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Background Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Purpose This study investigated association between smoking habit change and cancer-related mortality risk in Korean women. Materials and Methods Study population were women aged = 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk. Results Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold). Conclusion Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers. [ABSTRACT FROM AUTHOR]

Abstract Background Breast cancer is the most commonly diagnosed cancer in women worldwide, and underlying mechanistic pathways associated with breast cancer-specific and non-breast cancer-related deaths are of importance. Emerging evidence suggests a role of oxysterols, derivates of cholesterol, in multiple chronic diseases including breast cancer and coronary artery diseases. However, associations between oxysterols and survival have been minimally studied in women diagnosed with breast cancer. In this large breast cancer patient cohort, we evaluated associations between a panel of circulating oxysterols and mortality and recurrence outcomes. Methods Concentrations of 13 circulating oxysterols representing different pathways of cholesterol metabolism were quantified using liquid-chromatography mass-spectrometry. Associations between baseline levels of oxysterols and cause-specific mortality outcomes and recurrence following a breast cancer diagnosis were assessed in 2282 women from the MARIE study over a median follow-up time of 11 years. We calculated hazard ratios (HR) and 95% confidence intervals (CI) using multivariable Cox proportional hazard models and competing risks models. Results We observed no associations for circulating oxysterols and breast cancer-specific outcomes. Higher levels of six oxysterols were associated with an increased risk of cardiovascular disease death, including 24S-hydroxycholesterol (alternative bile acid pathway, HRlog2 = 1.73 (1.02, 2.93)), lanosterol (cholesterol biosynthesis pathway, HRlog2 = 1.95 (1.34, 2.83)), 7-ketocholesterol (HRlog2 = 1.26 (1.03, 1.55)), 5α,6α-epoxycholesterol (HRlog2 = 1.34 (1.02–1.77)), and 5a,6β-dihydroxycholestanol (HRlog2 = 1.34 (1.03, 1.76)). After adjusting for multiple comparisons, none of the associations were statistically significant. Conclusion We provide first evidence on a range of circulating oxysterols and mortality following a breast cancer diagnosis, contributing to a better understanding of associations between different pathways of cholesterol metabolism and prognosis in women with a breast cancer diagnosis. The findings of this study suggest circulating oxysterols may be associated with cardiovascular mortality among women diagnosed with breast cancer. Further studies are needed to evaluate these oxysterols as potential markers of risk for cardiovascular mortality among women with a breast cancer diagnosis as well as their clinical potential.

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer., Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated., Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC., Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Helga H Hektoen,1 Randi E Gislefoss,1 Jo S Stenehjem,1 Hilde Langseth,1 Karol Axcrona,2 Alison M Mondul,3 Trude E Robsahm,1 Bettina K Andreassen1 1Department of Research, Cancer Registry of Norway, Oslo, Norway; 2Department of Urology, Akershus University Hospital, Lørenskog, Norway; 3Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USACorrespondence: Helga H Hektoen Ullernchausseen 64, Oslo, 0379, NorwayTel +47 22 92 89 21Email Helga.helseth.hektoen@kreftregisteret.noPurpose: Circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with overall cancer mortality and selected cancers, while for urothelial bladder cancer (BC) this relationship is unclear. We aimed to examine the association between 25(OH)D and BC mortality.Materials and Methods: We used prediagnostic serum from 378 BC cases within the population-based Janus Cohort. Cox regression models estimated hazard ratios (HRs), with 95% confidence intervals (CIs), for the association between 25(OH)D and BC-specific and all-cause mortality. Restricted cubic splines were assessed to examine non-linear risk associations. Analyses were stratified by tumor invasiveness (non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC)). Additionally, the association between 25(OH)D and all-cause mortality was assessed for 378 cancer-free matched controls.Results: 25(OH)D deficiency (< 50 nmol/L) was associated with higher BC-specific mortality (HR 1.87, 95% CI 1.10– 3.20), when compared with insufficient levels (50– 74 nmol/L). Stratification by tumor invasiveness revealed that this result was evident for NMIBC only, both with respect to BC-specific mortality (HR 2.84, 95% CI 1.14– 7.12) and all-cause mortality (HR 1.97, 95% CI 1.06– 3.65). No association between 25(OH)D levels and all-cause mortality was found in cancer-free controls.Conclusion: 25(OH)D deficiency (< 50 nmol/L) prior to a BC diagnosis was associated with increased risk of BC-specific mortality, when compared to insufficient levels (50– 74 nmol/L). The results were evident among NMIBC patients only, suggesting a more critical role of vitamin D deficiency in an early stage of the disease.Keywords: cancer, vitamin D, mortality, cancer death, prospective study

Outcomes of early cancers after kidney transplantation are not well-understood. We included recipients of first live and deceased donor kidney transplants who developed de novo cancers in Australia and New Zealand between 1980-2016. We compared the frequency and stage of specific cancer types that developed early (≤12-months) and late (>12-months) post-transplantation. Risk factors for death were evaluated using multivariable Cox regression analyses. Of 2,759 recipients who developed de novo cancer, followed-up for 40,035 person-years, 243 (8.8%) patients were diagnosed with early cancer. Post-transplant lymphoproliferative disease, urinary cancers and melanoma were the most common cancer types (26%, 18%, and 12%) and the majority were either in-situ or locally invasive lesions (55%, 84%, and 86%). Tumors arising early from the gastrointestinal and respiratory systems were uncommon but aggressive, with 40% presenting with metastatic disease at time of diagnosis. Overall, 32% of patients with early cancers died within a median of 4.7 months (IQR:0.6-16) postdiagnosis and 91% were cancer-related deaths. Older recipient and donor age were associated with an increased risk of all-cause death. Early cancers, though infrequent in kidney transplant recipients, are associated with poor outcomes, as nearly 1 in 3 died from cancer-related death; with majority of deaths occurring within 12-months of cancer diagnosis. [ABSTRACT FROM AUTHOR]

Abstract Background Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes. Methods We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models. Results Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers. Conclusions PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.

The article focuses on substitution of unprocessed and processed red meat with poultry or fish and total and cause-specific mortality.

Background. Endometrial cancer (EC) is the most common gynecologic cancer in the U.S. The objective of this cohort study was to characterize the clinical and pathologic features that are associated with endometrial cancer--specific death for women cared for at a single National Cancer Institute--designated comprehensive cancer center. Patients, Materials, and Methods. This is a retrospective cohort from 2014 to 2017 including all women who had a hysterectomy for EC. Charts were reviewed for clinical and pathologic data, focusing on survival outcomes. Results. Seven hundred seventy-one patients with EC underwent hysterectomy with 760 informative for outcomes. Seventy-six (10%) deaths were related to their EC; 62 women died from recurrent EC. Nonendometrioid histology and advanced stage were predictors of recurrence and EC death. Among patients with endometrioid ECs, mismatch repair status was significantly associated with EC-specific survival (relative risk = 4.8; 95% confidence interval, 2.3--10.3; p < .0001). Most patients with EC who recurred died of their disease 62/83 (74.7%). Nearly half of the patients that recurred (27/62) had no additional therapy at the time of recurrence. Overall survival was significantly longer for those women who had additional treatment at the time of recurrence; however, the improvement in overall survival with therapy at recurrence was largely attributable to effects in those women who were adjuvant therapy naïve. Conclusion. Although there is benefit of treatment at the time of recurrence for treatment-naïve women; only approximately half of patients were able to receive therapy. There is an urgent need for continued efforts for more effective EC therapy in both the front-line and recurrent setting as well as early identification of cancer diagnosis and recurrence. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a leading cause for cancer deaths worldwide and its survival rate remains low. The one year- and five year-survival rate remain as low as 21% and 6-8% consecutively. Little is known about the survival rate of pancreatic cancer in Indonesia. This study aims to evaluate the survival rate of pancreatic cancer patients at Gastrointestinal Endoscopy Center, National Referral Hospital Dr. Cipto Mangunkusumo, Jakarta, during November 2018 to December 2018. Method: This retrospective cohort study extracted the registry data of newly diagnosed pancreatic cancer patients between November 2018 to December 2018 from the Gastrointestinal Endoscopy Center, Cipto Mangunkusumo Hospital, Jakarta. All patients were followed since they were diagnosed to two months after diagnosis or 31st December 2018 or to their date of death, whichever came first. Results: We found 12 newly diagnosed pancreatic cancer cases between November 2018 to December 2018. The mean age at diagnosis was 55 years old, with 58% male, 50% sundanese, and 75% patient come from low educated level. About 58% cases presented with cholangitis, and the mean bilirubin concentration at diagnosis was 26 mg/dL. All patient came with an obstructive jaundice symptoms, and 91% had endoscopic biliary drainage procedure. After 2 months of observation, we found 16% patient died due to unresolved infection. Conclusion: There were 12 cases of pancreatic cancer, of which 16% pancreatic cancer patients died within 2 months of follow up. Infection is the main cause of morbidity and mortality in pancreatic cancer patients.

Sophon Siwachat,1,* Nirush Lertprasertsuke,2,* Narumon Tanatip,1 Sarawut Kongkarnka,2 Juntima Euathrongchit,3 Yutthaphan Wannasopha,3 Thatthan Suksombooncharoen,4 Busayamas Chewaskulyong,4 Wil Lieberman-Cribbin,5 Emanuela Taioli,5 Somcharoen Saeteng,1 Apichat Tantraworasin1,6,7 1Department of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 2Department of Pathology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Department of Radiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 4Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 5Department of Population Health Science and Policy, Institute for Translational Epidemiology, Icahn Medical School at Mount Sinai, New York, NY, USA; 6Pharmacoepidemiology and Statistics Research Center (PESRC), Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand; 7Clinical Epidemiology and Clinical Statistic Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand*These authors contributed equally to this workCorrespondence: Apichat TantraworasinDepartment of Surgery, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, ThailandTel +665 3945767Fax +665 3936139Email ohm_med@hotmail.comPurpose: The aim of this study was to identify the association between Thailand’s insurance types and stage at presentation, surgical approach, tumor recurrence and cancer-specific survival in resectable non-small cell lung cancer (NSCLC) patients in northern Thailand.Patients and Methods: Medical records of patients with NSCLC who underwent pulmonary resection at Chiang Mai University Hospital from January 2007 through December 2015 were retrospectively reviewed. Patients were divided into two groups: patients with the Universal Coverage Scheme (UCS) or Social Security Scheme (SSS) and patients with the Civil Servant Medical Benefit Scheme (CSMBS) or private insurance (PI). Patient characteristics were assessed. The primary outcome was cancer-specific survival while the secondary outcome was tumor recurrence. Cox’s regression and matching propensity score analysis was used to analyze data.Results: This study included 583 patients: 344 with UCS or SSS and 239 with CSMBS or PI. Patients with UCS or SSS were more likely to be active smokers, have a lower percent predicted FEV1, present with higher-stage tumors and worse differentiated tumors, present with tumor necrosis, and undergo an open surgical approach than those with CSMBS or PI. At multivariable analysis of all patients cohort, there were no significant differences in terms of early stage at presentation (adjusted odds ratio (ORadj) = 0.94, 95% confidence interval (CI) = 0.65– 1.37), undergoing lobectomy (ORadj = 0.59, 95% CI = 0.24– 1.46), and recurrent-free survival (adjusted hazard ratio (HRadj) =1.20, 95% CI = 0.88– 1.65) between groups (UCS/SSS versus CSMBS/PI). However, patients with UCS or SSS had shorter cancer-specific survival (HRadj = 1.61, 95% CI = 1.22– 2.15). The results from the propensity score matched patient cohort were not different from those analyses on the full patient cohort.Conclusion: Thai insurance types have an effect on cancer-specific survival. The Thai government should recognize the importance of these differences, and further multi-center studies with a larger sample size are warranted to confirm this result.Keywords: Universal Coverage Scheme, Social Security Scheme, Civil Servant Medical Benefit Scheme, cancer death, coverage, pulmonary resection

Background: An increased risk of cancer death has been demonstrated for patients diagnosed with acute coronary syndrome (ACS). We are investigating possible geographic risk disparities. Methods: This prospective study included 541 ACS patients who were admitted to hospitals and discharged alive in three provinces of Italy's Veneto region. The patients were classified as residing in urban or rural areas in each province. Results: With 3 exceptions, all patients completed the 22-year follow-up or were followed until death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. Pre-existing malignancy was noted in 15 patients, whereas 106 patients developed cancer during the follow-up period, which represented 6232 person-years. No difference in the cancer death risk was found between the urban and rural areas or between southern and northern provinces (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.7–1.7; p = 0.59 and HR 1.1; 95% CI 0.9–1.4; p = 0.29, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 1.9; 95% CI 1.1–3.0; p = 0.01). The fully adjusted Cox regression and Fine-Gray competing risk regression models provided similar results. Interestingly, these results persisted, and even strengthened, after exclusion of the 22 patients who developed malignancy and survived to the end of follow-up. We did not observe an urban/rural difference in non-neoplastic death risk or a significant interaction between the geographic areas. Conclusion: Our analysis reveals that the cancer death risk among unselected ACS patients in Italy's Veneto region significantly differs by geography. The northern rural area has the highest risk. These results highlight the importance of implementing a preventive policy based on area-specific knowledge. [ABSTRACT FROM AUTHOR]

Objectives: Previous studies suggest that changes in body weight can lead to an increased risk of mortality in the general population, although the results are controversial. The current study sought to investigate this association further using data from the UK Biobank. Study design: This is a large prospective population-based cohort study. Data were derived from the UK Biobank, with the initial assessments commencing between 2006 and 2010. Methods: Proportional hazard models were used to assess the association between self-reported weight change and risk of all-cause, cancer and cardiovascular mortality. The effect of gender was also investigated. Results: Of 433,829 participants with data for self-reported weight change, the mean age was 56 (standard deviation [SD]: 8.1) years and 55% were female. In total, 55% of participants reported no weight change, 28% gained weight, 15% lost weight, 2% did not know and 0.1% preferred not to give an answer. The median follow-up was 7.1 (interquartile range [IQR]: 6.4–7.8) years. Compared with participants with no weight change, those with weight loss had an increased risk of all-cause mortality (adjusted hazard ratio [HR] 1.25, 95% confident interval [CI] 1.18–1.32), cancer death (HR 1.17, 95% CI 1.08–1.27) and cardiovascular death (HR 1.26, 95% CI 1.12–1.43). Similarly, participants reporting weight gain also had an increased risk of all-cause mortality (HR 1.08, 95% CI 1.02–1.13), cancer death (HR 1.14, 95% CI 1.07–1.22) and cardiovascular death (HR 1.27, 95% CI 1.14–1.42). Participants who had a response ‘do not know’ or ‘prefer not to answer’ showed an increased risk of all-cause and cardiovascular mortality, particularly in men. Conclusions: The results of this study highlight the importance of maintaining a stable weight in middle-aged adults. Further studies are needed to understand the pathophysiology of weight change and its effects on mortality.

BackgroundAn increased risk of cancer death has been demonstrated for patients diagnosed with acute coronary syndrome (ACS). We are investigating possible geographic risk disparities.MethodsThis prospective study included 541 ACS patients who were admitted to hospitals and discharged alive in three provinces of Italy’s Veneto region. The patients were classified as residing in urban or rural areas in each province.ResultsWith 3 exceptions, all patients completed the 22-year follow-up or were followed until death. Urban (46%) and rural (54%) residents shared most of their baseline demographic and clinical characteristics. Pre-existing malignancy was noted in 15 patients, whereas 106 patients developed cancer during the follow-up period, which represented 6232 person-years. No difference in the cancer death risk was found between the urban and rural areas or between southern and northern provinces (hazard ratio [HR] 1.1; 95% confidence interval [CI] 0.7–1.7; p = 0.59 and HR 1.1; 95% CI 0.9–1.4; p = 0.29, respectively) according to the unadjusted Cox regression analysis. Geographic areas, however, showed a strong positive interaction, with risk increasing from the urban to rural areas from southern to northern provinces (HR 1.9; 95% CI 1.1–3.0; p = 0.01). The fully adjusted Cox regression and Fine-Gray competing risk regression models provided similar results. Interestingly, these results persisted, and even strengthened, after exclusion of the 22 patients who developed malignancy and survived to the end of follow-up. We did not observe an urban/rural difference in non-neoplastic death risk or a significant interaction between the geographic areas.ConclusionOur analysis reveals that the cancer death risk among unselected ACS patients in Italy’s Veneto region significantly differs by geography. The northern rural area has the highest risk. These results highlight the importance of implementing a preventive policy based on area-specific knowledge.

This study examines the associations of cancer death and aspects of the 24-h circadian rest-activity rhythm (RAR) on depression symptoms in older spouses. Participants included 46 adults aged 60–94 years (M = 73 years) who experienced the death of a spouse. We tested a multivariate model using cancer death (vs. non-cancer death) and RAR variables as correlates of depression symptoms while controlling for age, sex, physical illness burden, and preparedness for death. We also present a case example to describe the behavioral activity patterns of a participant bereaved by cancer. Cancer death was associated with elevated levels of depression symptoms. However, the timing of the RAR moderated this association. Cancer bereavement was associated with depression symptoms when participants "settled-down" after 11:00 PM. The case example illustrates how intrusive thoughts about death quality impacts a widower's drive to stay busy with daily activities. Settling down earlier in the evening is important for older spouses bereaved by cancer, in terms of fewer symptoms of depression. Objectively specifying the activity patterns of older spouses bereaved by cancer is a promising avenue for interventions that aim to reduce depression symptoms. [ABSTRACT FROM AUTHOR]

Bettina K Andreassen,1 Helga H Hektoen,1 Karol Axcrona,2 Hilde Langseth,1 Jo S Stenehjem,1 Trude E Robsahm1 1Department of Research, Cancer Registry of Norway, Oslo, Norway; 2Department of Urology, Akershus University Hospital, Lørenskog, NorwayCorrespondence: Helga H Hektoen Email Helga.Helseth.Hektoen@kreftregisteret.no View the original paper by Dr Hektoen and colleagues This is in response to the Letter to the Editor

Background: Individuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes. Methods: We used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models. Results: Among 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers. Conclusions: PAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Abstract Background With improvement in hospice palliative care services and long-term care, Republic of Korea (hereafter South Korea) has recorded significant changes in places of death (e.g., hospital, home), especially among older adults. Over the last few decades, the most common places of death in South Korea were hospitals. However, Koreans, especially older adults, reportedly prefer to receive terminal care and eventually die at home. This study was conducted to investigate trends in places of death among older Korean adults and factors associated therewith. Methods Data were obtained from the Korean Death Registration Database maintained by the National Statistical Office. Decedents who died after the age of 65 years from 2001 to 2014 were included in the analysis. For descriptive analysis, proportions of places of death were analyzed and were used to plot graphs for visualizing trends during 13-year period. Logistic regression model was used to evaluate factors associated with places of death (hospital versus home). Results Two million three hundred fifty eight thousand two hundred eleven older adult decedents were included in final analysis. Hospitals were the most common places of death (57.82%), followed by homes (32.12%). Dying at social welfare facilities was rare (2.61%). A gradual increase in hospital deaths (31.38% in 2001 to 75.30% in 2014) and a subsequent decrease in home deaths (60.44% to 15.95% over the same period) were noted. Hospital deaths were more likely for younger patients (ORs 1.28, 95% CI 1.27-1.29), females (ORs 1.28, 95% CI 1.27-1.29), and single/divorced or widowed individuals (ORs 1.77, 1.49 and 1.03 respectively). A higher education level and living in urban areas were strongly associated with a higher likelihood of dying in a hospital. Conclusion Over the study period, there was a consistent increasing trend in hospital deaths in South Korea. Trends in place of death and factors associated therewith should be more intensely investigated and monitored. Resources and facilities should be increased to fulfill end-of-life care preferences and the needs of an increasingly older population in South Korea.

Background: Cancer and cardiovascular disease are the 2 leading causes of death in most developed countries, making up the majority of national health care expenditures. In this study, we investigated nationwide trends of cardiovascular disease and cancer drug expenditure in relation to concomitant trends in cardiovascular disease and cancer death rates.Methods: We obtained cardiovascular and cancer drug expenditure data in Denmark through the Danish Register of Medical Product Statistics. Trends in cancer deaths and cardiovascular disease deaths were observed by linkage to the cancer statistics for the Nordic Countries and Danish Heart Foundation databases.Results: Our data show that introduction and rapid uptake of generic versions of most cardiovascular disease drugs have resulted in a remarkable cost-neutral development in cardiovascular disease drug expenditure from 1995 to 2018 despite increased drug use. This development is contrasted to cancer drug expenditure, which has increased more than 15-fold in the same period. Since 2006, expenditure for cancer drugs has exceeded that for cardiovascular disease drugs and is now more than triple that cost. However, death rates for cancer have dropped a fraction as much as for cardiovascular disease.Conclusion: Our results point to a disproportionate high mortality-adjusted expenditure for cancer drugs compared to cardiovascular disease drugs and demonstrate an enormous potential for national health care savings when cheaper versions like biosimilars of many cancer drugs are introduced. [ABSTRACT FROM AUTHOR]

Nowadays, lung cancer is the leading cause of cancer death in both men and women. The early detection of potentially cancerous cells is the best way to improve the patient's chances of survival. In the medical field, computed tomography (CT) is the best imaging technique and it is helpful for doctors to accurately find the cancerous cells. The authors propose an automatic approach to analyse and segment the lungs and classify each lung into normal or cancer. Initially, the CT lung image is pre‐processed to remove noise. Then, they combine the histogram analysis with thresholding and morphological operations to segment and extract the lung regions. In feature extraction stage, the radiomic features of each lung image are extracted separately. Then to improve the classification accuracy, some of the optimum features are selected using modified graph clustering‐based whale optimisation algorithm. Finally, the selected features are classified using ensemble classifiers such as support vector machine, K‐nearest neighbour, and random forest. Experimental result demonstrates that the proposed method achieves better performance in terms of sensitivity, specificity, precision, recall, F‐measure, and accuracy when compared with other state‐of‐art approaches. [ABSTRACT FROM AUTHOR]

According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments. We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates. We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20–0.22) and 0.22 (95 % CI: 0.21–0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001). SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the third leading cause of cancer deaths in the United States. Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer, accounting for up to 90% of all cases. Patient-reported symptoms are often the triggers of cancer diagnosis and therefore, understanding the PDAC-associated symptoms and the timing of symptom onset could facilitate early detection of PDAC., Objective: This paper aims to develop a natural language processing (NLP) algorithm to capture symptoms associated with PDAC from clinical notes within a large integrated health care system., Methods: We used unstructured data within 2 years prior to PDAC diagnosis between 2010 and 2019 and among matched patients without PDAC to identify 17 PDAC-related symptoms. Related terms and phrases were first compiled from publicly available resources and then recursively reviewed and enriched with input from clinicians and chart review. A computerized NLP algorithm was iteratively developed and fine-trained via multiple rounds of chart review followed by adjudication. Finally, the developed algorithm was applied to the validation data set to assess performance and to the study implementation notes., Results: A total of 408,147 and 709,789 notes were retrieved from 2611 patients with PDAC and 10,085 matched patients without PDAC, respectively. In descending order, the symptom distribution of the study implementation notes ranged from 4.98% for abdominal or epigastric pain to 0.05% for upper extremity deep vein thrombosis in the PDAC group, and from 1.75% for back pain to 0.01% for pale stool in the non-PDAC group. Validation of the NLP algorithm against adjudicated chart review results of 1000 notes showed that precision ranged from 98.9% (jaundice) to 84% (upper extremity deep vein thrombosis), recall ranged from 98.1% (weight loss) to 82.8% (epigastric bloating), and F 1 -scores ranged from 0.97 (jaundice) to 0.86 (depression)., Conclusions: The developed and validated NLP algorithm could be used for the early detection of PDAC., (©Fagen Xie, Jenny Chang, Tiffany Luong, Bechien Wu, Eva Lustigova, Eva Shrader, Wansu Chen. Originally published in JMIR AI (https://ai.jmir.org), 15.01.2024.)

Purpose: This study investigated association between smoking habit change and cancer-related mortality risk in Korean women., Materials and Methods: Study population were women aged ≥ 40 years who underwent two biennial cancer screenings during 2009-2012 and were followed up until 2020. Participants were grouped into sustained nonsmokers, sustained quitters, new quitters, relapsers/smoking initiators, and sustained smokers. Outcomes included all-cause and cancer-related deaths. Cox regression and competing risk analysis was used to assess association between smoking habit change and mortality risk., Results: Of 2,892,590 women, 54,443 death cases were recorded (median follow-up of 9.0 years). Compared with sustained nonsmokers, mortality risk from all causes and cancer-related causes increased in all other smoking groups. Cancer-related risk increased 1.22-fold among sustained quitters (95% confidence interval [CI], 1.10 to 1.36), 1.56-fold (95% CI, 1.40 to 1.75) in new quitters, 1.40-fold (95% CI, 1.21 to 1.62) in relapsers/smoking initiators, and 1.61-fold (95% CI, 1.46 to 1.78) in sustained smokers compared with sustained nonsmokers. Women who were sustained smokers with higher smoking intensity had a higher mortality risk in terms of hazard ratios compared to nonsmokers (< 5 pack-years 2.12-fold, 5-10 pack-years 2.15-fold, and > 10 pack-years 2.27-fold)., Conclusion: Quitting smoking earlier is critical for preventing death from all causes and cancer among female smokers.

Because of the healthy worker effect, mortality rates increased in individuals who were employed and those who were unemployed, and decreased in those economically inactive at baseline in reported studies. To determine if such trends continue during economic recessions, we analyzed mortality rates in Spain before and during the Great Recession in these subgroups. We included 21,933,351 individuals who were employed, unemployed, or inactive in November 2001 and aged 30–64 years in each calendar-year of follow-up (2002–2011). Annual age-adjusted mortality rates were calculated in each group. The annual percentage change in mortality rates adjusted for age and educational level in employed and unemployed persons were also calculated for 2002–2007 and 2008–2011. In employed and unemployed men, mortality rates increased until 2007 and then declined, whereas in employed and unemployed women, mortality rates increased and then stabilized during 2008–2011. The mortality rate among inactive men and women decreased throughout the follow-up. In the employed and the unemployed, the annual percentage change was reversed during 2008–2011 compared with 2002–2007 (−1.2 vs. 3.2 in employed men; −0.3 vs. 4.1 in employed women; −0.8 vs. 2.9 in unemployed men; and −0.6 vs. 1.3 in unemployed women). The upward trends in mortality rates among individuals who were employed or unemployed in 2001 were reversed during the Great Recession (2008–2011). [ABSTRACT FROM AUTHOR]

Although several factors, including heart failure (HF) and inflammation, are known to increase the incidence of cancer, it remains unknown whether HF may increase cancer mortality, especially with a reference to inflammation. We examined 8843 consecutive cardiovascular patients without a prior history of cancer in our CHART-2 Study (mean 68 yrs., female 30.9%). As compared with patients without HF (Stage A/B, N = 4622), those with HF (Stage C/D, N = 4221) were characterized by higher prevalence of diabetes, previous myocardial infarction, atrial fibrillation, and stroke. During the median 6.5-year follow-up (52,675 person-years), 282 cancer deaths occurred. HF patients had significantly higher cancer mortality than those without HF in both the overall (3.7 vs, 2.8%, hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12–1.79, P = 0.004) and the propensity score-matched cohorts (HR 1.46, 95%CI 1.10–1.93, P = 0.008), which was confirmed in the competing risk models. The multivariable Cox proportional hazard model in the matched cohort showed that HF was associated with increased cancer mortality in patients with C-reactive protein (CRP) ≥ 2.0 mg/L (HR 1.87, 95%CI 1.18–2.96, P = 0.008) at baseline, but not in those with CRP < 2.0 mg/L (HR 0.89, 95%CI 0.54–1.45, P = 0.64) (P for interaction = 0.03). Furthermore, temporal changes in CRP levels were associated with cancer death in the overall cohort; HF patients with CRP ≥ 2.0 mg/L at both baseline and 1-year had significantly increased cancer death, while those with CRP ≥ 2.0 mg/L at baseline and < 2.0 mg/L at 1-year not. These results provide the first evidence that HF is associated with increased cancer death, especially when associated with prolonged inflammation. • We examined whether heart failure (HF) increases cancer mortality. • HF patients had significantly higher cancer mortality than those without HF. • Temporal changes in C-reactive protein levels were associated with cancer death. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a leading cause for cancer deaths worldwide and its survival rate remains low. The one year- and five year-survival rate remain as low as 21% and 6-8% consecutively. Little is known about the survival rate of pancreatic cancer in Indonesia. This study aims to evaluate the survival rate of pancreatic cancer patients at Gastrointestinal Endoscopy Center, Cipto Mangunkusumo Hospital, Jakarta, during November 2018 to December 2018. Method: This retrospective cohort study extracted the registry data of newly diagnosed pancreatic cancer patients between November 2018 to December 2018 from the Gastrointestinal Endoscopy Center, Cipto Mangunkusumo Hospital, Jakarta. All patients were followed since they were diagnosed to two months after diagnosis or 31st December 2018 or to their date of death, whichever came first. Results: We found 12 newly diagnosed pancreatic cancer cases between November 2018 to December 2018. The mean age at diagnosis was 55 years old, with 58% male, 50% sundanese, and 75% patient come from low educated level. About 58% cases presented with cholangitis, and the mean bilirubin concentration at diagnosis was 26 mg/dL. All patient came with an obstructive jaundice symptoms, and 91% had endoscopic biliary drainage procedure. After 2 months of observation, we found 16% patient died due to unresolved infection. Conclusion: There were 12 cases of pancreatic cancer, of which 16% pancreatic cancer patients died within 2 months of follow up. Infection is the main cause of morbidity and mortality in pancreatic cancer patients. [ABSTRACT FROM AUTHOR]

Studies of the relationship between circulating 25-hydroxyvitamin D (25(OH)D) and cancer risk have been inconsistent. We hypothesized that serum 25(OH)D was associated with total non-skin cancer incidence and mortality, and/or specifically with colorectal, lung, breast or prostate cancer in an Australian cohort. Serum 25(OH)D was measured in 3818 participants (2166 females) in the 1994/1995 Busselton Health Survey aged 25 to 84 years at baseline. Cancer mortality and events over 20 years follow-up were determined by data linkage. The mean serum 25(OH)D concentration was 60.6 ± 18.0 nmol/L, with 28%, 54% and 18% of participants in the lower (<50 nmol/L), middle (50-75 nmol/L) and higher (≥75 nmol/L) vitamin D status groups, respectively. During follow-up (excluding the first 2 years), 212 participants died from non-skin cancer and 634, 110 and 44 participants had non-skin, colorectal and lung cancer events, respectively; 113 women had breast cancer and 122 men had prostate cancer events. For colorectal cancer, lower circulating 25(OH)D was associated with significantly higher risk compared with the middle group (covariate-adjusted HR 1.62, 95% CI 1.04, 2.53). For breast cancer, women with a higher 25(OH)D level had lower risk than women in the middle group (HR 0.38, 95% CI 0.16, 0.89) and the lower group (HR 0.37, 95% CI 0.15, 0.89). Serum 25(OH)D was not associated with overall cancer death or event, or with lung or prostate cancer. In this community-based cohort, lower 25(OH)D levels were associated with increased risk of colorectal and breast cancer, but not overall cancer risk. [ABSTRACT FROM AUTHOR]

Spatial autocorrelation (SA) techniques were applied to analyze the deaths caused by three types of cancer in Ecuador. One of the aims of these methods is to describe the scale over which spatial patterns of mortalities occur, which may provide suggestions concerning the agents bringing about the patterns. The analysis was carried out using data from the 23 provinces of the country. Applying global spatial autocorrelation techniques as well as local ones (Global Moran's I and Anselin's local I statistics), it was found that in certain regions of the country there is an unusual pattern of the geographical distribution of cancer mortality indicating that a similar geographic structure could be associated with some risk factor. The data used for the study correspond to deaths due to the types of cancer studied for the years 2012 to 2015 and are available from the Statistics Institute of Ecuador. The results should stimulate further research on the possible causes underlying these clusters and associations. [ABSTRACT FROM AUTHOR]

Background: With improvement in hospice palliative care services and long-term care, Republic of Korea (hereafter South Korea) has recorded significant changes in places of death (e.g., hospital, home), especially among older adults. Over the last few decades, the most common places of death in South Korea were hospitals. However, Koreans, especially older adults, reportedly prefer to receive terminal care and eventually die at home. This study was conducted to investigate trends in places of death among older Korean adults and factors associated therewith. Methods: Data were obtained from the Korean Death Registration Database maintained by the National Statistical Office. Decedents who died after the age of 65 years from 2001 to 2014 were included in the analysis. For descriptive analysis, proportions of places of death were analyzed and were used to plot graphs for visualizing trends during 13-year period. Logistic regression model was used to evaluate factors associated with places of death (hospital versus home). Results: Two million three hundred fifty eight thousand two hundred eleven older adult decedents were included in final analysis. Hospitals were the most common places of death (57.82%), followed by homes (32.12%). Dying at social welfare facilities was rare (2.61%). A gradual increase in hospital deaths (31.38% in 2001 to 75.30% in 2014) and a subsequent decrease in home deaths (60.44% to 15.95% over the same period) were noted. Hospital deaths were more likely for younger patients (ORs 1.28, 95% CI 1.27-1.29), females (ORs 1.28, 95% CI 1.27-1.29), and single/divorced or widowed individuals (ORs 1.77, 1.49 and 1.03 respectively). A higher education level and living in urban areas were strongly associated with a higher likelihood of dying in a hospital. Conclusion: Over the study period, there was a consistent increasing trend in hospital deaths in South Korea. Trends in place of death and factors associated therewith should be more intensely investigated and monitored. Resources and facilities should be increased to fulfill end-of-life care preferences and the needs of an increasingly older population in South Korea. [ABSTRACT FROM AUTHOR]