Biomed Pharmacother. 2022 Sep;153:113376. doi: 10.1016/j.biopha.2022.113376. Epub 2022 Jul 12.

ABSTRACT

Metabolic reprogramming is one of the most prominent features underlying cancer cells progression and metastasis.Traditional Chinese medicine (TCM) has been widely used in the clinical treatment of cancer, with the advantages of multi-pathway, multi-target, multi-component anti-tumor pharmacological effects and low risk of adverse effects. However, the mechanisms underlying the anti-tumor effects of TCM are not fully understood, especially on cellular metabolic reprogramming. In this review, we summarize the role of glucose, lipid and amino acid metabolism in cancer metastasis, which is key in cancer cells and tumor micro-environment (TME) cell metabolism. Furthermore, we reviewed the potential mechanisms by which, most bioactive TCM compounds suppress cancer metastasis by regulating metabolic reprogramming and the possibility of sensitizing other anti-tumor drugs. TCM and its bioactive compounds have huge prospects for clinical application in the treatment of cancer metastasis. Unfortunately, little is currently known about the regulatory effects of Chinese herbal medicines and their bioactive compounds on the metabolic reprogramming of cancer cells and the combination therapy for cancers. This review provides novel insights into the regulation of metabolic reprogramming by TCM in combination with other anti-tumor drugs against cancer metastasis and the possibility of becoming sensitizers for other anti-tumor drugs.

PMID:36076519 | DOI:10.1016/j.biopha.2022.113376

Biomed Pharmacother. 2022 Sep;153:113401. doi: 10.1016/j.biopha.2022.113401. Epub 2022 Jul 16.

ABSTRACT

Ovarian cancer is one of the three most common female reproductive system cancers and has been a hot topic in the field of gynecology and oncology. Currently, surgery with chemotherapy is the common strategy in treatment of ovarian cancer, while it is always accompanied by drug resistance and some adverse effects. Over the past few years, traditional Chinese medicine (TCM) has been embraced by a large population of clinicians and researchers due to its high efficiency, low toxicity and minor side effects. Guizhi-Fuling Wan as a classical TCM formula has manifested certain efficacy in treating ovarian cancer. This article intends to further study the role and mechanism of Guizhi-Fuling Wan in treatment of ovarian cancer and explore the effective chemical components contained in the herbs of the formula. To this end, we reviewed the previous clinical studies and experiments to analyze the molecular mechanisms, pharmacological effects, active chemical components and their targets of action in treatment of ovarian cancer, thereby providing a theoretic basis for future studies and practices.

PMID:36076526 | DOI:10.1016/j.biopha.2022.113401

J Tradit Chin Med. 2022 Oct;42(5):810-817. doi: 10.19852/j.cnki.jtcm.20220719.004.

ABSTRACT

OBJECTIVE: To investigate the clinical efficacy of Fufang Huangqi decoction in combination with pyridostigmine bromide tablets, prednisone, and tacrolimus in the treatment of type I and II myasthenia gravis (MG) through changes in the clinical symptom scores of 100 patients with type I and II MG. This study also aimed to examine dose reductions and dis-continuation of these 3 Western medicines after administration of Fufang Huangqi decoction.

METHODS: The clinical data on 100 patients with type I or II MG who were treated in the outpatient department of the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, China, between June 2017 and June 2020 were collected. The patients were divided into 4 groups based on whether they had taken pyridostigmine bromide tablets, prednisone, and/or tacrolimus at the time of their hospital visit: the Fufang Huangqi decoction group (group A), the pyridostigmine bromide tablets + Fufang Huangqi decoction group (group B), the pyridostigmine bromide tablets + prednisone + Fufang Huangqi decoction group (group C), and the pyridostigmine bromide tablets + tacrolimus + Fufang Huangqi decoction group (group D). The average treatment time was (15.6 ± 11.5) months (range: 0.5-55 months). Changes in the clinical symptom scores of the 4 groups of patients after medication administration and dose reductions and discontinuation of the 3 Western medicines were analyzed.

RESULTS: An overall effectiveness rate of 86.00% was achieved in the 100 patients after treatment for (15.6 ± 11.5) months (range 0.5-55 months). The effectiveness rates were 85.71% in group A, 88.24% in group B, 76.92% in group C, and 80.00% in group D. The dosage of pyridostigmine bromide was reduced for 69.12% of the patients in group B for the first time after (4.2 ± 4.1) months, and 45.59% of the patients in group B discontinued pyridostigmine bromide after (8.8 ± 6.1) months. The dosage of pyridostigmine bromide was reduced for 46.15% of the patients in group C for the first time after (5.3 ± 3.4) months, and 23.08% of the patients in group C discontinued pyridostigmine bromide after (19.8 ± 11.0) months; 76.92% reduced hormone dosage after (2.8 ± 1.9) months, and 23.08% discontinued hormone treatment after (6.7 ± 2.9) months. The dosage of pyridostigmine bromide was reduced for 1 patient in group D after 1 month; this patient discontinued pyridostigmine bromide after 3 months and reduced tacrolimus dosage after 5 months. One patient in group D discontinued pyridostigmine bromide and tacrolimus on his own initiative at 0.5 months and took Fufang Huangqi decoction for 2 months without discontinuing Western medicine.

CONCLUSION: Fufang Huangqi decoction is effective for the treatment of type I and II MG and improves the associated clinical symptoms. Moreover, this agent is conducive to dose reductions and discontinuation of basic Western medicines, thereby reducing the side effects experienced by patients.

PMID:36083490 | DOI:10.19852/j.cnki.jtcm.20220719.004

Eur Stroke J. 2022 Sep;7(3):314-322. doi: 10.1177/23969873221098857. Epub 2022 May 27.

ABSTRACT

BACKGROUND: Current evidence suggest that 25%-33% of stroke-survivors develop post-stroke cognitive impairment (PSCI). The licensed drug Maraviroc, a CCR5-antagonist, is postulated to act via a neuroprotective mechanism that may offer the potential of preventing progression to vascular dementia. Our hypothesis: Maraviroc may have the potential to augment learning skills and cognitive performance by affecting synaptic plasticity, along with neuro-inflammatory modulation in patients with cerebral small vessel disease (SVD) and PSCI.

DESIGN: MARCH is a multi-center, double-blind randomized-control Phase-II trial of Maraviroc 150 or 600 mg/day versus placebo for 12-months in five stroke centers in Israel. Included are patients diagnosed with recent (1-24 months) subcortical stroke who experience mild PSCI and have evidence of white matter lesions and SVD on neuroimaging.

OUTCOMES: Primary outcomes: 1. Change in cognitive scores. 2. Drug related adverse events. Secondary outcomes: change in functional and affective scores, MRI-derived measures, inflammatory markers, carotid atherosclerosis, cerebrospinal-fluid biomarkers in a sub-study. A sample size of 60 in each treatment group and 30 in the placebo group (total - 150 participants) provides 80% power between the treatment and the placebo groups.

CONCLUSIONS: The results of this work could lead to a novel, readily available, therapeutic avenue to reduce PSCI, and possibly other pathologies. This study will test safety and effectiveness of Maraviroc in limiting cognitive deterioration and/or post stroke cognitive impairment in patients with cerebral small vessel disease.

SCHEDULE: First-patient first-visit was May 2021. Recruitment to complete in 2023, follow-up to complete in 2024.

PMID:36082248 | PMC:PMC9446318 | DOI:10.1177/23969873221098857

Front Pharmacol. 2022 Aug 23;13:953641. doi: 10.3389/fphar.2022.953641. eCollection 2022.

ABSTRACT

Purpose: This is the first study to compare the pharmacokinetics, safety and, immunogenicity of QL1209, a biosimilar of Perjeta®. Methods: This study was a randomized, double-blind, parallel-controlled clinical trial evaluating the biosimilarity between QL1209 (specification: 420 mg:14 ml, single use via, manufacturer: Qilu Pharmaceutical Co., Ltd., batch number: 201808001KJL) and Perjeta® (specification: 420 mg: 14 ml, single use via, manufacturer: Roche Pharma AG, batch number: H0309H02). The trial period was 99 days (blood samples for PK were collected 99 days after infusion). Serum concentrations were determined using a validated assay. PK parameters were calculated using a non-compartmental model and analyzed statistically. Anti-drug antibody (ADA)-positive samples were further tested for the presence of neutralization antibody detection (NAb). Results: A total of 137 healthy subjects were administrated. The subjects were randomized 1:1 to receive QL1209 or Perjeta® 420 mg intravenously. The geometric mean ratio (GMRs) for QL1209 versus Perjeta® are 104.14%, 104.09%, and 110.59% for Cmax, AUC0-t, and AUC0-∞, respectively, and their 90% confidence interval (CIs) all fell within the predefined bioequivalence margin 80.00-125%. The incidence of drug-related adverse events was 95.6% and 95.5% in the QL1209 and Perjeta® groups, respectively, also comparable between the two groups. Conclusion: The results of this comparative clinical pharmacology study demonstrated the PK similarity of QL1209 (420 mg: 14 ml) and Perjeta® (420 mg: 14 ml) and there was no significant difference in safety and immunogenicity between QL1209 and Perjeta® manufactured by Roche Pharma AG.

PMID:36081953 | PMC:PMC9445216 | DOI:10.3389/fphar.2022.953641

Biomed Pharmacother. 2022 Sep;153:113425. doi: 10.1016/j.biopha.2022.113425. Epub 2022 Jul 18.

ABSTRACT

Naoqingzhiming, whose active ingredient is echinacoside, is the first new Class I natural medicine approved for clinical trials for the therapeutic potential of vascular dementia in China. We report randomized, double-blind, placebo-controlled trials to evaluate the safety, tolerability and pharmacokinetics of single ascending doses of Naoqingzhiming tablet after oral administration in healthy Chinese subjects. The single ascending dose of Naoqingzhiming tablet (180-2160 mg) were well tolerated in all enrolled subjects, without serious adverse events and adverse events leading to withdrawal from the study. The most common drug-related treatment-emergent adverse events were elevated blood bilirubin and serum uric acid. No clinically significant findings were found in the physical examinations, vital signs or electrocardiograms. After single-dose administration of Naoqingzhiming tablet, echinacoside was absorbed with a Tmax at 1.25-1.75 h and declined with a t1/2 of 2.42-3.33 h. However, the proportionality coefficients for Cmax, AUC0-t and AUC0-∞ of echinacoside were not fully contained in the pre-defined 90 % CI criterion (0.91-1.09). As a result, the dose proportionality could not be concluded statistically within the dosage range of this study. Overall, the safety profile and PK properties support further development and use of Naoqingzhiming in vascular dementia.

PMID:36076546 | DOI:10.1016/j.biopha.2022.113425

Ment Health Clin. 2022 Aug 23;12(4):263-266. doi: 10.9740/mhc.2022.08.263. eCollection 2022 Aug.

ABSTRACT

BACKGROUND: Long-acting injectable medications have become an important tool in the treatment of schizophrenia and schizoaffective disorder due to the high rates of medication nonadherence. Olanzapine long-acting injection (OLAI) is a useful therapeutic option for patients who have good tolerability and efficacy to oral olanzapine. Postinjection delirium/sedation syndrome (PDSS) is a rare but potentially serious event with the proposed mechanism of inadvertent intravascular injection of OLAI. This concern necessitates the requirement of a 3-hour monitoring period postinjection. Based on a literature review, there are no clearly defined risk factors for developing PDSS.

CASE REPORT: A case is presented that describes PDSS in a transgender man undergoing hormone therapy with testosterone. The patient received OLAI for more than 3 years and developed PDSS 9 months after the initiation of injectable testosterone.

DISCUSSION: There are published case reports of PDSS with the use of OLAI; however, there are no documented cases in a patient undergoing concurrent testosterone therapy. The effect that testosterone has on the vascular system and how it may alter the pharmacokinetics of OLAI has not been studied.

CONCLUSION: Despite proper injection technique, PDSS can occur after injection with OLAI. Further research is necessary to identify specific risk factors for the development of PDSS, including the potential effect that hormone therapy may have.

PMID:36071735 | PMC:PMC9405634 | DOI:10.9740/mhc.2022.08.263

PLoS Comput Biol. 2022 Sep 7;18(9):e1010402. doi: 10.1371/journal.pcbi.1010402. eCollection 2022 Sep.

ABSTRACT

Drug-induced toxicity damages the health and is one of the key factors causing drug withdrawal from the market. It is of great significance to identify drug-induced target-organ toxicity, especially the detailed pathological findings, which are crucial for toxicity assessment, in the early stage of drug development process. A large variety of studies have devoted to identify drug toxicity. However, most of them are limited to single organ or only binary toxicity. Here we proposed a novel multi-label learning model named Att-RethinkNet, for predicting drug-induced pathological findings targeted on liver and kidney based on toxicogenomics data. The Att-RethinkNet is equipped with a memory structure and can effectively use the label association information. Besides, attention mechanism is embedded to focus on the important features and obtain better feature presentation. Our Att-RethinkNet is applicable in multiple organs and takes account the compound type, dose, and administration time, so it is more comprehensive and generalized. And more importantly, it predicts multiple pathological findings at the same time, instead of predicting each pathology separately as the previous model did. To demonstrate the effectiveness of the proposed model, we compared the proposed method with a series of state-of-the-arts methods. Our model shows competitive performance and can predict potential hepatotoxicity and nephrotoxicity in a more accurate and reliable way. The implementation of the proposed method is available at https://github.com/RanSuLab/Drug-Toxicity-Prediction-MultiLabel.

PMID:36070305 | PMC:PMC9451100 | DOI:10.1371/journal.pcbi.1010402

J Clin Oncol. 2022 Sep 7:JCO2200291. doi: 10.1200/JCO.22.00291. Online ahead of print.

ABSTRACT

PURPOSE: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.

METHODS: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light.

RESULTS: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported.

CONCLUSION: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

PMID:36070540 | DOI:10.1200/JCO.22.00291

Pharmacogenomics. 2022 Sep 7. doi: 10.2217/pgs-2022-0074. Online ahead of print.

ABSTRACT

Aim: A follow-up genome-wide association study (GWAS) in an extended cohort of rheumatoid arthritis (RA) patients starting low-dose methotrexate (MTX) treatment was performed to identify further genetic variants associated with alanine aminotransferase (ALT) elevation. Patients & methods: A GWAS was performed on 346 RA patients. Two outcomes within the first 6 months of MTX treatment were assessed: ALT >1.5-times the upper level of normal (ULN) and maximum level of ALT. Results: SPATA9 (rs72783407) was significantly associated with maximum level of ALT (p = 2.58 × 10-8) and PLCG2 (rs60427389) was tentatively associated with ALT >1.5 × ULN. Conclusion: Associations with SNPs in genes related to male fertility (SPATA9) and inflammatory processes (PLCG2) were identified.

PMID:36070248 | DOI:10.2217/pgs-2022-0074

Adv Ther. 2022 Sep 7. doi: 10.1007/s12325-022-02294-z. Online ahead of print.

ABSTRACT

INTRODUCTION: Clinical data of esaxerenone in hypertensive patients with diabetic kidney disease (DKD) are lacking. We evaluated the efficacy and safety of esaxerenone in patients with DKD and an inadequate response to blood pressure (BP)-lowering treatment.

METHODS: In this multicenter, open-label, prospective study, patients were divided into urinary albumin-to-creatinine ratio subcohorts (UACR < 30, 30 to < 300, and 300 to < 1000 mg/gCr). Esaxerenone was initiated at 1.25 mg/day and followed by incremental dose escalation based on BP and serum potassium level monitoring. The treatment period was 12 weeks. The primary endpoint was change in morning home systolic BP/diastolic BP (SBP/DBP) from baseline to end of treatment (EOT). Secondary endpoints included achievement rate of target BP, change in UACR from baseline, and safety.

RESULTS: In total, 113 patients were enrolled. Morning home SBP/DBP significantly decreased from baseline to EOT in the total population (- 11.6/- 5.2 mmHg, both p < 0.001) and in all UACR subcohorts (all p < 0.001). The target BP achievement rate was 38.5%. Significant reductions in bedtime home and office BPs were also shown in the total population and all UACR subcohorts. UACR significantly improved from baseline to EOT in the total (- 50.9%, p < 0.001) and all UACR subcohorts (all p < 0.001). Incidence of serum potassium elevation as drug-related treatment emergent adverse events was 2.7%. The change from baseline in estimated glomerular filtration rate (eGFR) was - 4.8 mL/min/1.73 m2.

CONCLUSION: Esaxerenone demonstrated a BP-lowering effect and improved albuminuria. The effects were consistent regardless of the severity of albuminuria without clinically relevant serum potassium elevation and eGFR reduction.

CLINICAL TRIAL REGISTRATION: jRCTs06119002.

PMID:36070133 | DOI:10.1007/s12325-022-02294-z

Methods Mol Biol. 2022;2547:201-240. doi: 10.1007/978-1-0716-2573-6_9.

ABSTRACT

Precision medicine exemplifies the emergence of personalized treatment options which may benefit specific patient populations based upon their genetic makeup. Application of pharmacogenomics requires an understanding of how genetic variations impact pharmacokinetic and pharmacodynamic properties. This particular approach in pharmacotherapy is helpful because it can assist in and improve clinical decisions. Application of pharmacogenomics to cardiovascular pharmacotherapy provides for the ability of the medical provider to gain critical knowledge on a patient's response to various treatment options and risk of side effects.

PMID:36068466 | DOI:10.1007/978-1-0716-2573-6_9

Methods Mol Biol. 2022;2547:95-140. doi: 10.1007/978-1-0716-2573-6_5.

ABSTRACT

Pharmacogenomics is a powerful tool to predict individual response to treatment, in order to personalize therapy, and it has been explored extensively in oncology practice. Not only efficacy on the malignant disease has been investigated but also the possibility to predict adverse effects due to drug administration. Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of those. This potentially severe and long-lasting/permanent side effect of commonly administered anticancer drugs can severely impair quality of life (QoL) in a large cohort of long survival patients. So far, a pharmacogenomics-based approach in CIPN regard has been quite delusive, making a methodological improvement warranted in this field of interest: even the most refined genetic analysis cannot be effective if not applied correctly. Here we try to devise why it is so, suggesting how THE "bench-side" (pharmacogenomics) might benefit from and should cooperate with THE "bed-side" (clinimetrics), in order to make genetic profiling effective if applied to CIPN.

PMID:36068462 | DOI:10.1007/978-1-0716-2573-6_5

Comput Math Methods Med. 2022 Aug 27;2022:5666067. doi: 10.1155/2022/5666067. eCollection 2022.

ABSTRACT

OBJECTIVE: To compare the clinical efficacy and adverse drug reactions of four different schemes in the treatment of pleural tuberculoma.

METHODS: A total of 120 patients with pleural tuberculoma admitted to the Tuberculosis Department of our hospital from January 2018 to January 2021 were selected as the research subjects. According to different treatment methods, the patients were divided into four groups, with 30 cases in each group. They were as follows: group A received classical HRZE regimen, group B received HRZE+pleural injection, group C received HZE+rifabutin, and group D received HZE+rifabutin+pleural injection. All patients were treated intensively for 3 months and then consolidated treatment for 6 months according to the patient's condition. The absorption of lesions in the four groups at different time was compared, and the occurrences of adverse drug reactions and treatment outcomes during treatment were recorded.

RESULTS: After 3 months of treatment, compared with groups A, B, and C, the number of significantly absorbed cases and effective cases in group D increased, while the number of invalid cases decreased. However, there was no statistical significance in the absorption of lesions between the four groups (χ 2 = 8.272, P = 0.507). In addition, pairwise comparison showed no significant difference in the absorption of lesions (P > 0.05). After 9 months of treatment, there was no significant difference in the absorption of lesions among the four groups (χ 2 = 8.795, P = 0.185), but the absorption of lesions in group D was significantly better than that in group A (P < 0.05). During treatment, the incidence of adverse reactions in the four groups was significantly different (χ 2 = 8.779, P = 0.032). Pairwise comparison showed that the incidence of adverse reactions in groups C and D was significantly lower than that in group A (P < 0.05). The total treatment course of group A was 9-16 months, and 10 cases (33.33%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group B was 9-12 months, and 7 cases (23.33%) still had residual lesions or pleural thickening at the end of the course of treatment. The total treatment course of group C was 9-16 months, and 8 cases (26.67%) still had residual lesions or pleural thickening at the end of treatment. The total course of treatment in group D was 9-12months, and there were still 2 cases of residual lesions (6.67%) at the end of the course.

CONCLUSIONS: HZE+rifabutin+pleural injection against tuberculosis therapy has a significant clinical efficacy in the treatment of pleural tuberculoma, which can more effectively improve the clinical symptoms of patients, improve the efficacy, and reduce complications, with a good prognosis, worthy of clinical promotion.

PMID:36065379 | PMC:PMC9440828 | DOI:10.1155/2022/5666067

Circulation. 2022 Sep 6;146(10):802-804. doi: 10.1161/CIRCULATIONAHA.122.060961. Epub 2022 Sep 6.

NO ABSTRACT

PMID:36067275 | DOI:10.1161/CIRCULATIONAHA.122.060961

Epidemiol Rev. 2022 Sep 5:mxac005. doi: 10.1093/epirev/mxac005. Online ahead of print.

ABSTRACT

In clinical trials, harms (adverse events) are often reported by simply counting the number of people who experienced each event. Reporting only frequencies ignores other dimensions of the data that are important for stakeholders, including severity, seriousness, rate (recurrence), timing, and groups of related harms. Additionally, application of selection criteria to harms prevents most from being reported. Visualization of data could improve communication of multidimensional data. We replicated and compared the characteristics of six different approaches for visualizing harms-Dot Plot, Stacked Bar Chart, Volcano Plot, Heatmap, Treemap, and Tendril Plot. We considered binary events using individual participant data (IPD) from a randomized trial of gabapentin for neuropathic pain. We assessed their value using a heuristic approach and group of content experts. We produced all figures using R and share the open-source code on GitHub. Most original visualizations propose presenting individual harms (e.g., dizziness, somnolence) alone or alongside higher level (e.g., by body systems) summaries of harms, although they could be applied at either level. Visualizations are able to present different dimensions of all harms observed in trials. Except for the Tendril plot, all other plots do not require IPD. The Dot Plot and Volcano Plot are favoured as visualization approaches to present an overall summary of harms data. Our value assessment found the Dot Plot and Volcano Plot were favoured by content experts. Using visualizations to report harms could improve communication. Trialists can use our provided code to easily implement these approaches.

PMID:36065832 | DOI:10.1093/epirev/mxac005

Front Public Health. 2022 Aug 11;10:930696. doi: 10.3389/fpubh.2022.930696. eCollection 2022.

ABSTRACT

Adverse drug reactions (ADRs) are major concerns to the public health. To monitor ADRs and ensure patients' safety, the Pharmacovigilance Programme of India (PvPI) has been established by the Government of India in 2010. The programme is intact with the Public-Private Partnership (3Ps) in pharmacovigilance for quality services, better management of human resources and risk minimization. The present work is aimed at assessing the 3Ps engagement, performance and tangible outcomes in PvPI and also mapping of resources. The study was carried out for the period of 2011 to 2021 by assessing the various benchmarking tools such as 3Ps categorization, utilization of ADRs reporting tools, trainings, and the Individual Case Safety Reports' (ICSRs) quantity, quality and transmission for regulatory intervention (RI). Under PvPI, Central or State Government medical institutions/hospitals and public health programmes constitute public partners while private medical institutions/hospitals, pharmaceutical companies, corporate hospitals and professional bodies account for private partners. We observed that public partners extensively used ADR reporting form and toll-free helpline number while private partners used mobile based app and emails/post as preferred tools for reporting ADRs. Contribution of public sector in training programmes organized, stakeholders trained and sharing of resource materials was way higher than the private sector. The study revealed that 55.1 and 44.9% ICSRs were received from public and private partners, respectively during the study period. The quality completeness of data received from public partners was found to be 0.92/1 as compared to 0.46/1 from the private partners. The ICSRs data transmitted for RI process from the public and private partners (till 2018) was found to be 79 and 21%, respectively. In terms of sharing of resources for training and capacity building, the public sector played a major role. The 3Ps in India are enabled to establish a robust system for medicines' safety surveillance; however a more focused approach is required in mapping the resources.

PMID:36062131 | PMC:PMC9435468 | DOI:10.3389/fpubh.2022.930696

Front Pharmacol. 2022 Aug 17;13:966910. doi: 10.3389/fphar.2022.966910. eCollection 2022.

ABSTRACT

Potassium para-aminobenzoate (POTABA) is used to treat Peyronie's disease by decreasing fibrosis and plaque size progression. Among potential side effects, drug-induced liver injury (DILI) attributed to POTABA administration has been reported in a few cases and inferred to immune hypersensitivity. In the present case, we investigated clinical, biochemical, and serological features as well as searched for non-drug-related causes, and applied the updated Roussel Uclaf Causality Assessment Method (RUCAM) confirming a highly probable causality of POTABA-induced liver injury. Moreover, we here observed specific activated CD3+ T lymphocytes during the acute phase of liver injury by monitoring of human leukocyte antigen receptor (HLA-DR) expression. Furthermore, improvement of biochemical markers of liver injury after POTABA withdrawal was associated with a rapid decline of CD3+ HLA-DR+ immune cells. In contrast, CD14+ monocytes expressing HLA-DR remained stable during recovery from liver injury. These observations implicate a specific involvement of activated T lymphocytes in liver injury mediated by POTABA. Clinicians should be aware of POTABA-induced liver injury, and measurement of activated immune cells by assessment of HLA-DR could provide pathomechanistic insights enabling biomonitoring of recovery from DILI.

PMID:36059975 | PMC:PMC9428317 | DOI:10.3389/fphar.2022.966910

Front Immunol. 2022 Aug 19;13:979983. doi: 10.3389/fimmu.2022.979983. eCollection 2022.

ABSTRACT

BACKGROUND: Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical.

METHODS: This retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis.

RESULTS: The onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A.

CONCLUSIONS: For the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.

PMID:36059468 | PMC:PMC9437944 | DOI:10.3389/fimmu.2022.979983

J Pediatr. 2022 Aug;247:123. doi: 10.1016/j.jpeds.2022.05.051.

NO ABSTRACT

PMID:36058594 | DOI:10.1016/j.jpeds.2022.05.051