Appropriate diagnosis and treatment of comorbidities is key to managing acromegaly given their adverse clinical impact on quality of life and survival; thus, it is important to increase overall awareness of complications and their individualized management.

This review examines the current literature on pathophysiology, diagnosis and clinical presentation of acromegaly complications, as well as impact of acromegaly therapy and current goals for treatment outcomes of these morbidities.

We focus on the most relevant acromegaly comorbidities including cardiorespiratory, metabolic, bone, and oncologic complications. Selected complications that may determine pharmacologic choices are also evaluated.

Sarcopenia is increasingly recognized as a major age-related disease with important clinical and public health implications, leading to updated international consensus definitions. We evaluated temporal changes in dual energy X-ray absorptiometry (DXA)-derived low muscle mass and estimated the prevalence and associated comorbidities of sarcopenia using nationally representative data.

We analyzed adults aged ≥50 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2011 and 2024. Appendicular lean mass was assessed using wholebody DXA. Low muscle mass was defined according to the Asian Working Group for Sarcopenia 2025 criteria. Sarcopenia, defined as the coexistence of low muscle mass and low handgrip strength, was assessed only in KNHANES 2024. Sampling weight was applied to all analyses.

The age-standardized prevalence of low muscle mass increased from 27.2% in 2008-2011 to 47.1% in 2024, with similar trends observed in men and women. Male sex, greater height, lower body weight, lower total energy intake, a higher proportion of energy derived from fat, and diabetes mellitus were independently associated with a higher prevalence of low muscle mass. The between-period difference in prevalence remained statistically significant after multivariable adjustment. In 2024, the overall prevalence of sarcopenia was 6.7% and increased with age, reaching 21.5% among adults aged ≥80 years. Sarcopenia was independently associated with diabetes mellitus, anemia, malnutrition, poor self-rated health, and recent bedridden status.

Low muscle mass and sarcopenia are increasingly prevalent among older adults in Korea and are strongly associated with comorbidities.

Incretin therapies have emerged as key interventions for glycemic control and weight reduction, and are now among Canada's costliest outpatient drug classes. This review synthesizes current clinical and economic evidence on the cost-effectiveness of incretin-based therapies, specifically glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual agonists (e.g., semaglutide, tirzepatide) in patients with type 2 diabetes mellitus (T2DM) or for weight loss. We review data from clinical trials and recent Canadian and international economic models, identify emerging indications, and discuss limitations in current health-technology assessment (HTA) frameworks. Implications for Canadian reimbursement are highlighted, with attention to price, patient selection, and outcome considerations.

Gestational diabetes mellitus (GDM), defined as glucose intolerance that starts during pregnancy, represents a major public health challenge because it is a major cause of adverse maternal and fetal outcomes and presents a significant high risk of diabetes, obesity, and cardiovascular disease for both mother and infant. The diagnosis of GDM is currently made through oral glucose tolerance tests (OGTT); other markers of glycemic control have notably failed for GDM diagnosis: Since the treatment of GDM reduces the incidence of adverse pregnancy outcomes, screening for GDM with OGTTs in pregnancy weeks 24-28 is the standard of care in most nations worldwide. However, universal screening is difficult to achieve due in part to the fact that OGTTs are cumbersome and uncomfortable. Thus, the importance of detecting glucose intolerance in pregnant women, the possibility of reducing with treatment the associated risks, the low sensitivity of glycemic markers in pregnancy, and the multiple problems associated with OGTTs highlight the significance of exploring alternative screening/diagnostic methods that are sensitive, accurate, and well tolerated by patients. In this review, we summarize our discovery, development, and clinical validation in six human studies of plasma glycated CD59 (pGCD59), the glucose modified form of the key complement inhibitor CD59, as a biomarker for screening, diagnosis, and monitoring of GDM.

Type 2 diabetes mellitus (T2DM) is a heterogeneous condition, and a proportion of patients show autoimmune features consistent with latent autoimmune diabetes in adults (LADA). This study assessed the prevalence of islet autoantibodies in newly diagnosed T2DM patients of Kazakh ethnicity.

A cross-sectional study was conducted in 240 patients (30-75 years) with newly diagnosed T2DM in the Aktobe region, Kazakhstan (May 2024-January 2025). Clinical data, HbA1c, and fasting C-peptide were measured. Autoantibodies (GADA, ZnT8A, IA-2A, ICA-ELISA) were determined by ELISA.

Overall, 25.8% of patients were positive for at least one islet autoantibody. ZnT8A (13.3%) and GADA (5.8%) were the most frequent, while IA-2A and ICA-ELISA were rare (0.8% each). Double positivity was observed in 4.6% of patients, and triple positivity in 0.4%. GADA was associated with lower BMI (kg/m²), higher HbA1c, and reduced C-peptide, while ZnT8A was linked to lower C-peptide. Logistic regression confirmed C-peptide as the main predictor of autoantibody positivity.

Emergency surgery is an infrequent but severe complication of percutaneous coronary intervention (PCI). The authors sought to examine clinical characteristics, procedural features, and outcomes of patients undergoing emergency cardiac surgery after PCI.

The authors analyzed the clinical characteristics and outcomes of 15 patients who underwent emergency surgery after PCI from the PROGRESS-COMPLICATIONS registry.

Of 18 691 patients who underwent PCI at 2 tertiary care centers between 2016 and 2023, 15 (0.08%) required emergency surgery: 14 underwent coronary artery bypass graft surgery (CABG) and 1 underwent aortic valve replacement and CABG. Patients had high prevalence of comorbidities such as hypertension (93.3%), diabetes mellitus (73.3%), dyslipidemia (93.3%), and prior heart failure (53.3%). The most common presentations included non-ST segment elevation acute myocardial infarction (40.0%) and stable angina (33.3%). Target lesions were complex and often had moderate/severe calcification (60.0%) or involved a bifurcation (40.0%). Mechanical circulatory support was used in 53.3% (intra-aortic balloon pump 12.5%; Impella 2.5 [Abiomed] 12.5%; Impella 5.0 37.5%; Impella CP 12.5%; venoarterial extracorporeal membrane oxygenation 25.0%). In-hospital mortality was 33.3%. The most common indications for emergent CABG were coronary dissection (46.7%), aortocoronary dissection (26.7%), and coronary perforation (26.7%). Post-CABG complications included death (33.3%), arrhythmia (33.3%), hemodynamic instability (26.7%), and cardiogenic shock (13.3%). The median hospital stay was 10.0 days (6.0-18.5). During a median follow-up of 24 months, 53.3% of patients experienced major adverse cardiovascular events (MACE), 46.7% died, and 26.7% required target vessel revascularization.

Patients who underwent emergency surgery after PCI had multiple comorbidities, complex coronary anatomy, and high incidence of MACE.

Hypoxia drives diabetic kidney disease (DKD) progression through Hypoxia Inducible Factor (HIF) signaling. The kidney's cellular heterogeneity and complex architecture pose challenges for directly assessing the pharmacologic effects on kidney oxygenation and hypoxia-responsive pathways in vivo, such as treatment with SGLT2 inhibitors (SGLT2i), presumed to impact kidney oxygenation. Using single-cell transcriptional profiling of kidney tissue from youth with type 2 diabetes (T2D) who showed minimal clinical evidence of DKD, we identified cell type enrichment of HIF-regulated genes, findings that replicated in people with later-stage DKD in the Kidney Precision Medicine Project (KPMP). Using conserved transcription factor (TF) binding motifs, higher-order promoter regulatory structures identified potential cooperating TFs that explained the cell type enrichment pattern. From these promoter elements, 7 interconnected regulatory pathways were identified, comprising a network of 237 genes. Analysis of multiome data from reference tissue in KPMP demonstrated that 80% of the network genes resided in accessible chromatin. Expression of network genes increased significantly in the late compared to the early stage DKD and was validated in a hypoxic human organoid model system. Kidney tissue from individuals with T2D treated with SGLT2i demonstrated reversal of the accumulated changes in the HIF network compared to those not treated with SGLT2i. Most high-confidence genes showed concordant differential expression in spatial transcriptomics from individuals with T2D. Hypoxic kidney organoids treated with SGLT2i confirmed these protective effects. Our promoter-anchored HIF regulatory network provides a multi-component read-out that captures disease progression and quantifies therapeutic response to SGLT2i.

Adipose tissue consists predominantly of lipid-filled adipocytes with limited cytoplasmic space, posing challenges for spatial transcriptomic analysis. Spatially-resolved laser-activated cell sorting (SLACS) enables precise isolation of tissue sections, offering a strategy to overcome these challenges.

Human visceral adipose tissue (VAT) samples from lean individuals and those with obesity and type 2 diabetes mellitus (Ob-DM) were analyzed. SLACS was used to isolate perivascular (PV) and adipocyte-rich (AD) areas, followed by full-length RNA sequencing to investigate pathways, cellular composition, and post-transcriptional regulation.

PV and AD areas exhibited distinct transcriptional patterns. Fibro-inflammatory signatures and vascular remodeling pathways were enriched in the PV, while lipid metabolism and antioxidant pathways were predominant in the AD. Cellular deconvolution suggested area- and disease-specific cell composition. Post-transcriptional modifications, including adenosine-to-inosine (A-to-I) RNA editing and isoform switching in metabolic genes were observed in Ob-DM, suggesting a potential contributor to adipose dysfunction.

This study demonstrates the technical feasibility of SLACS-based spatial transcriptomic profiling in human VAT, with exploratory biological findings that warrant validation in larger cohorts.

Painful diabetic peripheral neuropathy (DPN), a debilitating complication of diabetes mellitus (DM), significantly reduces quality of life. Vitamin D deficiency is common in patients with DM and has been associated with both the presence and severity of DPN.

This systematic review aims to investigate whether vitamin D supplementation improves neuropathic symptoms in patients with painful DPN.

A narrative review.

A systematic literature search was conducted in MEDLINE (PubMed), the Cochrane Library, Embase, Scopus, and the Web of Science for English-language articles published through August 7, 2025. Studies were included if they evaluated the effects of vitamin D supplementation in patients with painful DPN.

Overall, 50 articles were identified through the database search. After screening titles and abstracts, 39 articles were excluded for not meeting the inclusion criteria. The remaining 11 articles were assessed for full-text eligibility. Finally, 7 studies were included in this review. Most of those studies reported improvements in pain scores, quality of life, and serum 25(OH)D levels following vitamin D supplementation. The findings suggest that vitamin D alleviates neuropathic pain by modulating inflammatory responses, promoting nerve regeneration, and enhancing the expression of neurotrophic factors.

Further randomized controlled trials are needed to confirm the therapeutic efficacy of vitamin D supplementation and to establish the optimal dosage, frequency, and treatment duration associated with it.

The findings support the consideration of vitamin D supplementation as a potential adjunctive strategy for managing painful DPN.

Secondary primary solid malignancies (SPSMs) significantly impact long-term outcomes in lymphoma patients. However, subtype-specific differences remain unclear, such as diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL).

This study collected 1,377 DLBCL and 489 FL patients, identifying 50 DLBCL and 31 FL cases with SPSMs. Clinical characteristics, SPSM types, and survival were compared in these 81 patients. Demographic, clinical, treatment-related variables (including radiotherapy for primary lymphoma, recorded as yes/no), and survival outcomes were collected. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox proportional hazards models. The cumulative incidence of SPSMs was evaluated with competing risk analysis (death as a competing event), and group comparisons were performed with Gray's test. Prognostic factors identified in univariable analysis (p < 0.05) were included in a multivariable Cox model. A nomogram was developed, with discriminative ability assessed by the area under the receiver operating characteristic curve (ROC). Statistical significance was set at p < 0.05.

SPSMs were observed more frequently in FL (6.34%) than DLBCL (3.63%). Thyroid cancer predominated (22.2%, 18/81). DLBCL patients developed SPSMs earlier than FL patients (median 28.47 vs. 41.77 months, p = 0.031), though cumulative incidence accounting for competing risks did not differ significantly (Gray's test p = 0.34). DLBCL patients with SPSMs had inferior OS compared to FL patients (p = 0.04). Non-GCB DLBCL showed greater SPSM diversity and survival disadvantage. Multivariable analysis identified FL (vs. DLBCL) subtype (HR = 0.328, p = 0.018), bone marrow infiltration (HR = 2.815, p = 0.014), initial radiotherapy before SPSM diagnosis (HR = 3.475, p = 0.005), and shorter time to SPSM development (HR = 0.973 per month, p = 0.021) as independent prognostic factors for worse OS. The nomogram model showed acceptable discrimination, with an AUC of 0.761 in the time-dependent ROC analysis.

This study provides novel insights into SPSM characteristics and prognostic differences in DLBCL and FL patients within a Chinese cohort. SPSMs in FL patients were observed more frequently, while DLBCL patients, particularly those with non-GCB subtypes, experience earlier SPSM onset and poorer survival. The validated nomogram, incorporating lymphoma-related factors, enables personalized risk stratification. However, the single-center design, small sample size (n = 81), and lack of SPSM-specific data limit generalizability, necessitating multi-center studies with comprehensive SPSM characterization for validation.