Standard modifiable cardiovascular risk factors (SMuRFs) and non-SMuRFs are commonly used for risk stratification and therapeutic guidance after ST-elevation myocardial infarction (STEMI) in the general population. Their prognostic relevance with a potential implication for pharmacological and therapeutic management in individuals with established diabetes remains uncertain. This systematic review with meta-analysis aimed to identify prognostic factors associated with mortality in individuals with diabetes and STEMI qualifying for potential therapeutic targets. Studies evaluating prognostic factors for mortality in individuals with diabetes after STEMI were included up to May 3, 2025. Data extraction was performed independently by two reviewers. Certainty of evidence (CoE) was evaluated (GRADE). Thirty-seven studies were included, of which 25 had a high risk of bias. Mortality after STEMI in individuals with diabetes was consistently associated with non-SMuRFs (age, female sex, chronic kidney disease), acute cardiac dysfunction (Killip class III-IV, heart failure, cardiogenic shock), and atherosclerosis extent (anterior infarction, prior myocardial infarction, peripheral vascular disease). Diabetes-specific risk factors, including glycemic control parameters and insulin treatment, were also associated with increased risk of mortality (low to very low CoE). Once diabetes is established, no increased risk of mortality was observed for traditional SMuRFs, such as hypertension, smoking status, dyslipidemia, and obesity. These findings highlight the need for therapeutic strategies beyond conventional risk factor modification, with emphasis on acute hemodynamic management, tailored pharmacotherapy, and optimized glycemic control in this high-risk population. REGISTRATION PROSPERo: CRD42022378193.

To evaluate the evidence supporting combined sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in type 2 diabetes, focusing on cardiometabolic outcomes and practical treatment approaches.

Cardiovascular outcomes trials and real-world studies indicate that SGLT2is and GLP-1RAs confer complementary, non-redundant cardiovascular, kidney, and metabolic benefits. SGLT2is primarily reduce hospitalization for heart failure and slow kidney disease progression, while GLP-1RAs more effectively reduce atherosclerotic events, particularly stroke; dedicated kidney-outcome and heart-failure trials of GLP-1RAs in chronic kidney disease and obesity-related heart failure with preserved ejection fraction have further broadened their role. Randomized data show that each class retains its benefit irrespective of background use of the other, supporting independent mechanisms; whether this translates into reductions in hard outcomes is being tested prospectively. Emerging evidence supports a phenotype-guided approach that aligns therapy with dominant comorbidities such as atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, and obesity. Despite advances in pharmacotherapy, substantial cardiometabolic risk remains in type 2 diabetes. Combined SGLT2i and GLP-1RA therapy addresses multiple risk domains through complementary mechanisms and may be most effective within a phenotype-guided framework. This framework prioritizes therapy according to predominant comorbidity and reserves combination treatment for individuals with overlapping high-risk phenotypes.

Severe hypoglycemia from insulin overdose is a medical emergency that can be complicated by comorbidities and concurrent substance use. This case highlights a rare but fatal outcome of acute mesenteric ischemia in a patient with insulin overdose treated with Octreotide (Sandostatin, Novartis), compounded by recent methamphetamine use. The interplay of these factors may contribute to microvascular compromise and ischemia.

A 44-year-old male with chronic kidney disease stage 3b, body-mass-index of 23.23 kg/m2, insulin-dependent diabetes mellitus, and recent methamphetamine use presented with altered mental status following a self-reported insulin overdose of 240 units. Initial management included high-dose dextrose infusions, yet severe hypoglycemia persisted. Octreotide was administered to suppress endogenous insulin secretion, resulting in initial stabilization and resolution of altered mental status. Approximately five hours later, the patient developed acute abdominal pain, worsening encephalopathy, and respiratory distress requiring intubation. Computed tomography angiography revealed extensive portal and mesenteric venous gas. Emergency laparotomy revealed evidence of widespread microvascular ischemia but no full-thickness intestinal infarction, suggestive of non-occlusive mesenteric ischemia (NOMI). Despite surgical intervention and aggressive resuscitation, the patient deteriorated and succumbed to his illness.

This case highlights the critical importance of considering methamphetamine use and its potential synergistic effects with medications like octreotide in the management of complex medical conditions to prevent fatal complications such as severe intestinal ischemia.

Islet transplantation is a promising treatment for diabetes, but the shortage of donor islets limits its broad application. Induced pluripotent stem cells (iPSCs) provide an alternative source for generating insulin-producing cells; however, whether the somatic cell origin of human iPSCs influences pancreatic endocrine differentiation remains incompletely defined. In this study, we generated iPSCs from human pancreatic duct cells (HD-iPSCs) and compared their differentiation propensity and functional characteristics with human fibroblast-derived iPSCs (HF-iPSCs) under identical differentiation conditions. HD-iPSC-derived cells showed higher expression of pancreatic endocrine and β-cell-associated markers, including insulin, PDX1, and FOXA2, compared with HF-iPSC-derived cells. Flow cytometric analysis further confirmed a higher proportion of insulin-positive cells in differentiated HD-iPSC-derived cells. Functionally, HD-iPSC-derived cells exhibited greater glucose-stimulated C-peptide secretion than HF-iPSC-derived cells, although their secretory capacity remained lower than that of native human islets. Following transplantation into streptozotocin-induced diabetic mice, HD-iPSC-derived cells reduced blood glucose levels more effectively than HF-iPSC-derived cells, and insulin-positive grafts were detected in vivo. These findings suggest that human pancreatic duct cell-derived iPSCs have enhanced pancreatic endocrine differentiation potential compared with fibroblast-derived iPSCs. Although further maturation and optimization are required, pancreatic duct cells may represent a favorable somatic cell source for generating iPSC-derived insulin-producing cells for diabetes cell therapy.

Diabesity, defined as obesity accompanied by Type 2 diabetes mellitus, is characterized by metabolic dysfunction and mitochondrial impairment. Here, we investigate the role of N6-methyladenosine (m⁶A)-mediated RNA regulation in regulating hepatic mitochondrial function and fatty acid β-oxidation during diabesity progression. Diabesity was modeled in male C57BLKS/J db/db mice, with db/m lean mice as controls; in vitro models were established using primary hepatocytes isolated from male C57BL/6J mice exposed to high glucose and palmitate. Our results showed that MCM3 was significantly downregulated in diabesity models. MCM3 overexpression improved hepatic mitochondrial function and fatty acid β-oxidation. Mechanistically, MCM3 increased NRF2 in hepatocytes by competitive combination with KEAP1. In addition, RBM15 overexpression accelerated m⁶A-YTHDF2-mediated MCM3 mRNA decay. As expected, MCM3 knockdown negated the metabolic benefits of RBM15 knockdown. In conclusion, m⁶A-dependent MCM3 downregulation by RBM15/YTHDF2 impaired hepatic mitochondrial function and fatty acid β-oxidation in diabesity by reducing NRF2.

Osteosarcoma is the most common primary malignant bone tumor, typically affecting children and adolescents during rapid growth periods. With current treatments, the five-year survival rate for metastatic or recurrent cases remains only 20-30%, highlighting the need for new therapeutic approaches and better preclinical models. Our goal is to simulate the osteosarcoma bone microenvironment using melt electrowriting (MEW)-printed polycaprolactone (PCL) scaffolds with optimized calcium phosphate formation. To achieve this, we fabricated PCL scaffolds with distinct MEW micro-architectures, including rectangular, triangular, and hexagonal designs with comparable primary fiber spacing, and investigated two calcium phosphate formation methods: natural cell-generated mineralization and direct calcium phosphate cement coating. Using SaOS-2 osteosarcoma cells, we systematically evaluated cell behavior, mineralization dynamics, and scaffold mechanical properties. This approach aims to establish a biomimetic 3D model that bridges the gap between laboratory findings and clinical applications, enabling more pathophysiologically relevant drug testing platforms.

To compare radiographic and clinical outcomes of vestibular schwannoma management using stereotactic radiosurgery (SRS) and microsurgical resection, with emphasis on paired pre- and post-treatment changes in tumor size and patient outcomes.

A retrospective review was conducted of 87 patients treated for vestibular schwannoma between 2013 and 2024 at a single tertiary center. Demographic, clinical, and radiographic variables, including hearing loss, facial weakness, brainstem compression, tumor area, and Koos grade, were analyzed. Tumor area was determined from radiology reports and compared using nonparametric statistical tests, with significance defined as p < 0.05.

Microsurgery achieved a median 76% reduction in tumor area, while SRS was associated with relative stability or modest growth (+ 5%) (p < 0.001). Post-treatment rates of hearing loss and facial weakness were similar between groups, suggesting that substantial tumor reduction following microsurgery was not associated with increased morbidity in this cohort. Koos grade correlated with both brainstem compression and hearing loss, with higher grades favoring surgical management (p = 0.049). In the Koos IV subset, surgery achieved significant tumor reduction without disproportionate postoperative deficits compared with lower grades.

Microsurgery provides immediate and substantial tumor reduction without increased morbidity, while SRS maintains radiographic stability with favorable clinical outcomes. These findings underscore the complementary roles of both modalities and support the Koos classification as a practical and reliable framework for treatment selection.

Adolescent and young adult cancer patients (AYAs, aged 15-39) are at an elevated risk of experiencing psychosocial distress. Furthermore, most AYAs receive care in community oncology settings where little is known about distress screening and management for AYAs. We examined distress screening at National Cancer Institute Community Oncology Research Program (NCORP) across 100 practices previously identified as AYA-treating.

Using data from the 2022 Landscape Assessment survey, distress screening and availability of mental health care were evaluated. Univariable and multivariable analyses examined associations between on-site availability of mental health services and AYA-relevant practice characteristics (e.g., Children's Oncology Group affiliation, number of new AYAs annually, AYA program).

Nearly all (91%) AYA-treating practices reported routinely screening for distress, with 47% using the National Comprehensive Cancer Network (NCCN) Distress Thermometer. Additionally, 23% of practices reported they do not have mental health services onsite. Practices treating ≥ 100 new AYAs annually were more than 3 times as likely to have onsite mental health services than practices treating < 100 new AYAs annually in multivariable models (OR = 3.09, 95% CI = 1.04, 9.18; p = 0.042).

Although distress screening was widely conducted in AYA-treating NCORP practices, findings raise concerns about the sensitivity and specificity of measures used and access to onsite cancer-specific psychosocial care. Ultimately, the goal of distress screening is referral for assessment and intervention; referral to off-site services may create access barriers. Future studies should focus on understanding whether those who experience distress can and do access cancer-specific psychosocial care, and barriers to doing so.

To evaluate the efficacy and safety of 5-aminolevulinic acid photodynamic therapy (5-ALA PDT) for cervical squamous intraepithelial lesion (SIL). We systematically searched PubMed and other databases to compare the effectiveness of 5-ALA PDT with observation, ablation, and conization. Outcomes included overall response rate (ORR), complete remission (CR) rate, HPV clearance rate, and other relevant endpoints. Single-arm analyses were additionally performed by lesion grade. A total of 3,354 patients were included across 19 studies. The ORR with PDT was significantly higher than with observation (OR = 10.27, 95% CI: 3.87-27.27) and ablation (OR = 2.57, 95% CI: 2.00-3.30), with no significant difference compared with conization. At 6 months, HPV clearance rate was significantly higher with PDT than with observation (OR = 11.47, 95% CI: 3.16-41.68) and ablation (OR = 1.46, 95% CI: 1.01-2.13), but was comparable to conization. PDT also associated with a lower risk of progression than observation (OR = 0.19, 95% CI: 0.11-0.34) and a lower recurrence rate than ablation (OR = 0.30, 95%CI 0.14-0.63). ORR was 0.86 (95% CI: 0.83-0.89) in LSIL and 0.91 (95% CI: 0.87-0.94) in HSIL, with a significant difference between groups (P = 0.0289). 5-ALA PDT for cervical SIL improves ORR and HPV clearance compared with observation and ablation, with efficacy comparable to conization and only mild adverse events. It is effective across lesion grades, with slightly better responses in HSIL.

Requests for tissue donation for research are often made at times of heightened vulnerability, particularly around diagnosis and surgery. This study explored patient experiences of tissue donation discussions, perspectives on consent, and the acceptability of digital decision support in primary craniospinal tumour research.

A UK national online cross-sectional survey was conducted with 50 adults with a primary brain tumour or spinal sarcoma. The survey was developed with patient and public involvement; six patient contributors reviewed the initial questionnaire before launch. Descriptive statistics summarised closed responses, and open-text comments were grouped descriptively to contextualise quantitative findings. Reporting was informed by STROBE guidance.

Just over half of participants reported being invited to donate tissue for research (26/50, 52%). Respondents strongly preferred tissue donation to be discussed at or after a clinic appointment, and none selected the day of surgery as the preferred time. Among invited respondents, most reported that information was easy to understand (22/26, 85%), that they had an opportunity to ask questions (23/25, 92%), and that they had sufficient time to consider the decision (23/26, 88%). Sixteen of 26 invited respondents (62%) discussed the decision with family or friends; among invited respondents who had not done so, 7/10 (70%) would have liked the opportunity. Interest in a secure digital adjunct was high (46/49, 94%).

Overall experience was generally positive, but the data identify specific, practical opportunities to strengthen consent support in rare craniospinal tumour pathways, including appropriate timing, clear and revisitable information, opportunities for question-asking, and resources that support family-inclusive decision-making.