Safety and efficacy of oral nemonoxacin versus levofloxacin in treatment of community-acquired pneumonia: A phase 3, multicenter,randomized, double-blind,double-dummy,active-controlled,non-inferiority trial

Background/Purpose

Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP.

Community-dwelling older adults who are low-income and disabled weathering financial challenges

Despite interventions aiming to improve outcomes among older adults experiencing financial challenges, the challenges and strategies employed to handle them are poorly understood. This study examined the experiences of financial challenges among low-income adults aged ≥65 years. Eleven semi-structured interviews were analyzed using thematic analyses. An overarching theme was “I guess it balances”, capturing attempts to maintain hope and proactively address challenges despite stress, uncertainty and limitations. Balancing was demonstrated within four domains, including cognitive bandwidth (“think a lot” versus “I don't dwell on that”), emotional experience (“depressing” versus “be thankful”), learned resilience (“that was a shock” versus “there's always a way”), and meeting daily needs (“we learned to do without” versus “take a dollar and stretch it”). Participants described being weathered by challenges and using predominately high-effort coping strategies to weather the challenges. These findings call for strengthening the safety net for older adults facing financial challenges.     

Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery

PurposeThe aim of this study is to prospectively investigate the influence of ADRB and COMT gene polymorphisms on postoperative outcomes of patients undergoing cardiac surgery.MethodsThis prospective cohort study included 223 patients undergoing elective cardiac valve surgery using cardiopulmonary bypass. Demographic information, intraoperative data, postoperative data, and blood samples were collected. Patients were genotyped for single-nucleotide polymorphisms (SNPs) of ADRB1 rs1801253, ADRB2 rs1042713, and COMT rs4680. Major adverse cardiovascular and cerebrovascular events (MACCEs) were used as the primary outcome to evaluate the postoperative prognosis of patients. Secondary outcomes included the duration of mechanical ventilatory support, intensive care unit stay, postoperative hospital stay, and postoperative need of inotropic or vasoactive agents.FindingsThe overall incidence of MACCEs was 15.2%. Among 3 SNP loci, only different genotyped carriers of ADRB2 rs1042713 had statistically significant differences in the incidence of MACCEs (P = 0.005), especially for acute kidney injury (P = 0.023). The proportions of postoperative norepinephrine demand of patients carrying the AA genotype of ADRB2 rs1042713 (P = 0.016) and the AG genotype of COMT rs4680 (P = 0.018) were low. The duration of mechanical ventilatory support (P = 0.034) and postoperative hospital stay (P = 0.045) of patients carrying the AG genotype of COMT rs4680 was shortest. After multiple logistic regression analysis, we found that the G allele carriers of ADRB2 rs1042713 had a higher risk of MACCEs (AG vs AA genotype: odds ratio [OR] = 4.348; 95% CI, 1.529–12.359, P = 0.006; GG vs AA genotype: OR = 3.722; 95% CI, 1.060–13.071; P = 0.040), in particular with acute kidney injury (AG vs AA genotype: OR = 5.273; 95% CI, 1.093–25.451; P = 0.038; GG vs AA genotype: OR = 7.533; 95% CI, 1.275–44.522; P = 0.026). There was no SNP-SNP interaction found among the 3 SNPs with multifactor dimensionality reduction analysis.ImplicationThe ADRB2 rs1042713 polymorphism might be related to prognosis of patients undergoing cardiac surgery. Patients carrying the G allele of ADRB2 rs1042713 had a higher risk of developing MACCEs, especially acute kidney injury. chictr.org.com identifier: ChiCTR1800015105.     

Bone Texture Assessment on Lateral VFAs Using the Texture Research Investigational Platform (TRIP) and its Fracture Discrimination Ability

Texture Research Imaging Platform applies trabecular bone score (TBS) measurement principles to images acquired with multiple modalities to assess bone texture at various skeletal sites. This study aimed to assess the bone texture score in dual-energy X-ray absorptiometry-acquired lateral vertebral fracture assessment (VFA) images (BTS_VFA), evaluate its reproducibility, and vertebral fracture discrimination ability. Subjects included 178 VF cases and 178 non-VF controls, 136 women and 42 men in each group, age 55–92 years, from two research centers. Cases and controls were matched for age (±5 years), body mass index (±5 kg/m²) and TBS. All participants underwent dual-energy X-ray absorptiometry TBS assessment from standard posterior-anterior lumbar spine scans and BTS_VFA assessment. VF presence was determined using VFA images applying the Genant's method. BTS_VFA was lower among fractured women compared to non-fractured (0.626 ± 0.109 vs 0.675 ± 0.099, p < 0.01), but not among men. In a binary logistic regression adjusted for study center and sex, for each SD lower BTS_VFA, there was a 40% increase (OR 1.40, 95% CI (1.13–1.74)) in the risk of having a prevalent VF; area under the curve (95% CI) 0.616 (0.557–0.675). Inter-assessor and inter-centers ICCs for BTS_VFA measurements were very good; 0.96 (0.64–0.99) and 0.98 (0.95–0.99), respectively. The BTS_VFA precision (coefficient of variation) was 2.42%. This feasibility study demonstrates the potential to assess trabecular bone texture in lateral VFA images with good reproducibility. BTS_VFA can discriminate between fractured and non-fractured women independent of their age, body mass index and TBS. In conclusion, BTS_VFA, a potential trabecular texture assessment that excludes the posterior elements, may have value in fracture prediction or as a novel approach to be further investigated in spine surgery planning.     

Body Surface Area (BSA) is a Better Osteoporosis Associated Anthropometric Parameter Than Other Anthropometric Parameters in Elderly Population

Body surface area (BSA) is widely used for adjusting drug dose, while few studies have yet systematically evaluated its association with osteoporosis and compared its advantage with other anthropometric parameters in osteoporotic risk prediction. A total of 10,021 Chinese individuals aged over 65 years were enrolled in our study. Bone mineral density (BMD) was measured, and demographic information was also collected. Pearson correlation analysis, receiver operating characteristic (ROC) curves and predictive analysis were performed to assess the clinical practice of BSA for osteoporosis. BSA had the strongest correlation with BMD (0.544, p < 0.001) compared with conventional anthropometric indices. Besides, BSA had the highest power in osteoporosis prediction, with an area under the curve (AUC) reaching 0.81. After incorporating BSA into the osteoporosis risk prediction model, the AUC improved from 0.82 to 0.83 (p < 0.01). We found BSA provided additional diagnostic value beyond conventional anthropometric information with continuous and category NRIs were 30.40% (p < 0.01) and 3.29% (p < 0.01), respectively, and the IDI was 1.85% (p < 0.01). BSA was positively associated with osteoporosis and showed superior discriminative ability for osteoporosis risk prediction compared with other anthropometric parameters in the Chinese elderly population.     

Inhibition of phosphodiesterase-4 suppresses HMGB1/RAGE signaling pathway and NLRP3 inflammasome activation in mice exposed to chronic unpredictable mild stress

Inhibition of phosphodiesterase-4 (PDE4) produces robust anti-inflammatory and antidepressant-like effects in multiple animal models. However, the detailed mechanisms have not been well studied. Receptor for advanced glycation endproducts (RAGE) and inflammasome activation are implicated in the etiology of depression. Here, we aimed to investigate the involvement of RAGE and nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3) inflammasome in the antidepressant-like effects of PDE4 inhibition in mice. We found that inhibition of PDE4 by roflupram (ROF, 0.5, and 1.0 mg/kg, i.g.) exerted antidepressant-like effects in mice subjected to chronic unpredictable mild stress (CUMS). Simultaneously, ROF inhibited CUMS-induced microglial activation and restored the morphology of microglial cells in the hippocampus, as evidenced by reduced total process length, area, volume, number of branching points, number of terminal points and total sholl intersections of microglia. ROF also decreased the expression of ionized calcium-binding adapter molecule-1 and the level of interleukin-1β. Western blot analysis showed that PDE4 inhibition suppressed the high-mobility group box 1 protein (HMGB1)/RAGE signaling pathway, as the levels of HMGB1, RAGE, toll-like receptor 4, phosphorylated p38 mitogen-activated protein kinase, and nuclear factor κ-B were decreased in both hippocampus and cortex in mice after treatment with ROF. Moreover, ROF also attenuated the protein levels of NLRP3, the apoptosis-associated speck-like protein containing (ASC), and cysteine-requiring aspartate protease-1 (Caspase-1), which are key proteins in the NLRP3-mediated inflammasome signaling pathway. In summary, these results demonstrate that the down-regulation of HMGB1/RAGE signaling pathway and inflammasome suppression possibly contribute to the antidepressant-like effects of PDE4 inhibitors. And, ROF has potential as a candidate drug in the treatment of depression.     

Severe chronic active Epstein–Barr virus infection associated with multiple necrotic lesions in the liver

We report an atypical presentation of a chronic active Epstein–Barr virus (EBV) infection with multiple nodular coagulation necrosis in the liver, that appeared as hypodense areas on a CT scan. The patient, a 26-year-old man, was hospitalized following over 2 years of intermittent fever, weight loss and liver abnormalities after contracting infectious mononucleosis. We diagnosed his illness as a chronic active EBV infection (CAEBV) because of the high antibody titers against EBV and the histological evidence of organ disease with demonstration of EBV mRNA. A liver biopsy revealed EBV-infected T-cell infiltration with hemophagocytosis and marked hepatocytolytic necrosis. The patient developed multiple coagulation necrosis with well-defined borders surrounding T-cell aggregation in the liver 8 months later. He died of respiratory failure due to interstitial pneumonitis. The analysis of EBV-genome termini demonstrated a clonal proliferation of T-cells harboring EBV, but no T-cell antigen receptor (TCR) gene rearrangement was observed. We speculate that the pathogenesis of this disease was an atypical expression of organ damage as a result of an aberrant T-cell response to EBV infection.