Association of dietary vitamin C intake with depression in adults: A cross-sectional study of NHANES from 2005 to 2020.

BACKGROUND: The aim of this study was to evaluate the association between dietary vitamin C intake and depression in adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) during 2005 to 2020. Logistic regressions and restricted cubic spline (RCS) regression were used to assess the association between dietary vitamin C intake and depression. Additionally, we performed stratified and sensitivity analyses to evaluate the stability of the results. RESULTS: This study included 38,157 participants, with 3448 (9.04 %) of them experiencing depression. The vitamin C intake was negatively associated with depression after adjusting for all covariates (OR = 0.91, 95%CI: 0.88-0.94, P < 0.001). Similar inverse associations were observed when vitamin C intake was transformed into categorical variables. Individuals in higher quartiles of dietary vitamin C intake (Q2, Q3, and Q4) had lower odds ratios (ORs) compared to those in the lowest quartile (Q1), as indicated by adjusted ORs of 0.78 (95 % CI: 0.71-0.87, P < 0.001), 0.74 (95 % CI: 0.67-0.82, P < 0.001), and 0.73 (95 % CI: 0.65-0.81, P < 0.001), respectively. The RCS analysis found an L-shaped nonlinear relationship between dietary vitamin C intake and depression, after adjusting for all covariates (P for non-linearity<0.001). Consumption of vitamin C was inversely associated with depression (OR = 0.994, 95%CI: 0.993-0.996, P < 0.001) for intakes below 93.61 mg, but there was no association between dietary vitamin C intake and depression (P = 0.980) for intakes of 93.61 mg or higher. The inverse associations between vitamin C intake and depression remained robust in stratified and sensitivity analyses. LIMITATIONS: This study was a cross-sectional study, and therefore unable to establish a causal relationship between dietary vitamin C intake and depression. We are unable to fully eliminate the confounding effects resulted from other unmeasured or unknown factors. CONCLUSION: The study revealed a negative association between dietary vitamin C intake and depression, as well as an L-shaped nonlinear relationship between vitamin C intake and depression.

Adverse events with pemigatinib in the real world: a pharmacovigilance study based on the FDA Adverse Event Reporting System.

BACKGROUND: To data, there is insufficient large-scale data on the adverse events (AEs) of pemigatinib. Consequently, we conducted a pharmacovigilance study utilizing the Food and Drug Administration Adverse Event Reporting System (FAERS) database to investigate these AEs. RESEARCH DESIGN AND METHODS: The OpenVigil 2.1 was used to extract AE data from the FAERS database. Proportional reporting ratio (PRR), reporting odds ratios (ROR), and bayesian analysis confidence propagation neural network (BCPNN) were used to assess the association between pemigatinib and AEs. The clinical importance of AE signals were prioritized using a rating scale. RESULTS: A total of 848 AE reports were retrieved from the FAERS database, and 421 AE reports were identified after the data cleaning process. After accounting for indication bias and removal of medication errors, 59 positive signals were finally included. The 59 positive signals emerged in 11 system organ classes (SOCs). Besides, 19 positive AEs were classified as moderate clinical priority, while 40 were deemed weak in terms of priority. 9 positive AEs were not included in the drug label. CONCLUSIONS: This study provided valuable evidence for clinicians to mitigate the risk of pemigatinib-related toxicities in the real world.

Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system.

BACKGROUND: With the increased use of BCR-ABL1 tyrosine kinase inhibitors (TKIs) in cancer patients, adverse events (AEs) have garnered considerable interest. We conducted this pharmacovigilance study to evaluate the AEs of BCR-ABL1 TKIs in cancer patients using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: To query AE reports from the FAERS database, we used OpenVigil 2.1. Descriptive analysis was then employed to describe the characteristics of TKIs-associated AE reports. We also utilized the disproportionality analysis to detect safety signals by calculating the proportional reporting ratio (PRR) and reporting odds ratios (ROR). RESULTS: From the FAERS database, a total of 85,989 AE reports were retrieved, with 3,080 significant AE signals identified. Specifically, imatinib, nilotinib, dasatinib, bosutinib, and ponatinib had significant AE signals of 1,058, 813, 232, 186, and 791, respectively. These significant signals were further categorized into 26 system organ classes (SOCs). The AE signals of imatinib and ponatinib were primarily associated with general disorders and administration site conditions. On the other hand, nilotinib, dasatinib, and bosutinib were mainly linked to investigations, respiratory, thoracic and mediastinal disorders, and gastrointestinal disorders, respectively. Notably, new signals of 245, 278, 47, 55, and 253 were observed in imatinib, nilotinib, dasatinib, bosutinib, and ponatinib, respectively. CONCLUSIONS: The results of this study demonstrated that AE signals differ among the five BCR-ABL1 TKIs. Furthermore, each BCR-ABL1 TKI displayed several new signals. These findings provide valuable information for clinicians aiming to reduce the risk of AEs during BCR-ABL1 TKI treatment.

Pharmacovigilance Study of Infigratinib: A Safety Analysis of the FDA Adverse Event Reporting System.

BACKGROUND: Infigratinib is a fibroblast growth factor receptor (FGFR)-specifc tyrosine kinase inhibitor indicated for the treatment of patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma. However, few studies have been conducted to evaluated the safety of infigratinib in the real world. In this study, we conducted a pharmacovigilance study to evaluate the adverse events (AEs) of infigratinib by using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: OpenVigil 2.1 was employed to extract the FAERS database. Descriptive analysis was used to describe the characteristics of infigratinib-associated AE reports. Disproportionality analysis was performed by calculating the proportional reporting ratio (PRR), reporting odds ratios (ROR), and Bayesian analysis confidence propagation neural network (BCPNN) to detect positive signals. RESULTS: Our findings revealed 149 AE reports, among which 36 significant signals were identified. These significant AE signals were mainly observed in gastrointestinal disorders (N = 26, ROR = 26.03, PRR = 8.44, information component [IC] = 3.08) and skin and subcutaneous tissue disorders (N = 21, ROR = 92.13, PRR = 40.41, IC = 5.34). Notably, dehydration and skin exfoliation were unexpected AEs, but had relatively high signal intensities (ROR = 29.75, PRR = 26.64, IC = 4.74; ROR = 50.61, PRR = 45.24, IC = 5.50, respectively) despite not being listed on the drug label. Furthermore, our analysis showed that infigratinib dose differed statistically between severe and non-severe reports (113.82 ± 16.13 mg vs 125 ± 0.00 mg, t = - 4.28; p < 0.001). However, there were no significant differences in sex, age, and types of AEs between the two groups (p  = 0.06, p  = 0.86, and p = 0.93, respectively). CONCLUSIONS: These findings suggest that gastrointestinal and skin toxicities are the most common adverse reactions for infigratinib. It is important to recognize skin exfoliation and dehydration in clinical practice, as they are unexpected AEs. Additionally, our study indicates that infigratinib dose may correlate with an increased risk of AE severity, highlighting the need for dose adjustment of infigratinib when exposure to the drug is increased due to internal or external factors.

Transporter­mediated drug­drug interactions involving poly (ADP­ribose) polymerase inhibitors (Review).

Poly (ADP ribose) polymerase (PARP) inhibitors are novel targeted anticancer agents that have been widely used in patients with cancer, particularly in patients with breast-related cancer antigen 1/2 mutations. PARP inhibitors are administered orally and have been associated with improved efficacy and toxicity profiles when compared to conventional chemotherapy agents; this improvement is convenient and results in good compliance among patients with cancer. However, as PARP inhibitors are administered long-term and frequently concomitantly with other therapeutic agents, the risk of drug-drug interactions (DDIs) is increasing. Transporters are widely expressed in numerous types of tissue, where they have crucial roles in the membrane transport of several drugs. An alteration in the activity and expression of transporters may change the drug pharmacokinetics (PKs) and cause DDIs. As the five PARP inhibitors (olaparib, niraparib, rucaparib, talazoparib and veliparib) are transporter substrates, inhibitors or inducers, the potential transporter-mediated DDIs with the use of PARP inhibitors should be taken into consideration when co-administered with other agents. The present review focused on recent findings on transporter-mediated DDIs with PARP inhibitors to provide specific recommendations for reducing the occurrence of undesired DDIs.

Effects of hepatic or renal impairment on the pharmacokinetics of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have become the cornerstone in treating many solid and hematological cancers. The ICIs, including anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4), anti-programed cell death 1 (PD-1), and anti-programed death-ligand 1 (PD-L1) monoclonal antibodies, have significantly improved the prognosis of cancer patients. Meanwhile, the incidence of hepatic or renal impairment in cancer patients is increasing. However, data about the efficacy and safety of ICIs in patients with hepatic or renal impairment are limited. In this review, we characterize and summarize the pharmacokinetics (PK) of ICIs as well as the effects of hepatic or renal function on the PK of ICIs, and provide specific recommendations for clinicians when prescribing ICIs in patients with hepatic or renal impairment.

Dose Adjustment of Poly (ADP­Ribose) Polymerase Inhibitors in Patients with Hepatic or Renal Impairment.

Poly (ADP-ribose) polymerase (PARP) inhibitors are small-molecule inhibitors of PARP enzymes (including PARP1, PARP2, and PARP3) that exhibit activity against tumor cells with defects in DNA repair. In recent years, five PARP inhibitors, olaparib, niraparib, rucaparib, talazoparib and veliparib, have been developed for the treatment of solid tumors, particularly in patients with breast-related cancer antigen (BRCA) 1/2 mutations, or those without a functional homologous recombination repair pathway. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. The five PARP inhibitors are eliminated primarily via the liver and kidneys, hepatic or renal impairment may significantly affect their pharmacokinetics (PK). Therefore, it is important to know the effects of hepatic or renal impairment on the PK and safety of PARP inhibitors. In this review, we characterize and summarize the effects of hepatic and renal function on the PK of PARP inhibitors and provide specific recommendations for clinicians when prescribing PARP inhibitors in patients with hepatic or renal impairment.

Metabolism­related pharmacokinetic drug­drug interactions with poly (ADP­ribose) polymerase inhibitors (Review).

Poly (ADP­ribose) polymerase (PARP) inhibitors, including olaparib, niraparib, rucaparib, talazoparib and veliparib, have emerged as one of the most exciting new treatments for solid tumors, particularly in patients with breast­related cancer antigen 1/2 mutations. Oral administration is convenient and shows favorable compliance with the majority of patients, but it may be affected by numerous factors, including food, metabolic enzymes and transporters. These interactions may be associated with serious adverse drug reactions or may reduce the treatment efficacy of PARP inhibitors. In fact, numerous pharmacokinetic (PK)­based drug­drug interactions (DDIs) involve the metabolism of PARP inhibitors, particularly those metabolized via cytochrome P450 enzymes. The present review aims to characterize and summarize the metabolism­related PK­based DDIs of PARP inhibitors, and to provide specific recommendations for reducing the risk of clinically significant DDIs.

Aidi injection combined with chemotherapy in the treatment of cancer patients: a systematic review of systematic reviews and meta-analyses.

The objective of the study was to evaluate and summarize the evidence from systematic reviews and meta-analyses regarding the efficacy and safety of Aidi injection combined with chemotherapy in the treatment of cancer patients. PubMed, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chong qing VIP databases, and Wanfang databases were searched for systematic reviews/meta-analyses on the topic of Aidi treating cancer patients published from inception to 20 December 2020. Google Scholar and OpenGrey were searched for grey literature and International Prospective Register of Systematic Reviews for ongoing reviews. Two investigators independently selected eligible studies, extracted data, and assessed the methodological quality of included systematic reviews/meta-analyses using the measurement tool to assess systematic reviews 2 (AMSTAR-2) tool, and the strength of evidence was assessed with the grade of recommendation, assessment, development, and evaluation (GRADE) system. Twenty-seven systematic reviews/meta-analyses were identified in the study. The methodological quality of all 27 systematic reviews/meta-analyses were critically low when evaluated by AMSTAR-2, and the evidence quality of all outcomes rated as either low or very low based on the GRADE system. The available evidence is currently insufficient to support or refute the use of Aidi in the treatment of cancer patients, thus high-quality trials with large sample sizes are needed to explore its efficacy and safety in cancer patients.

Dose adjustment for tyrosine kinase inhibitors in non­small cell lung cancer patients with hepatic or renal function impairment (Review).

In recent years, a number of tyrosine kinase inhibitors (TKIs) have been approved for the treatment of non­small cell lung cancer. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. TKIs are administered orally, which has the advantages of improved flexibility and convenience for the patients. However, challenges have arisen in the use of these novel agents. Prescribing drugs for patients with hepatic or renal function impairment poses a challenge for clinicians due to the large pharmacokinetic variability in each individual patient. Moreover, several TKIs have been shown to cause laboratory test abnormalities normally associated with hepatic or renal injury. The aim of the present review was to discuss the effects of hepatic and renal function impairment on the pharmacokinetic variability of 17 TKIs and their potential hepatotoxicity and nephrotoxicity, and to recommend dose adjustment for patients with hepatic or renal impairment.

Elevated Endostatin Expression Is Regulated by the pIgA Immune Complex and Associated with Disease Severity of IgA Nephropathy.

BACKGROUND/AIMS: Renal vascular injury accounts for the poor outcomes of patients with IgA nephropathy (IgAN). In this study, we investigated whether endostatin, a potent inhibitor of angiogenesis, is associated with IgAN. METHODS: Serum endostatin levels were detected in patients with IgAN, disease controls, and healthy controls, and the correlation among endostatin and clinicopathologic manifestations, as well as prognosis in patients with IgAN, was analyzed. In addition, serum endostatin levels were compared in patients "before" and "after" treatment. Data on endostatin expression in the renal interstitium of patients with IgAN were downloaded and analyzed from the GSE35489 array in the GEO database. The poly-IgA1 (pIgA) immune complex is widely recognized as the "trigger" of IgAN initiation. pIgA in the plasma of patients was extracted and used to stimulate human glomerular endothelial cells (GECs). Endostatin, IL-6, and CXCL1 in the cell supernatant were detected by ELISA kits. RESULTS: We found that serum endostatin levels were significantly increased in patients with IgAN, as was endostatin expression in the renal interstitium. Patients with IgAN were divided into 2 groups according to the median value. The high endostatin expression group had significantly higher levels of serum creatinine and BUN and more severe tubular/interstitial damage. Moreover, patients with arteriolar injury and endothelial cell proliferation had higher serum endostatin levels. Patients with high serum endostatin levels had poor prognosis. According to the in vitro experiment, the GEC apoptosis rate and the supernatant levels of endostatin, IL-6, and CXCL1 were significantly increased following pIgA stimulation. CONCLUSION: Our study found that elevated endostatin expression was associated with disease severity and poor prognosis in patients with IgAN and can be upregulated by pIgA, but how it participates in the pathogenesis of IgAN deserves further exploration.

The soluble VEGF receptor sFlt-1 contributes to endothelial dysfunction in IgA nephropathy.

Endothelial injury is a common manifestation in IgA nephropathy (IgAN). After the previous identification of the upregulated soluble fms-like tyrosine kinase-1 (sFlt-1) correlated with endothelial injury in IgAN, in the present study, we further explored the role of sFlt-1 in endothelial injury in IgAN. We enrolled 72 patients with IgAN and detected the sFlt-1 levels. The polymeric IgA1 (pIgA1) complexes were isolated from the pooled plasma samples of another 10 patients with IgAN. Apoptosis proteins were detected in cultured human umbilical vein endothelial cells (HUVECs) with the stimulation of recombinant sFlt-1 or the caspase-9 inhibitor Z-LEHD-FMK. We identified there were positive correlations between sFlt-1 and IgA-IgG complex as well as vWF levels in patients with IgAN. The sFlt-1 levels in HUVECs were significantly upregulated by pIgA1 complex derived from IgAN patients in a concentration-dependent manner. The proliferation ability of HUVECs was damaged when stimulated with sFlt-1 protein in a time- and dose- dependent manner. And the apoptosis rate was up-regulated significantly as the stimulation concentrations of sFlt-1 increased. We found sFlt-1 challenge could significantly increase the expression of vWF. In addition, sFlt-1 increased the levels of caspase-9, caspase-3, Bax and mitochondrial membrane potential; facilitated the release of cytochrome C from mitochondria to cytoplasma. In contrast, Z-LEHD-FMK attenuated high sFlt-1-induced HUVECs apoptosis. In conclusion, our study demonstrated that sFlt-1 expression was up-regulated by the challenge of pIgA1 complex derived from patients with IgAN. Furthermore, increased sFlt-1 facilitated human umbilical vein endothelial cells apoptosis via the mitochondrial-dependent pathway.

Pharmacokinetic-Based Drug-Drug Interactions with Anaplastic Lymphoma Kinase Inhibitors: A Review.

Anaplastic lymphoma kinase (ALK) inhibitors are important treatment options for non-small-cell lung cancer (NSCLC), associated with ALK gene rearrangement. Patients with ALK gene rearrangement show sensitivity to and benefit clinically from treatment with ALK tyrosine kinase inhibitors (ALK-TKIs). To date, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, and entrectinib have received approval from the US Food and Drug Administration and/or the European Medicines Agency for use during the treatment of ALK-gene-rearrangement forms of NSCLC. Although the oral route of administration is convenient and results in good compliance among patients, oral administration can be affected by many factors, such as food, intragastric pH, cytochrome P450 enzymes, transporters, and p-glycoprotein. These factors can result in increased risks for serious adverse events or can lead to reduced therapeutic effects of ALK-TKIs. This review characterizes and summarizes the pharmacokinetic parameters and drug--drug interactions associated with ALK-TKIs to provide specific recommendations for oncologists and clinical pharmacists when prescribing ALK-TKIs.

Age is not a barrier to good outcomes following ambulatory high ligation and stripping for varicose veins: A prospective cohort study.

This was a prospective cohort study with a short-term follow-up. To explore whether age is a factor in the prognosis following high ligation and stripping (HLS) performed in an ambulatory care center. This study included 170 patients who underwent their first HLS for varicose veins in an ambulatory center from November 2016 to October 2017 at West China Hospital. The patients were categorized as two groups: the ≤60 years old group and the >60 years old group. We collected the two age groups data included Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification, Venous Clinical Severity Score (VCSS), Visual Analogue Score (VAS), Aberdeen Varicose Veins Questionnaire (AVVQ), Quality of Recovery (QoR-15), and postoperative complications at predetermined time points. The clinical correlation between age and prognosis following HLS in an ambulatory care center was prospectively studied after adjusting for potential confounders. The distribution of age and prognosis were also compared in the AVVQ improvement and VCSS improvement of patients at 6 weeks and 6 months after surgery. Our research comprised a total of 170 patients (236 limbs), of which 86 (50.6%) patients were female and 66 (38.8%) patients received bilateral procedures. After multivariable risk adjustment for potential confounding factors, we observed that age was not associated with the improvement of AVVQ (OR 0.3, 95%CI (1.3, 0.7), P = .54) and VCSS (OR 0.2, 95%CI (0.2, 0.6) P = .38) at 6 months after HLS, as well as AVVQ (OR 0.5,95%CI (1.2, 2.2), P = .57) at 6 weeks after HLS. However, at 6 weeks after HLS, age was related to the improvement of VCSS (OR -0.6, 95%CI (1.2, 0.1), P = .03), with the >60 years old group having a lower VCSS improvement compared to the 60 years old group. In postoperative complications, there were no significant differences in terms of complications between the two age groups (all P value >.05). Therefore, in our opinion, age is not a barrier for good outcomes following HLS in an ambulatory care center.

Elevated hsa-miR-590-3p expression down-regulates HMGB2 expression and contributes to the severity of IgA nephropathy.

Peripheral blood mononuclear cells (PBMCs) play important roles in the pathogenesis of IgA nephropathy (IgAN). Our study aimed to provide a deep understanding of IgAN and focused on the dysregulation of hsa-miR-590-3p and its target gene HMGB2 in PBMCs. Three gene expression profile datasets (GSE14795, GSE73953 and GSE25590) were downloaded from the GEO database. The DEGs (differentially expressed genes)-miRNA network that was associated with IgAN was constructed by Cytoscape, and HMGB2 and hsa-miR-590-3p were selected for further exploration. The dual-luciferase reporter system was utilized to verify their interaction. Then, the expression levels of HMGB2 and hsa-miR-590-3p in PBMCs were detected by qPCR in another cohort, and the correlation of their expression levels with the clinical pathological manifestations and serum Gd-IgA1(galactose-deficient IgA1) levels was also investigated. HMGB2 was identified as the target gene of hsa-miR-590-3p. Furtherly, the elderly patients had higher HMGB2 expression levels than the expression levels of the younger patients. As the serum creatinine, serum BUN levels increased, the expression of HMGB2 decreased; Besides, the HMGB2 expression was positively correlated with serum complement 3(C3) levels, and it also had a negative correlation with the diastolic blood pressure, but not reach statistical significance. What is more, both hsa-miR-590-3p and HMGB2 expression had a slight correlation tendency with serum Gd-IgA1 levels in the whole population. In conclusion, HMGB2, the target gene of hsa-miR-590-3p, was identified to correlate with the severity of IgAN, and this provides more clues for the pathogenesis of IgAN.

Atrial fibrillation following treatment with paclitaxel: A case report.

Paclitaxel (PTX) is an antimicrotubule agent, and is effective in treating a wide range of solid tumors. However, its use may lead to cardiovascular toxicities, the manifestations of which include arrhythmia, heart failure, acute myocardial ischemia and atrial fibrillation (AF). AF is among the severe reactions to the PTX cardiotoxicity, and a cause for substantial morbidity and mortality. However, the incidence of PTX-induced AF is reportedly low (1.0-1.7% worldwide), and few cases have been reported in the literature. Thus, to emphasize the need for awareness of this side effect of PTX among clinicians, the report herein presents a case of AF induced by PTX in a patient with non-small-cell carcinoma. A 51-year-old man experienced AF following treatment with PTX. Amiodarone and metoprolol were administered to the patient to control cardiac rhythm and rate. After 3 days, the electrocardiogram was normalized and indicated normal heart rate and rhythm. According to this case, thorough attention should be paid during PTX treatment to monitor for signs of AF or other abnormalities in cardiac function.