The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Association rule mining of real-world data: Uncovering links between race, glycemic control, lipid profiles, and suicide attempts in individuals with diabetes.

Aims: The increased risk of suicide among individuals with diabetes is a significant public health concern. However, few studies have focused on understanding the relationship between suicide attempts and diabetes. Association rule mining (ARM) is a data mining technique to discover a set of high-risk factors of a given disease. Therefore, this study aimed to utilize ARM to identify a high-risk group of suicide attempts among patients with diabetes using Cerner Real-World Data™ (CRWD). Methods: The study analyzed a large multicenter electronic health records data of 3,265,041 patients with diabetes from 2010 to 2020. The Least Absolute Shrinkage and Selection Operator regression with ten-fold cross-validation and the Apriori algorithm with ARM were used to uncover groups of high-risk suicide attempts. Results: Of the 52,217,517 unique patients in the CRWD, 3,266,856 were diagnosed with diabetes. There were 7764 (0.2%) patients with diabetes who had a history of suicide attempts. The study revealed that patients with diabetes who were never married and had average blood glucose levels below 150 mg/dl were more likely to attempt suicide. In contrast, patients with diabetes aged 60 and older who had diabetes for less than five years and A1C levels between 6.5 and 8.9% were less likely to attempt suicide. Risk factors were strongly associated with suicide attempts, including never married, White, blood glucose levels below 150 mg/dl, and LDL levels below 100 mg/dl. Conclusions: This is the first study utilizing ARM to discover the risk patterns for suicide attempts in individuals with diabetes. ARM showed the potential for knowledge discovery in large multi-center electronic health records data. The results are explainable and could be practically used by providers during outpatient clinic visits. Further studies are needed to validate the results and investigate the cause-and-effect relationship of suicide attempts among individuals with diabetes.

Role of circulating mitochondria in venous thrombosis in glioblastoma.

BACKGROUND: Many patients with glioblastoma multiforme (GBM) develop deep venous thrombosis or pulmonary emboli. Cell-free circulating mitochondria increase after brain injury and are associated with coagulopathy. OBJECTIVES: This study evaluated whether mitochondria play a role in the GBM-induced hypercoagulable state. METHODS: We examined the correlation between cell-free circulating mitochondria and venous thrombosis in patients with GBM and the impact of mitochondria on venous thrombosis in mice with inferior vena cava stenosis. RESULTS: Using plasma samples of 82 patients with GBM, we found that patients with GBM had a higher number of mitochondria in their plasma (GBM with venous thromboembolism [VTE],: 2.8 × 107 mitochondria/mL; GBM without VTE, 1.9 × 107 mitochondria/mL) than that in healthy control subjects (n = 17) (0.3 × 107 mitochondria/mL). Interestingly, patients with GBM and VTE (n = 41) had a higher mitochondria concentration than patients with GBM without VTE (n = 41). In a murine model of inferior vena cava stenosis, intravenous delivery of mitochondria resulted in an increased rate of venous thrombosis compared with that in controls (70% and 28%, respectively). Mitochondria-induced venous thrombi were neutrophil-rich and contained more platelets than those in control thrombi. Furthermore, as mitochondria are the only source of cardiolipin in circulation, we compared the concentration of anticardiolipin immunoglobulin G in plasma samples of patients with GBM and found a higher concentration in patients with VTE (optical density, 0.69 ± 0.04) than in those without VTE (optical density, 0.51 ± 0.04). CONCLUSION: We concluded that mitochondria might play a role in the GBM-induced hypercoagulable state. We propose that quantifying circulating mitochondria or anticardiolipin antibody concentrations in patients with GBM might identify patients at increased risk of VTE.

Predicting suicide attempts among people with diabetes using a large multicenter electronic health records dataset.

OBJECTIVE: People with diabetes have a higher risk of suicidal behaviors than the general population. However, few studies have focused on understanding this relationship. We investigated risk factors and predicted suicide attempts in people with diabetes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. METHOD: Data was retrieved from Cerner Real-World Data and included over 3 million diabetes patients in the study. LASSO regression was applied to identify associated factors. Gender, diabetes-type, and depression-specific LASSO regression models were analyzed. RESULTS: There were 7764 subjects diagnosed with suicide attempts with an average age of 45. Risk factors for suicide attempts in diabetes patients were American Indian or Alaska Native race (ß = 0.637), receiving atypical antipsychotic agents (ß = 0.704), benzodiazepines (ß = 0.784), or antihistamines (ß = 0.528). Amyotrophy was negatively associated with suicide attempts in males (ß = 2.025); in contrast, amyotrophy significantly increased the risk in females (ß = 3.339). Using a MAOI was negatively related to suicide attempts in T1DM patients (ß = 7.304). Age less than 20 was positively associated with suicide attempts in depressed (ß = 2.093) and non-depressed patients (ß = 1.497). The LASSO model achieved a 94.4% AUC and 87.4% F1 score. CONCLUSIONS: To our knowledge, this is the first study to use LASSO regression to identify risk factors for suicide attempts in patients with diabetes. The shrinkage technique successfully reduced the number of variables in the model to improve the fit. Further research is needed to determine cause-and-effect relationships. The results may help providers to identify high-risk groups for suicide attempt among diabetic patients.

Interactions between Platelets and Tumor Microenvironment Components in Ovarian Cancer and Their Implications for Treatment and Clinical Outcomes.

Platelets, the primary operatives of hemostasis that contribute to blood coagulation and wound healing after blood vessel injury, are also involved in pathological conditions, including cancer. Malignancy-associated thrombosis is common in ovarian cancer patients and is associated with poor clinical outcomes. Platelets extravasate into the tumor microenvironment in ovarian cancer and interact with cancer cells and non-cancerous elements. Ovarian cancer cells also activate platelets. The communication between activated platelets, cancer cells, and the tumor microenvironment is via various platelet membrane proteins or mediators released through degranulation or the secretion of microvesicles from platelets. These interactions trigger signaling cascades in tumors that promote ovarian cancer progression, metastasis, and neoangiogenesis. This review discusses how interactions between platelets, cancer cells, cancer stem cells, stromal cells, and the extracellular matrix in the tumor microenvironment influence ovarian cancer progression. It also presents novel potential therapeutic approaches toward this gynecological cancer.

Analysis of Healthy Coping Feedback Messages from Diabetes Mobile Apps: Validation Against an Evidence-Based Framework.

BACKGROUND: In this study, we focused on Healthy Coping, a key principle of ADCES7 Self-Care Behaviors® (ADCES7®) that enables people with diabetes to achieve health goals for self-care. We aimed to validate Healthy Coping-related feedback messages from diabetes mobile apps against the framework based on behavioral change theories. METHODS: We searched apps using the search terms: "diabetes," "blood sugar," "glucose," and "mood" from iTunes and Google Play stores. We entered a range of values on 3 Healthy Coping domains: (1) diabetes-related measures including blood glucose, blood pressure, HbA1c, weight, (2) physical exercise/activity, and (3) mood to generate feedback messages. We used a framework by adopting validated behavioral change theory-based models to evaluate the feedback messages against 3 dimensions of timing, intention, and content (feedback purpose and feedback response). The feedback purposes in this study were categorized into 7 purposes; warning, suggestion, self-monitoring, acknowledging, reinforcement, goal setting, and behavior contract. RESULTS: We identified 1,749 apps from which 156 diabetes mobile apps were eligible and generated 473 feedback messages. The majority of generated feedback messages were related to blood sugar measurement. Only feedback messages on blood sugar under diabetes-related measures and mood domains encompassed all 7 feedback purposes under the content dimension. CONCLUSIONS: Many feedback messages neither supported Healthy Coping domains nor followed the behavioral theory-based framework. It is important that feedback messages be structured around the dimensions of the behavioral theory-based framework to promote behavior change. Furthermore, our framework had the generalizability that can be used in other clinical areas.

SEE-diabetes, a patient-centered diabetes self-management education and support for older adults: Findings and information needs from providers' perspectives.

BACKGROUND AND AIMS: Diabetes self-management education and support (DSMES) can improve clinical and health outcomes of people with diabetes. However, DSMES has been underutilized because of many barriers. We aimed to develop a patient-centered educational aid, SEE-Diabetes (Support-Engage-Empower-Diabetes), that facilitates shared decision-making about DSMES between patient and provider during the follow-up visit. We investigated the information needs to inform the design of the SEE-Diabetes from the providers' perspective. METHODS: We conducted an online survey (N = 42) and three focus groups (N = 13) involving providers who have experience managing diabetes in older patients. Survey collected demographics and assessed knowledge of DSMES. During the subsequent focus groups, participants evaluated the Assessment and Plan section of three clinic notes of older people with diabetes. We also demonstrated the potential workflow of DSMES documentation using SEE-Diabetes during clinical practice. RESULTS: The survey showed 60% of providers were familiar with DSMES. Focus group findings showed clinic notes should convey concise information at an appropriate reading level, numbered problems, and less medical jargon to improve the readability of clinic notes. Application of SMART (Specific, Measurable, Attainable, Relevant, Time-bound) goals was suggested to deliver effective diabetes self-care information. CONCLUSIONS: Providers should consider adopting validated DSMES guidelines along with goal-setting strategies to provide patient-centered care. The research team will integrate the provider recommendations when we develop SEE-Diabetes.

The efficacy of gonadotropin-releasing hormone agonist treatment before hysteroscopic myomectomy for large-sized submucosal leiomyoma.

To evaluate the efficacy and safety of a gonadotropin-releasing hormone (GnRH) agonist for treating large-sized submucosal leiomyoma before hysteroscopic myomectomy. The data were retrospectively collected from patients who underwent a hysteroscopic myomectomy for a submucosal leiomyoma >3.5 cm in size from January 2009 to December 2018. The patients were divided into the GnRH group and the control group according to whether they were pretreated before surgery. A total of 61 patients were included in the study, 31 in the GnRH agonist group and 30 in the control group. At diagnosis, the maximum leiomyoma diameter was similar between the 2 groups (4.67 ± 0.6 cm in the GnRH agonist group vs 3.82 ± 0.6 cm in the control group, P = .061). After pretreatment with the GnRH agonist, the maximum diameter was significantly smaller in the GnRH agonist group compared to the control group (3.82 ± 0.6 vs 4.33 ± 0.8 cm, respectively, P = .004). The leiomyoma volume in the GnRH agonist group decreased by 55.6%, from 41.68 ± 15.7 to 23.19 ± 10.4 cm3, which led to significant differences in leiomyoma volume between the 2 groups (23.19 ± 10.4 cm3 in the GnRH agonist group vs 33.22 ± 24.7 cm3 in the control group, P = .042). The GnRH agonist group showed a shorter operation time (37.7 vs 43.9 minutes, P = .040) and less uterine distention media was used (6800 vs 9373.3 mL, P = .037) compared to the control group. Postoperative complications such as estimated blood loss, remnant leiomyoma, and recurrence were similar between the 2 groups. Treatment with a GnRH agonist before hysteroscopic myomectomy for large submucosal leiomyoma might decrease the volume of the leiomyoma, reduce operation time, and the amount of uterine-distension media used without surgical complications.

Platelets Increase the Expression of PD-L1 in Ovarian Cancer.

The interactions between platelets and cancer cells activate platelets and enhance tumor growth. Platelets increase proliferation and epithelial-mesenchymal transition in cancer cells, inhibit anoikis, enhance the extravasation of cancer cells, and protect circulating tumor cells against natural killer cells. Here, we have identified another mechanism by which platelets dampen the immune attack on cancer cells. We found that platelets can blunt the antitumor immune response by increasing the expression of inhibitory immune checkpoint (PD-L1) on ovarian cancer cells in vitro and in vivo. Platelets increased PD-L1 in cancer cells via contact-dependent (through NF-κB signaling) and contact-independent (through TFGßR1/Smad signaling) pathways. Inhibition of NF-κB or TGFßR1 signaling in ovarian cancer cells abrogated platelet-induced PD-L1 expression. Reducing platelet counts or inhibiting platelet functions reduced the expression of PD-L1 in ovarian cancer. On the other hand, an increase in platelet counts increased the expression of PD-L1 in tumor-bearing mice.

Novel Markers for Liquid Biopsies in Cancer Management: Circulating Platelets and Extracellular Vesicles.

Although radiologic imaging and histologic assessment of tumor tissues are classic approaches for diagnosis and monitoring of treatment response, they have many limitations. These include challenges in distinguishing benign from malignant masses, difficult access to the tumor, high cost of the procedures, and tumor heterogeneity. In this setting, liquid biopsy has emerged as a potential alternative for both diagnostic and monitoring purposes. The approaches to liquid biopsy include cell-free DNA/circulating tumor DNA, long and micro noncoding RNAs, proteins/peptides, carbohydrates/lectins, lipids, and metabolites. Other approaches include detection and analysis of circulating tumor cells, extracellular vesicles, and tumor-activated platelets. Ultimately, reliable use of liquid biopsies requires bioinformatics and statistical integration of multiple datasets to achieve approval in a Clinical Laboratory Improvement Amendments setting. This review provides a balanced and critical assessment of recent discoveries regarding tumor-derived biomarkers in liquid biopsies along with the potential and pitfalls for cancer detection and longitudinal monitoring.

SEE-Diabetes, a patient-centered diabetes self-management education and support for older adults: Findings and information needs from patients' perspectives.

AIMS: This study identified the information needs of people with diabetes aged 65 and older through surveys and focus groups to inform the development of a patient-centered educational decision aid for diabetes care, SEE-Diabetes (Support-Engage-Empower-Diabetes). METHODS: We conducted survey (N = 37) and three focus groups (N = 9). The survey collected demographics, diabetes duration, insulin usage, and clinic notes accessibility through a patient portal. In focus groups, participants evaluated the Assessment and Plan section of three selected deidentified clinic notes to assess readability and helpfulness for diabetes care. RESULTS: The mean age of participants was 66 (24-82, SD = 12), and 22 were female (60%). The mean diabetes duration was 20.9 years (1-63, SD=15). Most participants (80%) read their clinical notes via patient portal. In the focus groups, the readability of clinic notes was noted as a primary concern because of medical abbreviations and poor formatting. Participants found the helpfulness of clinic notes was negatively impacted by vague or insufficient self-care information. CONCLUSIONS: We found the high use of patient portal for reading clinic notes, which offers a use case opportunity for the proposed SEE-Diabetes educational aid. Feedback about the readability and helpfulness of clinic notes will be considered during the design process.

Transforming AADE7 for Use in an Evaluation Framework for Health Information Technology in Diabetes Mellitus.

There is no validated framework to evaluate health information technology (HIT) for diabetes self-management education and support (DSMES). AADE7 Self-Care Behaviors is a patient-centered DSMES designed by the American Association of Diabetes Educators (AADE). We developed a codebook based on the AADE7 Self-Care Behaviors principles as an evaluation framework. In this commentary, we demonstrate the real-life applications of this codebook through three diabetes research studies. The first study analyzed features of mobile diabetes applications. The second study evaluated provider documentation patterns in electronic health records (EHRs) to deliver ongoing patient-centered DSMES. The third study analyzed feedback messages from diabetes apps. We found that this codebook, based on AADE7, can be instrumental as a framework for research, as well as real-life use in HIT for DSMES principles.

Podoplanin promotes tumor growth, platelet aggregation, and venous thrombosis in murine models of ovarian cancer.

BACKGROUND: Podoplanin (PDPN) is a sialylated membrane glycoprotein that binds to C-type lectin-like receptor 2 on platelets resulting in platelet activation. PDPN is expressed on lymphatic endothelial cells, perivascular fibroblasts/pericytes, cancer cells, cancer-associated fibroblasts, and tumor stromal cells. PDPN's expression on malignant epithelial cells plays a role in metastasis. Furthermore, the expression of PDPN in brain tumors (high-grade gliomas) was found to correlate with an increased risk of venous thrombosis. OBJECTIVE: We examined the expression of PDPN and its role in tumor progression and venous thrombosis in ovarian cancer. METHODS: We used mouse models of ovarian cancer and venous thrombosis. RESULTS: Ovarian cancer cells express PDPN and release PDPN-rich extracellular vesicles (EVs), and cisplatin and topotecan (chemotherapies commonly used in ovarian cancer) increase the expression of podoplanin in cancer cells. The expression of PDPN in ovarian cancer cells promotes tumor growth in a murine model of ovarian cancer and that knockdown of PDPN gene expression results in smaller primary tumors. Both PDPN-expressing ovarian cancer cells and their EVs cause platelet aggregation. In a mouse model of venous thrombosis, PDPN-expressing EVs released from HeyA8 ovarian cancer cells produce more frequent thrombosis than PDPN-negative EVs derived from PDPN-knockdown HeyA8 cells. Blood clots induced by PDPN-positive EVs contain more platelets than those in blood clots induced by PDPN-negative EVs. CONCLUSIONS: In summary, our findings demonstrate that the expression of PDPN by ovarian cancer cells promotes tumor growth and venous thrombosis in mice.

Targeting DDX3X Triggers Antitumor Immunity via a dsRNA-Mediated Tumor-Intrinsic Type I Interferon Response.

Induction of nucleic acid sensing-mediated type I interferon (IFN) has emerged as a novel approach to activate the immune system against cancer. Here we show that the depletion of DEAD-box RNA helicase 3X (DDX3X) triggers a tumor-intrinsic type I IFN response in breast cancer cells. Depletion or inhibition of DDX3X activity led to aberrant cytoplasmic accumulation of cellular endogenous double-stranded RNAs (dsRNA), which triggered type I IFN production through the melanoma differentiation-associated gene 5 (MDA5)-mediated dsRNA-sensing pathway. Furthermore, DDX3X interacted with dsRNA-editing ADAR1 and dual depletion of DDX3X and ADAR1 synergistically activated the cytosolic dsRNA pathway in breast cancer cells. Loss of DDX3X in mouse mammary tumors enhanced antitumor activity by increasing the tumor-intrinsic type I IFN response, antigen presentation, and tumor infiltration of cytotoxic T and dendritic cells. These findings may lead to the development of a novel therapeutic approach for breast cancer by targeting DDX3X in combination with immune-checkpoint blockade. SIGNIFICANCE: This study elucidates the novel role of DDX3X in regulating endogenous cellular dsRNA homeostasis and type I IFN signaling in breast cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/13/3607/F1.large.jpg.

The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer.

We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets' prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein-coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gαi2 (Gi), Gα13 (G13), or Gαq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein-deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by >90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.

Evaluation of the Barricor Tube in 28 Routine Chemical Tests and Its Impact on Turnaround Time in an Outpatient Clinic.

BACKGROUND: We recently introduced the Barricor (BD, Franklin Lakes, NJ, USA) plasma separation tube, which uses a mechanical separator instead of a gel. We evaluated the effects of using the Barricor tube in a stat (statin) laboratory on the results and turnaround time (TAT) of routine chemical tests. We verified the impact of Barricor tube on reducing TAT and providing results similar to those obtained using serum separator tubes (SSTs). METHODS: We collected venous blood samples from 166 outpatients in Barricor tubes and SSTs and measured 28 routine analytes using an AU5800 instrument (Beckman Coulter, Brea, CA, USA). TAT indexes were compared before and after using Barricor tube. RESULTS: Mean percent differences were <5%, except for alanine aminotransferase , total CO2, high-density lipoprotein, phosphate, total protein, and direct bilirubin. The median TAT decreased from 45 to 38 minutes, and the rate of a TAT >60 minutes decreased from 7.84% to 2.66%, which was approximately one-third of that for SST. The reduction in TAT was attributable to a decrease in centrifugation time. Incomplete clotting and repeated centrifugation, which occurred frequently when using SST, also decreased after using the Barricor tubes. CONCLUSIONS: The Barricor tube is an alternative to SST for routine chemical tests in institutions aiming to reduce TAT, with clinically allowable differences in test results.

The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis.

Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell lines, and orthotopic mouse models. We demonstrated a previously unrecognized mechanism whereby nuclear PXN enhances angiogenesis by transcriptionally regulating SRC expression. SRC, in turn, increases PLAT expression through NF-ĸB activation; PLAT promotes angiogenesis via LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. These findings provide a new understanding of the role of PXN in regulating tumor angiogenesis and growth.

Evaluation of the Barricor Tube in 28 Routine Chemical Tests and Its Impact on Turnaround Time in an Outpatient Clinic

Background@#We recently introduced the Barricor (BD, Franklin Lakes, NJ, USA) plasma separation tube, which uses a mechanical separator instead of a gel. We evaluated the effects of using the Barricor tube in a stat (statin) laboratory on the results and turnaround time (TAT) of routine chemical tests. We verified the impact of Barricor tube on reducing TAT and providing results similar to those obtained using serum separator tubes (SSTs). @*Methods@#We collected venous blood samples from 166 outpatients in Barricor tubes and SSTs and measured 28 routine analytes using an AU5800 instrument (Beckman Coulter, Brea, CA, USA). TAT indexes were compared before and after using Barricor tube. @*Results@#Mean percent differences were 60 minutes decreased from 7.84% to 2.66%, which was approximately one-third of that for SST. The reduction in TAT was attributable to a decrease in centrifugation time. Incomplete clotting and repeated centrifugation, which occurred frequently when using SST, also decreased after using the Barricor tubes. @*Conclusions@#The Barricor tube is an alternative to SST for routine chemical tests in institutions aiming to reduce TAT, with clinically allowable differences in test results.

Associations between Living Alone and Smoking and Alcohol Consumption in Korean Adults.

BACKGROUND: Recently, single-person households have increased in Korea and this trend may have potential public health implications and affect various health behaviors. This study investigated the associations between living alone and health behaviors such as smoking and alcohol consumption among Korean adults. METHODS: We used data from the 6th Korea National Health and Nutrition Examination Survey between 2013 and 2015 and a total of 17,088 adults were included. We performed a multivariable logistic regression analysis and calculated odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Single-person households accounted for about 10% of the total participants. The proportions of currently smoking and heavy alcohol consumption were higher among individuals living alone than those living together among younger women and middle-aged and elderly men and women. In the multivariable logistic regression analysis, living alone was associated with increased odds of currently smoking compared to living together among middle-aged men and women (OR, 7.37; 95% CI, 2.33-23.32 in men and OR, 2.36; 95% CI, 1.04-5.36 in women) after adjusting for confounding variables. CONCLUSION: From this nationwide, population-based study, we found that living alone is associated with increased odds of currently smoking, especially in middle-aged people. Public health concerns may be warranted for middle-aged single-person households to reduce health risks related to smoking.