Influence of acute kidney injury and its recovery subtypes on patient-centered outcomes after lung transplantation.

This study aimed to investigate the association between acute kidney injury (AKI) recovery subtypes and days alive out of hospital within the first 3 months (DAOH-90) in patients undergoing lung transplantation. Patients who underwent lung transplantation from January 2012 to December 2021 were retrospectively analyzed and stratified into three groups: no-AKI, early recovery AKI (within 7 days), and non-early recovery AKI group. AKI occurred in 86 (35%) of patients, of which 40 (16%) achieved early recovery, and the remaining 46 (19%) did not. The median DAOH-90 was 21 days shorter in the AKI than in the no-AKI (P = 0.002), and 29 days shorter in the non-early recovery AKI group than in the no-AKI group (P < 0.001). Non-early recovery AKI and preoperative tracheostomy status were independently associated with shorter DAOH-90. The prevalence of CKD (76%), and 1-year mortality (48%) were highest in the non-early recovery AKI group. Postoperative AKI was associated with an adverse patient-centered quality measure for perioperative care, and shorter DAOH-90. The non-early recovery AKI group exhibited the worst prognosis in terms of DAOH-90, CKD progression, and 1-year mortality, highlighting the important role of AKI and early-recovery AKI on both the quality of life and clinical outcomes after lung transplantation.

Association of Metformin Treatment with Risk for Death in Diabetic Patients with Concomitant Gastric Cancer.

IMPORTANCE: Despite the existing guideline's recommendation of metformin therapy as the initial approach for managing diabetes mellitus (DM), there remains a scarcity of comprehensive documentation regarding metformin's impact on outcomes that are important for patients. OBJECTIVES: The objective of this study was to assess the potential impact of metformin treatment on the risk of death in individuals diagnosed with both gastric cancer and pre-existing diabetes mellitus (DM); Design, Setting, and Participants: The study made use of a dataset encompassing nationwide health insurance claims, allowing for a retrospective analysis of all patients with a history of gastric cancer diagnosis (classified under International Classification of Diseases 10th Revision code: C16.X) spanning from 1 January 2002 to 31 December 2012. The primary objective was to observe death within a 5-year follow-up period. The study population comprised 63,664 individuals who fell into two categories: those treated with metformin (n = 29,548) and those who did not receive metformin treatment (n = 34,116). This classification was based on the initial treatment allocation following the diagnosis of gastric cancer. EXPOSURES: Metformin treatment, comorbidities, concurrent medication, and procedural information. OUTCOMES: All-cause death, disease-specific death, cardiovascular death. RESULTS: During the 5-year follow-up period, the metformin treatment group exhibited a lower cumulative incidence of all-cause death (27.5%) in comparison to the group not receiving metformin treatment (32.8%). Furthermore, the relative hazards for all-cause death were significantly reduced in the metformin treatment group (HR: 0.80, 95% CI 0.78-0.82), indicating a lower risk of death when compared to the non-metformin group. In addition, metformin treatment was associated with lower occurrences of disease-specific death (related to gastric cancer) and cardiovascular death when compared to the group not undergoing metformin treatment. CONCLUSIONS: The findings demonstrated that the use of metformin was effective at improving prognosis among gastric cancer patients documented with prior DM. In this population-based cohort study, metformin treatment was associated with reduced risk of mortality.

The effects of hospice care on healthcare expenditure among cancer patients.

PURPOSE: It is necessary to estimate the hospice usage and hospice-related cost for entire cancer patients using nationwide cohort data to establish a suitable ethical and cultural infrastructure. This study aims to show the effects of hospital hospice care on healthcare expenditure among South Korean cancer patients. METHODS: This study is a retrospective cohort study using customized health information data provided by the National Health Insurance Service. Individuals who were diagnosed with stomach, colorectal, or lung cancer between 2003 and 2012 were defined as new cancer patients, which included 7,176 subjects. Patients who died under hospital-based hospice care during the follow-up period from January 2016 to December 2018 comprised the treatment group. Healthcare expenditure was the dependent variable. Generalized estimating equations was used. RESULTS: Among the subjects, 2,219 (30.9%) had used hospice care at an average total cost of 948,771 (± 3,417,384) won. Individuals who had used hospice care had a lower odds ratio (EXP(ß)) of healthcare expenditure than those who did not (Total cost: EXP(ß) = 0.27, 95% confidence intervals (CI) = 0.25-0.30; Hospitalization cost: EXP(ß) = 0.32, 95% CI = 0.29-0.35; Outpatient cost: EXP(ß) = 0.02, 95% CI = 0.02-0.02). CONCLUSION: Healthcare expenditure was reduced among those cancer patients in South Korea who used hospice care compared with among those who did not. This emphasizes the importance of using hospice care and encourages those hesitant to use hospice care. The results provide useful insights into both official policy and the existing practices of healthcare systems.

Association of polypharmacy with all-cause mortality and adverse events among elderly colorectal cancer survivors.

BACKGROUND: The risk of inappropriate drug exposure in elderly colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. This study investigated the association of polypharmacy (PP) with overall survival, hospitalization, and emergency room (ER) visits among older CRC survivors. METHODS: A retrospective cohort study was conducted using the Korean National Health Insurance claims data follow-up from 2002 to 2017. Participants comprised those aged ≥65 years who were hospitalized with a diagnosis of CRC received cancer treatment and survived at least 2 years from the initial CRC diagnosis between 2003 and 2012. PP was defined based on the number of individual drugs during the third year, after 2 years of survival since the initial cancer treatment. PP was categorized as follows: non-PP (zero to four prescribed drugs); PP (five to nine drugs), and excessive PP (≥10 drugs). Main outcomes are all-cause mortality, hospitalization, and ER visits. RESULTS: Of the 55,228 participants, 44.5% died, 83.1% were hospitalized, and 46.1% visited the ER. The PP and excess PP groups showed increased risk of all-cause mortality, hospitalization, and ER visit compared with the low PP group, and was highly associated among groups including patients aged 65 to 74 years and those in low-level frailty groups. CONCLUSIONS: These risks can be minimized by increasing awareness and enhancing behaviors among health care professionals, especially clinician and pharmacists, to be aware of potential drug interactions, review, and ongoing monitoring. PLAIN LANGUAGE SUMMARY: The risk of inappropriate drug exposure in older colorectal cancer (CRC) survivors after the initial cancer treatment has not been well studied. Polypharmacy was associated with adverse outcomes, including all-cause mortality, hospitalization, and emergency room visits among older CRC survivors and it was particularly associated with those who were 65 to 75 years and those with low risk of frailty. When prescribing drugs, physicians should be mindful of finding a balance between adequate treatment of diseases and avoiding adverse drug effects in survivors of CRC.

Metformin use is not associated with colorectal cancer incidence in type-2 diabetes patients: evidence from methods that avoid immortal time bias.

PURPOSE: Immortal time bias (ITB) continues to distort many observational studies on metformin use and cancer risk. Our objective was to employ three statistical methods proven to avoid ITB and compare their results to that of a naïve time-fixed analysis in order to provide further evidence of metformin's association, or none thereof, with colorectal cancer (CRC) incidence. METHODS: A total of 41,533 Korean subjects with newly diagnosed type-2 diabetes in 2005-2015 were selected from a prospectively maintained cohort (median follow-up of 6.3 years). Time-to-CRC incidence was regressed upon metformin use (yes/no, average prescription days/year) using time-dependent Cox, landmark, nested case-control, and time-fixed Cox analyses. Other CRC risk factors were included to adjust for possible confounding. RESULTS: Neither metformin ever-use nor average metformin prescription days/year was associated with incident CRC hazard in time-dependent Cox, landmark, and nested case-control analyses with HR (95% CI) of 0.88 (0.68-1.13), 0.86 (0.65-1.12), and 1.10 (0.86-1.40) for metformin ever-use, and 0.97 (0.90-1.04), 0.95 (0.88-1.04), and 1.02 (0.95-1.10) for average metformin prescription days/year, respectively. In contrast, time-fixed Cox regression showed a falsely exaggerated protective effect of metformin on CRC incidence. CONCLUSION: The association between metformin use and subsequent CRC incidence was statistically nonsignificant after accounting for time-related biases such as ITB. Previous studies that avoided these biases and meta-analyses of RCTs on metformin and cancer incidence were in agreement with our results. A definitive, large-scale RCT is needed to clarify this topic, and future observational studies should be explicit in avoiding ITB and other time-related biases.

Comparative effectiveness of second-line biological therapies for ulcerative colitis and Crohn's disease in patients with prior failure of anti-tumour necrosis factor treatment.

BACKGROUND: Therapeutic options for inflammatory bowel disease (IBD) have increased since the introduction of tumour necrosis factor (TNF) inhibitors a few decades ago. However, direct comparisons of the effectiveness of second-line biological agents in patients with ulcerative colitis (UC) and Crohn's disease (CD) are lacking. METHODS: Patients with UC or CD who experienced anti-TNF treatment failure and subsequently used vedolizumab, ustekinumab, or tofacitinib as a second-line drug were retrospectively recruited. The primary outcomes were the clinical remission rate at week 16 and the cumulative relapse rate 48 weeks after receiving induction therapy. RESULTS: A total of 94 patients with UC or CD experienced anti-TNF treatment failure and received vedolizumab (UC: 37; CD: 28), ustekinumab (CD: 16), or tofacitinib (UC: 13). The clinical remission rates were not significantly different between the vedolizumab and tofacitinib groups in UC patients (56.8% vs. 46.2%, p = 0.509). In CD patients, the clinical remission rates were not significantly different between the vedolizumab and ustekinumab groups (53.6% vs. 50.0%, p = 0.820). Moreover, the cumulative rates of clinical relapse were not significantly different between the vedolizumab and tofacitinib groups in UC patients and between the vedolizumab and ustekinumab groups in CD patients (p = 0.396 and p = 0.692, respectively). Safety profiles were also similar among the treatment groups in both UC and CD patients. CONCLUSIONS: After prior anti-TNF therapy failure, vedolizumab and tofacitinib in UC patients and vedolizumab and ustekinumab in CD patients were not significantly different in terms of the efficacy in inducing and maintaining a clinical response.

Increasing disparities in the proportions of active treatment and 5-year overall survival over time by age groups among older patients with gastric cancer in Korea.

Purpose: As older patients with gastric cancer increase in Korea, no consensus indicative of anti-cancer treatment exists for the oldest old (age 85+). We investigated potential disparities in the proportion of surgery-including active treatment and the degree of survival improvement over time by age groups, and whether heterogeneity exists in the protective effect of time period on overall survival (OS) by age at diagnosis clusters. Materials and methods: A nationwide cohort (N = 63,975) of older patients with gastric cancer (age at diagnosis 70+) in 2005-2012 were followed until the end of 2018. Patients were categorized into four time period groups by their year of diagnosis. Cancer treatment patterns and 5-year OS were analyzed accordingly, and a random coefficients Cox model with random intercepts and random slopes of time period by age at diagnosis clusters was employed. Results: The mean age of patients was 76.4, and 60.4% were males. Most patients had 0-1 comorbidities (73.3%) and low-risk frailty scores (74.2%). Roughly two-thirds of patients received some form of anti-cancer treatment (62.4%), and while the number of comorbidities and the proportion of high-risk frailty scores trended toward an increase, the proportion of patients receiving anti-cancer treatment increased from 58% in 2005-2006 to 69.6% in 2011-2012. The proportion of surgery-including active treatment increased to over 70% in the 70-74 years old group, while stagnating at 10% in the 90+ years old group. Differences in the slope of 5-year OS improvement resulted in a widening survival gap between the old (age 70-84) and the oldest old. The protective effect of time period on OS hazard in the oldest old was not monotonically reduced with increasing "chronological" age but varied quite randomly, especially among female patients. Conclusion: Our study showed no upper age limit in terms of benefiting from the advances in the detection and treatment of gastric cancer over time. Thus, "functional" age rather than "chronological" age should be the criterion for anti-cancer screening and treatment, and actual implementation of proven treatments in the oldest old patients to reduce their non-compliance with treatment in clinical practice is needed to improve gastric cancer survival for all.

Obesity measures at baseline, their trajectories over time, and the incidence of chronic kidney disease: A 14 year cohort study among Korean adults.

BACKGROUND AND AIMS: We investigated the association of baseline obesity measures, i.e. body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR), and their trajectories over time with incident chronic kidney disease (CKD). METHODS AND RESULTS: Utilizing data from 2001 to 2014 for 9796 Korean adults without CKD at baseline, the association of baseline obesity measures with incident CKD was evaluated using logistic regression. Further, among 5605 subjects with repeated measures, the effect of the trajectories in obesity measures on CKD incidence was investigated via Cox regression. Baseline obesity in terms of BMI, WC, and HC increased the odds of incident CKD (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.05-1.33; OR 1.22, 95% CI 1.07-1.38; and OR 1.25, 95% CI 1.11-1.41, respectively), while baseline WHR did not show such an association. A "became non-obese" BMI, WC, or WHR trajectory, and a "constantly not large" HC trajectory decreased the hazard of incident CKD (hazard ratio (HR) 0.70, 95% CI 0.50-0.99; HR 0.61, 95% CI 0.40-0.92; HR 0.55, 95% CI 0.35-0.85; and HR 0.81, 95% CI 0.69-0.95, respectively) when compared with a "constantly obese or became obese" trajectory. CONCLUSION: Both baseline obesity and obesity trajectories over time were associated with CKD incidence. BMI and WC were equally good measures of CKD risk, while WHR was not. Separately examining WC and HC components of WHR (= WC/HC) may explain WHR's inconsistency, and WHR's usefulness as a measure of CKD risk should be reevaluated.

The binary presence or absence of lymph node metastasis or extrathyroidal extension is not associated with survival in papillary thyroid cancers: Implications for staging systems.

BACKGROUND: The characteristics of diagnosed papillary thyroid cancer (PTC) have changed over time with the increasing trend of early diagnosis, and the survival impact of conventional prognostic factors such as lymph node metastasis (LNM) and extrathyroidal extension (ETE) is controversial. We investigated PTC prognostic factors for overall survival (OS) and disease specific survival (DSS), focusing on LNM, ETE, and their implications for PTC staging systems. METHODS: We assessed prognostic factors for OS and DSS in a nationwide sample of Korean PTC patients (N = 5192, median follow-up 121 months) using Cox regression. The binary presence or absence of LNM and ETE, as well as other measures of LNM and ETE, were examined for their survival impact. We also evaluated the relative performance of PTC staging systems before and after revising the staging criteria for LNM and ETE. RESULTS: The binary presence of LNM or ETE was not a prognostic factor for OS or DSS, nor were other various measures of LNM. However, the extent of ETE as none, microscopic, or gross independently influenced survival (OS hazard ratio for gross vs. none: 3.28, 95% confidence interval (CI) 1.97-5.46; DSS hazard ratio for gross vs. none: 3.75, 95% CI 1.59-8.81). The performance of PTC staging systems improved when the extent of ETE and/or location of LNM were used as staging components. CONCLUSION: The extent of ETE and/or location of LNM may be better survival indicators than their binary presence or absence, and we propose staging criteria revisions to pertinent staging systems to better reflect the contemporary PTC population.

Association Between Health Behaviors and Family History of Cancer According to Sex in the General Population.

INTRODUCTION: Family history of cancer and modifiable risk factors are each associated with cancer development, but no studies have assessed their association with each other by sex. This study aimed to examine modifiable risk factors in individuals with a family history of cancer compared with those without a family history of cancer, according to sex. METHODS: This study recruited 166,810 participants aged 40-79 years from Korea's Health Examinee Study cohort between 2004 and 2014. Results were calculated as AORs and 95% CIs to determine the relationship between family history of cancer in first-degree relatives and modifiable risk factors. Data analyses were performed in 2018. RESULTS: The prevalence of modifiable cancer risk factors, including current smoking, drinking alcohol, physical inactivity, obesity, and abdominal obesity, were different according to the presence of a family history of cancer, cancer type of such a family history, and sex. Male participants with a family history of cancer were less likely to be current smokers or obese (AOR=0.95, 95% CI=0.91, 0.99 and AOR=0.95, 95% CI=0.92, 0.99, respectively) than those without a family history of cancer, whereas female participants with a family history of cancer were more likely to be current smokers but less likely to be physically inactive (AOR=1.13, 95% CI=1.03, 1.23 and AOR=0.96, 95% CI=0.93, 0.98, respectively) than those without a family history of cancer. CONCLUSIONS: This study's findings suggest that, in general, males with a family history of cancer show better health behaviors, whereas females with a family history of cancer demonstrate worse health behaviors.

Total thyroidectomy's association with survival in papillary thyroid cancers and the high proportion of total thyroidectomy in low-risk patients: Analysis of Korean nationwide data.

BACKGROUND: Papillary thyroid cancer has an excellent prognosis, but the appropriate level of treatment is controversial. We compared survival between total thyroidectomy and less-than-total thyroidectomy, and examined the proportion of patients with papillary thyroid cancer in Korea undergoing total thyroidectomy. METHODS: A nationwide sample of 5,230 papillary thyroid cancer patients was included (total thyroidectomy: 4,262, less-than-total thyroidectomy: 968). Using multivariate Cox regression, we compared overall survival and cause-specific survival by the extent of thyroidectomy (total thyroidectomy versus less-than-total thyroidectomy) for a 1:1 optimal match via the propensity score and for the total study population. We also compared overall survival by extent of thyroidectomy and the proportion of total thyroidectomy in different risk groups using papillary thyroid cancer staging systems. RESULTS: We saw no difference in overall survival by extent of thyroidectomy in the propensity score matched population and the total study population (hazard ratio for less-than-total thyroidectomy 0.82, 95% confidence interval 0.52-1.29; hazard ratio for less-than-total thyroidectomy 1.03, 95% confidence interval 0.71-1.48, respectively). Similarly, there were no differences in thyroid cancer-specific survival by extent of thyroidectomy. None of the different risk groups showed differences in overall survival by surgical extent, although total thyroidectomy improved overall survival in older females with larger tumors. The proportion of papillary thyroid cancer patients who received a total thyroidectomy was 80% or greater regardless of risk group classification. CONCLUSION: Total thyroidectomy had no survival advantage over less-than-total thyroidectomy in Korean papillary thyroid cancer patients except in a specific high-risk group. 80% or more of low-risk papillary thyroid cancer patients received a total thyroidectomy. These results suggest that further patient-centered treatment which considers both quality of life and clinical outcome is needed.