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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.

BACKGROUND As indications for elective total hip arthroplasty (THA) expand to younger patients, we sought to (1) compare revision risk following primary elective THA in patients

Study design A retrospective cohort study with chart review. Objective To determine if there is a difference in reoperation rates for adjacent segment disease (operative ASD) in posterior cervical fusions (PCF) that stop at -C7 versus -T1/T2. Summary of background data There are surgical treatment challenges to the anatomical complexities of the cervicothoracic junction (CTJ). Current posterior cervical spine surgery is based on the belief that adjacent segment disease (ASD) occurs if fusions are stopped at C7 although there is varying evidence to support this assumption. Methods Patients were followed until validated reoperations for ASD, membership termination, death, or 03/31/2020. Descriptive statistics and five-year crude incidence rates and 95% confidence intervals (CI) for operative ASD for PCF ending at -C7 or -T1/T2 were reported. Time-dependent crude and adjusted, multivariable Cox-Proportional Hazards models were used to evaluate operative ASD rates with adjustment for covariates or risk change estimates more than 10%. Results We identified 875 patients with PCFs (beginning at C3 or C4 or C5 or C6) stopping at either -C7 (n = 470) or -T1/T2 (n = 405) with average follow-up time of 4.6 (±3.3) years and average time to operative ASD of 2.7 (±2.8) yrs. Crude overall incidence rates for stopping at -C7 (2.12% (1.02%-3.86%)) and -T1/T2 (2.48% (1.25%-4.40%)) were comparable with no statistical difference in risk (adjHR = 1.47, 95% CI = 0.61-3.53, P = 0.39). Additionally, we observed no differences in the probability of operative ASD in competing risk time-dependent models (Grey's Test P = 0.448). Conclusion A large cohort of 875 patients with PCFs stopping at -C7 or -T1/T2 with an average follow-up of > 4 years found no statistical difference in reoperation rates for ASD (operative ASD).Level of Evidence: 3.

BACKGROUND CONTEXT Although fusion rates between posterolateral fusions with pedicle screws (PLFs) and anterior lumbar interbody fusions with pedicle screws (ALIFs+PS) have been well studied, there has been no consensus on the better technique with respect to clinical outcome and nonunion rates. Most studies determine nonunion rates based on radiographic studies; however, many of these nonunions are asymptomatic. A more clinically useful measure is the operative nonunion rate. To date, data comparing operative nonunion rates in PLF and ALIF+PS are limited. PURPOSE To determine whether there is a difference between nonunion reoperation rates in PLFs vs anterior lumbar interbody fusions with pedicle screws (ALIFs+PS). STUDY DESIGN/SETTING Retrospective cohort. PATIENT SAMPLE The cohort comprised 8,340 patients aged ≥50 who underwent primary elective lumbar spinal fusion (L1-S1) for degenerative or deformity related spinal disorders (2009-2018). OUTCOME MEASURES Operative nonunions. METHODS Adult patients (≥18 years old) with degenerative disc disease who underwent primary elective PLFs and ALIFs+PS for 1-level and 2-level fusions (L4-S1) between 2009-2018 were identified using data from the Kaiser Permanente Spine Registry and followed until validated operative nonunion, membership termination, death, or 03/31/2019. Descriptive statistics and two-year incidence rates for validated operative nonunions were calculated by fusion level, fusion type, and levels fused. Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate operative nonunion rates with adjustment for covariates or risk change estimates more than 10%. RESULTS We identified 2,061 patients (PLF:1491, ALIF+PS:570) with average follow-up time of 4.8(±3.1) years, and average time to operative nonunion 1.3(±1.2) yrs. Comparatively, single and multilevel incidence rates for nonunion were higher in PLF vs ALIF+PS: 1-Level: 0.9% (95% CI=0.4-1.6) vs 0.6% (95% CI=0.1-2.1); 2-Level: 2.0% (95% CI=0.8-4.0) vs 0.9% (95% CI=0.1-3.3). There were no observed differences in risk of operative nonunions in multivariable models comparing ALIF+PS vs PLF (HR=0.3, 95% CI=0.1-1.1), 1-level vs 2-level fusions (HR=1.8, 95% CI=0.8-4.3), or by fusion level (L4-L5: HR=1.0, 95% CI=0.4-2.7; L5-S1: HR=2.0, 95% CI=0.7-5.4). CONCLUSIONS A large cohort of patients with >4 years follow-up found no difference in operative nonunions between PLF and ALIF+PS. Further research is warranted. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

BackgroundThe incidence of anal squamous cell carcinoma has been increasing, particularly in people living with HIV (PLWH). There is concern that radiosensitizing drugs, such as protease inhibitors, commonly used in the management of HIV, may increase toxicities in patients undergoing chemoradiation. This study examines treatment outcomes and toxicities in PLWH managed with and without protease inhibitors who are receiving chemoradiation for anal cancer.MethodsPatient demographic, HIV management, and cancer treatment information were extracted from multiple Veterans Affairs databases. Patients were also manually chart reviewed. Among PLWH undergoing chemoradiation for anal carcinoma, therapy outcomes and toxicities were compared between those treated with and without protease inhibitors at time of cancer treatment. Statistical analysis was performed using chi-square, Cox regression analysis, and logistic regression.ResultsA total of 219 PLWH taking anti-retroviral therapy undergoing chemoradiation for anal cancer were identified and included in the final analysis. The use of protease inhibitors was not associated with any survival outcome including colostomy-free survival, progression-free survival, or overall survival (all adjusted hazard ratiop-values> 0.05). Regarding toxicity, protease inhibitor use was not associated with an increased odds of hospitalizations or non-hematologic toxicities; however, protease inhibitor use was associated with increased hospitalizations for hematologic toxicities, including febrile neutropenia (p ConclusionThe use of protease inhibitors during chemoradiation for anal carcinoma was not associated with any clinical outcome or increase in non-hematologic toxicity. Their use was associated with increased hospitalizations for hematologic toxicities. Further prospective research is needed to evaluate the safety and efficacy of protease inhibitors for patients undergoing chemoradiation.

Background Recent case series have reported early failure with the use of high-viscosity cement (HVC) in total knee arthroplasty (TKA). We evaluated revision risk after TKA with HVC compared with medium-viscosity cement (MVC) in a large cohort. Methods We conducted a cohort study using data from Kaiser Permanente’s Total Joint Replacement Registry. Patients who underwent fully cemented primary TKA for osteoarthritis were identified (2001-2018). Only posterior-stabilized, fixed-mobility designs of the 3 highest-volume implant systems (DePuy PFC, Zimmer NexGen, and Zimmer Persona) were included to mitigate confounding from implant characteristics. Palacos (Zimmer/Heraeus) and Simplex (Stryker) cements comprised the HVC and MVC exposure groups, respectively. Propensity score–weighted Cox proportional hazards regression was used to evaluate risk for any revision during follow-up and risk for revision from aseptic loosening specifically. Results The final cohort comprised 76,052 TKAs, 41.1% using MVC. The crude 14-year cumulative revision probability was 4.55% and 5.12% for TKA with MVC and HVC, respectively. In propensity score–weighted Cox models, MVC compared with HVC had a lower risk of any revision (hazard ratio = 0.82, 95% confidence interval = 0.70-0.95) while no difference was observed for revision from aseptic loosening (hazard ratio = 0.80, 95% confidence interval = 0.56-1.13). Conclusion While we observed a lower risk for any revision with the use of Simplex MVC compared with Palacos HVC, we did not observe a difference in revision for aseptic loosening specifically. Given the widespread use of HVC, additional research to investigate other HVC and potential mechanisms for failure outside of loosening is warranted. Level of Evidence Level III.

A retrospective cohort study with chart review.To determine if there is a difference in risk of adverse outcomes following elective posterior instrumented lumbar spinal fusions for patients aged 80 years and above compared with patients aged 50 to 79 years.Patients aged 80 years and above are undergoing elective lumbar spinal fusion surgery in increasing numbers. There are conflicting data on the risks of intraoperative and postoperative complications in these patients.Patients aged 80 years and above were compared with 50 to 79 years (reference group) using time-dependent multivariable Cox proportional hazards regression with a competing risk of death for longitudinal outcomes and multivariable logistic regression for binary outcomes. Outcome measures used were: (1) intraoperative complications (durotomy), (2) postoperative complications: 30-day outcomes (pneumonia); 90-day outcomes (deep vein thrombosis, pulmonary embolism, emergency room visits, readmission, reoperations, and mortality); and two-year outcomes (reoperations and mortality).The cohort consisted of 7880 patients who underwent primary elective posterior instrumented lumbar spinal fusion (L1-S1) for degenerative disk disease or spondylolisthesis. This was subdivided into 596 patients were aged 80 years and above and 7284 patients aged 50 to 79. After adjustment, patients aged 80 years and above had a higher likelihood of durotomy [odds ratio (OR)=1.43, 95% confidence interval (CI)=1.02-2.02] and 30-day pneumonia (OR=1.81, 95% CI=1.01-3.23). However, there was a lower risk of reoperation within two years of the index procedure (hazard ratio=0.69, 95% CI=0.48-0.99). No differences were observed for mortality, readmissions, emergency room visits, pulmonary embolism, or deep vein thrombosis.In a cohort of 7880 elective posterior instrumented lumbar fusion patients for degenerative disk disease or spondylolisthesis, we did not observe any significant risks of adverse events between patients aged 80 years and above and those aged 50 to 79 except for higher durotomies and 30-day pneumonia in the former. We believe octogenarians can safely undergo lumbar fusions, but proper preoperative screening is necessary to reduce the risks of 30-day pneumonia.

Study design A retrospective cohort study with chart review. Objective The aim of this study was to compare the reoperation rates for symptomatic nonunions (operative nonunion rates) between posterolateral fusions with pedicle screws (PLFs) and posterior interbody fusion with pedicle screws (PLIFs). Summary of background data Although radiographic nonunions in PLFs and PLIFs are well documented in the literature, there is no consensus on which technique has lower nonunions. Since some radiographic nonunions may be asymptomatic, a more clinically useful measure is operative nonunions, of which there is minimal research. Methods A retrospective cohort study, using data from the Kaiser Permanente Spine Registry, identified adult patients (≥18 years' old) who had elective single and multilevel PLFs and PLIFs. Descriptive statistics and 2-year incidence rates for operative nonunions were calculated by fusion-level (1-3), fusion type (PLF vs. PLIF), and levels fused (L3 to S1). Time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate nonunion reoperation rates with adjustment for covariates. Results The cohort consisted of 3065 patients with PLFs (71.6%) and PLIFs (28.4%). Average age was 65.0 ± 11.7, average follow-up time was 4.8 ± 3.1 years, and average time to operative nonunion was 1.6 (±1.3) years. Single and multilevel incidence rates for nonunions after PLF versus PLIF were similar except for three-level fusions (2.9% [95% confidence interval, CI = 1.0-6.7] vs. 7.1% [95% CI = 0.2-33.9]). In adjusted models, there was no difference in risk of operative nonunions in PLIF compared to PLF (hazard ratio [HR]: 0.8, 95% CI = 0.4-1.6); however, patients with L5-S1 constructs with PLFs had 2.8 times the risk of operative nonunion compared to PLIFs (PLF: HR = 2.8, 95% CI = 1.3-6.2; PLIF: HR = 1.5, 95% CI = 0.4-5.1). Conclusion In a large cohort of patients with >4 years of follow-up, we found no difference in operative nonunions between PLF and PLIF except for constructs that included L5-S1 in which the risk of nonunion was limited to PLF patients.Level of Evidence: 3.

Background People living with HIV/AIDS (PLWH) have an excess risk for head and neck squamous cell carcinoma (HNSCC) compared to the general U.S. population, but little is known about HIV‐specific risk factors associated with the incidence and outcomes HNSCC. We aim to identify clinical and HIV‐specific risk factors associated with oropharyngeal and non‐oropharyngeal HNSCC incidence and outcomes separately. Methods We constructed a retrospective cohort study of 45,052 PLWH aged 18 or above from the national Veteran Affairs (VA) Corporate Data from 1999 to 2015. We extracted demographic data and risk factor information, including history of alcohol abuse, smoking, CD4 count (cells/μl), and percent of follow‐up time with undetectable HIV viral load as time‐updated variables. We calculated the age‐standardized incidence rates of oropharyngeal and non‐oropharyngeal HNSCC and estimated adjusted hazard ratios (HR). We also examined overall survival using Kaplan–Meier curves and adjusted HR. Results The standardized incidence rate of oropharyngeal and non‐oropharyngeal HNSCC in this veteran cohort of PLWH is 23.0 (95% confidence intervals (CIs): 17.1‐28.9) and 55.4 (95% CI: 46.5‐64.3) per 100,000 person‐years, respectively. Nadir CD4 count ≤200 was associated with an increased risk of non‐oropharyngeal HNSCC (HR: 1.78; 95% CI: 1.31‐2.30 vs >200). Five‐year overall survival of OPSCC (37.0%) was significantly lower than non‐oropharyngeal HNSCC (49.1%). Conclusions PLWH who receive care in the VA had higher age‐adjusted HNSCC incidence rates than reported in the general population, suggesting that HIV and immunosuppression play a role. Additional studies should be conducted to study the interaction between HPV and HIV., The elevated risk of both oropharynx cancer and non‐oropharyngeal head and neck cancer and poor survival among people living with HIV in the VA healthcare system suggests the host immune system interacts with smoking and HPV.

Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study.The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age-standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010.Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV-negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV-positive (N = 30 [81.1%]) than the HIV-negative veterans with OPSCC (N = 50 [67.6%]), although this difference was not significant (p = .135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk.The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV-positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

Previous studies have documented racial and ethnic disparities in total joint arthroplasty (TJA) utilization in the United States. A potential mediator of healthcare disparities is unequal access to care, and studies have suggested that disparities may be ameliorated in systems of universal access. The purpose of this study was to assess whether racial/ethnic disparities in TJA utilization persist in a universally insured population of patients enrolled in a managed healthcare system.This retrospective cohort study used data from a US integrated healthcare system (2015 to 2019). Patients aged 50 years and older with a diagnosis of hip or knee osteoarthritis were included. The outcome of interest was utilization of primary total hip arthroplasty and/or total knee arthroplasty, and the exposure of interest was race/ethnicity. Incidence rate ratios (IRRs) were modeled using multivariable Poisson regression controlling for confounders.There were 99,548 patients in the hip analysis and 290,324 in the knee analysis. Overall, 10.2% of the patients were Black, 20.5% were Hispanic, 9.6% were Asian, and 59.7% were White. In the multivariable analysis, utilization of primary total hip arthroplasty was significantly lower for all minority groups including Black (IRR, 0.55, 95% confidence interval [CI], 0.52-0.57, P0.0001), Hispanic (IRR, 0.63, 95% CI, 0.60-0.66, P0.0001), and Asian (IRR, 0.64, 95% CI, 0.61-0.68, P0.0001). Similarly, utilization of primary total knee arthroplasty was significantly lower for all minority groups including Black (IRR, 0.52, 95% CI, 0.49-0.54, P0.0001), Hispanic (IRR, 0.72, 95% CI, 0.70-0.75, P0.0001), and Asian (IRR, 0.60, 95% CI, 0.57-0.63, P0.0001) (all in comparison with White as reference).In this study of TJA utilization in a universally insured population of patients enrolled in a managed healthcare system, disparities on the basis of race and ethnicity persisted. Additional research is required to determine the reasons for this finding and to identify interventions which could ameliorate these disparities.

To evaluate the risks of esophageal and stomach carcinomas in people living with HIV (PLWH) compared with the general population and risk factors for these cancers in PLWH.Retrospective cohort study in the Veterans Health Administration.We compared incidence rates for esophageal and stomach cancers in 44,075 HIV-infected male veterans with those in a matched HIV-uninfected cohort (N = 157,705; 4:1 matched on age and HIV-index date). We used Cox regression models to estimate Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with HIV infection and for cancer risk factors in PLWH.In unadjusted models, HIV infection was associated with increased risks of esophageal squamous cell carcinoma (ESCC; HR, 2.21; 95% CI: 1.47 to 3.13) and gastric cardia cancer (HR, 1.69; 95% CI: 1.00 to 2.85) but associated with lower risk of esophageal adenocarcinoma (EAC; HR, 0.48; 95% CI: 0.31 to 0.74). After adjusting for age, race/ethnicity, smoking and alcohol use, HIV infection remained statistically significantly associated with elevated risk for ESCC [adjusted hazard ratio (aHR), 1.58; 95% CI: 1.02 to 2.47], especially among HIV-infected patients with CD4 count ≤200 (aHR, 2.20; 95% CI: 1.35 to 3.60). HIV infection was not associated with risks of EAC (aHR, 0.82; 95% CI: 0.53 to 1.26), gastric cardia (aHR, 0.80; 95% CI: 0.33 to 1.94), or noncardia (aHR, 1.06; 95% CI: 0.61 to 1.84) cancers. Risk factors for these cancers in HIV-infected patients were otherwise similar to those in general population (eg, Helicobacter pylori for gastric noncardia cancer).HIV-infected individuals with low CD4 count are at highest risk for ESCC, but HIV infection was not independently associated with EAC or gastric cancer after adjusting for confounders.

The purpose of this systematic review was to evaluate the existing scientific literature on e- and mHealth interventions promoting physical activity (PA) among African American (AA) and Hispanic women.Using Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, 5 electronic databases and gray literature sources were searched in August 2017. Inclusion criteria are published in English language peer-reviewed journals between 2000 and 2017, use of an e- or mHealth delivery strategy to promote PA, primary focus on AA or Hispanic women, and reported PA outcome data.Ten articles met inclusion criteria for review, 6 studies focused on AA women and 4 studies on Hispanic women. The majority (n = 8) were pilot studies; only 2 studies were full-scale randomized controlled trials and both focused on Hispanic women. Six studies (60%) used websites as the primary method of intervention delivery, 3 studies (30%) used text messaging, and 1 study (10%) used the social networking website Facebook. In total, 70% of the studies (n = 7) reported significant within- or between-group differences for at least 1 PA outcome.Findings provide preliminary support for e- and mHealth PA interventions among AA and Hispanic women. However, future large-scale, rigorously designed, randomized controlled trials are needed to further explore their effectiveness among AA and Hispanic women.

OBJECTIVE The challenges of posterior cervical fusions (PCFs) at the cervicothoracic junction (CTJ) are widely known, including the development of adjacent-segment disease by stopping fusions at C7. One solution has been to cross the CTJ (T1/T2) rather than stopping at C7. This approach may have undue consequences, including increased reoperations for symptomatic nonunion (operative nonunion). The authors sought to investigate if there is a difference in operative nonunion in PCFs that stop at C7 versus T1/T2. METHODS A retrospective analysis identified patients from the authors’ spine registry (Kaiser Permanente) who underwent PCFs with caudal fusion levels at C7 and T1/T2. Demographics, diagnoses, operative times, lengths of stay, and reoperations were extracted from the registry. Operative nonunion was adjudicated via chart review. Patients were followed until validated operative nonunion, membership termination, death, or end of study (March 31, 2020). Descriptive statistics and 2-year crude incidence rates and 95% confidence intervals for operative nonunion for PCFs stopping at C7 or T1/T2 were reported. Time-dependent crude and adjusted multivariable Cox proportional hazards models were used to evaluate operative nonunion rates. RESULTS The authors identified 875 patients with PCFs (beginning at C3, C4, C5, or C6) stopping at either C7 (n = 470) or T1/T2 (n = 405) with a mean follow-up time of 4.6 ± 3.3 years and a mean time to operative nonunion of 0.9 ± 0.6 years. There were 17 operative nonunions, and, after adjustment for age at surgery and smoking status, the cumulative incidence rates were similar between constructs stopping at C7 and those that extended to T1/T2 (C7: 1.91% [95% CI 0.88%–3.60%]; T1/T2: 1.98% [95% CI 0.86%–3.85%]). In the crude model and model adjusted for age at surgery and smoking status, no difference in risk for constructs extended to T1/T2 compared to those stopping at C7 was found (adjusted HR 1.09 [95% CI 0.42–2.84], p = 0.86). CONCLUSIONS In one of the largest cohort of patients with PCFs stopping at C7 or T1/T2 with an average follow-up of > 4 years, the authors found no statistically significant difference in reoperation rates for symptomatic nonunion (operative nonunion). This finding shows that there is no added risk of operative nonunion by extending PCFs to T1/T2 or stopping at C7.

Background Although the COVID-19 pandemic has disrupted elective shoulder arthroplasty throughput, traumatic shoulder arthroplasty procedures are less apt to be postponed. We sought to evaluate shoulder arthroplasty utilization for fracture during the COVID-19 pandemic and California's associated shelter-in-place order compared to historical controls. Methods We conducted a cohort study with historical controls, identifying patients who underwent shoulder arthroplasty for proximal humerus fracture in California using our integrated electronic health record. The time period of interest was following the implementation of the statewide shelter-in-place order: March 19, 2020-May 31, 2020. This was compared to three historical periods: January 1, 2020-March 18, 2020, March 18, 2019-May 31, 2019, and January 1, 2019-March 18, 2019. Procedure volume, patient characteristics, in-hospital length of stay, and 30-day events (emergency department visit, readmission, infection, pneumonia, and death) were reported. Changes over time were analyzed using linear regression adjusted for usual seasonal and yearly changes and age, sex, comorbidities, and postadmission factors. Results Surgical volume dropped from an average of 4.4, 5.2, and 2.6 surgeries per week in the historical time periods, respectively, to 2.4 surgeries per week after shelter-in-place. While no more than 30% of all shoulder arthroplasty procedures performed during any given week were for fracture during the historical time periods, arthroplasties performed for fracture was the overwhelming primary indication immediately after the shelter-in-place order. More patients were discharged the day of surgery (+33.2%, P = .019) after the shelter-in-place order, but we did not observe a change in any of the corresponding 30-day events. Conclusions The volume of shoulder arthroplasty for fracture dropped during the time of COVID-19. The reduction in volume could be due to less shoulder trauma due to shelter-in-place or a change in the indications for arthroplasty given the perceived higher risks associated with intubation and surgical care. We noted more patients undergoing shoulder arthroplasty for fracture were safely discharged on the day of surgery, suggesting this may be a safe practice that can be adopted moving forward. Level of Evidence Level III; Retrospective Case-control Comparative Study

Among people living with HIV (PWH), there has been an increasing incidence of non-small cell lung cancer (NSCLC) and metabolic abnormalities, including dyslipidemia, which can modulate NSCLC risk. In this article, we evaluate which metabolic risk factors are associated with incident risk among PWH who smoke. This is done through a retrospective cohort study, using data of HIV+ veterans who smoke from the nationwide Veterans Affairs (VA) healthcare system. Data on diagnostic codes, medication, and laboratory values of 33,351 veterans were obtained using the VA&rsquo, s Corporate Data Warehouse and Central Cancer Registry. We calculated NSCLC incidence and utilized Cox regression to determine metabolic factors associated with NSCLC risk. HIV+ cohort was 97.4% male, median age = 47 years and 20,050 (60.1%) well-controlled (&ge, 80% follow-up time undetectable viral load). Crude incidence rates were lower in well-controlled PWH (1.46 vs. 2.06/1000 PY). Metabolic factors associated with incident NSCLC risk included lower BMI at HIV diagnosis and cachexia history in both groups, while HDL and triglycerides were significant in non-well-controlled smokers only. Our findings that lower BMI at HIV diagnosis, history of cachexia among individuals with well-controlled HIV, and cachexia presence at diagnosis are associated with increased risk of developing NSCLC in PWH with a history of smoking have important implications.

Objective Radiographic nonunion rates in the literature for posterolateral lumbar fusions with pedicle screws (PLFs) range from 8.1% to 43.3% but may not represent nonunion rates. A few small studies have reported reoperations for symptomatic nonunions (operative nonunions) to range from 3.2% to 13.9%. The objective of this study is to determine operative nonunion rates for 1-level, 2-level, 3-level, and ≥4-level PLFs and to determine the risks for these nonunions. Methods A retrospective cohort study, using data from the Kaiser Permanente Spine Registry, identified adult patients (≥18 years old) who underwent PLFs for degenerative disc disease. Multivariable Cox proportional hazards regression and Kaplan-Meier survival estimates using the log-rank statistic were used to evaluate operative nonunion rates. Results The cohort consisted of 2591 patients with single-level and multilevel PLFs with mean follow-up of 4.6 years, time to operative nonunion of 1.52 years, and 2-year operative nonunion rate of 1.08%. Compared with single-level fusions, patients with 3-level and ≥4-level fusion had 2.8 and 3.7 times higher risk of operative nonunions. Patients with PLFs involving L5-S1 had 2.5 times the risk of an operative nonunion compared with those without. Conclusions Our study reports results from one of the largest cohort of patients for the first time with single-level and multilevel instrumented PLFs and found a 2-year operative nonunion rate of 1.08% with increased risk of nonunion for constructs that included L5-S1 and ≥3-level fusions. Operative nonunion combines clinical and radiographic data and provides an alternative measure of fusion rates.

BACKGROUND Despite advances in diagnosis and treatment of both HIV and Burkitt lymphoma (BL), persons living with HIV remain at high risk for BL. We conducted this study to evaluate if there have been any changes in the risk of or survival after BL diagnosis among persons living with HIV during the antiretroviral era. SETTING Veterans living with HIV (VLWH) and age-matched HIV-negative controls receiving care between 1999 and 2016 were retrospectively identified using Veterans Health Administration electronic medical records. METHODS We identified BL diagnoses through Veterans Health Administration Cancer Registry review and International Classification of Diseases, Ninth/Tenth Revisions, codes, and we extracted demographic, lifestyle, and clinical variables from electronic medical record. We estimated hazard ratios (HR) and 95% confidence intervals (CIs) for BL risk and survival using Cox proportional models. RESULTS We identified 45,299 VLWH. Eighty-four developed BL (incidence rate = 21.2 per 100,000 person years; CI: 17.1 to 26.3). Median CD4 count at BL diagnosis was 238 cells per milliliter (SD: 324.74) and increased over time. Survival was truncated in VLWH with BL (P < 0.05). The risk of BL in VLWH was 38% less in blacks compared with whites (HR: 0.620; CI: 0.393 to 0.979; P = 0.0401). VLWH with an undetectable viral load for at least 40% of follow-up were 74% less likely to develop BL (HR: 0.261; CI: 0.143 to 0.478; P < 0.0001) and 86% less likely to die after diagnosis (HR: 0.141; CI: 0.058 to 0.348; P < 0.0001). CONCLUSIONS BL incidence among VLWH did not improve between 2000 and 2016. Survival after BL diagnosis in VLWH remains dismal as compared with their HIV-negative counterparts, although veterans with prolonged periods of undetectable viral load had improved prognosis.

Tight junction and cell polarity proteins are paramount to epithelial cell polarity and transport. In vivo studies have shown the differential expression of tight junctions in colorectal cancer, with little to no human data to corroborate those findings. We investigated whether tight junction genes were differentially expressed in human colon cancer versus normal controls.

BACKGROUND CONTEXT Circumferential lumbar fusions combine anterior column support using an anterior approach (anterior lumbar interbody fusion, ALIF), a lateral approach (lateral lumbar interbody fusion, LLIF) or a posterior approach (posterior lumbar interbody fusion, PLIF/transforaminal lumbar interbody fusion, TLIF), with posterior support with pedicle screw fixation (PS). Circumferential fusions have shown biomechanical advantages compared to posterolateral fusion (PLF) with pedicle screw fixation, including restoration of lordosis, indirect foraminal decompression, and reduction of the slip via ligamentotaxis. However, they may increase the stiffness of the spine due to anterior column support and loading. Although several small comparative studies reporting radiographic adjacent segment degeneration (ASD) and meta-analyses on adjacent segment disease (ASDis) have been published, to our knowledge, there are currently no large-scale studies that report ASDis. PURPOSE To assess the incidence of and risk for operative adjacent segment disease (ASDis) after circumferential lumbar fusion, by surgical approach, vs PLF. STUDY DESIGN/SETTING Retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry. PATIENT SAMPLE A final retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry, consisting of 5,521 patients with lumbar fusions completed between 01/01/2009 and 12/31/2018. OUTCOME MEASURES Five-year incidence rate of ASDis requiring reoperation. METHODS A total of 5,521 patients aged ≥18 who underwent primary elective lumbar fusion (L3-S1) for degenerative disc disease (2009-2018). Five-year incidence rates of validated, operative ASDis were calculated by fusion type (PLF, ALIF/LLIF+PS, and PLIF/TLIF+PS) and fusion level (1-2 levels). Covariate-adjusted time-dependent multivariable Cox-Proportional Hazards regression was used to evaluate reoperation rates with using PLF as the reference group. RESULTS Fifty percent of fusions were PLIF/TLIF+PS (N=2,821), more than one-third were PLF+PS (N=2006), and the remaining were ALIF/LLIF+PS (N=694). Average cohort age was 61.8 years (SD±12.7) and average follow-up was 4.8 years (SD±3.1). Five-year incidence rates of operative ASDis were 7.0% (95% confidence interval [CI] =6.4-7.7). Five-year incidence of operative ASD was similar in PLF and PLIF/TLIF+PS (7.7, 95% CI=6.6-9.0 and 7.1% 95% CI=6.2-8.1, respectively) but slightly lower in ALIF/XLIF+PS (5.3%, 95% CI=3.8-7.3). Highest 5-year incidence rates were seen in 2-level circumferential PLIF/TLIF (8.3%, 95% CI=6.0-11.11). After adjustment, there were no significant differences in operative ASDis risk by fusion type compared to PLF (ALIF/XLIF+PS: HR=0.7, 95% CI=0.5-1.1); PLIF/TLIF+PS: HR=1.0, 95% CI=0.8-1.2). CONCLUSIONS Analysis from a large cohort of over 5000 lumbar fusion patients found no differences in operative ASDis comparing circumferential fusions to posterolateral fusion at 5 years. This information is useful in informed consent for the patient. Further research for risk of operative ASDis with larger numbers of patients undergoing an anterior approach, as well as a longer follow-up period, is warranted. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Background Patients can provide valuable information missing from traditional sources of safety data, thus adding new insights about factors that lead to preventable harm. In this study, researchers determined associations between patient-reported contributory factors and patient-reported harms experienced after an adverse event (AE). Methods A secondary analysis was conducted of a national sample of patient-reported AEs (surgical, medication, diagnostic, and hospital-acquired infection) gathered through an online questionnaire between January 2010 and February 2016. Generalized logit multivariable regression was used to assess the association between patient-reported contributory factors and patient-reported harms (grouped as nonphysical harm only, physical harm only, physical harm and emotional or financial harm, and all three harms) and adjusted for patient and AE characteristics. Results One third of patients (32.6%) reported experiencing all three harms, 27.3% reported physical harms and one additional harm, 25.5% reported physical harms only, and 14.7% reported nonphysical harms only. Patients reporting all three harms were 2.5 times more likely to have filed a report with a responsible authority (95% confidence interval [CI] = 1.23–5.01) and 3.3 times more likely to have also experienced a surgical complication (95% CI = 1.42–7.51). Odds of reporting problems related to communication between clinician and patients/families or clinician-related behavioral issues was 13% higher in those experiencing all three harm types (95% CI = 1.07–1.19). Conclusion Patients’ experiences are important to identify safety issues and reduce harm and should be included in patient safety measurement and improvement activities. These findings underscore the need for policy and practice changes to identify, address, and support harmed patients.

Background Although declining rates of incident AIDS-related Kaposi sarcoma (KS) have been reported, KS incidence rates have noted race/ethnic, age, and geographic diversity. We performed a comprehensive assessment of recent secular trends in AIDS-related KS incidence in the United States. Methods We identified incident KS diagnosed in men aged 20-54 years (who comprise most AIDS-related KS in the United States) using the US Cancer Statistics registry data. Joinpoint analysis assessed for trends in age-adjusted incidence rates between 2000 and 2014 calculating average annual percentage changes (AAPCs) with 95% confidence intervals. Heat maps were generated to compare age-adjusted HIV incidence rates with KS incidence rates. Results Age-adjusted KS incidence rates nationwide decreased from 1.44/100,000 to 0.95/100,000 between 2000 and 2014. Observed rate changes varied across subgroups; eg, there were significant decreases in 30-44 years (AAPC = -5.4%), particularly in Whites and Blacks, significant increases among 20-29 years (AAPC = 2.7), primarily in Blacks, and stable rates among 45-54 years (AAPC = -0.03). In Southern United States, the incidence rates among Blacks did not significantly change. The states with highest average age-adjusted rates over the study period were Georgia (2.71/100,000), New York (2.16/100,000), California (2.02/100,000), Florida (1.90/100,000), and Texas (1.39/100,000), with significantly decreasing trends over time, except Georgia where rates increased (AAPC = 1.8). Conclusions Although KS incidence rates have decreased nationally, age, racial, and geographic disparities persist, including increasing risk among younger Black men and particularly elevated rates in some southern states and urban areas. Further research is needed to address racial and geographic AIDS-related KS disparities.

Objectives The US Department of Veterans Affairs (VA) is the largest integrated health care provider for HIV-infected patients in the USA. VA data for HIV-specific clinical and quality improvement research are an important resource. We sought to determine the accuracy of using the VA Corporate Data Warehouse (CDW), a fully automated medical records database for all VA users nationally, to identify HIV-infected patients compared with a gold-standard VA HIV Clinical Case Registry (CCR). Methods We assessed the test performance characteristics of each of our CDW criteria-based algorithms (presence of one, two or all of the following: diagnostic codes for HIV, positive HIV laboratory tests, and prescription for HIV medication) by calculating their sensitivity (proportion of HIV-positive patients in the CCR accurately detected as HIV-positive by the CDW algorithm) and positive predictive value (PPV; the proportion of patients identified by the CDW algorithm who were classified as HIV-positive from the CCR). Results We found that using a CDW algorithm requiring two of three HIV diagnostic criteria yielded the highest sensitivity (95.2%) with very little trade-off in PPV (93.5%). Conclusions A two diagnostic criteria-based algorithm can be utilized to accurately identify HIV-infected cohorts seen in the nationwide VA health care system.

BACKGROUND CONTEXT Octogenarians, defined as patients aged ≥80 years, are undergoing elective lumbar spinal fusion surgery in increasing numbers. While it is commonly accepted that patients between 50-79 years of age with degenerative or deformity-related spinal disease can safely undergo spinal fusion, most clinicians approach octogenarians more cautiously given concerns for higher adverse outcome risks. PURPOSE To evaluate whether there is a difference in risk of adverse postoperative outcomes following elective lumbar spinal fusion for octogenarians compared to patients aged 50-79. STUDY DESIGN/SETTING Retrospective cohort study using integrated health care data from the Kaiser Permanente Spine Registry. PATIENT SAMPLE The cohort comprised 8,340 patients aged ≥50 who underwent primary elective lumbar spinal fusion (L1-S1) for degenerative or deformity-related spinal disorders (2009-2018). OUTCOME MEASURES Incidence of intraoperative durotomy; 90-day postoperative emergency department (ED) visit and readmission, infection, deep vein thrombosis (DVT), pulmonary embolism (PE); and 90-day and 2-year reoperation and mortality. METHODS Octogenarians were compared to patients aged 50-79 (reference group) using time-dependent multivariable Cox-Proportional Hazards regression with a competing risk of death and adjustment for confounders. Multivariable logistic regression was used to assess differences in operative durotomy. RESULTS A total of 576 patients aged ≥80 and 7,763 patients aged 50-79 were included. After adjustment for confounders, octogenarians had a higher likelihood of durotomy (odds ratio=1.6, 95% confidence interval [CI]=1.2-2.2), as well as higher risks of 90-day readmission (hazard ratio [HR]=1.4, 95% CI=1.1-1.8) and PE (HR=2.2, 95% CI=1.1-5.0), compared to their younger counterparts. No differences were observed for 90-day incidence of infection or DVT. As well, no differences were observed in reoperation risks at 90 days (HR=1.2, 95% CI=0.8-2-0) or 2 years (HR=0.8, 95% CI=0.6-1.1). Mortality risk was higher for octogenarians compared to their younger counterparts but did not vary at 90-day or 2-year timepoints (90-day: HR=2.6, 95% CI=1.3-5.1; 2-year: HR=2.6, 95% CI=1.8-3.9). In stratified analysis, octogenarians with ≥3 comorbidities had a higher risk of 90-day readmission (HR=1.8, 95% CI=1.0-3.3) and 2-year mortality (HR=4.7, 95% CI=1.6-13.3) than those with 0-2. CONCLUSIONS In a cohort of >8,000 elective lumbar fusion patients, no difference was observed in the risk of reoperation, infection or DVT when comparing octogenarians to their younger counterparts. However, the higher risk of intraoperative durotomy, 90-day PE, and 90-day readmission suggests closer intra- and postoperative surveillance may be warranted for these older patients. We did observe a higher mortality risk for octogenarians when compared to patients aged 50-79; this risk did not change between 90 days and 2 years, suggesting the elevated risk is unrelated to undergoing a lumbar fusion and more likely the age groups compared in this study. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Diagnostic error research has largely focused on individual clinicians' decision making and system design, while overlooking information from patients. We analyzed a unique new data source of patient- and family-reported error narratives to explore factors that contribute to diagnostic errors. From reports of adverse medical events submitted in the period January2010-February2016, we identified 184 unique patient narratives of diagnostic error. Problems related to patient-physician interactions emerged as major contributors. Our analysis identified 224 instances of behavioral and interpersonal factors that reflected unprofessional clinician behavior, including ignoring patients' knowledge, disrespecting patients, failing to communicate, and manipulation or deception. Patients' perspectives can lead to a more comprehensive understanding of why diagnostic errors occur and help develop strategies for mitigation. Health systems should develop and implement formal programs to collect patients' experiences with the diagnostic process and use these data to promote an organizational culture that strives to reduce harm from diagnostic error.

Nivolumab is a standard treatment option in several advanced malignancies, but safety and efficacy are still unknown in patients with human immunodeficiency virus (HIV) infection. We describe a case series of people living with HIV (PLWH) receiving nivolumab in the Veterans Health Administration (VA) and report responses and toxicities. We identified all PLWH who received nivolumab at any VA facility since 2000 in the Corporate Data Warehouse (CDW), which provides nationwide research access to VA electronic medical records. We identified 16 HIV-infected nivolumab recipients. The median number of nivolumab doses received was 6 (range, 1-32). Changes in CD4 count during therapy were variable, with 70% (7/10) of patients experiencing increases. Half of PLWH were treated for non-small-cell lung cancer; 2 for Hodgkin lymphoma (HL), 2 for renal cell carcinoma, and 4 for off-label cancers. For non-small-cell lung cancer, 7 patients had evaluable responses. Although 5 of 7 patients immediately progressed, 1 had a partial response and 1 had stable disease, which were both durable. Two of 16 (14%) PLWH had complete responses; both with HL (2/2 HL, 100%). The prevalence of immune-related adverse effects was 40% overall (6/15); 27% (4/15) had pneumonitis. To our knowledge, this is the largest case series reporting outcomes with nivolumab in PLWH. Outcomes were comparable with those seen in studies of HIV-uninfected patients, and particularly interesting for HL. The reason for the high proportions of immune-related adverse effects is unclear, but needs to be confirmed in larger studies.

Sleep duration has been associated with nonalcoholic fatty liver disease, but its association with liver cancer remains unknown.In the prospective Women's Health Initiative Study, 139,368 postmenopausal women reported sleep habits at baseline (1993-1998). We ascertained 175 incident liver cancer cases during an average 13.8 years of follow-up through August 2014. We used multivariable Cox proportional hazard regression models to estimate a hazard ratio (HR) and its 95% confidence interval (95% CI) for risk of liver cancer in association with nocturnal sleep duration.Compared to women reporting 6-8 hours of sleep, the HR for liver cancer was 1.94 (95% CI 1.07-3.53) for women reporting ≥9 hours of sleep. Among the obese women, the HR associated with ≥9 hours of sleep was 3.18 (95% CI 1.84-8.60). The HR was 0.93 (95% CI 0.34-2.53) among nonobese women (p value for interaction = 0.18). Short sleep duration (≤5 hours) was not associated with liver cancer risk.Long sleep duration was associated with a moderate increase in liver cancer risk in obese postmenopausal women in the United States. Larger study is needed to confirm our observation on effect modification by adiposity status.

(a) Although prostate cancer is projected to be one of the most frequently diagnosed cancers in HIV-infected men overall, little is known about its risk in the sub-group with well-controlled HIV-infection. (b) We performed a retrospective cohort study to determine age-adjusted incidence of prostate adenocarcinoma in HIV-positive male veterans utilizing Veterans Administration (VA) healthcare between 10/01/1999 and 12/31/2016. HIV infection and prostate adenocarcinoma diagnosis as well as related clinical, sociodemographic, and lifestyle risk factors were obtained using extant VA administrative healthcare databases, the VA cancer registry, and augmented prostate cancer diagnosis with direct electronic medical record (EMR) review. We defined well controlled HIV as >60% of time with an undetectable HIV viral load and limited our analyses to those with a minimum of 90 days between HIV and prostate diagnosis, death, their last recorded health care encounter, or study end. We employed time-varying Cox proportional hazard regression models and used backward elimination to identify risk factors associated with incident prostate adenocarcinoma; effects are reported as Hazard ratios (HR) and 95% confidence intervals (CI). (c) During an average 10.26 years of follow-up, we identified 587 incident prostate adenocarcinomas among our cohort of 19,079 HIV positive men with well-controlled infection (age-adjusted incidence rate [IR] = 83.31 per 100,000-person years, 95% CI: 76.83-90.33); with a significant increasing trend over time. We identified several factors associated with significant increased risk of incident prostate adenocarcinoma, after adjusting for HIV medication use, in our well-controlled HIV-positive cohort including substance abuse (HR=1.68, 95% CI: 1.27-2.24, p=0.0003), age at HIV diagnosis (HR=1.73, 95% CI: 1.25-2.39, p=0.0010), and black race (HR=2.07, 95% CI: 1.58-2.72, p (d) Further research is needed to confirm our findings and to better identify sub-groups of well-controlled HIV-positive men at greatest increased prostate cancer risk. Citation Format: Kathryn E. Royse, Jose M. Garcia, Donna L. White, Jennifer R. Kramer, Yongquan Dong, Suchismita Raychaudhury, Peter A. Richardson, Christine Hartman, Elizabeth Y. Chiao. Prostate adenocarcinoma incidence and risk factors in Veterans with well controlled HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5044.

The objective of this study was to compare the efficacy and safety of nivolumab in the HIV-infected and HIV-uninfected veteran populations. WHAT IS NEW: Most clinical trials highlighting checkpoint inhibitors excluded people living with HIV (PLWH). This is the first study to report equivalent nivolumab tumor response rates in PLWH, but higher rates of pneumonitis.METHODS: We searched the Corporate Data Warehouse (CDW) to identify all HIV-positive patients who used the Veterans Health Administration (VA) between 2000 and 2016. For this cohort of 46,916 PLWH, we obtained a 4:1 age-matched HIV-negative control cohort. We used pharmacy database to identify all nivolumab recipients through July 26, 2017. We reviewed patients' electronic medical records using Compensation and Pension Records Interchange (CAPRI) to obtain age, sex, geographic location, cancer type, number of nivolumab doses received, previous cancer therapy, adverse events, and response to therapy. We calculated summary descriptive measures for both groups and compared the proportion of patients experiencing adverse event or pneumonitis in groups by HIV status, using chi-square or Fisher's exact test. RESULTS: Sixteen PLWH and 68 HIV-negative controls received nivolumab during the study period. Only 51 controls had accessible data. Median age at nivolumab initiation was 65 years in both groups (range, 47-85 [IQR, 59-68] in PLWH; range, 42-79 [IQR 59-68] in controls); all patients were male. Overall, 63% received nivolumab for non-small cell lung cancer (NSCLC): 8/16 (50%) in PLWH, 34/51 (67%) in controls. Other indications in PLWH included renal cell carcinoma (RCC) (2/16 [13%]), Hodgkin lymphoma (HL) (2/16 [13%]), hepatocellular carcinoma (HCC) (2/16 [13%]). Other indications in controls were RCC (9/51 [18%]), melanoma (5/51, [10%]), and head and neck squamous cell carcinoma (3/51 [6%]).Regardless of HIV status, the median number of prior lines of therapy was 1, median number of nivolumab doses received was 6, and median progression-free survival (PFS) in NSCLC was 2.75 months. Half of each NSCLC group received radiation; fewer PLWH had COPD (50%, vs. 82% of controls). PLWH had a trend towards more adverse events (AEs) (6/15 [40%], vs. 13/51 [26%] of controls, p=0.28). A significantly higher proportion of PLWH experienced pneumonitis (4/15 [27%], vs. 2/51 [4%] of controls, p=0.007).Other AEs among PLWH were rash, hypothyroidism, and autoimmune diabetes mellitus. Other AEs among controls were fatigue, colitis, rash, hypothyroidism, arthritis, and hepatitis (1-3 patients each). CONCLUSION: Among veteran PLWH, rates of nivolumab administration, and PFS in NSCLC, were comparable to those of HIV-uninfected counterparts. Pneumonitis was significantly more frequent in PLWH. Further studies should investigate the mechanism of pneumonitis in this population, confirm the high frequency in larger cohorts of PLWH, and identify clinical risk factors for pneumonitis. Citation Format: Elaine Chang, Aaron P. Thrift, Donna L. White, Jennifer Kramer, Anita L. Sabichi, Christine Hartman, Kathryn E. Royse, Peter A. Richardson, Elizabeth Y. Chiao. Nivolumab efficacy and safety in veterans with and without HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 617.

Background: Diet is a modifiable risk factor for multiple cancers. It is also known to modulate gut microbial composition and metabolic activity, and plays an important role in maintaining gut homeostasis. However, our understanding of dietary quality and mucosa-associated microbiota in the large intestine in humans is limited. We examined the association between diet quality and gut microbiota in adults underwent routine colonoscopy in a cross-sectional study. Methods: We enrolled 21 men (50-75 years old, 71% White) who were found to have grossly normal colons at colonoscopy completed between July 2013 and April 2016. We obtained 98 colonic mucosa biopsies, with microbial DNA extracted from snap frozen biopsy. The 16S rRNA V4 region was amplified and sequenced on the Illumina MiSeq platform. The UPARSE and SILVA were used for operational taxonomic unit (OTU) classification. A self-administered BLOCK Food Frequency Questionnaire was used to assess dietary intake in the past year. Dietary quality was defined using the Healthy Eating Index (HEI)-2005, and further categorized as low or high using the median of total HEI or 12 individual component scores. We compared alpha-diversity (OTU and Shannon index), beta-diversity (Weighted UniFrac principal coordinates analysis), and relative abundance of bacterial phylum and genus by total HEI and all 12 individual HEI components using Mann-Whitney test. Reported P values were adjusted for multiple testing using false discovery rate. Results: The most abundant bacterial phyla observed were Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, and Fusobacteria. High-quality diet (total HEI score ≥ 63) was not associated with higher richness and evenness of gut microbiome (P = 0.12), but was significantly associated with bacterial composition (P = 0.046). Compared to men who had low-quality diet (total HEI score < 63), those with high-quality diet had a higher abundance of Proteobacteria (12.2% vs. 8.1%, P = 0.006), and lower abundance of Fusobacteria (0.13% vs. 3.37%, P = 0.004). At the genus level, those with high-quality diet had significantly lower abundance of Fusobacterium than those with low-quality diet (0.11% vs. 3.77%, P = 0.004). At the HEI component level, individuals with a higher consumption of solid fruits and milk had higher richness and evenness of gut microbiome (P < 0.05) as well as higher abundance of phylum Verrucomicrobia (P < 0.05) and genus Akkermansia (P < 0.001). Consuming more solid and saturated fat, alcohol, and added sugar were associated with a higher abundance of phylum Fusobacteria (P < 0.0001) and genus Fusobacterium (P = 0.0001). Conclusions: The colonic microbiome of men consuming a low-quality diet exhibited increased levels of Fusobacteria, which has been associated with colorectal cancer risk. If replicated in prospective research, our findings suggest low quality diet may contribute to colorectal cancer by modulating gut microbiome. Citation Format: Yanhong Liu, Nadim J. Ajami, Diane Hutchinson, David Graham, Sarah Plew, Ashley Johnson, Preksha Shah, Liang Chen, Kathryn Royse, Donna L. White, Jennifer Kramer, Matthew C. Wong, Rhonda Cole, Clark Hair, Jason Hou, Nisreen Husain, Maria Jarbrink-Sehgal, Fasiha Kanwal, Gyanprakash Ketwaroo, Rajesh Shah, Maria Velez, Melissa L. Bondy, Hashem B. El-Serag, Joseph F. Petrosino, Li Jiao. Healthy eating index 2005 and the mucosa associated gut microbiome in healthy individuals [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3265.

e21110Background: Anti-programmed cell death (anti–PD-1) response in patients with advanced non-small cell lung cancer (NSCLC) varies greatly. Higher neutrophil/lymphocyte ratio (NLR) or lower adva...

Receptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand N(ε)-(carboxymethyl)-lysine (CML) and trigger dysregulation of adipokines and chronic inflammation. Soluble RAGE (sRAGE) mitigates the detrimental effect of RAGE. We examined the associations between circulating levels of CML-AGE and sRAGE and colorectal cancer (CRC).In a case-cohort study of the Women's Health Initiative Study, blood levels of CML-AGE and sRAGE were measured using ELISA. We used multivariable Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CRC in relation to quartiles (Q) of biomarker levels.Average follow-up was 7.8 years for 444 cases and 805 subcohort members. In the subcohort, CML-AGE and sRAGE were inversely correlated with BMI (P values0.0001). Levels of CML-AGE and sRAGE were not associated with CRC. In BMI-specific analysis, the association between sRAGE and CRC was observed. Among women with BMI≥25kg/m(2), those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4versusQ1: 0.39; 95% CI: 0.17-0.91). This inverse association was not observed among women with BMI25kg/m(2) (P value for interaction=0.01).Among postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.

The National Children’s Study (NCS) Harris County, Texas Study Center participated in the NCS Provider Based Sampling (PBS) substudy of the NCS Vanguard Phase pilot. As part of the hospital-based birth cohort component of the PBS substudy, we conducted a secondary data analysis to evaluate the proportion of postpartum women who consented to future biospecimen collection alone and to both future collection and use of residual birth biospecimens. In phase 1, 32 postpartum women at one hospital were asked to consent only to maternal future biospecimen collection. In phase 2, 40 other postpartum women from the same hospital were asked for an additional consent to use residual clinical biospecimens from the birth event that otherwise would be discarded, including cord blood and maternal blood and urine. Among 103 eligible women, a total of 72 participated. They were 28.3 ± 5.9 years old on average; 58 % were Hispanic; 63 % consented in English, and 37 % in Spanish; 39 % had some college education; 42 % were married; 60 % had an annual family income

Background: Chronic inflammation is implicated in pancreatic cancer carcinogenesis. Advanced glycation end-products (AGEs), which are rich in cooked red meat and cigarette smoke, can perpetuate inflammation by binding to the receptor for advanced glycation end products (AGER, also known as RAGE). We hypothesized that genetic variation of the AGEs/AGER pathway affects pancreatic cancer risk by modulating chronic inflammation. Methods: We conducted a two-stage case-control study to examine the association between 96 single nucleotide polymorphisms (SNPs) in 21 genes (GLO1, MSR1, PINK1, KIF17, AGPAT1, AKR1B1, DDOST, CD36, SCARB1, AGER, APP, HMGB1, S100A8, S100B, S100P, S100A12, MMP9, ADAM10, PPARG, NOTCH4, and PDGF) of the AGEs/AGER pathway and risk of pancreatic cancer. The discovery study was conducted in 672 pancreatic cancer cases and 1361 controls ascertained from the Women’s Health Initiative (WHI) Study matched on age, race/ethnicity and study arm. The validation study was conducted in a PANC4 pooled hospital-based case-control study of 1,034 women cases and 989 women controls. A pooled analysis of 1706 cases and 2350 controls was also performed. SNP data were obtained or imputed from the previously performed GWASs. Pancreatic cancer risk was calculated as odds ratios (ORs) and 95% confidence intervals (Cis) using logistic regression models adjusting for age, race/ethnicity, body mass index (BMI), type 2 diabetes, and smoking using an additive genetic model. The potential interaction between individual SNP and red meat intake and cigarette smoking was examined. A false discovery rate (FDR) adjusted q value < 0.20 was considered statistically significant in the pooled analyses. We also conducted logistic-Kernel machine (LKM) test to examine the association between sets of SNP and risk of pancreatic cancer in the pooled dataset. Results: We identified 11 SNPs with raw P values < 0.10 in the discovery stage in the WHI study. However, none of the SNPs was validated in the validation and pooled dataset. The LKM test showed that sets of SNPs in CD36 (P = 9.3E-10), GLO1(P =2.0E-7), and DDOST (P = 2.5E-4) were significantly associated with pancreatic cancer risk. We found an interaction effect between the GLO1 SNP rs6932648 and smoking status (never versus ever) in the WHI study (P for interaction = 0.01) and the pooled dataset (P for interaction = 0.049). In the pooled dataset, the variant T allele of rs6932648 (MAF = 0.12) was associated with increased risk of pancreatic cancer among ever smokers (additive OR = 1.26, 95% CI: 1.02-1.55), but not among never smokers (additive OR = 0.94, 95% CI: 0.78-1.14), compared with the C allele. Summary and Conclusion: We did not observe significant association between any of 96 single SNP and pancreatic cancer risk. However, we found combined set of SNPs in the GLO1, DDOST, and CD36 genes were associated with risk of pancreatic cancer. GLO SNP rs6932648 may modify the association between smoking and risk of pancreatic cancer. GLO1, DDOST, and CD36 are involved in detoxification or clearance of AGEs compounds. Further investigation of AGEs and receptors systems in pancreatic cancer is warranted. Citation Format: Guochong Jia, Kathryn Royse, Hongwei Tang, Donghui Li, Liang Chen, Lesley Tinker, Gloria Petersen, Alison Klein, Peter Richardson, Donna White, Haleh Sangi-Haghapeykar, Hashem B. El-Serag, Li Jiao. Genetic variations in the AGEs/AGER pathway and risk of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-160. doi:10.1158/1538-7445.AM2017-LB-160

Genetic changes occurring in different stages of pre-cancer lesions reflect causal events initiating and promoting the progression to cancer. Coexisting pre-cancerous lesions including low- and high-grade squamous intraepithelial lesion (LGSIL and HGSIL), and adjacent “normal” cervical epithelium from six formalin-fixed paraffin-embedded (FFPE) samples were selected. Tissues from these 18 samples were isolated using laser capture microdissection, RNA was extracted and sequenced. RNA-sequencing (RNA-seq) generated 2.4 billion raw reads in 18 samples, of which approximately 50.1% mapped to known and annotated genes in the human genome. There were 40 genes up-regulated and 3 down-regulated (normal to LGSIL) in at least one third of the sample pairs (same direction and FDR p

Physical activity (PA) has been shown to enhance quality of life (QOL) in older adults. Findings from these studies indicate that the relationship between PA and QOL is indirect and likely mediated by variables such as physical self-esteem, exercise self-efficacy, and affect. As PA varies greatly by age, the purpose of the current study is to extend this area of research to young adults and explore the complex relationship between PA and QOL in this target population.Data were collected via anonymous questionnaire from N = 590 undergraduate students. PA was assessed with the Godin Leisure Time Exercise Questionnaire, and QOL was assessed by the Satisfaction with Life Scale. Path analysis was used to test the relationship between PA and QOL, with mediators of exercise self-efficacy, physical self-esteem, and affect.The PA model (RMSEA = .03, CFI = .99) accounted for 25 % of the variance in QOL. PA had positive direct effects on exercise self-efficacy (β = .28, P.001), physical self-esteem (β = .10, P.001), positive affect (β = .10, P.05), and negative affect (β = .08, P.05). Physical self-esteem was found to be the most powerful mediating variable on QOL (β = .30, P.001), followed by positive affect (β = .27, P.001) and negative affect (β = .14, P.001).Physical self-esteem and, to a lesser extent, positive affect emerged as integral components in the link between PA and QOL. Findings suggest that health education programs designed to promote regular PA and increase physical self-esteem may be effective in improving QOL in young adults.

Obesity is a recognized pancreatic cancer risk factor. Obesity-associated chronic inflammation and insulin resistance as well as western diet are associated with increased circulating levels of advanced glycation end products (AGEs) levels. When AGEs bind to their receptor (RAGE) on adipocytes, an inflammatory cascade is triggered and dysregulation of adipokines can occur. Soluble RAGE (sRAGE) mitigates this negative effect by acting as a decoy receptor for AGEs. In a nested case-control study in the prospective Women's Health Initiative study, we assessed the association between baseline levels of sRAGE and adiponectin and pancreatic cancer risk in post-menopausal women. Medical, lifestyle, diet data, anthropometric measurements and fasting blood were collected at baseline (1993-98). Serum sRAGE and adiponectin levels were immunoassay measured. With an average follow-up 14 years (thru 8/2013), we identified 494 incident cases with pancreatic cancer. Two controls were matched to each case by age, ethnicity, trial assignment and blood draw time (± 6 mos.). Multivariable conditional logistic regression analysis was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between sRAGE and adiponectin levels (quartile, Q) and pancreatic cancer after adjusting for waist-hip-ratio, diabetes, and dietary intake of alcohol, protein, saturated fat and carbohydrates. A total of 7.6% cases and 6.3% controls were current smokers. sRAGE was correlated with adiponectin among controls(r = 0.17, P Citation Format: Donna L. White, Ron Hoogeveen, Kathryn Royse, Liang Chen, Lesley Tinker, Tom Rohan, Eric Whitsel, Hashem B. El-Serag, Li Jiao. A prospective study of soluble receptor for advanced glycation end products and adiponectin and pancreatic cancer in postmenopausal women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-382.

Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age, especially among women with HIV-1 infection. Several bacterial products including lipopolysaccharides (LPS), lipoteichoic acids (LTA), and peptidoglycans (PGN) are stimulatory ligands for Toll-like receptors (TLRs), and recent evidence indicates the important role of variation in TLR genes for permitting overgrowth of gram negative and BV-type flora. We assessed whether genetic polymorphisms in five TLR genes ( TLR1 , TLR2 , TLR4 , TLR6 , and TLR9 ) could be determinants of differential host immune responses to BV in 159 HIV-1-positive African American adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. BV was assessed biannually and diagnosed either by a Nugent score of at least 7 of 10, or using the Amsel criteria. Cox-proportional hazards regression models, adjusted for concurrent Chlamydia and Gonorrhea infections, douching, and absolute CD4 cell count, were used to identify host genetic factors associated with BV. Two SNPs were associated with BV as diagnosed by the Nugent score and the combined criteria: a minor allele G of rs4986790 (frequency=0.07), which encodes a His to Tyr substitution in TLR4 (HR=1.47, 95% CI 1.15–1.87) and rs187084 (frequency=0.24) on TLR9 . The minor allele of rs1898830 (frequency=0.13) was associated with an increased hazard of BV defined by the Amsel criteria (HR=1.86, 95% CI 1.17–2.95). Further studies are warranted to confirm the associations of TLR gene variants and also to understand the underlying pathways and immunogenetic correlates in the context of HIV-1 infection.

Tight junctions perform significant and multifactorial functions in cellular polarity maintenance and paracellular transport. A number of studies have found structural disruption of epithelial colon cells can significantly impact early tumorigenesis and progression. However, little is known about the direct contribution of polarity gene expression in human colon cancer development. We compared the expression of tight junction genes in colon cancer with normal control mucosa. Total RNA was extracted from fresh frozen tissue biopsies of six white male patients (N = 3 for early stage tumore, N = 3 for late stage tumor, and N = 2 for normal adjacent controls) and four unrelated normal colon mucosa from polyp-free individuals. We used the Qiagen RT2 Profiler PCR array to determine the expression of 84 genes in the tight junction pathway. Student's t test was used to compare the expression levels between different groups (control vs. early-stage tumor and late-stage tumor) using normalized gene expression data. Functional annotation clustering of statistically significant genes by group was conducted using DAVID. Significant (P 2; while CLDN1 (FC = 15) was only significantly upregulated (P = 0.0007) in early-stage tumor. Down regulation (FC>2) of polarity complex gene PARD6A (P Citation Format: Kathryn E. Royse, Liang Chen, Jocelyn Uriostegui, Michael Ittmann, David Y. Graham, Hashem El-Serag, Li Jiao. Differential expression of tight junction polarity genes in human colon cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4591. doi:10.1158/1538-7445.AM2015-4591

Insulin resistance, adiposity, and chronic inflammation contribute to colorectal cancer (CRC) development. Nϵ-(carboxymethyl)-lysine (CML) is a well-characterized type of advanced glycation end product (AGE). It can bind to the receptor for AGEs (RAGE) and trigger insulin resistance and sustained chronic inflammation. Soluble RAGE (sRAGE) mitigates the detrimental effect of RAGE by acting as a decoy receptor for its ligands. In a case-cohort study within the Women's Health Initiative Observational study, we examined the association between CML-AGE, sRAGE and risk of CRC among 447 cases and 802 subcohort controls. Information on lifestyle, anthropometry, medical history, and diet were collected at baseline. Levels of CML-AGE and sRAGE were measured by ELISA using fasting blood collected at baseline. Circulating levels of adipokines, insulin, glucose, estradiol, and C-reactive protein were previously measured for the study subjects. Multivariate Cox proportional hazard regression model accounting for the case-cohort design was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for CRC according to quartile (Q) of biomarkers with adjustment for age, race, waist circumstance, smoking, family history of colorectal cancer, NASID, energy intake, physical activity, alcohol consumption, saturated fat intake, available carbohydrate intake, hypertension, hormone replacement therapy, calcium, folate equivalent, red meat, insulin, and adiponectin. Average participant follow-up was 7.8 years. Among 802 subcohort controls, CML-AGE and sRAGE were both significantly inversely correlated with BMI, waist circumference, serum insulin, glucose, and leptin, but positively correlated with adiponectin (P values < 0.05). sRAGE levels were inversely associated with CRC (HRQ2 vs Q1:0.53; 95% CI: 0.31-0.90; HRQ4 vs Q1: 0.81; 95% CI: 0.46-1.42) (Ptrend = 0.95). This inverse association was evident among women who had BMI ≥ 25 kg/m2 (HRQ2 vs Q1: 0.49; 95% CI: 0.25-0.99; HRQ4 vs Q1: 0.43, 95% CI: 0.19-0.97) (Ptrend = 0.22), but not among women with normal BMI (BMI < 25) (HRQ4 vs Q1: 1.72, 95% CI:0.53-5.55) (P value for interaction was 0.01). CML-AGE was not associated with CRC risk (HRQ4 vs Q1: 0.78, 95% CI: 0.48-1.37) (Ptrend = 0.18). We found pre-diagnostic sRAGE levels were inversely associated with risk of CRC among overweight and obese postmenopausal women. This study identifed the RAGE pathway as a potential etiological factor in obesity-associated CRC. Citation Format: Liang Chen, Zhigang Duan, Lesley Tinker, Haleh Sangi-Haghpeykar, Howard Strickler, Gloria Ho, Thomas Rohan, Marc Gunter, Craig Logsdon, Donna White, Kathryn Royse, Hashem El-Serag, Li Jiao. Soluble receptor for advanced glycation end-products is a player in obesity-related colorectal cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 937. doi:10.1158/1538-7445.AM2015-937