An Inverse Marker of Morbidity and Mortality in Patients With Myocardial Infarction

[Posted 27/Oct/2023]

AUDIENCE: Internal Medicine, Cardiology

KEY FINDINGS: Patients with the highest LDL-C levels at MI had the lowest incidence of mortality and morbidity. This seems to reflect lower age at MI, less underlying morbidities, paired with the modifiability of LDL-C. However, supporting the causal association between LDL-C and ischemic heart disease, elevated LDL-C was simultaneously associated with an increased risk of nonfatal MI.

BACKGROUND: The incidence of atherosclerotic cardiovascular disease increases with levels of low-density lipoprotein cholesterol (LDL-C). Yet, a paradox may exist where lower LDL-C levels at myocardial infarction (MI) are associated with poorer prognoses. Aim of this study is to assess the association between LDL-C levels at MI with risk factor burden and cause-specific outcomes.

DETAILS: Statin-naive patients hospitalized for a first MI and registered in SWEDEHEART were included. Data were linked to Swedish registers. Primary outcomes were all-cause mortality and nonfatal MI. Associations between LDL-C and outcomes were assessed using adjusted proportional hazards models. Among 63,168 patients (median age, 66 years), the median LDL-C level was 3.0 mmol/L (interquartile range 2.4-3.6). Patient age and comorbidities increased as LDL-C decreased. During a median follow-up of 4.5 years, 10,236 patients died, and 4973 had nonfatal MI. Patients with the highest LDL-C had a lower risk of mortality (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.80). The risk of hospitalization for pneumonia, hip fracture, chronic obstructive pulmonary disease, and new cancer diagnosis was lower with higher LDL-C (HR range, 0.40-0.81). Patients with the highest LDL-C had a greater risk of recurrent MI (HR 1.16; 95% CI 1.07-1.26).

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Schubert, J., Lindahl, B., Melhus, H., et al. (2023). Elevated Low-Density Lipoprotein Cholesterol: An Inverse Marker of Morbidity and Mortality in Patients With Myocardial Infarction. JIM. 2023; 294(5): 616-627. Published: November, 2023. DOI: 10.1111/joim.13656.

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 .

[Posted 11/Sep/2025]

AUDIENCE: Geriatric, Family Medicine

KEY FINDINGS: Plasma %p-tau217 was associated with progression from CU to MCI in both cohorts, although differences in biomarker associations may be related to differences in the two cohorts.

BACKGROUND: Plasma biomarkers' utility for predicting incident mild cognitive impairment (MCI) remains unclear. Authors evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies.

DETAILS: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models. The study included 381 MCSA and 584 BioFINDER-2 participants. Amyloid PET and percent phosphorylated to non-phosphorylated tau217 (%p-tau217) were strong predictors of progression to MCI in both cohorts: hazard ratios of 1.49 and 1.23 in the MCSA and 1.72 and 1.65 in BioFINDER, respectively. Amyloid beta 42/40 was a significant predictor in BioFINDER-2 only (hazard ratio 2.20).

Copyright © John Wiley & Sons, Inc. All rights reserved

Source: Cogswell, P. M., Wiste, H. J., Therneau, T. M., et al. (2024). Association of Plasma Alzheimer's Disease Biomarkers With Cognitive Decline in Cognitively Unimpaired Individuals. Alzheimers Dement.. 2025; Published: September, 2025. DOI: 10.1002/alz.70625.

[Posted 8/Sep/2025]

AUDIENCE: Ophthalmology, Internal Medicine

KEY FINDINGS: Larger optic disc size is associated with faster cpRNFL thinning in glaucoma, independent of race. Although previous studies have indicated that Black individuals may be at higher risk for glaucoma development, the present study suggests that race may not be a significant predictor of faster cpRNFL thinning when controlling for optic disc size and other clinical and demographic factors in glaucoma.

BACKGROUND: Aim of this study is to investigate the association between optic disc size and circumpapillary retinal nerve fiber layer (cpRNFL) thinning in eyes with preperimetric glaucoma and glaucoma.

DETAILS: A total of 841 eyes (554 primary open angle glaucoma and 287 preperimetric glaucoma) from 553 patients who had at least 4 visits and 2 years of follow-up using OCT participated in the study. Multivariable linear mixed-effects modeling was used to estimate the effect of optic disc size on cpRNFL thinning while controlling for covariates. To eliminate the floor effect, eyes with baseline visual field mean deviation less than -14 dB were excluded. Of the participants, 189 (34.2%) were Black, 338 (61.1%) were White, 20 (3.6%) were Asian, and 6 (1.1%) were another race or ethnicity. Mean follow-up period was 5.3 (95% confidence interval [CI], 5.2-5.5) years, and the mean rate of cpRNFL change was -0.54 (95% CI, -0.61 to 0.47) µm/year. After adjusting for covariates with the Littmann's formula correction, larger optic disc size was associated with faster cpRNFL thinning (-0.03; 95% CI, -0.05 to 0.00) µm/year faster per 0.1 mm² larger; P = 0.034), while no significant differences were found for race and its interaction with optic disc size.

Copyright © The American Academy of Ophthalmology. All rights reserved.

Source: Nishida, T., Vincent Q., Moghimi, S., et al. (2024). Optic Disc Size and Circumpapillary Retinal Nerve Fiber Layer Thinning in Glaucoma. Ophthalmology Glaucoma. 2025; 8(4): 343-350. Published: July-August, 2025. DOI: 10.1016/j.ogla.2025.02.003.

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.