Hip fractures (HF) are among the most serious consequences of osteoporosis. Many individuals who subsequently sustain a HF may already fulfill recognized criteria for fracture risk assessment, bone mineral density (BMD) evaluation, or anti-osteoporosis treatment before the event occurs, yet remain unidentified and untreated. We aimed to quantify these missed opportunities for osteoporosis management prior to fragility HF occurrence. We performed a cross-sectional analysis of 1,103 patients aged ≥ 50 years hospitalized for fragility HF and evaluated within a Fracture Liaison Service. Pre-fracture fracture risk was retrospectively estimated using FRAX^® based on clinical risk factors only, excluding the index HF. Eligibility for anti-osteoporosis treatment and BMD assessment was evaluated according to international recommendations and national reimbursement criteria. Only 82 patients (7.4%) had received anti-osteoporosis therapy before the index HF. Female sex, rheumatologic diseases, chronic glucocorticoid therapy, and previous fractures were independently associated with prior treatment, whereas diabetes mellitus was negatively associated. Among patients aged 50-90 years, 69.6% would have been classified as being at high or very high fracture risk before fracture occurrence, yet only 10.2% had received anti-osteoporosis therapy. Among the remaining patients, 90.3% already met indications for BMD assessment. Most patients who sustain a HF already meet recognized criteria for osteoporosis assessment or treatment but remain untreated. These findings highlight substantial missed opportunities for fracture prevention and support earlier identification and management of individuals at increased fracture risk.

Individuals with schizophrenia are at increased risk of type 2 diabetes and diabetes-related complications. Whether the detection of hyperglycemia in individuals with schizophrenia is followed by timely clinical action remains insufficiently understood. We hypothesized that glucose-lowering drug (GLD) treatment would be initiated later in individuals with schizophrenia with elevated glycated hemoglobin (HbA1c) than in matched individuals without schizophrenia, and that this delay would be reflected in worse HbA1c trajectories.

We identified all individuals with schizophrenia aged ≥30 years at the time of the first elevated HbA1c (≥48 mmol/mol) in nationwide Danish registers. These individuals were matched on age, sex, year of elevated HbA1c, and baseline HbA1c with up to five individuals without schizophrenia. In the year following the detection of elevated HbA1c, we compared time to GLD treatment between individuals with and without schizophrenia using a Cox proportional hazard model. Mean HbA1c levels over time were illustrated graphically and compared using linear mixed-effects models.

We identified 1527 individuals with schizophrenia and 7492 matched comparison individuals. In the year following detection of elevated HbA1c, schizophrenia was associated with a slower rate of GLD treatment initiation (hazard rate ratio [HRR] = 0.88, 95% confidence interval [CI]: 0.81-0.94). Consistently, HbA1c decreased more slowly among individuals with schizophrenia. Notably, schizophrenia was associated with a slower rate of GLD treatment initiation among males (HRR = 0.82, 95%CI: 0.74-0.90) but not females (HRR = 0.99, 95%CI: 0.87-1.11).

Schizophrenia was associated with a slower rate of GLD treatment initiation and slower reductions in HbA1c following detection of elevated HbA1c, particularly among males.

Diabetes is one of the most prevalent comorbidities among patients with head and neck cancer (HNC), and its burden is disproportionately higher in Asian American, Native Hawaiian, and Pacific Islander (ANHPI) populations. However, the incidence and risk factors for diabetes among ANHPI HNC patients remain unknown. The aim of our study was to examine the incidence and risk factors of developing Type 2 diabetes among older (≥ 66 years of age) ANHPI HNC patients in the United States, as well as differences across ANHPI subgroups. Using the SEER-Medicare linked database, we identified Non-Hispanic White (NHW) and ANHPI patients diagnosed with HNC from 2000 to 2019. Fine-Gray subdistribution hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for diabetes among ANHPI subgroups compared to three reference groups: NHW, East Asian, or Chinese HNC patients. The study included 2862 older NHW, 423 East Asian, 211 Southeast Asian, 139 South Asian, and 68 NHPI HNC survivors. South Asian HNC survivors had the highest incidence of Type 2 diabetes (19.4%) compared to other ANHPI subgroups (7%-14%) and non-Hispanic White (NHW) HNC survivors (7.5%) > 1 year after cancer diagnosis. East Asian (HR: 2.04; 95% CI: 1.36, 3.06; incidence: 14.0%) and South Asian (HR: 3.34; 95% CI: 1.86, 6.00) HNC survivors had higher diabetes risks compared to NHW HNC survivors > 1 year after cancer diagnosis, notably among Chinese and Asian Indian/Pakistani HNC survivors. Our results showed a 2- to 3-fold difference in risk of Type 2 diabetes for ANHPI HNC survivors compared to NHW HNC survivors. There was a high incidence of diabetes, especially in the South and East Asian HNC patients, highlighting the need for prevention in these groups. Small sample sizes among ANHPI subgroups with fewer than 100 HNC patients (Korean, Vietnamese, NHPI) warrant cautious interpretation of these findings.

Schisandra chinensis polysaccharide (SCP) has demonstrated antidiabetic properties in previous studies; however, the mechanisms underlying its regulation of autophagy in pancreatic protection remain poorly understood. This study investigated how SCP modulates autophagic pathways to alleviate diabetic pathology.

Diabetic rats were administered SCP orally, followed by histopathological and biochemical assessments of pancreatic islet function and tissue damage. Beta-TC-6 pancreatic β-cells were exposed to SCP to evaluate cellular viability, insulin secretion, and autophagic processes using immunohistochemistry, Western blotting, immunofluorescence, and transmission electron microscopy.

SCP dose-dependently attenuated diabetes-associated weight loss, reduced hyperglycemia, and improved β-cell function. Histological examination revealed amelioration of pancreatic islet disorganization, diminished collagen deposition, and reduced basement membrane thickening. Mechanistically, SCP enhanced autophagic activity in pancreatic tissues and Beta-TC-6 cells by inhibiting the PI3K/AKT/mTOR signaling cascade, with high-dose SCP exhibiting efficacy comparable to that of metformin. Chloroquine co-treatment abolished these effects, confirming autophagy dependence.

This study demonstrates that SCP alleviates diabetes by restoring β-cell function and inducing protective autophagy via the inhibition of the PI3K/AKT/mTOR pathway. These findings indicate SCP as a potential candidate for diabetes therapy.

Retroperitoneal sarcomas (RPS) pose major technical challenges because of their size, anatomical complexity, and need for multivisceral resection. We evaluated the feasibility of a standardized robotic approach for right- and left-sided retroperitoneal sarcoma (RPS) compartmental resection using the da Vinci Xi system in tumour-free human cadavers. In a two-phase IDEAL-D Stage 0 cadaveric study, two sarcoma surgeons first compared four trocar configurations in two cadavers to identify optimal port templates (Phase 1). Complete six-stage compartmental resection following a standardised protocol was then performed once on each side in a third cadaver (Phase 2). The confirmatory dissection was assessed with a 5-point anatomical reach rating per predefined landmark, an adapted System Usability Scale (SUS), and a structured safety surrogate log. Phase 1 yielded a horizontal suprasymphysial port template for the right side and an oblique xiphoid-to-right-lower-quadrant template for the left. In Phase 2, all six stages were completed bilaterally; all predefined landmarks were reached (pooled median reach 5/5, range 3-5; inter-rater agreement 90%). Three-dimensional visualization and instrument articulation were rated highly, the platform scored 72.5/100 on the System Usability Scale, and no unintended major injury occurred. A robotic platform can reproduce the anatomical exposure required for the six-stage compartmental resection concept in a tumour-free cadaveric model, using side-specific port templates. Because no tumour was present, these findings address anatomical access rather than oncological resection. Investigation in tumour-bearing models is required before clinical evaluation, which must remain restricted to highly selected patients at expert centres.

Non-functioning pancreatic neuroendocrine tumors (NF-pNETs) show a variable prognosis. Despite 40-60% of patients remaining recurrence-free after surgery, guidelines recommend ≥ 10 years of follow-up. Recent studies identify prognostic subgroups based on ATRX, DAXX, and MEN1 mutations and chromosomal aneuploidy, highlighting a subgroup with favorable prognosis. We aimed to classify resected NF-pNETs into molecular subgroups using ATRX, DAXX, and Menin immunohistochemistry as surrogate markers for genomic status. To do so, we retrospectively collected resected primary sporadic grade 1 and 2 NF-pNETs without synchronous metastases from five international local pathology archives. ATRX, DAXX, and Menin immunohistochemistry was performed, and tumors were categorized into three groups: ATRX-DAXX-loss-group (ATRX or DAXX loss), isolated-Menin-loss-group (Menin loss without ATRX and DAXX loss), and unspecified-group (retained Menin, ATRX and DAXX). Kaplan-Meier analysis evaluated prognostic differences, and multivariable Cox regression assessed the added value of molecular subgroups beyond established prognostic factors. In total, 139 patients with grade 1 (64%) and 2 (36%) NF-pNETs were included. The median follow-up was 28 months (range 0-195) and recurrences occurred in 20% (28/139). No recurrences occurred in the isolated-Menin-loss-group (0/33), versus 12.5% (8/64) in the unspecified-group and 48% (20/42) in the ATRX-DAXX-loss-group. Kaplan-Meier analysis showed better recurrence-free interval in the isolated-Menin-loss-group than other subgroups (P < 0.001). In univariate analysis, the isolated-Menin-loss-group had a lower recurrence hazard (HR 0.03; 95%CI: 0.00-0.55; P = 0.018), than other subgroups, with little change in the hazard ratio after adjustment, but loss of significance. In conclusion, molecular subclassification by immunohistochemistry identifies NF-pNET patients with a low risk of recurrence and lays the groundwork for future prospective studies assessing genetics-based risk stratification as a tool for guiding clinical management.

Intra-tumor heterogeneity in proliferation rates fundamentally influences cancer progression and treatment resistance. To investigate how continuous phenotypic variation shapes eco-evolutionary dynamics, we develop a phenotype-structured partial differential equation framework that explicitly models proliferation heterogeneity as a dynamic trait. Our model integrates three key biological principles: (1) phenotypic diffusion capturing heritable variation in proliferation rates, (2) global resource competition enforcing density-dependent growth constraints, and (3) an experimentally grounded life-history trade-off linking elevated proliferation to increased mortality. Using adaptive dynamics, we derive the optimum proliferation rate in a growing tumor, showing that the optimal phenotype dynamically shifts toward slower proliferation as tumors approach carrying capacity under control condition. We perform in silico treatment simulations for four different treatment regimes (uniform targeting, low-, mid-, and high-proliferation targeting) to show how therapeutic selective pressures reshape fitness landscapes. While all treatments slow down tumor growth, they induce divergent evolutionary trajectories. We connect these dynamics with changes in mean proliferation rates during and after treatment. Our work establishes a predictive, evolutionarily grounded framework for understanding how therapy reshapes tumor proliferation landscapes, offering a mechanistic basis for designing strategies that anticipate and counteract adaptive resistance.

Genetic counselling for hereditary cancer predisposition has evolved substantially over more than three decades, driven by advances in genomic technologies and the growing use of tumour and germline testing. These developments have expanded access to hereditary cancer testing, treatment and prevention, while also introducing new clinical, psychosocial and system-level challenges. This review examines the transition from traditional specialist-led genetic counselling to mainstreamed testing pathways. Using Lynch syndrome as a paradigm, we explore how service redesign, personalised risk communication and patient experience intersect in contemporary hereditary cancer care. This invited review synthesises clinical, academic and patient perspectives on the evolution of hereditary cancer genetic counselling. Lived experiences of Lynch syndrome were incorporated through patient and public involvement contributors involved in manuscript development and interpretation. Mainstreamed testing has expanded access to genomic information and strengthened opportunities for cascade testing and prevention within families. However, it has also increased testing volumes, complexity of results interpretation and reliance on non-genetics clinicians. As a result, effective care requires close coordination between genetics and cancer services, alongside support for shared decision-making, family communication and psychosocial needs. This review uniquely integrates clinical evidence and lived experience to highlight how mainstreaming has transformed the delivery of hereditary cancer genetic counselling but not the need for specialist genetics expertise. Lynch syndrome illustrates how genomics can be integrated into routine cancer care while maintaining personalised counselling and family-centred follow-up. These principles are relevant across hereditary cancer predispositions and inform the future development of genetic counselling services.

The optimal extent of resection (EOR) required to minimize recurrence risk in craniopharyngioma remains unclear. The objective of this study was to quantitatively evaluate postoperative tumor volume and EOR as determinants of progression-free survival (PFS) in surgically treated adamantinomatous craniopharyngiomas.

We retrospectively measured pre- and post-surgical tumor volumes in 60 patients using manual MRI-based segmentation. None received planned adjuvant radiotherapy. The median follow-up duration was 5 years. Clinical and volumetric variables were analyzed using Cox proportional hazards regression. Time-dependent receiver operating characteristic analysis at 3 years was also performed.

Tumor progression/recurrence occurred in 60% of patients. On univariable analysis, EOR was associated with improved PFS (HR 0.981 per 1% increase; 95% CI 0.966-0.997; p = 0.018), whereas increasing TV^solid (HR 1.178 per 1 cc increase; 95% CI 1.041-1.334; p = 0.010), residual cystic disease (HR 3.600; 95% CI 1.788-7.249; p < 0.001), and preoperative tumor volume (HR 1.006 per 1 cc increase; 95% CI 1.000-1.013; p = 0.044) were associated with increased progression risk. Given collinearity between EOR and TV^solid, separate multivariable models were constructed. EOR and TV^solid remained significantly associated with progression in their respective models, and residual cystic disease was associated with progression in both models. Optimism-corrected AUCs were 0.777 (95% CI, 0.649-0.927) for EOR and 0.813 (95% CI, 0.691-0.953) for TV^solid.

EOR, TV^solid and the presence of residual cystic disease are independently associated with progression after craniopharyngioma resection. Risk stratification using tumor volumetry may help individualize postoperative decision-making in terms of surveillance versus adjuvant radiotherapy.

Primary Large-B-Cell Lymphoma of the CNS (PCNS-LBCL) is a rare, aggressive tumor often sensitive to corticosteroid therapy (CST). This multicenter study investigated the spectrum of radiological responses to routine CST and evaluated its impact on patient prognosis.

The researchers utilized a prospective cohort of 18 patients for volumetric MRI analysis and a combined prospective-retrospective cohort of 31 patients for 2D tumor analysis. Patients received CST post-biopsy, with follow-up MRIs performed on the seventh day (median) after surgery. The study correlated radiological responses with CST dosage, LDH levels, and overall survival (OS) using Kaplan-Meier and Firth-corrected Cox regression.

In the prospective cohort, 83.3% of tumors regressed with a median regression of 40%, while 16.7% progressed despite CST resulting in a median progression of 46%. These changes were not dose-dependent, but there were indications of a correlation with LDH levels. Patients showing regression had a median OS of 31.4 months, compared to 3.9 months for tumors progressing during CST (p = 0.015). Firth-corrected Cox regression showed, despite the small sample size, that radiological response (p = 0.02) could be a promising prognostic factor in a model including age, type of therapy and Karnofsky performance status.

This study provides the first structured description of the range of radiological responses of PCNS-LBCL to CST. Furthermore, we found exploratory indications that radiological response to CST may predict outcome indicating shared sensitivity to other cytotoxic drugs. Further studies are necessary to fully understand diagnostic and prognostic implications of CST sensitivity in PCNS-LBCL and its underlying mechanisms.