Higher Incidence Of Adverse Events Research Articles

Efficacy and safety of immunosuppressive therapy versus cyclosporine combined with avatrombopag in older adults with severe aplastic anemia: a multicenter prospective study

This trial compared antithymocyte globulin (ATG) + cyclosporine A (CsA) + avatrombopag (AVA) and CsA + AVA in older adults with severe aplastic anemia (SAA). The patients were randomized to receive either ATG + CsA + AVA or CsA + AVA. Of 84 included patients, 42 were treated with ATG + CsA + AVA and 42 with CsA + AVA. With a median follow-up of 13 (0.3–17) months, the objective response rates (ORRs) at 3, 6, and 12 months and the end of follow-up were 53.7%, 65.9%, 80.6%, and 71.4% in the ATG + CsA + AVA group and 61.9%, 73.2%, 77.4%, and 64.3% in the CsA + AVA group, respectively (P > 0.05 at any time point). Three-month ORR was an independent predictor of 6-month complete response rates (P = 0.019). Patients in the ATG + CsA + AVA group showed a higher incidence of adverse events than those in the CsA + AVA group (64.3% vs. 35.7%, P = 0.009). The rates of relapse (P = 0.667), mortality (P = 1.000) and clonal evolution (P = 1.000) were comparable between the groups. The combination of CsA + AVA achieved comparable efficacy with superior safety compared to the combination of ATG + CsA + AVA in older adults newly diagnosed with SAA.

Pharmacodynamics of pregabalin and gabapentin as pain treatment in cervical and lumbar radiculopathy in adults

The general objective to analyze the pharmacodynamics of Pregabalin and Gabapentin as pain treatment in cervical and lumbar radiculopathy in adult patients of the Neurosurgery service at the Central Hospital of Maracay, Aragua State, Venezuela, during the period from April to September 2024.Materials and Methods An observational, evaluative, prospective and longitudinal study was conducted. The sample consisted of 21 patients, divided into two groups: Group A (n=14) treated with Gabapentin 300 mg and Group B (n=7) treated with Pregabalin 75 mg. The results the mean age was 52.07 ± 10.4 years in Group A and 47.71 ± 7.8 years in Group B (p = 0.300). Most patients were women (78.57% in Group A and 85.71% in Group B, p = 1,000). Both treatments significantly reduced pain (Gabapentin: 7.07 ± 2.2 to 4.78 ± 2.8; Pregabalin: 7.00 ± 2.2 to 5.28 ± 12.2, p = 0.813). Muscle strength improved in both groups, but did not reach statistical significance (p = 0.055). Sensitivity improved in both groups, however, it was lower in the Pregabalin group after treatment (p = 0.029). Adverse events were more frequent in the Pregabalin group (57.14%) compared to Gabapentin (42.86%, p = 0.659). In conclusion, both Pregabalin and Gabapentin are effective in reducing pain in patients with cervical and lumbar radiculopathy. Pregabalin had a higher incidence of adverse effects, which should be considered when choosing treatment. An individualized approach and ongoing follow-up are recommended to optimize neuropathic pain management.

Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant.

Efficacy and Safety of Simnotrelvir-Ritonavir Compared With Nirmatrelvir-Ritonavir in the Treatment of COVID-19: Real-World Evidence From a Retrospective Cohort Study During the Prevalence of the Omicron EG.5 Variant.

Challenges in the diagnosis and treatment of chronic pulmonary aspergillosis in Japan.

Challenges in the diagnosis and treatment of chronic pulmonary aspergillosis in Japan.

Inhaled tobramycin in non-cystic fibrosis bronchiectasis: A meta-analysis of randomized controlled trials.

Inhaled tobramycin in non-cystic fibrosis bronchiectasis: A meta-analysis of randomized controlled trials.

Angiotensin Receptor Neprilysin Inhibitors for Hypertension and Proteinuria Management During Atezolizumab/Bevacizumab Treatment for Hepatocellular Carcinoma

Background/AimVascular endothelial growth factor (VEGF) inhibitors, such as bevacizumab (Bev), are key in the pharmacological treatment of advanced hepatocellular carcinoma (HCC) but are associated with a high incidence of adverse events, including hypertension and proteinuria. Strategies to reduce proteinuria through blood pressure control are particularly important. A new angiotensin receptor neprilysin inhibitor (ARNI) (sacubitril/valsartan) was recently approved for the treatment of hypertension. ARNI exerts its antihypertensive effects through vasodilation, sympathomimetic inhibition, and natriuresis by enhancing the action of natriuretic peptides, together with suppression of the renin-angiotensin system by angiotensin II receptor blockers (ARB). Herein, the aim was to investigate the efficacy of ARNI for blood pressure control and proteinuria in advanced hepatocellular carcinoma (HCC) patients during treatment with atezolizumab plus Bev (Atez/Bev).Patients and MethodsWe retrospectively identified patients with advanced HCC under Atez/Bev treatment, who experienced inadequate blood pressure control with ARB and were transitioned to ARNI. Data on estimated glomerular filtration rate (eGFR), urinary protein/creatinine ratio (UPCR), and Bev continuation were analyzed.ResultsThe mean patient age was 76.6 years, and the liver background was hepatitis B virus (HBV) (n=1), hepatitis C virus (HCV) (n=4), or non-HBV/non-HCV (n=5). eGFR significantly improved from a mean of 52.87 to 59.46 ml/min/1.73 m2 (p=0.006); UPCR decreased from 2.31 to 0.79 (p=0.025) after switching to ARNI. Among patients with UPCR ≥2 (n=5), switch from ARB to ARNI improved eGFR from 50.54 to 58.62 ml/min/1.73 m2, (p=0.026), while UPCR decreased from a mean of 3.99 to 1.13 (p=0.025), allowing uninterrupted Bev treatment.ConclusionARNI appears to support renal function preservation and proteinuria reduction during Atez/Bev therapy, allowing the continuation of Bev treatment.

Lenvatinib for unresectable anaplastic thyroid cancer: real-world experiences in multi-institutional study.

Anaplastic thyroid carcinoma (ATC) is a rare, aggressive malignancy with poor prognosis. Lenvatinib has demonstrated moderate efficacy and is approved for unresectable ATC treatment in Japan. However, some patients are unable to tolerate the standard 24 mg daily dose and require dose reductions or interruptions due to its high incidence of adverse effects. This study aimed to evaluate the therapeutic effects of lenvatinib in patients with ATC, particularly assessing outcomes with reduced dosages across multiple institutions. Sixteen patients diagnosed with ATC and treated with lenvatinib were evaluated retrospectively. Overall survival (OS) and progression-free survival (PFS) were calculated. In addition, patients were divided into two groups based on 24 mg daily dose or reduced initial dose, and their therapeutic outcomes were compared. The objective response rate was 31%, and the median OS and PFS were 2.2 and 1.7 months, respectively. Among the 16 patients, 11 (69%) initiated treatment with 24 mg daily, while the remaining 5 (31%) received a reduced dose. The median OS and PFS were 2.0 months and 1.4 months, respectively, among patients in the 24 mg daily group, compared to 6.2 months and 2.4 months, respectively, among patients in the reduced dosage group. Our study demonstrated that lenvatinib has moderate efficacy for ATC. In addition, initiating treatment at a reduced dose could provide therapeutic benefit. Lenvatinib may serve as a treatment option for unresectable ATC when targeted therapies, including BRAF, RET, and NTRK inhibitors, are unavailable. Furthermore, although the standard 24 mg daily dose is recommended, a lower initial dosage may be effective for patients unable to tolerate the full dose.

Adverse Effects Related to SARS-CoV-2 Vaccination in Patients With Rheumatic Diseases and Psoriasis From Argentina.

Patients with systemic rheumatic diseases were initially excluded from coronavirus disease 2019 (COVID-19) vaccine trials. Real-world data on vaccine safety in this population remain limited, particularly for non-mRNA vaccines. The aim of this study was to evaluate the safety of COVID-19 vaccines in patients with rheumatic diseases and/or psoriasis. A longitudinal observational study including vaccinated patients ≥18 years old with rheumatic diseases and/or psoriasis vaccinated against COVID-19 was conducted. Adverse events (AEs) and disease flares were documented. Multivariable logistic regression analysis identified factors associated with AEs. Among 2160 patients with rheumatic diseases and/or psoriasis vaccinated against COVID-19 (3988 doses), 29.6% reported at least 1 AE, mostly mild/moderate flu-like symptoms and local hypersensitivity. AE incidence was highest for mRNA-1273 (316.7/1000 doses) and lowest for BBIBP-CorV (95.4/1000). Heterologous regimens and ChAdOx1 nCoV-19 as first dose were associated with increased AE risk, whereas BBIBP-CorV showed the opposite effect. Disease flares occurred in 2.5% of patients, predominantly arthritis and arthralgia, without association with any specific vaccines. COVID-19 vaccines were generally well tolerated, with AE rates comparable to the general population. Heterologous regimens and vector-based and mRNA vaccines had higher AE incidence. These findings provide valuable safety data on vaccines used in Argentina and the region.

Comparing fosfomycin and ciprofloxacin for uncomplicated UTI treatment in adults: better bacterial eradication but non-significant clinical remission-a systematic review and meta-analysis.

Urinary tract infections (UTIs) are common in young children and women and even more so in pregnant women. Ciprofloxacin has been a long-used regime to treat UTIs, although recently the paradigm has shifted towards Fosfomycin. This shift is driven by rising antibiotic resistance, safety concerns with fluoroquinolones, and the need for alternative treatments with broader efficacy and fewer adverse effects. This systematic review and meta-analysis assess the effectiveness and safety of Fosfomycin compared to Ciprofloxacin for treating urinary tract infections in adults. A systematic search was conducted across PubMed, EMBASE, Cochrane Library, Web of Science, Google Scholar, and Scopus using search strings combining "Fosfomycin," "Ciprofloxacin," and "urinary tract infections." Study selection and screening were managed using Covidence, with duplicates removed. Four randomized controlled trials met the inclusion criteria following primary and secondary screening. Data analysis was performed using Review Manager (RevMan), with results presented as forest plots. A random-effects model was applied in cases of significant heterogeneity. The outcomes assessed included clinical remission, bacterial eradication, and adverse effects, based on data from three of the included studies. Four studies matched our inclusion criteria and were processed further for analysis. For bacterial eradication, the total number of patients was 334 patients, bacterial eradication during 10days was achieved in 143 participants in the fosfomycin group and 110 participants in the ciprofloxacin group. Bacterial eradication was significantly higher in the fosfomycin group compared to the ciprofloxacin group (OR 2.03, 95% CI 1.22-3.36, p = 0.006). For clinical remission, no significant difference was found in 3 studies in a total of 278 patients (OR 1.26, 95% CI 0.72-2.21, p = 0.42). Out of a total of 356 patients, 74 experienced adverse effects in the fosfomycin group and 46 in the ciprofloxacin group. The appearance of adverse effects was significantly higher in the fosfomycin group (OR 2.66, CI 1.53-4.62, p = 0.0005). The results of our meta-analysis show that bacterial eradication was significantly higher in the Fosfomycin group compared to the Ciprofloxacin group. There was no difference between the two drugs in terms of clinical remission. The appearance of adverse effects was significantly higher in the Fosfomycin group. Despite a higher incidence of adverse effects, Fosfomycin demonstrated superior bacterial eradication, suggesting its potential role as an effective empirical option, particularly in regions with elevated fluoroquinolone resistance. Hence, it was deduced that Fosfomycin is more effective than Ciprofloxacin for bacterial eradication in the treatment of urinary tract infections. These findings are influenced by significant heterogeneity in study design, populations, and outcome definitions, which should be considered when interpreting the pooled estimates.

Predictive ability of the geriatric 8 screening tool for treatment completion of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin therapy in patients with urothelial carcinoma.

Dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) therapy is expected to provide superior therapeutic efficacy compared to gemcitabine and cisplatin therapy as systemic chemotherapy for urothelial carcinoma. However, its high incidence of adverse events raises concerns about tolerability, particularly in older patients. This study evaluated the utility of the Geriatric 8 (G8) screening tool in patients undergoing dd-MVAC therapy and assessed its association with treatment progress. A retrospective analysis was conducted on 65 patients with urothelial carcinoma who received dd-MVAC therapy between August 2018 and May 2023, with the goal of completing six treatment cycles. The G8 score was evaluated before treatment initiation, and its association with treatment completion and adverse events was examined. The median age of patients was 71 years (range, 43-84 years), with 65% male and 35% female. The median pretreatment G8 score was 13 (range, 7-17). Patients with a G8 score ≥14 demonstrated a significantly higher six-cycle treatment completion rate than those with a G8 score <14 (87% vs. 60%, P = 0.026). The incidence of adverse events did not differ between the groups. Furthermore, among various clinicopathological factors, the G8 score was identified as an independent predictor of six-cycle treatment completion (odds ratio: 0.17, P = 0.021), along with Eastern Cooperative Oncology Group Performance Status. Pretreatment G8 scores were associated with the treatment completion rates of dd-MVAC therapy.

Challenges in achieving the UNAIDS 95-95-95 targets: evaluation of the antiretroviral therapy program among adult HIV/AIDS patients at Woldia General Hospital, Northeast Ethiopia.

In Ethiopia and other resource-limited settings, antiretroviral therapy (ART) has been instrumental in reducing the harmful impact of the HIV pandemic. ART program aims to decrease morbidity and mortality, minimize healthcare costs, and enhance the quality of life for individuals living with HIV. However, the program faces several challenges, including poor medication adherence, a higher incidence of adverse effects, drug resistance, and persistent issues of discrimination and stigma. This study aimed to evaluate the implementation process of the antiretroviral therapy (ART) program among adult HIV/AIDS patients at Woldia General Hospital in Northeast Ethiopia. Between June 1 and June 30, 2020, a mixed-method case study was conducted. A total of 384 patient charts were reviewed, and 402 individuals living with HIV/AIDS were interviewed using systematic random sampling technique and interviewer administered questionnaire. Additionally, six key informant interviews were conducted, and 30 observations of healthcare professionals were recorded. The quantitative data were entered into Epidata version 4.6 and subsequently transferred to STATA version 14 for analysis. Bivariable analysis was performed to identify variables with p-values less than 0.2 as potential candidates for multivariable logistic regression, with statistical significance set at p < 0.05. The qualitative data underwent transcription, translation into English, coding, thematic analysis, and manual interpretation. The overall implementation status of the program was assessed based on predefined evaluation criteria. According to national guidelines, 74.8% of the program was implemented consistently. Patient satisfaction was reported at 77%, healthcare personnel adherence to guidelines at 66%, and resource availability at 88.4%. Key challenges included shortages of test kits, Plumpy'Nut, and medications for opportunistic infections, as well as inadequate data management and issues with patient file handling. Most laboratory tests were not done according to the national guidelines. Additionally, refreshment training for health care providers was not given. Factors associated with patient satisfaction included the ability to disclose their condition (AOR = 3.25; 95% CI: 1.46, 7.26) and a waiting time of less than 30 min (AOR = 3.88; 95% CI: 1.26, 11.97). The overall level of program implementation was very good. However, patient satisfaction did not meet the national target of 85%, and adherence to national guidelines was minimal. Essential supplies such as HIV test kits, Plumpy'Nut, viral load tests, and medications for opportunistic infections were not consistently available. Additionally, most laboratory tests were not conducted in accordance with the guidelines. Factors associated with patient satisfaction included the ability to disclose HIV status and waiting times of under 30 min.

Integrating gender medicine into modern healthcare: Progress and barriers.

Sex and gender are fundamental determinants of health, influencing disease risk, diagnosis, treatment, and outcomes across medical disciplines. While sex refers to biological characteristics, gender encompasses sociocultural dimensions, including behaviours and identities. The field of gender medicine has evolved significantly from its roots in the women's health movement of the 1960s and 1970s, which initially sought to address reproductive rights and the systematic exclusion of women from clinical research. Over time, the focus has expanded to recognize sex- and gender-based differences in all populations, including men and gender-diverse individuals. Despite progress, persistent challenges remain. Many clinical guidelines inadequately incorporate sex and gender considerations, and women continue to be underrepresented in clinical trials, resulting in suboptimal efficacy and a higher incidence of adverse effects in women. Recent initiatives, including government-funded research programs, specialized gender medicine professorships and regulatory measures promoting equitable clinical trial participation, represent positive steps forward. However, a systematic, interdisciplinary approach is required to fully integrate gender-sensitive medicine into research, education and clinical practice. This narrative review explores the historical development of gender medicine, current advancements and remaining challenges. We highlight the need for improved research methodologies, policy changes and targeted interventions to ensure equitable healthcare. A structured action plan emphasizing regulatory support, education, industry involvement and public awareness is essential to accelerate the field's integration. Recognising and addressing sex- and gender-sensitive health differences will lead to more personalised and effective medical care, ultimately improving health outcomes for all individuals.

Nutritional correction of iron metabolism in women of reproductive age: results of an open-label, prospective, postregistration study with active parallel-group control

BACKGROUND: Iron deficiency anemia is one of the most common conditions worldwide and ranks first in prevalence among women of reproductive age. Conventional iron formulations are frequently associated with a high incidence of adverse effects. Therefore, there is a need to identify novel iron compounds that offer improved tolerability without compromising efficacy. AIM: To compare the outcomes of dietary correction in nonpregnant women receiving iron bisglycinate vs those receiving iron sulfate. MATERIALS AND METHODS: The study included 120 women of reproductive age (18–49 years) with mild iron deficiency anemia who met the inclusion criteria. Patients were randomized into 2 groups. The main group received the investigational product containing 30 mg of elemental iron in chelated bisglycinate form combined with vitamins C, B6, B12, and L-methylfolate (the dietary supplement VitaFerr), administered as 1 capsule once a day with food. The control group received a preparation containing 100 mg of elemental iron as sulfate combined with 60 mg of vitamin C, taken as 2 tablets per day. The total duration of therapy was 60 days. RESULTS: After adjustment for baseline hemoglobin levels, the proportion of female patients who achieved the target hemoglobin level was 88.9% in the main group and 94.3% in the control group (p=0.240). No statistically significant between-group differences were observed in hemoglobin, ferritin, or serum iron levels after 60 days (p 0.05), indicating comparable efficacy of the treatment regimens. The study showed that a daily dose of 30 mg of iron bisglycinate significantly increased serum ferritin levels — from 24.1 to 32.3 ng/mL by day 15, with a mean ferritin concentration of 39.1 ng/mL on day 60 (p 0.001). A statistically significant difference in the frequency of adverse events was observed between groups: 16 (26.7%) in the main group and 37 (61.7%) in the control group (p 0.001). CONCLUSION: The dietary supplement VitaFerr may be considered an effective and safe option for the prevention and treatment of iron deficiency and anemia.

Advances in lenvatinib monotherapy and combination therapies in anaplastic thyroid cancer (Review).

Anaplastic thyroid cancer (ATC) is a highly malignant and aggressive endocrine tumor with the poorest prognosis among all thyroid cancer (TC) subtypes. Although ATC is extremely rare, treatment remains a notable challenge, as traditional therapies have exhibited very limited efficacy. Targeted small-molecule inhibitors that disrupt molecular signaling pathways offer a potential therapeutic approach for patients with ATC. Lenvatinib, a tyrosine kinase inhibitor, has emerged as a promising therapeutic agent, which targets various factors involved in angiogenesis and tumor progression, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor α, fibroblast growth factor receptor and mast/stem cell growth factor receptor. Preclinical and clinical trials have demonstrated the efficacy of lenvatinib, both as monotherapy and in combination with other targeted therapy, chemotherapy, immunotherapy, warranting a comprehensive review of these studies. However, lenvatinib monotherapy was associated with a high incidence of adverse events (including hypertension, anorexia and proteinuria) and certain limitations, particularly drug resistance, emphasizing the need for optimized therapeutic strategies. In the present review, the efficacy and safety of lenvatinib monotherapy and combination therapies in the treatment of ATC were examined. Furthermore, the feasibility and limitations of different combination therapies were analyzed and compared. The present review aimed to provide insights into potential lenvatinib-based regimens that could enhance survival outcomes and improve the quality of life for patients with ATC in the future.

Exposure-response relationship of fedratinib in patients with intermediate-2 or high-risk myelofibrosis.

Fedratinib is a potent, oral, Janus kinase inhibitor for the treatment of myelofibrosis (MF). This report describes exposure-response (E-R) analyses of fedratinib based on pooled data from phase 2/3 studies in patients with intermediate-2 or high-risk MF, with or without prior ruxolitinib exposure. Pharmacokinetic (PK) exposures were derived from the population PK analysis. Efficacy endpoints included spleen volume reduction ≥35% (SVR35) and total symptom score reduction ≥50% (TSS response). Safety endpoints included grade ≥3 anaemia or thrombocytopenia, any-grade nausea/vomiting and diarrhoea. The E-R models were developed using logistic regression analyses. Fedratinib exposure was positively associated with SVR35 (odds ratio [OR], 38.2; 95% confidence interval [CI], 12.4-118; P < 0.001) and TSS response (OR, 20.8; 95% CI, 6.27-69.2; P < 0.001), after adjusting for covariates. Baseline spleen volume was inversely associated with SVR35 (P = 0.029). Prior ruxolitinib exposure was not associated with SVR35 (P = 0.090) or TSS response (P = 0.326). Although numerically higher incidence of adverse events was observed in patients with higher fedratinib exposure, there was no statistically significant association between fedratinib exposure and any safety related endpoints. Prior ruxolitinib exposure was associated with experiencing grade ≥3 thrombocytopenia (P = 0.004). Lower baseline haemoglobin level (<10g/dL) and platelet count (<100 × 109/L) were associated with experiencing grade ≥3 anaemia (P < 0.001) and thrombocytopenia (P < 0.001), respectively. Antiemetic prophylaxis was associated with lower rates of nausea/vomiting (P < 0.001). Fedratinib exposure was positively associated with spleen volume reduction and TSS responses, without having significant impact on safety. Fedratinib 400 mg once daily is an appropriate dose for patients with MF regardless of ruxolitinib exposure.

Real-World Effectiveness and Safety of Dupilumab, Tralokinumab, and Upadacitinib in Patients with Atopic Dermatitis: A 52-Week International, Multicenter Retrospective Cohort Study.

Evaluating the real-world effectiveness, safety, and tolerability of targeted biologic and non-biologic therapies in patients with atopic dermatitis (AD) treated in routine clinical practice remains crucial. In this international, multicenter, retrospective, comparative study we aimed to evaluate the 52-week effectiveness, safety, and tolerability of dupilumab, tralokinumab, and upadacitinib in patients with AD aged ≥ 12years. Effectiveness was assessed at weeks16, 24, and 52 using Eczema Area and Severity Index (EASI) and itch Numerical Rating Scale (NRS) scores. Safety was measured via adverse events (AEs). A total of 1286 treatment courses were included: 62.5% received dupilumab, 24.3% received upadacitinib, and 13.1% received tralokinumab. Upadacitinib demonstrated higher effectiveness than dupilumab and tralokinumab across all time points and most evaluated outcomes both on the overall population and the biologic-/JAKi-naïve population, including stringent treatment targets such as EASI90 response and combined EASI90 + itch NRS0/1 response. While upadacitinib demonstrated superior effectiveness, it was associated with a higher incidence of AEs, both leading to and not leading to treatment discontinuation, including thromboembolic events, lipid abnormalities, and hematologic abnormalities. In contrast, conjunctivitis was the most frequently observed AE among patients receiving biologics. This study provides a comprehensive real-world comparison of dupilumab, tralokinumab, and upadacitinib in AD, highlighting upadacitinib's superior effectiveness in achieving stringent treatment targets, both in the short and long term, but also a higher incidence of AEs. However, the considerable heterogeneity of the study population, an inherent limitation of real-world studies, must be acknowledged when interpreting these findings.

Voriconazole in the management of invasive pulmonary aspergillosis in patients with severe liver disease: balancing efficacy and hepatotoxicity.

Voriconazole in the management of invasive pulmonary aspergillosis in patients with severe liver disease: balancing efficacy and hepatotoxicity.

Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial.

Efficacy and safety of first-line maintenance therapy with lurbinectedin plus atezolizumab in extensive-stage small-cell lung cancer (IMforte): a randomised, multicentre, open-label, phase 3 trial.

Prognostic Value of Cardiovascular MRI in Asymptomatic Patients with Moderate-to-Severe Aortic Regurgitation: A Network Meta-Analysis.

Purpose To determine the prognostic significance of cardiac MRI parameters in patients with moderate-to-severe aortic regurgitation (AR) and minimal or no symptoms through a network meta-analysis. Materials and Methods This systematic review and network meta-analysis searched in PubMed, Embase, and Cochrane Library databases for articles published from January 1, 2000, to March 1, 2024, investigating the prognostic value of cardiac MRI parameters in patients with moderate-to-severe AR. The composite outcome included all-cause death, heart failure hospitalization, aortic valve replacement, new-onset heart failure symptoms, New York Heart Association class progression, and left ventricular ejection fraction less than 50%. Both pairwise and network meta-analyses were performed. Results Eight studies with 1579 patients (1187 male patients [75%]; mean age, 55 years ± 5 [SD]) were included. Aortic regurgitant volume and regurgitant fraction were associated with a higher incidence of adverse events (pooled hazard ratio [HR], 1.04 per 1 mL increase [95% CI: 1.01, 1.06] and pooled HR, 1.09 per 1% increase [95% CI: 1.03, 1.16], respectively). Adverse remodeling, reflected by increased end-diastolic or end-systolic volume (pooled HR, 1.02 per 1 mL/m2 [95% CI: 1.01, 1.03] and pooled HR, 1.02 per 1 mL/m2 [95% CI: 1.01, 1.04], respectively), was predictive of worse outcome. Late gadolinium enhancement was associated with a twofold increased risk of developing the study end point (pooled HR, 1.86; 95% CI: 1.20, 2.89). T1 mapping and extracellular volume could not be assessed. Network meta-analysis disclosed that late gadolinium enhancement (P = .884) and regurgitant fraction (P = .727) were the most important prognostic factors. Conclusion This network meta-analysis demonstrated the strong prognostic value of regurgitant fraction and left ventricular adverse remodeling as assessed with cardiac MRI in risk stratification of patients with moderate-to-severe AR and no or minimal symptoms. Keywords: Meta-Analysis, Aortic Regurgitation, Late Gadolinium Enhancement, Cardiac MRI Supplemental material is available for this article. © RSNA, 2025.

Efficacy and safety of entinostat plus exemestane in hormone receptor-positive breast cancer: a systematic review meta-analysis of randomized controlled trials.

Hormone receptor-positive (HR+) breast cancer continues to be a significant global challenge, as resistance to endocrine therapy (ET) often reduces its effectiveness. Entinostat (ENT), a novel and selective histone deacetylase inhibitor (HDACi), has been suggested to overcome the resistance. However, there is still ongoing debate regarding its efficacy and safety. Our meta-analysis aims to assess the efficacy and safety of ENT plus exemestane (EXE) versus placebo (PL) plus EXE in patients with HR+ breast cancer. Following PRISMA guidelines, a systematic search was conducted across PubMed, Web of Science, and Cochrane Library up to November 2024, resulting in the inclusion of four randomized controlled trials (RCTs) involving 1371 patients. The primary outcomes were progression-free survival (PFS) and overall survival (OS), while secondary outcomes were the objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). Our meta-analysis was prospectively registered in PROSPERO (registration number: CRD42024615056). Our Analysis showed that ENT + EXE significantly enhanced PFS in the overall HR+ population Hazard Ratio (HR) = 0.79 (95% CI 0.68-0.92; P = 0.003), particularly among human epidermal growth factor receptor-2 (HER2-) negative patients (HR = 0.80; 95% CI 0.68-0.95; P = 0.01) when compared to PL + EXE. However, no significant improvements were noted in OS (HR = 0.91; 95% CI 0.63-1.30; P = 0.60), ORR with relative risk (RR) = 1.37 (95% CI 0.90-2.07; P = 0.14), CBR (RR = 1.15; 95% CI 0.89-1.74; P = 0.29). Furthermore, our safety analysis demonstrated that patients receiving ENT + EXE experienced significantly higher rates of adverse events (AEs) of all grades, with a RR of 1.33 (95% CI 0.99-1.78) and a significant increase in grade ≥ 3 AEs (RR = 3.04; 95% CI 2.52-3.67). The ENT + EXE combination demonstrates significant PFS benefits in HR + breast cancer patients compared to PL + EXE. However, no improvements were seen in OS, ORR, or CBR. In addition, the higher incidence of AEs, especially hematologic and gastrointestinal, highlights the need for careful patient selection and monitoring.