Acute Kidney Injury from Intravitreal Anti-vascular Endothelial Growth Factor Drugs: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Several observational studies have reported acute kidney injury from intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs for retinal diseases. However, systematic reviews and meta-analyses of randomized controlled trials on this critical topic are scant. OBJECTIVE: To evaluate acute kidney injury risk associated with intravitreal anti-VEGF drugs in patients with retinal diseases. METHODS: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials on 12 July, 2023, and included randomized controlled trials reporting acute kidney injury between anti-VEGF drugs (e.g., aflibercept, bevacizumab, brolucizumab, and ranibizumab) and controls for retinal diseases (e.g., age-related macular degeneration, polypoidal choroidal vasculopathy, diabetic retinopathy/diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization). Data were synthesized by a fixed-effects model for pooling odds ratios (ORs) using the Peto method. RESULTS: We included 13 randomized controlled trials (four and nine trials for aflibercept and ranibizumab, respectively) with a total of 4282 participants. The meta-analysis indicated intravitreal anti-VEGF drugs did not increase the acute kidney injury risk, compared with controls (odds ratio [OR]: 1.00, 95% confidence interval [CI] 0.49-2.04, I2: 0%), and no differences in the acute kidney injury risk were observed between different anti-VEGF drugs (OR: 1.10, 95% CI 0.27-4.43, I2: 0% for aflibercept; OR: 0.97, 95% CI 0.42-2.22, I2: 0% for ranibizumab) and between different retinal diseases (OR: 4.61, 95% CI 0.07-284.13, I2: not applicable for age-related macular degeneration; OR: 0.90, 95% CI 0.42-1.93, I2: 0% for diabetic retinopathy/diabetic macular edema; OR: 1.57, 95% CI 0.16-15.88, I2: 0% for retinal vein occlusion). CONCLUSIONS: Intravitreal anti-VEGF drugs were not associated with an acute kidney injury risk, regardless of which anti-VEGF drugs (aflibercept or ranibizumab) or retinal diseases (age-related macular degeneration, diabetic retinopathy/diabetic macular edema, or retinal vein occlusion) were involved. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO CRD42021267854.

Clinical and Epidemiological Characteristics of COVID-19 Patients in Chongqing China.

Objectives: To study in-depth the clinical and epidemiological characteristics of pneumonia resulting from COVID-19 and provide evidence for effective public health decisions. Methods: This was a retrospective, single-center research study. Participants were enrolled from patients presenting at the Chongqing Public Health Medical Treatment Center from Jan 24 to Feb 7, 2020, and were confirmed as having COVID-19. Results: A total of 114 COVID-19 patients (99 mild, 4 severe, 11 critical) of which 56 (56/114; 49.1%) were male, 58 (58/114; 50.9%) were female with a mean age of 46.05 years. Twenty nine (29/114; 25.44%) patients suffered from chronic diseases. Neutrophils counts in 23.68% (27/114) of patients were abnormally low and abnormally high in 21.05% (24/114). Erythrocyte sedimentation rate and the C-reactive protein levels were abnormally elevated in 76.5% (62/81) and 62.9% (66/105) of patients, respectively. Creatine kinase isoenzymes (CK-MB), pro-brain natriuretic peptide (pro-BNP) and troponin levels were above the normal range in 7.10% (8/112), 66.7% (10/15), and 100% of patients, respectively. The percentage of patients in which the partial pressure of oxygen (PaO2)/fraction of inspired O2(FiO2) ratio exceeded 200 was 60%. A total of 91 (91/114; 79.82%) patients displayed severe bilateral pneumonia, 52 (52/114; 45.61%) exhibited ground-glass opacity, and pulmonary consolidation was observed in 4 (3.51%) patients. Differences in shortness of breath, insomnia, inappetence, the procalcitonin (PCT) levels, FiO2 and PaO2/FiO2 among the three groups were statistically significant (p < 0.05). Differences between the mild and severe groups was observed in neutrophil and lymphocyte counts, CD4 expression, and levels of C-reactive protein, alanine aminotransferase, aspartate aminotransferase and albumin (P < 0.05). Between the mild and critical groups, differences were observed in neutrophils, platelets, and CD4 expression (P < 0.05). A difference in C-reactive protein levels between severe and critical groups was also found (P < 0.05). Conclusions: In the majority of cases no gender differences were observed and mostly the symptoms were mild. Evidence of efficient human-to-human virus transmission was found. The elderly with comorbidities were more prone to develop into severe or critical illness. Age and comorbidity may be risk factors for poor outcome.

Correlation of increased plasma osteoprotegerin and cardiovascular risk factors in patients with adult growth hormone deficiency.

Adult growth hormone deficiency (AGHD) is correlated to many adverse effects on metabolism and increases cardiovascular risk. 40 patients with AGHD and 40 healthy subjects were included. Anthropometric parameters such as body mass index, waist circumference, and waist-hip ratio were measured. Meanwhile, plasma levels of total cholesterol, triglyceride, high sensitivity C-relative protein, interleukin-6 and OPG were determined. Homeostasis model assessments for insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) were calculated using homeostasis model. Plasma OPG concentrations of AGHD patients were significantly higher than those in healthy subjects (131.82 ± 45.04 versus 81.02 ± 45.04, P < 0.01). Plasma OPG levels were positively correlated with age, body mass index, waist circumference, hip circumference, waist-hip ratio, fasting insulin, total cholesterol, triglyceride, high sensitivity C-relative protein and interleukin-6 (P < 0.05), but negatively correlated with high-density lipoprotein cholesterol (P < 0.05). Multiple linear stepwise regression analysis demonstrated that body mass index, triglyceride, and interleukin-6 were independently related to plasma OPG levels (P < 0.05). The levels of plasma OPG were increased in AGHD patients and were closely correlated with glycolipid metabolism and chronic inflammation. OPG might play an important role in the occurrence and development of cardiovascular diseases in AGHD patients.

Broad-spectrum antiviral activity of chebulagic acid and punicalagin against viruses that use glycosaminoglycans for entry.

BACKGROUND: We previously identified two hydrolyzable tannins, chebulagic acid (CHLA) and punicalagin (PUG) that blocked herpes simplex virus type 1 (HSV-1) entry and spread. These compounds inhibited viral glycoprotein interactions with cell surface glycosaminoglycans (GAGs). Based on this property, we evaluated their antiviral efficacy against several different viruses known to employ GAGs for host cell entry. RESULTS: Extensive analysis of the tannins' mechanism of action was performed on a panel of viruses during the attachment and entry steps of infection. Virus-specific binding assays and the analysis of viral spread during treatment with these compounds were also conducted. CHLA and PUG were effective in abrogating infection by human cytomegalovirus (HCMV), hepatitis C virus (HCV), dengue virus (DENV), measles virus (MV), and respiratory syncytial virus (RSV), at µM concentrations and in dose-dependent manners without significant cytotoxicity. Moreover, the natural compounds inhibited viral attachment, penetration, and spread, to different degrees for each virus. Specifically, the tannins blocked all these steps of infection for HCMV, HCV, and MV, but had little effect on the post-fusion spread of DENV and RSV, which could suggest intriguing differences in the roles of GAG-interactions for these viruses. CONCLUSIONS: CHLA and PUG may be of value as broad-spectrum antivirals for limiting emerging/recurring viruses known to engage host cell GAGs for entry. Further studies testing the efficacy of these tannins in vivo against certain viruses are justified.

Hydrolyzable tannins (chebulagic acid and punicalagin) target viral glycoprotein-glycosaminoglycan interactions to inhibit herpes simplex virus 1 entry and cell-to-cell spread.

Herpes simplex virus 1 (HSV-1) is a common human pathogen that causes lifelong latent infection of sensory neurons. Non-nucleoside inhibitors that can limit HSV-1 recurrence are particularly useful in treating immunocompromised individuals or cases of emerging acyclovir-resistant strains of herpesvirus. We report that chebulagic acid (CHLA) and punicalagin (PUG), two hydrolyzable tannins isolated from the dried fruits of Terminalia chebula Retz. (Combretaceae), inhibit HSV-1 entry at noncytotoxic doses in A549 human lung cells. Experiments revealed that both tannins targeted and inactivated HSV-1 viral particles and could prevent binding, penetration, and cell-to-cell spread, as well as secondary infection. The antiviral effect from either of the tannins was not associated with induction of type I interferon-mediated responses, nor was pretreatment of the host cell protective against HSV-1. Their inhibitory activities targeted HSV-1 glycoproteins since both natural compounds were able to block polykaryocyte formation mediated by expression of recombinant viral glycoproteins involved in attachment and membrane fusion. Our results indicated that CHLA and PUG blocked interactions between cell surface glycosaminoglycans and HSV-1 glycoproteins. Furthermore, the antiviral activities from the two tannins were significantly diminished in mutant cell lines unable to produce heparan sulfate and chondroitin sulfate and could be rescued upon reconstitution of heparan sulfate biosynthesis. We suggest that the hydrolyzable tannins CHLA and PUG may be useful as competitors for glycosaminoglycans in the management of HSV-1 infections and that they may help reduce the risk for development of viral drug resistance during therapy with nucleoside analogues.