Erythrocytosis in Gender-Affirming Care With Testosterone
Severe erythrocytosis (hematocrit above 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.
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.
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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.
What Is the Diagnostic Capacity of Existing Severity Scoring Tools for Nail Psoriasis?
Both N-NAIL and NAPSI provide accurate cutoff values in a psoriasis population. Therefore, these scoring tools may not only be used to assess severity but also in clinical trials for the inclusion of NP patients in a psoriasis population to create homogeneity between studies.
KEY FINDINGS: Both N-NAIL and NAPSI provide accurate cutoff values in a psoriasis population. Therefore, these scoring tools may not only be used to assess severity but also in clinical trials for the inclusion of NP patients in a psoriasis population to create homogeneity between studies. Authors prefer using the N-NAIL, with a cutoff value of 2, because it showed better accuracy compared to the NAPSI.
BACKGROUND: It is challenging to distinguish nail psoriasis (NP) from nonspecific nail changes, contributing to heterogeneity in clinical trials. Existing scoring tools for NP are currently used to assess severity after diagnosis is established. The aim of this study is to evaluate the diagnostic performance of two of these severity scoring tools.
DETAILS: A cohort study was conducted with psoriasis patients and matched controls. Fingernails were scored using the Nail Psoriasis Severity Index (NAPSI) and the Nijmegen-Nail Psoriasis Activity Index Tool (N-NAIL). To determine their diagnostic properties, cutoff values were established. Receiver operating characteristic (ROC) curves were constructed, and sensitivity and specificity were calculated for various cutoff points. The best cutoff value was chosen based on the Youden Index and clinical reasoning. In total, 104 psoriasis patients were included, of which 68 were clinically diagnosed with NP. For the N-NAIL, a cutoff value of 2 showed the best accuracy in the psoriasis population (sensitivity = 83.8% and specificity = 83.3%) and the general population (sensitivity = 83.8% and specificity = 67.3%). For the NAPSI, a cutoff value of 7 showed the best accuracy in the psoriasis population (sensitivity = 80.9% and specificity = 69.4%), while a cutoff value of 10 was optimal in the general population (sensitivity = 72.1% and specificity = 70.2%).
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Copyright © John Wiley & Sons Ltd. All rights reserved.
Source: Rikken, E. C. C., van Hal, T. W., van den Reek, J. M. P. A., et al. What Is the Diagnostic Capacity of Existing Severity Scoring Tools for Nail Psoriasis? International Journal of Dermatology. 2026; 65(1): 86-92. Published: January, 2026. DOI: 10.1111/ijd.70024.
Re-envisioning the Lifespan Approach to Cardiovascular Disease Prevention and Treatment in Women
The anticipated life course of women supports a broadening focus on CVD toward that of lifelong care and emphasize key transitional stages for women - early risk factor onset, pregnancy, menopausal transition, and so on. This review is a call to action to re-envision a health system approach for lifespan prevention, detection, and treatment pathways to reduce CVD risk in women.
KEY FINDINGS:
- Mortality: CVD deaths in women exceed combined deaths from breast and lung diseases.
- Gap in Care: Insufficient sex-specific evidence continues to hinder lifesaving care.
- Call to Action: Transition from episodic care to a lifelong cardiovascular health system for women.
BACKGROUND: Despite the common misconception that respiratory or oncological diseases pose the greatest threat to women, Cardiovascular Disease (CVD) accounts for more female deaths than breast cancer, lung cancer, and chronic lung disease combined, with a comparable mortality to that of men. Historically, both the public and the medical community have underestimated CVD risks in women, leading to diagnostic delays and a scarcity of sex-specific evidence to guide clinical interventions. While advances have been made in the diagnosis, treatment and outcomes of CVD in women, there often remains insufficient evidence to guide effective, lifesaving care of women.
DETAILS: This review of sex-specific and traditional CVD risk and risk-enhancing factors in women identifies areas of knowledge gaps to consider for investigation. A focus on the coronary vasculature reveals physiological differences of clinical relevance which can be interrogated. Inspection of and addressing disadvantage and gender bias in both the medical and lay communities should continue to be addressed. As CVD results from traditional risk factors and emerging risk-enhancing factors, a focus on the detection of preclinical cardiovascular disease may be of particular importance for women. Unique risk markers originate early in pre-menopausal women, as this is considered a healthy period of life. Awareness and implementation of the existing knowledge of sex-specific risk factors and sex-specific thresholds to educate women and physicians are needed. The anticipated life course of women supports a broadening focus on CVD toward that of lifelong care and emphasize key transitional stages for women-early risk factor onset, pregnancy, menopausal transition, and so on. This review is a call to action to re-envision a health system approach for lifespan prevention, detection, and treatment pathways to reduce CVD risk in women.
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Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis
The findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron-mediated hepcidin regulation in the absence of BMP2 and BMP6.
KEY FINDINGS: Together with other published data, these findings suggest a model whereby BMP2 and BMP6 can signal to hepcidin induction independently of HJV and HFE and vice versa. In contrast, BMP5, HJV, and HFE are all required for iron-mediated hepcidin regulation in the absence of BMP2 and BMP6.
BACKGROUND: The bone morphogenetic protein (BMP)-SMAD signaling pathway is central to regulating hepcidin, the master regulator of systemic iron homeostasis. Authors have previously demonstrated that BMP6, BMP2, and, to a lesser extent, BMP5 are the major ligands contributing to hepcidin and iron homeostasis regulation in vivo.
DETAILS: Hemojuvelin (HJV) and homeostatic iron regulator (HFE) are hepcidin modulators that are mutated in hereditary hemochromatosis. Although both HJV and HFE regulate hepcidin, at least partly, by functionally interacting with the BMP–SMAD pathway, the mechanisms are incompletely understood. Notably, both HJV and HFE can regulate hepcidin in a BMP6-independent manner. To understand whether HJV and HFE influence hepcidin regulation by BMP2 and/or BMP5, authors investigated the iron phenotype of mice with combined mutations in endothelial Bmp2/Hjv and Bmp5/Hfe. Authors found that endothelial Bmp2/Hjv double knockout (KO) mice exhibit more severe hepcidin deficiency and iron overload than single endothelial Bmp2 or Hjv KO mice, similar to previous findings in mice with double endothelial Bmp2/Hfe KO and Bmp6/Hjv KO, or a functional loss of both Bmp6 and Hfe. Moreover, authors found that iron completely fails to induce hepcidin in both endothelial Bmp2/Hjv and Bmp2/Hfe double KO mice. In contrast, a functional loss of BMP5 does not worsen hemochromatosis in Hfe KO mice.
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Source: Xiao, X., Moschetta, G. A., Chowdhury, S. B., et al. Hemochromatosis Proteins Hemojuvelin and Homeostatic Iron Regulator in Bone Morphogenetic Protein-Mediated Hepcidin Regulation and Iron Homeostasis. American Journal of Hematology. 2025; 100(12): 2175-2184. Published: December, 2025. DOI: 10.1002/ajh.70055.
Efficacy and Safety of Time-Restricted Eating in Metabolic Dysfunction-Associated Steatotic Liver Disease
This 16-week RCT compared TRE, CR, and standard of care in patients with MASLD. It effectively reduced steatosis, with similar benefits on weight loss, body composition, and metabolic parameters as CR. TRE is a practical dietary strategy for MASLD and warrants further long-term study. TRE's effectiveness in MASLD remains unclear despite its potential metabolic benefits.
KEY FINDINGS: TRE effectively reduces hepatic steatosis in MASLD, with comparable benefits on weight loss, body composition, and metabolic parameters as CR. This approach may serve as a practical dietary strategy for MASLD management.
BACKGROUND: Time-restricted eating (TRE) may improve weight loss, insulin resistance, and body composition, which are key factors in the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, evidence on the efficacy of TRE in patients with MASLD is limited. This study aimed to evaluate the potential benefits of TRE in patients with overweight or obesity and MASLD.
DETAILS: In this 16-week randomized controlled trial, patients with overweight or obesity and MASLD were randomized into three groups in a 1:1:1 ratio: standard of care (SOC), calorie restriction (CR), and TRE. The primary endpoint was an improvement in hepatic steatosis, measured using MRI-proton density fat fraction. Changes in liver fibrosis, body composition, lipid profiles, glucose homeostasis, and sleep quality were also analyzed. Among the 337 participants randomized, 333 were included in the full analysis set (113 in SOC, 110 in CR, and 110 in TRE). After the 16-week intervention, hepatic steatosis significantly decreased in the TRE group (-25.8%) compared to the SOC group (0.7%, p <0.001), with no significant difference between TRE and CR (-24.7%, p >0.999). The TRE group also showed greater reductions in body weight, waist circumference, and body fat mass compared to the SOC group, while changes were comparable between TRE and CR. Liver stiffness, glucose homeostasis, and sleep quality were similar between the TRE and CR groups. No serious adverse events were reported.
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Copyright © Elsevier Inc. All rights reserved.
Source: Oh, J. H., Yoon, E. L., Park, H., et al. Efficacy and Safety of Time-Restricted Eating in Metabolic Dysfunction-Associated Steatotic Liver Disease. Journal of Hepatology. 2025; 83(6): 1256-1265. Published: December, 2025. DOI: 10.1016/j.jhep.2025.06.005.
Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria
Within the studied participants, there were clear absolute benefits of SGLT2 inhibitors on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR.
KEY FINDINGS: Within the studied participants, there were clear absolute benefits of SGLT2 inhibitors on kidney, hospitalization, and mortality outcomes irrespective of diabetes status and level of UACR.
BACKGROUND: There is uncertainty about the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in participants with chronic kidney disease, with guidelines offering different strengths of recommendation based on diabetes status and urine albumin to creatinine ratio (UACR). Study was conducted to assess the relative and absolute effects of SGLT2 inhibitor use across efficacy and serious safety outcomes in participants stratified by diabetes status and UACR (>=200 mg/g or <200 mg/g). Included 8 randomized clinical trials that studied an SGLT2 inhibitor with a label indication for use in kidney disease and recorded longitudinal kidney outcomes and baseline data on albuminuria. Assessed the effects of SGLT2 inhibitor use on clinical efficacy and safety outcomes. Heterogeneity by baseline level of UACR was assessed separately by diabetes status.
DETAILS: A total of 58,816 participants (mean age, 64 [SD, 10] years; 35% were female; 48,946 with diabetes and 9870 without diabetes) were included from trials comparing an SGLT2 inhibitor vs placebo. Allocation to an SGLT2 inhibitor produced a lower rate of kidney disease progression (33 vs 48 for placebo per 1000 patient-years; hazard ratio [HR], 0.65 [95% CI, 0.60-0.70] in those with diabetes and 32 vs 46 per 1000; HR, 0.74 [95% CI, 0.63-0.85] in those without diabetes), a lower rate of acute kidney injury (14 vs 18 per 1000 [HR, 0.77; 95% CI, 0.69-0.87] with diabetes and 13 vs 18 per 1000 [HR, 0.72; 95% CI, 0.56-0.92] without diabetes), a lower rate of any hospitalization (202 vs 231 per 1000 [HR, 0.90; 95% CI, 0.87-0.92] with diabetes and 203 vs 237 per 1000 [HR, 0.89; 95% CI, 0.83-0.95] without diabetes), and a lower rate of any death (42 vs 47 per 1000 [HR, 0.86; 95% CI, 0.80-0.91] with diabetes and 42 vs 48 per 1000 [HR, 0.91; 95% CI, 0.78-1.05] without diabetes). Diabetes-specific HRs were similar in participants (with a UACR >=200 mg/g vs with a UACR <200 mg/g) considered separately. Higher absolute risk at a UACR of 200 mg/g or greater meant larger estimated absolute benefits on kidney disease progression were evident in this subgroup. Clear absolute benefits were evident for other efficacy outcomes, and particularly hospitalization, in participants with a UACR less than 200 mg/g. Net absolute benefits remained in the analyses of non–heart failure populations and when estimated glomerular filtration rate was less than 60 mL/min/1.73 m2.
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Copyright © American Medical Association. All Rights Reserved.
Source: Staplin, N., Roddick, A. J., Neuen, B. L., et al. Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis. JAMA. . 2025; Published online: November 7, 2025. DOI: 10.1001/jama.2025.20835.
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