Diabetic foot ulcers (DFUs) are a major source of morbidity among individuals with diabetes mellitus (DM), imposing a substantial burden on healthcare systems. Our institution established a multidisciplinary service aiming to facilitate early specialist intervention for DFU management. This study examined demographic and cardiovascular risk profiles associated with DFU, the clinical burden of DFU in a large population, and the impact of our multidisciplinary specialist care on clinical outcomes.

We conducted a retrospective cohort study using the SingHealth Diabetes Registry on patients aged ≥18 years with DM from a tertiary centre between August 2018 and December 2023. There were 22,830 individuals with DM analysed; 2527 (11.1%) were diagnosed with DFU. Baseline demographics and clinical characteristics data were collected. Subgroup analyses were performed among patients attending the Diabetic Rapid Evaluation and lower limb Amputation Management (DREAM) clinic to evaluate differences in outcomes.

Individuals with DFU were older, had a longer duration of DM, and had a significantly higher prevalence of cardiovascular and metabolic comorbidities compared with those without (p < 0.001). After multivariable adjustment, DFU was independently associated with increased mortality and prolonged hospitalization. Within the DFU cohort, referral to the multidisciplinary DREAM clinic in our institution was independently associated with a significantly reduced risk of major LEA, but not minor LEA, after multivariable adjustment.

DFU represent a substantial clinical burden in Singapore and are independently associated with adverse outcomes. Beyond preventive screening, early multidisciplinary, multi-specialty management is critical to reduce amputations, hospitalization, and hence mortality.

Epithelial ovarian cancer (EOC) incidence and mortality increase with age, driven in part by chronic inflammation, diminished T cell output, and heightened regulatory T cell (Treg) mediated immunosuppression. In aged EOC-bearing mice, we observed reduced survival, accompanied by impaired CD4⁺ and CD8⁺ T cell responses and a marked expansion of FOXP3⁺ Tregs exhibiting elevated IL-10 and TGFβ expression. Metabolic profiling revealed enhanced oxidative phosphorylation in Tregs from aged mice, along with a fivefold increase in intracellular succinate levels. This accumulation of succinate within the aged tumor microenvironment was found to potentiate Treg suppressive function. Notably, pharmacologic inhibition of α-ketoglutarate dehydrogenase reversed this effect, restoring effector T cell activity. These findings highlight succinate-driven metabolic reprogramming as a central mechanism of age-related Treg dysfunction in EOC and suggest that targeting succinate metabolism may offer a promising strategy to rejuvenate antitumor immunity in elderly patients.

The efficacy of osimertinib in patients with postoperative recurrent non-small-cell lung cancer (NSCLC) compared to those with Stage IV NSCLC harboring epidermal growth factor receptor (EGFR) mutations remains unclear.

This study evaluated the efficacy of osimertinib in patients with postoperative recurrent EGFR-mutated NSCLC. We retrospectively evaluated patients with NSCLC harboring EGFR mutations (exon 19 deletion or L858R mutation) who received osimertinib between September 2018 and July 2022 at a single institution. The efficacy of osimertinib was compared between patients with postoperative recurrent NSCLC (postoperative group) and those with Stage IV NSCLC (Stage IV group).

Among a total of 172 patients treated with osimertinib, 52 were classified into the postoperative group and 120 into the Stage IV group. The response rate (58.1% vs. 61.8%, p = 0.836) and progression-free survival (hazard ratio [HR]: 0.854, 95% confidence interval [CI]: 0.558-1.306, p = 0.465) were not significantly different between the postoperative and Stage IV groups. Overall survival (OS) was significantly longer in the postoperative group than in the Stage IV group (median: 39.2 months and 28.5 months, respectively; HR: 0.521, 95% CI: 0.293-0.927, p = 0.024). In the multivariable analysis of OS, postoperative recurrent disease and performance status were independent favorable prognostic factors.

Postoperative recurrent disease was an independent favorable prognostic factor in patients with NSCLC harboring EGFR mutations treated with osimertinib.

Allostatic load (AL) reflects the cumulative physiological burden of chronic stress across cardiovascular, metabolic, immune, and renal systems. While AL has been implicated in cancer development, evidence in Asian populations remains limited. We examined sociodemographic and lifestyle factors of AL and its association with colorectal cancer (CRC) risk in a multiethnic Asian cohort.

Data were drawn from 30,443 Chinese, Malay, and Indian adults (≥ 18 years) between 2004 and 2016. Participants were followed from baseline assessment until CRC diagnosis, death, or end of follow-up, whichever occurred first (median follow-up: 7.2 years). AL was derived from nine biomarkers, with high-risk cutoffs set at the 75th percentile (≤ p25 for HDL). High AL was defined as a score ≥ 3. CRC incidence was ascertained through linkage with the Singapore Cancer Registry. Modified Poisson regression was used to identify factors associated with high AL, and Cox proportional hazards models assessed associations with incident CRC. CRC incidence was ascertained through linkage with the Singapore Cancer Registry.

During follow-up, 162 CRC cases were observed; 60.3% of participants had high AL. Older age, male sex, Malay and Indian ethnicity, lower education, unemployment, diabetes, low physical activity, and prolonged sitting were significantly associated with higher AL scores. High AL was associated with increased CRC risk after adjustment for age, sex, ethnicity, and cohort (aHR = 1.53; 95% CI = 1.10, 2.14). The association remained similar in models additionally adjusting for SES, smoking, history of diabetes, or physical activity and sitting time.

These findings are consistent with prior research in Western populations and highlight AL as a potential biomarker for identifying individuals at increased CRC risk. Incorporating AL into population health strategies may support earlier detection and targeted prevention in Asian settings.

The 5-year survival rate for hepatocellular carcinoma (HCC) is stage-dependent, yet existing models lack accuracy in predicting hepatitis B virus-associated HCC (HBV-HCC). We therefore aimed to develop and validate an interpretable machine learning (ML) model integrating multidimensional biomarkers for HBV-HCC risk stratification.

This retrospective multicenter study included 3568 participants (1872 HBV-infected and 1696 HBV-HCC). Patients from Mengchao Hepatobiliary Hospital were divided into training and validation sets (3:1 ratio), while those from Eastern Hepatobiliary Surgery Hospital and the First Affiliated Hospital of Xiamen University formed the external validation set. Five key predictors were identified through random forest, LASSO regression, and XGBoost methods. Seven ML models were evaluated using area under the curve (AUC), sensitivity, specificity, accuracy, and F1-score, with the top model compared against previous models (GALAD, C-GALAD, C-GALAD II, and ASAP).

Key predictors were log₁₀DCP (mean SHAP value 1.784), log₁₀HBVDNA (1.063), log₁₀ALT (0.753), AFP-L3% (0.444), and log₁₀AFP (0.392). The XGBoost model achieved AUCs of 0.985 (95% CI: 0.981-0.989) in the training set, 0.978 (0.969-0.987) in the validation set, and 0.942 (0.911-0.973) in the external validation set. XGBoost significantly outperformed previous models in both the training and validation sets (DeLong test; p < 0.001). In the external validation set, XGBoost demonstrated superior individualized risk prediction accuracy (IDI = 0.228), net clinical benefit, calibration, and high-risk patient identification compared to the ASAP model. An interactive web tool was developed to facilitate clinical implementation.

We developed a novel diagnostic model for HBV-HCC that demonstrates higher accuracy in identifying HBV-HCC compared to existing models.

This study evaluated the aggregate index of systemic inflammation (AISI) for predicting postoperative recurrence in endometrial cancer (EC). A total of 1557 patients were enrolled and divided into training (n = 1030) and validation (n = 527) cohorts. The optimal AISI cutoff was determined by ROC curve analysis. Multivariate Cox regression identified eight independent prognostic factors for recurrence-free survival (all p < 0.05): age ≥ 60 (HR = 1.683, 95% CI 1.191-2.377), FIGO stage III (HR = 2.346, 95% CI 1.480-3.718), LVSI (HR = 1.792, 95% CI 1.226-2.618), CA125 ≥ 35 U/mL (HR = 1.457, 95% CI 1.030-2.062), deep myometrial invasion (HR = 2.021, 95% CI 1.393-2.930), histological type II (HR = 1.798, 95% CI 1.219-2.653), p53 abnormal (HR = 3.252, 95% CI 2.142-4.936), and high AISI (HR = 2.492, 95% CI 1.714-3.625). A prognostic nomogram incorporating these factors was constructed and validated, demonstrating superior predictive accuracy compared to conventional methods. Adjuvant therapy significantly improved outcomes in high-risk patients identified by the nomogram. This comprehensive tool enhances risk stratification and may guide personalized treatment planning.

Colorectal cancer (CRC) screening rates remain below recommended clinical guidelines, especially among people of color. This study aimed to assess CRC screening rates, identify barriers, and develop improvement strategies in racially diverse communities using community-based participatory design, engaging Community Health Action Teams (CHATs).

This mixed-methods study employed surveys and focus groups, with data collection instruments co-designed with community members to ensure relevance and accuracy. A random sample of households with screen-eligible residents received a survey, focusing on assessing screening rates and identifying facilitators and barriers to CRC screening. Focus groups used snowball sampling in the same communities to deepen understanding through qualitative insights.

Of 1,798 survey respondents, 81% reported participating in CRC screening, with 69% being up to date. Awareness of CRC's preventable and treatable nature, when detected early, (b = 0.647, p < 0.001, OR = 1.91); understanding its asymptomatic potential (b = 0.345, p < 0.001, OR = 1.42); and recognition of its ranking as the second most deadly cancer (b = 0.354, p = 0.007, OR = 1.42) were significant predictors of screening adherence. Knowledge of at-home tests increased compliance with screening (b = 0.752, p < 0.001, OR = 2.12). Barriers reported by unscreened respondents included a lack of symptoms (19%), absence of motivation (19%), being asymptomatic (20%), and for insured individuals, a lack of physician orders for screening (19%). Insights from focus groups, including 65 participants, revealed multi-level barriers, echoing survey findings where relationships with medical providers emerged as the strongest predictor of screening participation.

The study informed the creation of six key outreach messages and two strategies co-led by CHATs, emphasizing CRC screening importance, test options, and cost considerations. Suggested strategies include organizing community events to raise awareness and enhancing direct provider-to-patient communication to encourage screening uptake.

Most patients with head and neck squamous cell carcinoma (HNSCC) present with locally advanced disease at the time of diagnosis. Current standard treatment strategies mainly include surgery-based multimodal therapy or concurrent chemoradiotherapy. However, existing treatment approaches remain insufficient to meet the therapeutic needs of patients with locally advanced HNSCC. Surgical resection often requires extensive removal of tissues, resulting in functional impairment and substantial deterioration in quality of life. Although concurrent chemoradiotherapy is widely used, patients still face a high risk of early recurrence. The addition of induction chemotherapy may reduce organ dysfunction, but it has not demonstrated a clear improvement in long-term survival and is associated with considerable treatment-related toxicity. In recent years, immunotherapy has shown promising efficacy across multiple malignancies and has reshaped treatment paradigms in certain tumor types. Nevertheless, its application in HNSCC has largely been limited to patients with recurrent or metastatic disease. Based on the theoretical rationale for combining immunotherapy with radiotherapy and chemotherapy, increasing attention has been directed toward advancing the timing of immunotherapy to the neoadjuvant setting. Early integration of immunotherapy may help overcome immunosuppressive barriers, modulate the tumor immune microenvironment, induce durable antitumor immunity, and remodel the immune landscape, thereby promoting tumor regression. This approach has the potential to achieve tumor downstaging, increase resectability, preserve organ function, and improve patients' quality of life. This review summarizes and analyzes the biological mechanisms, current clinical evidence, and existing limitations of neoadjuvant immunotherapy in patients with HNSCC, with the aim of providing safer and more effective treatment options for locally advanced disease. Future perspectives on the development and optimization of neoadjuvant immunotherapy strategies in HNSCC are also discussed.

Neoadjuvant immunotherapy has demonstrated favorable efficacy in patients with resectable non-small cell lung cancer (NSCLC). However, its clinical application remains limited by the lack of reliable and non-invasive biomarkers. Although existing histological biomarkers such as programmed death-ligand 1 (PD-L1) and tumor mutation burden (TMB) can be used for reference, they rely on invasive sampling and are susceptible to tumor heterogeneity. This study evaluated a series of peripheral blood inflammation-related indicators, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and interleukin-6 (IL-6), to explore their potential as non-invasive predictive and prognostic biomarkers for NSCLC. Furthermore, a prediction model based on the above indicators was constructed to provide a practical and feasible tool for optimizing individualized clinical management in patients with resectable NSCLC.

A retrospective analysis was conducted on 144 patients with resectable (stage IB-IIIB) NSCLC who underwent surgery after receiving neoadjuvant immunotherapy combined with chemotherapy at the Second Xiangya Hospital, Central South University, between 2019 and 2022. Peripheral blood-related indicators at baseline and before surgery were collected. Clinical data that might influence treatment efficacy were also recorded, including age, sex, body mass index, smoking history, pathological type, clinical stage, and use of immune checkpoint inhibitors. The relationships between peripheral blood inflammatory indicators (NLR, LMR, PLR, SII, and IL-6) and objective response rate (ORR), pathological complete response (pCR), major pathological response (MPR), and disease-free survival (DFS) were analyzed. Receiver operating characteristic (ROC) curves were used to determine optimal cutoff values for each indicator. A prediction model for the efficacy of neoadjuvant immunotherapy in NSCLC was constructed using least absolute shrinkage and selection operator (LASSO) regression combined with a multivariate Cox proportional hazards model.

The median age of included patients was 58 years, and 91.0% (131/144) were male. Among pathological types, squamous cell carcinoma accounted for 74.3% (107/144), adenocarcinoma for 22.9% (33/144), and other types for 4 cases. The overall ORR, pCR, and MPR rates were 69.2%, 42.4%, and 61.5%, respectively. Univariate analysis showed that patients with squamous cell carcinoma had significantly higher ORR (P=0.007), pCR (P=0.027), and MPR (P=0.019). Lower baseline LMR was associated with a higher ORR. Elevated baseline PLR was significantly associated with pCR (P=0.014) and MPR (P=0.043). Increased baseline SII (P=0.015) and IL-6 (P=0.043) were associated with higher MPR rates. Multivariate analysis showed that squamous cell carcinoma was an independent predictor of MPR (OR=7.34, 95% CI 1.02 to 52.51, P=0.047), and lower baseline LMR was an independent predictor of ORR in NSCLC (OR=0.21, 95% CI 0.05 to 0.92, cutoff value 3.12; P=0.04). Further survival analysis indicated that low baseline NLR (HR=0.363, P=0.014), low preoperative LMR (HR=0.260, P=0.018), and high preoperative SII (HR=0.278, P=0.003) significantly reduced the risk of DFS. A prediction model including 9 factors (age, pathological type, baseline NLR, baseline neutrophils, baseline IL-6, baseline monocytes, preoperative lymphocytes, preoperative SII, and preoperative LMR) was established for predicting the efficacy of neoadjuvant immunotherapy in NSCLC, with an AUC of 0.818.

Neoadjuvant immunotherapy demonstrates favorable clinical efficacy in patients with NSCLC, particularly in those with squamous cell carcinoma. Meanwhile, peripheral blood inflammation-related indicators may serve as important biomarkers for predicting the efficacy and prognosis of neoadjuvant immunotherapy in NSCLC.

To examine factors influencing breast cancer liver metastases (BCLM) and assess the impact of underlying liver diseases (nonalcoholic fatty liver and HBsAg infection) on BCLM development.

Patients diagnosed with breast cancer at four affiliated hospitals in China between 2014 and 2024 were included. Logistic regression was used to identify factors associated with BCLM. Propensity score matching (PSM) and Kaplan-Meier analyses were performed to evaluate the prognostic impact of underlying liver diseases.

A total of 3653 breast cancer patients were included, among whom 387 (11%) were identified with liver metastasis (LM). Factors including nonalcoholic fatty liver (NAFL) and HBsAg (hepatitis B surface antigen) infection were independently associated with a lower risk of BCLM (NAFL: p < 0.001; HBsAg: p = 0.011). Subsequent analysis stratified by the severity of NAFL indicated that mild NAFL was associated with a lower risk of BCLM, whereas moderate-to-severe NAFL was associated with a higher risk of BCLM (p = 0.01 and p = 0.02, respectively). Survival analysis showed that HBsAg infection was associated with significantly longer liver metastasis-free survival (LMS) and overall survival (OS) (both p < 0.01). Further survival analysis, stratified by the presence of NAFL, revealed that mild NAFL could prolong both LMS and OS, while moderate-to-severe NAFL not only shortened LMS, but also shortened OS after LM (OSLM), so that OS was significantly shortened (p < 0.01 for mild NAFL; p < 0.05 for LMS and p < 0.01 for OSLM and OS in moderate-to-severe NAFL). Furthermore, consistent results on OS and OSLM were obtained even after employing 1:1 PSM to account for other covariate interferences (both p < 0.01).

Mild NAFL may be associated with reduced LM and improved prognosis, while moderate-to-severe NAFL appears to correlate with increased LM risk and worse clinical outcomes. Furthermore, HBsAg infection may be linked to suppressed LM and extended OS for patients with BCLM.