Main Adverse Effects Research Articles

Combining Phototherapy and Gold-Based Nanomaterials: A Breakthrough in Basal Cell Carcinoma Treatment

Basal cell carcinoma (BCC) is the most common type of skin carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic, and genetic factors. While conventional treatments such as surgery and topical therapies have demonstrated variable efficacy (some of them with limited efficacy), they are not free of adverse side effects, most of them debilitating. Thus, there is a notable gap in the literature regarding alternative and non-invasive therapeutic options. This review aims to address this gap, exploring the potential of photothermal therapy (PTT) combined with metallic nanoparticles, namely gold nanoparticles (AuNPs), as a minimally invasive treatment approach. Through a comprehensive review of the literature in the period from 2014 to 2024, using experimental investigations, this review seeks to elucidate the intricate interplay between genetic factors, environmental influences, and the tumor microenvironment in BCC disease progression, with PTT as a potential therapeutic strategy. Those studies confirmed an enhanced targeting of cancer cells and selective ablation of tumor tissue, using emerging technologies like PTT. A significant tumor reduction, often exceeding 50%, was observed, with some studies reporting complete elimination of the tumor. The main adverse effects noted were localized skin irritation and transient hyperpigmentation, but these were generally minimal and manageable, highlighting the promise of PTT as an effective treatment. Thus, by leveraging the unique properties of AuNPs to enhance the effectiveness of PTT, the targeting of cancer cells can more precisely occur, reducing collateral damage to healthy tissues. This approach not only aims to achieve better clinical results, but also contributes to the broader knowledge base in the field of BCC research. Continued research and clinical trials will be crucial in refining those techniques and validating their efficacy, ultimately paving the way for more effective and less invasive treatments for BCC.

Systematic Review on Current Managements of Irritable Bowel Syndrome by Complementary and Alternative Medicine

Irritable Bowel Syndrome (IBS) affects people worldwide. It causes physical and emotional anguish, typically alongside psychiatric illnesses. When conventional methods of treating irritable bowel syndrome (IBS) fail, patients may go to complementary and alternative medicine (CAM) for relief. The quality of the evidence is uneven, but complementary and alternative medicine (CAM) shows promise. A systematic review evaluates CAM efficacy, safety, and mechanisms for IBS treatment to identify gaps and guide future research. This systematic review evaluates and synthesises CAM’s efficacy and use in irritable bowel syndrome treatment. This systematic review (1998-2023) included 15 studies from diverse sources, utilizing keywords related to Irritable Bowel Syndrome (IBS). Qualitative data methods extracted insights into Complementary and Alternative Medicine (CAM) interventions for IBS. The evaluation covered main findings, clinical features, outcomes, adverse effects, and follow-up periods. PRISMA-guided data extraction, including a flowchart, ensured a systematic approach. Inclusion criteria comprised various study types, while exclusion criteria targeted inconsistent data and low-quality studies. This study examines numerous controlled, randomised, and multicenter studies on IBS therapies, including Ayurvedic formulations, conventional nutrition, and CAM techniques. Participants, study locations, and interventions vary in the global study. Results from various studies on IBS therapeutic efficacy, risk factors, and patient preferences are shown. Studies on Ayurvedic, homoeopathic, and CAM treatments provide a complete overview of IBS care. The study found that Ayurvedic and CAM treatments for IBS are helpful, but mainstream medications are risky. To improve efficacy, tailored, culturally relevant programmes need research and standardisation.

Phase I clinical trial evaluating the safety, tolerance, pharmacokinetics and pharmacodynamics of HSK21542 injection in healthy volunteers.

HSK21542 injection is a new peripheral kappa opioid receptor (KOR) agonist. To evaluate its safety, tolerability, pharmacokinetics and pharmacodynamics, this study was conducted in healthy volunteers, consisting of two parts: a single ascending dose (0.2-3.375 μg/kg, 15-min infusion) and different infusion durations (0.2 and 1μg/kg, 2- or 15-min infusion). The area under the plasma concentration-time curve (AUC) and peak concentration (Cmax) of HSK21542 were dose-linear among 0.2-3.375 μg/kg. After intravenous injection, HSK21542 was rapidly eliminated with a half-life (t1/2) of 1.5h, and the majority (48.02%) of the dose was excreted unchanged in urine. Pharmacodynamic results showed that HSK21542 increased prolactin release and reached a peak at 1-2h after administration but had no significant effect on vasopressin levels. There was a brief increase in urine volume within the initial 2h after administration. HSK21542 was well tolerated; most of the adverse effects (AEs) in the trial group were grade 1, and only 2 cases (4.0%) were grade 2. The main AE was paresthesia, which appeared in 42% (21/50) in the trial group. No serious adverse event (SAE) was observed. No subject withdrew early due to AEs. These results suggest that HSK21542 may be a potential treatment for pain and pruritic conditions.

Adverse effects resulting from the use of zolpidem hemitartrate: A literature review

Objective: To investigate and discuss the risks associated with the use of the drug in order to clarify the possible damage to health. Methods: Through an integrative review, using the guiding question “What are the main adverse effects and impacts of using zolpidem?”. The search was carried out in the main databases: Latin American and Caribbean Health Sciences Literature (LILACS), Medical Literature and Retrieval System onLine (MEDLINE/PubMed®), Periódicos CAPES and Scientific Electronic Library Online (Scielo). MESH (Medical Subject Headings) and DeCs (Health Sciences Descriptors) were used as descriptors in the search strategy. The search strategy followed the criteria of the Boolean operator “AND”, which combines terms. The terms used were zolpidem “AND” adverse effects AND overdose, during the month of September 2024. Results: Zolpidem is a drug of paramount importance for the treatment of cases of insomnia, and long-term medical therapy should be monitored to assess efficacy, the emergence of adverse effects and the onset or worsening of comorbid conditions. Conclusion: Strict prescription control and continuous evaluation of its impact on patients' physical and mental health are essential to avoid abuse and serious complications.

The Efficacy, Safety, and Persistence of Therapy after Non-Medical Switching from an Originator Adalimumab in Inflammatory Bowel Disease: Real-Life Experience from Two Tertiary Centres.

During the last two decades, an increased number of molecules with multiple mechanisms of action have been approved for the treatment of inflammatory bowel disease (IBD), with a substantial increase in the costs related to therapy, which has become a concern for payers, regulators, and healthcare professionals. Biosimilars are biologic medical products that are highly structurally similar to their reference products; have no clinically meaningful differences in terms of immunogenicity, safety, or effectiveness; and are available at a lower price. Materials and Methods: This was an observational prospective study conducted in two IBD centres in Bucharest and included 53 patients, 27 male (M) and 26 female (F), diagnosed with IBD according to standard clinical, endoscopic, radiological, and histological criteria, who were non-medically switched at the indication of the National Insurance House to a biosimilar of Adalimumab. Aims: The aim was to determine the rates of clinical remission, adverse effects, and treatment persistence at one year. Results: No significant differences were found in terms of the faecal calprotectin (FC) and C-reactive protein (CRP) levels 6 and 12 months after changing from the originator biologic treatment to a biosimilar. Only one patient required a change in their biological treatment following the clinical and biological loss of response. The main adverse effect reported by the patients was pain at the injection site. Of the 53 patients, only 2 reported pain at the injection site, and 1 patient reported experiencing abdominal pain and rectal bleeding immediately after the switch, but no recurrence was observed clinically or endoscopically. Conclusions: This observational study is the first to be carried out in Romania that shows that, after a non-medical switch, biosimilars of Adalimumab are as efficient and safe as the originator Adalimumab in the clinical treatment of patients with IBD.

Teleworking and Mental Well-Being: A Systematic Review on Health Effects and Preventive Measures

Background: In the aftermath of the Coronavirus pandemic and the resulting lockdown and social distancing policies, a new form of work, already existing in the past, has been further enlarged. Teleworking is “full- or part-time electronic work, on-line or off-line, performed at home by self-employed or office workers” and today represents an important lever for companies, including for sustainability, allowing employees to work flexibly, efficiently and remotely. The relationship between telework and sustainability in economic, social, and environmental aspects is also being questioned. The aim of this systematic review is to investigate the effects this has had on workers’ mental health. Methods: PRISMA guidelines were followed. The research was performed on Pubmed and Scopus without restrictions on study type and time limits. The methodological quality of the studies included was assessed using AMSTAR-2, INSA and NOS scales. A meta-analysis of the main adverse effects found in observational studies was also carried out. Results: A total of 38 articles were included in the systematic review. A large proportion of the studies examined showed a correlation between teleworking and worsening mental health. The meta-analysis showed increased levels of mental ill-health (38.8%), stress (28.4%), isolation (6.3%), anxiety (23%), depression (22.6%), work–family conflicts (19.5%), poor sleep quality (56.4%), fatigue (16.1%) and irritability (39.6%). Conclusions: Although most of the works analyzed show a deterioration in the mental health of workers, positive effects were noted in some. There is the need for more studies to optimally investigate the cause–effect relationship between teleworking and mental health deterioration.

Association of Therapeutic Monitoring of Tacrolimus with Laboratory Markers of Kidney Function in Receptors of Kidney Allograft

Introduction: Kidney transplantation is the most commonly performed type of transplant in Brazil. Tacrolimus is one of the primary drugs used in post-transplant immunosuppressive therapy, and one of its main adverse effects is nephrotoxicity. Laboratory tests to assess renal function are of great importance in monitoring post-kidney transplant patients, helping to diagnose events indicative of graft dysfunction. Objective: !e present study aimed to evaluate the association between laboratory changes in renal function and blood levels of tacrolimus in post-kidney transplant patients. Methods: Observational, analytical and cross-sectional study. !e results of blood levels of tacrolimus and measurements of urea, creatinine and estimated Glomerular Filtration Rate (eGFR) were analyzed, as well as the sociodemographic data of kidney transplant recipients followed at a university hospital who underwent laboratory tests between months from January 2021 to July 2022 in a period close to 1 year after the transplant. !e variables analyzed in the research were collected from the patient's medical records and subsequently analyzed; the statistical analyses considered p < 0.05. !e project was approved by the Ethics Committee of the Walter Cantídio University Hospital under opinion number 5,436,434 and CAAE number 57396622.1.0000.5045. Results: !e sample was mainly composed of males, mixed race, with an average age of 51.5 years (SD ± 12.5) and from cities in the interior of Ceará. Regarding the percentage of patients with laboratory changes, 50.62% (n = 45) showed changes in tacrolimus blood levels. 56.79% (n = 46) had changes in serum creatinine levels, 49.38% (n = 40) had changes in serum urea levels, and 59.26% (n = 48) had altered eGFR. !e correlation analyses suggested a low signi#cance between variations of the variables studied. Conclusion: !e results indicate no relationship between variations in tacrolimus blood concentrations and the appearance of changes in the results of classic renal biomarkers at the end of the #rst year post-transplant. However, it is necessary to carry out new studies to understand better the impact of changes in blood levels of tacrolimus on the renal function of renal allograft recipients.

Efficacy and safety analysis of the OR-CHOP regimen for the treatment of MCD subtype diffuse large B cell lymphoma in the real-world setting

Objective: To investigate the efficacy and safety of orelabrutinib combined with R-CHOP in the treatment of MCD subtype diffuse large B cell lymphoma (DLBCL) . Methods: Twenty-three MCD subtype patients whose gene-subtype classification was based on baseline tumor tissue and/or baseline plasma using the LymphGen algorithm from June 2022 to June 2023 in the First Affiliated Hospital of Nanjing Medical University were retrospectively enrolled in the analysis. All patients were treated with R-CHOP or R-miniCHOP in Course 1, OR-CHOP or OR-miniCHOP (21 days for one course) in Courses 2-6, and R-monotherapy in Courses 7-8. Results: Of the 23 patients, the median age was 58 years (range: 30-81 years), and 11 (47.8% ) aged >60 years. Fifteen cases (65.2% ) had international prognostic index (IPI) scores of 3 to 5. The top 10 mutated genes in the gDNA tissues were PIM1 (78.3% ), MYD88 (69.6% ), ETV6 (43.5% ), BTG1 (39.1% ), CD79B (43.5% ), HIST1H1E (39.1% ), BTG2 (34.8% ), KMT2D (30.4% ), CD58 (26.1% ), and CDKN2B (21.7% ). The consistency rate of the tissue and plasma mutations was 80%, while the baseline plasma ctDNA burden was closely correlated with the LDH levels and IPI scores (P<0.05). All patients received 5 courses of OR-CHOP regimens. The mid-term (after 3 courses) evaluation showed that the overall response rate (ORR) was 100% (23/23), with 22 patients (95.65% ) achieving complete remission (CR), and 1 patient (4.35% ) achieving partial remission (PR). The ORR after the end of treatment (EOT) was 95.65% (22/23). Moreover, 21 patients (91.30% ) obtained CR, 1 patient (4.35% ) obtained PR, and 1 patient (4.35% ) obtained progression disease (PD). Of the 21 patients who had the dynamic EOT-ctDNA burden, only four patients (19.0% ) did not achieve EOT-ctDNA clearance, while the other 17 patients (81.0% ) achieved EOT-ctDNA clearance. The median follow-up time was 20.8 (15.3-30.0) months, while the median progression-free survival (PFS) and overall survival (OS) were not reached. The 2-year PFS rate was 71.8% (95% CI 54.7% -94.2% ), while the 2-year OS rate was 91.3% (95% CI 80.5% -100.0% ). Furthermore, the OR-CHOP regimen was generally well tolerated during clinical use, with hematological toxicity being the main adverse effect. Conclusion: This study revealed that the OR-CHOP regimen can be used as an effective and safe first-line treatment for MCD subtype DLBCL.

Universal Basic Income: Inspecting the Mechanisms

Abstract We examine the mechanisms driving the aggregate and distributional impacts of Universal Basic Income (UBI) through model analysis of various UBI programs and financing schemes. The main adverse effect is the distortionary tax increase to fund UBI, reducing labor force participation. Secondary channels are a decline in demand for self-insurance, depressing aggregate capital, and a positive income effect that further deters labor force participation. Due to these channels, introducing UBI alongside existing social programs reduces output and average welfare. Partially substituting existing programs with UBI mitigates the adverse effects, increases average welfare, but does not deliver a Pareto improvement.

Evaluating cardiovascular disease risk in type 2 diabetes mellitus patients in a tertiary care hospital in Hyderabad, Sindh, Pakistan

Type 2 Diabetes Mellitus (DM) is the most common type of diabetes. The main adverse effect of diabetes type 2 involves a higher risk of cardiovascular disease. Diabetes patients with this type are more likely to suffer cardiovascular problems. Consequently, this study investigated demographics, CVR factors, age, gender, physical activity, BMI, hemodynamics, HbA1c stage, and lipid profile of 120 patients with type 2 diabetes in Hyderabad, Sindh, Pakistan. The current study covered 120 patients with type 2 diabetes, out of which 40 were male (33.3%) and 80 were female (66.6%), aged 50 to 70. Out of these 120 patients, 17 (14.1%) had coronary artery disease, 15 (12.5) had atherosclerosis, and 8% (6.6) experienced a stroke, according to the findings. Approximately 37.5% of patients had overweight obesity, 54% had poor diabetes control, and 10% had reasonable control based on their HbA1c readings. Furthermore, 55% were hypertensive, and around 12.5% had both macro and microvascular problems. In general, around 33.3% of all Type 2 DM patients have cardiovascular diseases (CVD), indicating that patients with Type 2 DM have a greater risk of increasing CVD. As a result, proper strategies should be implemented to avoid catastrophic outcomes and disease development.

Meta-analysis of genome-wide association studies for cancer therapy-related cardiovascular dysfunction and functional mapping highlight an intergenic region close to TP63

Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case–control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value < 1 × 10–5) with CTRCD in case–control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10–6) in the case–control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncology.

Impact of SARS-CoV-2 vaccination in patients with vascular liver diseases: Observations from a VALDIG multicenter study

Background and AimsPatients with vascular liver diseases(VLD) are at higher risk for both severe courses of COVID-19 disease and thromboembolic events. The impact of the SARS-CoV-2 vaccination in VLD patients has not been described and represent the aim of our study. MethodsInternational multicenter prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation. In a subgroup of patients, the humoral and cellular responses to vaccination were also analyzed. Results898 patients from 14 European centers part of the VALDIG network were included, 872(97.1%) patients received two vaccine doses (fully vaccinated), and 674(75.1%) three doses.Of the total cohort, 151/898 had a COVID-19 infection prior to vaccination, of which 9/151(5.9%) were re-infected. Of the previously 747/898 patients who were not previously infected, 11.2%(84/747) were diagnosed with a COVID-19 infection during the study period.Two infected patients required ICU admission and infection was fatal in two fully vaccinated patients. Main adverse effects were reported in around 40% of patients, being local side effects the most frequent.During the study period, 31(3.5%) patients had thromboembolic events and 21(2.3%) hepatic decompensations. No vaccine-induced-thrombocytopenia (VITT) case was reported.Vaccine immunogenicity was assessed in 36 patients; seroconversion reached 100% and IFNy-T cell responses significant increased post two mRNA-1273 vaccine doses. ConclusionPatients with VLD seems to have a preserved immune response to SARS-CoV-2 vaccination, which appears to be safe and effective in preventing severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, however the contribution of vaccination as a cofactor in VLD remains to be elucidated.

PSYCHOTIC DISORDER INDUCED BY CLOMIPHENE CITRATE IN A MAN: A RARE CASE REPORT

The clomiphene citrate is one of the selective estrogen receptor modulators and its function is to indirectly induce ovulation, stimulating the secretion of pituitary gonadotropins (follicle-stimulating hormone (FSH) and luteinizing hormone (LH)), subsequently increasing testosterone circulation levels. Its main adverse effects include increased ovarian volume, vasomotor symptoms, pelvic discomfort, and hepatic dysfunction. However, some reactions to this medication may be unknown or poorly reported in the scientific literature. Hormonal effects may be responsible for the unfavorable psychotic outcomes in conjunction with the antiestrogenic activity of clomiphene. The appearance of psychotic symptoms, especially in women with a pre-existing psychiatric history, has been previously studied [1,4]. The effects were attributed to an enhanced testosterone-androgen receptor interaction in the brain, subsequently leading to alteration of emotional conditions. Proposed neurobiological targets include catecholaminergic cells in the hypothalamus and other limbic regions of the brain.). Nevertheless, the occurrence of such symptoms has not been reported in the literature in males. This letter aims to report the case of a 36-year-old male patient who presented an adverse reaction that is not clear in the literature on Clomiphene Citrate, since the majority of reported cases are in the female population with some previous psychiatric comorbidity. The patient had a previous diagnosis of fibromyalgia. Approximately 20 days after the introduction of the medication, he presented his first psychotic episode with manifest characteristics, with increased energy, hypersexualization, low need for sleep, grandiose delusions, impulsive and inappropriate behavior lasting an average of 4 days. The patient's family reported that he had never exhibited similar behavior. The second psychotic episode occurred approximately 20 days after the first. In the latter, the patient presented with persecutory delusions, risky behavior, paranoid behavior, risk of self- and hetero-aggression, and was taken to his first psychiatric hospitalization. It was reported that he used clomiphene citrate up to 15 days before psychiatric hospitalization. The use of other psychoactive substances was also ruled out (a toxicological test with a negative result) and admission and neuroimaging exams (magnetic resonance imaging of the skull) were carried out, with all results within normal limits. The patient was admitted to our service being introduced to valproic acid 1000mg/day, risperidone 2mg/day, quetiapine 100mg/day and gabapentin 900mg/day (already being used to treat chronic pain) and clomiphene was suspended. He presented rapid remission of delusions in two days with criticism present in the first week of hospitalization. Due to the absence of psychiatric history, as well as other possible causes for the appearance of symptoms, the psychotic condition described was therefore attributed to the use of clomiphene. Thus, the possibility of this medication inducing the appearance of symptoms should be considered, especially in patients experiencing their first psychotic episode [2,3].

Loncastuximab Tesirine in the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma.

Currently, a significant percentage of patients with DLBCL are refractory or relapse after a first line of immunochemotherapy. Second relapses after autologous stem cell transplantation or chimeric antigen receptor T-cell therapies present few treatment options and do not yield good results. New molecules have entered the immunotherapy arsenal. Loncastuximab tesirine comprises a humanized anti-CD19 monoclonal conjugated antibody, which consists of an anti-CD19 antibody and cytotoxic alkylating agent, SG3199. Several studies have proven its efficacy in the treatment of refractory cases of DLBCL with a good safety profile, with the main adverse effects being neutropenia, thrombopenia, and liver enzyme involvement. In this review, we explain the mechanism of action of this molecule, the clinical data that have led to its acceptance by the FDA, and the new therapeutic options that are proposed in association with this drug.

Fermentation of Luffa cylindrica by Lactiplantibacillus plantarum P101 enhanced functional properties: Insights into immune modulation, intestinal barrier repair, and intestinal microbiota regulation

Luffa cylindrica is a multifunctional plant resource with excellent but little-known functional properties, limited by its low processing and utilization rates. The emerging probiotic fermentation processing is an efficient and convenient way to improve the utilization rate of fruits and vegetables. To investigate the impact of probiotic fermentation on the functional properties of Luffa cylindrica, we fermented Luffa cylindrica with Lactiplantibacillus plantarum P101 and compared the intervention effects of Luffa cylindrica juice (LJ) and Luffa cylindrica fermentation broth (LF) on the damage caused by cyclophosphamide (CTX). After 14 days of intervention with LJ or LF, we collected samples from the thymus, spleen, blood, ileum, and cecum contents from BALB/C mice for subsequent analysis. The results indicate that LF provides better relief from CTX-induced damage than LJ. The main adverse effects caused by immune dysregulation, thymic atrophy, decreased blood leukocyte (WBC) count, and intestinal cytokine levels, were further improved by LF intervention. In addition, under the intervention of LF, intestinal epithelial cells and crypts were further protected, and their tight junction protein expression and mucus secretion were also promoted. Intestinal microbial dysbiosis, positively correlated with intestinal barrier disruption and immunosuppression, was also further alleviated by LF intervention. In summary, fermentation significantly enhanced immune modulation, intestinal barrier repair, and intestinal microbiota regulation of Luffa cylindrica. The results of our study may help people realize the little-known valuable functional properties of Luffa cylindrica, and may be expected to expand the types of functional foods.

Efficacy of intra lesional injection of 5-flourouracil on keloid scar: A prospective open clinical trial

Background and objectives: The management of keloids stayed unsatisfactory. Intralesional 5-fluorouracil has not been broadly and intensively studied as a monotherapy in the treatment of keloids worldwide. So, the aim of this study was to evaluate the efficacy and safety of intralesional injection of 5-flourouracil in patients with keloids. Methods: In this prospective clinical trial study, a total of 20 patients aged &gt;18 years at Shahid Jabar Dermatological Teaching Center, Sulaimaniyah, Iraq, from January 2022 to August 2022 were enrolled. Patients were treated at 1-week interval with intralesional injection of 5-flurouracil (50 mg/mL) at maximum of 6 sessions. Average injection volume was 0.2 mL/cm2. All patients were followed up for 6 months. Results: Most of the patients were aged &lt;50 years (90%) with no family history of keloid (75%). Additionally, 45% of patients had keloid in the trunk region with a size of ?10 cm2 (65%). Most patients (80%) had the disease for ?5 years that caused by inflammation (55%), especially skin type IV (65%). After 6 sessions of treatment, 70% of patients showed moderate improvement, while 30% of patients showed minimum improvement. The main adverse effects after 6 sessions of treatment were hyperpigmentation in 3 patients, bullae in 2 patients, and tissue sloughing only in 1 patient. A significant correlation was found between the patient’s response and age/keloid location. Moreover, mean Redness, Elevation, Hardness, Itching, and Tenderness score after treatment was significantly lower than before treatment (p&lt;0.001). Conclusions: Our results concluded that 5-flurouracil is a safe and effective therapy for the treatment of keloids.

Phase II study of tislelizumab combined with concurrent chemoradiotherapy for locally advanced cervical cancer.

e17523 Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer (LACC). However, local recurrence and distant metastasis are the main modes of treatment failure in LACC, especially for patients with stage IIIA ~IVA as well as patients with large masses (&gt;4cm) and regional lymph node metastasis. This study aimed to evaluate the efficacy and safety of tislelizumab (anti-PD-1 antibody) combined with concurrent chemoradiotherapy for locally advanced cervical cancer. Methods: Eligible patients were age 18-75 years, ECOG performance status of 0-1 and untreated cervical cancer (2018 FIGO stage IIIA, IIIB, IVA, or cervical tumor diameter &gt; 4cm with regional lymph node metastasis, or paracervical invasion with regional lymph node metastasis). All patients received CRT plus tislelizumab 200mg Q3W for 1 year or disease progression or intolerable toxicity. The CRT includes at least 4 cycles of cisplatin 40mg/m2 QW + EBRT 45~50Gy/25f then BT 28~30Gy/4~5f. The primary endpoint was tumor regression ratio before brachytherapy. Secondary endpoints were 3-month and 6-month objective response rate (ORR), 1-year and 3-year OS and PFS, safety. Results: From August 24, 2022 to February 4, 2024, 30 patients were enrolled. 25 patients completed CRT and were available for evaluation. The median age was 59 years (range 40-75). The tumor regression ratio before brachytherapy was 90.6%. The ORR at 3 and 6 months were 100%, The OS and PFS rate at 1 year were 100%. The main adverse effect was neutropenia (36% for grade 3-4 and 20% for grade 1-2). Radiation enteritis incidence was 64% and were grade 1-2. Other adverse effect such as nausea, vomiting, and dizziness occurred during CRT and could be alleviated after symptomatic treatment. No immune-related adverse events were observed. Conclusions: Our results suggest that Tislelizumab combined with concurrent chemoradiotherapy showed valuable antitumor activity and controllable safety in LACC. We will keep strictly implementing our study protocol for further PFS and OS. Clinical trial information: NCT05588219 .

Incidence and management of the main serious adverse events reported after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause-effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, and transverse myelitis reported in the context of COVID-19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post-vaccination. Regardless of the ongoing discussion about the safety of COVID-19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications.

Effects of compound Anoectochilus roxburghii (Wall.) Lindl. oral liquid on relative metabolic enzymes and various biochemical indices in Wistar rats with isoniazid-induced liver injury

Isoniazid (INH) is the first-line anti-tuberculosis drug in clinical practice, and its main adverse effect is drug-induced liver injury (DILI). This study aimed to investigate the hepatoprotective effect of Compound Anoectochilus roxburghii (Wall.) Lindl. Oral Liquid (CAROL) and to provide a new strategy for the search of potential drugs against INH-induced liver injury in Wistar rats. Animal experiment was based on INH (100 mg/kg) induced liver injury to explore the intervention effects of CAROL at doses of 1.35, 2.70, and 5.40 mL/kg. LC-QTOF-MS/MS was used to identify hepatoprotective components in CAROL and its’ exposed components in rat serum. The hepatoprotective effect of CAROL was evaluated by pathological observation of rat liver tissue and changes in levels of biochemical indices and cytokines in serum or liver tissue. Of the 58 hepatoprotective components identified, 15 were detected in the serum of rats with liver-injured treated by high-dose CAROL. Results of animal experiments showed that the levels of various biochemical indexes and cytokines were significantly reversed with CAROL intervention. In particular, the expression level of cytokeratin-18 and high-mobility group box 1, as specific and sensitive indicators of DILI, was significantly reduced in the serum of rats with CAROL intervention compared with the INH model group. The same reversal was observed in the levels of TBIL, ALP, ALT, and AST in serum, as well as in the levels of TNF-α, IL-6, SOD, and MDA in liver tissue. For INH-metabolizing enzymes, an evident expression inhibition was observed in N-acetyltransferase 2 and glutathione S-transferases with CAROL intervention, which may be the key to controlling INH hepatotoxicity. CAROL has a favorable hepatoprotective effect on INH-induced liver injury. This study takes the first step in studying the hepatoprotective mechanism of CAROL against INH hepatotoxicity and provides reference for wider clinical applications.

PARTIALLY REVERSIBLE DILATED CARDIOMYOPATHY ASSOCIATED WITH AMPHOTERICIN B THERAPY

Abstract Background Amphotericin B (AmB) is an antifungal drug commonly used in a broad spectrum of infections, including leishmaniasis. Leishmaniasis, transmitted through insect bites, has cutaneous, mucocutaneous, or visceral (particularly liver and spleen) involvement. The main adverse effects of AmB are cardiotoxicity and nephrotoxicity, often reversible, but with yet unclear pathophysiology. Reversible dilated cardiomyopathy is a rare disease with very few cases described in the literature (less than 10). The Case A 41–year–old man with a silent cardiological history (only cocaine and alcohol abuse in past) is admitted for visceral leishmaniasis. Cardiological evaluation: LBBB in ECG (none previous available); no abnormality detected on ECOCG (EF 55%). Ten days after the AmB cycle, onset of worsening dyspnoea needing hospital treatment after a further two weeks for heart failure (HF). At ECOCG severe left ventricular dysfunction (EF 30%), no rise of cardiac enzymes was detected. Coronary angiography showed 50–75% stenosis on RCA and LAD, treated by angioplasty and stenting. Cardiac MRI showed: dilated left ventricle with diffuse biventricular hypokinesis (FE 16% left and 22% right), areas of LGE of non–ischemic appearance. HFrEF GDMTs were prescribed, with progressive clinical improvement over the next four weeks; at cardiac MRI performed one month later, partially recovery of biventricular function (FE sn 41% right 48%) was found. The ECG showed regression of LBBB. No myocardial biopsy was performed, so it is not possible to get to an unequivocal cardiac dysfunction’s cause. However, the time relationship between the use of AmB and the clinical findings evolution, consistently with the few literature available, suggests a probable diagnosis of AmB toxic cardiomyopathy. An ischaemic cause of the dysfunction is unlikely by the MRI feature and by coronary angiography findings. Literature data suggest that the presence of predisposing factors for cardiac dysfunction, rather than the duration of treatment or preparation used, is the most relevant factor in the development of AmB–related cardiomyopathy. It’s important to perform cardiac monitoring in all patients receiving AmB therapy. In all reported cases, cardiac function recovered substantially after cessation of AmB treatment.