Search Results (337)

Monoclonal antibodies (mAbs) have revolutionized the landscape of cancer therapy, offering unprecedented specificity and diverse mechanisms to combat malignant cells. These biologic agents have emerged as a cornerstone in targeted cancer treatment, binding to specific antigens on cancer cells and exerting their therapeutic effects through various mechanisms, including inhibition of signaling pathways, antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and antibody-dependent cellular phagocytosis (ADCP). The unique ability of mAbs to engage the immune system and directly interfere with cancer cell function has significantly enhanced the therapeutic armamentarium against a broad spectrum of malignancies. mAbs were initially studied in oncology; however, today, treatments have been developed for eye diseases. This review discusses the current applications of mAbs for the treatment of ocular diseases, discussing the specificity and the variety of mechanisms by which these molecules exhibit their therapeutic effects. The benefits, drawbacks, effectiveness, and risks associated with using mAbs in ophthalmology are highlighted, focusing on the most relevant ocular diseases and mAbs currently in use. Technological advances have led to in vitro production methods and recombinant engineering techniques, allowing the development of chimeric, humanized, and fully human mAbs. Nowadays, many humanized mAbs have several applications, e.g., for the treatment of age-related macular disease, diabetic retinopathy, and uveitis, while studies about new applications of mAbs, such as for SARS-CoV-2 infection, are also currently ongoing to seek more efficient and safe approaches to treat this new ocular disease. Full article

Background: Inborn errors of glutathione metabolism may cause high anion gap metabolic acidosis due to pyroglutamic acid accumulation. Since 1988, cases of this acidosis have been reported in individuals without these defects. Methods: Given the poorly characterized predisposing factors, presentation, management, and prognosis of acquired pyroglutamic acidosis, we conducted a systematic review using the National Library of Medicine, Excerpta Medica, Web of Science, and Google Scholar databases. Results: A total of 131 cases were found. Most patients were females (79%), adults (92%) aged 51 years or older (66%) with pre-existing conditions (74%) such as undernutrition, alcohol-use disorder, or kidney disease, and had an ongoing infection (69%). The clinical features included diminished consciousness (60%), Kussmaul breathing (56%), and nausea or vomiting (27%). At least 92% of patients were on paracetamol therapy for >10 days at an appropriate dose, 32% on a β-lactamase-resistant penicillin, and 2.3% on vigabatrin. Besides severe anion gap acidosis, patients also presented with hypokalemia (24%) and kidney function deterioration (41%). Management involved discontinuing the offending drug (100%), bicarbonate (63%), acetylcysteine (42%), and acute kidney replacement therapy (18%). The fatality rate was 18%, which was higher without acetylcysteine (24%) compared to with it (11%). Conclusions: Acquired pyroglutamic acidosis is a rare, potentially fatal metabolic derangement, which usually occurs after paracetamol use, frequently combined with a β-lactamase-resistant penicillin or vigabatrin. This condition predominantly affects adults, especially women with factors like undernutrition, alcohol-use disorder, or kidney disease, often during infection. Increased awareness of this rare condition is necessary. Full article

Background: Potentially inappropriate medication prescribing is prevalent and well studied in older adults. However, limited data are available on inappropriate drug dosing in those with dementia or cognitive impairment and renal impairment. Objectives: We aimed to examine the prevalence of, and factors associated with, inappropriate drug dosing in older patients with dementia or cognitive impairment and renal impairment. Methods: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline and the Cochrane Handbook for Systematic Reviews of Interventions. We searched Medline, Embase, CINAHL, and PubMed for studies on inappropriate drug dosing in older patients with dementia or cognitive impairment and renal impairment, published from 1 January 2000 to 31 August 2024, with English language restriction following the PICOS search strategy. Two reviewers independently screened all titles and abstracts, extracted data from included studies, and undertook quality assessment using the Joanna Briggs Institute (JBI) tool. Descriptive statistics were used to summarise and present findings. Results: In total, eight retrospective cohort studies were included. Of the total number of patients with dementia who had renal impairment (n = 5250), there were 2695 patients (51.3%; range: 0–60%) who had inappropriate drug dosing. Drugs commonly prescribed in inappropriate doses in patients with dementia who had renal impairment included memantine, baclofen, nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, digoxin, morphine, and allopurinol. The studies did not identify statistically significant risk factors for inappropriate drug dosing. Conclusions: Inappropriate drug dosing among older adults with dementia or cognitive impairment and renal impairment appears to occur frequently. While our findings should be interpreted with caution owing to the small number of studies and substantial heterogeneity, proactive prevention, recognition, and management of inappropriate drug dosing in this population is warranted. Full article

This meta-analysis was designed to compare the risk of postoperative wound complications in various orthopedic surgeries (OSs) affected by the perioperative use of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The odds ratio (OR) and mean difference (MD), with 95% confidence intervals (CIs), were calculated using dichotomous or continuous random or fixed-effect models, based on the meta-analysis data. This study incorporated 14 investigations conducted between 2005 and 2023, encompassing a total population of 19,021 individuals undergoing diverse OSs. Participants who continued their bDMARDs exhibited a substantially higher incidence of postoperative surgical site infections (OR, 1.39; 95% CI, 1.12–1.72, p = 0.002) compared to those who withheld bDMARDs. However, the study did not find any statistically significant difference between the continuation or withholding of bDMARDs regarding delayed wound healing (OR, 2.02; 95% CI, 1.00–4.06, p = 0.05) or disease flares (OR, 0.59; 95% CI, 0.28–1.25, p = 0.17). The results show that patients who continued their bDMARDs had a notably higher incidence of postoperative surgical site infections. However, no significant differences were observed in delayed wound healing or disease flares when compared to those who withheld bDMARDs. It is important to acknowledge the limitations of this analysis, such as the relatively small number of participants and the limited number of studies available for certain comparisons, which may impact the validity of the findings. Full article

Cardiovascular disease and cardiovascular risk factors are global healthcare problems, given their high prevalence and the recognized low rates of adequate control despite the abundant body of evidence on different therapeutic options. The World Heart Federation has scrutinized the reasons for poor control of cardiovascular risk factors. Among these reasons, patients’ poor adherence to treatment regimens as well as limited rates of evidence-based therapy prescription from healthcare providers play a substantial role in the challenge of cardiovascular risk management. Polypills are fixed-dose combinations including two or more active drugs, from different pharmacological classes, combined in a single dosage form. Polypills were designed to simplify the clinical management of pharmacotherapy and increase adherence to treatment. From this perspective, we discuss the current literature on the use of polypills in the primary and secondary prevention of cardiovascular disease as well as future challenges and the potentials of this treatment strategy. Full article

Background: Hemodialysis patients are at high risk for developing Pneumocystis jirovecii pneumonia (PJP), and trimethoprim–sulfamethoxazole (TMP–SMX) is the first-line agent for treating this disease. However, there is a lack of consensus on the required dosage of TMP–SMX for hemodialysis patients. Methods: This study used the nationwide Japanese Diagnosis Procedure Combination database to review hemodialysis patients hospitalized for PJP from April 2014 to March 2022. Eligible patients were divided into high-dose and low-dose groups based on the median daily dose per body weight of TMP. The 90-day mortality and adverse events after propensity score matching were compared between the groups. Results: A total of 126 hemodialysis patients with PJP were included, and the median daily dose per body weight of TMP was 5.74 mg/kg/day (interquartile range: 4.33–8.18 mg/kg/day). Thirty-two pairs were analyzed after the propensity score matching. No significant differences in the 90-day mortality and proportion of adverse events were observed between the high-dose and low-dose groups. Conclusions: A high dose of TMP–SMX is unlikely to decrease the in-hospital mortality and adverse events among hemodialysis patients with PJP. However, the results should be interpreted with caution, given the lack of power and lack of long-term follow-up. Additional prospective interventional studies are required to validate these results. Full article

Background: Quality of life (QoL) is traditionally assessed using multiple-item questionnaires. These can be either general, global assessments of QoL or disease-specific questionnaires. However, the use of single-item QoL scales is becoming increasingly popular, as these are more time- and cost-effective, with a readily available and easy-to-interpret outcome. In particular, these are often preferred for quick assessments (e.g., ‘at home’ testing and mobile phone assessments), and other cases when time constraints are common (e.g., clinical trials and clinical practice). Previous research revealed that multiple-item questionnaires and single-item assessments of QoL have the same validity and reliability. Here we further evaluate the relationship of QoL, assessed with a single-item QoL scale, with well-being, mood, health correlates (e.g., immune fitness, and having underlying diseases), and lifestyle (e.g., sleep, nutrition). Methods: Data from two online surveys are presented. In Study 1, 100 students participated. The single-item QoL score was compared with the World Health Organization Well-Being Index (WHO-5), a single-item score of sleep quality, the Regensburg Insomnia Scale (RIS) score, and the Healthy Diet Scale (HDS). Study 2 comprised a survey among 1415 Dutch adults. Single-item QoL was evaluated and compared with assessments of mood, health correlates (immune fitness and disease status), and lifestyle factors (e.g., sleep, nutrition, stress). Results: The first study revealed significant correlations between QoL and well-being, sleep quality, insomnia ratings, and attaining a healthy diet. The second study revealed significant correlations between QoL and mood, health status, and lifestyle factors (e.g., the ability to cope with stress). Conclusions: The results presented here demonstrate that the single-item QoL scale is an effective and easy-to-implement assessment tool that can be used in both clinical practice and research. Full article

Background: Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). Objectives/Methods: The present study aimed to evaluate the post-exercise oxidative stress and inflammation in a group of subjects with obesity treated with melatonin (2 mg/die) or placebo, undergoing a 2-week BWRP, with the administration of a single bout of acute exercise at the start and the end of the protocol (G1–G15). Results: Eighteen adults with obesity were enrolled and distributed to the two arms of the study: the melatonin group (F/M: 7/2; age: 27.8 ± 5.6 years; body mass index [BMI]: 43.0 ± 4.9 kg/m²) and the placebo group (F/M: 6/3; age: 28.8 ± 5.0 years; BMI: 42.8 ± 4.0 kg/m²). BWRP induced a decrease in BMI and waist circumference (WC) in both groups; plasma glucose, blood glycated hemoglobin (HbA_1c), and neutrophil to lymphocyte ratio (NLR) were reduced only in the placebo group. Importantly, plasma biological antioxidant potential (BAP) increased throughout BWRP. Paradoxically, melatonin enhanced post-exercise production of plasma derivatives of reactive oxygen metabolites (d-ROMs) and erythrocytic glutathionyl-Hb (HbSSG) (at G1 and G15). Finally, differently from the placebo group, melatonin-treated subjects did not exhibit the BWRP-induced decrease in plasma levels of interleukin-6 (IL-6), before and after exercise, at the end of two weeks (G15). Conclusions: Melatonin is presumably an antioxidant with “conditional” prooxidant actions. The use of melatonin as a supplement in subjects with obesity might be deleterious due to the abolishment of BWRP-induced cardiometabolic benefits. Full article

Ranolazine is an anti-anginal medication that has demonstrated antiarrhythmic properties by inhibiting both late sodium and potassium currents. Studies have shown promising results for ranolazine in treating both atrial fibrillation and ventricular arrhythmias, particularly when used in combination with other medications. This review explores ranolazine’s mechanisms of action and its potential role in cardiac arrhythmias treatment in light of previous clinical studies. Full article

Background: Matrix metalloproteinases (MMPs) play an important role in the pathophysiology of atherosclerosis. Reportedly, statins can decrease MMP activity in patients with atherosclerotic cardiovascular disease, but this effect has not been studied in healthy individuals. Methods: MMPs 2, 7, and 9 and several other parameters were measured before and after a four-week course of moderate-dose atorvastatin (20 mg/day) in 21 healthy individuals. Results: Atorvastatin treatment resulted in lower total cholesterol, LDL-cholesterol, non-HDL-cholesterol, and triglycerides (p < 0.001 for all), but higher levels of plasma enzymes AST, ALT, CK, and LDH (p < 0.05 for all). No effect of atorvastatin on plasma MMP median concentrations was recorded. Before treatment, moderate positive significant correlations were found between MMP-7 and age, blood lipids, and blood count-derived inflammatory markers. Pre-treatment MMP-7 was best predicted by the total cholesterol-to-HDL cholesterol ratio in a remnant cholesterol-weighted least squares regression model. After atorvastatin treatment, MMP-7 no longer correlated with these markers. Conclusions: While the effect of statins on plasma MMPs in atherosclerosis is controversial, short-term moderate-dose atorvastatin treatment does not seem to affect levels of MMPs 2, 7, and 9 in healthy individuals. However, an intriguing correlation between MMP-7 and atherosclerosis-related blood lipids and neutrophil-associated inflammatory biomarkers seems to be disrupted by atorvastatin independently of hsCRP, possibly via pleiotropic effects. Full article

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options to treat both type 2 diabetes mellitus and nondiabetic overweight/obesity. Stemming from successful demonstration of their cardiometabolic modulation and reduction of major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling cardiovascular protective properties. Studies spanning from the bench to preclinical and large-scale randomised controlled trials have consistently corroborated the cardiovascular benefits of this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, with preclinical data indicating that they may do so by directly modifying the burden and composition of atherosclerotic plaques. This narrative review examines the underlying pharmacology and clinical evidence behind the cardiovascular benefits of GLP-1 RAs, with particular focus on atherosclerotic cardiovascular disease. It also delves into the mechanisms that underpin their putative plaque-modifying actions, addresses existing knowledge gaps and therapeutic challenges and looks to future developments in the field, including the use of combination incretin agents for diabetes and weight loss management. Full article

Background/Objectives: The use of food thickeners with ciprofloxacin tablets may result in a gelatinous appearance and experience delayed dissolution, which presents a challenge for the drug’s efficacy, creating a healthcare economic issue. However, the pharmacokinetic impact of this compound in humans remains uncertain. Therefore, a comparative pharmacokinetic study of ciprofloxacin was conducted on healthy adult Japanese males. Methods: We compared the effects of administering tablets with water or thickened water and crushed tablets mixed with thickened water. The maximum blood concentration (C_max) of ciprofloxacin determines the drug’s efficacy. Results: There were variations in drug absorption across different administration methods. The group who took the tablets immersed in thickened water exhibited different results in the area under the blood drug concentration–time curve (AUC) and C_max compared to the group who took the tablets in regular water. Notably, the group that consumed the crushed tablets mixed with thickened water demonstrated equivalent results for both AUC and C_max. Conclusions: Administering crushed tablets in thickened water may yield pharmacokinetics comparable to those of tablets taken with water. However, the process of crushing tablets may result in the loss of active ingredients and compromise the formulation, necessitating a comprehensive assessment before administration. Full article

Background: The most important factors contributing to multi-drug resistance in oral cancer include overexpression of the EGFR protein and the downstream malignancy regulators that are associated with it. This study investigates the impact of solanine on inflammation, proliferation, and angiogenesis inhibition in multidrug-resistant oral cancer KB-Chr-8-5 cells through inhibition of the EGFR/PI3K/Akt/NF-κB signaling pathway. Methods: Cell viability was assessed using an MTT assay to evaluate cytotoxic effects. Production of reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨM), and AO/EtBr staining were analyzed to assess apoptosis and mitochondrial dysfunction. Western blotting was employed to examine protein expression related to angiogenesis, apoptosis, and signaling pathways. Experiments were conducted in triplicate. Results: Solanine treatment at concentrations of 10, 20, and 30 μM significantly increased ROS production, which is indicative of its antioxidant properties. This increase was associated with decreased mitochondrial membrane potential (ΔΨM) with p < 0.05, suggesting mitochondrial dysfunction. Inhibition of EGFR led to reduced activity of PI3K, Akt, and NF-κB, resulting in decreased expression of iNOS, IL-6, Cyclin D1, PCNA, VEGF, Mcl-1, and HIF-1α and increased levels of the apoptotic proteins Bax, caspase-9, and caspase-3. These changes collectively inhibited the growth of multidrug-resistant (MDR) cancer cells. Conclusions: Solanine acts as a potent disruptor of cellular processes by inhibiting the EGFR-mediated PI3K/Akt/NF-κB signaling pathway. These results suggest that solanine holds promise as a potential preventive or therapeutic agent against multidrug-resistant cancers. Full article

Objectives: The objective of this study was to evaluate the real-world drug survival, adherence, and discontinuation risk of biologics disease-modifying anti-rheumatic drugs (bDMARDs) among patients with ankylosing spondylitis (AS). Methods: This was a retrospective study using a computerized database. Biologic-naïve and biologic-experienced AS patients who initiated treatment with bDMARDs (tumor necrosis factor alpha inhibitors {TNF-αis} or interleukin-17 inhibitor {IL-17i}) during 2015–2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Drug survival was analyzed using Kaplan–Meier estimates. Risk of discontinuation was estimated by the Cox proportional hazard model. Results: We identified 343 eligible patients utilizing 481 lines of therapy. The mean age was 44.6 years (SD ± 13.4), 57.7% were males, and 69.7% were biologic-naïve at baseline. The proportion of highly adherent patients (PDC ≥ 0.8) in the biologic-naïve group was 63.5% for golimumab, 69.2% for etanercept, and 71.6% for adalimumab (p > 0.9). Among the biologic-experienced group, secukinumab had the highest proportion of adherent patients (75.7%) and etanercept the lowest (50.0%) reaching statistical difference (p < 0.001). The Kaplan–Meier analysis did not show a significant difference in drug survival in either the biologic-naïve or the biologic-experienced groups (p = 0.85). Multivariable analysis demonstrated a similar risk for discontinuation for etanercept, golimumab, and secukinumab compared with adalimumab, regardless of biologic-experience status. Conclusions: Adherence, drug survival, and risk for discontinuation were similar for all TNF-αis and the IL-17i SEC, regardless of biologic-experience status. As drug survival is an indirect measure of drug efficacy, n, in real-world settings, we believe caregivers can integrate these results into treatment considerations. Full article

Background: This study investigated the effectiveness and safety of pharmacopuncture for pain relief and functional improvement in patients with traffic accident (TA)-induced acute tension headaches. Methods: The study employed a parallel, single-centered, pragmatic, randomized controlled trial design. Eighty patients complaining of acute tension headaches were randomized into the integrative Korean medicine treatment (IKM treatment) group and the pharmacopuncture group on suboccipital muscles (suboccipital muscles pharmacopuncture + IKM treatment), with 40 participants assigned to each group. The patients in the pharmacopuncture group underwent pharmacopuncture as an add-on therapy, consisting of three sessions. Both groups were reassessed 2 months post-intervention. To assess the outcomes, the Numeric Rating Scale (NRS) for Headache, NRS for Neck Pain, Headache Disability Index, Headache Impact Test-6, EuroQol 5-Dimension, and Patient Global Impression of Change were used. Results: The improvement in the outcomes of the pharmacopuncture group was significantly greater than that of the comparison group on day 4 of hospitalization in terms of pain (difference in NRS of headache −2.59, 95% CI −3.06 to −2.12; NRS of Neck pain −1.05, 95% CI −1.50 to −0.59) and function (difference in HDI −24.78, 95% CI, −31.79 to −17.76; HIT-6 −6.13, 95% CI, −9.47 to −2.78). Additionally, in 2 months of follow-up, the recovery rate of headache was significantly higher in the pharmacopuncture group than in the comparison group. Conclusions: The pharmacopuncture group demonstrated superior outcomes in symptom improvement than the comparison group did, providing insights into novel and useful applications of pharmacopuncture in the clinical practice of Korean medicine. Full article