Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study

Background Atrial fibrillation (AF) is a common arrhythmia in patients with hypertension. ELABELA, which has cardioprotective effects, is decreased in the plasma of patients with hypertension and might be associated with AF in the hypertensive population. This study aims to measure the ELABELA plasma levels in hypertension patients with and without AF and to analyse the related factors. Methods A total of 162 hypertension patients with or without AF were recruited for our monocentric observational study. Subjects were excluded if they had a history of valvular heart disease, rheumatic heart disease, cardiomyopathy, thyroid diseases, or heart failure. The patients’ histories were recorded, and laboratory examinations were conducted. Plasma ELABELA was detected by immunoassay. Echocardiographs were performed, and parameters were collected by two experienced doctors. Binary logistic regression analysis was used to identify the association between ELABELA plasma level and AF in patients with hypertension. Results Plasma ELABELA levels were lower in hypertension patients with AF than in those without AF (2.0 [1.5, 2.8] vs. 4.0 [3.4, 5.0] ng/ml, P < 0.001). ELABELA levels were correlated with age, heart rate, BNP levels and left atrial dimension. In addition to the left atrial dimension, ELABELA plasma levels were associated with AF in patients with hypertension (OR 0.081, 95% CI 0.029–0.224, P < 0.001). ELABELA levels were further decreased in the persistent AF subgroup compared with the paroxysmal AF subgroup (1.8 [1.4, 2.5] vs. 2.2 [1.8, 3.0] ng/ml, P = 0.012) and correlated with HR, BNP and ESR levels. Conclusions ELALABELA levels were decreased in hypertension patients with AF and further lowered in the persistent AF subgroup. Decreased ELABELA plasma levels were associated with AF in hypertension patients and may be an underlying risk factor.

Longitudinal associations between inhibitory control and externalizing and internalizing symptoms in school-aged children

Inhibitory control (IC) deficits have been associated with psychiatric symptoms in all ages. However, longitudinal studies testing the direction of the associations in childhood are scarce. We used a sample of 2,874 children (7 to 9 years old) to test the following three hypotheses: (a) IC deficits are an underlying risk factor with a potentially causal role for psychopathology, (b) IC deficits are a complication of psychopathology, and (c) IC deficits and psychopathology are associated at the trait level but not necessarily causally related. We used the go/no-go task to assess IC, the parent-rated Strengths and Difficulties Questionnaire to evaluate externalizing/internalizing symptoms, and the random intercepts cross-lagged panel model to test the hypotheses. The results showed no support for the underlying risk factor hypothesis, suggesting that IC unlikely has a causal role in this age group's psychopathology. The complication hypothesis received support for externalizing symptoms, suggesting that externalizing symptoms may hamper the normal development of IC. IC deficits and both externalizing and internalizing symptoms were correlated at the trait level, indicating a possible common origin. We suggest that it may be useful to support children with externalizing symptoms to promote and protect their IC development.

A horse and a zebra: an atypical clinical picture including Guillain-Barré syndrome, recurrent fever and mesenteric lymphadenopathy caused by two concomitant infections

Background While Campylobacter jejuni represents the most common cause of bacterial gastroenteritis, Yersinia pseudotuberculosis infections are very rarely diagnosed in adults. Case We report on a previously healthy patient who presented several times at our hospital with fever, Guillain-Barré syndrome, recurrent abdominal symptoms and distinct mesenteric lymphadenopathy, respectively. This complicated and diagnostically challenging course of disease was caused by a C. jejuni and Y. pseudotuberculosis coinfection. Antibiotic treatment with doxycycline was effective. Conclusion Broad serology testing was crucial to discover that two concomitant infections were causing the symptoms. This case demonstrates that when a clinical picture is not fully explained by one known infection, another infection with the same underlying risk factor has to be considered, hence “a horse and a zebra”.

Fulminant Sphingomonas paucimobilis keratitis: case study and review of literature

Sphingomonas paucimobilis is a low-virulence gram-negative bacillus known to cause various ocular infections such as endophthalmitis, panophthalmitis and keratitis that are usually associated with an underlying risk factor such as peri-partum or postpartum phase, cataract surgery, contact lens use, neurotrophic keratopathy or ocular trauma. We report a case of spontaneously occurring perforated corneal ulcer caused by the organism in a young man managed by penetrating keratoplasty. The course was followed by endophthalmitis with graft infection culminating in phthisis bulbi despite aggressive medical and surgical management. Along with reporting this case, we also present a review of literature on ocular infections caused by the same organism.

Lifestyle profile of elderly living with non-communicable disease in Bangkok and Surabaya

Lifestyle is one of the underlying risk factor of non-communicable disease (NCD). Dietary habit and exercise pattern are two indicators of lifestyle. Elderly are prone to NCD due to increased age which being independent risk factor. This study aimed to analyze and compare the lifestyle profile of elderly living with NCD between Bangkok and Surabaya, in term of dietary habit and exercise pattern, and to determine the best predictor of sedentary lifestyle among this population. This cross-sectional study involved 100 and 96 elderly with HT and/or DM in communities of Bangkok and Surabaya respectively (n=196). Self-developed instrument was used in data collection (r=0.178–0.715, Chronbach Alpha=0.644). Mann-Whitney U and regression tests were used in data analysis (α&lt;0.05). There was a significant difference of lifestyle in elderly living with NCD between Bangkok and Surabaya (p=0.008), especially in term of eat variety food (p=0.002), oily food (p=0.015), and curry with coconut milk (p=0.026). Eat vegetable and fruit could not predict dietary habit in elderly living with NCD (p=0.064). Eat fermented food was came up as the best predictor of lifestyle (p=0.000). It was accounted for 52.1% variance in lifestyle score in this population.

Characterization of the tumor mutation burden in hepatobiliary tumors.

295 Background: Hepatobiliary tumors are aggressive tumors with emerging evidence for increasing sensitivity to immune checkpoint inhibitors (ICI). Tumor mutation burden (TMB) was found to be a quantitative biomarker associated with production of neoantigens within the tumor and predict the sensitivity to immune therapy. Herein, we explore the TMB as a potential biomarker of response to immune therapy in hepatobiliary tumors. Methods: We retrospectively assessed all patients with hepatobiliary malignancies who have undergone next generation sequencing (NGS) between January 2013 and September 2018. We then analyzed the tumor mutation burden of these tumors and also identified frequency of patients with no clinically actionable mutations. Results: Of the 65 total patients with hepatobiliary tumors, 49 patients (75%) had at least one clinically actionable mutation while 16 patients (25%) had no clinically actionable mutations. Among 65 patients, 44 patients had hepatocellular carcinoma, 15 patients had cholangiocarcinoma and 6 patients had gallbladder carcinoma. The TMB data is available for 15 patients. The mean TMB reported was 2.7 (1.16 – 4.25), which suggests low mutation burden in general in all our HB tumors. Among the patients with available TMB, the underlying risk factor was noted as hepatitis C in 3, NASH in 1, others in 6, unknown in 5 patients. Conclusions: Our data suggests the TMB in hepatobiliary tumors is low in general irrespective of their underlying risk factors. Future larger studies are needed to evaluate TMB as a potential biomarker in hepatobiliary tumors to help select patients that will benefit from immune therapy.

Inhibiting Cellular Senescence: A New Therapeutic Paradigm for Age-Related Osteoporosis

Context With the aging of the population and projected increase in osteoporotic fractures coupled with the declining use of osteoporosis medications, there is a compelling need for new approaches to treat osteoporosis. Given that age-related osteoporosis generally coexists with multiple other comorbidities (e.g., atherosclerosis, diabetes, frailty) that share aging as the leading risk factor, there is growing interest in the “Geroscience Hypothesis,” which posits that manipulation of fundamental aging mechanisms will delay the appearance or severity of multiple chronic diseases because these diseases share aging as the underlying risk factor. In this context, one fundamental aging mechanism that has received considerable attention recently as contributing to multiple age-related morbidities is cellular senescence. This mini-review provides an overview on cellular senescence with a focus on its role in mediating age-related bone loss. Methods This summary is based on the authors’ knowledge of the field supplemented by a PubMed search using the terms “senescence,” “aging,” and “bone.” Results There is compelling evidence from preclinical models and supportive human data demonstrating an increase in senescent cells in the bone microenvironment with aging. These cells produce a proinflammatory secretome that leads to increased bone resorption and decreased bone formation, and approaches that either eliminate senescent cells or impair the production of their proinflammatory secretome have been shown to prevent age-related bone loss in mice. Conclusions Targeting cellular senescence represents a novel therapeutic strategy to prevent not only bone loss but potentially multiple age-related diseases simultaneously.

Primary Liver Cancers, Part 2

Hepatocellular carcinoma (HCC) and primary intrahepatic cholangiocarcinoma (ICC) have been increasing in incidence worldwide and are leading causes of cancer death. Studies of the molecular alterations leading to these carcinomas provide insights into the key mechanisms involved. A literature review was conducted to identify articles with information relevant to current understanding of the etiologies and molecular pathogenesis of HCC and ICC. Chronic inflammatory diseases are the key etiological risk factors for both HCC and ICC, although other diseases play a role, and for many ICCs, an underlying risk factor is not identified. Mutations in catenin beta 1 ( CTNBB1) and tumor protein 53 (P53) are the main genetic alterations in HCC. Isocitrate dehydrogenases 1 and 2 (IDH1/2), KRAS protooncogene GTPase (KRAS), a RAS Viral Oncogene Homolog in neoroblastoma (NRAS) and P53 are primary genetic alterations in ICC. In both diseases, the mutational landscape is dependent on the underlying etiology. The most significant etiologies and genetic processes involved in the carcinogenesis of HCC and ICC are reviewed.

Abstract 132: Monocytes Activation by Salt is Associated With Cardiovascular Risk Factors

Several studies have established a relationship between hypertension and salt intake; however the mechanisms by which salt causes hypertension are poorly understood. There is also evidence that sodium (Na+) accumulates in the interstitium with aging and hypertension in concentrations exceeding the plasma. We tested the hypothesis that increased NaCl would convert human monocytes to an inflammatory phenotype and to define mechanisms involved. We exposed monocytes from 17 human volunteers to normal physiological NaCl (NS: 150 mM/L), elevated NaCl (HS: 190 mM/L), or an equiosmoloar concentration of mannitol. Exposure of human monocytes to high salt, but not mannitol, increased formation of immunogenic isolevuglandins (isoLG) (NS: 1688±384 vs Mann:1762±429 vs HS: 2381± 635 MFI p<0.002). This was associated with an increase in the dendritic cell (DC) marker CD83 (NS: 503±81 vs Mann: 530± 106 vs HS: 764 ± 136 MFI p<0.001). Exposure to high salt also stimulated production of IL-6 (NS: 2145±771, Mann: 1122±295 and HS: 5187±1146 pg/mL, p=0.04), IL-β (NS: 94±35, Mann: 62±16 and HS: 224±98 pg/mL, p=0.01) and TNF-α (NS:1.9±0.3, Mann: 3.42±1.4 and HS: 4.4±2.1, p<0.0001). In additional experiments, we found that prolonged (7 day) exposure to high salt increased surface expression of CD209, another DC marker (NS: 22±9 vs HS: 34 ± 14, p=0.001) and promoted conversion of the cells to a DC morphology. The propensity for monocytes to respond to NaCl was influence by the patient’s risk factors. The increase in IsoLG (HS-NS) correlated with pulse pressure (mmHg, r=0.51, <0.04), BMI (Kg/m2, r=0.66, p=0.005), total cholesterol (mg/dL, r=0.55, p<0.05) and glucose (mg/dL, r=0.72, p=0.003). Stepwise multivariate regression revealed that BMI and pulse pressure are independent predictors of IsoLG formation in response to salt. These findings suggest that high extracellular NaCl promotes differentiation and activation of monocytes and that these pleotropic inflammatory cells exhibit a previously undefined salt sensitivity corresponding to patients’ underlying risk factor profile.