To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID‐19). PubMed, Embase, Web of Science, Cochrane Library, ...ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID‐19 outpatients were included. The Cochrane risk‐of‐bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID‐19‐related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19–0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17−0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05−0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64–1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19–0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID‐19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.
Highlights
Neutralizing monoclonal antibodies (mABs) decreased risk of hospitalization or emergence department visits in coronavirus disease 2019 (COVID‐19) outpatients.
Neutralizing mABs reduced mortality in COVID‐19 outpatients.
Neutralizing mABs had no increased risk of any adverse events (AEs) and lower risk of serious AEs.
Hepatitis B surface antigen (HBsAg) loss is a rare event during nucleos(t)ide analogue (Nuc) therapy. Limited data suggest that stopping Nuc therapy may increase HBsAg loss rate in hepatitis B e ...antigen–negative patients. A large study was conducted to investigate this issue in more detail. Of the 1,075 hepatitis B e antigen–negative patients treated with Nuc for a median of 156 (61‐430) weeks, 5 showed HBsAg seroclearance during treatment at an estimated annual incidence of 0.15%. Of the patients who remained HBsAg‐seropositive, 691 (52.3 years old, 86% male, 44.6% cirrhosis) had stopped Nuc therapy by the Asian‐Pacific Association for the Study of the Liver stopping rule and then were prospectively followed up. Baseline and on‐treatment clinical and viral features, treatment duration, consolidation duration, time to undetectable hepatitis B virus DNA, time to normal alanine aminotransferase, end‐of‐treatment HBsAg, and HBsAg log reduction were compared between patients with and without HBsAg seroclearance after end of treatment. During a median off‐therapy follow‐up period of 155 (2‐614) weeks, HBsAg seroclearance was confirmed in 42 patients. The 6‐year cumulative incidence was 13% with an estimated annual incidence of 1.78%. Cox regression analysis showed that shorter time to undetectable hepatitis B virus DNA (<12 weeks), greater HBsAg reduction during therapy (>1 log10), lower end‐of‐treatment HBsAg level (<100 IU/mL), patients with sustained response, and relapsers not retreated were factors for off‐therapy HBsAg seroclearance. Conclusion: The incidence of HBsAg seroclearance after stopping Nuc was much higher than that during therapy and highest in patients without virologic and clinical relapse; patients with clinical relapse who remained untreated had a 7.34 times higher incidence of HBsAg clearance than those who received retreatment, suggesting that transient untreated clinical relapse may drive sufficient immune control to functional cure. (Hepatology 2017).
Quercetin, a bioflavonoid derived from vegetables and fruits, exerts anti-inflammatory effects in various diseases. Our previous study revealed that quercetin could suppress the expression of matrix ...metalloprotease-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) to achieve anti-inflammatory effects in tumor necrosis factor-α (TNF-α)-stimulated human retinal pigment epithelial (ARPE-19) cells. The present study explored whether quercetin can inhibit the interleukin-1β (IL-1β)-induced production of inflammatory cytokines and chemokines in ARPE-19 cells. Prior to stimulation by IL-1β, ARPE-19 cells were pretreated with quercetin at various concentrations (2.5-20 µM). The results showed that quercetin could dose-dependently decrease the mRNA and protein levels of ICAM-1, IL-6, IL-8 and monocyte chemoattractant protein-1 (MCP-1). It also attenuated the adherence of the human monocytic leukemia cell line THP-1 to IL-1β-stimulated ARPE-19 cells. We also demonstrated that quercetin inhibited signaling pathways related to the inflammatory process, including phosphorylation of mitogen-activated protein kinases (MAPKs), inhibitor of nuclear factor κ-B kinase (IKK)α/β, c-Jun, cAMP response element-binding protein (CREB), activating transcription factor 2 (ATF2) and nuclear factor (NF)-κB p65, and blocked the translocation of NF-κB p65 into the nucleus. Furthermore, MAPK inhibitors including an extracellular signal-regulated kinase (ERK) 1/2 inhibitor (U0126), a p38 inhibitor (SB202190) and a c-Jun N-terminal kinase (JNK) inhibitor (SP600125) decreased the expression of soluble ICAM-1 (sICAM-1), but not ICAM-1. U0126 and SB202190 could inhibit the expression of IL-6, IL-8 and MCP-1, but SP600125 could not. An NF-κB inhibitor (Bay 11-7082) also reduced the expression of ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1. Taken together, these results provide evidence that quercetin protects ARPE-19 cells from the IL-1β-stimulated increase in ICAM-1, sICAM-1, IL-6, IL-8 and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways to ameliorate the inflammatory response.
The AMP-activated protein kinase (AMPK) signaling system plays a key role in cellular stress by repressing the inflammatory responses induced by the nuclear factor-kappa B (NF-κB) system. Previous ...studies suggest that the anti-inflammatory role of AMPK involves activation by adenine, but the mechanism that allows adenine to produce these effects has not yet been elucidated. In human umbilical vein endothelial cells (HUVECs), adenine was observed to induce the phosphorylation of AMPK in both a time- and dose-dependent manner as well as its downstream target acetyl Co-A carboxylase (ACC). Adenine also attenuated NF-κB targeting of gene expression in a dose-dependent manner and decreased monocyte adhesion to HUVECs following tumor necrosis factor (TNF-α) treatment. The short hairpin RNA (shRNA) against AMPK α1 in HUVECs attenuated the adenine-induced inhibition of NF-κB activation in response to TNF-α, thereby suggesting that the anti-inflammatory role of adenine is mediated by AMPK. Following the knockdown of adenosyl phosphoribosyl transferase (APRT) in HUVECs, adenine supplementation failed to induce the phosphorylation of AMPK and ACC. Similarly, the expression of a shRNA against APRT nullified the anti-inflammatory effects of adenine in HUVECs. These results suggested that the role of adenine as an AMPK activator is related to catabolism by APRT, which increases the cellular AMP levels to activate AMPK.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mesoporous anatase TiO2 beads with high surface areas and controllable pore sizes are prepared by using a combined sol–gel and solvothermal process. Dye‐sensitized solar cells made from these ...mesoporous beads gave a total power conversion efficiency of 7.20% under AM 1.5 sunlight, higher than that obtained using Degussa P25 films of similar thickness (5.66%).
This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web ...of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.
In this paper, we conduct mathematical and numerical analyses for COVID-19. To predict the trend of COVID-19, we propose a time-dependent SIR model that tracks the transmission and recovering rate at ...time t. Using the data provided by China authority, we show our one-day prediction errors are almost less than 3%. The turning point and the total number of confirmed cases in China are predicted under our model. To analyze the impact of the undetectable infections on the spread of disease, we extend our model by considering two types of infected persons: detectable and undetectable infected persons. Whether there is an outbreak is characterized by the spectral radius of a 2 X 2 matrix. If R 0 > 1, then the spectral radius of that matrix is greater than 1, and there is an outbreak. We plot the phase transition diagram of an outbreak and show that there are several countries on the verge of COVID-19 outbreaks on Mar. 2, 2020. To illustrate the effectiveness of social distancing, we analyze the independent cascade model for disease propagation in a configuration random network. We show two approaches of social distancing that can lead to a reduction of the effective reproduction number R e .
This article presents the 38-GHz phased array 32-element Tx and 16-element Rx with 2-GHz IF and 5-GHz LO for fifth-generation (5G) millimeter-wave (MMW) communications. The Tx and Rx beamformers and ...upconverters/downconverters are fabricated in 65-nm CMOS. The PAs and LNAs near antenna ends are fabricated in 0.15-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> GaAs pHEMT. The eight-element Tx and four-element Rx phased array printed circuit board (PCB) modules integrated with multiple integrated circuits (ICs) and endfire antennas are implemented as unit cells. Four pieces of Tx modules are vertically stacked to construct an <inline-formula> <tex-math notation="LaTeX">8\times {4} </tex-math></inline-formula> brick array (planar array), while four Rx modules are to construct a <inline-formula> <tex-math notation="LaTeX">4\times {4} </tex-math></inline-formula> array. According to 38-GHz over-the-air (OTA) measurements, the 32-element Tx shows 47.5-dBm equivalent isotropic radiated power (EIRP) at OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1 ~dB}} </tex-math></inline-formula> with −35.2-dB image rejection ratio (IMRR) and −37.4-dB <inline-formula> <tex-math notation="LaTeX">\times 8 </tex-math></inline-formula> LORR. The 16-element Rx at 38 GHz shows −4-dBm OP<inline-formula> <tex-math notation="LaTeX">_{\mathrm {1~dB}} </tex-math></inline-formula> with −28-dB IMRR and −36.6-dB LORR. The Tx and Rx support the beam scanning around ±60° azimuth and ±30° elevation planes. The Tx-to-Rx wireless data link demonstrates 64 quadrature amplitude modulation (QAM)/400 M-BR, 256 QAM/200 M-BR, and 512 QAM/100 M-BR in 20 m. To the best of our knowledge, this work is the first 5G 37-/39-GHz phased array Tx/Rx using the scalable brick array configuration and demonstrating competitive performances compared with previous works.
The influence of inhaled corticosteroids (ICS) on COVID-19 outcomes remains uncertain. To address this, we conducted a systematic review and meta-analysis, analyzing 30 studies, to investigate the ...impact of ICS on patients with COVID-19. Our study focused on various outcomes, including mortality risk, hospitalization, admission to the intensive care unit (ICU), mechanical ventilation (MV) utilization, and length of hospital stay. Additionally, we conducted a subgroup analysis to assess the effect of ICS on patients with chronic obstructive pulmonary disease (COPD) and asthma. Our findings suggest that the prior use of ICS did not lead to significant differences in mortality risk, ICU admission, hospitalization, or MV utilization between individuals who had used ICS previously and those who had not. However, in the subgroup analysis of patients with COPD, prior ICS use was associated with a lower risk of mortality compared to non-users (OR, 0.95; 95% CI, 0.90-1.00). Overall, while the use of ICS did not significantly affect COVID-19 outcomes in general, it may have beneficial effects specifically for patients with COPD. Nevertheless, more research is needed to establish a definitive conclusion on the role of ICS in COVID-19 treatment. PROSPERO registration number: CRD42021279429.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Introduction
Hypothyroidism is a rare and possible cause of hyponatremia. However, the clinical epidemiology and risk of mortality (ROM) when they coexist still remain elusive.
Objectives
We ...assessed the epidemiology and ROM among index patients with coexisting hypothyroidism and hyponatremia via a national population database.
Patients and methods
This retrospective cohort study utilized Taiwan’s National Health Insurance program database. Distributions of definite sociodemographic factors were analyzed. The annual incidence among the overall group and sex-subgroups was investigated. In addition, potential factors influencing the ROM were also evaluated.
Results
Of 4,549,226 patients from 1998 to 2015, a total of 3,140 index patients with concurrent hypothyroidism and hyponatremia were analyzed. The incidence rate increased tenfold from 1998 to 2015; average annual incidence rate was 174. Among the total participants, 57.1% were women; mean age was 72.6 ± 14.7 years and 88.8% were aged > 55 years. Although average length of stay (LOS) was 13.1 ± 15.4 days, the mortality group had significantly longer LOS than that in the survival group (12.9 days vs 22.2 days). Old age, catastrophic illness, cardiac dysrhythmia, and low hospital hierarchy were independent predictors of hospital mortality. The optimal LOS cutoff value for ROM prediction was 16 days. Index patients with LOS > 16 days increased ROM by 2.3-fold.
Conclusions
Coexistent hypothyroidism and hyponatremia is rare, although the incidence increased gradually. Factors influencing the ROM, such as old age, underlying catastrophic status, cardiac dysrhythmia, hospital hierarchy, and LOS should be considered in clinical care.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
