Drug-induced Adverse Events

Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Antitubercular drugs: possible role of natural products acting as antituberculosis medication in overcoming drug resistance and drug-induced hepatotoxicity

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Dual-Stimuli-Activatable Hybrid Prodrug for the Self-Immolative Delivery of an Anticancer Agent and Hydrogen Sulfide with Turn-on Fluorescence

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Clozapine and Sweet's syndrome: case report

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Ondansetron-Induced Anaphylactic Shock: An In-Depth Analysis of a Rare Adverse Event

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Clarithromycin-induced acute liver injury in a patient with positive <em>Helicobacter pylori</em>: a case report and review of the literature

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Diagnostic pitfalls in young onset parkinsonism and its unique challenges: A case report from rural Nepal

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

A Modified 14-Day Dual Therapy with Vonoprazan and Amoxicillin Amplified the Advantages Over Conventional Therapies for Eradication of <em>Helicobacter pylori</em>: A Non-Inferiority Clinical Trial

Mon, 2023-09-04 06:00

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

Categories: Literature Watch

Electrochemotherapy in metastatic melanoma

Sun, 2023-09-03 06:00

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

Categories: Literature Watch

Amiodarone but not propafenone impairs bioenergetics and autophagy of human myocardial cells

Sun, 2023-09-03 06:00

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

Categories: Literature Watch

Side effects following vaccination in multiple sclerosis: a prospective, multi-centre cohort study

Sat, 2023-09-02 06:00

Sci Rep. 2023 Sep 2;13(1):14480. doi: 10.1038/s41598-023-41271-6.

ABSTRACT

Vaccines play a crucial role in preventing infections in patients with multiple sclerosis (MS), although concerns have been raised about potential worsening of the underlying disease. To investigate this, we conducted a prospective, multicentre, non-randomized observational study assessing changes in disease activity, safety, and clinical tolerability of vaccination in 222 MS patients on disease-modifying drugs. The majority of patients were female (76.6%) and 89.6% had relapsing-remitting MS. The vaccines administered were primarily seasonal influenza (56.3%) or tetanus-based vaccines (33.8%). Disease activity, as measured by annualized relapse rate, decreased significantly from 0.64 the year prior to vaccination to 0.38 in the following year. Moreover, the extended disability status scale remained stable within six months after vaccination in comparison to pre-vaccination values. Side effects were reported in 19.2% of vaccinated subjects, most commonly local side effects (65.2%) or flu-like symptoms (34.8%). Our findings suggest that standard non-live vaccines are safe and well-tolerated in MS patients and do not negatively impact disease activity.

PMID:37660223 | PMC:PMC10475060 | DOI:10.1038/s41598-023-41271-6

Categories: Literature Watch

Childhood nephrotic syndrome

Sat, 2023-09-02 06:00

Lancet. 2023 Sep 2;402(10404):809-824. doi: 10.1016/S0140-6736(23)01051-6.

ABSTRACT

Idiopathic nephrotic syndrome is the most common glomerular disease in children. Corticosteroids are the cornerstone of its treatment, and steroid response is the main prognostic factor. Most children respond to a cycle of oral steroids, and are defined as having steroid-sensitive nephrotic syndrome. Among the children who do not respond, defined as having steroid-resistant nephrotic syndrome, most respond to second-line immunosuppression, mainly with calcineurin inhibitors, and children in whom a response is not observed are described as multidrug resistant. The pathophysiology of nephrotic syndrome remains elusive. In cases of immune-mediated origin, dysregulation of immune cells and production of circulating factors that damage the glomerular filtration barrier have been described. Conversely, up to a third of cases of steroid-resistant nephrotic syndrome have a monogenic origin. Multidrug resistant nephrotic syndrome often leads to kidney failure and can cause relapse after kidney transplant. Although steroid-sensitive nephrotic syndrome does not affect renal function, most children with steroid-sensitive nephrotic syndrome have a relapsing course that requires repeated steroid cycles with significant side-effects. To minimise morbidity, some patients require steroid-sparing immunosuppressive agents, including levamisole, mycophenolate mofetil, calcineurin inhibitors, anti-CD20 monoclonal antibodies, and cyclophosphamide. Close monitoring and preventive measures are warranted at onset and during relapse to prevent acute complications (eg, hypovolaemia, acute kidney injury, infections, and thrombosis), whereas long-term management requires minimising treatment-related side-effects. A subset of patients have active disease into adulthood.

PMID:37659779 | DOI:10.1016/S0140-6736(23)01051-6

Categories: Literature Watch

Efficacy and Safety of Pegvisomant in the Treatment of Acromegaly

Sat, 2023-09-02 06:00

Arch Med Res. 2023 Aug 31:102884. doi: 10.1016/j.arcmed.2023.102884. Online ahead of print.

ABSTRACT

Pegvisomant, the first and currently only clinically available growth hormone receptor antagonist, is an effective therapeutic option for the medical treatment of acromegaly, a rare disorder characterized by excessive growth hormone secretion. With now over 20 years of real world experience, its safety and efficacy is well-established. However, several aspects of its clinical use are still controversially discussed. The high cost of pegvisomant has limited its use in several countries, and recent studies have reported a lower efficacy than the initial clinical trials. A reported increase in tumor volume under therapy varies between studies and has been attributed to either actual growth or re-expansion after cessation of somatostatin receptor ligand therapy. Furthermore, different combinations of pegvisomant and other therapeutic agents aiming at reduction of acromegaly disease activity have been proposed to increase or retain effectiveness while lowering side effects and cost. This review aims to assess current clinical data on the safety and efficacy of pegvisomant while also addressing controversies surrounding its use.

PMID:37659952 | DOI:10.1016/j.arcmed.2023.102884

Categories: Literature Watch

Factors that impact on recruitment to vaccine trials in the context of a pandemic or epidemic: a qualitative evidence synthesis

Fri, 2023-09-01 06:00

Cochrane Database Syst Rev. 2023 Sep 1;9(9):MR000065. doi: 10.1002/14651858.MR000065.pub2.

ABSTRACT

BACKGROUND: The World Health Organization declared the COVID-19 pandemic on 11 March 2020. Vaccine development and deployment were swiftly prioritised as a method to manage and control disease spread. The development of an effective vaccine relies on people's participation in randomised trials. Recruitment to vaccine trials is particularly challenging as it involves healthy volunteers who may have concerns around the potential risks and benefits associated with rapidly developed vaccines.

OBJECTIVES: To explore the factors that influence a person's decision to participate in a vaccine trial in the context of a pandemic or epidemic.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was June 2021.

SELECTION CRITERIA: We included qualitative studies and mixed-methods studies with an identifiable qualitative component. We included studies that explored the perspectives of adults aged 18 years or older who were invited to take part in vaccine trials in the context of a pandemic or epidemic.

DATA COLLECTION AND ANALYSIS: We assessed the title, abstracts and full texts identified by the search. We used a sampling frame to identify data-rich studies that represented a range of diseases and geographical spread. We used QSR NVivo to manage extracted data. We assessed methodological limitations using an adapted version of the Critical Skills Appraisal Programme (CASP) tool for qualitative studies. We used the 'best-fit framework approach' to analyse and synthesise the evidence from our included studies. We then used the Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) assessment to assess our confidence in each finding and develop implications for practice.

MAIN RESULTS: We included 34 studies in our review. Most studies related to HIV vaccine trials. The other studies related to Ebola virus, tuberculosis, Zika virus and COVID-19. We developed 20 key findings, under three broad themes (with seven subthemes), that described the factors that people consider when deciding whether to take part in a vaccine trial for a pandemic or epidemic disease. Our GRADE-CERQual confidence was high in nine of the key findings, moderate in 10 key findings and low in one key finding. The main reason for downgrading review findings were concerns regarding the relevance and adequacy of the underlying data. As a result of the over-representation of HIV studies, our GRADE-CERQual assessment of some findings was downgraded in terms of relevance because the views described may not reflect those of people regarding vaccine trials for other pandemic or epidemic diseases. Adequacy relates to the degree of richness and quantity of data supporting a review finding. Moderate concerns about adequacy resulted in a downgrading of some review findings. Some factors were considered to be under the control of the trial team. These included how trial information was communicated and the inclusion of people in the community to help with trial information dissemination. Aspects of trial design were also considered under control of the trial team and included convenience of participation, provision of financial incentives and access to additional support services for those taking part in the trial. Other factors influencing people's decision to take part could be personal, from family, friends or wider society. From a personal perceptive, people had concerns about vaccine side effects, vaccine efficacy and possible impact on their daily lives (carer responsibilities, work, etc.). People were also influenced by their families, and the impact participation may have on relationships. The fear of stigma from society influenced the decision to take part. Also, from a societal perspective, the level of trust in governments' involvement in research and trial may influence a person's decision. Finally, the perceived rewards, both personal and societal, were influencing factors on the decision to participate. Personal rewards included access to a vaccine, improved health and improved disease knowledge, and a return to normality in the context of a pandemic or epidemic. Potential societal rewards included helping the community and contributing to science, often motivated by the memories of family and friends who had died from the disease.

AUTHORS' CONCLUSIONS: This review identifies many of the factors that influence a person's decision to take part in a vaccine trial, and these reflect findings from reviews that examine trials more broadly. However, we also recognise some factors that become more important in connection with a vaccine trial in the context of a pandemic or epidemic. These factors include the potential stigma of taking part, the possible adverse effects of a vaccine, the added motivation for helping society, the role of community leaders in trial dissemination, and the level of trust placed in governments and companies developing vaccines. These specific influences need to be considered by trial teams when designing, and communicating about, vaccine trials in the context of a pandemic or epidemic.

PMID:37655964 | PMC:PMC10472890 | DOI:10.1002/14651858.MR000065.pub2

Categories: Literature Watch

Cold Case of Thrombolysis: Cold Recombinant Tissue Plasminogen Activator Confers Enhanced Neuroprotection in Experimental Stroke

Fri, 2023-09-01 06:00

J Am Heart Assoc. 2023 Sep 5;12(17):e029817. doi: 10.1161/JAHA.123.029817. Epub 2023 Sep 1.

ABSTRACT

Background Thrombolysis and endovascular thrombectomy are the primary treatment for ischemic stroke. However, due to the limited time window and the occurrence of adverse effects, only a small number of patients can genuinely benefit from recanalization. Intraarterial injection of rtPA (recombinant tissue plasminogen activator) based on arterial thrombectomy could improve the prognosis of patients with acute ischemic stroke, but it could not reduce the incidence of recanalization-related adverse effects. Recently, selective brain hypothermia has been shown to offer neuroprotection against stroke. To enhance the recanalization rate of ischemic stroke and reduce the adverse effects such as tiny thrombosis, brain edema, and hemorrhage, we described for the first time a combined approach of hypothermia and thrombolysis via intraarterial hypothermic rtPA. Methods and Results We initially established the optimal regimen of hypothermic rtPA in adult rats subjected to middle cerebral artery occlusion. Subsequently, we explored the mechanism of action mediating hypothermic rtPA by probing reduction of brain tissue temperature, attenuation of blood-brain barrier damage, and sequestration of inflammation coupled with untargeted metabolomics. Hypothermic rtPA improved neurological scores and reduced infarct volume, while limiting hemorrhagic transformation in middle cerebral artery occlusion rats. These therapeutic outcomes of hypothermic rtPA were accompanied by reduced brain temperature, glucose metabolism, and blood-brain barrier damage. A unique metabolomic profile emerged in hypothermic rtPA-treated middle cerebral artery occlusion rats characterized by downregulated markers for energy metabolism and inflammation. Conclusions The innovative use of hypothermic rtPA enhances their combined, as opposed to stand-alone, neuroprotective effects, while reducing hemorrhagic transformation in ischemic stroke.

PMID:37655472 | DOI:10.1161/JAHA.123.029817

Categories: Literature Watch

Acupuncture is an effective therapy for macular damage: A case report

Fri, 2023-09-01 06:00

Medicine (Baltimore). 2023 Aug 25;102(34):e34735. doi: 10.1097/MD.0000000000034735.

ABSTRACT

RATIONALE: Many factors can contribute to the development of macular injury, which results in vision loss as a result of a disease. Heredity, age, underlying eye illness, internal eye surgery, or eye trauma can all cause it. A safer alternative to current therapies for macular degeneration is urgently needed since they all induce ocular irritation and postoperative recurrence as well as a host of other adverse effects.

PATIENT CONCERNS: A 12-year-old girl was the patient. A laser pen burnt her right eye. There was a spot and a shadow in the middle of her right eye's visual field.

DIAGNOSES: Macular degeneration.

INTERVENTIONS: Given the patient's age, we opted out of medicine and instead used acupuncture as a symptomatic treatment.

OUTCOMES: Two months after therapy concluded, optical coherence tomography result report indicate that the macula region of the right eye is better than it was previously. The corrected visual acuity of the right eye recovered from 0.25 to 1.0, and the clinical accompanying symptoms of the right eye disappeared.

LESSONS: No additional medication or surgical procedure was employed in this instance. We treated the macular damage with acupuncture, which relieved the patient's clinical symptoms and had no adverse effects. This demonstrates that acupuncture may be beneficial in treating ophthalmopathy in this direction.

PMID:37653781 | PMC:PMC10470758 | DOI:10.1097/MD.0000000000034735

Categories: Literature Watch

The apoptotic effect of the Lycopodium clavatum extracts on MCF-7 human breast cancer cells

Fri, 2023-09-01 06:00

Med Oncol. 2023 Sep 1;40(10):289. doi: 10.1007/s12032-023-02159-7.

ABSTRACT

Breast cancer is a significant health problem worldwide, and the search for effective treatments is critical. Side effects of cancer treatments such as surgery, radiotherapy, and chemotherapy reduce the patient's standard of living. Recently, natural compounds from plants have gained attention as potential anticancer agents due to their safety, low toxicity, and potential efficacy. Lycopodium Clavatum (LC) is an herb abundant in tropical regions and Europe and is known for its various medicinal properties. In this study, we investigated the cytotoxic and apoptotic effects of LC Water Extract (LC-WE) and LC Ethanol Extract (LC-EE) plant extracts on MCF-7 human breast cancer cells. Our results showed that LC treatment led to a dose and time-dependent cytotoxic effect on MCF-7 cells, indicating its potential as an anticancer agent against human breast cancer. Additionally, we observed that LC treatment activated apoptosis-related proteins, including BAX, Caspase-3, and Caspase-9. These results suggest that LC may induce apoptosis as a mechanism underlying its cytotoxic effect on MCF-7 human breast cancer cells. Previous studies have shown the anti-cancer potential of LC against different types of cancer. However, the anti-cancer effect of LC on human breast cancer cells has not been investigated to date. Therefore, our study provides novel insights into the potential of LC as an anti-cancer agent against breast cancer. Overall, our results highlight the potential of LC as a promising natural compound for breast cancer treatment.

PMID:37658180 | DOI:10.1007/s12032-023-02159-7

Categories: Literature Watch

Evaluation of Extracurricular Medical Education in Cardiothoracic Surgery and Cardiology; Students' Opinion On Current Medical Training

Fri, 2023-09-01 06:00

J Med Syst. 2023 Sep 1;47(1):96. doi: 10.1007/s10916-023-01988-3.

ABSTRACT

Medical students in the Netherlands have a relatively low exposure to cardiothoracic surgery and cardiology. This results in discrepancies between starting levels of medical residents and expected standards in clinical practice. Another side effect is the international decline in interest in a career in these cardiovascular fields. To compensate for this, extracurricular education programs focused on cardiothoracic surgery and cardiology have been set up. This study aims to evaluate the impact and benefits of an extracurricular education program on students' knowledge of cardiothoracic surgery and cardiology and to explore possible factors involved in (academic) career decision making. 66 participants were enrolled in the extracurricular education program VECTOR and were included in a cross-sectional cohort study. All participants scored their familiarity with different aspects of cardiothoracic surgery and cardiology prior to and after the course. Data was analyzed using Linear regression and Wilcoxon Signed Rank testing. Participants demonstrated a significant trend towards improved familiarity with cardiothoracic surgery and cardiology after the program (p = < .001). Significant increased knowledge scores were reported for all specified subdomains after the course with an increase in academic interest in cardiology (p = < .001) and cardiothoracic surgery (p = < .001). Students revealed that clinical responsibilities and a healthy work-life balance were considered most important when deciding upon their future career. This study highlights the benefit of an extracurricular education program in cardiothoracic surgery and cardiology for undergraduates and could possibly aid students in preparing for clinical practice.

PMID:37656317 | PMC:PMC10473978 | DOI:10.1007/s10916-023-01988-3

Categories: Literature Watch

Continued dysregulation of the B cell lineage promotes multiple sclerosis activity despite disease modifying therapies

Fri, 2023-09-01 06:00

F1000Res. 2022 Aug 8;10:1305. doi: 10.12688/f1000research.74506.2. eCollection 2021.

ABSTRACT

A clear understanding of the origin and role of the different subtypes of the B cell lineage involved in the activity or remission of multiple sclerosis (MS) is important for the treatment and follow-up of patients living with this disease. B cells, however, are dynamic and can play an anti-inflammatory or pro-inflammatory role, depending on their milieu. Depletion of B cells has been effective in controlling the progression of MS, but it can have adverse side effects. A better understanding of the role of the B cell subtypes, through the use of surface biomarkers of cellular activity with special attention to the function of memory and regulatory B cells (Bregs), will be necessary in order to offer specific treatments without inducing undesirable effects.

PMID:37655229 | PMC:PMC10467621 | DOI:10.12688/f1000research.74506.2

Categories: Literature Watch

Pre- and post-operative comprehensive nursing care versus conventional nursing care: An evaluation of quality of life, postoperative pain, adverse effects, and treatment satisfaction of patients who underwent surgeries and interventional therapies for...

Fri, 2023-09-01 06:00

Medicine (Baltimore). 2023 Aug 25;102(34):e34643. doi: 10.1097/MD.0000000000034643.

ABSTRACT

Interventional therapies including chemotherapies and radiotherapies are the most preferred treatment for liver cancer. However, these therapies have adverse effects. Therefore, careful care is required to relieve these adverse effects. The objectives of this study were to evaluate the quality of life, pain, anxiety, depression, adverse effects, and satisfaction of patients with liver cancer who received pre- and post-operative comprehensive nursing care against those of patients who received conventional nursing care. Patients with liver cancer who underwent surgeries and interventional therapies for liver cancer received pre- and post-operative comprehensive nursing care (CMN cohort, n = 105) or conventional nursing care (CNN cohort, n = 135), or did not receive any kind of nursing care (NNC cohort, n = 175). Before the non-treatment intervention(s) (BL), none of the patients had absent post-operative pain, all patients had mild or moderate anxiety and depression, and patients had ≤70 overall quality of life score. In the NNC cohort, a few of the patients reported being completely dissatisfied with overall personal satisfaction, and anxiety, depression, and overall the quality of life of patients were clinically worse during the follow-up period generally after completion of all doses of chemo radiotherapies (EL) as compared to BL. Hospital stays due to surgery, visual analog scale (VAS) score, Zung Self-rating Anxiety Scale score, the Self-rating Depression Scale score, and rehospitalization due to any reason(s) in follow-up were fewer and overall quality of life score and overall personal satisfaction score were higher for patients of the CMN cohort than those of patients at BL and those of patients of the CNN and the NNC cohorts at EL (P < .05 for all). Fever, bleeding, urinary retention, gastrointestinal disturbance, and hepatic and renal impairments reported in patients of the NNC cohort. Fever, bleeding, and urinary retention reported in patients of the CNN cohort (P < .05 for all). Nursing non-treatment intervention(s) is necessary for liver cancer patients after surgery, in the follow-up, and between 2 doses of chemoradiotherapies. Pre- and post-operative comprehensive nursing care relieves postoperative pain, psychological burden and improves quality of life in the follow-up period in patients who underwent surgeries and interventional therapies for liver cancer (Level of Evidence: IV; Technical Efficacy: Stage 5).

PMID:37653829 | DOI:10.1097/MD.0000000000034643

Categories: Literature Watch

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