Cardiovascular, Bone, and Mortality Outcomes in Older Adults
A UK emulated target trial involving 19,027 adults found that initial levothyroxine dosing above 1.0 microgram per kg per day was associated with increased long-term risks of cardiovascular events, bone outcomes, and all-cause mortality. The findings highlight the importance of cautious dose selection and individualized titration in older adults, although prospective studies are needed to confirm these associations.
KEY FINDINGS: Among adults older than 50 years initiating levothyroxine, an initial dose exceeding 1.0 μg/kg per day was associated with higher long-term risks of cardiovascular events, bone outcomes, and all-cause mortality compared with lower initial dosing. The findings support careful consideration of initial dose and subsequent titration in older patients. However, the observational design does not establish that higher dosing directly caused these outcomes, and prospective studies are needed to validate the findings.
BACKGROUND: Levothyroxine is commonly prescribed for hypothyroidism, but determining an appropriate initial dose in older adults remains challenging. Both insufficient and excessive thyroid hormone replacement may adversely affect cardiovascular health, bone integrity, and survival. This study used an emulated target trial approach to evaluate the association between initial weight-based levothyroxine dosing and long-term clinical outcomes in adults older than 50 years.
DETAILS: This observational study used data from The Health Improvement Network, a UK primary care database, covering January 1, 2006, through December 31, 2021. Eligible participants were adults older than 50 years with diagnosed hypothyroidism, at least one recorded thyroid-stimulating hormone (TSH) measurement exceeding 4.0 mU/L, and a new levothyroxine prescription during the study period. The investigators compared patients initiating levothyroxine at more than 1.0 μg/kg per day with those receiving 1.0 μg/kg per day or less. Dosing was assessed using both total bodyweight and lean bodyweight. Participants were followed for up to 10 years for cardiovascular events, bone outcomes, and all-cause mortality. Inverse probability of treatment weighting was used to adjust for baseline confounders, and weighted Cox proportional hazards models were applied to estimate outcome associations.
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A total of 19,027 records were eligible, including 14,296 women (75%) and 4,731 men (25%). The cardiovascular analysis included 15,463 adults, the bone health analysis included 14,947, and all 19,027 participants were included in the mortality analysis. Unweighted event rates were higher among patients initiating levothyroxine at more than 1.0 μg/kg per day than among those receiving lower doses. Cardiovascular events occurred in 20% versus 18%, bone outcomes in 13% versus 9%, and all-cause mortality in 18% versus 17%, respectively. Higher initial dosing was associated with increased risk of cardiovascular events (adjusted hazard ratio [HR], 1.18; 95% CI, 1.08-1.29), bone outcomes (HR, 1.29; 95% CI, 1.16-1.43), and all-cause mortality (HR, 1.17; 95% CI, 1.09-1.25).
Using total bodyweight-based dosing, the weighted 10-year absolute risk differences between the higher- and lower-dose groups were 1.3% (95% CI, 0.3-3.0) for cardiovascular events, 3.0% (95% CI, 1.6-4.5) for bone outcomes, and 3.4% (95% CI, 1.7-5.1) for all-cause mortality. Similar associations were observed in analyses using lean bodyweight-based dosing.
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Source: Holley, M., Wilkes, S., Moss, E. D., et al. Weight-based levothyroxine dosing and long-term cardiovascular, bone, and mortality outcomes in older adults: an emulated target trial using UK primary care data. The Lancet Primary Care. 2026; 2(8): 100194. Published: August, 2026. DOI: 10.1016/j.lanprc.2026.100194.
Aztreonam/Avibactam Retains Activity Against Drug-Resistant Enterobacterales
An analysis of 80,927 Enterobacterales isolates from 103 US medical centers found that aztreonam/avibactam retained in vitro activity against 98.1% of carbapenem-resistant isolates and 98.4% of metallo-beta-lactamase producers. Meanwhile, MBLs were identified in 36.1% of CRE isolates collected during 2023–2024. These findings highlight the potential value of aztreonam/avibactam against resistant Gram-negative bacteria and the need for continued antimicrobial resistance surveillance.
KEY FINDINGS: Aztreonam/avibactam retained substantial in vitro activity against Enterobacterales resistant to other advanced beta-lactam/beta-lactamase inhibitor combinations, including MBL-producing organisms. The findings are particularly relevant as NDM and other MBLs increasingly complicate the treatment of CRE infections. These results support the potential role of aztreonam/avibactam as a treatment option for selected infections caused by resistant Gram-negative bacteria. However, laboratory susceptibility findings do not establish clinical effectiveness in individual patients. Treatment decisions should incorporate susceptibility testing, infection site, patient factors, and applicable clinical guidance. Continued surveillance is also necessary to monitor emerging resistance.
BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are an increasing clinical concern because resistance to newer antibiotics, including ceftazidime/avibactam and meropenem/vaborbactam, limits treatment options for serious infections. Metallo-beta-lactamase (MBL)-producing organisms pose a particular challenge because these enzymes can inactivate many beta-lactam antibiotics. Aztreonam/avibactam combines aztreonam's stability against MBL-mediated hydrolysis with avibactam's inhibition of several other beta-lactamases. This study assessed its in vitro activity against resistant Enterobacterales collected from US medical centers.
DETAILS: Investigators analyzed 80,927 Enterobacterales isolates collected from 103 US medical centers between 2016 and 2024, with one isolate per patient. Antimicrobial susceptibility was evaluated using broth microdilution. The analysis focused on isolates that were not susceptible to ceftazidime/avibactam, meropenem/vaborbactam, or both, as well as carbapenem-resistant and MBL-producing isolates. Whole-genome sequencing was used to identify carbapenemase genes in resistant isolates. Among the collected isolates, 194 (0.24%) were not susceptible to ceftazidime/avibactam or meropenem/vaborbactam, 115 (0.14%) were not susceptible to both combinations, and 832 (1.0%) were carbapenem resistant.
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Aztreonam/avibactam demonstrated activity against 91.9% of ceftazidime/avibactam-nonsusceptible isolates and 94.0% of meropenem/vaborbactam-nonsusceptible isolates. Activity was observed against 98.1% of CRE isolates and 98.4% of MBL-producing isolates. Cefiderocol was active against 78.8% of ceftazidime/avibactam-nonsusceptible isolates, 83.2% of meropenem/vaborbactam-nonsusceptible isolates, 94.7% of CRE isolates, and 82.1% of MBL producers. Genetic analysis identified carbapenemase genes in 159 (82.0%) of isolates nonsusceptible to ceftazidime/avibactam or meropenem/vaborbactam and in 683 (80.1%) of CRE isolates. New Delhi metallo-beta-lactamase (NDM) was the most common carbapenemase among the resistant isolates, identified in 114 (58.8%). Notably, MBL-producing organisms accounted for 36.1% (73/202) of CRE isolates collected during 2023–2024, highlighting the importance of continued resistance surveillance.
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Source: Sader, H. S., Papp-Wallace, K. M., Kimbrough, J. H., et al. Antimicrobial activity of aztreonam/avibactam and molecular characterization of Enterobacterales not susceptible to ceftazidime/avibactam and/or meropenem/vaborbactam from US medical centres (2016-2024). Journal of Antimicrobial Chemotherapy. 2026; 81(10). Published: October, 2026. DOI: 10.1093/jac/dkag308.
Frailty and Hospitalization Risk in Older Adults Presenting to the Emergency Department
A Japanese study of 3,127 emergency department visits among adults aged 65 years or older found that frailty was associated with higher odds of hospitalization in patients assigned moderate- and lower-acuity triage categories. The overall interaction between frailty and triage urgency was not statistically significant, underscoring the need for further research into how frailty can support geriatric emergency assessment and disposition decisions.
KEY FINDINGS: This study suggests that frailty may provide clinically relevant information when assessing hospitalization needs in older adults presenting to the emergency department. The association was most apparent in patients assigned lower triage urgency categories, although the formal analysis did not confirm a statistically significant difference across categories.
Incorporating frailty assessment into geriatric emergency care may help clinicians consider functional vulnerability alongside acute illness severity. However, the findings are based on a single-center retrospective study and do not establish that frailty itself causes hospitalization. Further prospective, multicenter research is needed to clarify how frailty, social circumstances, clinical decision-making, and healthcare-system factors influence disposition.
BACKGROUND: Emergency department (ED) triage systems prioritize patients according to the urgency of their acute medical conditions. However, among older adults, frailty may also influence the need for hospitalization, even when patients have similar triage-assessed urgency. Understanding the relationship between frailty and hospital admission may help clinicians improve geriatric assessment and disposition decisions in emergency care.
DETAILS: This single-center retrospective cohort study was conducted at an urban tertiary hospital in Japan. Investigators analyzed emergency department visits by patients aged 65 years or older between November 2025 and March 2026. Frailty was defined as a score of 5 or higher on the Clinical Frailty Scale (CFS). Triage urgency was classified using the Japan Triage and Acuity Scale (JTAS). The primary outcome was hospitalization at the study hospital or transfer to another acute-care hospital. The investigators used mixed-effects logistic regression, adjusting for age, sex, mode of arrival, injury- or poisoning-related visits, living arrangements, and long-term care needs certification. The analysis also examined whether the association between frailty and hospitalization differed across triage categories.
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The study included 3,127 emergency department visits, of which 1,526 resulted in hospitalization. Among patients in JTAS category 2, frailty was not significantly associated with hospitalization (adjusted odds ratio [OR], 1.00; 95% CI, 0.65–1.55). In category 3, frailty was associated with higher odds of hospitalization (OR, 1.54; 95% CI, 1.19–1.99). In the combined JTAS categories 4 and 5, the adjusted odds of hospitalization were approximately twice as high among frail patients (OR, 2.01; 95% CI, 1.13–3.58). The association between frailty and hospitalization appeared stronger in the lower-acuity categories. However, the overall interaction between frailty and triage category was not statistically significant (P = 0.091), so the study did not establish that the association differed across triage levels.
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Source: Hata, N., Nagae, M., and Umegaki, H. Frailty and Hospitalization After Emergency Department Evaluation Within Triage Categories in Older Patients: A Retrospective Cohort Study. Academic Emergency Medicine. 2026; 33(10). Published: August 22, 2026. DOI: 10.1111/acem.70419.
Body Composition Abnormalities in Heart Failure May Be Underestimated by BMI
A UK Biobank imaging study found that patients with heart failure had greater visceral fat, lower muscle volume, and more muscle fat infiltration than age-, sex-, and BMI-matched controls. Body composition patterns varied across heart failure phenotypes, while sarcopenia prevalence differed substantially depending on the diagnostic criteria used. The findings highlight the limitations of BMI alone in assessing metabolic and muscular abnormalities in heart failure.
KEY FINDINGS: This study found that HF was associated with increased visceral adiposity, reduced muscle volume, and greater muscle fat infiltration, even when patients were compared with controls matched for BMI. The differing patterns across HF phenotypes suggest that body composition abnormalities are not uniform among patients with heart failure.
The findings indicate that BMI and conventional anthropometric measures may underestimate clinically relevant metabolic and muscular abnormalities. Advanced imaging and more consistent definitions of sarcopenia may improve characterization of these abnormalities, although further research is needed to determine their prognostic value and implications for treatment.
BACKGROUND: Heart failure (HF) is associated with metabolic and musculoskeletal abnormalities that may not be adequately captured by body mass index (BMI). Excess visceral fat, reduced skeletal muscle volume, and increased fat infiltration within muscle can coexist and may differ across HF phenotypes. This study used advanced imaging to characterize body composition in patients with HF compared with matched controls and to examine differences among HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF).
DETAILS: Researchers analyzed participants in the UK Biobank Imaging Study. A total of 185 individuals with HF and available ejection fraction measurements were matched in a 1:5 ratio with 925 controls matched for age, sex, and BMI. Whole-body magnetic resonance imaging (MRI) was used to quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, liver fat, thigh fat-free muscle volume, and muscle fat infiltration (MFI). Dual-energy x-ray absorptiometry (DXA) was used to measure total fat and appendicular lean mass. Personalized z-scores adjusted for sex and body size were calculated. Adverse muscle composition (AMC) was defined by the combination of low muscle volume and high muscle fat infiltration. The investigators also assessed sarcopenia using grip strength and DXA-derived lean mass criteria.
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Compared with matched controls, participants with HF had significantly greater visceral adipose tissue (z-score, 0.46 ± 1.1 vs 0.07 ± 1.0; P < 0.001) and muscle fat infiltration (8.4% ± 2.3% vs 7.6% ± 2.0%; P < 0.001). Adverse muscle composition was present in 36% of participants with HF compared with 17% of controls (P < 0.001). Muscle volume was also lower in the HF group (z-score, −0.7 ± 1.0 vs −0.1 ± 0.9; P < 0.001). Body composition patterns differed across HF phenotypes. HFmrEF was associated with the highest visceral adipose tissue levels and lowest muscle volume. HFpEF showed greater overall fat and muscle fat infiltration, whereas HFrEF had the highest prevalence of adverse muscle composition and the weakest grip strength.
Despite the MRI-detected muscle abnormalities, the estimated prevalence of sarcopenia varied considerably according to the diagnostic criteria applied, highlighting inconsistencies among current definitions.
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Source: Butler, J., Fioretti, F., Anker, S. D., et al. Body Composition in Heart Failure: A Magnetic Resonance Imaging and Dual X-Ray Absorptiometry Assessment in the UK Biobank Study. JACC: Heart Failure. 2026; 14(10): 103242. Published: October, 2026. DOI: 10.1016/j.jchf.2026.103242.
Total Body Photography for Early Skin Cancer Detection
A systematic review of 36 studies found that total body photography is evolving through digital imaging, 3D technology, and AI-assisted skin surveillance. However, only 6 studies reported implementation-related outcomes, and none used a formal implementation science framework. The findings highlight the need to evaluate not only diagnostic potential but also feasibility, workforce requirements, and integration into routine skin cancer care.
Summary
Clinical Implementation and Emerging Opportunities
[Posted 9/Oct/2026]
AUDIENCE: Dermatology, Oncology, Family Medicine
KEY FINDINGS: Total body photography has evolved from conventional photographic documentation to digitally enabled and increasingly automated systems that may support longitudinal skin surveillance and early lesion identification. However, the available literature provides limited evidence on implementation processes, workforce requirements, patient and clinician acceptability, and sustainable integration across primary, secondary, and tertiary care.
The authors identify opportunities to extend TBP into a broader range of clinical environments, including resource-constrained settings. Future research should evaluate implementation outcomes alongside clinical effectiveness to establish how these technologies can be adopted reliably and equitably in real-world skin cancer care.
BACKGROUND: Early detection is an important component of skin cancer management, particularly in individuals at elevated risk of melanoma. Total body photography (TBP) provides baseline images of the skin surface, allowing clinicians to document lesions and identify new or evolving abnormalities during follow-up. Recent developments in digital imaging, three-dimensional (3D) photography, and artificial intelligence (AI) have expanded its potential role in skin cancer surveillance.
However, evidence regarding how these technologies are adopted, integrated, and sustained across different healthcare settings remains limited. This systematic review examined the evolution of TBP implementation, clinical workflows, workforce involvement, and factors influencing its use in routine care.
DETAILS: The review followed Cochrane guidance and PRISMA reporting recommendations. Investigators searched PubMed, Scopus, Web of Science, and Embase for studies published from database inception through July 2025. Studies were eligible if they described the clinical use, implementation, integration, or utility of TBP technologies for skin cancer detection. Thirty-six studies were included, covering different healthcare settings, imaging technologies, clinical workflows, personnel, and patient populations. Because of substantial heterogeneity in study designs, objectives, and reporting, findings were synthesized narratively rather than through meta-analysis. The review assessed how TBP was delivered, the resources and personnel involved, reported barriers and facilitators, and whether implementation outcomes such as feasibility, acceptability, and appropriateness were evaluated.
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The 36 included studies demonstrated considerable variation in TBP technologies and clinical applications. Developments included automated and digitally enabled systems for lesion documentation, longitudinal monitoring, and diagnostic decision support, including AI-assisted imaging. Despite these technological advances, the fundamental clinical workflows for TBP remained broadly consistent over time, although the sequence of processes varied across settings. Several studies reported that healthcare professionals from different disciplines could perform TBP-supported skin examinations.
Only 6 of the 36 studies reported implementation-related information, including feasibility of reproducing protocols across healthcare settings, user perceptions, and practical use of TBP technologies or AI features. None used a formal implementation science framework.
The review therefore identified a substantial gap between the growing availability of imaging technologies and the evidence needed to guide their systematic integration into routine clinical practice.
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Source: Hussain, N. A. B., Ansah-Sasraku, F. A., Fernández-Peñas, P., et al. Implementation of Total Body Photography for Skin Cancer Early Detection: A Systematic Review. International Journal of Dermatology. 2026; Published: August 22, 2026. DOI: 10.1111/ijd.70679.
Higher Ferritin Levels Associated With Increased Type 2 Diabetes Risk, Particularly in Women
A dose-response meta-analysis of 15 prospective studies involving 77,352 participants found that higher ferritin levels were associated with increased type 2 diabetes risk in both sexes. The association appeared stronger in women, with each 100-microgram-per-liter increase linked to a 53% higher risk compared with 21% in men. These findings highlight the potential value of investigating ferritin as a sex-specific marker of diabetes risk.
KEY FINDINGS: Higher circulating ferritin levels were associated with increased T2D risk in both men and women, with a stronger association observed in women in the primary sex-specific analysis after exclusion of a heterogeneous study. These findings suggest that ferritin may provide additional information for sex-specific diabetes risk assessment.
However, the meta-analysis establishes an association rather than causation. Differences in study populations, substantial between-study heterogeneity, and insufficient information on menopausal status limit interpretation. Further prospective research is needed to determine whether ferritin improves diabetes risk prediction beyond established clinical factors and whether the observed sex difference is consistent across diverse populations.
BACKGROUND: Iron metabolism has been implicated in glucose regulation and the development of type 2 diabetes (T2D). Ferritin, a marker of iron stores, has been associated with diabetes risk in observational studies, although findings have varied across populations. Because circulating ferritin concentrations differ between men and women, investigators conducted a dose-response meta-analysis to examine whether the association between ferritin levels and incident T2D varies by sex.
DETAILS: Researchers systematically searched PubMed, Web of Science, and EMBASE for prospective studies published through August 1, 2018. Fifteen studies involving 77,352 participants aged 20 to 80 years and 18,404 incident T2D cases were included. Follow-up ranged from approximately 3 to 17 years. The investigators assessed the relationship between circulating ferritin concentrations and T2D risk using pooled relative risk estimates and dose-response analyses. Sex-specific analyses were conducted to evaluate potential differences in the association between ferritin levels and diabetes development.
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Across all participants, each 100-microgram-per-liter increase in circulating ferritin was associated with a 22% higher risk of T2D (RR, 1.22; 95% CI, 1.14-1.31). In sex-specific analyses, after excluding a study contributing substantial heterogeneity, each 100-microgram-per-liter increase in ferritin was associated with a 53% higher T2D risk in women (RR, 1.53; 95% CI, 1.29-1.82), compared with a 21% increase in men (RR, 1.21; 95% CI, 1.15-1.27). The difference between sexes was statistically significant (P=0.020).
Nonlinear dose-response analyses also indicated that the association between ferritin and T2D risk was stronger in women than in men at comparable ferritin concentrations. The association remained evident after adjustment for several potential confounders, including inflammatory markers, body mass index, liver enzymes, and metabolic factors.
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Source: Jiang, L., Wang, K., Lo, K., et al. ex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. The Journal of Clinical Endocrinology & Metabolism. 2026; 104(10): 4539-4551. Published: August 22, 2026. DOI: 10.1210/jc.2019-00495.
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