[Posted 30/Oct/2023]

AUDIENCE: Family Medicine

KEY FINDINGS: Severe erythrocytosis (hematocrit >54%) is a rare outcome of gender-affirming testosterone therapy. Clinical recommendations should reconsider the need for routine frequent erythrocytosis screening within the first year of testosterone therapy for patients who prefer to minimize laboratory draws.

BACKGROUND: Gender-affirming hormone therapy (GAHT) is safe overall, with few adverse effects. One potential effect from using testosterone for GAHT is an increase in hemoglobin and/or hematocrit, known as secondary erythrocytosis. Current guidelines recommend monitoring hemoglobin or hematocrit routinely in the first year, some as frequently as every 3 months, which can create barriers to care. The study explored the incidence of erythrocytosis in the first 20 months of testosterone therapy among people receiving gender-affirming care.

DETAILS: This is a descriptive fixed cohort study of hematocrit and hemoglobin data from the charts of 282 people taking testosterone for GAHT. During the first 20 months of testosterone therapy, the cumulative incidence of hematocrit >50.4% was 12.6%, hematocrit >52% was 1.0%, and hematocrit >54% was 0.6%. All people were taking injectable testosterone cypionate, with a median dose of 100 mg weekly.

Copyright © Annals of Family Medicine, Inc. All rights reserved.

Source: Porat, A. T., Ellwood, M., Rodina, M., et al. (2023). Erythrocytosis in Gender-Affirming Care With Testosterone. Ann Fam Med. 2023; 21(5): 403-407. Published: September/October, 2023. DOI: 10.1370/afm.3018.

A Post Hoc Analysis of the WISDM Study.

[Posted 28/Jan/2026]

AUDIENCE: Endocrinology, Nephrology

KEY FINDINGS: In older adults with type 1 diabetes, CGM improves hypoglycemia; however, its role in improving IAH is variable, depending on the scoring method. This study highlights the limitations of the Clarke score.

BACKGROUND: Although continuous glucose monitoring (CGM) reduces hypoglycemia and may improve impaired awareness of hypoglycemia (IAH), its effectiveness in older adults at high risk remains unknown.

DETAILS: This post hoc analysis of the WISDM study focuses on CGM use over 52 weeks. IAH was assessed using the Clarke original score (Clarke-full) and its subscales, Hypoglycemia Awareness Factor (HAF) and Severe Hypoglycemia Experienced Factors (SHEF), at baseline, 26 weeks, and 52 weeks. After 26 weeks (n = 184) and 52 weeks (n = 94) of CGM use, Clarke-SHEF decreased significantly (P = 0.02 and P < 0.0001, respectively), whereas Clarke-full and Clarke-HAF remained unchanged. After 52 weeks, Clarke-full but not Clarke-HAF improved in the IAH subgroup, highlighting the importance of selecting the appropriate scoring method for IAH.

Copyright © American Diabetes Association. All rights reserved.

Source: Bilal, A., Yi, F., Whitaker, K., et al. Effects of Continuous Glucose Monitoring on Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study. Diabetes Care . 2026; 49(1): 86-91. Published: January, 2026. DOI: 10.2337/dc25-0971.

[Posted 27/Jan/2026]

AUDIENCE: Dermatology, Endocrinology

KEY FINDINGS: This research provides the first comprehensive, high-resolution molecular atlas of the human facial sebaceous gland. By decoding the dynamic process of sebocyte differentiation and identifying site-specific gene markers, the study offers a critical reference for future investigations into the pathophysiology of acne and other sebaceous-related disorders, potentially identifying new therapeutic targets.

BACKGROUND: The sebaceous gland (SG) is a critical component of the pilosebaceous unit (PSU), responsible for producing sebum that maintains skin homeostasis through lubrication and barrier protection. Pathological dysregulation of SG activity is central to several common dermatological conditions, including acne vulgaris, seborrheic dermatitis, and various forms of alopecia. Historically, our understanding of human SG molecular biology has been limited by a heavy reliance on murine models, which do not fully mirror human physiology, and the technical difficulty of analyzing mature sebocytes, which often rupture during standard single-cell processing.

DETAILS: This study utilized a multi-omic approach to dissect the human SG at cellular resolution:

• Study Population: Facial skin samples were obtained from $n=3$ healthy female White donors between the ages of 49 and 57 years.
• Technological Integration: The researchers integrated Stereo-seq (spatial transcriptomics) with single-cell RNA sequencing (scRNA-seq) and validated findings using multiplexed error-robust FISH (MERFISH).
• Resolution: Stereo-seq provided high-resolution mapping with a bin size of 50, corresponding to approximately 25 µm cell diameter, allowing for the capture of transcriptomic profiles while preserving spatial orientation.
• Cellular Mapping: A total of 9,374 cells were analyzed, identifying various clusters including basal sebocytes, differentiating sebocytes, and "bursted" sebocytes representing holocrine secretion remnants.

The study yielded several significant molecular insights into the human SG:

• Differentiation Stages: Researchers identified four distinct stages of sebocyte differentiation, each characterized by a unique transcriptomic signature.
• Novel Genetic Markers: New markers for basal sebocytes were identified, including NNAT, IL-1R2, TINAGL1, and WFDC2. Additionally, S100A7, S100A8, S100A9, TYMP, and SERPINB4 were pinpointed as more effective markers for infundibular keratinocytes than traditional markers like K79.
• Signaling Pathways: Cyclophilin A (CyPA) was identified as a dominant autocrine signaling pathway within the SG. A previously unreported immune interaction was discovered where CD6, secreted by immune cells, is received by basal sebocytes via the ALCAM receptor.
• Spatial Dynamics: Unlike the anticipated radial pattern, differentiation was observed to progress apically from the gland's edge toward the sebaceous duct.

Copyright © Skyscape Editorial Team. All rights reserved.

Source: Düz, T., Torocsik, D., Simmering, A., et al. et al. High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation. J Invest Dermatol.. 2026; 146(1): 40-54. Published: January, 2026. DOI: 10.1016/j.jid.2025.04.041.

A Systematic Review and Meta-Analysis.

[Posted 23/Jan/2026]

AUDIENCE: Psychiatry, Family Medicine

KEY FINDINGS: Results of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.

BACKGROUND: Aim of this study is to estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders.

DETAILS: Study screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021. Among 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22,048,504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders.

Copyright © American Medical Association. All Rights Reserved.

Source: Gupta, A., Tejpal, T., Seo, C., et al. Mental Disorders as a Risk Factor of Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. JAMA Psychiatry.. Published: January 14, 2065. DOI: 10.1001/jamapsychiatry.2025.4253.

A randomised, open-label, phase 4 clinical trial

[Posted 22/Jan/2026]]

AUDIENCE: Infectious Disease, Family Medicine

KEY FINDINGS: Artemether-lumefantrine was associated with a higher risk of recurrent malaria than other antimalarial combinations tested, and K13 mutations were associated with delayed parasite clearance. Changes in first-line therapy for uncomplicated malaria must be considered in response to suboptimal efficacy of artemether-lumefantrine.

BACKGROUND: Anti-malarial artemisinin-based combination therapies (ACTs) might be losing efficacy in east Africa, with the spread of artemisinin partial resistance and reduced partner drug activity. Our trial aimed to measure the efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine in three sites in Uganda.

DETAILS: This randomised, open-label, phase 4 clinical trial was carried out at three sites in the Agago, Arua, and Busia districts of Uganda. Children aged 6 months to 10 years with uncomplicated Plasmodium falciparum malaria were randomly assigned to receive either artemether-lumefantrine (20 mg artemether; 120 mg lumefantrine; twice a day for 3 days) in all sites or dihydroartemisinin-piperaquine (40 mg dihydroartemisinin and 320 mg piperaquine, once a day for 3 days) in Agago, artesunate-amodiaquine (25 mg artesunate and 67.5 mg amodiaquine for children <9 kg or 50 mg artesunate and 135 mg amodiaquine for children >=9 kg, once a day for 3 days) in Busia; and artesunate-pyronaridine (60 mg artesunate and 180 mg pyronaridine for children >15 kg or 20 mg artesunate and 60 mg pyronaridine for children <15 kg, once a day for 3 days) in Arua, with follow-up to 42 days. Participants were not blinded to group assignments; however, investigators and those assessing outcome were masked. The primary outcome was parasitaemia, assessed by microscopy, either uncorrected or PCR-corrected to distinguish recrudescence from new infection. All participants who received the treatment per protocol and were not lost to follow-up were included in the primary outcome. All participants who were randomly allocated to treatment groups were included in the safety analyses. This study is registered with the Pan African Clinical Trials Registry, number PACTR202301796134887, and is complete. Between Nov 7, 2022, and March 24, 2023, 808 participants (437 [54%] female) were enrolled and assigned to treatment groups; 15 (2%) were lost to follow-up and 793 (98%) completed follow-up. The uncorrected adequate clinical and parasitological response for artemether-lumefantrine was 87 (51.8%; 95% CI 44.0-59.5) of 168 participants in Arua, 88 (51.8%; 44.0-59.4) of 170 and Busia, and 131 (79.4%; 72.3-85.1) of 165 in Agago. This response for artemether-lumefantrine was lower than that of the other ACTs at all sites: 97 (98.0%; 92.2-99.6) of 99 for dihydroartemisinin-piperaquine in Agago, 95 (99.0%; 93.5-99.9) of 96 for artesunate-amodiaquine in Busia, and 73 (73.7%; 63.8-81.8) of 99 for artesunate-pyronaridine in Arua. PCR-corrected 28-day efficacies were 88 (81.5%; 72.6-88.1) of 108 for artemether-lumefantrine and 95 (100%; 95.2-100.0) of 95 for artesunate-amodiaquine in Busia; 131 (97.0%; 92.1-99.0) of 135 for artemether-lumefantrine and 97 (100%; 95.3-100.0) of 97 for dihydroartemisinin-piperaquine in Agago; and 87 (82.1%; 73.2-88.6) of 106 for artemether-lumefantrine and 73 (92.4%; 83.6-96.9) of 79 for artesunate-pyronaridine in Arua. All regimens were well tolerated. The most common adverse events were upper respiratory tract infection, diarrhoea, and anaemia. None of the reported adverse events were attributed to the study drugs. There were two serious adverse events, both cases of severe malaria in Arua, one in each of the treatment groups. Parasite clearance half-lives were prolonged with parasites carrying the PfK13 Cys469Tyr (median 4.2 h; IQR 3.4-4.9) and Ala675Val (4.9 h; 3.4-5.7) mutations compared with wild-type parasites (2.8 h; 2.3-3.6; p<0.0001).

Copyright © Elsevier Ltd. All rights reserved.

Source: Kamya, M. R., Nankabirwa, J. I., Ebong, C., et al. Efficacies of artemether-lumefantrine, artesunate-amodiaquine, dihydroartemisinin-piperaquine, and artesunate-pyronaridine for the treatment of uncomplicated Plasmodium falciparum malaria in children aged 6 months to 10 years in Uganda: a randomised, open-label, phase 4 clinical trial. The Lancet Infectious Diseases. 2026; 26(1): 67-68. Published: January, 2026. DOI: 10.1016/S1473-3099(25)00407-4.

[Posted 21/Jan/2026]

AUDIENCE: Neurology, Cardiology, Internal Medicine

KEY FINDINGS: Among patients with high-grade stenosis without recent symptoms, the addition of stenting led to a lower risk of a composite of perioperative stroke or death or ipsilateral stroke within 4 years than intensive medical management alone. Carotid endarterectomy did not lead to a significant benefit.

BACKGROUND: Improvements in medical therapy, carotid-artery stenting, and carotid endarterectomy call into question the preferred management of asymptomatic carotid stenosis. Whether adding revascularization to intensive medical management would provide greater benefit than intensive medical management alone is unclear.

DETAILS: Authors conducted two parallel, observer-blinded clinical trials that enrolled patients with high-grade (>=70%) asymptomatic carotid stenosis across 155 centers in five countries. The stenting trial compared intensive medical management alone (medical-therapy group) with carotid-artery stenting plus intensive medical management (stenting group); the endarterectomy trial compared intensive medical management alone (medical-therapy group) with carotid endarterectomy plus intensive medical management (endarterectomy group). The primary outcome was a composite of any stroke or death, assessed from randomization to 44 days, or ipsilateral ischemic stroke, assessed during the remaining follow-up period up to 4 years. A total of 1245 patients underwent randomization in the stenting trial and 1240 in the endarterectomy trial. In the stenting trial, the 4-year incidence of primary-outcome events was 6.0% (95% confidence interval [CI], 3.8 to 8.3) in the medical-therapy group and 2.8% (95% CI, 1.5 to 4.3) in the stenting group (P=0.02 for the absolute difference). In the endarterectomy trial, the 4-year incidence of primary-outcome events was 5.3% (95% CI, 3.3 to 7.4) in the medical-therapy group and 3.7% (95% CI, 2.1 to 5.5) in the endarterectomy group (P=0.24 for the absolute difference). From day 0 to 44, in the stenting trial, no strokes or deaths occurred in the medical-therapy group and seven strokes and one death occurred in the stenting group; in the endarterectomy trial, three strokes occurred in the medical-therapy group and nine strokes occurred in the endarterectomy group.

Copyright © Massachusetts Medical Society. All rights reserved.

Source: Brott, T. G., Howard, G., Lal, B. K., et al. Medical Management and Revascularization for Asymptomatic Carotid Stenosis. NEJM. 2025; 394(3): 219-231. Published: November, 2025. DOI: 10.1056/NEJMoa250880.