Five-year Cumulative Incidence Research Articles

The Contemporary Natural History of Minor Amputation Among Diabetic Patients with Peripheral Arterial Disease.

The growing prevalence of diabetes and concomitant PAD(DM/PAD) has led to an increase in patients at-risk for adverse limb events in current practice. Despite a widespread perception that minor amputation may result in both limb salvage and preserved functionality, the natural history of minor amputations remains unknown. Thus, we sought to quantify the rates of subsequent major amputation and survival among DM/PAD patients with any prior minor amputation. We performed a retrospective cohort study using US Medicare claims from 2007-2019. We included patients with DM/PAD based on ICD-9 and ICD-10 diagnosis codes. We excluded patients lacking continuous fee-for-service coverage or with incomplete demographic data. The primary exposure was prior minor(below-ankle) amputation. The primary outcome was major(above-ankle) amputation. Statistical analyses were performed using the Kaplan-Meier method and Cox proportional hazards modeling. We identified 12,257,174 patients(age 73±11 years,48% male,76% White) with DM/PAD. Of these patients, 2.2%(N=274,225) underwent prior minor amputation. Patients with prior minor amputation were more likely to be male(63% versus 47%,p<0.0001), Black non-Hispanic(17% versus 13%,p<0.0001), and rural(25% versus 21%,p<0.0001) than those without prior minor amputation. The five-year Kaplan-Meier cumulative incidence of major amputation was 27%(N=58,613) of patients with prior minor amputation, compared to 1.4%(N=129,872) of patients without prior minor amputation. After risk-adjustment, patients with prior minor amputations were 6.1-fold more likely to require a subsequent major amputation(HR 6.11[6.04-6.18]) compared to those without prior minor amputations. This contemporary claims-based analysis demonstrates that approximately 25% of Medicare beneficiaries with DM/PAD and prior minor amputation will necessitate a major amputation within five years. Prior minor amputation carries a risk of major amputation comparable to de novo tissue loss, and is a stronger predictor than any demographic or socioeconomic exposure. These results help to inform both clinical decision-making and anticipated real-world outcomes among those at greatest risk for limb loss.

Overview of the risk of myocardial infarction in patients with aortic stenosis: insights from the VALVENOR Registry

Abstract Background Close interaction between aortic stenosis (AS) and coronary artery disease (CAD) has been suggested. However, the risk of myocardial infarction (MI) in patients with AS is poorly described outside the context of aortic valve replacement. Objectives To assess the incidence, correlates and impact on outcomes of MI occurrence in patients with different degrees of AS severity. Methods Between 2016 and 2017, the multicenter prospective VALVENOR registry enrolled 2,830 outpatients with native valvular AS (peak aortic jet velocity (Vmax) ≥ 2.5m/s). AS was defined as mild (Vmax 2.5-2.9), moderate (Vmax 3-3.9) or severe (Vmax ≥4). MI was defined using the 4th universal definition (type 2 MI were not considered). Results The mean age was 76.0 years, 54% of the patients were men and 18.3% had experienced prior coronary event (PCE). Altogether, one third (n=820 [30.3%]) of the patients had diabetes. At 5 years, the cumulative incidence of MI (death as competing event) was only 2.5% (n=72, 1/3 of ST-elevation MI). Sixty MI (83.3%) were categorized as type 1 MI while 12 were peri-procedural MI (surgical aortic valve replacement, n=5; transcatheter aortic valve replacement, n=2; coronary artery bypass surgery, n=1; percutaneous coronary intervention, n=3; coronary angiography, n=1). PCE and angina symptoms were associated with an increased risk, whereas female gender with a decreased risk. By contrast, AS severity was not associated with the risk of MI. Five-year cumulative incidence of MI was 6.5% [95% CI, 4.5 - 8.9] in patients with PCE vs. 1.7% [95% CI, 1.2 - 2.3] in patients with no PCE (P&amp;lt;0.001), 8.3% [95% CI, 4.1 - 14.4] in patients with angina vs. 2.3% [95% CI, 1.8 - 2.9] in patients without angina (P&amp;lt;0.001), and 3.2% [95% CI, 2.4 - 4.2] in men vs. 1.8% [95% CI, 1.1 - 2.6] in women (P=0.014). Subsequent mortality was high and at 52.8% during follow-up (median 648 days after MI occurrence). When analyzed as a time-dependent variable, incident MI was a powerful predictor of mortality (HR=2.00, P&amp;lt;0.001 after adjustment). Conclusions In patients with AS, the risk of MI is relatively low especially in patients without PCE and without angina. No association between the risk of MI and AS severity was observed. Although rare, incident MI is strongly associated with subsequent mortality.

Revascularisation after discharge in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Background Multivessel coronary artery disease frequently occurs in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS), which is associated with a higher mortality rate. Previous studies have focused on revascularisation during the initial admission. The need for revascularisation after discharge has not yet been well-studied. Purpose To determine the incidence of revascularisation after discharge in patients initially hospitalised with AMICS compared to ST-elevation myocardial infarction (STEMI) patients without CS. Methods Data from a cohort of individually validated AMICS patients admitted to two tertiary cardiac centres in Denmark between 2010 and 2017 - the RETROSHOCK cohort - were included (fig.1). Data were cross-linked with The National Patient Register, containing diagnostic and procedural codes for all hospital contacts for Danish citizens. For comparison, an age- and sex-matched cohort of STEMI patients (4:1 ratio) without CS treated at the same centres and within the same timeframe was established from The National Patient Register. The incidence of revascularisation (percutaneous coronary intervention (PCI) and/or coronary artery bypass grafting (CABG)) was assessed in patients surviving a "blanking period" of 60 days after discharge to take staged elective revascularisation into account and until a maximum follow-up of 5 years. The cumulative incidence function with death as a competing event was used. Gray’s test was used for comparison of incidence functions. Results A total of 1,716 AMICS patients were included, of whom 753 (44%) survived to 60 days after discharge – of those, 538 (71%) patients had STEMI. Revascularisation was performed during follow-up and after the 60-day ‘blanking period’ in 68 patients (9%) – median follow-up time was 3.4 years in the AMICS group and 3.5 years in the control group. Multivessel disease, out-of-hospital cardiac arrest and hyperlipidaemia at index hospitalisation were more prevalent in patients revascularised during the follow-up period (69% vs. 52% p=0.009, 62% vs. 47% p=0.018 and 42% vs. 27% p=0.014) for revascularised vs. not-revascularised). No significant differences in sex or age were present in revascularised vs. not-revascularised patients. The five-year cumulative incidence rate for revascularisation after discharge was 10.0% (95% Confidence Interval (CI) 7.9-12.7%), which was similar compared to the matched STEMI cohort without CS (11.5% 95% (CI) 10.7-12.4%), HR 0.88 95% (CI) 0.68-1.13, p=0.319) (fig.1a). The finding was similar in a subgroup analysis of STEMI-only patients with CS compared to the non-CS cohort. Conclusions The cumulative incidence of revascularisation after discharge for AMICS patients was comparable to STEMI patients without CS during five years follow-up. Multivessel disease, out-of-hospital cardiac arrest and hyperlipidaemia at index admission were more prevalent in patients who were revascularised during follow-up.

Early and Late Aortic-Related Mortality and Rupture After Fenestrated-Branched Endovascular Aortic Repair of Thoracoabdominal Aortic Aneurysms: A Prospective Multicenter Cohort Study.

Fenestrated-branched endovascular aortic repair (FB-EVAR) has been used as a minimally invasive alternative to open surgical repair to treat patients with thoracoabdominal aortic aneurysms (TAAAs). The aim of this study was to evaluate aortic-related mortality (ARM) and aortic aneurysm rupture after FB-EVAR of TAAAs. Patients enrolled in 8 prospective, nonrandomized, physician-sponsored investigational device exemption studies between 2005 and 2020 who underwent elective FB-EVAR of asymptomatic intact TAAAs were analyzed. Primary end points were ARM, defined as any early mortality (30 days or in hospital) or late mortality from aortic rupture, dissection, organ or limb malperfusion attributable to aortic disease, complications of reinterventions, or aortic rupture. Secondary end points were early major adverse events, TAAA life-altering events (defined as death, permanent spinal cord injury, permanent dialysis, or stroke), all-cause mortality, and secondary interventions. A total of 1109 patients were analyzed; 589 (53.1%) had extent I-III and 520 (46.9%) had extent IV TAAAs. Median age was 73.4 years (interquartile range, 68.1-78.3 years); 368 (33.2%) were women. Early mortality was 2.7% (n=30); congestive heart failure was associated with early mortality (odds ratio, 3.30 [95% CI, 1.22-8.02]; P=0.01). Incidence of early aortic rupture was 0.4% (n=4). Incidence of early major adverse events and TAAA life-altering events was 20.4% (n=226) and 7.7% (n=85), respectively. There were 30 late ARMs; 5-year cumulative incidence was 3.8% (95% CI, 2.6%-5.4%); older age and extent I-III TAAAs were independently associated with late ARM (each P<0.05). Fourteen late aortic ruptures occurred; 5-year cumulative incidence was 2.7% (95% CI, 1.2%-4.3%); extent I-III TAAAs were associated with late aortic rupture (hazard ratio, 5.85 [95% CI, 1.31-26.2]; P=0.02). Five-year all-cause mortality was 45.7% (95% CI, 41.7%-49.4%). Five-year cumulative incidence of secondary intervention was 40.3% (95% CI, 35.8%-44.5%). ARM and aortic rupture are uncommon after elective FB-EVAR of asymptomatic intact TAAAs. Half of the ARMs occurred early, and most of the late deaths were not aortic related. Late all-cause mortality rate and the need for secondary interventions were 46% and 40%, respectively, 5 years after FB-EVAR. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02089607, NCT02050113, NCT02266719, NCT02323581, NCT00583817, NCT01654133, NCT00483249, NCT02043691, and NCT01874197.

A Predictive Model for Gastric Cancer-Specific Death after Gastrectomy: A Competing-Risk Nomogram.

We aimed to assess the likelihood of cause-specific death and other causes of death after gastrectomy for gastric cancer (GC). Additionally, a competing-risk nomogram was developed for patient counseling and decision-making. Eligible GC patients who had gastrectomy between 2007 and 2015 were included in the study from the Surveillance, Epidemiology, and End Results (SEER) database. Death from gastric cancer and death from other causes were considered as separate competing events. Cumulative incidence functions (CIF) were calculated for each event, and a competing-risk nomogram was developed. Overall, 8,808 patients who underwent gastrectomy were analyzed. Among them, 4,659 (52.90%) died from gastric cancer and 1,284 (14.58%) died from other causes. The five-year cumulative incidence of cause-specific death for gastric cancer was 50.4%, and 10.2% for deaths from other causes. Several independent factors, such as age at diagnosis, tumor site, grade, size, lymph node examination results, pathological T status, pathological N status, metastatic status, Lauren classification, radiation, and chemotherapy, were found to be associated with gastric cancer-specific death. The nomogram, based on results from the competing risk regression model, demonstrated good performance. We have developed a nomogram aimed at predicting gastric cancer-specific mortality in patients following gastrectomy. The model has undergone internal validation, demonstrating good accuracy and reliability. It serves as useful tool that can assist physicians and patients in making more informed clinical decisions.

Porto-sinusoidal vascular liver disorder with portal hypertension: Natural history and long-term outcome

Current knowledge of the natural history of patients with porto-sinusoidal vascular disorder (PSVD) is derived from small studies. The aim of the present study was to determine the natural history of PSVD and prognostic factors in a large multicenter cohort of patients. We performed a retrospective study on patients with PSVD and signs of portal hypertension (PH) prospectively registered in 27 centers. A total of 587 patients were included, median age of 47 years and 38% were women. Four-hundred and one patients had an associated condition, which was graded as severe in 157. Median follow-up was 68 months. At diagnosis, 64% of patients were asymptomatic while 36% had a PH-related complication: PH-related bleeding in 112 patients, ascites in 117, and hepatic encephalopathy in 11. In those not presenting with bleeding, the incidence of first bleeding was 15% at 5 years, with a 5-year rebleeding rate of 18%. The 5-year cumulative incidence of new or worsening ascites was 18% and of developing portal vein thrombosis was 16%. Fifty (8.5%) patients received a liver transplantation and 109 (19%) died, including 55 non-liver-related deaths. Transplant-free survival was 97% and 83% at 1 and 5 years, respectively. Variables independently associated with transplant-free survival were age, ascites, serum bilirubin, albumin and creatinine levels at diagnosis and severe associated conditions. This allowed for the creation of a nomogram that accurately predicted prognosis. The prognosis of PSVD is strongly determined by the severity of the associated underlying conditions and parameters of liver and renal function. Porto-sinusoidal vascular liver disorder (PSVD) is a rare entity that usually affects young people, frequently causes severe complications of portal hypertension, and may reduce life expectancy. To date, there is scarce information regarding its clinical manifestations, natural history and prognostic factors. The present study, including the largest number of patients with PSVD reported so far, shows that overall, when managed at centers of expertise, the prognosis of patients with PSVD is good, with LT-free survival rates of 83% and 72% at 5 and 10 years, respectively. Presence and severity of an underlying associated condition, presence of ascites, age and bilirubin, albumin and creatinine levels were associated with poor prognosis. These results are important to know for hepatologists. A final model combining these parameters enabled development of a nomogram that predicts prognosis with good discrimination and calibration capacity and can be easily applied in clinical practice.

Sleep Disorders and Dementia Risk in Older Patients with Kidney Failure: A Retrospective Cohort Study.

Community-dwelling older adults with sleep disorders are at higher risk of developing dementia. Greater than 50% of older patients with kidney failure experience sleep disorders, which may explain their high burden of dementia. Among 216,158 patients (age ≥66 years) with kidney failure (United States Renal Data System; 2008-2019), we estimated the risk of dementia (including subtypes) associated with sleep disorders using Cox proportional-hazard models with propensity score weighting. We tested whether positive airway pressure (PAP) therapy was associated with reduced dementia risk among patients with obstructive sleep apnea (OSA). 26.3% of patients were diagnosed with sleep disorders; these patients had a higher five-year unadjusted cumulative incidence for any type of dementia (36.2% vs. 32.3%; P<0.001), vascular dementia (4.4% vs. 3.7%; P<0.001), and other/mixed dementia (29.3% vs. 25.8%; P<0.001). Higher risk of any type of dementia was identified in patients with insomnia (aHR=1.42; 95%CI: 1.34-1.51), sleep-related breathing disorders (SRBDs) (aHR=1.20; 95%CI: 1.17-1.23), and other sleep disorders (aHR=1.24; 95%CI: 1.11-1.39). Higher vascular dementia risk was observed in patients with insomnia (aHR=1.43; 95%CI: 1.19-1.73), SRBDs (aHR=1.15; 95%CI: 1.07-1.24). Patients with SRBDs (aHR=1.07; 95%CI: 1.00-1.15) were at higher risk of Alzheimer's disease. Among patients with OSA, PAP therapy was associated with lower risk for any type of dementia (aHR=0.82; 95%CI: 0.76-0.90), and vascular dementia (aHR=0.65; 95%CI: 0.50-0.85). Older patients with kidney failure and sleep disorders are at a higher risk of dementia. Sleep is an important modifiable factor that should be considered for targeted interventions to mitigate dementia risk in patients with kidney failure. For patients with OSA, PAP therapy is associated with lower dementia risk.

Investigation of the Association between Sleep Disorders with Subsequent Depression in Children and Adolescents-A Retrospective Cohort Study with 62,796 Patients.

Poor quality of sleep is a widespread issue in modern society, and even children are being diagnosed with sleep disorders nowadays. Sleep disruption in children can lead to poor mental health in the long term. The present study aimed to evaluate the association between sleep disorders and subsequent depression in children and adolescents. This retrospective cohort study used electronic medical records from the IQVIATM Disease Analyzer database. It included children and adolescents aged 6-16 with an initial diagnosis of a sleep disorder and age- and gender-matched patients without sleep disorders treated by one of 274 office-based pediatricians in Germany between January 2010 and December 2022. The five-year cumulative incidence of depression in the cohorts with and without sleep disorders was studied with Kaplan-Meier curves using the log-rank test. Multivariable Cox regression analyses were used to assess the association between sleep disorders and depression. The present study included 10,466 children and adolescents with and 52,330 without sleep disorder diagnosis (mean age 10 ± 3 years, 48% female). Within five years after the index date, 5% of sleep disorder patients and 2% of the matched non-sleep disorder cohort had been diagnosed with depression. A strong and significant association was observed between sleep disorders and subsequent depression (HR: 2.34; 95% CI: 2.09-2.63). This association was stronger in adolescents (HR: 3.78; 95% CI: 3.13-4.56) than in children. Upon the exclusion of depression diagnoses in the first year after the index date, the association between sleep disorders and depression remained strong and significant (HR: 1.92; 95% CI: 1.68-2.19). This study indicates a strong and significant association between sleep disorders and depression.

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Abstract GS02-02: Are nodal ITCs after neoadjuvant chemotherapy an indication for axillary dissection? The OPBC05/EUBREAST-14R/ICARO study

Vena cava replacement and major hepatectomy for liver tumors: international multicenter retrospective cohort study.

Involvement of the inferior vena cava (IVC) and hepatic veins has been considered a relative contraindication to hepatic resection for primary and metastatic liver tumors. However, patients affected by tumors extending to the IVC have limited therapeutic options and suffer worsening of quality of life due to IVC compression. Cases of primary and metastatic liver tumors with vena cava infiltration from 10 international centers were collected (7 European, 1 US, 2 Brazilian, 1 Indian) were collected. Inclusion criteria for the study were major liver resection with concomitant vena cava replacement. Clinical data and short-term outcomes were analyzed. Thirty-six cases were finally included in the study. Median tumor max size was 98mm (range: 25-250). A biliary reconstruction was necessary in 28% of cases, while a vascular reconstruction other than vena cava in 34% of cases. Median operative time was 462min (range: 230-750), with 750 median ml of estimated blood loss and a median of one pRBC transfused intraoperatively (range: 0-27). Median ICU stay was 4 days (range: 1-30) with overall in-hospital stay of 15 days (range: 3-46), postoperative CCI score of 20.9 (range: 0-100), 12% incidence of PHLF grade B-C. Five patients died in a 90-days interval from surgery, one due to heart failure, one due to septic shock, and three due to multiorgan failure. With a median follow-up of 17 months (interquartile range: 11-37), the estimated 5 years overall survival was 48% (95% CI: 27-66%), and 5-year cumulative incidence of tumor recurrence was 55% (95% CI: 33-73%). Major liver resections with vena cava replacement can be performed with satisfactory results in expert HPB centers. This surgical strategy represents a feasible alternative for otherwise unresectable lesions and is associated with favorable prognosis compared to nonoperative management, especially in patients affected by intrahepatic cholangiocarcinoma.

Epidemiology of Diabetic Kidney Disease among US Veterans.

With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown. We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population. We performed a retrospective observational research using electronic health-care records and administrative databases. The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022. We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines. Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points. A total of 685,288 patients (male [96%], mean age 62 years, Caucasian [64%], non-Hispanic [87%]) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases. More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.

Five-year clinical outcomes of scanning carbon-ion radiotherapy for prostate cancer.

Carbon-ion radiotherapy (CIRT) has been associated with favorable clinical outcomes in patients with prostate cancer. At our facility, all patients are treated using scanning CIRT (sCIRT). We retrospectively analyzed five-year clinical outcomes of prostate cancer treated with sCIRT to investigate treatment efficacy and toxicity. In this study, we included 253 consecutive prostate cancer patients treated with sCIRT at the Kanagawa Cancer Center from December 2015 to December 2017. The total dose of sCIRT was set at 51.6 Gy (relative biological effect) in 12 fractions over three weeks. We employed the Phoenix definition for biochemical relapse. The overall survival (OS), biochemical relapse-free (bRF) rate, and cumulative incidence of late toxicity were estimated using the Kaplan-Meier method. Toxicity was assessed using the Common Terminology Criteria for Adverse Events version 4.0. The median age of the patients was 70 years (range: 47-86 years). The median follow-up duration was 61.1 months (range: 4.1-80.3 months). Eight (3.2%), 88 (34.8%), and 157 (62.1%) patients were in the low-risk, intermediate-risk, and high-risk groups, respectively, according to the D'Amico classification system. The five-year OS and bRF were 97.5% and 93.3%, respectively. The five-year bRF rates for the low-risk, intermediate-risk, and high-risk groups were 87.5%, 93.7%, and 93.4%, respectively (p = 0.7215). The five-year cumulative incidence of Grade 2 or more late genitourinary and gastrointestinal toxicity was 7.4% and 1.2%, respectively. The results of this study show that sCIRT has a favorable therapeutic effect and low toxicity in the treatment of prostate cancer.

Secondary central nervous system involvement in patients with diffuse large B-cell lymphoma treated with rituximab combined CHOP therapy – a supplementary analysis of JCOG0601

Secondary central nervous system involvement (sCNSi) in diffuse large B-cell lymphoma (DLBCL) is fatal. However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9 years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28–14.73]). Median overall survival after sCNSi was 1.3 years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement.Clinical trial registrationJCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019).

Comparison of Incidence of Metabolic Syndrome and Five Obesity- and Lipid-Linked Indicators for Predicting Metabolic Syndrome Among Normal-Weight and Overweight Adults.

Metabolic syndrome (MetS) is an increasingly prevalent issue in China's public health landscape. Few studies have investigated the metabolic syndrome (MetS) in overweight people. We proposed to analyze and contrast the occurrence of MetS in normal-weight and overweight individuals and identify potential indicators for forecasting MetS in adults in Zhejiang Province. This cohort study included 359 adults aged 40-65 years and followed up for five years in Zhejiang Province. The study assessed the predictive capabilities of five indicators linked to obesity and lipid levels, namely body mass index (BMI), waist-to-height ratio (WHtR), triglyceride-glucose index (TyGi), and their combined indices (TyG-BMI, TyG-WHtR). The evaluation was done employing the area under the Receiver Operating Characteristic (ROC) Curve (AUC). DeLong test was applied to compare area under different ROC curves.We evaluated the relationships between five variables and MetS using multivariate logistic regression. In normal-weight individuals, the five-year cumulative incidence of MetS was 21.85%, but in overweight people, it was 60.33%. After adjusting for confounding factors, BMI, WHtR, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in normal-weight individuals, while BMI, TyGi, TyG-BMI, and TyG-WHtR were independently linked to MetS in overweight individuals. In normal-weight individuals, the WHtR (AUC=0.738 and optimal threshold value =0.469) and TyG-WHtR (AUC=0.731 and optimal threshold value =4.121) had the larger AUC, which was significantly greater than that of the different three indicators. The TyG-BMI (AUC=0.769 and optimal threshold value = 211.099) was the best predictor of MetS in overweight individuals. The five-year cumulative incidence of MetS in overweight people was approximately triple that of normal-weight people in Zhejiang Province. In the overweight population, the TyG-BMI performed better than the other indices in predicting MetS. WHtR and TyG-WHtR outperformed BMI, TyGi, and TyG-BMI in anticipating MetS in a normal-weight population.

Comparing the Risk of Poor Outcomes Among Hepatitis C–Infected, Cured, and Never-Infected Controls

Studies show decreased rates of poor outcomes after hepatitis C virus (HCV) cure. However, there are no data comparing risk of poor outcomes to that of HCV never infected; results that could have implications for those who may not need ongoing specialty follow-up after cure. Retrospective cohort study conducted among Kaiser Permanente Northern California adults ages 18 and up between 2002 and 2019. Three cohorts were identified: 1) chronic HCV, 2) HCV cured, and 3) every chronic HCV and HCV-cured individual was matched by age, sex and race-ethnicity to 3 HCV negative controls. Outcomes of interest were cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and all-cause mortality. A low-risk group of HCV cured individuals without significant liver disease and/or concomitant liver disease cofactor(s) were identified. We identified 21,184 chronic HCV, 11,950 HCV cure, and 99,402 control individuals. Five-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality was 10% vs 3.6% vs 0.8%, 12% vs 2.6% vs 0.6%, 3.9% vs 1.6% vs 0.07%, and 14% vs 2.8% vs 2.2% for chronic HCV, HCV cure, and control individuals, respectively (log-rank P < .01 for all). Compared to controls, HCV cured low-risk individuals had numerically similar 5-year cumulative incidence of cirrhosis, decompensated cirrhosis, HCC and all-cause mortality (1.2% vs 0.8%, P < .01; 0.9% vs 0.6%, P < .01; 0.5% vs 0.1%, P < .01; 1.7% vs 2.2%, P < .01). HCV cure provides significant health benefits but does not universally return risk of poor outcomes to that of the general population. A simple stratification at the time of HCV cure could identify low-risk individuals who can potentially be discharged from specialty clinics/HCC surveillance.

Abstract 16789: Modeling the Optimal Strategy of Natriuretic Peptide Testing for Heart Failure Prevention in Diabetes: A Pooled Cohort Analysis

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with heart failure (HF) risk and measurement is recommended in diabetes. Incorporation of NT-proBNP with WATCH-DM, a HF risk score validated in diabetes, improved HF risk prediction in low-risk individuals (score &lt;13). Whether WATCH-DM can improve the yield of NT-proBNP testing and inform allocation of SGLT2 inhibitors is unknown. Methods: Adults with diabetes and free of HF at baseline from ARIC, CHS, CRIC, DHS, FOS, and MESA cohorts were included. Participants without cardiovascular disease (CVD) were stratified into high- vs. low-risk categories based on 4 approaches: 1) WATCH-DM (score ≥ vs. &lt;13); 2) NT-proBNP (≥ vs. &lt;125 pg/mL); 3) WATCH-DM plus NT-proBNP (both high vs. not); 4) WATCH-DM-based NT-proBNP (if score &lt;13, measure NT-proBNP) (either high vs. not). Five-year cumulative incidence rates of HF, number needed to treat (NNT 5 ) and number needed to screen (NNS 5 ) were estimated based on pooled treatment effects of SGLT2 inhibitors. Results: The study included 6,410 participants (47.5% women, 35.1% Black, 20.5% with CVD) with 428 (6.7%) incident HF events over 5-year follow-up. The 5-year risk of HF was 12.3% among participants with CVD and comparable to those without CVD identified as high-risk based on all 4 approaches ( Figure ). Among participants without CVD, WATCH-DM-based NT-proBNP identified 46% of participants as high-risk and accounted for 80% of HF events. The NNT 5 with an SGLT2 inhibitor to prevent 1 HF event in participants with CVD was 25 and similar to the primary prevention population identified as high-risk ( Figure ). The NNS 5 was lowest in the WATCH-DM-based NT-proBNP strategy ( Figure ). Conclusions: Selective NT-proBNP assessment based on a validated clinical risk score for HF improved the yield of testing and may represent an efficient approach to risk stratification and allocation of therapies among individuals with diabetes.

Clonal Hematopoiesis Is Associated with Cardiovascular Disease Risk and Worse Survival after Autologous Hematopoietic Cell Transplantation for Lymphoma

Introduction: Autologous hematopoietic cell transplantation (HCT) is an effective treatment for patients with relapsed or refractory lymphoma, and use of HCT has contributed to a growing number of survivors. Despite these improvements in outcomes, long-term survivors of lymphoma are at high risk of developing clinically significant cardiovascular disease (CVD) which, to date, has largely been attributed to pre-HCT cardiotoxic therapeutic exposures (e.g. anthracyclines, radiation) and modifiable risk factors (e.g. hypertension, diabetes, dyslipidemia) after HCT. In the general population, clonal hematopoiesis of indeterminate potential (CHIP), which refers to clonal expansion of hematopoietic stem cells with somatic mutations, has been associated with aging-related health conditions including CVD. Accumulating data suggests CHIP is more prevalent in cancer patients compared to age-matched controls, due in part to clonal selection after genotoxic stressors. There is a paucity of information about the association between CHIP and CVD after HCT, including its interaction with modifiable risk factors and subsequent impact on survival after HCT. Methods: This was a retrospective cohort study of 861 consecutive patients who underwent autologous HCT for lymphoma between 2010 and 2016, with available pre-HCT DNA obtained from peripheral blood stem cells. We performed targeted exome sequencing of DNA (92 pre-defined gene panel with 1000x sequencing depth) to determine the presence of CHIP (variant allele frequency ≥2%). CVD outcomes of interest included de novo heart failure, coronary artery disease and stroke after HCT. Five-year cumulative incidence of CVD was calculated taking into consideration competing risk of death. Fine-Gray multivariable regression was used to evaluate the association between CHIP and CVD, adjusting for demographic, clinical and therapeutic factors. The Kaplan-Meier method was used to examine the effect of CHIP on overall survival after HCT. Results: Median age at HCT was 55.7 years (range 18.4-78.1 years); 63.3% were male; race/ethnicity: non-Hispanic White (56.9%), Hispanic (26.1%), Asian (10.8%), Black (5.1%); 78.0% had non-Hodgkin lymphoma; comorbidities at HCT: hypertension (32.1%), dyslipidemia (16.4%), diabetes (10.1%), high (≥3) HCT-comorbidity index (CI) score (46.1%). Nearly all patients (94.3%) had received anthracycline-based chemotherapy prior to HCT, and 63.3% were treated with cumulative dose ≥300mg/m 2; 6% had chest radiotherapy. Overall, 186 patients (21.7% of the cohort) had at least one CHIP variant and 57 (6.6%) had ≥2 variants. DNMT3A, PPM1D, TET2 and TP53 were the most frequently mutated genes. In total, 74 patients developed CVD within five years from HCT. The 5-year cumulative incidence of CVD was significantly higher in patients with CHIP (20.9% vs 9.1%, p&amp;lt;0.001), compared to those without CHIP, and there was a graded relationship between number of CHIP variants and incidence of CVD. In the adjusted (age, cancer diagnosis, HCT-CI, modifiable cardiovascular risk factors) multivariable model, CHIP was significantly and independently associated with a nearly two-fold (HR: 1.8, 95% CI=1.1-3.1; P=0.020) risk of CVD, as well as the individual outcome of heart failure (HR: 2.3, 95%CI=1.3-4.3; P=0.008). Patients who had both CHIP and hypertension had a 3-fold (HR: 3.0, 95%CI=1.4-6.5, p=0.006) risk of CVD (reference: no CHIP, no hypertension). Overall 5-year survival after HCT was significantly worse in patients with CHIP, compared to those without CHIP (47.2% vs 68.2%, p&amp;lt;0.001; adjusted HR: 1.9, 95%CI=1.4-2.6), attributed to the higher burden of non-relapse mortality in patients with CHIP. Conclusions: In this well-characterized and demographically diverse cohort of lymphoma patients undergoing HCT, CHIP was highly prevalent and associated with a significantly higher risk of CVD after HCT, with the highest risk among those with CHIP and hypertension. We confirmed the poor overall survival rate in patients with CHIP, independent of patient and disease-related risk factors. These findings highlight the potential role of CHIP as a novel biomarker to better define CVD risk in patients with lymphoma prior to HCT, setting the stage for better screening and implementation of interventions (e.g., aggressive management of modifiable risk factors) to reduce the risk of CVD and to ultimately improve long-term health outcomes after HCT.

Post-Transplant Cyclophosphamide (PTCY) Compared to ATG in Patients with Myelodysplastic Neoplasms Allografted with an Unrelated Donor: A Registry Study of the Chronic Malignancies Working Party of the EBMT

Background Prospective randomized trials have reported a benefit for ATG-based GVHD prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation (alloHSCT) with an unrelated donor (UD). However, the best GVHD prophylaxis has been recently challenged by the use of PTCY, first in haplo-identical transplant and then in HLA mismatched or matched unrelated transplantation. We here present the outcomes of PTCY vs ATG as GVHD prophylaxis in MDS patients from the EBMT registry transplanted with an unrelated donor. Method A total of 969 patients transplanted from 2012 to 2019 in 92 participating centers, receiving either PTCY or ATG, were included in this study. The primary outcomes were progression free survival (PFS) and overall survival (OS). Competing risks analyses were performed to analyze non-relapse mortality (NRM) with competing event relapse, and acute GvHD grade II-IV, chronic GvHD and neutrophil engraftment with competing events relapse and death. Cox proportional hazards regression with a predefined covariate constellation (age, IPSS-R cytogenetics, donor HLA matching, age, hypomethylating agents (HMA) prior to transplantation, comorbidity score and MDS classification (MDS with or without excess blast, EB) was used to obtain adjusted effect estimates of ATG compared to PTCY for OS and PFS. Results Overall, 214 patients received PTCY and 755 received ATG as GVHD prophylaxis for UD alloHSCT. Patients of the ATG group were older (60.1 year-old [IQR: 50.6-65.2] vs 57.2 year-old [IQR: 46.4-61.1], p=0.008). Disease characteristics were similar in both group: there were a total of 583 MDS with EB at diagnosis, 510 MDS-EB at transplantation, and 207 patients transformed into AML. Among patients with available data for IPSS-R at MDS diagnosis (n=760) 44 (5.8%) were Very Low, 114 (15%) Low, 209 (27.5%) Intermediate, 232 (30.5%) High and 161 (21.2%) Very High. Patients of the PTCY group received more frequently HMA before transplantation (72.4% vs 57.3%, p=0.001) and were preferentially transplanted from an HLA mismatched 9/10 donor (37.9% vs 21.6%, p&amp;lt;0.001). Conditioning regimen was more frequently myeloablative in the PTCY group (55.4% vs 38.7%, p&amp;lt;0.001). Neutrophil engraftment at 28 days was significantly better with ATG (93% vs 84%, p&amp;lt;0.001). With a median follow-up of 4.4 (95% CI 4.2 - 4.8) years, five-year OS was 57% (49-64) with PCTY and 49% (95% 46-53%) in ATG group, p=0.127. Five-year cumulative incidence of relapse was similar in both groups (22%, 95%CI 16-29 in PTCY vs 25%, 95%CI 22-28 in ATG; p=0.28). Notably, 5-year PFS was marginally higher for PTCY with 52% (95%CI 44-59) vs 44% (95%CI 40-48) for ATG, p=0.075, whereas 5-year NRM was 26% (95% CI 20-32%) vs 31% (95% CI 27-34) in PTCY and ATG, respectively, p=0.28. Grade II-IV acute GVHD incidence was lower using PTCY (22% [95% CI 17-28%] vs 30% [95% CI 26-33%]), p=0.035 while there was no difference for chronic GVHD (36% (29-43% with PTCY vs 38% (34-41%) in ATG at 5 years). Multivariable analyses confirmed a better OS and PFS for PTCY, with a HR of ATG of 1.34 (95% CI 1.02-1.76), p=0.04, and a better PFS for PTCY with a HR for ATG of 1.31 (95%CI 1.01-1.69) (Table 1). There was no apparent interaction between GvHD prophylaxis and IPSS-R or HLA matching, suggesting an effect exclusive to the type of GVHD prophylaxis used. Conclusion: This EBMT registry study suggests that MDS patients who received a transplant from an unrelated donor had a better OS and PFS using PTCY compared to ATG. This confirms that PTCY instead of ATG in this setting is a valid option.

Factors associated with survival in patients with clear cell sarcoma.

Clear cell sarcoma (CCS) of soft-tissue is a rare melanocytic subtype of mesenchymal malignancy. The aim of this study was to investigate the clinical and therapeutic factors associated with increased survival, stratified by clinical stage, in order to determine the optimal treatment. The study was a retrospective analysis involving 117 patients with histologically confirmed CCS, between July 2016 and November 2017, who were enrolled in the Bone and Soft Tissue Tumour Registry in Japan. The five- and ten-year survival rates were 41% (95% confidence interval (CI) 29 to 52) and 37% (95% CI 25 to 49), respectively. On multivariable analysis, the size of the tumour of > 10 cm (p = 0.006), lymph node metastasis at the time of diagnosis (p < 0.001), distant metastases at the time of diagnosis (p < 0.001), and no surgery for the primary tumour (p = 0.019) were independently associated with a poor survival. For N0M0 CCS (n = 68), the development of distant metastases was an independent prognostic factor for survival (early (< 12 months), hazard ratio (HR) 116.78 (95% CI 11.69 to 1,166.50); p < 0.001; late (> 12 months), HR 14.79 (95% CI 1.66 to 131.63); p = 0.016); neoadjuvant/adjuvant chemotherapy (p = 0.895) and/or radiotherapy (p = 0.216) were not significantly associated with survival. The five-year cumulative incidence of local recurrence was 19% (95% CI 8 to 35) and the size of the tumour was significantly associated with an increased rate of local recurrence (p = 0.012). For N1M0 CCS (n = 18), the risk of mortality was significantly lower in patients who underwent surgery for both the primary tumour and lymph node metastases (HR 0.03 (95% CI 0.00 to 0.56); p = 0.020). For M1 CCS (n = 31), excision of the primary tumour was independently associated with better survival (HR 0.26 (95% CI 0.09 to 0.76); p = 0.013). There was no significant difference in survival between the different types of systemic treatment (p = 0.523). Complete excision of the primary tumour and lymph nodes is associated with a better survival in patients with CCS. Systemic treatment appears to provide limited benefits, demonstrating a pressing need for novel systemic agents.

Fuzheng Huayu capsules reducing development of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B based on the ratio of neutrophils/lymphocytes

Objective: To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC). Methods: 916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ(2) test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results: There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ(2) = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ(2) = 4.519, P = 0.029; 13.2% vs. 26.2%, χ(2) = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group (P = 0.38). Conclusion: Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.