Crude Cumulative Incidence Research Articles

Association Between Graft Type and Risk of Repeat Revision Anterior Cruciate Ligament Reconstruction: A Cohort Study of 1747 Patients

Background: With an increasing number of primary anterior cruciate ligament reconstructions (ACLRs), the burden of revision ACLR (rACLR) has also increased. Graft choice for rACLR is complicated by patient factors and the remaining available graft options. Purpose: To examine the association between graft type at the time of rACLR and the risk of repeat rACLR (rrACLR) in a large US integrated health care system registry while accounting for patient and surgical factors at the time of revision surgery. Study Design: Cohort study; Level of evidence, 3. Methods: Data from the Kaiser Permanente ACLR registry were used to identify patients who underwent a primary isolated ACLR between 2005 and 2020 and then went on to have rACLR. Graft type used at rACLR, classified as autograft versus allograft, was the exposure of interest. Multivariable Cox proportional hazard regression was used to evaluate the risk of rrACLR, with ipsilateral and contralateral reoperation as secondary outcomes. Models included factors at the time of the rACLR (age, sex, body mass index, smoking status, staged revision, femoral fixation, tibial fixation, femoral tunnel method, lateral meniscal injury, medial meniscal injury, and cartilage injury) and a factor from the primary ACLR (activity at injury) as covariates. Results: A total of 1747 rACLR procedures were included. The crude cumulative rrACLR incidence at 8-year follow-up was 13.9% for allograft and 6.0% for autograft. Cumulative ipsilateral reoperation incidence at 8-year follow-up was 18.3% for allograft and 18.9% for autograft; contralateral reoperation cumulative incidence was 4.3% for allograft and 6.8% for autograft. With adjustment for covariates, a 70% lower risk for rrACLR was observed for autograft compared with allograft (hazard ratio [HR], 0.30; 95% CI, 0.18-0.50; P < .0001). No differences were observed for ipsilateral reoperation (HR, 1.05; 95% CI, 0.73-1.51; P = .78) or contralateral reoperation (HR, 1.33; 95% CI, 0.60-2.97; P = .48). Conclusion: The use of autograft at rACLR was associated with a 70% lower risk of rrACLR compared with allograft in this cohort from the Kaiser Permanente ACLR registry. When accounting for all reoperations outside of rrACLR after rACLR, the authors found no significant difference in risk between autograft and allograft. To minimize the risk of rrACLR, surgeons should consider using autograft for rACLR when possible.

A Large Retrospective Cohort Study on the Risk of Alzheimer's Disease and Related Dementias in Association with Vascular Diseases and Cancer Therapy in Men with Prostate Cancer.

No study was conducted on the long-term risk of Alzheimer's disease (AD) and related dementias (ADRD) in association with vascular diseases in men with prostate cancer. To determine the 26-year risk of ADRD in association with cardiovascular disease (CVD), stroke, hypertension, and diabetes in a nationwide cohort of men with prostate cancer. Retrospective cohort study. Surveillance, Epidemiology, and End Results (SEER) areas of the United States. 351,571 men diagnosed with prostate cancer at age ≥65 years. Main exposures were CVD, stroke, hypertension, and diabetes. Main outcome was the incidence of ADRD. The crude 26-year cumulative incidence of any ADRD was higher in those with versus without CVD (33.80% vs 29.11%), stroke (40.70% vs 28.03%), hypertension (30.88% vs 27.31%), and diabetes (32.23% vs 28.68%). Men with CVD (adjusted hazard ratio: 1.17, 95% CI: 1.15-1.20), stroke (1.59, 1.56-1.61), hypertension (1.13, 1.11-1.14), and diabetes (1.25, 1.23-1.27) were significantly more likely to develop ADRD than those without. Patients with 4 of these vascular diseases were 161% more likely to develop ADRD (2.61, 2.47-2.76) than those without. The risk of AD (0.89, 0.87-0.91) and ADRD (0.91, 0.90-0.93) became significantly lower in men with prostate cancer who received androgen deprivation therapy as compared to those who did not after considering death as a competing risk. In men with prostate cancer, vascular diseases were associated with significantly higher risks of developing ADRD. Androgen deprivation therapy was associated with a significantly decreased risk of AD in men with prostate cancer.

Deciphering changes in the incidence of the Guillain-Barré syndrome during the COVID-19 pandemic: a nationwide time-series correlation study

BackgroundPostinfectious autoimmunity is a hallmark of Guillain-Barré syndrome (GBS), and GBS incidence closely parallels that of its immune triggers. Sociobehavioural interventions implemented during the COVID-19 pandemic have altered the infectious...

International Differences in Baseline Characteristics and Practice Patterns in Patients with NEWLY Diagnosed Multiple Myeloma Undergoing Upfront Autologous STEM Cell Transplantation

Background: Worldwide, patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics and survival outcomes, likely due to variances in transplant activity, patient and health economic factors including access to new myeloma therapies. The goal of this retrospective study was to analyze differences in regional outcomes. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Results: 61725 patients from 629 were included: 37549 (61%) from EBMT, 16217 (26%) CIBMTR), 3815 (6%) APBMT (3122 Japan, 524 Taiwan and 169 Malaysia), 3,164 (5%) ANZTCT, 543 (0.9%) EMBMT, 339 (0.5%) LABMT and 188 (0.3%) Ottawa). The annual number of ASCTs steadily increased between 2013 (n=11317) and 2017 (n=13498) with the biggest relative increase seen in LABMT (from 36 to 109). Males comprised 58% and the median age at diagnosis was 59.9 years (IQR: 53.6-64.9). Race data was available in 45%: 73% White, 16% Asian and 11% African American. The predominant phenotypes were IgG (54%), light chain (24%) (lowest (4%) in Malaysia and highest (38%) in EMBMT), and IgA (19%) (lowest (13%) in EMBMT and highest (24%) in Ottawa). The ISS stage at diagnosis (54% available) was I in 38%, II 35% and III 27% (III lowest (24%) in ANZTCT and highest (45%) in LABMT). Cytogenetic risk (44% available) was standard in 70% and high in 30% (high risk was lowest (5%) in EMBMT, and highest (62%) in Ottawa). The median time from diagnosis to ASCT was 7 months (IQR:5.5-9.9) (shortest (6.4) in CIBMTR and Ottawa, and longest (13) in LABMT). The median age at ASCT was 60.8 years (IQR: 54.6-65.8) (lowest (53.6) in EMBMT, and highest (62) in Ottawa). Only 5% of patients were older than 70 years (lowest (3.5%) in EBMT, and highest (9.8%) in CIBMTR). HCT-CI at ASCT (28% missing) was reported as low risk (0) in 52%, intermediate (1-2) 25% and high risk (≥3) 23% (high risk was lowest (5.5%) in LABMT and highest (42%) in CIBMTR). The Karnofsky score at ASCT (2.2 % missing) was 100 in 40% and ≤90 in 60% (≤90 was lowest (44%) in LABMT and highest (92%) in Ottawa). Disease status (9.7% missing) was CR in 19%, VGPR 38%, PR 36%, MR/SD 5% and refractory 2%. A ≥VGPR status at ASCT was 60% in EBMT, 55% CIBMTR, 39% ANZTCT, 51% Japan, 64% EMBMT, 71% Taiwan, 76% LABMT, 51% Ottawa and 54% Malaysia. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) (lowest (60%) in Malaysia and highest (90%) in Ottawa), 140 mg/m2 accounted for 14% and others for 4%. Tandem ASCT was reported in 6.7% (10% in EBMT, 1.3% in CIBMTR and 0.6% LABMT and Taiwan). The source of stem cells was peripheral blood in 99.8%. Of the 11% reported with post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5-41.6, IQR:19.2-60.4). Regionally, at 3 years, the OS was : 81%, 84%, 82%, 83%, 77%, 75%, 84%, 82%, 69% (p<0.001), the PFS was 46%, 55%, 48%, 63%, 44%, 53%, 56%, 53%, 43% (p<0.001) (Figure) and the RI was:16%, 15%, 16%, 17%, 24%, 16%, 16%, 13%, 24% (p<0.001) for EBMT, CIBMTR, ANZTCT, Japan, EMBMT, Taiwan, LABMT, Ottawa and Malaysia, respectively. NRM at 1 year was between 1-2% in each registry (Figure). Conclusions: This large worldwide study of patients with NDMM treated with upfront ASCT revealed marked regional differences in transplant activity and patient characteristics. NRM was low worldwide but with differences in relapse incidence and survival potentially reflect variable health economic factors, including different access to new myeloma drugs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Worldwide Network for Blood and Marrow Transplantation (WBMT) Global Study on Baseline Characteristics and Clinical Outcomes in NEWLY Diagnosed Multiple Myeloma Patients Undergoing Upfront Autologous STEM Cell Transplantation, a Study Off 61,725 Patients from 629 Centers

Background: Patients with newly diagnosed multiple myeloma (NDMM) undergoing upfront autologous stem cell transplantation (ASCT) have different characteristics worldwide, likely due to variances in transplant activity, patient factors and health economic factors including access to new myeloma therapies. The first aim of this retrospective study was to analyze the global baseline patient characteristics and outcomes of upfront ASCT in NDMM. Methods: Data on patient characteristics and transplant outcomes for patients with NDMM who received an upfront ASCT between 2013 and 2017 were provided to the Worldwide Network for Blood and Marrow Transplantation (WBMT) by the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Australia and New Zealand Transplant and Cellular Therapies Registry (ANZTCT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant Group (LABMT), and the Ottawa Canadian Registry. There primary endpoints were overall (OS) and non-relapse mortality (NRM) and the secondary were progression-free survival (PFS) and relapse incidence (RI). The Kaplan-Meier estimator and log-rank test were used for OS and PFS, and the crude cumulative incidence estimator and Gray's test were used for competing events (RI and NRM). Age at ASCT, sex, year of ASCT, disease stage, Karnofsky score, MM classification, preparative regimen, time between diagnosis and ASCT, ISS stage at diagnosis, cytogenetic risk, and HCT-CI score were studied for prognostic value. Multivariable (cause specific) models included a random effect for each country and were censored at 3 years for OS and PFS and at 1 year for RI and NRM. Results: 61,725 patients from 629 centers (median patients/center = 67) were included: 61% from EBMT, 26% CIBMTR, 6% APBMT (5% Japan, 1% Taiwan, 0.3% Malaysia), 5% AZTCT, 1% EMBMT, 0.5% LABMT and 0.3% Ottawa, Canada. The patient baseline characteristics are shown in Table 1. Males comprised 58% and the median age at diagnosis was 60 years. The predominant phenotypes were IgG (54%), light chain (24%) and IgA (19%). The ISS stage at diagnosis was I (38%), II (35%) or III (27%) and cytogenetic risk was standard in 70% and high in 30%. The median time from diagnosis to ASCT was 7.1 months. The year of ASCT was equally distributed between 2013 and 2017 (the annual percentage varied between 18% and 22%). The median age at ASCT was 60.8 years with 5.1% of patients older than 70 years. The HCT-CI risk at transplant was low in 52%, intermediate in 25% and high in 23%. The Karnofsky score at ASCT was 100 in 40% and ≤90 in 60%.Disease status was CR in 19%, VGPR in 38%, PR in 36%, MR/SD in 5% and refractory in 2%. The most frequent preparative regimen was melphalan 200 mg/m2 (82 %) and 140 mg/m2 comprised 14%. Tandem ASCT was reported in 6.7%. Of the 11% of patients with data on post-ASCT maintenance treatment, 51% received lenalidomide. The median follow-up was 41.1 months (95% CI: 40.5 to 41.6, IQR:19.2-60.4). Outcomes: non-relapse mortality (NRM) at 12 months was 1% (95% CI 1-2%); OS at 4 and 8 years was 76% (75-76%) and 45% (42-48%) respectively; PFS at 2 and 4 years was 65% (95% CI: 64-65%) and 40% (40-41%) respectively; RI at 6 and 12 months was 7% (7-7%) and 16% (15-16%) respectively. In the multivariate analysis (Table 2), later calendar year of ASCT, a better disease response at time of ASCT, higher Karnofsky score, and an IgG phenotype were all associated with an improved OS. A lower ISS stage, a lower HCT-CI score and standard risk cytogenetics were also associated with better OS (Table 2). Overall NRM was low. Younger age, higher Karnofsky score, higher melphalan dose, better disease response at ASCT, lower ISS stage at diagnosis and lower HCT-CI score were associated with a lower NRM. Conclusions: This study represents the largest study to date characterizing the outcomes of ASCT performed worldwide. The most frequent preparative regimen was melphalan 200 mg/m2. Unmeasured confounding (pre-existing toxicities/frailties) may partially explain the higher NRM in those with low dose melphalan. Globally, NRM was low at 1% at 12 months, while RI was 16%. Median OS was 7 years, median PFS was 3 years and differed across various risk factors. ASCT remains an effective and safe procedure for patients with NDMM world-wide. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Epidemiologic features, clinical characteristics, and predictors of mortality in patients with candidemia in Alameda County, California; a 2017–2020 retrospective analysis

BackgroundBloodstream infections caused by Candida species are responsible for significant morbidity and mortality worldwide, with an ever-changing epidemiology. We conducted this study to assess trends in the epidemiologic features, risk factors and Candida species distribution in candidemia patients in Alameda County, California.MethodsWe analyzed data collected from patients in Alameda County, California between 2017 and 2020 as part of the California Emerging Infections Program (CEIP). This is a laboratory-based, active surveillance program for candidemia. In our study, we included incident cases only.ResultsDuring the 4-year period from January 1st, 2017, to December 31st, 2020, 392 incident cases of candidemia were identified. The mean crude annual cumulative incidence was 5.9 cases per 100,000 inhabitants (range 5.0–6.5 cases per 100,000 population). Candida glabrata was the most common Candida species and was present as the only Candida species in 149 cases (38.0%), followed by Candida albicans, 130 (33.2%). Mixed Candida species were present in 13 patients (3.3%). Most of the cases of candidemia occurred in individuals with one or more underlying conditions. Multivariate regression models showed that age ≥ 65 years (RR 1.66, CI 1.28–2.14), prior administration of systemic antibiotic therapy, (RR 1.84, CI 1.06–3.17), cirrhosis of the liver, (RR 2.01, CI 1.51–2.68), and prior admission to the ICU (RR1.82, CI 1.36–2.43) were significant predictors of mortality.ConclusionsNon-albicans Candida species currently account for the majority of candidemia cases in Alameda County.

Associations Between Vascular Diseases and Alzheimer's Disease or Related Dementias in a Large Cohort of Men and Women with Colorectal Cancer.

Long term risk of Alzheimer's disease (AD) and related dementias (ADRD) associated with vascular diseases in people with colorectal cancer is unknown. To determine the risk of ADRD in association with cardiovascular diseases (CVD), stroke, hypertension, and diabetes in a cohort of patients with colorectal cancer. This retrospective cohort study consisted of 210,809 patients diagnosed with colorectal cancer at age≥65 years in 1991-2015 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with follow-up from 1991-2016, who were free of any ADRD at the baseline (<12 months prior to or < 30 days after the date of cancer diagnosis). The crude 26-year cumulative incidence of total ADRD in men and women with colorectal cancer was higher in those with versus without CVD (31.92% versus 28.12%), with versus without stroke (39.82% versus 26.39%), with versus without hypertension (31.88% versus 24.88%), and with versus without diabetes (32.01% versus 27.66%). After adjusting for socio-demographic and tumor factors, the risk of developing ADRD was significantly higher in patients with CVD (adjusted hazard ratio: 1.17, 95% confidence intervals: 1.14-1.20), stroke (1.65, 1.62-1.68), hypertension (1.07, 1.05-1.09), and diabetes (1.26, 1.24-1.29) versus persons without. For those with 1, 2, 3 and 4 vascular diseases present versus absent, the risk of AD increased from 1.12 (1.07-1.16) to 1.31 (1.25-1.36), 1.66 (1.57-1.75), and 2.03 (1.82-2.27). In older patients with colorectal cancer, a significant dose-response relationship was observed between an increasing number of these vascular diseases and the risk of all types of dementia.

Role of Radiation Therapy in Mortality among Adolescents and Young Adults with Lymphoma: Differences According to Cause of Death.

Simple SummaryDespite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. However, the most current research studying the association between RT and outcome is based only on groups of lymphoma patients and is not compared with the general population, which could more accurately reveal the impact of RT on outcomes. This population-based analysis showed that after adjusting for potential confounders, RT administration is associated with a low risk of cause-specific mortality, including death due to the original diagnosis, second malignant neoplasms (SMNs), and noncancer causes, among AYA patients with lymphoma. This analysis may play a guiding role in the design of future lymphoma studies and the formulation of healthcare policies regarding the widespread use of RT, especially for AYA survivors.Background: Despite its efficacy, emerging concerns exist regarding radiation therapy (RT)-associated toxicity in adolescent and young adult (AYA) lymphoma patients. Few long-term follow-up studies have examined the association between RT and outcomes. Methods: Lymphoma patients aged 15–39 years were identified in the Surveillance, Epidemiology and End Results (SEER) database from 1992 to 2016. Mortality was assessed by comparing those with and without RT using the Fine–Gray competing risk model. Standardized mortality ratios (SMRs) were used to assess the relative risk of death compared with the general U.S. population. Results: In total, 29,686 patients were included; 10,708 (36.07%) received RT. Cause-specific mortality was compared between patients with and without RT while considering other competing events, including death due to index cancer, second malignant neoplasms (SMNs), and noncancer causes. Patients with RT had a lower probability of death and crude 5-year cumulative incidence of death. Moreover, there were significantly lower SMRs in patients with RT than in patients without RT. Differences between the two groups were greatest for mortality due to hematological malignancies and infections. Additionally, in the RT cohort, the SMR for index-cancer-related death was highest in the first year after diagnosis and gradually decreased. Hematological malignancies and infections were the most common specific SMN and noncancer causes of death, respectively. Conclusions: RT did not increase mortality from index cancer, SMNs, or noncancer causes in AYA patients with lymphoid malignancies. The current analysis may serve as a reference for healthcare providers monitoring RT application for AYA lymphoid malignancy survivors.

S3472 Rumble in the Tummy: Atypical Location of Abdominal Thrombosis Post-COVID

Introduction: More than 532 million cases of COVID-19 infection have been documented, and hundreds of thousands are being added every day. COVID-19 is linked to a number of co-morbidities, one of which, hypercoagulability, has piqued the interest of many researchers. Here, we present a case of a portal vein and superior mesenteric vein thrombosis in a patient with subclinical COVID-19 infection. Case Description/Methods: A healthy 30-year-old male presented 3 weeks after having mild, asymptomatic COVID with epigastric abdominal pain, nausea, and vomiting. His only complaints when he had COVID was a decreased appetite, but no other gastrointestinal (GI) or respiratory symptoms. Upon admission, initial CT with contrast showed thrombophlebitis of superior mesenteric vein (SMV) and portal vein (PV), decreased contrast within the intrahepatic PVs; follow up MR Angiography revealed PV intraluminal filling defect beginning just distal to the superior mesenteric vein and splenic vein confluence and involving the intrahepatic PV with periportal edema. He denied any prior clots nor family history of clotting disorder. GI and hematology were consulted. He received catheter-directed tPA for 2 days due to abdominal pain and follow up CT angiogram with no evidence of occlusion in arteries. The cause for his extensive abdominal vasculature thrombosis is thought to be secondary to COVID hypercoagulability, and the location has not been well delineated. Abdominal pain improved, he continued anticoagulation (AC), did not require repeat sessions with plans for close follow up imaging. (Figure) Discussion: Klok et al. reported a crude cumulative thrombosis incidence in COVID19 ICU patients is of 57% (95% CI 47–67%). In terms of intestinal damage, prothrombotic effects of the virus rises the incidence of mesenteric ischemia from 0.09–0.2% in the normal population to 1.9–3.8% in COVID-19 patients. Thrombosis is a known outcome, but in our case, this location is atypical, and he required catheter directed tPA by IR due to abdominal pain, that is a large measure and not typically done for thrombosis so it is also an aggressive management for thrombosis (done due to unrelenting abdominal pain). Hereby, we conclude that any vascular complication without an underlying reason should raise suspicion of an underlying COVID-19 infection, and more research should be done to determine the risk of such complications.Figure 1.: A,B: MRI Coronal view. Portal vein intraluminal filling defect beginning just distal to the superior mesenteric vein and splenic vein confluence and involving the intrahepatic portal vein with periportal edema Figure C,D: MRI Axial View of portal vein intraluminal filling defect with periportal edema Figure E: CT images post tPA show The portal vein, and SMV appear prominent in size and demonstrate perivascular stranding which can be seen with thrombosis.

Incidence rate of schizophrenia after the Tangshan earthquake in China: a 44-year retrospective birth cohort study

Preliminary evidence indicates that natural disasters are associated with an increased risk for schizophrenia. With few longitudinal studies on earthquakes, this retrospective cohort study examined exposure to the 1976 Tangshan earthquake and the subsequent risk of schizophrenia. Population counts and visits to all nine psychiatric hospitals in Tangshan city were collected. We created three cohort groups by earthquake exposure: infant (August 1972 to July 1976 births), fetal (August 1976 to May 1977 births), and unexposed (June 1977 to May 1981 births). The cumulative incidence of schizophrenia in each cohort was calculated by dividing the number of schizophrenia patients by total births in the corresponding period. Altogether, 6424 schizophrenia patients were identified, with 2786 in the infant group, 663 in the fetal group, and 2975 in the unexposed group. The crude cumulative incidence of schizophrenia in the infant, fetal and unexposed groups were 7.64 (95% confidence interval [CI] = 7.36–7.92), 9.07 (95% CI = 8.38–9.76), and 7.40 (95% CI = 7.13–7.66) per thousand population respectively. Adjusted for mortality, the corresponding figures were 7.73 (95% CI = 7.44–8.01), 9.30 (95% CI = 8.60–10.01) and 7.44 (95% CI = 7.18–7.71) per thousand population respectively. The mortality-adjusted risk ratio (aRR) was 1.25 (95% CI = 1.15–1.36) between fetal and unexposed groups (χ2 = 27.31, P < 0.001). Males exposed as infants did not differ from the unexposed in cumulative schizophrenia incidence. People with fetal exposure to the 1976 earthquake had 25% higher risk of developing schizophrenia compared to unexposed counterparts.

Poster 251: Autograft Associated with Lower Risk of Repeat Revision Anterior Cruciate Ligament Reconstruction than Allograft: Results from a Large Integrated Healthcare System

Objectives:With the rising utilization of primary anterior cruciate ligament reconstruction (ACLR), the burden of revision ACLR (rACLR) has also increased. Graft choice for rACLR is complicated by patient factors and the remaining available graft options. This study examines the relationship between graft type at the time of rACLR and the risk of repeat rACLR (rrACLR).Methods:We conducted a cohort study from a US integrated healthcare system’s ACLR registry. The study population included patients with a primary isolated ACLR, between 2005-2020, who then went on to have an aseptic rACLR. Graft type used at revision surgery, classified as autograft versus allograft, was the exposure of interest. Multivariable Cox proportional hazard regression was used to evaluate the risk of aseptic rrACLR with ipsilateral and contralateral reoperation as secondary outcomes. Models included factors at the time of the revision procedure (age, gender, body mass index, smoking status, staged revision, femoral fixation, tibial fixation, femoral tunnel method, lateral meniscus injury, medial meniscus injury, and cartilage injury) and a factor from the primary ACLR (activity at injury) as covariates.Results:1747 rACLR procedures were included. The crude cumulative aseptic rrACLR incidence at 8-years follow-up was 13.9% for allograft and 6.0% for autografts (Figure 1). Cumulative ipsilateral reoperation incidence at 8-years follow-up was 18.3% for allograft and 18.9% for autograft; contralateral reoperation cumulative incidence was 4.3% for allograft and 6.8% for autograft. With adjustment for covariates, a lower aseptic rrACLR risk was observed for autografts compared with allografts (HR=0.30, 95% CI=0.18-0.50, p <0.0001). No differences were observed for ipsilateral reoperation (HR=1.05, 95% CI=0.73-1.51, p=0.78) nor for contralateral reoperation (HR=1.33, 0.60-2.97, p=0.48) for autografts compared with allografts.Conclusions:The use of autograft at rACLR was associated with a 70% reduced risk of rrACLR compared to allograft in this large integrated health care system registry. When accounting for all reoperations after rACLR, we found no significant difference in risk between autograft and allograft. In order to minimize the risk of rrACLR, surgeons should consider using autograft for rACLR when possible.Figure 1.Cumulative Incidence of Asceptic Re-revision by Graft Type.

Outcomes in pleomorphic liposarcoma of the extremity and trunk: Is multimodality therapy indicated?

e23545 Background: In comparison to the more common histologic subtypes of liposarcoma (e.g., well differentiated/dedifferentiated; myxoid round cell), pleomorphic liposarcoma (PLPS) is poorly understood but generally regarded as more aggressive, with a high risk of distant metastasis. In this study, we sought to 1) assess outcomes after surgery for primary, non-metastatic PLPS and 2) explore indications for multimodality therapy (e.g., perioperative chemotherapy, radiation therapy) in this ultra-rare malignancy. Methods: Clinicopathologic data were retrospectively collected for eligible adult patients treated from 2002-2019 at our sarcoma referral center. Descriptive data was summarized and Kaplan-Meier plots were constructed for overall survival (OS) and crude cumulative incidences (CCI) of disease-specific death (DSD), local recurrence (LR) and distant metastasis (DM). Univariable models were performed to assess the association of specific variables of interest (e.g., tumor size) on outcome. Results: In total, 51 PLPS patients were included in this study. Mean tumor size was 9.7 cm. Tumors originated mostly in the extremity (67%), were deep in location (73%), and high grade (FNCLCC 3/3, 78%). All patients underwent complete (R0/R1) resection. Chemotherapy was given in 33% of patients and radiation therapy in 69%. With a median follow-up of 62 months, OS was 76% at 5 years. CCI of DSD, LR and DM at 5 years was 16%, 2% and 26%. Greater tumor size was observed to be strongly associated with worse OS (p = 0.002) and DSD (p = 0.006). Survival did not seem to be affected by pre-referral inadequate excision once patients (n = 18) underwent re-excision at our center. A separate subgroup of patients (n = 14) was identified with smaller (mean: 5.4 cm), superficial, lower grade tumors who underwent surgery alone without any DSD. Conclusions: In primary, non-metastatic PLPS, adequate surgery combined with perioperative chemotherapy and radiation therapy, when appropriate, is associated with favorable outcomes. Subgroups with potentially better clinical outcomes likely exist suggesting heterogeneity within PLPS. Multidisciplinary collaborative efforts across sarcoma centers are needed to better characterize these subgroups and determine the optimal strategies for management.

Intrauterine device-related uterine perforation incidence and risk (APEX-IUD): a large multisite cohort study

Reports of perforation risk related to intrauterine devices (IUDs) inserted immediately post partum and among non-post-partum individuals are scarce, and previous studies with only 12-month follow-ups underestimate the risk. Breastfeeding at IUD insertion and insertion within 36 weeks post partum have been associated with increased risk of uterine perforation. The aim of these analyses was to compare the incidence and risks of IUD-related uterine perforations by non-post-partum and post-partum intervals at IUD insertion, and among post-partum individuals, to assess the impact of breastfeeding on these outcomes. We did a multisite cohort study in the USA, using electronic health records (EHR). Study sites were three health-care systems and a site that used data from a health-care information exchange. The study population included individuals who were aged 50 years or younger and had an IUD insertion between Jan 1, 2001, and April 30, 2018. Individuals were excluded if they had not been in the health-care system for at least 12 months before IUD insertion. The primary outcome for this analysis was any IUD-related uterine perforation diagnosis for the first IUD insertion in this time period. Both complete and partial IUD-related perforations were identified. Chart abstraction was done to validate EHR-based algorithms or confirm perforations. The crude rate and cumulative incidence of uterine perforation were evaluated by non-post-partum and post-partum intervals at IUD insertion in the full cohort, and by breastfeeding status in a subcohort of post-partum individuals. Cox models estimated crude and adjusted hazard ratios (aHRs). Data from 326 658 individuals in the full cohort and 94 817 individuals in the post-partum subcohort were analysed. In the full cohort, we identified 1008 uterine perforations (51·2% complete), with the 5-year cumulative incidence being the lowest in the non-post-partum group (0·29%, 95% CI 0·26-0·34). The aHR for the post-partum interval relative to non-post partum ranged from 2·73 (95% CI 1·33-5·63; 0 to 3 days post partum) to 6·71 (4·80-9·38; 4 days to ≤6 weeks post partum). The post-partum subcohort of individuals with breastfeeding information had 673 uterine perforations (62% complete), with a 5-year cumulative incidence of 1·37% (95% CI 1·24-1·52) and an increased risk with breastfeeding (aHR 1·37, 95% CI 1·12-1·66). Although the risk for uterine perforation with IUD insertion 4 days to 6 weeks or less post partum is nearly seven times that of insertion non-post partum, perforation remains an incredibly rare event for all clinical time points. Despite a slight increased risk of perforation with breastfeeding at IUD insertion, the benefits of breastfeeding and effective contraception generally outweigh risks and should have little clinical impact. Therefore, IUD insertion timing should be based on individual desire for IUD contraception and patient convenience to assure an IUD insertion can occur. Careful follow-up of individuals at higher risk of uterine perforation is warranted. Bayer AG.

Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study

Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion. This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States. The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders. Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion. After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.

Concomitant Mitral Regurgitation in Severe Aortic Stenosis - A Report From the CURRENT AS Registry.

The clinical significance of concomitant mitral regurgitation (MR) has not been well addressed in patients with severe aortic stenosis (AS).Methods and Results:We analyzed 3,815 patients from a retrospective multicenter registry of severe AS in Japan (CURRENT AS registry). We compared the clinical outcomes between patients with moderate/severe MR and with none/mild MR according to the initial treatment strategy (initial aortic valve replacement [AVR] or conservative strategy). The primary outcome measure was a composite of aortic valve-related death or heart failure hospitalization. At baseline, moderate/severe MR was present in 227/1,197 (19%) patients with initial AVR strategy and in 536/2,618 (20%) patients with a conservative strategy. The crude cumulative 5-year incidence of the primary outcome measure was significantly higher in patients with moderate/severe MR than in those with none/mild MR, regardless of the initial treatment strategy (25.2% vs. 14.4%, P<0.001 in the initial AVR strategy, and 63.3% vs. 40.7%, P<0.001 in the conservative strategy). After adjusting confounders, moderate/severe MR was not independently associated with higher risk for the primary outcome measure in the initial AVR strategy (hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.67-1.83, P=0.69), and in the conservative strategy (HR 1.13, 95% CI 0.93-1.37, P=0.22). Concomitant moderate/severe MR was not independently associated with higher risk for the primary outcome measure regardless of the initial treatment strategy.

Refining the Approach to Patients with Primary Soft Tissue Sarcoma of the Extremities and Trunk Wall: Outcome Improvement Over Time at a Single Institution.

The improved outcome of extremity soft tissue sarcoma patients surgically treated until 2007 at the authors' institution was previously reported. This study updates the analysis at a later follow-up and extends the patients'cohort to assess changes in outcomes over time for extremity and superficial trunk soft tissue sarcoma (ESTSTS) treated at a single referral center. All consecutive patients with primary localized adult-type ESTSTSsurgically treated at the authors' institution between 1987 and 2017 wereincluded and divided into group 1 (1987-2002) and group 2 (2003-2017) according to primary surgery year. Crude cumulative incidence (CCI) of sarcoma-specific mortality (SSM), local recurrence (LR), and distant metastases (DM)were calculated in a competing-risks framework. DM-free survival (DMFS) and post-DM survivalwere also assessed. The study identified 2382 patients. The median follow-up was 104 months (range, 63-127 months), and the post-DM follow-up was 76 months (range, 37-126 months). Since 2003, an increased adoption of preoperative treatments was observed: the use ofchemotherapy, radiotherapy and combined chemoradiotherapy went from 10.5% to 23.7%, from 1.7% to 17.8%, and from 1% to 11.8%respectively. This change in treatment strategies was associated to an improvementin CCI-SSM (27.8% vs 19.5%; P < 0.001), CCI-LR (14.1 vs 7.5%; P < 0.001), DMFS (57.9% vs 65.8%; P = 0.004), and post-DM (12.2% vs 20.1%; P = 0.012), but not in CCI-DM. Increased adoption of preoperative treatments and greater availability of medical agents in the recent years were associated to better outcomes. New treatments are eagerly awaited for further improvement of outcome for ESTSTS patients because no major changes have been observed since 2003.

Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management

BackgroundVascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population.Patients and methodsIn this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs.ResultsA total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001).ConclusionsMACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Characterizing the risk interplay between alcohol intake and body mass index on cirrhosis morbidity.

It is thought that alcohol intake and body mass index (BMI) interact supra-additively to modulate the risk of cirrhosis, but evidence for this phenomenon is limited. We investigated the interrelationship between alcohol and BMI on the incidence of cirrhosis morbidity for participants of the United Kingdom Biobank (UKB) study. The primary outcome was the cumulative incidence of cirrhosis morbidity, defined as a first-time hospital admission for cirrhosis (with noncirrhosis mortality incorporated as a competing risk). All UKB participants without a previous hospital admission for cirrhosis were included in the analysis. We determined the ratio of the 10-year cumulative incidence in harmful drinkers versus safe drinkers according to BMI. We also calculated the excess cumulative incidence at 10 years for individuals with obesity and/or harmful alcohol compared to safe drinkers with a healthy BMI of 20-25.0 kg/m2 . A total of 489,285 UK Biobank participants were included, with mean of 10.7 person-years' follow-up. A total of 2070 participants developed the primary outcome, equating to a crude cumulative incidence of 0.36% at 10 years (95% CI:0.34-0.38). The 10-year cumulative incidence was 8.6 times higher for harmful (1.38%) versus safe drinkers (0.16%) if BMI was healthy. Conversely, it was only 3.6 times higher for obese participants (1.99% vs. 0.56%). Excess cumulative incidence was 1.22% (95% CI:0.89-1.55) for harmful drinkers with a healthy BMI, 0.40% (95% CI:0.34-0.46) for obese individuals drinking at safe levels, and 1.83% (95% CI:1.46-2.20) for obese harmful drinkers (all compared to safe drinkers with a healthy BMI). Alcohol intake and obesity are independent risk factors for cirrhosis morbidity, but they do not interact supra-additively to modulate the cumulative incidence of this outcome.

Symptomatic and Asymptomatic Peripheral Artery Disease and the Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

A prospective cohort study was performed at visit 1 (1987-1989) and a cross-sectional cohort study was performed at visit 5 (2011-2013) from four U.S. communities (Washington County, Md; suburban Minneapolis, Minn; Jackson, Miss; Forsyth County, NC) in the Atherosclerosis Risk in Communities (ARIC) study. Of 14,148 participants (55% female, 26% black, 1% with symptomatic peripheral arterial disease), after a median follow-up of 23 years, 3.7% had developed incident abdominal aortic aneurysms (AAAs). The presence of symptomatic peripheral artery disease (PAD) resulted in a higher hazard ratio (HR) of incident AAA (HR, 4.9), as did asymptomatic PAD with an ankle brachial index (ABI) of ≤0.9 (HR, 2.33) compared with the reference ABI of >1.1. The crude 15-year cumulative incidence of AAAs was 12% in the symptomatic PAD group, 4% in the asymptomatic PAD group with an ABI of <0.9, and 2% in the asymptomatic PAD group with an ABI of >1.1. The cross-sectional analysis demonstrated similar patterns for ultrasound-based AAAs, with odds ratio for AAAs of 2.5 for symptomatic PAD and 4.0 for asymptomatic PAD in a demographically adjusted model. These prospective and cross-sectional data showed an elevated risk of AAAs in patients with symptomatic and asymptomatic PAD. These data support the current recommendation of AAA screening for symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well.

Comparative Study of Unrelated and Haploidentical Donor Hematopoietic Cell Transplant for Chronic Myeloid Leukemia with Post Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis: A Study from the Chronic Malignancies Working Party of EBMT

Comparative Study of Unrelated and Haploidentical Donor Hematopoietic Cell Transplant for Chronic Myeloid Leukemia with Post Transplant Cyclophosphamide As Graft-Versus-Host Disease Prophylaxis: A Study from the Chronic Malignancies Working Party of EBMT