Eur Rev Med Pharmacol Sci. 2023 Aug;27(16):7768-7780. doi: 10.26355/eurrev_202308_33431.

ABSTRACT

OBJECTIVE: The aim of this study was to systematically assess the effects of different targeted therapies associated with adjuvant chemotherapy on clinical remission, survival and safety of patients with triple-negative breast cancer (TNBC).

MATERIALS AND METHODS: This study searched for case-control trials of TNBC patients from January 2010 to May 2022. Two researchers independently extracted data. RevMan 5.3 statistical software was used for analysis.

RESULTS: This study included a total of 7 clinical controlled studies, containing 620 samples. The results showed that compared with the control group, the study group showed significant differences in objective response rate [OR = 2.44, 95% CI (1.69, 3.5), p < 0.00001], 1-year survival rate [OR = 3.59, 95% CI (2.01, 6.39), p < 0.0001], progression-free survival (PFS) [MD = 2.04, 95% CI (1.68, 2.41), p < 0.00001], with statistical significance (p < 0.05), while there are no significant differences in overall survival [MD = 6.33, 95% CI (-1.65, 14.30), p = 0.12] and incidence of adverse events [OR = 0.73, 95% CI (0.52, 1.02), p = 0.006] (p > 0.05).

CONCLUSIONS: Targeted therapy associated with adjuvant chemotherapy can remarkably enhance the outcome of patients with advanced TNBC, prolonging their progression-free survival (PFS) and overall survival (OS) without increasing adverse effects. The validity of this research, however, will require higher quality studies and longer follow-ups.

PMID:37667955 | DOI:10.26355/eurrev_202308_33431

Ned Tijdschr Tandheelkd. 2023 Sep;130(9):373-375. doi: 10.5177/ntvt.2023.09.23034.

ABSTRACT

Dry mouth has a complex aetiology which makes proper diagnosis complicated. Until now, dry mouth diagnosis has mainly focused on the overall oral dryness, without taking into account regional differences within the mouth. This research showed, among other things, that there are unique patterns of oral dryness, each with its own cause. For example, patients suffering from Sjogren's syndrome mainly experienced dryness of the posterior of the palate. Patients with dry mouth due to the side effects of medication, in contrast, experienced the front part of the tongue as the driest. These findings suggest that mapping of intraoral dryness may be a useful diagnostic tool to differentiate between possible causes of dry mouth.

PMID:37667634 | DOI:10.5177/ntvt.2023.09.23034

Expert Opin Emerg Drugs. 2023 Sep 5. doi: 10.1080/14728214.2023.2254686. Online ahead of print.

ABSTRACT

INTRODUCTION: Despite the availability of a variety of therapeutic compounds and improved management strategies, one-third of UC patients with moderate-to-severe disease do not benefit from the existing treatments or experience drug-related side effects. This has boosted intensive research focusing on the development of new drugs for UC therapy. This article aims to summarize the available evidence on oral drugs, which are now being explored in clinical trials or are ready to enter the clinics.

AREAS COVERED: From 15 May to 11 June, we searched on PubMed using the keywords 'oral drugs ulcerative colitis,' 'ulcerative colitis clinical trials,' 'UC phase 2 and 3 trials' excluding case reports, case series, phase 1 and 4 studies, and studies about approved therapies.

EXPERT OPINION: The findings discussed in this article suggest that the future treatment of UC patients will be probably characterized by the possibility of using various small-molecule drugs. All these new compounds, even those belonging to the same class, differ in terms of efficacy and safety. Identification of predictors of response could help optimize the efficacy and safety of these treatments, thus improving resource allocation through a pre-treatment stratification of patients.

PMID:37668153 | DOI:10.1080/14728214.2023.2254686

J Clin Hypertens (Greenwich). 2023 Sep 4. doi: 10.1111/jch.14700. Online ahead of print.

ABSTRACT

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

PMID:37667532 | DOI:10.1111/jch.14700

BMC Infect Dis. 2023 Sep 4;23(1):578. doi: 10.1186/s12879-023-08544-x.

ABSTRACT

HIV post- exposure prophylaxis (PEP) is a prevention tool for individuals with a recent potential exposure to HIV. Doravirine has been available since 2019 in combination with tenofovir disoproxil fumarate and lamivudine and has not been evaluated as a PEP. DOR/3TC/TDF is our department's most commonly prescribed PEP treatment since 2021. This study evaluates the completion rate of the DOR/3TC/TDF as compared to EVG/c/FTC/TAF for PEP, which was the regimen prescribed until 2020 in our hospital.This retrospective observational study was conducted between January 2020 and September 2021. The subjects included consecutively were adults who consulted for an HIV sexual exposure accident and for whom DOR/3TC/TDF in 2021 or EVG/c/FTC/TAF in 2020 was prescribed. The outcomes were the completion rate to the end of treatment (28 days), the seroconversion rate, and the description of side effects.During the study period, 311 people were included: 140 treated with DOR/3TC/TDF and 171 treated with EVGc/FTC/TAF. Considering subjects with a follow-up visit, the completion rate was 96.8% (90/93) in the DOR/3TC/TDF group, and 94.6% (123/130) in the EVG/c/FTC/TAF group (p-value: 0.53). The number of people lost to follow-up was nearly equivalent in both groups: 27.1% (38/140) in the DOR/3TC/TDF group and 23.4% (40/171) in the EVG/c/FTC/TAF group (p-value: 0.45). A side effect was described for 38% (36/94) in the DOR/3TC/TDF group, and 29.7% (38/128) in the EVG/c/FTC/TAF group. No cases of seroconversion were observed.DOR/3TC/TDF appears to have a similar safety profile to EVG/c/FTC/TAF. Due to its lower cost, it seems to be a treatment option for consideration in the context of HIV-exposure accidents.

PMID:37667182 | PMC:PMC10478445 | DOI:10.1186/s12879-023-08544-x

J Int Med Res. 2023 Aug;51(8):3000605231197069. doi: 10.1177/03000605231197069.

ABSTRACT

Postoperative intractable hiccups slow patient recovery and generate multiple adverse effects, highlighting the importance of investigating the pathogenesis and terminating the hiccups in a timely manner. At present, medical and physical therapies account for the main treatments. We encountered a case in which postoperative intractable hiccups after biliary T-tube drainage removal ceased with the application of an ultrasound-guided block of the unilateral phrenic nerve and stellate ganglion. No complications developed, and the therapeutic effect was remarkable. To our knowledge, this approach has not been reported to date. Simultaneously blocking the phrenic nerve and stellate ganglion may be a treatment option for intractable hiccups.

PMID:37666219 | PMC:PMC10478533 | DOI:10.1177/03000605231197069

Int J Qual Stud Health Well-being. 2023 Dec;18(1):2253001. doi: 10.1080/17482631.2023.2253001.

ABSTRACT

BACKGROUND: The original project, where older persons received reablement performed by an interprofessional team showed success factors for IHR. However, since there is a lack of knowledge about why some persons do not recover despite receiving IHR, this study follows up patients' experiences of IHR.

AIM: To describe older persons' perceived dilemmas in the reablement process within the framework of IHR.

METHOD: 11 CIT interviews with participants who have previously received IHR, were analysed, interpreted and categorized according to CIT. The study was approved by the Swedish Ethical Review Authority.

RESULTS: The results showed disease-related dilemmas, fatigue or pain so that participants could not cope with the prescribed exercises. New diseases appeared, as well as medication side effects made exercising difficult, and painkillers became a prerequisite for coping with IHR. Low self-motivation and mistrust towards the staff emerged like lack of trust due to otherness such as sex, cultural background, or language also became critical.

CONCLUSIONS: Interventions that consider individual- and contextual dilemmas are very important. By recognizing critical situations, this study can work as a basis of evidence to further develop interventions for older people living in their own homes and to ensure them to stay there.

PMID:37665969 | PMC:PMC10478589 | DOI:10.1080/17482631.2023.2253001

Psychol Sport Exerc. 2023 May;66:102399. doi: 10.1016/j.psychsport.2023.102399. Epub 2023 Feb 1.

ABSTRACT

Kinesiology aspires to be an integrated, interdisciplinary field that studies human movement from multiple perspectives. However, the main societal deliverables of the field, namely exercise prescriptions and physical activity recommendations, still reflect fragmentation, placing more emphasis on physiological outcomes than on behavioral and other considerations. Recently, researchers have called for the introduction of High-Intensity Interval Training (HIIT) to the domain of public health, based on the argument that HIIT can maximize fitness and health benefits for a fraction of the time recommended by the prevailing model of physical activity in public-health guidelines. Here, we show that an unintended side-effect of arguments underpinning the implementation of HIIT in the domain of public health might have been the exacerbation of segmentation. To highlight the value of interdisciplinarity, four foundational claims in support of HIIT are critiqued by tapping into cognate literatures: (1) the primary reason people do not exercise is lack of time, (2) HIIT is relevant to public health, (3) HIIT is being proposed as merely another option, so there is no basis for controversy, and (4) HIIT is safe and well tolerated. These claims are contradicted by credible lines of evidence. To improve the accuracy and effectiveness of its public claims, kinesiology should remain committed to the ideals of integration and interdisciplinarity.

PMID:37665861 | DOI:10.1016/j.psychsport.2023.102399

Pain Res Manag. 2023 Aug 23;2023:1523834. doi: 10.1155/2023/1523834. eCollection 2023.

ABSTRACT

The purpose of this systematic review and meta-analysis was to assess the short-, mid-, and long-term effectiveness of dry needling in improving pain and functional capacity of patients with chronic neck pain. Search strategy was performed on PubMed, Web of Science, Scopus, PEDro, and Cochrane Library Plus biomedical databases. The risk of bias was assessed using the RoB2 tool. Randomised controlled clinical trials in which at least 1 of the groups received dry needling were included. 662 studies were found; 14 clinical trials were selected for qualitative analysis and 13 for quantitative analysis. The quality of most of the studies included was "high." All the studies reported improvements in cervical pain and/or disability, regardless of the protocol followed and the muscles targeted. No serious adverse effects were reported. Dry needling showed to be more effective when compared with other therapies in both women and men, without differences by sex. When the analysis was carried out by age, patients over 40 years old benefitted more than those below 40 years old. Our meta-analysis supports the use of dry needling to improve pain and functional capacity in patients with chronic neck pain at short- and mid-term intervals.

PMID:37664417 | PMC:PMC10469395 | DOI:10.1155/2023/1523834

Biol Pharm Bull. 2023;46(9):1332-1337. doi: 10.1248/bpb.b23-00157.

ABSTRACT

Infusion-related reactions (IRRs) are the major side effects of rituximab administration. Although several studies have reported predictive markers for IRRs in patients with malignancies, there are no such reports for patients without malignancies. Accordingly, we aimed to clarify the predictive markers for rituximab-induced IRRs in renal transplant recipients. This retrospective study included 116 inpatients aged ≥18 years who received an initial dose of 150 mg/m2 of rituximab for desensitization before renal transplantation with loxoprofen and diphenhydramine before rituximab infusion between June 2007 and February 2022. Overall, 45 patients were evaluated and 71 patients were excluded in this study. IRRs were observed in 12 (26.7%) patients. The proportion of men in the IRRs group was significantly higher than that in the non-IRRs group (p = 0.023). Additionally, body weight, body surface area (BSA), and body mass index (BMI) were significantly higher in the IRRs group than in the non-IRRs group (body weight, p = 0.0058; BSA, p = 0.0051; BMI, p = 0.017). Their cutoff values for predicting rituximab-induced IRRs, based on the receiver-operating characteristic curve, were 74.850 kg, 1.910 m2 and 24.164 kg/m2, respectively. In conclusion, the male sex, high actual body weight, BSA, and BMI may be new predictive markers for rituximab-induced IRRs in renal transplant recipients. Therefore, clinicians should carefully monitor patients who receive rituximab before renal transplantation and present with the predictive markers.

PMID:37661411 | DOI:10.1248/bpb.b23-00157

Adv Mater. 2023 Sep 4:e2305095. doi: 10.1002/adma.202305095. Online ahead of print.

ABSTRACT

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. We believe that our review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy. This article is protected by copyright. All rights reserved.

PMID:37665594 | DOI:10.1002/adma.202305095

Naunyn Schmiedebergs Arch Pharmacol. 2023 Sep 4. doi: 10.1007/s00210-023-02679-z. Online ahead of print.

ABSTRACT

Mycobacterium tuberculosis (Mtb) is a pathogenic bacterium which causes tuberculosis (TB). TB control programmes are facing threats from drug resistance. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb strains need longer and more expensive treatment with many medications resulting in more adverse effects and decreased chances of treatment outcomes. The World Health Organization (WHO) has emphasised the development of not just new individual anti-TB drugs, but also novel medication regimens as an alternative treatment option for the drug-resistant Mtb strains. Many plants, as well as marine creatures (sponge; Haliclona sp.) and fungi, have been continuously used to treat TB in various traditional treatment systems around the world, providing an almost limitless supply of active components. Natural products, in addition to their anti-mycobacterial action, can be used as adjuvant therapy to increase the efficacy of conventional anti-mycobacterial medications, reduce their side effects, and reverse MDR Mtb strain due to Mycobacterium's genetic flexibility and environmental adaptation. Several natural compounds such as quercetin, ursolic acid, berberine, thymoquinone, curcumin, phloretin, and propolis have shown potential anti-mycobacterial efficacy and are still being explored in preclinical and clinical investigations for confirmation of their efficacy and safety as anti-TB medication. However, more high-level randomized clinical trials are desperately required. The current review provides an overview of drug-resistant TB along with the latest anti-TB medications, drug-induced hepatotoxicity and oxidative stress. Further, the role and mechanisms of action of first and second-line anti-TB drugs and new drugs have been highlighted. Finally, the role of natural compounds as anti-TB medication and hepatoprotectants have been described and their mechanisms discussed.

PMID:37665346 | DOI:10.1007/s00210-023-02679-z

Chemistry. 2023 Sep 4:e202302197. doi: 10.1002/chem.202302197. Online ahead of print.

ABSTRACT

Stimuli-responsive fluorogenic prodrugs are advantageous for the targeted drug delivery enabling real-time non-invasive monitoring with turn-on fluorescence. We report herein the dual-stimuli (ROS and CA)-responsive thiocarbamate-based prodrug (AM-TCB) for the turn-on fluorogenic delivery of the naphthalimide-based anticancer agent amonafide along with the gasotransmitter hydrogen sulfide (H2S). A carbamate-based prodrug AM-CB was also designed, capable of releasing the anticancer agent amonafide without any H2S. The prodrugs were synthesized using multi-step organic synthesis. UV-Vis and fluorescence spectroscopic studies revealed selective reactivity of the boronate ester group of prodrugs towards ROS (primarily H2O2) with the release of amonafide and COS/CO2 via self-immolative processes. Hydrolysis of the generated COS by carbonic anhydrase (CA) produces H2S. While the prodrug AM-TCB retained the anticancer activity of free amonafide in cancer cells (MDA-MB-231 and HeLa), unlike amonafide, it enhanced the cellular viability of the non-malignant cells (HEK-293). Fluorescence imaging in HeLa cells revealed the simultaneous delivery of the anticancer agent and H2S from AM-TCB with turn-on fluorescence. Western blot studies further revealed the cytoprotective effects of the released H2S from AM-TCB. The present adjuvant strategy therefore would be helpful in future for ameliorating the anticancer drug-induced side-effects.

PMID:37665099 | DOI:10.1002/chem.202302197

BJPsych Open. 2023 Sep 4;9(5):e166. doi: 10.1192/bjo.2023.513.

ABSTRACT

A patient developed fever, raised inflammatory markers and a maculopapular rash following commencement of clozapine for treatment of his schizoaffective disorder. Skin biopsy confirmed Sweet's syndrome. Identification of the cause was challenging, with a number of possible considerations including infection, malignancy and various potential drug triggers.This case highlights the difficulties in the diagnosis of Sweet's syndrome, as well as in identifying the original trigger, which can have significant consequences for management. Withdrawal of potentially causative drugs must be balanced with their benefits, and decisions must be made in the best interests of the patient. Following two courses of prednisolone and withdrawal of clozapine, the patient's rash and systemic symptoms resolved. This confirmed the diagnosis of drug-induced Sweet's syndrome, with clozapine as the offending agent. His mental state stabilised on an alternative antipsychotic.

PMID:37665047 | DOI:10.1192/bjo.2023.513

Cureus. 2023 Aug 3;15(8):e42894. doi: 10.7759/cureus.42894. eCollection 2023 Aug.

ABSTRACT

Ondansetron, a drug predominantly employed in most general anesthesia cases, is critical for mitigating postoperative nausea and vomiting prompted by anesthetics. Although infrequent side effects such as serotonin syndrome are recognized, the drug is generally acknowledged for its safety. Nonetheless, some reports showed cases of anaphylactic shock associated with ondansetron. In this context, we have meticulously analyzed an anaphylactic case triggered by ondansetron that we encountered. Our deep-dive investigation suggests that the reaction might not be a traditional type I allergic reaction, typically associated with the drug. Instead, we present the possibility that the response could be mediated through Mas-related G protein-coupled receptor X2 (MRGPRX2), a divergent pathway leading to comparatively milder symptoms of anaphylaxis. In addition to the crucial role of adrenaline in unstable hemodynamics, our case highlights the effective use of antihistamines in rapidly managing such reactions. This finding suggests a need to further examine the safety profiles of common drugs like ondansetron and the potential involvement of MRGPRX2 in drug-induced hypersensitivity reactions.

PMID:37664335 | PMC:PMC10474905 | DOI:10.7759/cureus.42894

Ann Med Surg (Lond). 2023 Aug 7;85(9):4629-4632. doi: 10.1097/MS9.0000000000001135. eCollection 2023 Sep.

ABSTRACT

INTRODUCTION AND IMPORTANCE: While 14-day triple therapy with clarithromycin is a common approach for eradicating Helicobacter pylori infection, it is essential to note that this treatment does not come without potential side effects.

CASE PRESENTATION: We present the case of a 34-year-old male who presented to the emergency department with severe vomiting and abdominal pain. Subsequent evaluation revealed that the patient had developed drug-induced liver injury (DILI).

CLINICAL DISCUSSION: DILI can cause acute hepatocellular or cholestatic damage, and chronic injury can lead to hepatocellular, cholestatic, vascular, or neoplastic manifestations.

CONCLUSION: Clinicians should exercise caution and be alert to the potential hepatotoxic effects of medications, especially when initiating triple therapy for H. pylori infection.

PMID:37663679 | PMC:PMC10473337 | DOI:10.1097/MS9.0000000000001135

SAGE Open Med Case Rep. 2023 Aug 30;11:2050313X231197062. doi: 10.1177/2050313X231197062. eCollection 2023.

ABSTRACT

Parkinson's disease is a neurodegenerative disease resulting from the loss of dopamine-secreting neurons present in the substantia nigra of the brain. Parkinson's disease is classified as early-onset and late-onset disease based on the time of its presentation. Since young patients with Parkinson's disease have an atypical clinical presentation and have to deal with their careers, raising families, or both at the time of diagnosis and also have a higher risk of drug-related side effects, it poses unique challenges for the patient, clinical team, and community. We present the case of a 40-year-old female with young onset Parkinson's disease from rural Nepal and the challenges faced during and after the disease in a resource-limited setting.

PMID:37663151 | PMC:PMC10474787 | DOI:10.1177/2050313X231197062

Infect Drug Resist. 2023 Aug 28;16:5637-5645. doi: 10.2147/IDR.S417711. eCollection 2023.

ABSTRACT

PURPOSE: The emergence of resistant strains has greatly reduced the eradication rate of H. pylori (HP) in conventional bismuth-containing quadruple therapy. Meanwhile, the new 7-day dual therapy with vonoprazan (VPZ) and amoxicillin (AMO) failed to achieve the expected therapeutic effect in China.

PATIENTS AND METHODS: A total of 256 untreated HP-infected patients are included in this non-inferiority clinical trial. The patients were randomly divided into three groups: 14-day dual therapy group (VPZ 20mg b.i.d + AMO 750mg t.i.d for 14 days, VA14), 14-day modified triple therapy group (VA14 + Jinghua Weikang Capsule 160mg t.i.d, VAC), and conventional bismuth-containing quadruple therapy group for 14 days (BCQ). Eradication rates, drug-related adverse events (AEs), patient compliance, and drug costs were compared among the three groups.

RESULTS: The eradication rates in the BCQ, VA14, and VAC were 78.67, 77.33%, and 86.49% by intention-to-treat analysis, respectively, and 96.72%, 90.63%, and 92.75% by pre-protocol or modified intention-to-treat analysis, respectively. VA14 therapy indicated a non-inferiority eradication rate and advanced safety and economics to BCQ therapy. JWC further improved the eradication rate and reduced the incidence of AEs.

CONCLUSION: A modified 14-day dual therapy with VPZ and AMO provides satisfied efficacy as the first-line treatment for HP infection in China.

PMID:37662977 | PMC:PMC10473400 | DOI:10.2147/IDR.S417711

Orv Hetil. 2023 Sep 3;164(35):1381-1386. doi: 10.1556/650.2023.32849. Print 2023 Sep 3.

ABSTRACT

INTRODUCTION: In metastatic melanoma, despite the increased survival rates with new innovative therapies, therapeutic response is still quite heterogenous, not always durable. In the case of oligoprogression, several additional therapeutic modalities are available such as electrochemotherapy in the local treatment of cutaneous or subcutaneous metastases.

OBJECTIVE: Analysis of our experiences with electrochemotherapy in patients with metastatic melanoma.

METHOD AND RESULTS: 23 patients with metastatic melanoma (10 male and 13 female) were treated with electrochemotherapy, between 2016 and 2021 in our Institute. Median age was 74.5 years. The location of metastases varied. 13 of our patients (57%) had metastases on the lower limbs, in 5 cases (22%) metastases were located in the head and neck region, in 4 cases (17%) on the upper limbs, and one (4%) patient received electrochemotherapy for metastases located on the chest. Prior to electrochemotherapy, 7 patients (30%) received chemotherapy, 6 patients (26%) were treated with immunotherapy and 2 patients (9%) received targeted therapy, while electrochemotherapy was first-line treatment for 8 patients (35%). Complete remission was achieved in 12 cases (52%), and partial remission in 6 cases (26%). In 1 case (4%) stable disease was observed, and in 4 patients (35%) progression was detected. We continued the previous systemic therapy which was effective in other localizations after the electrochemotherapy in 8 patients (35%) and in the case of 4 patients (17%) no further systemic therapy was needed. Side effects were observed in 8 patients (35%), 1 had severity of G3.

CONCLUSION: Electrochemotherapy in melanoma results in effective local tumor control, improved quality of life, and survival advantage in most of the patients, with tolerable side effects. Orv Hetil. 2023; 164(35): 1381-1386.

PMID:37660345 | DOI:10.1556/650.2023.32849

Toxicol Appl Pharmacol. 2023 Sep 1:116676. doi: 10.1016/j.taap.2023.116676. Online ahead of print.

ABSTRACT

Cardiac and extra-cardiac side effects of common antiarrhythmic agents might be related to drug-induced mitochondrial dysfunction. Supratherapeutic doses of amiodarone have been shown to impair mitochondria in animal studies, whilst influence of propafenone on cellular bioenergetics is unknown. We aimed to assess effects of protracted exposure to pharmacologically relevant doses of amiodarone and propafenone on cellular bioenergetics and mitochondrial biology of human and mouse cardiomyocytes. In this study, HL-1 mouse atrial cardiomyocytes and primary human cardiomyocytes derived from the ventricles of the adult heart were exposed to 2 and 7 μg/mL of either amiodarone or propafenone. After 24 h, extracellular flux analysis and confocal laser scanning microscopy were used to measure mitochondrial functions. Autophagy was assessed by western blots and live-cell imaging of lysosomes. In human cardiomyocytes, amiodarone significantly reduced mitochondrial membrane potential and ATP production, in association with an inhibition of fatty acid oxidation and impaired complex I- and II-linked respiration in the electron transport chain. Expectedly, this led to increased anaerobic glycolysis. Amiodarone increased the production of reactive oxygen species and autophagy was also markedly affected. In contrast, propafenone-exposed cardiomyocytes did not exert any impairment of cellular bioenergetics. Similar changes after amiodarone treatment were observed during identical experiments performed on HL-1 mouse cardiomyocytes, suggesting a comparable pharmacodynamics of amiodarone among mammalian species. In conclusion, amiodarone but not propafenone in near-therapeutic concentrations causes a pattern of mitochondrial dysfunction with affected autophagy and metabolic switch from oxidative metabolism to anaerobic glycolysis in human cardiomyocytes.

PMID:37661063 | DOI:10.1016/j.taap.2023.116676