[Posted 7/Oct/2025]

AUDIENCE: Cardiology, Emergency Medicine

KEY FINDINGS: Endovascular treatment for BTK PAD is more often performed in patients with CLTI compared with IC, where it is often combined with an inflow artery intervention or complex lesion crossings. Despite similar procedural success, 1-year MALE is significantly higher in CLTI, driven mainly by over a 2-fold increase in all-cause mortality and major amputations.

BACKGROUND: There are unresolved questions regarding indications and outcomes of endovascular below-the-knee (BTK) interventions in patients with symptomatic peripheral artery disease (PAD) in real-world clinical practice. We analyzed 884 patients from the multicenter XLPAD registry between 2006 and 2023 with nonstent BTK PAD interventions. Primary outcome: freedom from major adverse limb events (MALE) at 1 year, a composite of all-cause death, major amputation, or clinically driven revascularization.

DETAILS: Majority (62.8%) of the BTK interventions were performed for chronic limb threatening ischemia (CLTI), while remaining (37.2%) in patients with intermittent claudication (IC), performed together with an inflow femoropopliteal artery intervention in 58% or involving complex lesion crossings (11.8%). Nearly, 74% were men, mean age 68.0 ± 10.7 years. Mean Rutherford class was 4.65 in CLTI and 2.71 in IC groups. Moderate to severe calcification was present in 25% of cases. Significantly greater number of lesions were treated in the CLTI group (1.84 ± 1.52 vs 2.08 ± 1.61; p = 0.029). Lesion lengths (CLTI: 129.3 ± 85.1 mm vs IC: 115.5 ± 82.5; p = 0.075) were comparable. Nearly, 92% of lesions were treated with balloon angioplasty. Drug-coated balloon use was higher in IC (5% vs 15%, p <0.001), whereas atherectomy use was high in both groups (CLTI: 45.4% vs IC: 49.9%; p = 0.201). Procedural success was similar (CLTI: 92% vs IC: 88.8%; p = 0.098), however 1-year MALE was significantly higher in CLTI patients (30.5% vs 15.8% vs; p <0.0.001), driven by higher all-cause mortality (5.6% vs 2.1% vs; p = 0.014) and major amputations (14% vs 3.7%; p 0.001).

Copyright © Elsevier Inc. All rights reserved.

Source: Rozol, Z. P., Sayfo, S., Fernandez-Vazquez, D., et al. (2025). Indications and Treatment Outcomes of Below-the-Knee Peripheral Artery Interventions in the XLPAD Registry. American Journal of Cardiology. 2025; 251: 38-45. Published: September 15, 2025. DOI: 10.1016/j.amjcard.2025.05.011 .

A Randomized Controlled Trial

[Posted 6/Oct/2025]

AUDIENCE: Nephrology, Cardiology, Internal Medicine

KEY FINDINGS:

• Physical exercise before hemodialysis is as cardioprotective as intradialytic exercise.
• Predialytic exercise potentially addresses several modality-specific barriers and challenges encountered by both health care providers and patients.
• These are likely mediated by mechanisms inherent to exercise itself, rather than by transient central and/or systemic hemodynamic alterations.

BACKGROUND: Hemodialysis induces left ventricular regional wall motion abnormalities (RWMAs) due to myocardial hypoperfusion. Although acute intradialytic exercise (IDE) has shown cardioprotective effects, its routine implementation faces feasibility challenges, and the potential of predialysis exercise as an alternative remains unexplored. This study aimed to compare the effect of predialysis exercise and IDE on hemodialysis-induced myocardial stunning.

DETAILS: In this open-label, randomized cross-over trial, 25 patients with ESKD underwent to each of three hemodialysis conditions, administrated in random order: standard hemodialysis (HD-_CONT), hemodialysis with IDE (HD-_PER), and hemodialysis preceded by exercise (HD-_PER). Two-dimensional echocardiography and whole blood viscosity (WBV) measurements were performed both immediately before hemodialysis onset (T₀) and at peak stress of hemodialysis (T_peak). Left ventricular longitudinal strain from an 18-segment model was used to assess the presence of RWMAs. Regular monitoring of cardiovascular hemodynamics was set up with measurements staggered every 30 minutes. Compared with HD-CONT, there was a significant reduction in RWMAs during both HD-_PER (estimated difference, 1.60 segments; 95% confidence interval, 0.09 to 3.10; P = 0.04) and HD-_PRE (estimated difference, 1.72 segments; 95% confidence interval, 0.21 to 3.22; P = 0.02). The magnitude of the exercise-induced reduction in myocardial stunning did not differ between HD-_PER and HD-_PRE (P = 0.86). Apart from the exercise period itself, kinetics of all hemodynamic variables were similar between HD-CONT and HD-_PER, whereas they were totally similar between HD-CONT and HD-_PRE. No associations of changes in RWMAs and hemodynamics variables between HD-CONT versus HD-_PRE or HD-_PER were found (P > 0.42). Comparing HD-CONT versus HD-_PER, WBV was preserved in HD-_PER and changes in RWMAs were associated with changes in WBV at high shear rates (225 s^-1: P = 0.006; 90 s^-1: P = 0.04).

Copyright © American Society of Nephrology. All rights reserved.

Source: Josse, M., Turc-Baron, C., Patrier, L., et al. (2025). Acute Exercise before Dialysis Is as Cardioprotective as during Dialysis: A Randomized Controlled Trial. Clinical Journal of the American Society of Nephrology. 2025; 20(9): 1236-1246. Published: September, 2025. DOI: 10.2215/CJN.0000000767.

A Retrospective Repeated Cross-Sectional Study

[Posted 3/Oct/2025]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Medicare beneficiaries aged 65 years and older with HIV in the USA were more likely to receive opioid prescriptions and have OUD indicators than matched beneficiaries without HIV. Findings could help guide clinical opioid prescription guidelines and public health surveillance among this vulnerable ageing population.

BACKGROUND: There is longstanding concern that people with HIV receive prescription opioids at higher rates and have a disproportionate burden of opioid use disorder (OUD) compared with their counterparts without HIV. We aimed to evaluate trends of opioid prescriptions and indicators of OUD in an understudied but growing population of older adults with HIV.

DETAILS: For this retrospective repeated cross-sectional study, authors constructed annual cohorts through a nationally representative sample of fee-for-service Medicare beneficiaries aged 65 years and older in the USA with Part D coverage (ie, prescription drug) enrolled between Jan 1, 2008, and Dec 31, 2021. Beneficiaries were eligible for inclusion in each cross-sectional cohort if they had reached the age of 65 years by Jan 1 of the calendar year and had 1 year of continuous Medicare enrolment in Part A (inpatient hospital care), B (outpatient care), and D. Beneficiaries with HIV were matched in a 1:3 ratio to beneficiaries without HIV on age, sex, race or ethnicity, US state, and dual eligibility status (Medicare and Medicaid). The main outcomes were receipt of at least one opioid prescription and any indicator of OUD (ie, formal diagnosis, medication for OUD, or opioid-related or emergency department visits) during each calendar year. Generalised estimating equations were used to estimate odds ratios (ORs) of each outcome, comparing matched beneficiaries with or without HIV. Due to data availability, our analysis of indicators of OUD was restricted to 2008-16. Across all years, 163,429 beneficiaries with HIV and 490,287 beneficiaries without HIV were included (475,516 [72.7%] were male, 178,200 [27.3%] were female; 305,776 [46.8%] were non-Hispanic White, 238,172 [36.4%] were Black [or African American], 84,128 [12.9%] were Hispanic, 8964 [1.4%] were Asian or Pacific Islander, and 16,676 [2.6%] were other races or ethnicities). During 2008-21, 57,373 (35.1%) of 163,429 people with HIV and 138,547 (28.3%) of 490,287 people without HIV received at least one opioid prescription. During 2008-16, 2408 (3.1%) of 76,637 people with HIV and 2831 (1.2%) of 229,911 people without HIV had any indicator of OUD. Across all analysed years, beneficiaries with HIV had significantly increased odds of receiving at least one opioid prescription (OR 1.38, 95% CI 1.36-1.39) and having indicators of OUD (2.61, 2.47-2.76) compared with their matched counterparts without HIV.

Copyright © The Author(s). Elsevier Ltd. All rights reserved.

Source: Shiau, S., Drago, F., Kinkade, C. W., et al. (2024). Prescription Opioid Use and Opioid Use Disorder Among Older Adults With HIV in the USA From 2008 to 2021: A Retrospective Repeated Cross-Sectional Study. The Lancet Primary Care. 2025; 1(3): 100017. Published: September, 2025. DOI: 10.1016/j.lanprc.2025.100017.

A Systematic Review and Individual Patient Data Meta-Analysis

[Posted 15/Sep/2025]

AUDIENCE: Infectious Disease, Pediatric

KEY FINDINGS: Regardless of malaria transmission intensity and age group, a single dose of 0.25 mg/kg primaquine is safe and efficacious for reducing P falciparum transmission. These findings underscore the need for primaquine formulations suitable for young children, and also provide supportive evidence to expand the use of single low-dose primaquine in regions with a moderate-to-high transmission rate that are threatened by artemisinin partial resistance.

BACKGROUND: Adding a single dose of primaquine to artemisinin-based combination therapy (ACT) for the treatment of falciparum malaria can reduce the transmission of Plasmodium falciparum and could limit the spread of artemisinin partial resistance, including in Africa, where the disease burden is greatest. Authors aimed to compare the safety and efficacy of single-dose primaquine plus ACT between young children (aged <5 years) and older children (aged 5 years to <15 years) and adults (aged >=15 years), and between low and moderate-to-high transmission areas.

DETAILS: For this systematic review and individual patient data meta-analysis, authors searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus, OpenGrey.eu, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform, from database inception to April 3, 2024, with no language restrictions. Authors included prospective studies on efficacy against falciparum malaria that enrolled at least one child younger than 15 years and involved a study group given a single dose of primaquine (<=0.75 mg/kg) plus ACT. Studies involving mass drug administration, healthy volunteers, or patients with severe malaria or mixed (with non-falciparum) infections were excluded. For inclusion in the efficacy analysis, data on transmission potential (as determined by gametocytaemia, infectivity, or both) at enrolment and follow-up (day 3, day 7, or day 14) were required; the safety analysis required data on haemoglobin concentrations or haematocrit values at enrolment and at one or more follow-up visits by day 7, any data on adverse events, or both. After independent screening of the search results by two reviewers, the investigators of eligible studies were invited to contribute individual patient data. Authors quantified day 7 gametocyte carriage, probability of infecting a mosquito, decreases (>25%) in haemoglobin concentration associated with anaemia, and adverse events until day 28 using regression analyses, with random study-site intercepts to account for clustered data. These analyses were registered with PROSPERO, CRD42021279363 (safety) and CRD42021279369 (efficacy). Of 5697 records identified by the search, 30 studies were eligible for analysis. Of these, individual patient data were shared for 23 studies, including 6056 patients from 16 countries: 1171 (19.3%) young children (aged <5 years), 2827 (46.7%) older children (aged 5 years to <15 years), and 2058 (34.0%) adults (aged >=15 years). Adding a single low dose of primaquine (0.2-0.25 mg/kg) to ACTs reduced day 7 gametocyte positivity (adjusted odds ratio [aOR] 0.34, 95% CI 0.22-0.52; p<0.001) and infectivity to mosquitoes over time (aOR per day 0.02, 0.01-0.07, p<0.001). No difference was found in the effect of single low-dose primaquine both on gametocyte positivity in young children compared with older children (1.08, 0.52-2.23; p=0.84) and adults (0.50, 0.20-1.25; p=0.14) and between low-transmission and moderate-to-high transmission settings (1.07, 0.46-2.52; p=0.86), and on infectivity to mosquitoes in young children compared with older children (1.36, 0.07-27.71; p=0.84) and adults (0.31, 0.01-8.84; p=0.50) and between low-transmission and moderate-to-high transmission settings (0.18, 0.01-2.95; p=0.23). Gametocyte clearance was also similar for different ACTs (dihydroartemisinin-piperaquine vs artemether-lumefantrine) when combined with a primaquine target dose of 0.25 mg/kg (1.56, 0.65-3.79; p=0.32 at day 7). However, patients given a primaquine dose of less than 0.2 mg/kg with dihydroartemisinin-piperaquine were more likely to have gametocytaemia than those treated with artemether-lumefantrine (5.68, 1.38-23.48; p=0.016 at day 7). There was no increase in anaemia-associated declines in haemoglobin concentration (>25%) at a primaquine dose of 0.25 mg/kg, regardless of age group, transmission setting, and glucose-6-phosphate dehydrogenase status. The risks of adverse events of grade 2 or higher and of serious adverse events were similar between primaquine and no-primaquine groups, including in young children.

Copyright © The Author(s). Published by Elsevier Ltd. All rights reserved.

Source: Yilma, D., Stepniewska, K., Bousema, T., et al. (2024). Safety and Efficacy of Single-Dose Primaquine to Interrupt Plasmodium Falciparum Malaria Transmission in Children Compared With Adults: A Systematic Review and Individual Patient Data Meta-Analysis. The Lancet Infectious Diseases. 2025; 25(9): 965-976. Published: September, 2025. DOI: 10.1016/S1473-3099(25)00078-7.

[Posted 13/Sep/2025]

AUDIENCE: Cardiology, Emergency Medicine

KEY FINDINGS: There was an association of lower operator radiation dose in the thorax, abdomen, left eye, and right eye for tall operators as compared to regular height operators. Authors recommend regular height operators be exceedingly vigilant with their personal radiation protection techniques. Furthermore, these same protection techniques should be considered with patients that have a higher likelihood of generating greater dose-area-products.

BACKGROUND: Radiation exposure is one of the most adverse occupational hazards faced by interventional cardiologists. Operator height can influence operator radiation exposure.

DETAILS: This single-center retrospective study (n = 534) assessed the cumulative radiation (CR) exposure in µSv and normalized radiation exposure (CR/DAP) using three different ranges of height (short, regular, and tall) of the primary operator at four anatomical locations when using a radial artery approach. A multivariate linear regression analyses for cumulative operator radiation dose found that tall operator height had significantly lesser values than regular operator height for the thorax (p <0.001), abdomen (p = 0.01), left eye (p <0.001), and right eye (p <0.001). Short operator height did not significantly differ from regular operator height. Multivariate linear regression analyses for normalized operator radiation dose found that tall operator height had significantly lesser values than regular operator height for the thorax (p <0.001), abdomen (p = 0.01), left eye (p <0.001), and right eye (p = 0.002). Short operator height did not significantly differ from regular operator height.

Copyright © Elsevier Inc. All rights reserved.

Source: Casazza, R., et al. (2024). The Influence of Height on Occupational Radiation Exposure of Interventional Cardiologists During Selective Coronary Angiography Using a Radial Artery Approach. Am J Cardiol.. 2025; 251: 1-8. Published: September 15, 2025. DOI: 10.1016/j.amjcard.2025.04.027 .

A Randomised, Open-Label, Multicentre, Phase 3 Trial

[Posted 28/Aug/2025]

AUDIENCE: Hematology, Oncology

KEY FINDINGS: With the limitation of a smaller sample size than planned due to the trial's early interruption, these results, to authors' knowledge, showed for the first-time high rates of MRD negativity with weekly carfilzomib added to lenalidomide-dexamethasone in patients with transplantation-ineligible newly diagnosed multiple myeloma. In the carfilzomib-lenalidomide-dexamethasone group, higher MRD negativity rates were associated with a progression-free survival advantage over lenalidomide-dexamethasone. Toxicities were predictable and generally manageable.

BACKGROUND: Before the introduction of daratumumab-lenalidomide-dexamethasone as a first-line treatment for patients with newly diagnosed transplant-ineligible multiple myeloma, lenalidomide-dexamethasone was a standard of care. Authors aimed to explore whether addition of the second-generation proteasome inhibitor carfilzomib to lenalidomide-dexamethasone improved the rates of measurable residual disease (MRD) negativity and progression-free survival.

DETAILS: EMN20 is a randomised, open-label, multicentre, phase 3 trial comparing weekly carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed transplant-ineligible multiple myeloma, conducted in 27 centres in Italy. Key inclusion criteria included fit or intermediate-fit status according to the International Myeloma Working Group (IMWG) frailty score, measurable disease according to IMWG criteria, and Eastern Cooperative Oncology Group performance status lower than 3. Patients randomly assigned to the carfilzomib-lenalidomide-dexamethasone group received 28-day carfilzomib-lenalidomide-dexamethasone cycles (carfilzomib 20 mg/m² intravenously on day 1 for cycle 1, followed by 56 mg/m² intravenously on days 8 and 15 for cycle 1, then 56 mg/m² intravenously on days 1, 8, and 15 for cycles 2-12, and 56 mg/m² intravenously on days 1 and 15 from cycle 13 until 5 years after randomisation; lenalidomide 25 mg orally on days 1-21 until disease progression or intolerance; dexamethasone 40 mg orally on days 1, 8, 15, and 22 until disease progression or intolerance). Patients assigned to the lenalidomide-dexamethasone group received 28-day cycles with lenalidomide-dexamethasone (same dosing and schedule used in the carfilzomib-lenalidomide-dexamethasone group). Primary endpoints were MRD negativity by next-generation sequencing (sensitivity 10-5) after 2 years of treatment and progression-free survival; and were assessed in the intention-to-treat (ITT) population (all patients who were eligible to receive treatment and who were randomly assigned to one of the treatment groups). On Nov 23, 2021, after enrolling 30% of planned patients (101/340), the trial was prematurely stopped due to the introduction of daratumumab-lenalidomide-dexamethasone as a first-line treatment in Italy, which caused the lenalidomide-dexamethasone control group to no longer be considered a standard treatment. This trial is registered with ClinicalTrials.gov, NCT04096066, and study recruitment is complete. Between Nov 14, 2019, and Nov 23, 2021, 82 of 101 enrolled patients were assessed for eligibility and were randomised to receive carfilzomib-lenalidomide-dexamethasone (n=42) or lenalidomide-dexamethasone (n=40). In the ITT population, 35 (43%) of 82 patients were female and 47 (57%) were male. At data cutoff (March 29, 2024), the median follow-up was 35.2 months (IQR 30.3-38.7). The 2-year MRD negativity rates were 25 (60% 95% CI 43-74) of 42 patients with carfilzomib-lenalidomide-dexamethasone versus 0 (0%; 0-9) of 40 patients with lenalidomide-dexamethasone (p<0.0001). Median progression-free survival was not reached (not reached-not reached) with carfilzomib-lenalidomide-dexamethasone versus 20.9 months (15.7-not reached) with lenalidomide-dexamethasone (hazard ratio 0.24 [95% CI 0.11-0.56], p=0.00084). One patient was excluded from the safety analysis because they died before starting treatment. The most frequent grade 3 or worse adverse events were neutropenia (nine [22%] of 41 patients), thrombocytopenia (four [10%]), diarrhoea (four [10%]), cardiac events (three [7%]), infections (three [7%]), and arterial hypertension (two [5%]) with carfilzomib-lenalidomide-dexamethasone, and neutropenia (six [15%] of 40) and skin rash (four [10%]) with lenalidomide-dexamethasone. The most common serious adverse event was SARS-CoV-2-related pneumonia in both the carfilzomib-lenalidomide-dexamethasone group (two [5%] of 41 patients) and lenalidomide-dexamethasone group (three [7%] of 40 patients). Treatment-emergent adverse events leading to death were observed in two patients in the carfilzomib-lenalidomide-dexamethasone (two SARS-CoV-2 infections) and four patients in the lenalidomide-dexamethasone group (one acute myocardial infraction, one heart failure, one septic shock, and one SARS-CoV-2 infection).

Copyright © Elsevier Ltd. All rights reserved.

Source: Bringhen, S., Cani, L., Antonioli, E., et al. (2024). Carfilzomib-Lenalidomide-Dexamethasone Versus Lenalidomide-Dexamethasone in Patients With Newly Diagnosed Myeloma Ineligible for Autologous Stem-Cell Transplantation (EMN20): A Randomised, Open-Label, Multicentre, Phase 3 Trial. The Lancet Haematology. 2025; 12(8): e621-e634. Published: August, 2025. DOI: 10.1016/S2352-3026(25)00162-0.