Front Endocrinol (Lausanne). 2023 Mar 23;14:1149256. doi: 10.3389/fendo.2023.1149256. eCollection 2023.

ABSTRACT

Type 2 diabetes mellitus (T2DM), a major driver of mortality worldwide, is more likely to develop other cardiometabolic risk factors, ultimately leading to diabetes-related mortality. Although a set of measures including lifestyle intervention and antidiabetic drugs have been proposed to manage T2DM, problems associated with potential side-effects and drug resistance are still unresolved. Pharmacomicrobiomics is an emerging field that investigates the interactions between the gut microbiome and drug response variability or drug toxicity. In recent years, increasing evidence supports that the gut microbiome, as the second genome, can serve as an attractive target for improving drug efficacy and safety by manipulating its composition. In this review, we outline the different composition of gut microbiome in T2DM and highlight how these microbiomes actually play a vital role in its development. Furthermore, we also investigate current state-of-the-art knowledge on pharmacomicrobiomics and microbiome's role in modulating the response to antidiabetic drugs, as well as provide innovative potential personalized treatments, including approaches for predicting response to treatment and for modulating the microbiome to improve drug efficacy or reduce drug toxicity.

PMID:37033254 | PMC:PMC10076675 | DOI:10.3389/fendo.2023.1149256

J Am Med Dir Assoc. 2023 Apr 7:S1525-8610(23)00282-7. doi: 10.1016/j.jamda.2023.03.003. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate properties of psychotropic adverse drug event (ADE) monitoring tools intended for use in long-term care facilities.

DESIGN: Systematic review.

SETTING AND PARTICIPANTS: Adults aged 18 years and older in nursing homes and other long-term care facilities.

METHODS: Medline, CINAHL, Embase, and PsycInfo were searched from inception to August 2022 for studies reporting the development, validation, or application of tools to monitor psychotropic ADEs. Screening, data extraction, and quality assessment were performed independently by 2 authors. Each tool was assessed under the domains of test-retest reliability, interrater reliability, content validity, and construct validity.

RESULTS: Eight studies that described 6 tools were included. Tools were developed in Wales (n = 2), United States (n = 1), Ireland (n = 1), Canada (n = 1), and Singapore (n = 1). Tools monitored 4 to 95 items related to antipsychotics (n = 6 tools), antidepressants (n = 4), benzodiazepines or hypnotics (n = 4), antiepileptics (n = 4), and dementia medications (n = 1). Tools commonly monitored sedation, tiredness, or sleepiness (n = 6); falls (n = 4); and tremor or extrapyramidal symptoms (n = 4). Tools were designed for application by nurses (n = 4), during family conferences (n = 1), and by general medical practitioners before repeat prescribing (n = 1). Two tools were reported to require 10 to 60 minutes to administer. Four tools were determined to have adequate content validity and 2 tools adequate interrater reliability. No tools reported test-retest reliability or construct validity.

CONCLUSIONS AND IMPLICATIONS: Six published psychotropic ADE monitoring tools are heterogeneous in design and intended application. Existing tools are predominately designed for application by nurses with or without direct involvement of the wider multidisciplinary team. Further research is needed into models of care that facilitate psychotropic ADE monitoring in the long-term care facility setting, and the extent to which application of specific tools is associated with reduced medication-related harm.

PMID:37037347 | DOI:10.1016/j.jamda.2023.03.003

Front Med (Lausanne). 2023 Mar 23;10:1159453. doi: 10.3389/fmed.2023.1159453. eCollection 2023.

ABSTRACT

INTRODUCTION: Inverse signals produced from disproportional analyses using spontaneous drug adverse event reports can be used for drug repositioning purposes. The purpose of this study is to predict drug candidates using a computational method that integrates reported drug adverse event data, disease-specific gene expression profiles, and drug-induced gene expression profiles.

METHODS: Drug and adverse events from 2015 through 2020 were downloaded from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), information component (IC) and empirical Bayes geometric mean (EBGM) were used to calculate the inverse signals. Psoriasis was selected as the target disease. Disease specific gene expression profiles were obtained by the meta-analysis of the Gene Expression Omnibus (GEO). The reverse gene expression scores were calculated using the Library of Integrated Network-based Cellular Signatures (LINCS) and their correlations with the inverse signals were obtained.

RESULTS: Reversal genes and the candidate compounds were identified. Additionally, these correlations were validated using the relationship between the reverse gene expression scores and the half-maximal inhibitory concentration (IC50) values from the Chemical European Molecular Biology Laboratory (ChEMBL).

CONCLUSION: Inverse signals produced from a disproportional analysis can be used for drug repositioning and to predict drug candidates against psoriasis.

PMID:37035327 | PMC:PMC10076533 | DOI:10.3389/fmed.2023.1159453

Front Immunol. 2023 Mar 21;14:1135701. doi: 10.3389/fimmu.2023.1135701. eCollection 2023.

ABSTRACT

INTRODUCTION: The mechanism of the immediate adverse drug reactions (ADRs) induced by ShenMai injection (SMI) has not been completely elucidated. Within 30 minutes, the ears and lungs of mice injected with SMI for the first time showed edema and exudation reactions. These reactions were different from the IV hypersensitivity. The theory of pharmacological interaction with immune receptor (p-i) offered a new insight into the mechanisms of immediate ADRs induced by SMI.

METHODS: In this study, we determined that the ADRs were mediated by thymus-derived T cells through the different reactions of BALB/c mice (thymus-derived T cell normal) and BALB/c nude mice (thymus-derived T cell deficient) after injecting SMI. The flow cytometric analysis, cytokine bead array (CBA) assay and untargeted metabolomics were used to explain the mechanisms of the immediate ADRs. Moreover, the activation of the RhoA/ROCK signaling pathway was detected by western blot analysis.

RESULTS: In BALB/c mice, the vascular leakage and histopathology results showed the occurrence of the immediate ADRs induced by SMI. The flow cytometric analysis revealed that CD4+ T cell subsets (Th1/Th2, Th17/Treg) were imbalanced. And the levels of cytokines such as IL-2, IL-4, IL12P70 and INF-γ increased significantly. However, in BALB/c nude mice, all the indicators mentioned above have not changed significantly. The metabolic profile of both BALB/c mice and BALB/c nude mice was significantly changed after injecting SMI, and the notable increase in lysolecithin level might have a greater association with the immediate ADRs induced by SMI. The Spearman correlation analysis revealed that LysoPC (18:3(6Z,9Z,12Z)/0:0) showed a significant positive correlation with cytokines. After injecting SMI, the levels of RhoA/ROCK signaling pathway-related protein increased significantly in BALB/c mice. Protein-protein interaction (PPI) showed that the increased lysolecithin levels might be related to the activation of the RhoA/ROCK signaling pathway.

DISCUSSION: Together, the results of our study revealed that the immediate ADRs induced by SMI were mediated by thymus-derived T cells, and elucidated the mechanisms of such ADRs. This study provided new insights into the underlying mechanism of immediate ADRs induced by SMI.

PMID:37026017 | PMC:PMC10070857 | DOI:10.3389/fimmu.2023.1135701

Nat Commun. 2023 Apr 7;14(1):1951. doi: 10.1038/s41467-023-37359-2.

ABSTRACT

Malaria parasites like Plasmodium falciparum multiply in red blood cells (RBC), which are cleared from the bloodstream by the spleen when their deformability is altered. Drug-induced stiffening of Plasmodium falciparum-infected RBC should therefore induce their elimination from the bloodstream. Here, based on this original mechanical approach, we identify safe drugs with strong potential to block the malaria transmission. By screening 13 555 compounds with spleen-mimetic microfilters, we identified 82 that target circulating transmissible form of P. falciparum. NITD609, an orally administered PfATPase inhibitor with known effects on P. falciparum, killed and stiffened transmission stages in vitro at nanomolar concentrations. Short exposures to TD-6450, an orally-administered NS5A hepatitis C virus inhibitor, stiffened transmission parasite stages and killed asexual stages in vitro at high nanomolar concentrations. A Phase 1 study in humans with a primary safety outcome and a secondary pharmacokinetics outcome ( https://clinicaltrials.gov , ID: NCT02022306) showed no severe adverse events either with single or multiple doses. Pharmacokinetic modelling showed that these concentrations can be reached in the plasma of subjects receiving short courses of TD-6450. This physiologically relevant screen identified multiple mechanisms of action, and safe drugs with strong potential as malaria transmission-blocking agents which could be rapidly tested in clinical trials.

PMID:37029122 | DOI:10.1038/s41467-023-37359-2

Behav Brain Res. 2023 Apr 5:114420. doi: 10.1016/j.bbr.2023.114420. Online ahead of print.

ABSTRACT

BACKGROUND: Antipsychotic drugs prescribed to elderly patients with neuropsychiatric disorders often experience severe extrapyramidal side effects. Previous studies from our group suggest that changes in histone modifications during aging increase the risk for antipsychotic drug side effects, because co-administration of antipsychotics with class 1 histone deacetylase (HDAC) inhibitors could mitigate the severity of motor side effects in aged mice. However, which HDAC subtype contributes to the age-related sensitivity to antipsychotic drug side effects is unknown.

METHODS: In this study, we overexpressed histone deacetylase type 1(HDAC1) in the striatum of 3-month-old mice and knocked down HDAC 1 in the striatum of 21-month-old mice by microinjection of AAV9-HDAC1-GFP or AAV9-CRISPR/Cas9-HDAC1-GFP vectors. Four weeks after the viral-vector delivery, the typical antipsychotic drug haloperidol was administered daily for 14 days, followed by motor function assessments through the open field, rotarod, and catalepsy behavioral tests.

RESULTS: Young mice with overexpressed HDAC1 showed increased cataleptic behavior induced by haloperidol administration, which is associated with the increased HDAC1 level in the striatum. In contrast, aged mice with HDAC1 knocked down rescued locomotor activity, motor coordination, and decreased cataleptic behavior induced by haloperidol administration, which is associated with decreased HDAC1 level in the striatum.

CONCLUSIONS: Our results suggest that HDAC1 is a critical regulator in haloperidol-induced severe motor side effects in aged mice. Repression of HDAC1 expression in the striatum of aged mice could mitigate typical antipsychotic drug-induced motor side effects.

PMID:37028517 | DOI:10.1016/j.bbr.2023.114420

PLoS One. 2023 Apr 7;18(4):e0284053. doi: 10.1371/journal.pone.0284053. eCollection 2023.

ABSTRACT

OBJECTIVE: To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and factors associated with their occurrence in the hospital setting.

METHODOLOGY: This is an observational, longitudinal, prospective study that included 571 hospitalized pregnant women with hypertension and gestational diabetes mellitus using at least one medication. DRPs were classified according to the Classification for Drug-Related Problems (PCNE V9.00). In addition to descriptive statistics, a univariate and multivariate logistic regression model was employed to determine the factors associated with the DRPs.

RESULTS: A total of 873 DRPs were identified. The most frequent DRPs were related to therapeutic ineffectiveness (72.2%) and occurrence of adverse events (27.0%) and the main drugs involved were insulins and methyldopa. These were followed in the first five days of treatment by: the ineffectiveness of insulin (24.6%), associated with underdosage (12.9%) or insufficient frequency of administration (9.5%) and methyldopa associated with the occurrence of adverse reactions (40.2%) in the first 48h. Lower maternal age (OR 0.966, 95% CI 0.938-0.995, p = 0.022), lower gestational age (OR 0.966, 95% CI 0.938-0.996, p = 0.026), report of drug hypersensitivity (OR 2.295, 95% CI 1.220-4.317, p = 0.010), longer treatment time (OR 1.237, 95% CI: 1.147-1.333, p = 0.001) and number of prescribed medications (OR 1.211, 95% CI: 0.240-5.476, p = 0.001) were risk factors for occurrence of DRPs.

CONCLUSION: DRPs are frequent in pregnant women with hypertension and gestational diabetes mellitus, and they are mainly related to therapeutic ineffectiveness and the occurrence of adverse events.

PMID:37027363 | DOI:10.1371/journal.pone.0284053

Indian J Ophthalmol. 2023 Apr;71(4):1263-1269. doi: 10.4103/IJO.IJO_2782_22.

ABSTRACT

Dry eye disease encompasses a broad range of etiologies and disease subtypes which have similar clinical manifestations. Medications can cause dry eye disease or symptoms of dryness as a side effect by either interfering with the lacrimal gland or meibomian gland function, or both, and by other mechanisms that affect the ocular surface homeostasis. This is important to know and recognize as eliminating the offending medication can reverse the symptoms and, in many cases, prevent further deterioration of the ocular surface inflammation. This review focuses on drugs like systemic isotretinoin and taxanes, which cause meibomian gland dysfunction; immune checkpoint inhibitors that cause lacrimal gland dysfunction; gliptins and topical antiglaucoma medications that cause cicatrizing conjunctivitis; and epidermal growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, and belantamab mafodotin, which cause mucosal epitheliopathy. Many of these medications, particularly the newer anticancer agents, have only recently been introduced for clinical use, and knowledge and awareness of their ocular side effects are still evolving. This review aims to update ophthalmologists on the drug-induced causes of dry eye disease or symptoms of dryness, which is avoidable by discontinuation of the incriminating agent or can be mitigated by reducing the dose or frequency of usage.

PMID:37026257 | DOI:10.4103/IJO.IJO_2782_22

BJUI Compass. 2023 Jan 13;4(3):322-330. doi: 10.1002/bco2.220. eCollection 2023 May.

ABSTRACT

OBJECTIVES: This study aimed to investigate the anti-PD-1 inhibitor pembrolizumab as a potential agent for use in non-muscle-invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run-in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT).

PATIENTS AND METHODS: Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1 and adequate end-organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of six doses. Intra-patient dose escalation was performed in three paired patient cohorts with doses starting at 50 mg and increasing through 100 mg to a maximum of 200 mg. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug-related, Grade 4 haematological or Grade 3 or higher non-haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient.

RESULTS: Six patients were treated with no DLTs seen during dose escalation. Drug-related AEs were of low grade and included dysuria and fatigue. All patients completed six doses of treatment as planned. Pharmacokinetic and pharmacodynamic assays did not detect any pembrolizumab in the serum following repeated intravesical administration, and no changes in peripheral immune cell populations were observed.

CONCLUSIONS: Administration of intravesical pembrolizumab was well tolerated and did not raise any safety concerns in patients with NMIBC following TURBT. There was no evidence of systemic absorption or systemic immune effects following intravesical administration. Further studies are required to assess whether intravesical administration has anti-tumour activity.

PMID:37025470 | PMC:PMC10071078 | DOI:10.1002/bco2.220

JHEP Rep. 2023 Mar 15;5(4):100686. doi: 10.1016/j.jhepr.2023.100686. eCollection 2023 Apr.

ABSTRACT

BACKGROUND & AIMS: Bulevirtide is a first-in-class entry inhibitor of hepatitis B surface antigen. In July 2020, bulevirtide was conditionally approved for the treatment of hepatitis D, the most severe form of viral hepatitis, which frequently causes end-stage liver disease and hepatocellular carcinoma. Herein, we report the first data from a large multicenter real-world cohort of patients with hepatitis D treated with bulevirtide at a daily dose of 2 mg without additional interferon.

METHODS: In a joint effort with 16 hepatological centers, we collected anonymized retrospective data from patients treated with bulevirtide for chronic hepatitis D.

RESULTS: Our analysis is based on data from 114 patients, including 59 (52%) with cirrhosis, receiving a total of 4,289 weeks of bulevirtide treatment. A virologic response defined as an HDV RNA decline of at least 2 log or undetectable HDV RNA was observed in 87/114 (76%) cases with a mean time to virologic response of 23 weeks. In 11 cases, a virologic breakthrough (>1 log-increase in HDV RNA after virologic response) was observed. After 24 weeks of treatment, 19/33 patients (58%) had a virologic response, while three patients (9%) did not achieve a 1 log HDV RNA decline. No patient lost hepatitis B surface antigen. Alanine aminotransferase levels improved even in patients not achieving a virologic response, including five patients who had decompensated cirrhosis at the start of treatment. Treatment was well tolerated and there were no reports of drug-related serious adverse events.

CONCLUSIONS: In conclusion, we confirm the safety and efficacy of bulevirtide monotherapy in a large real-world cohort of patients with hepatitis D treated in Germany. Future studies need to explore the long-term benefits and optimal duration of bulevirtide treatment.

IMPACT AND IMPLICATIONS: Clinical trials proved the efficacy of bulevirtide for chronic hepatitis D and led to conditional approval by the European Medical Agency. Now it is of great interest to investigate the effects of bulevirtide treatment in a real-world setting. In this work, we included data from 114 patients with chronic hepatitis D who were treated with bulevirtide at 16 German centers. A virologic response was seen in 87/114 cases. After 24 weeks of treatment, only a small proportion of patients did not respond to treatment. At the same time, signs of liver inflammation improved. This observation was independent from changes in hepatitis D viral load. The treatment was generally well tolerated. In the future, it will be of interest to investigate the long-term effects of this new treatment.

PMID:37025462 | PMC:PMC10071092 | DOI:10.1016/j.jhepr.2023.100686

Front Public Health. 2023 Apr 6;11:1155372. doi: 10.3389/fpubh.2023.1155372. eCollection 2023.

ABSTRACT

With the trend of aging population getting more obvious, stroke has already been a major public health problem worldwide. As a main disabling motor impairment after stroke, spasticity has unexpected negative impacts on the quality of life and social participation in patients. Moreover, it brings heavy economic burden to the family and society. Previous researches indicated that abnormality of neural modulation and muscle property corelates with the pathogenesis of poststroke spasticity (PSS). So far, there still lacks golden standardized treatment regimen for PSS; furthermore, certain potential adverse-events of the mainstream therapy, for example, drug-induced generalized muscle weakness or high risk related surgery somehow decrease patient preference and compliance, which brings challenges to disease treatment and follow-up care. As an essential non-pharmacological therapy, acupuncture has long been used for PSS in China and shows favorable effects on improvements of spastic hypertonia and motor function. Notably, previous studies focused mainly on the research of antispastic acupoints. In comparison, few studies lay special stress on the other significant factor impacting on acupuncture efficacy, that is acupuncture technique. Based on current evidences from the clinic and laboratory, we will discuss certain new insights into acupuncture technique, in particular the antispastic needling technique, for PSS management in light of its potential effects on central modulations as well as peripheral adjustments, and attempt to provide some suggestions for future studies with respect to the intervention timing and course, application of acupuncture techniques, acupoint selection, predictive and aggravating factors of PSS, aiming at optimization of antispastic acupuncture regimen and improvement of quality of life in stroke patients. More innovations including rigorous study design, valid objective assessments for spasticity, and related experimental studies are worthy to be expected in the years ahead.

PMID:37089473 | PMC:PMC10117862 | DOI:10.3389/fpubh.2023.1155372

Aust J Gen Pract. 2023 Apr;52(4):173-180. doi: 10.31128/AJGP-08-22-6547.

ABSTRACT

BACKGROUND: Deprescribing is an integral part of patient care. The term 'deprescribing' may be new to some, but the concept is not. Deprescribing refers to the planned withdrawal of medicines that are causing harm or not helping an individual.

OBJECTIVE: This article collates the latest evidence on deprescribing to guide general practitioners (GPs) and nurse practitioners on how to deprescribe for their elderly patients.

DISCUSSION: Deprescribing is a safe and effective method of reducing polypharmacy and high-risk prescribing. The challenge for GPs in deprescribing medicines for older people is to avoid adverse drug withdrawal events. Strategies to deprescribe confidently in partnership with patients include incorporating a 'stop slow, go low' approach and careful consideration of the medicine withdrawal plan.

PMID:37021442 | DOI:10.31128/AJGP-08-22-6547

BMC Cancer. 2023 Apr 6;23(1):316. doi: 10.1186/s12885-023-10781-x.

ABSTRACT

PURPOSE: Drug-induced interstitial lung disease (ILD) is not a rare adverse event in the current chemotherapy strategy for pancreatic ductal adenocarcinoma (PDAC). Thus, we aimed to find the optimal management for PDAC patients with a history of ILD induced by a gemcitabine-based regimen.

METHODS: We conducted a multicenter retrospective study. The primary endpoint was the overall survival (OS) of patients who underwent either S-1 monotherapy or FOLFOX after the onset of ILD. Toxicity data was also analyzed in the 2 groups.

RESULTS: Twenty-four patients were diagnosed with ILD and 17 patients who received subsequent chemotherapy were enrolled in the study. Among 17 patients who were managed with subsequent chemotherapy after recovering from ILD, we did not observe significant difference in OS between S-1 and FOLFOX (290.0 days vs. undefined, p = 0.39). Relapse of drug-induced ILD was not observed in all cases during the course. Overall, severe adverse events (CTCAE Grade 3 or 4) were observed in 3 patients (23.1%) in S-1 treatment group and 1 patient (25.0%) in FOLFOX treatment group (p = 0.93).

CONCLUSIONS: S-1 monotherapy and FOLFOX are comparable as the subsequent chemotherapy after gemcitabine-based chemotherapy-induced ILD in unresectable PDAC.

PMID:37024781 | DOI:10.1186/s12885-023-10781-x

Sante Publique. 2023;34(6):795-801. doi: 10.3917/spub.226.0795.

ABSTRACT

INTRODUCTION: In order to reduce the under-reporting of adverse drug reactions (ADR) in general practice, the Caen Normandie regional pharmacovigilance center (CRPV) has implemented a training program for the French health insurance representatives (DAM) of the Manche department in order to raise awareness among general practitioners (GPs) to ADR reporting.

PURPOSE OF RESEARCH: During quarterly visits of DAM to GPs, the mode of operation and the value of pharmacovigilance reporting was presented. This pilot study presents the impact of these DAM visits to GPs in term of ADRs reporting quantification.

RESULTS: Assessment of this first year showed a doubling of ADR reporting by GPs of the Manche department in 2019 compared to 2017 and 2018. This phenomenon was not found in the two control departments (departments of Calvados and Orne) where the information had not been issued. These ADRs first concerned drugs of the renin-angiotensin system, then psychotropic drugs and anti-infectives. These were cutaneous, then neurological and gastrointestinal ADRs, preferentially affecting women.

CONCLUSIONS: This experimentation should continue on a larger scale. The longer-term evaluation of this tool also requires evaluating its relevance.

PMID:37019792 | DOI:10.3917/spub.226.0795

Pharmacoepidemiol Drug Saf. 2023 Apr 5. doi: 10.1002/pds.5629. Online ahead of print.

ABSTRACT

PURPOSE: Studies on the detection of COVID-19 vaccine signals in South Korea are insufficient. Therefore, to investigate adverse events (AEs) that might be associated with COVID-19 vaccines, signals were detected using spontaneous reports from South Korea. We compared the signals with the vaccine insert lists of the regulators in the four countries.

METHODS: Spontaneous reports from 62 sites were collected by the National Medical Center between January 2013 and May 2022. A descriptive analysis of AEs associated with COVID-19 vaccines (Pfizer, Moderna, AstraZeneca, and Janssen) was performed, and the proportional reporting ratio, reporting odds ratio, and information component were calculated. We performed five analyses, with five cases and one control group.

RESULTS: During the study period, 68,355 cases were reported, of which 12,485 were COVID-19 vaccine AEs. Injection site pain (2,198 cases, 17.6%), myalgia (1,552 cases, 12.4%), headache (1,145 cases, 9.2%), pyrexia (1,003 cases, 8.0%), and fatigue (735 cases, 5.9%) were frequently reported. When comparing all COVID-19 vaccines with other viral vaccines, 20 signals were detected, of which cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in all four countries. Overall, 20, 17, 29, and 9 signals were detected in vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, respectively.

CONCLUSIONS: Based on a disproportionate analysis of COVID-19 vaccine AEs using spontaneous reports from South Korea, different signals were detected for each vaccine manufacturer.

PMID:37019851 | DOI:10.1002/pds.5629

J Thorac Cardiovasc Surg. 2023 Mar 3:S0022-5223(23)00185-X. doi: 10.1016/j.jtcvs.2023.02.025. Online ahead of print.

ABSTRACT

OBJECTIVE: The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization.

METHODS: In this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation.

RESULTS: No drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging-discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease).

CONCLUSIONS: Intraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.

PMID:37019717 | DOI:10.1016/j.jtcvs.2023.02.025

Drug Ther Bull. 2023 Apr 4:dtb-2023-000018. doi: 10.1136/dtb.2023.000018. Online ahead of print.

ABSTRACT

Overview of: Penner LS, Gavan SP, Ashcroft DM, et al Does coprescribing nonsteroidal anti-inflammatory drugs and oral anticoagulants increase the risk of major bleeding, stroke and systemic embolism? Br J Clin Pharmacol 2022;88:4789-811.

PMID:37019462 | DOI:10.1136/dtb.2023.000018

Front Immunol. 2023 Apr 4;14:1138483. doi: 10.3389/fimmu.2023.1138483. eCollection 2023.

ABSTRACT

Immune checkpoint inhibitors (ICI) therapy based on programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) has changed the treatment paradigm of advanced non-small cell lung cancer (NSCLC) and improved the survival expectancy of patients. However, it also leads to immune-related adverse events (iRAEs), which result in multiple organ damage. Among them, the most common one with the highest mortality in NSCLC patients treated with ICI is checkpoint inhibitor pneumonitis (CIP). The respiratory signs of CIP are highly coincident and overlap with those in primary lung cancer, which causes difficulties in detecting, diagnosing, managing, and treating. In clinical management, patients with serious CIP should receive immunosuppressive treatment and even discontinue immunotherapy, which impairs the clinical benefits of ICIs and potentially results in tumor recrudesce. Therefore, accurate diagnosis, detailedly dissecting the pathogenesis, and developing reasonable treatment strategies for CIP are essential to prolong patient survival and expand the application of ICI. Herein, we first summarized the diagnosis strategies of CIP in NSCLC, including the classical radiology examination and the rising serological test, pathology test, and artificial intelligence aids. Then, we dissected the potential pathogenic mechanisms of CIP, including disordered T cell subsets, the increase of autoantibodies, cross-antigens reactivity, and the potential role of other immune cells. Moreover, we explored therapeutic approaches beyond first-line steroid therapy and future direction based on targeted signaling pathways. Finally, we discussed the current impediments, future trends, and challenges in fighting ICI-related pneumonitis.

PMID:37081866 | PMC:PMC10110908 | DOI:10.3389/fimmu.2023.1138483

BMC Geriatr. 2023 Apr 5;23(1):215. doi: 10.1186/s12877-023-03942-x.

ABSTRACT

BACKGROUND: Older patients are vulnerable to experiencing drug related problems (DRPs), which may result in emergency department (ED) visits. However, it is not standard practice to conduct medications reviews during ED visit. The aim of this study was to assess the number of DRPs in older patients living with frailty at the ED, identified through pharmacist-led medication reviews within a geriatric care team, and to determine the acceptance rate of pharmacists' recommendations among hospital physicians and general practitioners or elderly care specialists.

METHODS: A retrospective observational study was performed in patients ≥ 70 years living with frailty at the ED at Tergooi Medical Center. Pharmacist-led medication reviews were conducted to identify and classify DRPs as part of a larger geriatric assessment. The acceptance rate of given recommendations was determined during follow-up.

RESULTS: A total of 356 ED visits were included. The mean (standard deviation, SD) age of patients was 83 (6.8) years. About 76% of patients had at least one DRP. In total, 548 DRPs were identified with a mean of 1.5 DRP (SD 1.3) per patient. The acceptance rate of medication recommendations in admitted patients was 55%, and 32% among general practitioners/elderly care specialists in discharged patients.

CONCLUSIONS: Pharmacist-led medication reviews as part of a geriatric care team identified DRPs in 76% of older patients living with frailty at the ED. The acceptance rate was substantially higher in admitted patients compared to discharged patients.

PMID:37016324 | PMC:PMC10074685 | DOI:10.1186/s12877-023-03942-x

Eur Rev Med Pharmacol Sci. 2023 Mar;27(6):2277-2287. doi: 10.26355/eurrev_202303_31761.

ABSTRACT

OBJECTIVE: Although methotrexate (MTX) is used to treat several malignancies and chronic inflammatory diseases, its clinical use is constrained because of its negative side effects, the most prevalent of which are hepatotoxicity and nephrotoxicity. So, this study aims to determine whether α-lipoic acid (ALA) and vitamin C can protect mice against the liver damage that methotrexate causes.

MATERIALS AND METHODS: A total of 49 male mice were divided into seven groups at random. Group I received sodium bicarbonate, while groups II to VII received an intraperitoneal injection of MTX (20 mg/kg) on the tenth day, following ten days of pretreatment with ALA (60 mg/Kg), ALA (120 mg/Kg), vitamin C (100 mg/Kg), vitamin C (200 mg/Kg), ALA (60 mg/Kg), and vitamin C (100 mg/kg).

RESULTS: When compared to mice in group I, mice in group II (the control group) had significantly higher levels of the enzymes malondialdehyde (MDA), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and significantly lower (p <0.05) levels of the enzymes superoxide dismutase (SOD) and glutathione (GSH). As compared to the control group, pretreatment groups with ALA and vitamin C showed a dose-dependent substantial rise (p <0.05) in GSH and SOD levels, a dose-dependent notable decrease (p <0.05) in MDA, ALT, ALP, and LDH levels, and better liver histological architecture. In order to increase the antioxidant capacity, pretreatment with ALA and vitamin C may be able to prevent MTX-induced hepatotoxicity.

CONCLUSIONS: These results imply that ALA and vitamin C are useful in the treatment of MTX-induced liver damage.

PMID:37013745 | DOI:10.26355/eurrev_202303_31761