Efficacy Of Treatment Research Articles

Semaglutide for the secondary prevention of cardiovascular disease in people with overweight or obesity, but without diabetes: a cost-effectiveness analysis

Abstract Background The recently published trial, SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) [1], was the first study to demonstrate that the glucagon-like peptide 1 receptor agonist, semaglutide, was superior to placebo in reducing the risk of major cardiovascular events in people with existing cardiovascular disease (CVD) and a body mass index of ≥27kg/m² but without diabetes. Despite the promising clinical benefits, the high cost of the medication has raised concerns about its financial viability and accessibility within healthcare systems. Purpose To explore whether use of semaglutide in addition to standard care (background use of lipid lowering, anti-hypertensive and/or anti-platelet therapies) for the secondary prevention of CVD in people with overweight or obesity is cost effective from the Australian healthcare perspective. Methods A Markov model was developed based on the SELECT trial, to evaluate the clinical outcomes and costs of a hypothetical population treated with semaglutide versus placebo over 20 years. With each annual cycle, subjects were at risk of having non-fatal CVD events (MI or stroke) or dying. Treatment efficacy, transition probabilities, and utilities were derived from the SELECT trial and published literature. Costs were obtained from Australian sources. The cost of semaglutide at a dosage of 2.4 mg/week (in line with SELECT) was estimated to be ~A$80 per week or A$4175 per year. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. All outcomes and costs were discounted by 5% per year. Costs are reported in 2023 Australian dollars (A$). Results Over a 20 year time horizon, treatment of 1000 hypothetical subjects with overweight or obesity and existing CVD with semaglutide compared to placebo prevented 126 non-fatal CVD events and 81 deaths, and yielded an additional 0.46 discounted life years and 0.48 discounted QALYs per person. The difference in total discounted costs was A$43,955 per person. This equated to ICERs of A$99,853 per YoLS and A$96,055 per QALY gained. Conclusions Assuming a willingness-to-pay-threshold of A$50,000 per QALY gained, semaglutide would not be considered cost-effective for the secondary prevention of CVD in people with overweight or obesity in Australia at current prices. A price reduction of 52% to less than A$2000 per year would be required for it to be considered a cost-effective treatment strategy in this setting. Given the modest event rates reported in SELECT, cost-effectiveness is likely to improve if use of semaglutide is targeted to higher risk groups. Moreover, SELECT primarily focused on cardiovascular benefits, however data supporting the impact of semaglutide on a number of other weight-related complications are anticipated and will inform a more holistic understanding of its cost effectiveness.

Objective and subjective physical activity assessment in obese patients with eating disorders

Abstract Background Discrepancies between objective and subjective measures of physical activity have been reported in healthy populations but remain unexplored in adults with obesity and psychosomatic disorders. Exercise is key for reducing these disorders, yet physiological and psychosomatic factors may complicate valid activity assessments in this population. Here, we compare self-reporting with actigraph data in a clinical setting. Methods Over two years, 27 obese patients (21 female, 6 male; 43±14 yrs; 41.3±5.7 kg·m−2) with eating disorders (EDE-Q) were recruited from an Austrian Psychosomatic Center. Total physical activity was assessed using the metabolic equivalent (MET min/w) and sitting time (min/d). Objective data were collected using the SenseWear® wristband (SWA) during weeks 3-4 of patients’ clinical stay. SWA was worn for ≥18 h/d on ≥ 4 days, including one weekend day. Patients self-administered the International Physical Activity Questionnaire (IPAQ-SF) in alignment with the ∼7 days of SWA wear. Concurrent validity - SWA as a criterion - was assessed using regression analyses, and proportional bias was examined with regression and equality line similarity analyses. Results Comparison showed an overestimation of total activity (+45%; p<.001) and underestimation of sitting time (-28%; p<.001) with IPAQ-SF vs SWA. Within-patient correlations were poor for MET (r=.92, p<.001) and impractical for sitting time (r=.27, p=.018), with a proportional bias for both outcomes (p≤.001). Converting objective to subjective measures yielded typical errors of 232 (total activity) and 90 min (sitting time). Conclusions The observed disparities emphasize the need to integrate sensor-based assessment of physical activity into clinical practice or tailored public health initiatives for adult obesity and psychosomatic disorders. However, further research is needed to evaluate the long-term impact of incorporating accurate SWA data on intervention efficacy in this vulnerable group. Key messages • There was strong evidence for meaningful differences in objective vs subjective physical activity assessments in obese patients with eating disorders. • Integrating objective measures into treatment seems crucial to improve exercise-guided interventions and address the global obesity and psychosomatic disorders pandemic.

Cardiotoxicity in cancer immunotherapy: challenges in diagnosing and managing ICI-associated myocarditis

Immunotherapy has revolutionized cancer treatment, particularly through immune checkpoint inhibitors (ICIs), which enhance the body's immune response against tumors. However, these therapies can also trigger immune-related adverse events (irAEs), with myocarditis being one of the most severe but rare complications. This article reviews the pathophysiology, clinical manifestations, and current management strategies for ICI-induced myocarditis. While significant advancements have been made, the early diagnosis of this condition remains a challenge due to nonspecific symptoms. Current treatment relies heavily on the discontinuation of ICIs and the use of corticosteroids, but there is an urgent need for standardized diagnostic criteria and optimized therapeutic protocols. This review highlights the gaps in existing knowledge and emphasizes the importance of further research to improve patient outcomes. Understanding these complexities is crucial for ensuring that the benefits of immunotherapy outweigh the risks, ultimately improving the safety and efficacy of cancer treatments, as these treatments are essential for sustaining individual life.

Effects of Concurrent Administration of Spironolactone in Veterans with Metastatic Prostate Cancer Receiving Abiraterone: A Real-World Retrospective Study.

Prostate cancer is the most common cancer in men in the United States with low survival rates once metastasized. Abiraterone is approved for use in castrate-sensitive and castrate-resistant prostate cancer and is used extensively in the Veterans Affairs (VA) healthcare system. Spironolactone, a diuretic used to treat heart failure, edema, ascites, and hypertension, may increase androgen levels and reduce effectiveness of abiraterone when used concurrently to treat prostate cancer patients. While previous case studies support this, no large epidemiology studies have been conducted. The current study utilizes the large, VA prostate cancer data core and evaluates the effect of concomitant spironolactone on efficacy of abiraterone treatment in metastatic prostate cancer patients. The study selected 18,943 veterans with metastatic prostate cancer on abiraterone treatment. Of these, 581 patients (3.1%) were also on concomitant spironolactone. The concomitant treatment group, abiraterone + spironolactone, significantly differed from the abiraterone-only group in body mass index, prevalence rates of heart failure and liver disease, and being previously treated with docetaxel. A 1:1 propensity score matching method was used to balance sample sizes and baseline traits between the two treatment groups, abiraterone versus abiraterone + spironolactone. Kaplan-Meier curves and Cox proportional hazard model were used to compare 5-year overall survival and all-cause mortality outcomes, respectively, between the two groups. After propensity score matched, the abiraterone + spironolactone group was treated with abiraterone significantly longer than the abiraterone-only group (mean ± standard deviation days 549.0 ± 552.3 vs. 435.5 ± 474.1; p = 0.0002) and had a higher 5-year overall survival rate (44% vs. 37%; p = 0.0116). Veterans with metastatic prostate cancer treated with abiraterone + spironolactone also had a lower 5-year all-cause mortality compared to those only on abiraterone (hazard ratio 0.80, 95% confidence intervals 0.61-0.96; p = 0.012). This large VA observational study suggests that concomitant use of spironolactone does not compromise cancer control or survival of metastatic prostate cancer patients treated with abiraterone.

REverse transcriptase ACTivity (REACT) assay for point-of-care measurement of established and emerging antiretrovirals for HIV treatment and prevention.

Maintaining adequate levels of antiretroviral (ARV) medications is crucial for the efficacy of HIV treatment and prevention regimens. Monitoring ARV levels can predict or prevent adverse health outcomes like treatment failure or drug resistance. However, conventional ARV measurement using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is slow, expensive, and centralized delaying clinical and behavioral interventions. We previously developed a rapid enzymatic assay for measuring nucleotide reverse transcriptase inhibitors (NRTIs) - the backbone of HIV treatment and prevention regimens - based on the drugs' termination of DNA synthesis by HIV reverse transcriptase (RT) enzyme. Here, we expand our work to include non-nucleoside reverse transcriptase inhibitors (NNRTIs) - an ARV class used in established and emerging HIV treatment and prevention regimens. We demonstrate that the REverse Transcriptase ACTivity (REACT) assay can detect NNRTIs including medications used in oral and long-acting/extended-release HIV treatment and prevention. We demonstrate that REACT can measure NNRTIs spiked in either buffer or diluted plasma and that fluorescence can be measured on both a traditional plate reader and an inexpensive portable reader that can be deployed in point-of-care (POC) settings. REACT measured clinically relevant concentrations of five NNRTIs spiked in aqueous buffer. REACT measurements showed excellent agreement between the plate reader and the portable reader, with a high correlation in both aqueous buffer (Pearson's r = 0.9807, P < 0.0001) and diluted plasma (Pearson's r = 0.9681, P < 0.0001). REACT has the potential to provide rapid measurement of NNRTIs in POC settings and may help to improve HIV treatment and prevention outcomes.

Intramyocardial fatty infiltration lesion in sporadic inclusion body myositis: a case report.

Sporadic inclusion body myositis (sIBM), the most common inflammatory muscle disorder in adults over 50 years, is often misdiagnosed due to its gradual onset and its common but unspecific muscle weakness in older adults. Diagnosis relies on clinical, radiological, and pathological features. Cardiac involvement is rare, prompting this case description and a comprehensive literature analysis. A 73-year-old woman diagnosed with sIBM in 2021 through muscle biopsy had been experiencing muscular symptoms since 2015. Her condition progressively worsened, affecting daily activities. Annual follow-ups revealed a moderate obstructive syndrome on respiratory testing, prompting a cardiac evaluation. Cardiac magnetic resonance (CMR) imaging identified intramyocardial lesions consistent with fatty infiltration, highlighting the interest of advanced imaging in sIBM management. Cardiac involvement in sIBM is presumed rare compared to other idiopathic inflammatory myopathies, though the exact frequency remains unclear. Early identification of heart alterations by CMR in sIBM can be prognostically valuable, guiding follow-up and interventions. However, literature on this subject is limited to small cohort studies and case reports describing complications. Given the slow progression of sIBM and the limited efficacy of current treatments, the discovery of myocardial lesions could warrant closer cardiological monitoring. Larger cohort studies are needed to explore potential new therapeutic approaches. Our case underscores the importance of CMR in detecting subtle cardiac manifestations in sIBM and illustrates the potential prognostic value of cardiac assessment in the management of sIBM.

Assessing the predictive value of intraductal carcinoma of the prostate (IDC-P) in determining abiraterone efficacy for metastatic hormone-sensitive prostate cancer (mHSPC) patients.

This study explored the value of intraductal carcinoma of the prostate (IDC-P) in predicting the efficacy of abiraterone treatment in metastatic hormone-sensitive prostate cancer (mHSPC) patients. A retrospective study of 925 patients who underwent prostate biopsies to detect IDC-P was conducted, with participants divided into two cohorts. The first cohort of 165 mHSPC patients receiving abiraterone treatment was analyzed to compare therapeutic effectiveness between IDC-P positive and negative cases. Utilizing propensity score matching (PSM) to reduce bias, outcomes such as PSA response, progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival were assessed. Additionally, the second cohort of 760 mHSPC patients compared the efficacy of abiraterone with conventional hormone therapy, focusing on differences between IDC-P positive and negative individuals. After PSM, our first cohort included 108 patients with similar baseline characteristics. Among them, 50% (54/108) were diagnosed with IDC-P, with 22.2% (12/54) having IDC-P pattern 1 and 77.8% (42/54) with IDC-P pattern 2. While no notable difference was seen in PSA responses between IDC-P positive and negative patients, IDC-P presence linked to worse clinical outcomes (PSA-PFS: 18.6 months vs. not reached [NR], p = 0.009; rPFS: 23.6 months vs. NR, p = 0.020). Further analysis showed comparable outcomes for IDC-P pattern 1 but significantly worse prognosis for IDC-P pattern 2 (PSA-PFS: 18.6 months vs. NR, p = 0.002; rPFS: 22.4 months vs. NR, p = 0.010). Subgroup analysis revealed IDC-P pattern 2 consistently predicted poorer outcomes across patient subgroups. Remarkably, both IDC-P positive and negative patients gained more from androgen deprivation therapy with abiraterone than conventional treatment, with IDC-P negative patients showing a more significant survival advantage, supported by better hazard ratios (0.47 and 0.66). This study found that IDC-P, especially pattern 2, predicts poor prognosis in mHSPC patients on abiraterone therapy. Also, abiraterone's advantage over hormone therapy is reduced in cases with IDC-P compared to those without.

Real world evidence of Sacubitril/Valsartan in octogenarian patients with heart failure. Results From the PARACHUTE-HF Study

Abstract Introduction The beneficial effects of Angiotensin Receptor Neprilysin Inhibitors (ARNI) on heart failure (HF) patients, particularly those with reduced left ventricular ejection fraction (LVEF), have been highlighted in several randomized controlled trials. Since 2020, ARNI has been available for HF treatment in Japan, a country known for its aging population. However, the inclusion of octogenarians in previous trials has been limited, leaving a gap in evidence regarding ARNI's effectiveness in the elderly. Objective This study aims to explore the real-world efficacy and safety of ARNI treatment among octogenarian HF patients in Japan, reflecting its status as a leading aging society. Methods The Prospective Area Registry of ARNI for Congestive Heart failUre in Tokyo East (PARACHUTE) trial, a multicenter registry, was conducted. It involved patients newly prescribed ARNI for chronic HF regardless of LVEF between 2020 and 2021. We compared patient backgrounds, changes in NT-proBNP levels at 6 months, and the rate of ARNI discontinuation between groups aged below and above 80 years. Results The study enrolled 105 patients, with an average age of 75 years. Forty-six patients (44%) were over 80 years old, and the majority (72%) were male. Among the younger group, 50% had preserved LVEF, compared to 32% in the octogenarian group (p=0.01). Median NT-proBNP levels across all patients decreased significantly from 2,540 pg/mL at baseline to 998 pg/mL at 6 months. The reduction in NT-proBNP was similar between the two age groups, with no significant interaction (p=0.46). Discontinuation rates due to any cause were not significantly different between younger and older patients (7% vs. 13%, p=0.28). Conclusion ARNI treatment resulted in significant reductions in NT-proBNP levels in HF patients, both under and over 80 years of age, with comparable discontinuation rates. These findings highlight the effectiveness and safety of ARNI in the management of chronic HF in the elderly, offering valuable real-world evidence from Japan's unique demographic context.

Real-life experience with rilonacept for the treatment of recurrent pericarditis

Abstract Background Rilonacept, a soluble Interleukin-1 (IL-1) receptor fusion protein that neutralizes IL-1α and IL-1β, has shown efficacy in symptom resolution, weaning of standard-of-care therapies, and reducing the frequency of recurrent pericarditis (RP) episodes in clinical trials. Purpose We aimed to review the efficacy, safety, and duration of treatment with Rilonacept reliance in managing RP in our practice. Methods We analyzed 22 patients with RP treated with Rilonacept, 55 [43-69] years, 11 (50%) females. We reviewed clinical characteristics and outcomes, including the time since initial diagnosis of pericarditis, the presence of pericardial effusion/thickening, the duration of Rilonacept treatment, the ability to wean off steroids, and the recurrence of pericarditis symptoms attempting discontinuation. Results The length of time from the initial diagnosis of pericarditis to Rilonacept initiation was 9 [4-32] months. Fifteen patients out of 22 (68%) had pericardial effusion, 3 (20%) with tamponade requiring pericardiocentesis. Median length of treatment with Rilonacept was 14 [6-23] months, with 17/22 (77%) of patients being treated for ≥ 6 months. All patients who were on steroids (14/22, 64%) were able to discontinue their usage 1 [1-9] months after starting Rilonacept. Of the seventeen who were treated for 6 months or more, 12 (70%) remained on Rilonacept 160 mg weekly at the most recent assessment, 3 (18%) continued treatment with Rilonacept 160 mg every 2 or 4 weeks, and 2 (12%) discontinued Rilonacept treatment after 6 and 50 months. Of the 12 patients who remained on weekly treatment after a period of 6 months, 8 (67%) required Rilonacept for symptom control, 1 (8%) had recurrent symptoms after treatment every 2 weeks, and the remaining 3 (25%) preferred to continue despite a lack of symptoms (Figure 1). Conclusions The efficacy of Rilonacept in treating patients with RP and the ability to stop steroid therapy in the real world is in line with the efficacy data from clinical trials.Figure 1

Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac amyloid transthyretin: results of treatment beyond 12 months in the open-label extension of study NI006-101

Abstract Introduction ALXN2220 (formerly NI006) is an investigational human monoclonal antibody in development for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ALXN2220 is designed to deplete cardiac amyloid transthyretin (ATTR) deposits in patients with ATTR-CM on top of standard of care. Data from the first-in-human, ascending dose study NI006-101 show that ALXN2220 is safe and well tolerated. A reduction of surrogate markers of cardiac amyloid load and cardiac biomarkers was observed in participants receiving doses of ≥ 10mg/kg of ALXN2220 over a period of 12 months of treatment. Purpose Long-term safety, tolerability and efficacy of ALXN2220 treatment beyond 12 months was studied in a prolonged Open-Label Extension (OLE) of the NI006-101 study. Methods Participants completing 12 months in dose cohorts ≤ 30 mg/kg were allowed to receive additional 6 to 12 monthly open-label ALXN2220 infusions with up-titration of all participants to 30 mg/kg. Cardiac biomarkers were measured centrally, and serial cardiac imaging was performed with echocardiography and cardiac MRI or scintigraphy. Results Out of 27 participants completing 12 months, 23 (18 ATTRwt, all male, median age 70 years at screening (range 28-83)) continued treatment in the prolonged OLE. Median number of infusions of ALXN2220 received and median time followed across the full study were 20 infusions (range 11-24) and 125 weeks (range 83-153). Overall adherence to treatment was high in the prolonged OLE, 97% of planned infusions administered, 87% of participants received all planned doses. No severe or serious adverse events were considered related to ALXN2220 or resulted in the discontinuation during OLE, and no events of cytokine release syndrome or thrombocytopenia were observed. None of the participants had anti-drug antibodies throughout the trial. Cardiac biomarkers (NT-proBNP, troponin) and cardiac imaging indicated continued treatment effects beyond 12 months and supported the up-titration of participants who previously received lower doses of ALXN2220. Conclusions Up-titration and long-term treatment at a dose level of 30 mg/kg in the OLE was safe and well tolerated, with overall good adherence to treatment. Cardiac imaging and cardiac biomarker data indicated continued treatment effects beyond 12 months and supported the up-titration of patients to 30 mg/kg.

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (&amp;lt;25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value &amp;lt;0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI &amp;lt;25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI &amp;lt;25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI &amp;lt;25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.

Closing the Gaps: Testing the Efficacy of Carbapenem and Cephalosporin Treatments of Late-Stage Anthrax in Rabbits

Anthrax is a fatal zoonotic disease caused by exposure to Bacillus anthracis spores. The CDC’s guidelines divide anthrax treatment into three categories according to disease progression: post-exposure prophylaxis (PEP), systemic, and systemic with a suspicion of CNS infection. While the prognosis for PEP or the early treatment of systemic anthrax is very good, ingress of the bacteria into the CNS poses a substantial clinical challenge. Here, we use rabbits to test the efficacy of a combined treatment of meropenem and doxycycline, which is the first choice in the CDC recommendations for treating systemic patients with an indication of CNS infection. In addition, we test the efficacy of the first-generation cephalosporin, cefazolin, in treating different stages of the disease. We found that the combination of doxycycline and meropenem is highly effective in treating rabbits in our inhalation model. Cefazolin was efficient only for PEP or systemic-stage treatment and not for CNS-infected animals. Our findings support the CDC recommendation of using a combination of doxycycline and meropenem for systemic patients with or without indications of CNS infection. We found that cefazolin is a decent choice for PEP or early-stage systemic disease but recommend considering using this antibiotic only if all other options are not available.

Leveraging digital tools to enhance diversity and inclusion in clinical trial recruitment

Clinical research is pivotal in assessing the safety and efficacy of new treatments in healthcare. However, the success of such research depends on the inclusion of a diverse and representative participant sample, which is currently lacking. This lack of diversity in biomedical research participants has significant repercussions, limiting the real-world applicability and accessibility of medical interventions, especially for underrepresented groups. Barriers to diverse participation include historical mistrust, logistical challenges, and financial constraints. Recent guidelines by government agencies and funding bodies emphasize the need for diversity in clinical trials, but specific strategies for inclusive recruitment are often lacking. This paper explores the use of digital methods to enhance diversity and inclusion in research recruitment. Digital tools, such as electronic medical records, social media, research registries, and mobile applications, offer promising opportunities for reaching diverse populations. Strategies include culturally tailored messaging, collaborations with community organizations, and the use of SEO to improve visibility and engagement. However, challenges such as privacy concerns, digital literacy gaps, and ethical considerations must be addressed. The promotion of diversity in clinical research recruitment is crucial for advancing health equity. By leveraging digital tools and adopting inclusive strategies, study teams can improve the diversity of study participants, ultimately leading to more applicable and equitable healthcare outcomes.

Acute Myeloid Leukemia as a Trigger for Hemolytic–Uremic Syndrome

Acute myeloid leukemia (AML) has not been identified as a cause of secondary hemolytic–uremic syndrome (HUS). This case report describes a woman who developed severe HUS at the time of AML diagnosis and responded favorably to initial treatment with eculizumab, which stabilized her condition and allowed for treatment of the AML. After one year, with stable renal function and genetic studies reported as normal, eculizumab was successfully discontinued. The prompt use of eculizumab was critical to the patient’s survival and improvement in renal function, highlighting the efficacy of early eculizumab treatment in secondary HUS.

10 years after treatment with renal denervation of the sympathetic nerves for resistant hypertension: what happened to the patients and their office blood pressure? An observational study

Abstract Background Catheter-based renal denervation of the sympathetic nerves (RDN) for resistant hypertension has long been controversial. A renewed clinical and scientific interest in defining the appropriate role of RDN in the treatment of resistant hypertension has become evident in recent years. The efficacy and safety of RDN treatment is mainly based on available data up to three years, whereas data concerning the long-term effect and safety are scarce. Purpose We therefore wanted to investigate the long time change in blood pressure (BP) in patients treated with RDN for resistant hypertension. Methods A review of data from the electronic patient journal concerning all RDN treated patients was initiated and completed in October 2023. Every registration of an office BP listed in the patient file, antihypertensive treatment, cardiovascular events, and renal function between 2012 and 2023 were registered. For each patient the average of all office post RDN blood were averaged for every year and for their complete follow-up. The outcome in blood pressure was the change in BP from baseline pre RDN office to follow-up Results Between January 2012 and October 2013, 19 consecutive patients underwent RDN treatment, 10 men and 9 women with a median age of 63 years (range 35-74 years). At baseline the median systolic office BP was 181 mmHg (range 162–230 mmHg) and the diastolic office BP 97 mmHg (range 82-123 mmHg) on a median of 5 (range 0-7 ) antihypertensive drugs. During follow-up the number of antihypertensive drugs were reduced in 7, unchanged in 10, and increased in 2 patients. Two patients left the outpatient clinic with normal BP after 2 years. Two patients developed heart failure after 7 years and were censored at that time-point. 15 (79%) patients had office BP recorded up to 9 or 10 years. In the 15 (79%) patients with available office BP 9 to 10 years after RDN the median systolic and diastolic office BPs were reduced by 39 mmHg (range -2 to - 66 mmHg) and 18 mmHg (range -11 to - 55 mmHg) respectively, relative reduction 22% (range 5-36%) and 20% (range 6-32), respectively. Conclusion During a follow-up of 9 to 10 years after RDN without a step-up in antihypertensive medication a relative decrease of ~20% in systolic and diastolic BP was observed.

Reassessing pharmacological trials with positive composite outcome driven by reduction in nonfatal myocardial infarction: a systematic review and meta-analysis

Abstract Background Nonfatal myocardial infarction (MI) inadequately predicts cardiovascular and all-cause mortality in contemporary RCTs. The perceived efficacy of new treatments could be overstated if positivity in composite outcome is primarily attributed to reduction in nonfatal MI. Purpose This study seeks to assess pharmacological RCTs with positive results influenced by nonfatal MI reductions and scrutinize the associated clinical guideline recommendations. Methods Pharmacological RCTs focusing on mortality and nonfatal MI published from 2000 to 2023 were searched in PubMed and Web of Science, with subsequent citation tracking in Web of Science and Google Scholar for candidate RCTs referenced in English-language clinical guidelines. Main outcomes included: 1) relative risk reduction in the composite outcome excluding nonfatal MI; 2) relevant guideline recommendations based on the supporting trials. The impact of nonfatal MI on composite outcome was assessed by using the leave-one-out method. Meta-analysis utilized a random effects model. Results After reviewing 19,825 records, we identified 8 RCTs where positive composite outcomes were driven by reductions in non-fatal MI (Figure 1A). These were divided into three therapeutic groups: anti-thrombotic (3 trials), lipid-lowering (3 trials), and anti-inflammatory (2 trials). In guidelines citing these RCTs, lipid-lowering trials (IMPROVE-IT, FOURIER, CLEAR Outcomes; the latter has not been cited yet; a total of 60 recommendations across 17 guidelines; Figure 2) outperformed anti-thrombotic (27 recommendations across 15 guidelines) and anti-inflammatory trials (3 recommendations in 3 guidelines), with significantly higher Class I (45%) and IIa (33.3%) recommendations, and fewer Class IIb (21.7%) recommendations, compared to anti-thrombotic (0%, 22.2%, 66.7%) and anti-inflammatory (0%, 0%, 100%) trials (Figure 1B). In a meta-analysis of all trials on combined intensive lipid-lowering on top of maximally-tolerated statins (the ODYSSEY OUTCOMES, IMPROVE-IT, and FOURIER trials), the exclusion of nonfatal MI data sustained the negative findings (HR 0.94, 95% CI: 0.88 to 1.01). Conclusions Despite the overestimation of efficacy in certain anti-thrombotic, anti-inflammatory, and lipid-lowering RCTs due to the inclusion of nonfatal MI, lipid-lowering trials, particularly those supporting combined intensive therapy with statins, still receive disproportionately favorable guideline recommendations. This underscores the need to reassess the strength of evidence for these trials in guidelines, advocating for a more equitable and evidence-based approach to cardiovascular guideline recommendations.

Shorter duration of Blinatumomab administration to 14 days has same efficacy and safety profile in treatment of relapsed/refractory B-cell precursor acute lymphoblastic leukemia: A retrospective single‐center study

Introduction: Treatment of patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) remains a significant clinical challenge. Many new strategies are changing the treatment landscape of r/r BCP-ALL in recent years. Blinatumomab has improved outcomes in r/r BCP-ALL, though high treatment costs and extended hospital stays are significant concerns. We considered that shortening the duration of blinatumomab administration during induction therapy might solve these problems. Methods: We retrospectively analyzed 19 patients with r/r BCP-ALL treated with different duration of blinatumomab, where 10 patients received blinatumomab for 14 days (Bli 14 D group) and 9 received it for a longer duration (LT group, 21-28 days). Results: The overall response rate (ORR) was 63.2% (12/19) of patients in total, and the ORR rates in 14 D and LT groups were almost the same (60% and 66.6%, respectively). The median overall survival (OS) was not reached in either groups. The median event-free survival (EFS) time was 4.1 months in LT group and not reached in D14 group. The most common adverse events were consistent with previous reports, including cytokine release syndrome (CRS), neurologic toxicity, and hematological toxicity. Conclusion: A 14-day blinatumomab administration may be a promising and well-tolerated regimen in r/r BCP-ALL, offering the same ORR and survival rates.

Application of Endovenous Laser Treatment Combined with Foam Sclerotherapy for the Minimally Invasive Treatment of Great Saphenous Vein Varicosity

Objective: To evaluate the efficacy of endovenous laser treatment (EVLT) combined with foam sclerotherapy (FS) in the treatment of great saphenous vein varicosity (GSVV). Methods: A total of 50 patients with GSVV, treated between March 2021 and March 2024, were selected and randomly divided into two groups using a random number table. The combination group (25 cases) underwent EVLT combined with FS, while the conventional group (25 cases) underwent EVLT alone. The total effective rate, complication rate, disease severity score, and serological indicators were compared between the two groups. Results: The total effective rate in the combination group was higher, and the complication rate was lower compared to the conventional group (P &lt; 0.05). One week after surgery, the disease severity score in the combination group was lower, coagulation function indicators were better, and inflammatory factor levels were lower compared to the conventional group (P &lt; 0.05). Conclusion: EVLT combined with FS can improve the clinical efficacy in GSVV patients, prevent postoperative complications, reduce disease severity, protect patients’ coagulation function, and alleviate postoperative inflammatory responses, showing significant advantages in combined surgery.

Efficacy and safety of inclisiran in real-world clinical practice. Results from the CHOLINET Registry

Abstract Background/Introduction Inclisiran has been recently introduced in clinical practice. Thus, efficacy and safety data from real-world settings are limited. Purpose Cholinet (Cholesterol inclisiran Italian network) is an Italian multicenter prospective phase 4 registry including 36 Italian centers, designed to assess efficacy, safety, adherence and persistence of inclisiran treatment, and clinician’s behavior on LLT in very high CV risk patients with atherosclerotic CV disease and/or familial hypercholesterolemia (FH). Methods From November 2022 through February 2024, the Cholinet registry enrolled patients receiving inclisiran according to standard clinical practice. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at subsequent follow-up. Results We enrolled 668 patients in treatment with inclisiran (15.1% with FH, 30.7% female, mean age 63 years), Data on follow-up at 3 months (booster time) were available for 495 of them. At the time of inclisiran first prescription median LDL-C was 102 mg/dl and reached 51 mg/dl at the time of 3 months observation (50% mean reduction, 51 mg/dl absolute median reduction). None of the 495 patients reaching 3 months follow up missed the reinjection dose administration. Of 668 patients enrolled, 553 patients (82.7%) were on LLT, of them 107 (19.3%) were on ezetimibe alone, 67 (12.1%) on statin alone and 379 (68.5%) on a statin and ezetimibe combination. Of the enrolled patients, 45 (6.7%) were previously treated with evolocumab and 34 (5%) with alirocumab. Among the patients evaluated at the 3-month follow-up, 307 patients (62%) achieved the LDL cholesterol target; of them, 450 (91%) were treated with inclisiran and statin±ezetimibe. Evaluating the distribution of the percentage reduction in LDL cholesterol values, a heterogeneity emerged that was partly explainable by the concomitant lipid-lowering therapy and partly by the previous exposure to PCSK9 inhibitors. Conclusions These preliminary data from the Cholinet Italian registry show that inclisiran effectively reduces (50%) LDL-C in real-world settings. The LDL-C target was achieved in 62% of patients; of them 91% were on lipid-lowering therapy, showing that combination therapy is necessary in most of these patients.

Efficacy of digital interventions for smoking prevention among children: a systematic review

Abstract Background Smoking remains a leading preventable cause of morbidity and mortality globally, with initiation often occurring in childhood. Early smoking onset is linked to increased difficulty in quitting and higher risk of long-term health complications. Traditional prevention strategies have not fully succeeded in curbing youth smoking rates, highlighting the need for innovative approaches. Digital interventions (DI), such as gamified education, social media campaigns, and virtual reality, offer a novel avenue for engagement and education. This systematic review aims to assess the efficacy of DI in preventing smoking, and improving knowledge and awareness about smoking damages, among children. This review is part of the PRIN project, whose goal is to evaluate the effectiveness of a DI aimed at school-aged children, intended to increase knowledge about the negative effects of smoking and prevent its use. Methods On the 18th of March 2024, PubMed, Scopus, and PsycINFO were surfed for trials and observational studies evaluating DI for smoking prevention among children aged 6-12 years. Study quality will be evaluated using the Cochrane Risk of Bias Tool and New Castle-Ottawa scale. The protocol has been registered in PROSPERO. Results From 3,081 initially identified articles, 328 papers were removed because duplicate. The screening process is ongoing. Conclusions DI are a promising tool for engaging young populations through platforms they are familiar with and receptive to. By leveraging the high penetration of digital technology in the daily lives of children, these interventions have the potential to deliver smoking prevention messages in a compelling and interactive manner. Understanding the effectiveness of DI in smoking prevention can significantly contribute to public health by providing viable alternatives to traditional methods and potentially reducing future smoking-related health burdens. Key messages • Evaluating digital strategies for smoking prevention among children could offer vital alternatives to traditional methods, potentially reducing long-term health risks. • Digital interventions (DI) offer promising new ways to engage young audiences on smoking prevention using familiar platforms, potentially reshaping public health approaches.