[Posted 8/Nov/2022]

AUDIENCE: Family Medicine, Infectious Disease

KEY FINDINGS: Sinus tachycardia followed by atrial fibrillation and right bundle branch block are common ECG changes in patients with COVID-19 infection with raised IL-6. The possible association of cardiac injury in patients with COVID-19 infection with coexisting raised IL-6 levels should be explored further.

BACKGROUND: Cardiac injury is associated with high mortality in patients with COVID-19 infection. Electrocardiographic changes can give clues to the underlying cardiovascular abnormalities. Raised inflammatory markers like raised interleukin-6 (IL-6) are associated with arrhythmia, heart failure, and coronary artery disease. However, past studies have not highlighted the electrocardiographic abnormalities in patients with COVID-19 infection with raised IL- 6 levels. This study compared the electrocardiogram (ECG) changes in COVID-19 patients with high and normal IL-6 levels.

DETAILS: A retrospective analysis of ECG of 306 patients with COVID-19 infection was done, out of which 250 patients had normal IL- 6 levels, whereas 56 patients had raised IL-6 levels. IL-6 levels were measured in all the patients. Detailed clinicodemographic profile of all the serial COVID-19 patients admitted with moderate to severe COVID-19 pneumonia was noted from the hospital record section. Electrocardiographic findings and biochemical parameters of all the patients were noted. Out of 56 patients with raised IL-6 levels, 41 (73.2%) patients had ECG abnormalities compared to 177 (70.8%) patients with normal IL-6 levels. This difference was not statistically significant. However, ECG abnormality such as sinus tachycardia was significantly more common in patients with raised IL-6 levels than those with normal levels. Among patients with raised IL-6 levels who were discharged, 5 (16.6%) had sinus tachycardia, 2 (6.6%) had ST/T wave changes as compared to 15 (57.6%), and 10 (38.4%) who had tachycardia and ST/T wave change respectably succumbed to death. This difference was statistically significant.

Copyright © Journal of Family Medicine and Primary Care. All rights reserved.

Source: Kaeley, N., Mahala, P., Walia, R., et al. (2022). Electrocardiographic Abnormalities In Patients With Covid-19 Pneumonia And Raised Interleukin-6. J Family Med Prim Care. 2022; 11(10): 5902-5908. Published: October, 2022. DOI: 10.4103/jfmpc.jfmpc_135_22.

A Quantitative Susceptibility Mapping MRI and PET Study

[Posted 12/Sep/2025]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: The findings suggest that lower levels of non-neuromelanin-bound iron in the SN-VTA contribute to striatal hyperdopaminergia in schizophrenia. Further investigation is warranted to understand the role of low iron in schizophrenia and its potential as a treatment target.

BACKGROUND: Neuroimaging studies have independently associated schizophrenia with low iron and elevated dopamine synthesis. While preclinical research demonstrates that midbrain iron deficiency leads to striatal hyperdopaminergia, this relationship has not been studied in schizophrenia. The authors conducted a case-control study to examine differences in tissue magnetic susceptibility, a marker of brain iron, and correlated these with striatal dopamine synthesis capacity.

DETAILS: Magnetic susceptibility in the substantia nigra and ventral tegmental area (SN-VTA) was measured using quantitative susceptibility mapping (QSM) MRI in 159 participants (control subjects, N=80; early-course schizophrenia, N=79, including patients who were antipsychotic-naïve or antipsychotic-free). Because magnetic susceptibility is increased by neuromelanin and reduced by myelin, neuromelanin-sensitive MRI (NM-MRI) and diffusion tensor imaging (DTI) were employed to investigate the influence of neuromelanin and myelin on the QSM findings in 99 participants (control subjects, N=38; schizophrenia patients, N=61). Dopamine synthesis capacity (K_i ^cer) was then assessed with [¹⁸F]-DOPA positron emission tomography in 40 people from the schizophrenia group to test whether low SN-VTA magnetic susceptibility was related to high striatal K_i ^cer. SN-VTA magnetic susceptibility was lower in patients with schizophrenia than in control subjects (d=-0.66, 95% CI=-0.98, -0.34). This difference remained significant in analyses controlling for mean diffusivity (a DTI measure inversely correlating with myelin concentration) and NM-MRI contrast-to-noise ratios. SN-VTA magnetic susceptibility was significantly inversely correlated with striatal K_i ^cer, independent of mean diffusivity and NM-MRI contrast-to-noise ratios (r=-0.44). In both analyses, the strongest effects were observed in the ventral SN-VTA.

Copyright © American Psychiatric Association. All rights reserved.

Source: Vano, L. J., McCutcheon, R. A., Sedlacik, J., et al. (2024). Reduced Brain Iron and Striatal Hyperdopaminergia in Schizophrenia: A Quantitative Susceptibility Mapping MRI and PET Study. American Journal of Psychiatry. 2025; 182(9): 830–839. Published: September, 2025. DOI: 10.1176/appi.ajp.20240512.

[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.

Results From the BE BRIGHT Open-Label Extension Trial

[Posted 10/Sep/2025]

AUDIENCE: Dermatology, Family Medicine

KEY FINDINGS: Almost two-thirds of bimekizumab-treated patients achieved and maintained complete skin clearance through 4 years, making bimekizumab an effective, rapid, and durable long-term treatment option.

BACKGROUND: Patients with moderate to severe psoriasis experience significant burden on quality of life. Long-term management with latest-generation biologics can facilitate sustained complete skin clearance and improved patient well-being. Aim of this study is to report 4-year end-of-study bimekizumab efficacy and safety in patients with moderate to severe psoriasis.

DETAILS: Data were pooled from 3 phase 3 trials (BE VIVID, BE READY, and BE SURE) and their open-label extension (OLE; BE BRIGHT). Efficacy is reported for patients who received bimekizumab continuously from baseline into the OLE. Safety is reported for patients who received >=1 bimekizumab dose. Seven hundred seventy-one patients received bimekizumab from baseline into the OLE. A high proportion achieved complete skin clearance (100% improvement from baseline in Psoriasis Area and Severity Index) at Week 52 (76.2%) and maintained this to Week 196 (64.7%). The rate of treatment-emergent adverse events over 4 years was 169.8/100 patient-years (N = 1495) and did not increase with longer exposure. The most common treatment-emergent adverse events were nasopharyngitis, oral candidiasis, and upper respiratory tract infection, consistent with bimekizumab's known safety profile.

Copyright © Elsevier Ltd. All rights reserved.

Source: Blauvelt, A., Langley, R. G., Lebwohl, M., et al. (2024). Bimekizumab Durability of Efficacy Through 196 Weeks and Safety Through 4 Years in Patients With Moderate to Severe Plaque Psoriasis: Results From the BE BRIGHT Open-Label Extension Trial. Journal of the American Academy of Dermatology. 2025; 93: 644-653. Published: September, 2025. DOI: 10.1016/j.jaad.2025.04.038.

[Posted 9/Sep/2025]

AUDIENCE: Hospice & Palliative Nursing, Emergency Nursing

KEY FINDINGS: Despite the challenging environment of the emergency department, nurses who recognize their important role in the process of life-sustaining treatment withdrawal are more likely to provide high-quality EOL care. The perception of nurses' roles is especially influential on psychological care performance, and alternative approaches may be necessary for spiritual care.

BACKGROUND: This study aimed to identify predictors of end-of-life (EOL) care provided by emergency nurses in South Korea.

DETAILS: A cross-sectional survey was conducted using a structured questionnaire. Data were collected using Google Forms between June 21 and 30, 2022. A total of 154 emergency nurses from 10 tertiary hospitals in a metropolitan area were recruited using convenience sampling, and 139 completed surveys were analyzed. Multiple linear regression was employed to examine the effects of nurses' knowledge of life-sustaining treatment withdrawal (knowledge), their perceptions of their role in the withdrawal process (role perception), and job stress on EOL care. The mean scores for knowledge, role perception, job stress, and EOL care were 13.09±1.75 (max 6), 4.18±0.44 (max 5), 3.55±0.32 (max 4), and 2.48±0.40 (max 4), respectively. Among the EOL care subdomains, psychological domain scores were the highest. Multiple linear regression analysis indicated that nurses' role perception significantly predicted EOL care performance, particularly in the psychological (F=3.924, P=0.001) and spiritual (F=2.171, P=0.020) domains.

Copyright © Journal of Hospice and Palliative Care. All rights reserved.

Source: Park, H. J., Hong, E. A., Min, S. H., et al. (2024). Effects of Emergency Nurses' Life-Sustaining Treatment Withdrawal Knowledge, Role Perception, and Job Stress on Providing End-of-Life Care. J Hosp Palliat Care. 2025; 28(3): 89-98. Published: September 1, 2025. DOI: 10.14475/jhpc.2025.28.3.89.

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.