Notably, metabolic dysregulation stands as a prominent characteristic of cancer. The identification of biomarkers through blood metabolomics presents a novel approach for the diagnosis and treatment of gastric cancer. We performed a 2-sample Mendelian randomization (MR) analysis to assess the causality from genetically proxied 486 blood metabolites to gastric cancer. In this study, MR analysis was employed to assess the correlation between 486 serum metabolites and gastric cancer. Five different methods, namely inverse-variance weighting, MR-Egger method, weighted median method, simple mode method, and weighted mode method, were utilized for evaluation. Sensitivity analysis was conducted, encompassing heterogeneity testing, horizontal pleiotropy testing, and leave-one-out testing. Furthermore, the study encompassed linkage disequilibrium score (LDSC) genetic association and directionality assessment, metabolic pathway analysis, and reverse MR analysis. The findings revealed the presence of 21 metabolites, comprising 14 known metabolites and 7 unidentified metabolites that potentially play a causal role in gastric cancer. The reverse MR and directional assessment indicated the absence of reverse causality between gastric cancer and the candidate metabolites. Moreover, the LDSC genetic association solely identified a genetic association between gastric cancer and the unknown metabolite X-11315. Additionally, the metabolic pathway analysis identified 3 pathways that may be implicated in the development of the disease. We observed negative correlations between 12 serum metabolites and the risk of gastric cancer, while 9 serum metabolites showed positive correlations. Notably, 3-methyl-2-oxovalerate exhibited promising therapeutic potential, whereas 2-aminobutyrate displayed a higher risk factor. The integration of genomics and metabolomics in our investigation offers novel insights into the underlying mechanisms of gastric cancer, thereby holding significant implications for the screening and prevention of this disease.

Ewing sarcoma (ES) mainly affects children and adolescents; thus, treatment protocols for adult patients are adapted from pediatric protocols. Long treatment durations often lead to treatment discontinuation for adults. This single-center retrospective study evaluated real-world outcomes and compliance with standard chemotherapy regimens in adult patients with localized ES. Adult patients diagnosed with localized ES who underwent curative intent treatment between 2007 and 2022 were retrospectively analyzed. Patients who were intended to receive the vincristine, adriamycin, and cyclophosphamide (VAC)/(ifosfamide, etoposide) regimen, consisting of 18 cycles along with local treatment, were included in this study. Adherence to the treatment protocol and outcomes were evaluated. Event-free survival (EFS) and overall survival were calculated, and predictors of treatment completion were assessed. A total of 31 patients were analyzed. Median age was 28 years (range, 18-71 yr); 17 patients were male (54.8%) and 14 were female (45.2%). Fourteen (45.1%) patients underwent surgery, 10 (32.3%) received radiotherapy, and 7 (22.5%) received both treatments. Eighteen (58.1%) patients completed 18 chemotherapy cycles. Patients undergoing surgical resection were likelier to complete all the chemotherapy cycles (odds ratio: 0.117, 95% confidence interval: 0.016-0.835). The estimated 5-year EFS and overall survival rates were 37% and 58%, respectively. Multivariate analysis identified a neutrophil-lymphocyte ratio ≥ 5 as an independent predictor of EFS (hazard ratio: 4.50, 95% confidence interval: 1.52-13.30, P = .006). Compliance with the 51-week-long vincristine, adriamycin (doxorubicin), and cyclophosphamide/ifosfamide and etoposide chemotherapy regimen remains a critical issue for adult patients. Our findings suggest that surgical resection may be associated with better compliance with the chemotherapy protocol, and a neutrophil-lymphocyte ratio of ≥5 may be linked to poorer outcomes.

Herein, we aimed to analyze the final diagnosis in a well-defined cohort of fever of unknown origin (FUO) cases whose erythrocyte sedimentation rate (ESR) was 100 mm/h or more during the admission. The subgroup of the FUO patients with an ESR of 100 mm/h or more during the FUO evaluation, was extracted from the study database of a previously published multicenter study (European Journal of Clinical Microbiology & Infectious Diseases. April 15, 2023;42 (4):387-98). Data for 139 patients (17.6%, 139/788 of the original cohort) who fulfilled the study inclusion criteria, were obtained from 29 centers from 11 countries. Infections, neoplasms, and noninfectious inflammatory diseases were found to be the reason of fever in [n = 74 (53.2%)], [n = 14 (10%)], and [n = 13 (9.3%)] of 139 patients, respectively. Regardless of the diseases subgroup top 6 diseases that were determined to be the reasons of FUO were tuberculosis [n = 15 (10.8%)], HIV/AIDS [n = 13 (9.3%)], urinary tract infection [n = 9 (6.5%)], infective endocarditis [n = 9 (6.5%)], lymphoma [n = 9 (6.5%)], and abscess [n = 9 (6.5%)]. The most common infectious diseases were tuberculosis (15/74, 20.2%), HIV/AIDS (13/74, 17.5%), and infective endocarditis (9/74, 12.1%), along with urinary tract infection [n = 9 (6.5%)] and abscess [n = 9 (6.5%)]. The most common noninfectious inflammatory diseases were adult onset Still disease (3/13, 23%) and giant cell arteritis, also known as temporal arteritis (3/13, 23%), and followed by polyarteritis nodosa (2/13, 15.3%). The most common neoplasm was lymphoma (9/14, 64.2%), followed by lung cancer (2/14, 14.2%). Reason of fever could not be defined in (29/139, 20.8%) patients. The invasive procedures were performed in (64/139, 46%) patients. Gender, age > 50 or not, and income level (high-middle-low) of the participating country were not associated with a significant difference in the final diagnosis category of the FUO case (P > .05). To the best of our knowledge, this is the first study evaluating the FUO in the subgroup of cases with extreme ESR elevation and infectious diseases comprised the most cause of the FUO in this particular subgroup.

Non-Hodgkin lymphoma (NHL) patients are highly susceptible to respiratory infections due to immunosuppression from both the disease and its treatments. Understanding mortality trends and disparities in this population is crucial for improving care and reducing the burden of coexisting conditions. This study analyzed death certificates from the Center of Disease Control Wide-Ranging Online Data for Epidemiologic Research database for individuals aged ≥ 25 years who died between 1999 and 2020 with both NHL and respiratory infections. Age-adjusted mortality rates (AAMRs) and annual percent change were computed by year, gender, age group, race/ethnicity, geographic region, and urbanization status. From 1999 to 2020, 66,986 deaths were related to coexisting NHL and respiratory infections. AAMR decreased from 17.1 to 14.6 per 1,000,000 individuals. A significant decline in AAMR occurred between 1999 and 2018, followed by a significant rise from 2018 to 2020. Men had nearly double the AAMR compared to women. Older adults had the highest AAMRs, followed by middle-aged adults and young adults. Among racial and ethnic groups, non-Hispanic (NH) White individuals had the highest AAMR, followed by NH American Indian or Alaska Natives, Hispanic or Latino, NH Asian or Pacific Islanders, and NH Black or African American populations. Non-metropolitan areas had a higher AAMR than metropolitan areas. The overall AAMR decreased from 1999 to 2020, but a significant rise was observed in recent years. Mortality disparities were notable among men, older adults, NH White individuals, and residents of non-metropolitan areas, underscoring the need for targeted interventions to address these disparities.

Targeting the urgent need for diagnostic biomarkers in breast cancer, the most common female malignancy, this study evaluates the diagnostic and prognostic potential of disulfidptosis-related ferroptosis genes (DRFGs), leveraging the emerging roles of disulfidptosis and ferroptosis in cancer biology. Ferroptosis- and disulfidptosis-related genes of patients with breast cancer were collected from The Cancer Genome Atlas database, then 154 identified prognosis-associated DRFGs were analyzed using Pearson correlation analysis, and developed a DRFG-associated risk model containing 19 DRFGs by applying the least absolute shrinkage and selection operator Cox regression analysis. We then assessed the prognostic performance of the risk model between the high- and low-risk groups. The risk scores and clinical variables were combined to construct a nomogram. Bioinformatics analyses including functional enrichment analysis and protein-protein interaction networks were conducted. Besides, we examined the biological functions, immune checkpoints, and drug sensitivity of the model. Finally, ANO6 overexpression effects on breast cancer cell invasion and metastasis were examined via wound healing and Transwell assays. The high-risk group showed poorer overall survival (OS) rates (P <.001) and lower receiver operating characteristic curve area under receiver operating characteristic values compared to the low-risk group. The results of univariate and multivariate Cox regression analyses confirmed that the established nomogram model served as an independent prognostic indicator. Functional enrichment analysis revealed the involvement of DRFGs in biological processes and signaling pathways beyond disulfidptosis and ferroptosis. The level of expressions of immune checkpoints for TDO2 and PVR were increased in the high-risk group. Drug sensitivity analysis showed that high-risk patients benefited more from AKT.inhibitor.VIII. Moreover, anoctamin 6 overexpression inhibited breast cancer cell invasion and metastasis. This study successfully established a DRFG-related prognostic model for patients with breast cancer, and anoctamin 6 has emerged as a promising therapeutic target for breast cancer.

Klotho, a longevity hormone, exerts diverse anticancer activities. However, evidence regarding the association between serum Klotho and mortalities among cancer survivors is lacking. We examined the association between serum Klotho and the risks of all-cause and cancer mortalities among 1602 cancer adults from the National Health and Nutrition Examination Survey (NHANES) (2007-2016) using multivariate Cox proportional hazard models. The nonlinear relationship was determined using the likelihood ratios test, and the inflection points and 2-piecewise Cox proportional hazards regression models were computed. After a median follow-up period of 84.0 months, U-shaped associations between circulating Klotho and all-cause and cancer mortality were observed (P for nonlinear = .04, .02, respectively), with identified inflection points (pg/mL) of 765.5 for all-cause and 767.6 for cancer mortality. Klotho below these thresholds was inversely associated with all-cause mortality (Hazard ratio, HR, 95% confidence interval, CI) (0.72, 0.53-0.98) and cancer mortality (0.61, 0.39-0.96); Klotho above the threshold showed a trend of positive associated with cancer mortality (1.22, 0.99-1.50). Effect modification of age was apparent (P interaction .007); Klotho was associated positively with cancer mortality risk among participants aged under 60 (1.50, 1.09-2.05). The U-shaped associations between serum Klotho and all-cause and cancer mortality indicate that maintaining an ideal Klotho level in cancer patients could reduce mortality risks. This provides insight into the knowledge of nonlinearity relationship between serum Klotho, a longevity hormone, and survival outcomes in cancer populations.

Although numerous studies have explored the connection between breast cancer surgery and sexual function, research on chemotherapy's temporal effects is limited. Addressing the impact of chemotherapy on sexual dysfunction is critical for improving quality of life. The aim of this study is to investigate changes in sexual function before, during, and after chemotherapy treatment, with a focus on associated factors. A total of 101 sexually active, reproductive-aged women diagnosed with locally advanced breast cancer were included in the study. The sexual dysfunction was evaluated by using the female sexual function index (FSFI) across 3 treatment phases: before, during, and after chemotherapy. Covariates such as age, baseline sexual dysfunction, tumor localization, comorbidity, family history of cancer, and receptor-related factors were analyzed for their influence on score changes during specific periods. A mixed-effects model was employed to evaluate associations and interactions between these variables and sexual function outcomes. Sexual function scores significantly declined across treatment phases. Notable reductions were observed in desire (P < .001), arousal (P < .001), lubrication (P < .001), orgasm (P < .01), and satisfaction (P < .01), while pain scores increased (P < .01). Total FSFI scores significantly dropped during and after chemotherapy (P < .001 and P < .01, respectively). Patients with preexisting sexual dysfunction experienced significantly greater declines in desire, lubrication, and satisfaction, along with more pronounced increases in pain-related discomfort scores, particularly in the FSFI pain subscale (P < .01). Older age, comorbidity, and tumor localization were significantly associated with worsening sexual function, whereas receptor status and histopathology showed no meaningful effect. Our findings confirm a high prevalence of sexual dysfunction among women with breast cancer. These results highlight the multifaceted impact of chemotherapy on sexual function and reveal a clear temporal pattern of changes across treatment phases.

Adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma (MEC) are common malignant tumors of the salivary glands. This study aimed to compare ACC and MEC regarding clinical features and survival factors. Data from all ACC and MEC cases between 2000 and 2020 were extracted from the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Clinical features, overall survival (OS), and disease-specific survival (DSS) were assessed for both cancer types. The study included 1426 ACC cases and 3190 MEC cases. In ACC, 580 patients (40.7%) were male, while in MEC, 1494 patients (46.8%) were male. The mean OS was significantly higher for MEC than for ACC (79.33 ± 58.62 months vs 73.44 ± 57.18 months, P < .001), and the mean DSS was greater for MEC (46.80 ± 39.26 months vs 29.06 ± 29.79 months, P < .001). Independent predictors of worse OS and DSS in ACC included age ≥ 60 years, male gender, submandibular gland involvement, advanced stage, lymph node involvement, distant metastasis, and surgical treatment (all P < .05). This study found that MEC has a significantly better prognosis than ACC, with several common factors linked to worse outcomes for both types, including age ≥60 years and male gender, while surgery acted as a significant protective factor.

Giant cell tumors (GCTs) of the distal ulna are rare. Despite their benign nature, these tumors can exhibit local aggressiveness and have the potential to recur after undergoing conventional treatment involving curettage and bone grafting. For aggressive GCTs, radical resection is more suitable. However, these methods have inherent shortcomings, including a high postoperative recurrence rate and poor mechanical stability. Medical applications of the 3D printing technique are on the rise, with orthopedic repair and reconstruction benefiting from the successful implementation of custom-made prostheses created via 3D printing technology.

A 38-year-old male patient presented to a local clinic complaining of a slow-growing painless on over the ulnar aspect of his left wrist for 1 month. The biopsy confirmed the diagnosis of GCTs and was graded as Campanacci grade III.

The diagnosis of GCTs of the distal ulnar was confirmed by biopsy.

The patient received a 2-month preoperative adjuvant chemotherapy with denosumab. Then, a radical distal ulnar resection and hemiarthroplasty are performed using a 3D-printed prosthesis to reconstruct wrist joint function.

During the 2-year follow-up after the surgery, there were no signs of recurrence, and the left wrist function of the patient remained normal.

A well-fitted personalized prosthesis, made using 3D printing techniques, can effectively reconstruct joint function and bone defects resulting from radical distal ulnar resection due to GCTs. This case demonstrates that the combination of radical resection of a GCT in the distal ulna and reconstruction with a 3D printed personalized prosthesis could lead to successful oncologic and functional outcomes.

Employing multivariate statistical methods, we aimed to construct and validate predictive models for distant metastasis (DM) risk and overall survival (OS) in patients with gallbladder cancer (GBC), using data from the surveillance, epidemiology, and end results database maintained by the National Cancer Institute. These models were visualized through the development of intuitive nomograms. We extracted clinical data of all patients diagnosed with GBC between 2010 and 2015 from the surveillance, epidemiology, and end results database. Both univariate and multivariate logistic regression analyses were conducted utilizing R software (Version 4.2.1) to identify independent risk predictors for DM in GBC patients, and univariate and multivariate Cox regression analyses were performed to determine independent prognostic factors for OS among GBC patients with DM. The discriminatory capabilities and predictive accuracies of the developed nomograms were examined through calibration curves, receiver operating characteristic curves, and decision curve analysis. In our study, 3071 patients with GBC were included, of which 759 (24.72%) had DM. Race, T stage, N stage, and tumor size were identified as independent risk factors for DM, while age, surgical intervention, and chemotherapy were independent prognostic factors for OS in GBC patients with DM. The area under the curve for the prognostic nomogram reached 0.726 and 0.730 in the training and validation sets, respectively. The area under the curve for the same nomogram at 6, 9, and 12 months was 0.744, 0.740, and 0.704 for the training set, and 0.798, 0.774, and 0.776 for the validation set, respectively. The calibration curves, decision curve analysis, and Kaplan-Meier survival curves further demonstrated the effectiveness of the nomograms in predicting DM occurrence and the prognosis of GBC patients with DM. Race, T stage, N stage, and tumor size emerged as independent risk factors for DM in GBC patients; whereas age, surgical treatment, and chemotherapy were found to be independent prognostic factors for OS in GBC patients with DM. We successfully established and validated a predictive nomogram for DM occurrence and a prognostic nomogram for OS in GBC patients with DM, both showing high accuracy and clinical utility.