecular mechanism of eosinophilia, there are different subtypes of HES. Diagnosis of HES subtype can be challenging, especially in the absence of overt lymphoid/myeloid neoplasms or discernable secondary causes. Long-term outpatient follow-up with periodic complete blood count and repeated bone marrow biopsy may be needed to monitor disease activity. Somatic signal transducer and activation transcription 5b (STAT5b) N642H mutation was recently found to be associated with myeloid neoplasms with eosinophilia. We report a case of HES who presented with pulmonary embolism and acute eosinophilic pneumonia, found to have recurrent STAT5b N642H mutation by next-generation sequencing, suggesting possible underlying myeloid neoplasm.

A Unique Case of Combined Nodular and Tracheobronchial Amyloidosis.

Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of misfolded proteins that can affect either systemically or locally confined to one system. Pulmonary amyloidosis is rare and can be classified into three forms according to the anatomic site of involvement: nodular pulmonary amyloidosis, tracheobronchial amyloidosis and diffuse alveolar-septal amyloidosis. The former two usually represent localized amyloid disease and the latter represents systemic disease. Typically lung parenchymal and tracheobronchial amyloidosis do not present together in localized forms of pulmonary amyloidosis. Here we report a unique case of localized pulmonary immunoglobulin light-chain amyloidosis, manifested as both parenchymal nodules and tracheobronchial amyloid deposition.

Patterns of Cardiometabolic Health as Midlife Women Transition to Menopause: A Prospective Multiethnic Study.

CONTEXT: Cardiometabolic conditions increase in midlife, but early customized prevention strategies are not established for such women. OBJECTIVE: To characterize and identify factors longitudinally related to constellations of cardiometabolic risk components in multiracial/ethnic women in midlife. DESIGN: We conducted a prospective, longitudinal, multiethnic cohort study of 3003 midlife women undergoing menopausal transition (MT). Metabolic syndrome (MetS) was defined as having at least three of five components: high fasting triglyceride (hTG) level, low high-density lipoprotein cholesterol (lHDL-C) level, high fasting plasma glucose (hGluc) level, large waist circumference (abdominal obesity; Ob), and hypertension (HTN). We described the patterns of constellations and estimated hazard ratios (HRs) for constellations at (i) incident MetS and (ii) recovery from MetS, using multivariable-adjusted Cox regression. SETTING: Seven US sites. PARTICIPANTS: In all, 1412 non-Hispanic white, 851 black, 272 Japanese, 237 Hispanic, and 231 Chinese women. EXPOSURES: Race/ethnicity, lifestyle factors, and MT stage. MAIN OUTCOMES MEASURES: Cardiometabolic constellations, incident MetS, and MetS recovery. RESULTS: Central obesity was the most frequent component. Having no components was the most frequent (31%) baseline constellation. Physical activity (HR = 1.68; 95% CI: 1.06, 2.68) and lower caloric intake (HR = 0.96; 95% CI: 0.93, 0.99 per 100 cal/d) were associated with recovery from MetS. Ob/hTG/lHDL-C (18%), Ob/HTN/lHDL-C (16%), and Ob/HTN/hGluc (14%) were frequent incident constellations. Physically active women had 26% to 62% lower hazards of incident MetS than inactive women. CONCLUSIONS: Modifiable lifestyle behaviors were related to recovery from MetS and decreased risk of the most frequent MetS constellations in midlife women.

Mysterious quad of constrictive pericarditis, recurrent pleural effusions, bone involvement and interstitial lung disease.

Erdheim-Chester disease (ECD) is a rare multisystemic non-Langerhans cell histiocytic neoplasm. The rarity of the disease and heterogenous clinical presentations often leads to delayed diagnosis. Historically, ECD lacked effective treatment and the prognosis was poor. Following the recent discovery of frequent BRAF-V600E mutation in patients with ECD, vemurafenib, a selective BRAF V600 kinase inhibitor has been approved for BRAF-mutated ECD patients. The prognosis of ECD has dramatically improved with early recognition of the disease and available treatment. ECD affects nearly every organ system. Cardiac involvement with pericardial effusion is common but rarely with constrictive physiology or requiring pericardiectomy. We present a case of a 56-year-old woman with recurrent pericarditis with constrictive physiology along with pleural effusion and interstitial lung disease that was diagnosed with ECD 3 years after initial presentation. The patient's symptoms were relieved with pericardiectomy and targeted therapy.