[Posted 20/Jun/2022]

AUDIENCE: Endocrinology

KEY FINDINGS: These findings provide novel evidence that the increase in EGP induced by SGLT2i is present during an oral glucose load. The fact that stimulation of EGP occurs despite elevated plasma insulin and glucagon suggests that additional factors must be involved.

BACKGROUND: Purpose of this trial is to examine the effect of SGLT2 inhibitors (SGLT2i) on endogenous glucose production (EGP) in patients with type 2 diabetes after an oral glucose load.

DETAILS: Forty-eight patients with type 2 diabetes received an 8-h [3-3H]-glucose infusion (protocol I) to assess EGP response to: 1) dapagliflozin (DAPA), 10 mg; 2) exenatide (EXE), 5 μg s.c.; 3) DAPA/EXE; and 4) placebo (PCB). After 2 weeks (protocol II), patients were restudied with a 5-h double-tracer (i.v. [3-3H]-glucose and oral [1-14C]-glucose) oral glucose tolerance test (OGTT) preceded by PCB, DAPA, EXE, or DAPA/EXE. Protocol I: EGP decreased (P < 0.01) with PCB (2.16 ± 0.15 to 1.57 ± 0.08 mg/kg/min) and EXE (2.13 ± 0.16 to 1.58 ± 0.03) and remained unchanged (P = NS) with DAPA (2.04 ± 0.17 vs. 1.94 ± 0.18) and DAPA/EXE (2.13 ± 0.10 vs. 2.09 ± 0.03). During OGTT, EGP decreased (P < 0.01) with PCB (2.30 ± 0.05 to. 1.45 ± 0.06 mg/kg/min) and EXE (2.53 ± 0.08 to 1.36 ± 0.06); with DAPA (2.20 ± 0.04 vs. 1.71 ± 0.07) and DAPA/EXE (2.48 ± 0.05 vs. 1.64 ± 0.07), the decrease in EGP was attenuated (both P < 0.05). During OGTT, the insulin/glucagon (INS/GCN) ratio increased in PCB (0.26 ± 0.03 vs. 0.71 ± 0.06 μU/mL per pg/mL), whereas in DAPA (0.26 ± 0.02 to 0.50 ± 0.04), the increase was blunted (P < 0.05). In EXE, INS/GCN increased significantly (0.32 ± 0.03 to 1.31 ± 0.08) and was attenuated in DAPA/EXE (0.32 ± 0.03 vs. 0.78 ± 0.08) (P < 0.01).

Copyright © American Diabetes Association. All rights reserved.

Source: Alatrach, M., Agyin, C., Solis-Herrera, C., et al. (2022). Dapagliflozin Impairs the Suppression of Endogenous Glucose Production in Type 2 Diabetes Following Oral Glucose. Diabetes Care . 2022; 45(6): 1372-1380. Published: June 6, 2022. DOI: 10.2337/dc21-1798.

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 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.

Tissue Sensor Implementation in a Clinical System

[Posted 20/Jan/2026]

AUDIENCE: General Surgery, Nephrology, Internal Medicine

KEY FINDINGS: The developed optical guidance system provides real-time feedback during laser lithotripsy, improving safety and precision by reducing the risk of accidental tissue damage. The proposed technology is expected to enhance outcomes in minimally invasive urological laser procedures.

BACKGROUND: Purpose of this study is to develop an optical feedback system compatible with a commercial surgical laser for automatically distinguishing between urinary stones and soft tissues during laser lithotripsy, thereby enhancing procedural safety.

DETAILS: The system, based on diffuse reflectance spectroscopy (DRS), was implemented in an engineered clinical theranostic platform. In vivo experiments were conducted to collect and analyze DRS spectra of tissues during laser lithotripsy. Illumination was performed via the endoscope, and detection was performed via the treatment fiber. Classification of urinary stones and soft tissues was performed using machine learning methods, i.e., Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA). The system demonstrated high diagnostic performance, with 93% sensitivity for soft tissue identification and 93% specificity for stone detection evaluated by the LDA method. This real-time differentiation effectively minimized unintended laser exposure to non-target tissues.

Copyright © Wiley Periodicals LLC. All rights reserved.

Source: Korneva, N., Budylin, G., Tseregorodtseva, P., et al. Optical Feedback for Safe Automatic Laser Lithotripsy: Tissue Sensor Implementation in a Clinical System. Lasers Surg. Med.. 2026; 58(1): 38-48. Published: January, 2026. DOI: 10.1002/lsm.70081.

[Posted 5/Jan/2026]

AUDIENCE: Cardiology, Ob/Gyn

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.

Copyright © Authors. All rights reserved.

Source: Appleman, Y., Gulati, M., Roeters van Lennep, J. E., et al. Cardiovascular Disease in Women: Traditional and Sex-Specific Risk Factors. European Heart Journal. 2025; Published: December, 2025. DOI: 10.1093/eurheartj/ehaf1001.