Identification and validation of the clinical prediction model and biomarkers based on chromatin regulators in colon cancer by integrated analysis of bulk- and single-cell RNA sequencing data.

Background: Chromatin regulators (CRs) are implicated in the development of cancer, but a comprehensive investigation of their role in colon adenocarcinoma (COAD) is inadequate. The purpose of this study is to find CRs that can provide recommendations for clinical diagnosis and treatment, and to explore the reasons why they serve as critical CRs. Methods: We obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Weighted Gene Co-Expression Network Analysis (WGCNA) screened tumor-associated CRs. LASSO-Cox regression was used to construct the model and to screen key CRs together with support vector machine (SVM), the univariate Cox regression. We used single-cell data to explore the expression of CRs in cells and their communication. Immune infiltration, immune checkpoints, mutation, methylation, and drug sensitivity analyses were performed. Gene expression was verified by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Pan-cancer analysis was used to explore the importance of hub CRs. Results: We finally obtained 32 tumor-associated CRs. The prognostic model was constructed based on RCOR2, PPARGC1A, PKM, RAC3, PHF19, MYBBP1A, ORC1, and EYA2 by the LASSO-Cox regression. Single-cell data revealed that the model was immune-related. Combined with immune infiltration analysis, immune checkpoint analysis, and tumor immune dysfunction and exclusion (TIDE) analysis, the low-score risk group had more immune cell infiltration and better immune response. Mutation and methylation analysis showed that multiple CRs may be mutated and methylated in colon cancer. Drug sensitivity analysis revealed that the low-risk group may be more sensitive to several drugs and PKM was associated with multiple drugs. Combined with machine learning, PKM is perhaps the most critical gene in CRs. Pan-cancer analysis showed that PKM plays a role in the prognosis of cancers. Conclusions: We developed a prognostic model for COAD based on CRs. Increased expression of the core gene PKM is linked with a poor prognosis in several malignancies.

Potential Ability of Probiotics in the Prevention and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer in the world, and its incidence rate and mortality are on the rise in many countries. In recent years, with the improvement of economic conditions, people's living habits have changed, including lack of physical activity, poor diet patterns and circadian rhythm disorder. These risk factors can change the colon environment and the composition of intestinal microbiota. This state is called intestinal imbalance, which increases the risk of cancer. Probiotics, a class of microorganisms that help maintain gut microbial homeostasis and alleviate dysbiosis, may help prevent inflammation and colorectal cancer. These probiotics inhibit or ameliorate the effects of dysbiosis through the production of short-chain fatty acids (SCFAs), modulation of immunity, maintenance of the intestinal epithelial barrier, pro-apoptotic mechanisms, and other mechanisms. This review aims to explain the interaction between probiotics, the gut microenvironment and the gut microbiota, and summarize reports on the possibility of probiotics in the prevention and treatment of colorectal cancer.

Machine learning and single-cell sequencing reveal the potential regulatory factors of mitochondrial autophagy in the progression of gastric cancer.

BACKGROUND: As an important regulatory mechanism to remove damaged mitochondria and maintain the balance between internal and external cells, mitochondrial autophagy plays a key role in the progression and treatment of cancer Onishi (EMBO J 40(3): e104705, 2021). The purpose of this study is to comprehensively analyze the role of mitochondrial autophagy-related genes in the progression of gastric cancer (GC) by RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq). METHODS: GSE26942, GSE54129,GSE66229,GSE183904 and other data sets were obtained by GEO databases. Using support vector machine recursive feature elimination (SVM-RVF) algorithm and random forest algorithm, the mitochondrial autophagy-related genes related to gastric cancer were obtained, respectively. After that, the model was constructed and the inflammatory factors, immune score and immune cell infiltration were analyzed. Furthermore, according to the scRNA-seq data of 28,836 cells from 13 GC samples, 18 cell clusters and 7 cell types were identified by scRNA-seq analysis. The expression level and signal pathway of related genes were verified by cell communication analysis. Finally, the regulatory network of cells was analyzed by SCENIC. RESULTS: MAP1LC3B, PGAW5, PINK1, TOMM40 and UBC are identified as key genes through machine learning algorithms. CXCL12-CXCR4, LGALS9-CD44, LGALS9-CD45 and MIF (CD74 + CD44) pathways may play an important role in endothelial cells with high score scores of T cells and monocytes in tumor environment. CEBPB, ETS1, GATA2, MATB, SPl1 and XBP1 were identified as candidate TF with specific regulatory expression in the GC cell cluster. CONCLUSION: The results of this study will provide implications for the study of the mechanism, diagnosis and treatment of mitochondrial autophagy in GC.

Comparison of the Feasibility and Diagnostic Performance of ACR CEUS LI-RADS and a Modified CEUS LI-RADS for HCC in Examinations Using Sonazoid.

OBJECTIVES: The present study aimed to determine the feasibility of the American College of Radiology's (ACR) contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) (version 2017) in examinations using Sonazoid and compare its diagnostic performance with that of modified LI-RADS in patients at high risk of hepatocellular carcinoma (HCC). METHODS: This retrospective study's sample population consisted of 137 participants with a total of 140 nodules who underwent CEUS with Sonazoid and pathological confirmation via surgery or biopsy from January 2020 to February 2022. The lesions were evaluated and classified based on the reference standards (ie, ACR CEUS LI-RADS and modified LI-RADS). The overall diagnostic capabilities of the two systems were evaluated in terms of accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with 95% confidence intervals (CIs). RESULTS: The participants had a median age of 51 years and an interquartile range of 43-58 years. Regarding LR-5 as a predictor of HCC, the accuracy results of the ACR LI-RADS and modified LI-RADS algorithms were 72.9 and 71.4%, respectively (P = .50). The sensitivity of both systems was the same (69.7%; 95% CI: 60.7-77.8%). Regarding LR-M as a predictor of non-HCC malignancy, the diagnostic performance of the algorithms was the same, with accuracy and sensitivity results of 76.4 and 73.3%, respectively (95% CI: 44.9-92.2%). CONCLUSION: The findings indicate that modified LI-RADS had a moderate level of diagnostic performance for HCC in examinations using Sonazoid, which was comparable to ACR LI-RADS.

Causes of death among early-onset colorectal cancer population in the United States: a large population-based study.

Background: Early-onset colorectal cancer (EOCRC) has an alarmingly increasing trend and arouses increasing attention. Causes of death in EOCRC population remain unclear. Methods: Data of EOCRC patients (1975-2018) were extracted from the Surveillance, Epidemiology, and End Results database. Distribution of death was calculated, and death risk of each cause was compared with the general population by calculating standard mortality ratios (SMRs) at different follow-up time. Univariate and multivariate Cox regression models were utilized to identify independent prognostic factors for overall survival (OS). Results: The study included 36,013 patients, among whom 9,998 (27.7%) patients died of colorectal cancer (CRC) and 6,305 (17.5%) patients died of non-CRC causes. CRC death accounted for a high proportion of 74.8%-90.7% death cases within 10 years, while non-CRC death (especially cardiocerebrovascular disease death) was the major cause of death after 10 years. Non-cancer death had the highest SMR in EOCRC population within the first year after cancer diagnosis. Kidney disease [SMR = 2.10; 95% confidence interval (CI), 1.65-2.64] and infection (SMR = 1.92; 95% CI, 1.48-2.46) were two high-risk causes of death. Age at diagnosis, race, sex, year of diagnosis, grade, SEER stage, and surgery were independent prognostic factors for OS. Conclusion: Most of EOCRC patients died of CRC within 10-year follow-up, while most of patients died of non-CRC causes after 10 years. Within the first year after cancer diagnosis, patients had high non-CRC death risk compared to the general population. Our findings help to guide risk monitoring and management for US EOCRC patients.

Novel m7G-related lncRNA signature for predicting overall survival in patients with gastric cancer.

Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan-Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model's reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS' correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.

Case report: Diagnosis and treatment of a chinchilla's old radius and ulna fracture.

The cortex of the limb bones of chinchillas is very thin and brittle, so it is prone to fractures of the limb bones, among which fractures of the tibia, radius and ulna are the most frequent types. When a chinchilla has a closed fracture, it can be immobilized with a splint, cast, or bandage. If the broken end of the fracture pierces the skin, it is best to choose internal fixation or external fixation brackets for treatment. In this report, a 0.661 kg, 2-year-old male uncastrated chinchilla was presented to the Veterinary Teaching Hospital of Huazhong Agricultural University due to an old fracture of the right forearm. With the consent of the owner, we decided to use a 25-gauge needle as an IM pin to fix the fracture. Ten days after surgery, the wound had healed well, and the limb could support body weight, but the palm did not show a grasping position. Twenty four days after the operation, the affected limb had not regained the ability to grasp. The X-ray showed a slight rotation of the IM pin and good callus growth in the ulna, but not in the radius. One month after the operation, it was found that the function of the affected limb of the chinchilla was normal and the grasping ability was restored through follow-up consultation and the return visit.

The effect of O-antigen length determinant wzz on the immunogenicity of Salmonella Typhimurium for Escherichia coli O2 O-polysaccharides delivery.

Attenuated Salmonella Typhimurium is a promising antigen delivery system for live vaccines such as polysaccharides. The length of polysaccharides is a well-known key factor in modulating the immune response induced by glycoconjugates. However, the relationship between the length of Lipopolysaccharide (LPS) O-antigen (OAg) and the immunogenicity of S. Typhimurium remains unclear. In this study, we assessed the effect of OAg length determined by wzzST on Salmonella colonization, cell membrane permeability, antimicrobial activity, and immunogenicity by comparing the S. Typhimurium wild-type ATCC14028 strain to those with various OAg lengths of the ΔwzzST mutant and ΔwzzST::wzzECO2. The analysis of the OAg length distribution revealed that, except for the very long OAg, the short OAg length of 2-7 repeat units (RUs) was obtained from the ΔwzzST mutant, the intermediate OAg length of 13-21 RUs was gained from ΔwzzST::wzzECO2, and the long OAg length of over 20 RUs was gained from the wild-type. In addition, we found that the OAg length affected Salmonella colonization, cell permeability, and antibiotic resistance. Immunization of mice revealed that shortening the OAg length by altering wzzST had an effect on serum bactericidal ability, complement deposition, and humoral immune response. S. Typhimurium mutant strain ΔwzzST::wzzECO2 possessed good immunogenicity and was the optimum option for delivering E. coli O2 O-polysaccharides. Furthermore, the attenuated strain ATCC14028 ΔasdΔcrpΔcyaΔrfbPΔwzzST::wzzECO2-delivered E. coli O2 OAg gene cluster outperforms the ATCC14028 ΔasdΔcrpΔcyaΔrfbP in terms of IgG eliciting, cytokine expression, and immune protection in chickens. This study sheds light on the role of OAg length in Salmonella characteristics, which may have a potential application in optimizing the efficacy of delivered polysaccharide vaccines.

Proteomics profiling of nontumor liver tissues identifies prognostic biomarkers in hepatitis B-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) often occurs following chronic hepatitis B virus (HBV) infection, leading to high recurrence and a low 5-year survival rate. We developed an overall survival (OS) prediction model based on protein expression profiles in HBV-infected nontumor liver tissues. We aimed to demonstrate the feasibility of using protein expression profiles in nontumor liver tissues for survival prediction. A univariate Cox and differential expression analysis were performed to identify candidate prognostic factors. A multivariate Cox analysis was performed to develop the liver gene prognostic index (LGPI). The survival differences between the different risk groups in the training and validation cohorts were also estimated. A total of 363 patients, 159 in the training cohort, and 204 in the validation cohort were included. Of the 6478 proteins extracted from nontumor liver tissues, we identified 1275 proteins altered between HCC and nontumor liver tissues. A total of 1090 out of 6478 proteins were significantly related to OS. The prognostic values of the proteins in nontumor tissues were mostly positively related to those in the tumor tissues. Protective proteins were mainly enriched in the metabolism-related pathways. From the differentially expressed proteins, the top 10 most significant prognosis-related proteins were submitted for LGPI construction. In the training and validation cohorts, this LGPI showed a great ability for distinguishing patients' OS risk stratifications. After adjusting for clinicopathological features, the LGPI was an independent prognostic factor in the training and validation cohorts. We demonstrated the prognostic value of protein expression profiling in nontumor liver tissues. The proposed LGPI was a promising predictive model for estimating OS in HBV-related HCC.

The Association Between Gut Microbiota, Toll-Like Receptors, and Colorectal Cancer.

The large number of microbes found in the gut are involved in various critical biological processes in the human body and have dynamic and complex interactions with the immune system. Disruptions in the host's gut microbiota and the metabolites produced during fermentation promote the development of intestinal inflammation and colorectal cancer (CRC). Toll-like receptors (TLRs) recognize specific microbial-associated molecular patterns specific to microorganisms whose signaling is involved in maintaining intestinal homeostasis or, under certain conditions, mediating dysbiosis-associated intestinal inflammation. The signaling pathways of TLRs are described first, followed by a discussion of the interrelationship between gut microbes and TLRs, including the activation of TLRs by gut microbes and the effect of TLRs on the distribution of gut microbiota, particularly the role of microbes in colorectal carcinogenesis via TLRs. Finally, we discuss the potential roles of various TLRs in colorectal cancer.

Mapping Lymph Node during Indocyanine Green Fluorescence-Imaging Guided Gastric Oncologic Surgery: Current Applications and Future Directions.

Huge strides have been made in the navigation of gastric cancer surgery thanks to the improvement of intraoperative techniques. For now, the use of indocyanine green (ICG) enhanced fluorescence imaging has received promising results in detecting sentinel lymph nodes (SLNs) and tracing lymphatic drainages, which make it applicable for limited and precise lymphadenectomy. Nevertheless, issues of the lack of specificity and unpredictable false-negative lymph nodes were encountered in gastric oncologic surgery practice using ICG-enhanced fluorescence imaging (ICG-FI), which restrict its application. Here, we reviewed the current application of ICG-FI and assessed potential approaches to improving ICG-FI.

Igniting Hope for Tumor Immunotherapy: Promoting the "Hot and Cold" Tumor Transition.

The discovery of immune checkpoint inhibitors (ICIs) has ushered a new era for immunotherapy against malignant tumors through the killing effects of cytotoxic T lymphocytes in the tumor microenvironment (TME), resulting in long-lasting tumor suppression and regression. Nevertheless, given that ICIs are highly dependent on T cells in the TME and that most tumors lack T-cell infiltration, promoting the conversion of such immunosuppressive "cold" tumors to "hot" tumors is currently a key challenge in tumor immunotherapy. Herein, we systematically outlined the mechanisms underlying the formation of the immunosuppressive TME in cold tumors, including the role of immunosuppressive cells, impaired antigen presentation, transforming growth factor-ß, STAT3 signaling, adenosine, and interferon-γ signaling. Moreover, therapeutic strategies for promoting cold tumors to hot tumors with adequate T-cell infiltration were also discussed. Finally, the prospects of therapeutic tools such as oncolytic viruses, nanoparticles, and photothermal therapy in restoring immune activity in cold tumors were thoroughly reviewed.

Mental health disorders are more common in patients with Hodgkin lymphoma and may negatively impact overall survival.

BACKGROUND: Long-term mental health outcomes were characterized in patients who were diagnosed with Hodgkin lymphoma (HL), and risk factors for the development of mental health disorders were identified. METHODS: Patients who were diagnosed with HL between 1997 and 2014 were identified in the Utah Cancer Registry. Each patient was matched with up to five individuals from a general population cohort identified within the Utah Population Database, a unique source of linked records that includes patient and demographic data. RESULTS: In total, 795 patients who had HL were matched with 3575 individuals from the general population. Compared with the general population, patients who had HL had a higher risk of any mental health diagnosis (hazard ratio, 1.77; 95% confidence interval, 1.57-2.00). Patients with HL had higher risks of anxiety, depression, substance-related disorders, and suicide and intentional self-inflicted injuries compared with the general population. The main risk factor associated with an increased risk of being diagnosed with mental health disorders was undergoing hematopoietic stem cell transplantation, with a hazard ratio of 2.06 (95% confidence interval, 1.53-2.76). The diagnosis of any mental health disorder among patients with HL was associated with a detrimental impact on overall survival; the 10-year overall survival rate was 70% in patients who had a mental health diagnosis compared with 86% in those patients without a mental health diagnosis (p < .0001). CONCLUSIONS: Patients who had HL had an increased risk of various mental health disorders compared with a matched general population. The current data illustrate the importance of attention to mental health in HL survivorship, particularly for patients who undergo therapy with hematopoietic stem cell transplantation.

Expression, prognosis value, and immune infiltration of lncRNA ASB16-AS1 identified by pan-cancer analysis.

Long non-coding RNA known as ASB16 antisense RNA1 (ASB16-AS1) has been proven to be an oncogene, and the relationship between ASB16-AS1 and immunity is still under studied. This study aims to explore the expression and prognostic potential of ASB16-AS1, and to visualize the relationship between ASB16-AS1 expression and immune infiltration in pan-cancer analysis. We clarified ASB16-AS1 expression patterns and its relationship with prognosis through multi-platform and multi-database sources. We also verified the function of ASB16-AS1 in liver hepatocellular carcinoma (LIHC). A  variety of immune cell content evaluation methods were used to mutually verify the correlation between ASB16-AS1 and immune infiltration. Finally, the relationships between ASB16-AS1 and molecular characteristics were further explored. In terms of comprehensive analysis, compared with non-tumor tissues, ASB16-AS1 was highly expressed in tumor tissues, and indicated the value of poor prognosis in multiple cancer types. Functional assays, such as counting kit-8 assay, transwell assay and scratch-wound assay verified that high ASB16-AS1 expression promoted tumor progression in LIHC. ASB16-AS1 was positively correlated with B cells, T cells CD4+ and T cells CD8+ in most cancer types, and negatively correlated with macrophages, dendritic cells and neutrophils in some cancer types. In addition, there were different interaction modes between ASB16-AS1 and molecular features, such as the relationship with oncogenic signaling pathways, showing that the high ASB16-AS1 expression was related to alterations in oncogenic signaling pathways. Our study emphasizes that ASB16-AS1 is a potential pan-cancer prognostic marker, whichs is associated with the immune infiltration in multiple cancer types.

Integrated multi-omics analysis of the clinical relevance and potential regulatory mechanisms of splicing factors in hepatocellular carcinoma.

Splicing factors (SFs) have been increasingly documented to perturb the genome of cancers. However, little is known about the alterations of SFs in hepatocellular carcinoma (HCC). This study comprehensively delineated the genomic and epigenomic characteristics of 404 SFs in HCC based on the multi-omics data from the Cancer Genome Atlas database. The analysis revealed several clinically relevant SFs that could be effective biomarkers for monitoring the onset and prognosis of HCC (such as, HSPB1, DDX39A, and NELFE, which were the three most significant clinically relevant SFs). Functional enrichment analysis of these indicators showed the enrichment of pathways related to splicing and mRNA processes. Furthermore, the study found that SF copy number variation is common in HCC and could be a typical characteristic of hepato-carcinogenesis; the complex expression regulation of SFs was significantly affected by copy number variant and methylation. Several SFs with significant mutation patterns were identified (such as, RNF213, SF3B1, SPEN, NOVA1, and EEF1A1), and the potential regulatory network of SFs was constructed to identify their potential mechanisms for regulating clinically relevant alternative splicing events. Therefore, this study established a foundation to uncover the broad molecular spectrum of SFs for future functional and therapeutic studies of HCC.

Biomimetic injectable hydrogel microspheres with enhanced lubrication and controllable drug release for the treatment of osteoarthritis.

The occurrence of osteoarthritis (OA) is highly associated with the reduced lubrication property of the joint, where a progressive and irreversible damage of the articular cartilage and consecutive inflammatory response dominate the mechanism. In this study, bioinspired by the super-lubrication property of cartilage and catecholamine chemistry of mussel, we successfully developed injectable hydrogel microspheres with enhanced lubrication and controllable drug release for OA treatment. Particularly, the lubricating microspheres (GelMA@DMA-MPC) were fabricated by dip coating a self-adhesive polymer (DMA-MPC, synthesized by free radical copolymerization) on superficial surface of photo-crosslinked methacrylate gelatin hydrogel microspheres (GelMA, prepared via microfluidic technology), and encapsulated with an anti-inflammatory drug of diclofenac sodium (DS) to achieve the dual-functional performance. The tribological test and drug release test showed the enhanced lubrication and sustained drug release of the GelMA@DMA-MPC microspheres. In addition, the functionalized microspheres were intra-articularly injected into the rat knee joint with an OA model, and the biological tests including qRT-PCR, immunofluorescence staining assay, X-ray radiography and histological staining assay all revealed that the biocompatible microspheres provided significant therapeutic effect against the development of OA. In summary, the injectable hydrogel microspheres developed herein greatly improved lubrication and achieved sustained local drug release, therefore representing a facile and promising technique for the treatment of OA.

Regulated delayed attenuation improves vaccine efficacy in preventing infection from avian pathogenic Escherichia coli O78 and Salmonella typhimurium.

Avian pathogenic Escherichia coli (APEC) O78 and Salmonella typhimurium (S. Typhimurium) are two leading bacterial pathogens that cause significant economic loss in the poultry industry. O-antigen is an important immunogen of these two bacteria to induce host protective immune responses during infection. To develop a bivalent vaccine against APEC O78 and S. Typhimurium, the attenuated Salmonella ST01 (Δasd ΔrfbP Δcrp) was genetically constructed to deliver APEC O78 O-antigen polysaccharide (OPS), which stably expresses OPS with asd+ balanced-lethal system in vitro and in vivo. After oral immunization, the recombinant attenuated Salmonella vaccine (RASV) strain ST01 (pSS26-O78) provided insufficient protection against the APEC O78 challenge. Therefore, the regulated delayed attenuation strain ST02 (Δasd ΔrfbP ΔPcrp::TTaraC PBADcrp) was further constructed by regulating cyclic AMP receptor protein (crp) with araC PBAD cassette to better present the heterologous O-antigen to the host immune system. The innovative recombinant strain ST02 (pSS26-O78) stimulated robust antibody responses against APEC O78 and S. Typhimurium OPS, with serum titers over 1:800 for both IgG and IgA, thereby providing the complement-mediated bactericidal activity and stronger protection against APEC O78 and S. Typhimurium infection. Collectively, this study demonstrates a biologically-conjugated polysaccharide vaccine candidate that can enhance homologous protection against APEC O78 and S. Typhimurium.

Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study.

OBJECTIVE: While genitourinary complications during treatment for ovarian cancer are well-known, long-term adverse outcomes have not been well characterized. The number of ovarian cancer survivors has been increasing. The aim of this study was to investigate long-term adverse genitourinary outcomes in a population-based cohort. METHODS: We identified a cohort of 1270 ovarian cancer survivors diagnosed between 1996 and 2012 from the Utah Cancer Registry, and 5286 cancer-free women were matched on birth year and state from the Utah Population Database. Genitourinary disease diagnoses were identified through ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to estimate hazard ratios (HR) for genitourinary outcomes at 1 to <5 years and 5+ years after ovarian cancer diagnosis. RESULTS: Ovarian cancer survivors had increased risks for urinary system disorders (HR: 2.53, 95% CI: 2.12-3.01) and genital organ disorders (HR: 1.88, 95% CI: 1.57-2.27) between 1 and <5 years after cancer diagnosis compared to the general population cohort. Increased risks were observed for acute renal failure, chronic kidney disease, calculus of kidney, hydronephrosis, pelvic peritoneal adhesions, and pelvic organ inflammatory conditions. Increased risks of several of these diseases were observed 5+ years after cancer diagnosis. CONCLUSIONS: Ovarian cancer survivors experience increased risks of various genitourinary diseases compared to women in the general population in the long-term. Understanding the multimorbidity trajectory among ovarian cancer survivors is important to improve clinical care after cancer treatment is completed.

Long-term diabetes risk among endometrial cancer survivors in a population-based cohort study.

OBJECTIVE: The majority of endometrial cancer patients are overweight or obese at cancer diagnosis. Obesity is a shared risk factor for both endometrial cancer and diabetes, but it is unknown whether endometrial cancer patients have increased diabetes risks. The aim of our study was to investigate diabetes risk among endometrial cancer patients. METHODS: Endometrial cancer patients diagnosed between 1997 and 2012 in Utah (n = 2,314) were identified. Women from the general population (n = 8,583) were matched to the cancer patients on birth year and birth state. Diabetes diagnoses were identified from electronic medical records and statewide healthcare facility databases. Cox proportional hazards models were used to estimate hazard ratios for diabetes after cancer diagnosis. RESULTS: Endometrial cancer survivors had a significantly higher risk of type II diabetes when compared to women from the general population in the first year after cancer diagnosis (HR = 5.22, 95% CI = 4.05, 6.71), >1-5 years after cancer diagnosis (HR = 1.67, 95% CI = 1.31, 2.12), and >5 years after cancer diagnosis (HR = 1.65, 95% CI = 1.29, 2.11). Endometrial cancer patients who were obese at cancer diagnosis had a three-fold increase in type II diabetes risk (HR = 2.99, 95%CI = 2.59, 3.45). Although endometrial cancer patients diagnosed at distant stage had a higher risk of diabetes, cancer treatment did not appear to contribute to any diabetes risks. CONCLUSIONS: In conclusion, endometrial cancer survivors had a higher risk of diabetes than women in the general population. These results suggest that long term monitoring for diabetes is indicated for endometrial cancer survivors.

Adverse respiratory outcomes among head and neck cancer survivors in the Utah Cancer Survivors Study.

BACKGROUND: The number of head and neck cancer (HNC) survivors has been increasing because of improving survival in the United States. The aim of this study was to evaluate the incidence of respiratory disease diagnoses in HNC survivors in comparison with cancer-free individuals. A second aim was to investigate risk factors for respiratory disease among HNC survivors. METHODS: Patients with HNC diagnosed from 1996 to 2012 were identified in the Utah Cancer Registry (n = 1901). Up to 5 cancer-free individuals from the general population (n = 7796) were matched to each HNC survivor by birth year, sex, birth state, and follow-up time. Electronic medical records and statewide health care facility data were used to identify a disease diagnosis after the cancer diagnosis. Cox proportional hazards models were used to estimate the risks of respiratory diseases. RESULTS: The median follow-up times were 4.5 years for HNC survivors and 7.8 years for the general population cohort. The risks of respiratory infection (hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.40-1.90), chronic obstructive pulmonary diseases and bronchiectasis (HR, 2.65; 95% CI, 2.13-3.29), and aspiration pneumonitis (HR, 6.21; 95% CI, 3.98-9.68) were higher among HNC survivors than the general population cohort more than 5 years after the cancer diagnosis. Age at diagnosis, baseline body mass index, sex, baseline smoking status, treatment modality, primary site, and stage were associated with the risk of adverse respiratory outcomes among HNC survivors. CONCLUSIONS: The risk of adverse respiratory outcomes was much higher among HNC survivors than the general population cohort. Multidisciplinary care is needed to prevent the occurrence of adverse respiratory outcomes among HNC survivors.