Kaiser Permanente Lone Tree Medical Offices

Importance: The notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s. Objective: To evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy. Evidence Review: A panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained. Findings: Thirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment. Conclusions and Relevance: Physicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.

IMPORTANCE: Universal screening of patients with newly diagnosed cancer for hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV is not routine in oncology practice, and experts disagree about whether universal screening should be performed. OBJECTIVE: To estimate the prevalence of HBV, HCV, and HIV infection among persons with newly diagnosed cancer. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective cohort study of patients with newly diagnosed cancer (ie, identified within 120 days of cancer diagnosis) at 9 academic and 9 community oncology institutions affiliated with SWOG (formerly the Southwest Oncology Group) Cancer Research Network, a member of the National Clinical Trials Network, with enrollment from August 29, 2013, through February 15, 2017. The data analysis was conducted using data available through August 17, 2017. MAIN OUTCOMES AND MEASURES: The accrual goal was 3000 patients and the primary end point was the presence of HBV infection (previous or chronic), HCV infection, or HIV infection at enrollment. Patients with previous knowledge of infection as well as patients with unknown viral viral status were evaluated. RESULTS: Of 3092 registered patients, 3051 were eligible and evaluable. Median (range) age was 60.6 (18.2-93.7) years, 1842 (60.4%) were female, 553 (18.1%) were black, and 558 (18.3%) were Hispanic ethnicity. Screened patients had similar clinical and demographic characteristics compared with those registered. The observed infection rate for previous HBV infection was 6.5% (95% CI, 5.6%-7.4%; n = 197 of 3050 patients); chronic HBV, 0.6% (95% CI, 0.4%-1.0%; n = 19 of 3050 patients); HCV, 2.4% (95% CI, 1.9%-3.0%; n = 71 of 2990 patients); and HIV, 1.1% (95% CI, 0.8%-1.6%; n = 34 of 3045). Among those with viral infections, 8 patients with chronic HBV (42.1%; 95% CI, 20.3%-66.5%), 22 patients with HCV (31.0%; 95% CI, 20.5%-43.1%), and 2 patients with HIV (5.9%; 95% CI, 0.7%-19.7%) were newly diagnosed through the study. Among patients with infections, 4 patients with chronic HBV (21.1%; 95% CI, 6.1%-45.6%), 23 patients with HCV (32.4%; 95% CI, 21.8%-44.5%), and 7 patients with HIV (20.6%; 95% CI, 8.7%-37.9%) had no identifiable risk factors. CONCLUSIONS AND RELEVANCE: Results of this study found that a substantial proportion of patients with newly diagnosed cancer and concurrent HBV or HCV are unaware of their viral infection at the time of cancer diagnosis, and many had no identifiable risk factors for infection. Screening patients with cancer to identify HBV and HCV infection before starting treatment may be warranted to prevent viral reactivation and adverse clinical outcomes. The low rate of undiagnosed HIV infection may not support universal screening of newly diagnosed cancer patients.

BACKGROUND: Anti-PD-1 and PD-L1 (collectively PD-[L]1) therapies are approved for many advanced solid tumors. Biomarkers beyond PD-L1 immunohistochemistry, microsatellite instability, and tumor mutation burden (TMB) may improve benefit prediction. METHODS: Using treatment data and genomic and transcriptomic tumor tissue profiling from an observational trial (NCT03061305), we developed Immunotherapy Response Score (IRS), a pan-tumor predictive model of PD-(L)1 benefit. IRS real-world progression free survival (rwPFS) and overall survival (OS) prediction was validated in an independent cohort of trial patients. RESULTS: Here, by Cox modeling, we develop IRS-which combines TMB with CD274, PDCD1, ADAM12 and TOP2A quantitative expression-to predict pembrolizumab rwPFS (648 patients; 26 tumor types; IRS-High or -Low groups). In the 248 patient validation cohort (248 patients; 24 tumor types; non-pembrolizumab PD-[L]1 monotherapy treatment), median rwPFS and OS are significantly longer in IRS-High vs. IRS-Low patients (rwPFS adjusted hazard ratio [aHR] 0.52, p = 0.003; OS aHR 0.49, p = 0.005); TMB alone does not significantly predict PD-(L)1 rwPFS nor OS. In 146 patients treated with systemic therapy prior to pembrolizumab monotherapy, pembrolizumab rwPFS is only significantly longer than immediately preceding therapy rwPFS in IRS-High patients (interaction test p = 0.001). In propensity matched lung cancer patients treated with first-line pembrolizumab monotherapy or pembrolizumab+chemotherapy, monotherapy rwPFS is significantly shorter in IRS-Low patients, but is not significantly different in IRS-High patients. Across 24,463 molecularly-evaluable trial patients, 7.6% of patients outside of monotherapy PD-(L)1 approved tumor types are IRS-High/TMB-Low. CONCLUSIONS: The validated, predictive, pan-tumor IRS model can expand PD-(L)1 monotherapy benefit outside currently approved indications.

LBA3 Background: Bortezomib (btz) combined with lenalidomide (len) and dexamethasone (dex) (VRd) is a standard initial therapy for NDMM. Carfilzomib (cfz), a next-generation proteasome inhibitor, in combination with len-dex (KRd) has shown higher efficacy in phase II trials. This randomized phase III trial was designed to examine if KRd improves progression free survival (PFS) compared to VRd in NDMM (current results), and whether indefinite maintenance with len improves OS compared with two-year maintenance (to be analyzed once data matures). Methods: Patients (Pts) with NDMM, were randomized to receive VRd or KRd in a 1:1 fashion for 36 weeks followed by a second randomization (1:1) to indefinite versus two years of len maintenance. Pts without del17p, t (14;16), t(14;20), plasma cell leukemia or high-risk GEP70 profile, were enrolled. VRd arm included btz 1.3 mg/m 2 on days(d) 1, 4, 8, and 11 (d 1, 8 for cycles 9-12), len 25 mg d 1-14, and dex 40 mg d 1, 2, 4, 5, 8, 9, 11, 12 of a 3-week (wk) cycle for 12 cycles, while pts in the KRd arm received cfz 36 mg/m 2 d 1, 2, 8, 9, 15, 16 with len 25 mg daily on d 1-21 and dex 40 mg wkly, in 4 wk cycles for 9 cycles. Maintenance included len 15mg d 1-21 every 4 wks. The study was designed to detect a hazard ratio (HR)=0.75 with 80% power at 1-sided 2.5% alpha and 399 PFS events (progression or death regardless of intervening therapy). Results: The study accrued 1087 pts (VRd=542, KRd=545). The median age was 65y. Treatment, efficacy, and toxicity data are in the table. At the second of 3 planned interim analyses, with PFS HR=1.04 (95% CI, 0.8 to 1.3, p=0.74), futility was met. Median PFS was VRd=34.4m and KRd=34.6m; no differences were seen based on age (<65 or ≥65), presence or absence of t(4;14) or ISS stage. The three-year OS (95% CI) was similar: VRd 84% (80 to 88) and KRd 86% (82 to 89). Conclusions: In this randomized phase 3 trial, KRd did not improve PFS compared with VRd in NDMM. A significantly higher rate of cardio-pulmonary and renal toxicity was observed with KRd, while neuropathy rates were higher with VRd. VRd remains the standard triplet induction regimen in standard and intermediate risk NDMM, and a suitable backbone for 4 drug combinations. Clinical trial information: NCT01863550 . [Table: see text]

PURPOSE PIK3CA mutations frequently contribute to oncogenesis in solid tumors. Taselisib, a potent and selective inhibitor of phosphoinositide 3-kinase, has demonstrated clinical activity in PIK3CA-mutant breast cancer. Whether PIK3CA mutations predict sensitivity to taselisib in other cancer types is unknown. National Cancer Institute–Molecular Analysis for Therapy Choice Arm EAY131-I is a single-arm, phase II study of the safety and efficacy of taselisib in patients with advanced cancers. METHODS Eligible patients had tumors with an activating PIK3CA mutation. Patients with breast or squamous cell lung carcinoma, or whose cancer had KRAS or PTEN mutations, were excluded. Patients received taselisib 4 mg, orally once daily continuously, until disease progression or unacceptable toxicity. The primary end point was objective response rate. Secondary end points included progression-free survival (PFS), 6-month PFS, overall survival (OS), and identification of predictive biomarkers. RESULTS Seventy patients were enrolled, and 61 were eligible and initiated protocol therapy. Types of PIK3CA mutations included helical 41 of 61 (67%), kinase 11 of 61 (18%), and other 9 of 61 (15%). With a median follow-up of 35.7 months, there were no complete or partial responses. Six-month PFS was 19.9% (90% CI, 12.0 to 29.3) and median PFS was 3.1 months (90% CI, 1.8 to 3.7). Six-month OS was 60.7% (90% CI, 49.6 to 70.0) and median OS was 7.2 months (90% CI, 5.9 to 10.0). Individual comutations were too heterogeneous to correlate with clinical outcome. Fatigue, diarrhea, nausea, and hyperglycemia were the most common toxicities, and most were grade 1 and 2. CONCLUSION In this study, taselisib monotherapy had very limited activity in a heterogeneous cohort of heavily pretreated cancer patients with PIK3CA-mutated tumors; the presence of a PIK3CA mutation alone does not appear to be a sufficient predictor of taselisib activity.

BACKGROUND: Anemia management clinics have demonstrated favorable impacts on clinical and economic outcomes and patient satisfaction. Clinical pharmacists are uniquely qualified to manage complex drug therapies requiring intensive monitoring. The complexity, risks associated with inappropriate treatment, and high cost of erythropoietin-stimulating agents (ESAs) make patients on these medications excellent candidates for clinical pharmacist-based management. Integrating ESA management into a clinical pharmacist-managed service has the potential to improve anemia management not only by improving patient outcomes and patient safety, but also by decreasing medication costs. OBJECTIVES: To (a) assess adherence to monitoring guidelines, efficacy, and safety outcomes and (b) quantify medication utilization expenditures among patients using ESA therapy managed by a clinical pharmacy service compared with usual care. METHODS: This is a retrospective longitudinal cohort study of patients with anemia caused by chronic kidney disease who were on ESA treatment for at least 6 months between January 2008 and December 2010. Adherence to monitoring guidelines, efficacy, safety, and drug utilization outcomes were compared between the 2 groups. RESULTS: A total of 101 patients were included in the study. Of that number, 31 were managed by the pharmacist-managed anemia service, and 70 were in the usual care group. The pharmacist-managed patients had improved adherence to guidelines for hemoglobin monitoring (32.3% vs. 14.3%, P = 0.049) and iron monitoring (61.3% vs. 30.0%, P = 0.005) compared with similar patients receiving usual care. Time to achievement of hemoglobin target was 28 days in the pharmacist-managed group compared with 41 days in the usual care group (P = 0.135), while the proportion of patients achieving target hemoglobin was 96.8% compared with 95.7%, respectively (P = 0.654). Patients in the pharmacist-managed group used less epoetin alfa during the 6-month period, leading to an annualized savings of $1,288 per patient in drug expenditures. CONCLUSIONS: A clinical pharmacist-managed anemia service resulted in improved adherence to national monitoring guidelines, equivalent quality and safety outcomes, and lower medication utilization compared with usual care.

PURPOSE: This study aimed to determine whether switching from balanced salt solution (BSS) to vancomycin 20 g/mL BSS for incision hydration and eye pressurization reduces the rate of postcataract endophthalmitis. METHODS: This was a patient safety/quality improvement project, including all patients undergoing cataract surgery at the Kaiser Permanente Colorado Ophthalmology Department from January 2002 to December 2014. Throughout the study, patients received vancomycin 20 μg/mL in the irrigating solution. During the baseline period from 2002 to 2005, surgeons pressurized eyes and hydrated incisions with plain BSS. During the intervention period from 2006 through 2014, surgeons switched from BSS to the vancomycin/BSS irrigating solution for eye pressurization and incision hydration. RESULTS: A total of 57,263 cataract operations were performed by 24 surgeons at seven surgical centers: 12,400 in the baseline period and 44,863 in the intervention period. The rate of post-cataract endophthalmitis declined significantly from 5/12,400 (rate: 0.4/1,000) in the baseline period to 1/44,863 (rate: 0.022/1,000) during the intervention period (odds ratio [OR]: 18.1, 95% confidence interval [CI]: 2.11-154.9; χ (2)=13.5, P=0.00024). Accounting for an estimated 2.05-fold risk reduction due to confounding variables, the risk reduction attributed to the intervention remained significant: (adjusted OR: 8.78, 95% CI: 1.73-44.5; χ (2)=10.06, P=0.0015). Since 2009, we have not experienced any cases of postcataract endophthalmitis after 32,753 operations. CONCLUSION: We experienced a significant reduction in postcataract endophthalmitis when we switched from BSS to the vancomycin/BSS irrigating solution for incision hydration and eye pressurization. The pharmacokinetics profile indicates that this switch was important for effective prophylaxis.

4117 Background: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Methods: Patients with metastatic adenocarcinoma of the pancreas were randomized in a 2:1 fashion to gemcitabine 1000 mg/m2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800mg/m2 via 2-hr continuous IV (CIV) infusions given twice weekly for 3 weeks of a 4-week cycle (RIG+GEM) versus gemcitabine 1000mg/m2 weekly for 3 weeks in a 4-week cycle (GEM). Results: A total of 160 patients were enrolled globally and randomly assigned to RIG+GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG+GEM group vs. 6% in the GEM group), hyponatremia (17% vs. 4%), and anemia (8% vs. 4%). The primary outcome of the study, median overall survival (OS), was 6.1 months for RIG+GEM versus 6.4 months for GEM (hazard ratio (HR), 1.24; 95% confidence interval [CI], 0.85-1.81). The median progression-free survival (PFS) was 3.4 months for both groups (HR = 0.96; 95% CI, 0.68-1.36). The partial response rate by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 was 19% versus 13% for RIG+GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40/47, 85%). Other mutations detected included TP53 (13 cases) and PIK3CA(1 case). No correlation between mutational status and efficacy was detected. Conclusions: The combination of RIG+GEM failed to demonstrate an improvement in survival or response compared to GEM in metastatic pancreatic adenocarcinoma. Rigosertib had a similar safety profile to that observed in other trials of the IV formulation. Clinical trial information: NCT01360853.

Human health is dependent on the health of the planet. Overwhelming evidence indicates that environmental degradation and climate change is negatively affecting planetary health and is on a worsening trajectory. The health of our children, especially those who live in poverty, suffer from chronic disease, or are otherwise disadvantaged, will benefit most from successful efforts to change this trajectory or will suffer the most if we do nothing. School nurses, members of the largest and most trusted group of healthcare providers, have a professional and ethical obligation to address environmental degradation and the impact on our students and communities. Research suggests that knowledge about climate change and the associated health impacts are positively correlated to school nurses' attitudes and behaviors. This article aims to raise school nurse awareness, understanding, and agency regarding the possible trajectories of environmental degradation, implications to the health and well-being of current and future generations of children, and evidence-based actions to positively influence the trajectory. The Framework for 21st Century School Nurse Practice™ advocates a practice model that is student centered and provides a mind-set for school nursing to approach the topic of planetary and environmental health.

Purpose: Immune checkpoint inhibitor and VEGFR inhibitor combinations are effective treatments for patients with metastatic renal cell carcinoma (mRCC). This phase I/II clinical trial evaluated the safety and efficacy of pembrolizumab and cabozantinib in patients with mRCC. Experimental Design: Eligible patients had mRCC with clear-cell or non-clear cell histology, adequate organ function, Eastern Cooperative Oncology Group 0-1 performance status, and no prior exposure to pembrolizumab or cabozantinib. The primary endpoint was objective response rate (ORR) at the recommended phase II dose (RP2D). Secondary endpoints included safety, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Results: Forty-five patients were enrolled. A total of 40 patients were treated at the RP2D of pembrolizumab 200 mg i.v. every 3 weeks and cabozantinib 60 mg orally once daily, 38 of which were evaluable for response. The ORR was 65.8% [95% confidence interval (CI), 49.9-78.8] for all evaluable patients [78.6% as first-line therapy, 58.3% as second-line therapy]. The DCR was 97.4% (95% CI, 86.5-99.9). Median DoR was 8.3 months (interquartile range, 4.6-15.1). At a median follow-up of 23.54 months, the median PFS was 10.45 months (95% CI, 6.25-14.63) and median OS was 30.81 months (95% CI, 24.2-not reached). The most common grade 1 and/or 2 treatment-related adverse events (TRAE) were diarrhea, anorexia, dysgeusia, weight loss, and nausea. The most common grade 3 and/or 4 TRAEs were hypertension, hypophosphatemia, alanine transaminase elevation, diarrhea, and fatigue. There was one grade 5 TRAE of reversible posterior encephalopathy syndrome related to cabozantinib. Conclusions: Pembrolizumab and cabozantinib treatment in patients with mRCC demonstrated encouraging preliminary efficacy and a manageable toxicity profile comparable with other available checkpoint inhibitor-tyrosine kinase inhibitor combinations. Trial Registration: ClinicalTrials.gov Identifier: NCT03149822 https://clinicaltrials.gov/ct2/show/NCT03149822. Significance: This study evaluated the safety and effectiveness of the combination of pembrolizumab and cabozantinib in patients with mRCC. The safety profile was manageable. The combination showed promising activity with an objective response rate of 65.8%, median PFS of 10.45 months, and median OS of 30.81 months.

: Evidence on the favorable efficacy, safety, and cost effectiveness of lumbar total disc replacement (TDR) compared with fusion for lumbar degenerative disc disease is mounting; however, a key barrier identified for TDR utilization is lack of coverage by US health insurers. Although economic considerations in a fee-for-service model should not be a determining factor in patient access, concerns regarding the budget impact of lumbar TDR surgery may unfortunately underlie coverage decisions. On the basis of the data available and economic modeling, the panel agreed that there is no indication that there would be a dramatic increase in patients seeking lumbar TDR. Considering several possible scenarios on potential growth in TDR utilization with coverage, as well as growth in the overall surgical pool of patients, economic modeling demonstrated that adoption of lumbar TDR would result in minimal or no budget impact for commercial insurance plans. Considering these model results and the economic literature, the panel concluded that adopting lumbar TDR within a coverage policy is expected to remain cost neutral for the insurer.

We live in a century of technological revolution. Like every other sphere of our life, diabetes-related technology is moving forward with lightning speed. New and improved insulin administration devices, increased capacity for monitoring one's blood glucose levels, and the ability to communicate directly with the device supplying insulin as well as with the patient and his or her healthcare provider have changed the landscape of diabetes therapy forever. However, diabetes technology is progressing faster than healthcare professionals can incorporate these advances into their practices. To bridge this gap, Diabetes Technology provides an historical overview of diabetes technology, addresses the clinical science of new and advancing technologies, and illustrates the use of diabetes technology in different treatment settings. This guide also explores the personal stories of healthcare providers who treat their own diabetes with modern diabetes technology.

NCT03743077.

<h2>Abstract</h2><h3>Background</h3> Initial stability of cementless stems is important to minimize the risk of subsidence, pain, and periprosthetic fracture after total hip arthroplasty (THA). Collared stems improve initial component stability when contacting the femoral calcar. Direct contact is not always achieved, and collared stem performance has not been studied in this context. We hypothesized that collared stems achieving direct contact would demonstrate reduced subsidence. <h3>Methods</h3> A single-surgeon retrospective study of 482 consecutive primary THAs implanted between February 2020 and May 2023 using collared cementless stems was performed. The 2 cohorts included stems with initial collar-calcar contact vs stems without. Subsidence was evaluated by comparing intraoperative fluoroscopy to postoperative 8-week radiographs. Binary logistic regression identified independent risk factors for subsidence. Chi-square tests were used for categorical variables and <i>t</i>-tests for continuous variables. <h3>Results</h3> Of stems, 63.9% achieved initial collar-calcar contact, while 36.1% did not. The rate (1.3% vs 19.0%; <i>P</i> < .001) and magnitude (0.02 mm, range 0-3 mm vs 0.35 mm, range 0-3 mm; <i>P</i> < .001) of subsidence were significantly higher among stems without initial contact. Stems without initial collar-calcar contact (<i>P</i> < .001) and male gender (<i>P</i> = .007) were independent risk factors for subsidence. Two patients with initial contact had nondisplaced calcar cracks and <3 mm of subsidence at 4 weeks, which healed with protected weight-bearing. Stem survivorship was 100% in both groups, with all achieving osteointegration and none needing revision. <h3>Conclusions</h3> Excellent performance of collared cementless stems was observed at 8 weeks after primary THA. Initial collar-calcar contact lowered the risk and magnitude of minor subsidence but did not affect survivorship or fracture risk. <h3>Level of Evidence</h3> Level III.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) provides functional stability to an injured knee. While multiple techniques can be used to drill the femoral tunnel during ACLR, a single technique has yet to be proven as clinically superior. One marker of postoperative functional stability is subsequent meniscal tears; a lower risk of subsequent meniscal surgery could be expected with improved knee stability. PURPOSE: To determine if there is a meniscal protective effect when using an anteromedial portal (AMP) femoral tunnel drilling technique versus transtibial (TT) drilling. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Data from Kaiser Permanente's ACLR registry were used to identify patients who had a primary isolated ACLR between 2009 and 2018; those with previous surgery in the index knee and meniscal pathology at the time of ACLR were excluded. The exposure of interest was TT (n = 2711) versus AMP (n = 5172) drilling. Multivariable Cox proportional hazard regression was used to evaluate the risk of a subsequent ipsilateral meniscal reoperation with adjustment for age, sex, femoral fixation, and graft choice. We observed a shift in surgeon practice from the TT to AMP over the study time frame; therefore, the relationship between technique and surgeon experience on meniscal reoperation was evaluated using an interaction term in the model. RESULTS: At the 9-year follow-up, the crude cumulative meniscal reoperation probability for AMP procedures was 7.76%, while for TT it was 5.88%. After adjustment for covariates, we observed a higher risk for meniscal reoperation with AMP compared with TT (hazard ratio [HR], 1.53; 95% CI, 1.05-2.23). When stratifying by surgeon experience, this adverse association was observed for patients who had their procedure performed by surgeons with less AMP experience (no previous AMP ACLR: HR, 1.26; 95% CI, 0.84-1.91) while a protective association was observed for patients who had their procedure with more experienced surgeons (40 previous AMP ACLRs: HR, 0.34; 95% CI, 0.13-0.92). CONCLUSION: Drilling the femoral tunnel via the AMP was associated with a higher risk of subsequent meniscal surgery compared with TT drilling. However, when AMP drilling was used by surgeons experienced with the technique, a meniscal protective effect was observed.

Objectives: The purpose of this study was evaluate the incidence of thromboembolic events in patients undergoing arthroscopic surgery of the knee in surgery centers located at elevations near sea level and comparing those rates with the patients undergoing the same operations at surgery centers located in cities at high altitude. Methods: A retrospective review was conducted using a database of a major health care system with surgery centers located throughout the United States. Over 115 surgery centers located in 15 different states were analyzed for any reported thromboembolic events including deep vein thromboses (DVT) and pulmonary embolism (PE) in patients who had undergone knee arthroscopy over a 2 year period. The surgical centers located at elevations lower than 1000 ft were considered sea level centers. Those centers located at elevations above 4000 ft were considered high altitude centers. Any surgical center located between 1000 ft and 4000 ft elevation was excluded. Results: 35,877 patients underwent a knee arthroscopy procedure at a low altitude center between 2011-2012. 10,181 patients underwent a knee arthroscopy procedure at a high altitude center between 2011-2012. During that same time period, 45 total VTEs including 12 PEs occurred at centers considered low altitude while 50 VTEs including 4 PEs occurred at centers considered high altitude. The incidence of VTE at centers considered low altitude was 0.13%. The incidence of VTE at centers considered high altitude was 0.49%. The difference was statistically significant with a p-value &lt;0.0001. The relative risk of developing a VTE was 3.8 times higher at high altitude. Conclusion: Patients undergoing arthroscopic procedures of the knee in cities located at high altitude are at higher risk of developing a VTE than those undergoing the same procedures at cities located at elevations near sea level.

342 Background: Rigosertib (ON 01910.Na), a dual non-ATP inhibitor of polo-like kinase 1 (Plk1) and phosphoinositide 3-kinase (PI3K) pathways, was assessed in patients with treatment-naïve metastatic pancreatic adenocarcinoma. Methods: Patients with metastatic adenocarcinoma of the pancreas were randomized in a 2:1 fashion to gemcitabine 1000 mg/m 2 weekly for 3 weeks of a 4-week cycle plus rigosertib 1800mg/m 2 via 2-hr CIV infusions given twice weekly for 3 weeks of a 4-week cycle versus gemcitabine 1000mg/m 2 weekly for 3 weeks in a 4-week cycle. Results: A total of 160 patients were enrolled globally and randomly assigned to rigosertib plus gemcitabine (106 patients) or gemcitabine (54). The most common grade 3 or higher adverse events were neutropenia (8% in the rigosertib plus gemcitabine group vs. 6% in the gemcitabine group), hyponatremia (17% vs. 4%), and anemia (8% vs. 4%). The primary outcome of the study, median OS, was 6.1 months in the gemcitabine plus rigosertib arm versus 6.4 months with gemcitabine alone (hazard ratio (HR), 1.24; 95% confidence interval [CI], 0.85-1.81). The median PFS was 3.4 months for both groups (HR, 0.96; 95% CI, 0.68-1.36). The overall best response between arms were partial response rates of 19% versus 13% and stable disease in 50% versus 56% in the gemcitabine plus rigosertib versus gemcitabine alone, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40/47, 85%), which included c.35G&gt;T, p.G12V (12 cases), c.35G&gt;A, p.G12D (21 cases), c.34G&gt;C, p.G12R (4 cases), c.34G&gt;T, p.G12C (1 case) and c.183C&gt;A, p.Q61H (2 cases). Other mutations detected included TP53 (13 cases) and PIK3CA(1 case). No correlation between mutational status and efficacy was detected. Conclusions: The combination of rigosertib plus gemcitabine failed to demonstrate an improvement in survival or response compared to gemcitabine alone in metastatic pancreatic adenocarcinoma. Clinical trial information: NCT01360853.

3552 Background: Bevacizumab-awwb was the first biosimilar approved by the U.S. Food and Drug Administration (FDA) for treatment of cancer and became available for use in July 2019. Clinical comparative efficacy and safety of bevacizumab-awwb to bevacizumab was established in a single study of adult patients with advanced non-squamous non-small cell lung cancer. Approval based on extrapolation was granted by the FDA for all other indications, including metastatic colorectal cancer (mCRC). The objective of this study was to evaluate the real-world effectiveness and safety outcomes of patients with mCRC initiated on bevacizumab-awwb versus bevacizumab in an integrated healthcare delivery system. Methods: This was an observational cohort study of patients with mCRC in Kaiser Permanente California, Colorado, and Mid-Atlantic States who were initiated on bevacizumab-awwb between July 2019 and March 2020 or reference bevacizumab between July 2015 and June 2018. Patients with history of bevacizumab use in the 6 months prior to the index treatment date were excluded. Patients were followed until 12 months after treatment initiation, end of plan membership, or death, whichever occurred first. The primary outcome of overall survival (OS) was analyzed using a non-inferiority test with lower margin of 10% and Cox proportional-hazards modeling. Secondary outcomes included count of doses received, treatment duration, all-cause hospitalizations, and incidence of serious adverse events. Results: A total of 1,445 patients initiated on either bevacizumab-awwb (n=239) or bevacizumab (n=1,206) were included in the analysis. The mean overall age was 60 ± 13 years and 54% of patients were male. The OS rate was 72.8% and 73.1% for patients receiving bevacizumab-awwb and bevacizumab, respectively ( p&lt;0.01 for non-inferiority). The adjusted hazard ratio for mortality was 1.01 (0.77-1.33, p=0.93). There were no statistically significant differences in secondary outcomes between the 2 study groups (Table). Conclusions: Bevacizumab-awwb is a safe and effective option when compared to the reference bevacizumab in the treatment of mCRC. Future studies should evaluate outcomes after longer follow-up time and in different cancer types. [Table: see text]

Propofol is used for sedation, anxiolysis, anesthesia induction, and as an anticonvulsant. In cases of refractory status epilepticus (RSE), propofol is more efficient than barbiturates. We present a case of a 3-year-old female with RSE who developed propofol-related infusion syndrome (PRIS) despite low dosage after failed attempts with multiple anti-epileptic drips and bolus therapies. Careful consideration must be made before initiating propofol administration for RSE. We discuss our PRIS treatment approach with extracorporeal membrane oxygenation, therapeutic plasma exchange, and continuous renal replacement therapy leading to our patient recovering to baseline and being discharged home from the hospital.

OBJECTIVE: The SWOG S1609 Dual Anti-CTLA-4 &amp; Anti-PD-1 blockade in Rare Tumors (DART) trial is the first basket study to include a sub-cohort assessing ipilimumab and nivolumab in patients with primary vaginal cancers with differing histology. METHODS: DART is a prospective, open-label, multicenter, multi-cohort phase II clinical trial of ipilimumab (1 mg/kg intravenously) 6 weekly plus nivolumab (240 mg intravenously) 2 weekly across multiple rare tumor cohorts, with the vagina cohort (any vaginal histology) reported here. The primary endpoint was objective response rate (ORR) per RECISTv1.1; progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; overall response plus stable disease [SD] ≥6 months), and toxicity are secondary endpoints. RESULTS: Seven evaluable patients (median age, 60 years; performance status 0-1; no prior exposure to immunotherapy) were analyzed, of whom 3 had adenocarcinoma, 2 had squamous cell carcinoma (SCC), one had small-cell carcinoma and one had undifferentiated histology. The ORR was 29%, with 1 patient (14%) with undifferentiated histology achieving complete response (lasting 14.8 months) and 1 patient with SCC histology (14%) attaining a partial response (lasting 45.2 months). The CBR was 43%. The 6-month PFS rate was 43% and the median OS was 11.7 months. Five patients (71.4%) experienced an adverse event (AE) with 4 (57.1%) having grade 3-4 AE's. CONCLUSION: Ipilimumab plus nivolumab showed efficacy (ORR was 29% and CBR of 43%) and durability (one patient with prolonged SD >6 months) in a sub cohort of patients with vaginal cancer of differing histology without new safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02834013.