Multivariate Cox Proportional-hazards Regression Models Research Articles

Incidence and predictors of loss to follow-up among HIV-positive adults in northwest Ethiopia: a retrospective cohort study

BackgroundDespite the rapid expansion of antiretroviral therapy services, ‘loss to follow-up’ is a significant public health concern globally. Loss to follow-up of individuals from ART has a countless negative impact on the treatment outcomes. There is, however, limited information about the incidence and predictors of loss to follow-up in our study area. Thus, this study aimed to determine the incidence rate and predictors of loss to follow-up among adult HIV patients on ART.MethodsA retrospective cohort study was undertaken using 484 HIV patients between January 30, 2008, and January 26, 2018, at Debre Markos Referral Hospital. All eligible HIV patients who fulfilled the inclusion criteria were included in this study. Data were entered into Epi-data Version 4.2 and analyzed using STATATM Version 14.0 software. The Nelson-Aalen cumulative hazard estimator was used to estimate the hazard rate of loss to follow-up, and the log-rank test was used to compare the survival curve between different categorical variables. Both bivariable and multivariable Cox-proportional hazard regression models were fitted to identify predictors of LTFU.ResultsAmong a cohort of 484 HIV patients at Debre Markos Referral Hospital, 84 (17.36%) were loss their ART follow-up. The overall incidence rate of loss to follow-up was 3.7 (95% CI 3.0, 5.0) per 100 adult-years. The total LTFU free time of the participants was 2294.8 person-years. In multivariable Cox-regression analysis, WHO stage IV (AHR 2.8; 95% CI 1.2, 6.2), having no cell phone (AHR 1.9; 95% CI 1.1, 3.4), and rural residence (AHR 0.6; 95% CI 0.37, 0.99) were significant predictors of loss to follow-up.ConclusionThe incidence of loss to ART follow-up in this study was low. Having no cell phone and WHO clinical stage IV were causative predictors, and rural residence was the only protective factor of loss to follow-up. Therefore, available intervention modalities should be strengthened to mitigate loss to follow-up by addressing the identified risk factors.

Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study

BackgroundHydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. ObjectiveWe set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. MethodsIn a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatment weighting by propensity scores, with the addition of subgroup analyses. ResultsOut of 3,451 COVID-19 patients, 76.3% received HCQ. Death rates (per 1,000 person-days) for patients receiving or not HCQ were 8.9 and 15.7, respectively. After adjustment for propensity scores, we found 30% lower risk of death in patients receiving HCQ (HR=0.70; 95%CI: 0.59 to 0.84; E-value=1.67). Secondary analyses yielded similar results. The inverse association of HCQ with inpatient mortality was particularly evident in patients having elevated C-reactive protein at entry. ConclusionsHCQ use was associated with a 30% lower risk of death in COVID-19 hospitalized patients. Within the limits of an observational study and awaiting results from randomized controlled trials, these data do not discourage the use of HCQ in inpatients with COVID-19.

A three-mRNA status risk score has greater predictive ability compared with a lncRNA-based risk score for predicting prognosis in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the fifth most common cause of cancer-associated mortality in men, and the seventh in women, worldwide. The aim of the present study was to identify a reliable and robust RNA-based risk score for the survival prediction of patients with hepatocellular carcinoma (HCC). Gene expression data from HCC and healthy control samples were obtained from The Cancer Genome Atlas to screen differentially expressed mRNAs and long non-coding RNAs (lncRNAs). Univariate and multivariate Cox proportional-hazards regression models and the LASSO algorithm for the Cox proportional-hazards model (LASSO Cox-PH model) were used to identify the prognostic mRNAs and lncRNAs among differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs), respectively. Prognostic risk scores were generated based on the expression level or status of the prognostic lncRNAs and mRNAs, and the predictive abilities of these RNAs in TCGA and validation datasets were compared. Functional enrichment analyses were also performed. The results revealed a total of 154 downregulated and 625 upregulated mRNAs and 18 upregulated lncRNAs between tumor and control samples in TCGA dataset. A three-mRNA and a five-lncRNA expression signatures were identified using the LASSO Cox-PH model. Three-mRNA and five-lncRNA expression and status risk scores were generated. Using likelihood ratio P-values and area under the curve values from TCGA and the validation datasets, the three-mRNA status risk score was more accurate compared with the other risk scores in predicting the mortality of patients with HCC. The three identified mRNAs, including hepatitis A virus cellular receptor 1, MYCN proto-oncogene BHLH transcription factor and stratifin, were associated with the cell cycle and oocyte maturation pathways. Therefore, a three-mRNA status risk score may be valuable and robust for risk stratification of patients with HCC. The three-mRNA status risk score exhibited greater prognostic value compared with the lncRNA-based risk score.

Prediction of gastrointestinal bleeding events in patients with acute coronary syndrome undergoing percutaneous coronary intervention: An observational cohort study (STROBE compliant).

Bleeding complications of acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI) are strongly associated with adverse patient outcomes, and gastrointestinal bleeding (GIB) is the most common major bleeding event, especially in the early post-PCI period. Current guidelines recommend routinely conducting bleeding risk assessments. The existing tools are mainly used to evaluate the overall bleeding risk and guide the adjustment of antithrombotic strategies after 1 year. However, there are no specific tools for GIB risk assessment.Between January 2015 and June 2015, 4943 ACS patients underwent PCI were consecutively enrolled in the derivation cohort. GIB, cardiovascular, and cerebrovascular events were recorded within 1 year of follow-up. A validation cohort including 1000 patients who met the same inclusion and exclusion criteria was also established by propensity-score matching baseline characteristics. Multivariable cox proportional-hazards regression model was used to derive a risk-scoring system, and predictive variables were selected. A risk score nomogram based on the risk prediction model was created to estimate the 1-year risk of GIB.In this study, we found that the usage of clopidogrel (hazard ratio, HR: 2.52, 95% confidence intervals, CI: 1.573–4.021) and glycoprotein IIb/IIIa receptor inhibitors (HR: 1.863, 95% CI: 1.226–2.829), history of peptic ulcers (HR: 3.601, 95% CI: 1.226–2.829) or tumor (HR: 4.884, 95% CI: 1.226–2.829), and cardiac insufficiency (HR: 11.513, 95% CI: 7.282–18.202), renal insufficiency (HR: 2.010, 95% CI: 1.350–2.993), and prolonged activated partial thromboplastin time (HR: 4.639, 95% CI: 2.146–10.032) were independent risk factors for GIB 1 year after PCI. Based on these 7 factors, a nomogram and scoring system was established. The area under curve of risk score was 0.824 in the deviation cohort and 0.810 in the verification cohort. In both cohorts, the GIB score was significantly better than that of 3 classical bleeding scores (all P < .05).This score could well predict the risk of GIB within 1 year after PCI and could be used to guide antithrombotic strategies.

Impact of environmental exposure to persistent organic pollutants on lung cancer risk

BackgroundRecent studies suggest that high pre-diagnostic serum concentrations of persistent organic pollutants (POPs) might result in the development of cancers in the general population. However, the association between pre-diagnostic serum POP concentrations and lung cancer risk has not been studied. Here, we evaluated associations between low-dose environmental exposure to POPs and risk of lung cancer using pre-diagnostic serum samples in a case-cohort study based on a population-based prospective cohort. MethodsWe conducted a case-cohort study based on the Korean National Cancer Center Community Cohort, from which we included 118 lung cancer cases and 252 controls. Serum concentrations of POPs were measured by high resolution gas chromatography/high-resolution mass spectrometry, and data were analyzed using multivariable Cox proportional-hazards regression models. ResultsRisk of lung cancer increased per unit increase in the natural log-transformed concentrations of the sum of chlordane congeners, total PCBs, and all PCBs subgrouped by the number of chlorines or ortho- substituted chlorines on the molecules, except for tri/tetrachlorobiphenyls, in all models. Among individual POP analytes with a detection rate >80%, after Bonferroni adjustment, only trans-nonachlor was associated with lung cancer risk. In categorical models, risk of lung cancer was associated with serum concentration of chlordane (4th vs. 1st quartile, hazard ratio [95% confidence interval], 8.79 [2.77–27.97]). Dose-dependent relationships were also found between risk of lung cancer and serum concentrations of PCBs regardless of their degree of chlorination, substitution pattern, or binding affinity to receptors (total PCBs, P = 0.002; mid-chlorinated PCBs, P = 0.004; high-chlorinated PCBs, P < 0.001; non- and mono-ortho PCBs, P = 0.031; di-ortho PCBs, P = 0.003; PCBs with dioxin-like activity, P = 0.011; non-dioxin-like non-/mono-ortho PCBs, P = 0.060). ConclusionsSerum concentrations of chlordane and PCBs are associated with risk of lung cancer in the general population, even decades after the ban on their production and use.

P0759ORTHOSTATIC SYSTOLIC BLOOD PRESSURE CHANGE AND THE RISK OF CHRONIC KIDNEY DISEASE: A COMMUNITY-BASED PROSPECTIVE STUDY IN KOREA

Abstract Background and Aims There have been no studies which explored the relationship between orthostatic blood pressure (BP) change and incident chronic kidney disease (CKD) in Asian population. Method We reviewed the data of 7,461 non-CKD adults aged 40-69 years who participated in Ansung_Ansan Cohort, a prospective community-based cohort study. BP was measured on supine position and 2 minute–upright position, and the difference was defined as orthostatic BP change. Incident CKD was defined as the first event to be estimated glomerular filtration rate &amp;lt; 60 ml/min/1.73 m2, which was confirmed at least 2 or more times thereafter. Results Of 7,461, orthostatic diastolic BP change was not associated with incident CKD in multivariate Cox proportional-hazard regression model. However, per 1 mmHg increase of orthostatic systolic BP was associated with decreased hazard of incident CKD: hazard ratio 0.988 and 95% confidence interval (0.982-0.994, P &amp;lt;0.001). In penalized spline curve analysis, we identified L-shaped relationship between orthostatic systolic BP change and incident CKD, with the threshold of - 2.4 mmHg. In subgroup analysis, the relationship between orthostatic systolic BP change and incident CKD was evident, particularly in participants without central obesity and reduced high density lipoprotein cholesterol and those with increased white blood cells. Conclusion Orthostatic SBP change was independently associated with incident CKD development. Future studies need to be followed to confirm the results.

Abstract A053: Association between socioeconomic status and access to specialized cancer consultation and treatment among advanced gastrointestinal cancers

Abstract Introduction: Gastrointestinal (GI) cancers of the pancreas, esophagus, stomach, colon and rectum often present at an incurable stage. Treatments such as chemotherapy and radiotherapy can improve quality and quantity of life for patients with these advanced gastrointestinal (GI) cancers. However, many patients fail to receive such treatments or even consult with a cancer specialist to determine if treatment is an option. Socioeconomic status (SES) is associated with cancer outcomes, but the mechanisms as to why, such as access to specialized care, are not clearly established. This study examined the association between SES and receipt of specialized cancer consult and treatment in Ontario, Canada. Methods: This was a population-based retrospective cohort study of advanced GI cancer patients diagnosed between 2007 and 2017 using linked administrative databases. The exposure of SES was defined using the deprivation item in the Ontario Marginalization Index. The outcome of oncology consult was defined as a consultation with either a radiation oncologist or a medical oncologist and the outcome of treatment was defined as receipt of chemotherapy or radiotherapy. Both were measured in the year following diagnosis. Multivariable Cox-proportional hazards regression models were used to determine association of deprivation with oncology consult and treatment. Confounders identified a priori include age, sex, comorbidities and cancer site. Results: 29,297 patients had a diagnosis of advanced GI cancer and were included in the study. 27.4% of the cohort did not have an oncology consult and 53.7% did not receive treatment in the year following diagnosis. The most deprived quintile compared to the least deprived quintile was associated with decreased consult (HR 0.89 (0.85-0.93)) and decreased treatment (HR 0.81 (0.77-0.86)) after adjusting for confounders. Conclusion: This study found that even in a single-payer universal healthcare system, SES is associated with access to specialized cancer care. Future research should examine mechanisms through which policy might help low SES patients access specialized cancer care. Citation Format: Laura E Davis, Natalie G Coburn, Julie Hallet, Craig C Earle, Sten Myrehaug, Ying Li, Alyson L Mahar. Association between socioeconomic status and access to specialized cancer consultation and treatment among advanced gastrointestinal cancers [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A053.

Investigating the impact of medical comorbidities in patients taking beta blockers and treated with immunotherapy for metastatic melanoma.

e15162 Background: Combined administration of β-adrenergic antagonist with IL-2, anti-PD-1, and/or anti-CTLA-4 immunotherapy was associated with a better overall survival in metastatic melanoma patients. This result was also reinforced by the significant reduction in tumor growth in a murine melanoma model when a β2-selective antagonist was combined with anti-PD1/IL-2 immunotherapy. Here we sought to elucidate the impact of the various comorbidities behind the indications of β-blockers, and how they might have influenced the patients’ immunotherapy treatment response. Methods: A single-institution retrospective chart review was performed to examine the medical comorbidities with indications for β-blockers in the melanoma patients who received IL-2, αPD-1 and/or αCTLA-4 immunotherapy between January 2000 and March 2015. Two groups were identified: one that took a selective β-1 blocker (N = 41), and another that took a nonselective pan β-blocker (N = 17). The primary analysis compared the distribution of different comorbidity types between two groups, using the Fisher’s exact test. A secondary analysis examined the association of overall survival and the β-blocker groups by further controlling for comorbid conditions, using the multivariate Cox Proportional-Hazard regression model. Results: Seven different comorbidities with indications for β-blocker usage were identified. Of those comorbidities, only the presence of ischemic heart disease was marginally different between the two groups (β-1 group 19.5% vs. pan-β group 47.1%, p-value = 0.0697). There was no difference for overall survival between each of the comorbidity conditions. When performing the multivariate Cox Proportional-Hazard regression model, β-blocker usage still remained statistically significant for the overall survival (HR 0.27, CI 0.0966-0.768, p = 0.0139), even after controlling for the comorbid conditions. Conclusions: Immunotherapy with pan β-adrenergic blockade was associated with a significantly improved overall survival rate for metastatic melanoma. Furthermore, having a comorbid condition that indicated for the prescription of β-blockers was not a factor in establishing this survival rate.

Effect of sorafenib and prophylactic TACE for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion

Objective: To study the effect of sorafenib and prophylactic transarterial chemoembolization (TACE) for prevention of postoperative relapse in patients with liver cancer combined with microvascular invasion (MVI) after using radical hepatectomy. Methods: A retrospective analysis was performed on 137 cases that underwent radical hepatectomy at the First Affiliated Hospital of Zhengzhou University from August 2015 to January 2018. Clinical data of liver cancer patients with MVI were diagnosed by postoperative pathology. General data of the three groups were analyzed. Kaplan-Meier was used to calculate the tumor-free survival rate. COX proportional hazards-model was used to analyze the independent risk factors for postoperative recurrence of liver cancer with MVI recurrence. Counting data was compared by x(2) test between groups, and log-rank test was used to compare the tumor-free survival rates. Results: A, B, and C groups had 49, 36, and 52 cases, respectively. General clinicopathological data of the three groups were not statistically significant. The postoperative tumor-free survival rates at 1-, 2-, and 3-years were 71.4%, 51.0%, 38.8%, 86.1%, 75.0%, 66.7%, and 82.7%, 75.0%, and 59.6% respectively in A, B, and C groups. Multivariate Cox proportional-hazards regression model showed that patients' age (HR = 0.622, P = 0.046), maximum tumor diameter (HR = 1.661, P = 0.033), prophylactic TACE (HR = 0.544, P = 0.019), and postoperative use of sorafenib (HR = 0.419, 0.222, 0.791, P = 0.007) were independent risk factors for postoperative recurrence of liver cancer with MVI. Conclusion: Sorafenib or prophylactic TACE use can significantly reduce the recurrence rate within 3 years after radical surgery in patients with liver cancer who were confirmed to have MVI by postoperative pathology.

Incidence and Risk Assessment for Atrial Fibrillation at 5 Years: Hypertensive Diabetic Retrospective Cohort.

(1) Background: The link between diabetes and hypertension is mutual and reciprocal, increasing the risks for the development of atrial fibrillation (AF). The main objective was to develop a prediction model for AF in a population with both diabetes and hypertension at five years of follow-up. (2) Methods: A multicenter and community-based cohort study was undertaken of 8237 hypertensive diabetic patients without AF between 1 January 2103 and 31 December 2017. Multivariate Cox proportional-hazards regression models were used to identify predictors AF and to stratify risk scores by quartiles. (3) Results: AF incidence was 10.5/1000 people/years (95% confidence interval (CI) 9.5–11.5), higher in men. The independent prognostic factors identified: age (hazard ratio (HR) 1.07 95% CI 1.05–1.09, p < 0.001), weight (HR 1.03 95% CI 1.02–1.04, p < 0.001), CHA2DS2VASc score (HR 1.57 95% CI 1.16–2.13, p = 0.003) and female gender (HR 0.55 95% CI 0.37–0.82, p = 0.004). Q4 (highest-risk group for AF) had the highest AF incidence, stroke and mortality, and the smallest number needed to screen to detect one case of AF. (4) Conclusions: Risk-based screening for AF should be used in high cardiovascular risk patients as the hypertensive diabetics, for treatment of modifiable cardiovascular risk, and monitoring AF detection.

The Impact of Insurance and Marital Status on Survival in Patients with Nasopharyngeal Carcinoma.

Objective: This study aimed to explore the influence of social support on the survival outcomes of patients with nasopharyngeal carcinoma (NPC). We examined whether the combined proxy influenced whether patients were more likely to receive radiotherapy. Methodology: data were collected from the 18 registries of the National Cancer Institute’s Surveillance, Epidemiology, and End Results database. The association between both insurance status and marital status and disease-specific survival rates were evaluated with a multivariate Cox proportional-hazards regression model to calculate the hazard ratios and associated confidence intervals. Odds ratio (OR) computed by logistic regression was also used to examine the relationship between the receipt of radiotherapy and insurance and marital status. Results: insured and uninsured patients differed significantly in T-stage, N-stage, M-stage, radiotherapy use, race, and marital status. The uninsured-non-married patients showed the lowest 5-year disease-specific survival rates. We further found unmarried patients with either Medicaid (OR, 0.40), or no insurance (OR, 0.24) had lower odds of receiving radiotherapy than those with insurance at diagnosis. Conclusions: uninsured-unmarried NPC patients had a significantly higher risk of distant metastasis at diagnosis, poorer 5-year disease-specific survival, and were less likely to receive radiotherapy than insured-married patients.

Incidence and Predictors of Tuberculosis among Adult Diabetic Patients, Debre Markos Referral Hospital, Northwest Ethiopia, 2018: A Retrospective Cohort Study.

BackgroundTuberculosis remains a serious global public health problem. It mainly affects the lungs, and occurs in every part of the world. The link between tuberculosis and diabetes mellitus is essential to inform programs and policies, yet there is a scarcity of information in our study area. Therefore, this study aimed to investigate the incidence and predictors of tuberculosis among diabetic patients at Debre Markos Referral Hospital, northwest Ethiopia.MethodsThis institutionally based retrospective cohort study was undertaken among 433 diabetic patients of Debre Markos Referral Hospital between January 2013 and December 2017. All eligible diabetic patients who met the inclusion criteria were included in the study. Data were entered using EpiData version 3.1 and analyzed using Stata version 14. The survival time of diabetic patients was estimated using Kaplan–Meier survival curves, and survival time among different categorical variables compared using the log-rank test. Both bivariate and multivariate Coxproportional-hazard regression models were fitted to identify independent predictors of tuberculosis among diabetic patients.ResultsAmong the cohort of 43326 (6%) developed tuberculosis during follow-up. The overall tuberculosis-incidence rate was 2.4 per 100 with 95% CI. The total time allotted to follow up the study participants was 1,101.5 person-years. Using multivariate Cox regression analysis, history of alcohol consumption (adjusted incidence ratio 4, 95% CI 1.2–13; P=0.02) and history of tuberculosis (12, 95% CI 3–39; P=0.01) significantly increased the risk of tuberculosis, but normal body-mass index and above (≥18.5 kg/m2) was associated with a rate reduction (0.34, 95% CI 0.14; P=0.80; 0.03) forincidence of tuberculosis.ConclusionIn this study, we found a high rate of tuberculosis among diabetic patients. Factors significantly linked with increased risk of tuberculosis included history of alcohol consumption, history of tuberculosis, and low body-mass index. Early screening and treatment for tuberculosis is highly recommended at diabetes mellitus follow-up for patients with these risk factors.

Neonatal mortality in the neonatal intensive care unit of Debre Markos referral hospital, Northwest Ethiopia: a prospective cohort study

BackgroundNeonatal mortality remains a serious global public health problem, but Sub-Saharan Africa (SSA), in particular, is largely affected. Current evidence on neonatal mortality is essential to inform programs and policies, yet there is a scarcity of information concerning neonatal mortality in our study area. Therefore, we conducted this prospective cohort study to determine the incidence and predictors of neonatal mortality at Debre Markos Referral Hospital, Northwest Ethiopia.MethodsThis institutionally-based prospective cohort study was undertaken among 513 neonates admitted to the neonatal intensive care unit of Debre Markos Referral Hospital between December 1st, 2017 and May 30th, 2018. All newborns consecutively admitted to the neonatal intensive care unit during the study period were included. An interviewer administered a questionnaire with the respective mothers. Data were entered using Epi-data™ Version 3.1 and analyzed using STATA™ Version 14. The neonatal survival time was estimated using the Kaplan-Meier survival curve, and the survival time between different categorical variables were compared using the log rank test. Both bi-variable and multivariable Cox-proportional hazard regression models were fitted to identify independent predictors of neonatal mortality.ResultsAmong a cohort of 513 neonates at Debre Markos Referral Hospital, 109 (21.3%) died during the follow-up time. The overall neonatal mortality rate was 25.8 deaths per 1, 000 neonate-days (95% CI: 21.4, 31.1). In this study, most (83.5%) of the neonatal deaths occurred in the early phase of neonatal period (< 7 days post-partum). Using the multivariable Cox-regression analysis, being unemployed (AHR: 1.6, 95% CI: 1.01, 2.6), not attending ANC (AHR: 1.9, 95% CI: 1.01, 3.5), not initiating exclusive breastfeeding (AHR: 1.7, 95% CI: 1.02, 2.7), neonatal admission due to respiratory distress syndrome (AHR: 2.0, 95% CI: 1.3, 3.1), and first minute Apgar score classification of severe (AHR: 2.1, 95% CI: 1.1, 3.9) significantly increased the risk of neonatal mortality.ConclusionIn this study, we found a high rate of early neonatal mortality. Factors significantly linked with increased risk of neonatal mortality included: unemployed mothers, not attending ANC, not initiating exclusive breastfeeding, neonates admitted due to respiratory distress syndrome, and first minute Apgar score classified as severe.

Biofilm-active antibiotic treatment improves the outcome of knee periprosthetic joint infection: Results from a 6-year prospective cohort study

Biofilm-active antibiotics are suggested to improve the outcome in periprosthetic joint infection (PJI). However, the type, dose and duration of antibiotic treatment is rarely specified and their impact on outcomes is unknown. In this prospective cohort study, the infection and functional outcome were compared in 131 patients with knee PJI treated with or without biofilm-active antibiotics. The infection and functional outcome were evaluated by the Kaplan-Meier survival method to estimate the probability of infection-free survival; comparison between subgroups was performed by log-rank test. The influence of variables on the survival probability was analysed using univariate and multivariate Cox proportional-hazards regression models. Functional outcome was evaluated by pain intensity and the Knee injury and Osteoarthritis Outcome Score (KOOS). Among the 131 patients, 55 (42%) were treated with biofilm-active antibiotics and 76 (58%) were treated with non-biofilm-active antibiotics. The median follow-up period was 3.7 years (range, 2.0-7.6 years), and the infection-free survival probability was 74% (95% CI 61-85%) after 1 year and 56% (95% CI 47-66%) after 2 years. Infection-free survival after 1 year was better for patients who received biofilm-active antibiotics compared with those who did not (83% vs. 70%; P=0.040) and remained superior after 2 years (67% vs. 48%; P=0.038). In addition, biofilm-active antibiotic treatment was associated with lower pain intensity (P=0.006) and higher KOOS on all five subscales. In patients with knee PJI, biofilm-active antibiotic therapy was associated with better infection outcome, lower pain intensity and better joint function.

Main pancreatic duct to parenchymal thickness ratio and degree of atrophy are associated with overall survival in primarily resected pancreatic cancer

Background: Ductal adenocarcinoma of the pancreatic head induces morphological changes of the gland structure, with potential parenchymal degeneration and main pancreatic duct (MPD) dilation. Aim of this study was to evaluate whether these radiologic findings are associated with oncologic outcomes. Material & Methods: From an institutional prospectively maintained database, patients who underwent upfront pancreatoduodenectomy and had a preoperative CT-scan imaging available were assessed. Included patients were divided into short- (3-12 months following surgery) and long-term (≥36 months) survivors. Thickness of the pancreatic gland, parenchymal atrophy, size of the MPD, and distance of the tumor from the ampulla were assessed at the preoperative CT-scan. Results: One-hundred-eighteen patients were included, 68 (57.6%) in the short- and 50 (42.4%) in the long-term survival group. Patients in the short-term survival group had significantly higher Ca19-9 levels (p=0.027), larger tumors (32.6±12.1mm vs. 26.5±11.6mm, p=0.008), poorer differentiation (p=0.003), higher positive R-status rate (p=0.008), and reduced receipt of adjuvant chemotherapy (p=0.020). A significant difference in parenchymal atrophy between groups was also detected (p=0.032). Moreover, the MPD-to-pancreatic thickness ratio normalized for the distance from the ampulla was significantly lower in the short-term group (3.6±6.2 vs. 8.2±12.0mm, p=0.016). At survival analysis, the MPD-to-pancreatic thickness ratio and the degree of parenchymal atrophy were associated with OS (p=0.01 and p=0.020, respectively; log-rank test). At a multivariate Cox-proportional hazards regression model, only the MPD-to-pancreatic thickness ratio, dichotomized at the best predictive value, was independently associated with OS (HR=0.48; p=0.015), together with positive R-status (HR=1.78; p=0.040), and receipt of adjuvant treatment (HR=0.48; p=0.015). Conclusions: A high MPD-to-pancreatic thickness ratio normalized for the distance from the ampulla predicts improved long-term survival in patients undergoing upfront resection for cancer of the pancreatic head. Whether these radiologic features are related to different biological tumor behavior remains elusive and should be addressed in further studies.

Lung function as a predictor of incident type 2 diabetes in community-dwelling adults: A longitudinal finding over 12 years from the Korean Genome and Epidemiology Study

AimReduced lung function is associated with type 2 diabetes (T2D), but there are limited data in East Asian populations on the relationship between them. For this reason, this study investigated the longitudinal relationship of lung function with incident T2D in Korean adults. MethodsThe study included 7583 non-diabetic adults aged 40–69 years from the Korean Genome and Epidemiology Study. Participants were divided into four groups according to gender-specific quartiles (Q1–Q4) of %PFVC and %PFEV1. Also, HRs with 95% CIs for incident T2D were prospectively analyzed as per American Diabetes Association criteria using multivariate Cox proportional-hazards regression models. ResultsDuring a 12-year follow-up, 1403 (18.5%) participants presented with newly developed T2D. HRs (95% CIs) of incident T2D in Q1 vs. Q4 (reference) of %PFVC were 1.67 (1.35–2.07) for men and 1.77 (1.39–2.24) for women and, of %PFEV1, 1.58 (1.28–1.95) for men and 1.61 (1.27–2.03) for women, after adjusting for age, waist circumference, smoking status, alcohol intake, regular exercise, education levels, monthly household income, family history of diabetes, HOMA-IR, triglycerides, HDL cholesterol and high-sensitivity C-reactive protein levels. ConclusionReduced lung function precedes and significantly predicts the future development of T2D independently of obesity, smoking and inflammation in community-dwelling middle-aged and elderly people.

Incidence and predictors of tuberculosis among HIV-positive adults on antiretroviral therapy at Debre Markos referral hospital, Northwest Ethiopia: a retrospective record review

BackgroundTuberculosis is the leading cause of morbidity and mortality among people living with human immunodeficiency virus. Almost one-third of deaths among people living with human immunodeficiency virus are attributed to tuberculosis. Despite this evidence, in Ethiopia, there is a scarcity of information regarding the incidence and predictors of tuberculosis among people living with HIV. Thus, this study assessed the incidence and predictors of tuberculosis among HIV-positive adults on antiretroviral therapy.MethodsThis study was a retrospective record review including 544 HIV-positive adults on antiretroviral therapy at Debre Markos Referral Hospital between January 1, 2012 and December 31, 2017. The study participants were selected using a simple random sampling technique. The data extraction format was adapted from antiretroviral intake and follow-up forms. Cox-proportional hazards regression model was fitted and Cox-Snell residual test was used to assess the goodness of fit. Tuberculosis free survival time was estimated using the Kaplan-Meier survival curve. Both the bi-variable and multivariable Cox-proportional hazard regression models were used to identify predictors of tuberculosis.ResultsIn the final analysis, a total of 492 HIV-positive adults were included, of whom, 83 (16.9%) developed tuberculosis at the time of follow-up. This study found that the incidence of tuberculosis was 6.5 (95% CI: 5.2, 8.0) per 100-person-years (PY) of observation. Advanced World Health Organization clinical disease stage (III and IV) (AHR: 2.1, 95% CI: 1.2, 3.2), being ambulatory and bedridden (AHR: 1.8, 95% CI: 1.1, 3.1), baseline opportunistic infections (AHR: 2.8, 95% CI: 1.7, 4.4), low hemoglobin level (AHR: 3.5, 95% CI: 2.1, 5.8), and not taking Isonized Preventive Therapy (AHR: 3.9, 95% CI: 1.9, 7.6) were found to be the predictors of tuberculosis.ConclusionThe study found that there was a high rate of tuberculosis occurrence as compared to previous studies. Baseline opportunistic infections, being ambulatory and bedridden, advanced disease stage, low hemoglobin level, and not taking Isonized Preventive Therapy were found to be the predictors of tuberculosis. Therefore, early detection and treatment of opportunistic infections like tuberculosis should get a special attention.

Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)

Identifying a Simple Clinical Prognostic Model for Aggressive Adult T-Cell Leukemia/Lymphoma in Latin American Population and Its Validation: A Large International Study of the Latin America Working Group for Lymphomas (GELL)

A Multi-Institutional Validation of the Prognostic and Predictive Value of the Neutrophil-to-Lymphocyte Ratio in Patients with Diffuse Large B- Cell Lymphoma: A Study from the Latin American Working Group for Lymphomas (GELL)

Introduction: Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequent subtype of high-grade lymphoma in Latin American patients. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe, and the United States. We previously reported that NLR ≥4 was an adverse prognostic factor for overall survival (OS) in DLBCL patients treated with chemoimmunotherapy. We aim to assess the prognostic and predictive role of NLR ≥4 in a learning cohort of DLBCL patients from South America and confirm the findings in a validation cohort of DLBCL patients from Mexico. Methods: The study period was from January 2002 through January 2018, and included patients with de novo DLBCL treated with standard chemoimmunotherapy with a curative intent. A cohort of patients from South America (Peru, Argentina, Venezuela, Chile and Colombia) was the learning cohort, a cohort of patients from Mexico was the validation cohort. Univariate and multivariate logistic regression analysis and Cox proportional-hazard regression models were fitted for complete response (CR) as well as for OS in the learning cohort and the validation cohort, separately. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 597 patients with a diagnosis of DLBCL were included. The learning cohort included 274 patients, and the validation cohort included 323 patients. In the learning cohort, CR rates for DLBCL patients with NLR ≥4 and NLR &lt;4 were 62% and 78%, respectively (p=0.003). In the multivariate analyses for CR, advanced stage and NLR ≥4 were associated with lower odds of CR (OR 0.39, 95% CI 0.21-0.70, p=0.002; and OR 0.46, 95% CI 0.27-1.63, p=0.006, respectively). NLR ≥4 was independently associated with lower rates of CR when adjusted for the IPI and the NCCN-IPI scores (OR 0.46, 95% CI 0.27-0.79, p=0.005; and OR 0.47,95% CI 0.28-0.81, p=0.006, respectively). The 5-year OS rates for DLBCL patients with NLR ≥4 was 58% versus 70% for patients with NLR &lt;4. In the multivariate analyses for OS, advanced stage (HR 2.47, 95% CI 1.55-3.93; p&lt;0.001) and NLR ≥4 (HR 1.55, 95% CI 1.20-2.36; p=0.04) were statistically significant factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for the IPI and the NCCN-IPI scores (HR 1.50, 95% CI 1.01-2.28; p=0.04; and HR 1.47, 95% CI 1.01-2.21; p=0.04, respectively). In the validation cohort, CR rates for DLBCL patients with NLR ≥4 and NLR &lt;4 were 64% and 81%, respectively (p=0.001). In the multivariate analyses for CR, elevated LDH level and NLR ≥4 were associated with lower odds of CR (OR 0.53, 95% CI 0.29-0.97, p=0.04; and OR 0.49, 95% CI 0.27-0.88, p=0.01, respectively). NLR ≥4 was independently associated with lower rates of CR when adjusted for IPI score and the NCCN-IPI score (OR 0.46,95% CI 0.26-0.82, p=0.008; and OR 0.46, 95% CI 0.25-0.81, p=0.007, respectively). The 5-year OS rates for DLBCL patients with NLR ≥4 was 48% versus 68% for patients with an NLR&lt;4. In the multivariate analysis for OS; ECOG ≥1 (HR 1.85, 95% CI 1.24-2.77; p&lt;0.003), advanced stage (HR 2.04, 95% CI 1.28-3.26, p=0.003) and NLR ≥4 (HR 1.80, 95% CI 1.22-2.65; p=0.03) were independent factors associated with worse OS. NLR ≥4 was an adverse prognostic factor after adjusting for IPI score and NCCN-IPI score (HR 1.81, 95% CI 1.24-2.64; p=0.002; and HR 1.96, 95% CI 1.34-2.86; p=0.001, respectively). Conclusion: This multi-institutional collaborative study identifies and validates an easy-to-use tool, NLR ≥4, as an independent factor predictive of lower rates of CR and prognostic of worse survival, independent of the IPI and the NCCN-IPI scores, in Latin-American patients with DLBCL treated with standard chemoimmunotherapy. Disclosures M: Roche-Mexico: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Merck-Sharp-Dome: Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Ramirez-Ibarguen:Roche-Mexico: Consultancy, Speakers Bureau. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Castillo:Pharmacyclics: Consultancy, Research Funding; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding.

The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy

Currently, prostate-specific membrane antigen-radioligand therapy (PSMA-RLT) is considered a last-line treatment option in advanced castration-resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA-RLT and whether the changes assessed after PSMA-RLT correlate with the OS. The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro-gastrin-releasing peptide (pro-GRP). For the evaluation, we performed blood tests before each PSMA-RLT cycle and during follow-up visits (which were 2-3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional-hazards regression model. The significance level was set at P < .05. The study included 137 patients who received a total of 487 PSMA-RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut-off), LDH (248 U/L cut-off), and PSA (first quartile cut-off) correlated significantly with survival post-PSMA-RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro-GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS. Along with the established tumor marker PSA, ALP, LDH, BAP, and pro-GRP were correlated with the OS post-PSMA-RLT in the univariate and multivariate analyses.