Int J Oral Maxillofac Surg. 2023 Nov 28:S0901-5027(23)00875-5. doi: 10.1016/j.ijom.2023.11.001. Online ahead of print.

ABSTRACT

The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population - much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients.

PMID:38030483 | DOI:10.1016/j.ijom.2023.11.001

Seizure. 2023 Nov 22;114:9-17. doi: 10.1016/j.seizure.2023.11.010. Online ahead of print.

ABSTRACT

PURPOSE: The Liverpool Adverse Event Profile (L AEP) is commonly applied in clinical practice and pharmacological trials for the monitoring of side effects of anti-seizure medication (ASM). However, additional symptoms need to be assessed and normative data would be appreciated to put patients´ complaints into perspective.

METHODS: An extended 32-item AEP (E AEP) was given to 537 healthy subjects and 1,605 patients with epilepsy as part of the Bonn ASM side effect registry. The tool was factor-analyzed, normed with regard to age, gender, and repeated application, and related to drug load and individual substances (with N> 100) on item and scale level (total E AEP and its subscales cognition, dizziness, energy, mood, bodily symptoms, aggression, and sexuality).

RESULTS: Compared to non-normalized results, on item level, between one and two-thirds less problematic responses were noted after normalization. Binary regression analyses revealed differential effects of antiseizure-drug treatment, but also of antidepressants and neuroleptics on complaint domains. The explained variance was better for bodily than psychic domains. The results reflect both known drug side effects and indications. Patients´ explicit attribution of problems to their drugs barely improved the correlation of the E AEP and treatment parameters.

CONCLUSION: Application of a normed AEP is highly recommended to avoid an overestimation of treatment related problems in patients with epilepsy. It allows evaluation on item and scale level for individuals as well as groups in drug trials. Plausible relations to individual drugs and to drug load can be demonstrated. The explanatory power was better for physical than psychic domains. Drug-related complaint patterns reflect known drug side effects (e.g. perampanel and brivaracetam with aggression) as well as drug indications (e.g. lamotrigine for depression), the latter particularly when considerations of side effects found their way into treatment decisions. Longitudinal evaluation with repeated application of the E AEP along with changes of drug treatment is in progress.

PMID:38029647 | DOI:10.1016/j.seizure.2023.11.010

Front Genet. 2023 Nov 7;14:1238140. doi: 10.3389/fgene.2023.1238140. eCollection 2023.

ABSTRACT

Introduction: Scientific articles serve as vital sources of biomedical information, but with the yearly growth in publication volume, processing such vast amounts of information has become increasingly challenging. This difficulty is particularly pronounced when it requires the expertise of highly qualified professionals. Our research focused on the domain-specific articles classification to determine whether they contain information about drug-induced liver injury (DILI). DILI is a clinically significant condition and one of the reasons for drug registration failures. The rapid and accurate identification of drugs that may cause such conditions can prevent side effects in millions of patients. Methods: Developing a text classification method can help regulators, such as the FDA, much faster at a massive scale identify facts of potential DILI of concrete drugs. In our study, we compared several text classification methodologies, including transformers, LSTMs, information theory, and statistics-based methods. We devised a simple and interpretable text classification method that is as fast as Naïve Bayes while delivering superior performance for topic-oriented text categorisation. Moreover, we revisited techniques and methodologies to handle the imbalance of the data. Results: Transformers achieve the best results in cases if the distribution of classes and semantics of test data matches the training set. But in cases of imbalanced data, simple statistical-information theory-based models can surpass complex transformers, bringing more interpretable results that are so important for the biomedical domain. As our results show, neural networks can achieve better results if they are pre-trained on domain-specific data, and the loss function was designed to reflect the class distribution. Discussion: Overall, transformers are powerful architecture, however, in certain cases, such as topic classification, its usage can be redundant and simple statistical approaches can achieve compatible results while being much faster and explainable. However, we see potential in combining results from both worlds. Development of new neural network architectures, loss functions and training procedures that bring stability to unbalanced data is a promising topic of development.

PMID:38028616 | PMC:PMC10668010 | DOI:10.3389/fgene.2023.1238140

Clin Case Rep. 2023 Nov 20;11(11):e8247. doi: 10.1002/ccr3.8247. eCollection 2023 Nov.

ABSTRACT

KEY CLINICAL MESSAGE: Drug-induced pleural effusion is extremely rare. It is the diagnosis of exclusion. This condition can be suspected if the patient has been exposed to a likely causative drug, develops new signs and symptoms, and has a remittance of these symptoms once the drug is withheld.

ABSTRACT: Etoricoxib has been a very popular nonsteroidal anti-inflammatory drug and is prescribed widely due to its fewer gastrointestinal side effects. Pleural effusion caused by etoricoxib is rarest among the side effects. Here, we report a case of a 45-year-old female with pleural effusion induced by etoricoxib.

PMID:38028070 | PMC:PMC10661311 | DOI:10.1002/ccr3.8247

Open Med (Wars). 2023 Oct 30;18(1):20230823. doi: 10.1515/med-2023-0823. eCollection 2023.

ABSTRACT

Autoimmune hepatitis (AIH) is a chronic liver inflammatory disease with various immune system manifestations, showing a global trend of increased prevalence. AIH is diagnosed through histological abnormalities, clinical manifestations, and biochemical indicators. The biochemical markers involve interfacial hepatitis, transaminase abnormalities, positive autoantibodies, etc. Although AIH pathogenesis is unclear, gene mutations and immunological factors could be the leading factors. AIH usually presents as a chronic liver disease and sometimes as acute hepatitis, making it challenging to distinguish it from drug-related hepatitis due to similar clinical symptoms. Normalizing transaminases and serum IgG levels is essential in assessing the remission status of AIH treatment. Glucocorticoids and azathioprine are the first-line AIH treatment, with lifelong maintenance therapy in some patients. The quality of life and survival can be improved after appropriate treatment. However, certain limitations jeopardize the quality of treatment, including long treatment cycles, side effects, poor patient compliance, and inability to inhibit liver fibrosis and cirrhosis. Accurate AIH animal models will help us understand the pathophysiology of the disease while providing fresh perspectives for avoiding and treating AIH. This review will help us understand AIH better, from the cellular and molecular causes to the clinical features, and will provide insight into new therapy techniques with fewer side effects.

PMID:38025543 | PMC:PMC10655690 | DOI:10.1515/med-2023-0823

J Pediatr Pharmacol Ther. 2023;28(7):643-648. doi: 10.5863/1551-6776-28.7.643. Epub 2023 Nov 23.

ABSTRACT

PURPOSE: Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter.

METHODS: An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes.

RESULTS: No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions.

CONCLUSION: Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.

PMID:38025152 | PMC:PMC10681083 | DOI:10.5863/1551-6776-28.7.643

EJHaem. 2023 Oct 3;4(4):1110-1116. doi: 10.1002/jha2.801. eCollection 2023 Nov.

ABSTRACT

Hyperkalemia, an elevated blood potassium concentration exceeding 5.0 mEq/L, is associated with adverse outcomes and is frequently observed in hospitalized patients. Drug-induced hyperkalemia accounts for a significant proportion of cases, with heparin, commonly used for venous thrombosis prevention, suspected to contribute, though less recognized than other heparin-related side effects. Both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been implicated in inducing hyperkalemia, primarily through the suppression of aldosterone levels and modulation of angiotensin II receptors. This systematic review examines the relationship between heparin, particularly LMWH, and hyperkalemia. Thirteen studies involving 1407 patients were analyzed. Findings indicated a lack of highquality evidence, with no significant increase in potassium levels associated with LMWH use. LMWH did not exhibit a dose-response relationship with hyperkalemia incidence. Additionally, mechanisms underlying the hypothetical LMWHinduced hyperkalemia remained inconclusive. While this suggests that LMWH is unlikely to be a primary cause of hyperkalemia, caution is warranted, especially in patients with elevated baseline potassium levels.

PMID:38024642 | PMC:PMC10660614 | DOI:10.1002/jha2.801

Front Oncol. 2023 Nov 13;13:1227461. doi: 10.3389/fonc.2023.1227461. eCollection 2023.

ABSTRACT

BACKGROUND: Effective adjuvant therapy for osteosarcoma is necessary for improved outcomes. Previous studies demonstrated that apatinib plus doxorubicin-based chemotherapy may improve the efficacy of neoadjuvant therapy. This study aimed to clarify the effectiveness and safety of apatinib plus doxorubicin and cisplatin (AP) as neoadjuvant therapy for osteosarcoma.

METHODS: The clinical data of osteosarcoma patients who underwent neoadjuvant therapy and surgery between August 2016 and April 2022 were retrospectively collected and analyzed. Patients were divided into two groups: the apatinib plus AP (apatinib + AP) group and the methotrexate, doxorubicin, and cisplatin (MAP) group.

RESULTS: This study included 42 patients with nonmetastatic osteosarcoma (19 and 23 patients in the apatinib + AP and MAP groups, respectively). The 1- and 2-year disease-free survival rates in the apatinib + AP group were higher than those in the MAP group, but the difference was not significant (P=0.165 and 0.283, respectively). Some adverse events were significantly more common in the apatinib + AP group than in the MAP group, including oral mucositis (grades 3 and 4) (52.6% vs. 17.4%, respectively, P=0.023), limb edema (47.4% vs. 17.4%, respectively, P=0.049), hand-foot syndrome (31.6% vs. 0%, respectively, P=0.005), proteinuria (26.3% vs. 0%, respectively, P=0.014), hypertension (21.1% vs. 0%, respectively, P=0.035), and hypothyroidism (21.1% vs. 0%, respectively, P=0.035). No drug-related deaths occurred. There was no statistically significant difference in the incidence of postoperative complications between the groups (P>0.05).

CONCLUSION: The present study suggests that apatinib + AP may be a promising candidate for neoadjuvant therapy for osteosarcoma, warranting further validation in prospective randomized controlled clinical trials with long-term follow-up.

PMID:38023239 | PMC:PMC10679406 | DOI:10.3389/fonc.2023.1227461

Adv Pharm Bull. 2023 Nov;13(4):688-700. doi: 10.34172/apb.2023.071. Epub 2023 Jan 23.

ABSTRACT

Glycogen synthase kinase-3 (GSK-3) was discovered to be a multifunctional enzyme involved in a wide variety of biological processes, including early embryo formation, oncogenesis, as well cell death in neurodegenerative diseases. Several critical cellular processes in the brain are regulated by the GSK-3β, serving as a central switch in the signaling pathways. Dysregulation of GSK-3β kinase has been reported in diabetes, cancer, Alzheimer's disease, schizophrenia, bipolar disorder, inflammation, and Huntington's disease. Thus, GSK-3β is widely regarded as a promising target for therapeutic use. The current review article focuses mainly on Alzheimer's disease, an age-related neurodegenerative brain disorder. GSK-3β activation increases amyloid-beta (Aβ) and the development of neurofibrillary tangles that are involved in the disruption of material transport between axons and dendrites. The drug-binding cavities of GSK-3β are explored, and different existing classes of GSK-3β inhibitors are explained in this review. Non-ATP competitive inhibitors, such as allosteric inhibitors, can reduce the side effects compared to ATP-competitive inhibitors. Whereas ATP-competitive inhibitors produce disarrangement of the cytoskeleton, neurofibrillary tangles formation, and lead to the death of neurons, etc. This could be because they are binding to a site separate from ATP. Owing to their interaction in particular and special binding sites, allosteric ligands interact with substrates more selectively, which will be beneficial in resolving drug-induced resistance and also helpful in reducing side effects. Hence, in this review, we focussed on the allosteric GSK-3β inhibitors and discussed their futuristic opportunities as anti-Alzheimer's compounds.

PMID:38022801 | PMC:PMC10676556 | DOI:10.34172/apb.2023.071

Cureus. 2023 Oct 27;15(10):e47807. doi: 10.7759/cureus.47807. eCollection 2023 Oct.

ABSTRACT

Drug-induced autoimmune hepatitis (DIAIH) is a poorly understood form of drug-induced liver injury that presents with features mimicking autoimmune hepatitis. Statins, commonly prescribed for lowering cholesterol and for cardiovascular disease prevention, have been documented in rare cases as being responsible for DIAIH. In this case report, we detail a case where a patient developed DIAIH due to her atorvastatin. We also highlight the diagnostic approach and management strategies for DIAIH.

PMID:38021877 | PMC:PMC10679798 | DOI:10.7759/cureus.47807

Cureus. 2023 Oct 26;15(10):e47742. doi: 10.7759/cureus.47742. eCollection 2023 Oct.

ABSTRACT

INTRODUCTION: Levetiracetam (LEV) and valproic acid (VPA) are two anti-epileptic drugs (AEDs) routinely used for post-traumatic seizure (PTS) prophylaxis at our institution. In our practice, VPA is used for its beneficial effects on behavioral agitation and headaches, but it is also associated with abnormal liver function tests (LFTs). Both medications may be associated with thrombocytopenia. There is less literature comparing the adverse effect profiles and discontinuation rates of LEV and VPA in the context of PTS prophylaxis. We conducted a quality improvement (QI) analysis to determine the safety of LEV and VPA for traumatic brain injury (TBI) patients at our institution. In particular, our QI analysis involved calculating the rates of discontinuation or change of drug regimen due to the adverse effects.

METHODS: Our QI analysis focused on patients treated for TBI at our institution during a six-year period. We recorded the AED used and if the AED was discontinued or switched due to thrombocytopenia, behavioral agitation, headaches, or elevated LFTs (including elevated aspartate aminotransferase or alanine aminotransferase values). We also recorded the incidence of early PTS, defined as seizures within seven days of the TBI.

RESULTS: Our QI analysis included patients with a mean age of approximately 49 years with nearly 75% males. The mean Glasgow Coma Scale (GCS) score was 12.88, with 73.11% of patients having a mild GCS. The three leading injury mechanisms were fall, assault, and motor vehicle collision. The three leading types of TBI were traumatic subarachnoid hemorrhage, subdural hematoma, and cerebral contusion. Among patients with no prior history of seizures, we found an early PTS incidence of 7.28%. For patients administered LEV and VPA, 0.11% (1/898) and 3.85% (4/104) had the medication discontinued or changed because of thrombocytopenia (p < 0.001), respectively. For patients on LEV, 4.01% (36/898) and 1.78% (16/898) had the medication discontinued or changed because of behavioral agitation and headaches, respectively. For patients on VPA, 2.88% (3/104) had the medication discontinued or changed because of hepatotoxicity. In total, 5.90% versus 6.73% (p > 0.5) of patients on LEV and VPA, respectively, had their medication regimens changed due to the adverse effects.

CONCLUSIONS: The incidence of early PTS in our patients is within the range of what has been reported in the literature. The rate of discontinuation of LEV and VPA on account of adverse events is low in the context of PTS prophylaxis. Both medications had similar overall rates of discontinuation. VPA was discontinued more frequently than LEV due to thrombocytopenia, but discontinuation was not common in either case. LEV is associated with behavioral agitation and headaches, which makes VPA a desirable alternative for patients suffering from these symptoms.

PMID:38021754 | PMC:PMC10676217 | DOI:10.7759/cureus.47742

CNS Drugs. 2023 Nov 29. doi: 10.1007/s40263-023-01042-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Depression, anxiety, and/or panic disorder are often comorbid and have a complex etiology mediated through the same neuronal network. Cholecystokinin-tetrapeptide (CCK-4), a synthetic analog of the endogenous neuropeptide cholecystokinin (CCK), is thought to be implicated in this network. The CCK-4 challenge model is an accepted method of investigating the pathophysiology of panic and has been shown to mediate neuronal activation via the transient receptor potential canonical (TRPC) ion channels.

OBJECTIVES: This study aimed to assess the pharmacodynamic effects of BI 1358894, a small-molecule inhibitor of TRPC ion channel members 4 and 5 (TRPC4/5), on CCK-4-induced anxiety/panic-like symptoms and evaluate circuit engagement.

METHODS: Twenty healthy male CCK-4-sensitive volunteers entered a Phase I, double blind, randomized, two-way cross-over, single dose, placebo-controlled trial. Randomization was to oral BI 1358894 100 mg in the fed state followed by oral placebo in the fed state, or vice versa. Treatments were administered 5 h prior to intravenous CCK-4 50 µg. The primary endpoint was maximum change from baseline of the Panic Symptom Scale (PSS) sum intensity score after CCK-4 injection. Further endpoints included the emotional faces visual analog score (EVAS), the Spielberger State-Trait Anxiety Inventory (STAI), plasma adrenocorticotropic hormone (ACTH), and serum cortisol values. The safety and tolerability of BI 1358894 was assessed based on a number of parameters including occurrence of adverse events (AEs). All pharmacodynamic, pharmacokinetic, and safety endpoints were analyzed using descriptive statistics.

RESULTS: Single oral doses of BI 1358894 were generally well tolerated by the healthy male volunteers included in this study. Adjusted mean maximum change from baseline in PSS sum intensity score was 24.4 % lower in volunteers treated with BI 1358894 versus placebo, while adjusted mean maximum change from baseline of EVAS was reduced by 19.2 % (BI 1358894 vs placebo). The STAI total score before CCK-4 injection was similar in both groups (placebo: 25.1; BI 1358894: 24.3). Relative to placebo, BI 1358894 reduced CCK-4-induced mean maximum plasma ACTH and serum cortisol values by 58.6 % and 27.3 %, respectively. Investigator-assessed drug-related AEs were reported for 13/20 participants (65.0 %). There were no serious or severe AEs, AEs of special interest, AEs leading to discontinuation of trial medication, or deaths.

CONCLUSIONS: Overall, BI 1358894 reduced psychological and physiological responses to CCK-4 compared with placebo, as measured by PSS, subjective EVAS and objectively measured stress biomarkers. BI 1358894 had a positive safety profile, and single oral doses were well tolerated by the healthy volunteers. This trial (NCT03904576/1402-0005) was registered on Clinicaltrials.gov on 05.04.19.

PMID:38019356 | DOI:10.1007/s40263-023-01042-3

CNS Drugs. 2023 Nov 29. doi: 10.1007/s40263-023-01041-4. Online ahead of print.

ABSTRACT

INTRODUCTION: The transient receptor potential canonical (TRPC) ion channels have been implicated in the pathophysiology of major depressive disorder (MDD), and TRPC inhibition has been shown to reduce depressive-like behaviour in rodent models of depression. BI 1358894, a small-molecule inhibitor of TRPC ion channels, is currently being developed for the treatment of MDD.

OBJECTIVE: Two phase I studies assessed the safety, tolerability, and pharmacokinetics (PK) of oral BI 1358894 in fed and fasted states following a single ascending dose (SAD) [NCT03210272/1402-0001] and multiple ascending doses (MAD) [NCT03754959/1402-0002] in healthy male volunteers. In addition, any potential food effect was evaluated after a single dose.

METHODS: In both studies, eligible healthy male volunteers (aged 18-45 years; body mass index of 18.5-29.9 kg/m2) were allocated to receive BI 1358894 or placebo. In the SAD study (1402-0001), volunteers were randomised 3:1 to receive BI 1358894 or placebo in fasted (3, 6, 10, 25, 50, 100, or 200 mg) and fed states (200 mg). The food effect part was conducted as an open-label, randomised, two-way crossover study at doses of 50 and 100 mg in fasted and fed states (high-calorie, high-fat breakfast). For the MAD study (1402-0002), volunteers were randomised 4:1 to receive BI 1358894 (10, 25, 50, 100, or 200 mg) or placebo once daily for 14 days under fed conditions. Primary endpoint (both studies): number of volunteers with drug-related adverse events (DRAEs). Secondary PK endpoints for study 1402-0001: area under the concentration-time curve (AUC) from time zero extrapolated to infinity (AUC∞), maximum plasma concentration (Cmax), and AUC from time zero to the last quantifiable data time point (AUC0-tz). Secondary PK endpoints for study 1402-0002: AUC over 0-24 h (AUC0-24), Cmax after the first dose, and steady-state AUC and Cmax over a uniform dosing interval (AUCτ,ss and Cmax,ss, respectively) after the last dose.

RESULTS: BI 1358894 was well tolerated at doses ≤ 200 mg under all tested conditions and no dose dependency was observed in DRAE frequency for either study. In the SAD study, BI 1358894 exposure increased dose proportionally across 3-50 mg in the fasted state and across 50-200 mg in the fed state. A positive food effect was observed at the tested doses. In the MAD study, BI 1358894 exposure increased less than dose proportionally across 10-200 mg.

CONCLUSIONS: These studies demonstrate that BI 1358894 is well tolerated in healthy male volunteers following single and multiple doses, with no dose dependency observed in DRAE frequency. BI 1358894 exposure increased dose dependently in both the SAD and MAD studies, with higher exposure of BI 1358894 observed in the fed state.

CLINICALTRIALS REGISTRATION: These trials have been registered on ClinicalTrials.gov: NCT03210272/1402-0001 (registered on 6 July 2017) and NCT03754959/1402-0002 (registered on 27 November 2018).

PMID:38019355 | DOI:10.1007/s40263-023-01041-4

J Gerontol Nurs. 2023 Dec;49(12):5-10. doi: 10.3928/00989134-20231107-02. Epub 2023 Dec 1.

ABSTRACT

Older adults have an increased risk of adverse drug events related to polypharmacy and potentially inappropriate medication (PIM) use. These patients are even more vulnerable as they transition through different health care settings. In 2023, the American Geriatrics Society published an updated version of the Beers Criteria®, providing updated guidance on identifying and managing PIMs. Nurses and nurse practitioners play important roles in medication management across the continuum of care. The current article aims to illustrate key concepts regarding medication safety and deprescribing for older adult patients during transitions of care. [Journal of Gerontological Nursing, 49(12), 5-10.].

PMID:38015150 | DOI:10.3928/00989134-20231107-02

Ital J Dermatol Venerol. 2023 Dec;158(6):437-444. doi: 10.23736/S2784-8671.23.07542-4.

ABSTRACT

BACKGROUND: Cutaneous adverse events (CAEs) related to oncological therapies are a common scenario in daily clinical practice.

METHODS: This is a retrospective observational study collecting the data regarding CAEs of patients treated with immune checkpoints inhibitors (ICIs) in four different Italian centers.

RESULTS: Of 323 patients included, 305 were evaluable for this analysis; 182 patients (59.7%) had metastatic cutaneous melanoma (CM), 99 (32.5%) non-small cell lung cancer (NSCLC) and 24 (7.8%) renal cell carcinoma (RCC). The most frequent CAEs that we found, considering all the 305 patients, were pruriginous maculopapular rash (10.2% of the patients), vitiligo-like areas (7.2% of the patients), psoriasiform rash (6.2% of the patients), asymptomatic maculopapular rash (4.6% of the patients), and lichenoid rash (4.3% of the patients). Vitiligo-like areas occurred more frequently in patients with CM, while a lichenoid rash was more frequently observed in patients with RCC. Treatment interruption was related to drug-induced CAEs in 15.4% of melanoma patients and 0.0% of lung and kidney patients. Patients developing a cutaneous adverse event had better overall response rate and higher progression free survival and overall survival than the patients without CAEs.

CONCLUSIONS: Our study brings new information on the characteristics of CAEs related to ICIs treatment in three different types of cancers, CM, NSCLC and RCC.

PMID:38015482 | DOI:10.23736/S2784-8671.23.07542-4

Expert Opin Drug Saf. 2023 Nov 28. doi: 10.1080/14740338.2023.2289176. Online ahead of print.

ABSTRACT

INTRODUCTION: Acute myeloid leukemia (AML) treatment has primarily focused on 7 + 3 chemotherapy, but in the last decade there has been a significant increase in new therapies, mostly targeted agents, approved for the treatment of AML. We performed a comparative analysis of the unique safety profile of each of these new agents.

AREAS COVERED: We conducted a review of the current literature on public databases (PubMed, ClinicalTrials.gov, and U.S. Food and Drug Administration) regarding new AML drugs that were approved from 2017 to 2023.

EXPERT OPINION: The diagnosis of AML typically carries a poor prognosis but with an increase in the number of drugs that are now available, patients' outcomes are improving. With novel mechanisms of action, the use of these agents introduces different safety profiles, occasionally with adverse events not previously seen with standard chemotherapy or at different frequencies. An understanding of the drugs available and the safety concerns associated with each one is crucial to selecting the best available option for each patient, and early recognition and appropriate management of drug-related adverse effects.

PMID:38014918 | DOI:10.1080/14740338.2023.2289176

Women Health. 2023 Nov 28:1-9. doi: 10.1080/03630242.2023.2286264. Online ahead of print.

ABSTRACT

Cyclophosphamide is a drug used in chemotherapy. However, it has side effects, including changes in reproductive system functioning. Some herbal compounds can reduce the harmful effects of cyclophosphamide. This study aims to investigate the protective role of crocin against changes caused by Cyclophosphamide in ovarian tissue through changes in the expression of genes involved in the hypothalamic-pituitary-gonadal axis. This experimental study was performed on 24 adult female Wistar rats. Mice were divided into four groups (normal saline, 30 mg/kg cyclophosphamide, 100 mg/kg crocin and 30 mg/kg cyclophosphamide, and 200 mg/kg crocin and 30 mg/kg cyclophosphamide). At the end of the treatment period, the hypothalamus and ovaries were also removed to evaluate ob-Rb, ob-Ra, and NPY genes expression using real-time PCR and histological changes in the ovaries. Data were analyzed by SPSS statistical software. The expression of genes, number of follicles, and follicle diameter significantly decreased in the cyclophosphamide-treated groups compared with the control group. In the crocin and cyclophosphamide-treated groups, drug-induced reproductive complications were mitigated. The current findings indicate that by increasing the expression of genes ob-Rb, ob-Ra, and NPY, crocin could modulate the harmful effects of cyclophosphamide.

PMID:38014433 | DOI:10.1080/03630242.2023.2286264

Curr J Neurol. 2020 Jul 5;19(3):103-106. doi: 10.18502/cjn.v19i3.5422.

ABSTRACT

Background: The study aimed to judge the safety and possible side effects of rituximab (RTX) drug in patients with multiple sclerosis (MS). Methods: This retrospective observational study was performed on 91 patients with MS who had been treated with RTX between 2016 and 2019. Each patient was visited and examined a minimum of once. The side effects of the drug and therefore the drug-related reactions to the injection were asked via phone calls, which were recorded separately as mild, moderate, and severe modes with the necessity for hospitalization. Results: A total of 91 patients were enrolled within the study: 80 patients with relapsing-remitting MS (RRMS), 6 patients with secondary progressive MS (SPMS), and 5 patients with primary progressive MS (PPMS). The mean age of the patients was 32.18 ± 8.71 years (18 to 60 years). The injection-related side effects occurred in 30.8% of the injections, most of which were mild and one of the mild complications was urinary tract infection (UTI). Two cases of complications with moderate severity were recorded. Conclusion: The observations from this study demonstrated that RTX did not cause serious complications in patients with MS.

PMID:38011421 | PMC:PMC8185590 | DOI:10.18502/cjn.v19i3.5422

Shock. 2023 Nov 22. doi: 10.1097/SHK.0000000000002277. Online ahead of print.

ABSTRACT

AIMS: We conducted a systemic review and meta-analysis to evaluate the therapeutic efficacy and safety of soluble guanylate cyclase(sGC) stimulators in patients with heart failure with preserved ejection fraction(HFpEF).

METHODS: We systematically searched PubMed, EMBASE and Cochrane Library databases for original randomized controlled trials comparing sGC stimulators with placebo in HFpEF patients. A random-effects model was applied to evaluate the mortality, quality of life and drug-related adverse events. This meta-analysis is registered in PROSPERO under the number CRD42023457382.

RESULTS: We included five studies involving 1600 HFpEF patients. Comprehensively, the combined risk ratio (RR) for mortality was not significant(RR(95% CI) = 1.44 (0.71-2.91), p = 0.31). Furthermore, there were no statistically significant differences in the Kansas City Cardiomyopathy Questionnaire (KCCQ) results, including the Clinical Summary Score(CSS) (WMD (95% CI) =0.32( -7.38-8.02), p = 0.94) and the Overall Summary Score(OSS) (WMD (95% CI) = -0.87( -8.87-7.14), P = 0.83). Similarly, there was no significant improvement in the 6-minute walk distance(6MWD) (WMD(95% CI) = -6.22(-18.56-6.12), p = 0.32). Additionally, drug-related adverse events were more common in patients treated with sGC stimulators(RR(95%CI) = 1.63,(1.25-2.14), p < 0.05).

CONCLUSIONS: Oral sGC stimulators do not significantly improve mortality outcomes, functional capacity and quality of life in HFpEF patients but are associated with increased drug-related adverse events. Therefore, we should consider using sGC stimulators in HFpEF patients carefully.

PMID:38010279 | DOI:10.1097/SHK.0000000000002277

Australas J Dermatol. 2023 Nov 27. doi: 10.1111/ajd.14190. Online ahead of print.

NO ABSTRACT

PMID:38009895 | DOI:10.1111/ajd.14190