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Limited data is available to guide non-surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long-term therapeutic and functional outcomes.We reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA).The 2-/5-year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non-intensity-modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease-free survival; and age70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow-up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither.We report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery.Level 4 Laryngoscope, 2022.

To evaluate the efficacy of chemotherapy in patients with microsatellite instability-high (MSI-high) gastric cancer.Although MSI-high gastric cancer is associated with superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population.Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000-2018 were eligible. MSI status, determined by next generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, and overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were assessed.In 535 patients, 82 (15.3%) had an MSI-high tumor and approximately 20% better OS, DSS, and DFS. Grade 1 (90-100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone (P=0.48). In the MSS group, this was 61% versus 59%, respectively (P=0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (HR 0.53, 95% CI 0.28-0.99) or treated with surgery alone (HR 0.15 vs. MSS, 95% CI 0.02-1.17).MSI-high locally advanced gastric cancer was associated with superior survival compared to MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was approximately 9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival.

This study evaluates the relationship of tumour and anatomical features with operative difficulty in robotic low anterior resection performed by four experienced surgeons in a high-volume colorectal cancer practice.Data from 382 patients who underwent robotic low anterior resection by four expert surgeons between January 2016 and June 2019 were included in the analysis. Operating time was used as a measure of operative difficulty. Univariate and multivariate mixed models were used to identify associations between baseline characteristics and operating time, with surgeon as a random effect, thereby controlling for variability in surgeon speed and proficiency. In an exploratory analysis, operative difficulty was defined as conversion to laparotomy, a positive margin or an incomplete mesorectum.Median operating time was 4.28 h (range 1.95-11.33 h) but varied by surgeon from 3.45 h (1.95-6.10 h) to 5.93 h (3.33-11.33 h) (P 0.001). Predictors of longer operating time in multivariate analysis were male sex, higher body mass index, neoadjuvant radiotherapy, low tumour height, greater sacral height and larger mesorectal area at the S5 vertebral level. Conversion occurred in two cases (0.5%), and incomplete mesorectum and positive margins were found in nine (2.4%) and 19 (5.0%) patients, respectively. Neoadjuvant radiotherapy and larger pelvic outlet were the only characteristics associated with the exploratory measure of difficulty.Predicting operative difficulty based on easy to identify, preoperative radiological and clinical variables is feasible in robotic anterior resection.

Background Intra-articular (IA) injections of corticosteroid (CO) and hyaluronic acid (HA) are commonly used for osteoarthritis. The efficacy of these interventions is controversial. Furthermore, research regarding the potential association of IA injection with later postoperative pain trajectories is lacking. Methods We performed analysis on Truven Health MarketScan database (2012-2016) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). Trends over time were assessed. Multivariable logistic regression analyses were executed to evaluate the impact of IA injections on postoperative chronic opioid use. Results Preoperative CO and HA injections decreased throughout the study period in both THA and TKA. Preoperative CO and HA injections, regardless of frequency, had no significant impact on the odds of THA patients becoming chronic opioid users postoperatively. TKA patients who had 1 CO injection in the year before surgery experienced lower odds of postoperative chronic opioid use (odds ratio [OR], 0.89; 95% confidence interval [95% CI], 0.82-0.97), whereas patients who had 2 or more CO injections experienced significantly greater odds (OR, 1.14; 95% CI, 1.04-1.24). TKA patients who received 2 or more HA injections before surgery had significantly lower odds of chronic opioid use (OR, 0.90; 95% CI, 0.81-0.99). Conclusion The utilization of IA injections in patients with hip and knee osteoarthritis appears to be decreasing over time. TKA patients who received 2 or more preoperative CO injections experienced greater odds of chronic opioid utilization, whereas TKA patients with 2 or more HA injections in the year before surgery had decreased odds of chronic opioid use.

BackgroundTranexamic acid (TXA) has been used extensively to minimize blood loss in cardiac surgery and more recently in orthopedic surgery. Despite a generally good safety profile, an increased risk of seizures has been observed in patients with cardiac disease. However, this issue has not been adequately addressed in the orthopedic literature.MethodsAfter institutional review board approval, we queried a large national database to identify patients who had undergone total hip and total knee arthroplasties (2012–2016). Patients were divided based on their exposure to TXA and history of seizures. The main outcome of interest was a perioperative seizure. We conducted univariable comparisons and a multivariable regression analysis to elucidate a potential independent association between TXA administration and seizures in the perioperative period (with or without a history of seizures).ResultsTXA was used overall in 45.9% (n=4 21 890) of joint arthroplasty recipients (n=9 18 918), with more frequent use over time. Utilization rates did not differ between those with and without a history of seizures; 42.2% (3487/8252) of patients with a seizure history received TXA. Rates of perioperative seizure were low and did not differ between those who did and did not receive TXA (0.01% vs 0.02%, p=0.11); when subgrouping patients by history of seizures, we found no difference in incidence of perioperative seizures between groups (0.06% vs 0.02%, p=0.39). Our adjusted analysis further confirmed these results.ConclusionDespite increasing TXA utilization in total joint arthroplasty, we found an overall low seizure incidence. TXA use was not associated with elevated odds of perioperative seizure, even in patients with history of seizure.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been shown to benefit recovery after several operations. However, large-scale data on the association between the level of ERAS use and perioperative complications are scarce, particularly in surgeries with increasing ERAS uptake, including total hip (THA) and knee arthroplasty (TKA). Using US national data, we examined the relationship between the number of ERAS components implemented ('level') and perioperative outcomes.METHODS: After ethics approval, we included 1 540 462 elective THA/TKA procedures (2006-2016, as recorded in the Premier Healthcare claims database) in this retrospective cohort study. Main outcomes were any complication, cardiopulmonary complications, mortality, blood transfusions, and length of stay. Eight commonly used ERAS components were included. Mixed-effects models measured associations between ERAS level and outcomes, with odds ratios (OR) and confidence intervals (CI) reported.RESULTS: ERAS use increased over time; overall, 21.6% (n=324 437), 62.7% (n=965 953), and 18.0% (n=250 072) of cases were classified as 'High', 'Medium', or 'Low' ERAS. 'High ERAS', 'Medium ERAS', and 'Low ERAS' level of use were defined as such if they received either >6, 5-6, or CONCLUSIONS: ERAS components were used more frequently over time, and the level of utilisation was independently associated with incrementally improved complication odds and reduced length of stay during the primary admission. Possible indication bias limits the certainty of these findings.

STUDY DESIGN Retrospective database study. OBJECTIVE We sought to investigate trends and risk factors for new-onset anxiety and/or depression within 6 months after elective spine surgery. SUMMARY OF BACKGROUND DATA Surgery represents a stressful experience associated with a number of physiological and psychological consequences. A subset of patients develop clinically significant symptoms of new-onset anxiety or depression. However, the incidence of and risk factors for these adverse outcomes after spine surgery remain ill-defined. METHODS We performed a retrospective analysis including anterior cervical discectomy and fusion and posterior lumbar fusion cases from 2012 to 2015, utilizing the Truven MarketScan database. Primary outcomes were new-onset depression, new-onset anxiety, and new-onset depression and/or anxiety after surgery. Potential risk factors included patient demographics, comorbidities, hospital and procedural characteristics as well as perioperative opioid regimens. Multivariable logistic regression models measured associations between risk factors and outcomes. Odds ratios (OR) were reported and results with P

BACKGROUND Hip fracture patients represent various perioperative challenges related to their significant comorbidity burden and the high incidence of morbidity and mortality. As population trend data remain rare, we aimed to investigate nationwide trends in the United States in patient demographics and outcomes in patients after hip fracture repair surgery. METHODS After Institutional Review Board (IRB) approval (IRB#2012-050), data covering hip fracture repair surgeries were extracted from the Premier Healthcare Database (2006-2016). Patient demographics, comorbidities, and complications, as well as anesthesia and surgical details, were analyzed over time. Cochran-Armitage trend tests and simple linear regression assessed significance of (linear) trends. RESULTS Among N = 507,274 hip fracture cases, we observed significant increases in the incidence in preexisting comorbid conditions, particularly the proportion of patients with >3 comorbid conditions (33.9% to 43.4%, respectively; P < .0001). The greatest increase for individual comorbidities was seen for sleep apnea, drug abuse, weight loss, and obesity. Regarding complications, increased rates over time were seen for acute renal failure (from 6.9 to 11.1 per 1000 inpatient days; P < .0001), while significant decreasing trends for mortality, pneumonia, hemorrhage/hematoma, and acute myocardial infarction were recorded. In addition, decreasing trends were observed for the use of neuraxial anesthesia either used as sole anesthetic or combined with general anesthesia (7.3% to 3.6% and 6.3% to 3.4%, respectively; P < .0001). Significantly more patients (31.9% vs 41.3%; P < .0001) were operated on in small rather than medium- and large-sized hospitals. CONCLUSIONS From 2006 to 2016, the overall comorbidity burden increased among patients undergoing hip fracture repair surgery. Throughout this same time period, incidence of postoperative complications either remained constant or declined with the only significant increase observed in acute renal failure. Moreover, use of regional anesthesia decreased over time. This more comorbid patient population represents an increasing burden on the health care system; however, existing preventative measures appear to be effective in minimizing complication rates. Although, given the proposed benefits of regional anesthesia, decreased utilization may be of concern.

STUDY DESIGN Retrospective database study. OBJECTIVE We sought to identify trends in demographics, comorbidities, and postoperative complications among patients undergoing ACDF and PLF. SUMMARY OF BACKGROUND DATA As demand for anterior cervical discectomy and fusion (ACDF) and posterior lumbar fusion (PLF) surgery continues to increase, it is important to understand changes in the healthcare system and patient populations undergoing these procedures. METHODS We identified 220,520 ACDF and 151,547 PLF surgeries (2006-2016; Premier Healthcare database). Annual proportions or medians were calculated for patient and hospital characteristics, and (Elixhauser) comorbidities. Postoperative complications, including blood transfusions, cardiovascular, pulmonary, renal, or wound complications, hemorrhage, stroke, sepsis, thromboembolism, delirium, inpatient falls, and mortality, were reported per 1000 inpatient days. Trends were assessed by Cochran-Armitage tests and linear regression for binary and continuous variables, respectively. RESULTS The median age of patients undergoing ACDF and PLF increased significantly from 2006 to 2016 (50 to 57 yr and 58 to 61 yr, respectively; P

OBJECTIVE To determine the influence of rectal hydrogel spacer placement (HSP) on late rectal toxicity outcomes in prostate cancer patients treated with low-dose-rate (LDR) brachytherapy, with or without supplemental external beam radiotherapy (EBRT). PATIENTS AND METHODS A total of 224 patients underwent LDR brachytherapy with HSP, as monotherapy or combined with EBRT, between January 2016 and December 2019. Dosimetric variables reflecting the extent of rectal sparing and late rectal toxicity outcomes were evaluated. This spacer cohort was retrospectively compared to a similar patient group (n = 139) in whom HSP was not used. RESULTS Hydrogel spacer placement was associated with significantly reduced rectal doses for all dosimetric variables; the median percentage rectal dose to 1 cc of rectum and rectal dose to 2 cc of rectum of the spacer cohort were all significantly lower compared to the non-spacer cohort. The incidence rates of overall (any grade) and grade ≥2 rectal toxicity were lower in patients with HSP compared to patients who did not undergo HSP: 12% and 1.8% vs 31% and 5.8%, respectively. The 3-year cumulative incidence of overall rectal toxicity was significantly lower with HSP than without (15% vs 33%; P

Despite the perception that ultrasound-guided regional anesthesia (UGRA) is becoming a universally adopted tool for peripheral nerve blocks (PNBs), actual data on the utilization of ultrasound for regional anesthesia remain limited. The primary aim of this study was to define the incidence of

Postoperative loss of airway requiring reintubation is a rare but potentially catastrophic complication following anterior cervical discectomy and fusion (ACDF). We sought to identify risk factors asscociated with reintubation within one day following ACDF. Attention was focused on patient demographics, comorbidities, and factors potentially linked to soft tissue swelling and hematoma formation that could compromise the upper airway. We performed a retrospective cohort study of patients who underwent ACDF procedures at a high-volume institution from 2005 to 2014 (n = 3,041), participating hospitals in the National Surgical Quality Improvement Program (NSQIP) (n = 47,425), and Premier Healthcare (n = 233,633) databases from 2006 to 2016. Separate multivariable logistic regression models using the NSQIP and Premier samples were used to identify risk factors for reintubation within one day of ACDF. Odds ratios (OR) and 95% confidence intervals (CI) are reported. Incidence of reintubation within one day of ACDF was 0.19% in the institutional database and 0.21% in NSQIP and Premier databases. Risk factors for reintubation included older age, male sex, high comorbidity burden, procedures performed at large hospitals, non-elective procedures, Medicaid insurance, and use of heparin or more than one anticoagulant. Intravenous or oral steroid use (OR, 0.45; 95% CI, 0.36 to 0.56; P < 0.001) and delayed extubation (OR, 0.28 95% CI, 0.16 to 0.49; P < 0.001) were found to decrease risk of reintubation. Across three complementary data sets, incidence of reintubation within one day of ACDF was approximately 0.20%. Increased risk of reintubation associated with anticoagulant administration suggests upper airway hematoma as an underlying etiology. Steroid administration and delayed extubation may be useful in patients considered to be at higher risk for reintubation.

BackgroundArthroplasty is one of the most commonly performed procedures in the USA with projections of continuous growth. As this field undergoes continuous changes, the goal of this study was to provide an analysis of patient-related and healthcare system-related trends. This is important as it allows practitioners, administrators and policy makers to allocate needed resources appropriately.MethodsThe study included total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures from 2006 to 2016. Demographic information, comorbidities and complications were extracted and analyzed from the Premier Healthcare database.ResultsThe surgical volume increased annually over the observation period by an average of 5.54% for TKA and 7.02% for THA, respectively. The average age of the patient population and the types of anesthesia used remained relatively consistent over time. Comorbidity burden increased, especially for obesity (16.52% in 2006 and 29.77% in 2016 for TKA, 11.15% in 2006 and 20.92% in 2016 for THA), obstructive sleep apnea (OSA) (6.82% in 2006 and 17.03% in 2016 for TKA, 4.69% in 2006 and 12.72% in 2016 for THA) and renal insufficiency (2.81% in 2006 and 7.01% in 2016 for TKA, 2.78% in 2006 and 6.43% in 2016 for THA). Minor trends of increases were also observed in the prevalence of liver disease, depression and hypothyroidism. All postoperative complications were trending lower except for acute renal failure, where an increase was noted (4.39% in 2006 and 8.10% in 2016 for TKA, 4.99% in 2006 and 8.42% in 2016 for THA).DiscussionSignificant trends in the care of patients who undergo TKA and THA were identified. Individuals undergoing these procedures presented with a higher prevalence of comorbidities. Despite these trajectories, complications declined over time. These data can be used to inform future research and to allocate resources to address changes in populations cared for and complications encountered.

Information regarding the impact of provider characteristics on perioperative outcomes in the spine surgery setting is limited. Existing studies primarily consider the impact of surgical provider volume. This analysis sought to identify the impact of anesthesiologist and surgeon volume and experience as well as anesthesia care team composition on adverse outcomes following anterior cervical discectomy and fusions (ACDF) and posterior lumbar fusions (PLF). We identified 5900 patients who underwent ACDF or PLF procedures at a high-volume orthopedic institution from 2005 to 2014. Provider characteristics of interest were anesthesiologist and surgeon volume and experience along with anesthesia care team composition. Multivariable logistic regression models were used to evaluate the outcomes of any complication, cardiopulmonary complication, and prolonged length of stay (> 7 days). Intraclass correlation coefficients were calculated to determine how much variation in outcomes could be explained by provider characteristics. There were no significant relationships between provider characteristics and perioperative outcomes among ACDF patients. Within the PLF cohort, surgeon annual case volume > 25 was associated with decreased odds of prolonged length of stay, while anesthesia resident involvement was associated with increased odds of prolonged length of stay. Surgeon characteristics explained the greatest proportion of variation in outcomes while anesthesiologist characteristics explained the least. Anesthesia provider volume and experience did not significantly impact the odds of adverse outcome for ACDF and PLF patients. Higher surgeon volume was exclusively associated with decreased odds of prolonged length of stay following PLF. Further study is necessary to determine if these relationships persist in a less-specialized setting. These slides can be retrieved under Electronic Supplementary Material.

Pretreatment-predicted postoperative diffusing capacity of the lung for carbon monoxide (DLCO) has been associated with operative mortality in patients who receive induction therapy for resectable non-small cell lung cancer (NSCLC). It is unknown whether a reduction in pulmonary function after induction therapy and before surgery affects the risk of morbidity or mortality. We sought to determine the relationship between induction therapy and perioperative outcomes as a function of postinduction pulmonary status in patients who underwent surgical resection for NSCLC.We retrospectively reviewed data for 1001 patients with pathologic stage I, II, or III NSCLC who received induction therapy before lung resection. Pulmonary function was defined according to American College of Surgeons Oncology Group major criteria: DLCO ≥50% = normal; DLCO50% = impaired. Patients were categorized into 5 subgroups according to combined pre- and postinduction DLCO status: normal-normal, normal-impaired, impaired-normal, impaired-impaired, and preinduction only (without postinduction pulmonary function test measurements). Multivariable logistic regression was used to quantify the relationship between DLCO categories and dichotomous end points.In multivariable analysis, normal-impaired DLCO status was associated with an increased risk of respiratory complications (odds ratio, 2.29 [95% CI, 1.12-4.49]; P = .02) and in-hospital complications (odds ratio, 2.83 [95% CI, 1.55-5.26]; P .001). Type of neoadjuvant therapy was not associated with an increased risk of complications, compared with conventional chemotherapy.Reduced postinduction DLCO might predict perioperative outcomes. The use of repeat pulmonary function testing might identify patients at higher risk of morbidity or mortality.

BackgroundSeveral studies have identified excess risk associated with undergoing simultaneous (compared with unilateral or staged) bilateral total knee arthroplasty (BTKA). However, few have addressed subsequent chronic opioid use. Given the substantial morbidity and mortality associated with prolonged opioid use, we evaluated the incidence of postoperative chronic opioid use following simultaneous versus staged BTKA, based on the different timing strategies of staged procedures.MethodsIn this retrospective cohort study, patients who underwent BTKA procedures (2012–2016; Truven Health MarketScan; n=14 407) were classified as having undergone simultaneous or staged BTKA (ResultsUnadjusted frequency of chronic opioid use did not differ between groups, (Simultaneous: 11.3%, staged 6 months: 10.2%; p=0.247). In an adjusted model, there was no significant difference in the odds of becoming chronic opioid users between staged and simultaneous BTKA (staged 6 months OR 0.96, 95% CI 0.82 to 1.13; p=0.755). Patients undergoing staged BTKAs ConclusionAlthough patients undergoing staged BTKA

We report pre-clinical and first-in-human-brain-cancer data using a targeted poly(ADP-ribose)polymerase1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment related changes. In a pre-clinical mouse model, we illustrated that [18F]PARPi crosses the blood-brain barrier and specifically binds to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment related changes, independent of blood brain-barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancers than non-cancers. Specificity was also corroborated by blocking fluorescent tracer uptake with excess of unlabeled PARP inhibitor in fresh cancer tissue derived from a patient. Although larger studies are necessary to confirm and further explore this tracer, we describe an encouraging role for the use of [18F]PARPi as a diagnostic tool in evaluating patients with brain cancers and possible treatment related changes.One Sentence summaryPET imaging with [18F]PARPi can differentiate active brain cancer from treatment related changes with encouraging results for use during treatment follow-up.

Currently, there is no generalized consensus regarding perioperative prophylaxis of venous thromboembolism (VTE) in patients undergoing spine surgery. In the absence of large-scale studies, we aimed to use national data to study the association between anticoagulant prophylaxis and VTE in spine surgical patients. Our secondary outcomes were hematoma and blood transfusion.We included anterior cervical discectomy and fusion (ACDF) and posterior lumbar fusion (PLF) cases from 2006 to 2016 recorded in the Premier Healthcare database. Anticoagulant prophylaxis was categorized into aspirin, regular heparin, and low molecular weight heparin given on the day of surgery. Mixed-effects models measured the association between anticoagulation categories and outcomes. Cohorts were adjusted to reduce the risk of "confounding by indication" and to distinguish between prophylactic and therapeutic use of anticoagulants. We report odds ratios (OR) and Bonferroni-corrected confidence intervals (CI).Among 83,839 individuals undergoing ACDF and PLF, 0.45% (n = 374) had a hematoma, 8.1% (n = 6,769) received a blood transfusion, and 0.13% (n = 113) experienced VTE. After adjustment for relevant covariates, prophylactic aspirin (OR, 1.48; CI, 1.17 to 1.86) and regular heparin (OR, 2.01; CI, 1.81 to 2.24) were associated with increased odds of blood transfusion. No detectable differences in the odds of hematoma or VTE were observed for any anticoagulant.Although low molecular weight heparin was used much less frequently than regular heparin, it was associated with a lower incidence of transfusion compared with aspirin and regular heparin. All three anticoagulants were associated with similar incidence of VTE and hematoma. Varying subgroup-specific VTE risks may further inform future studies to identify patients expected to benefit the most from chemical thromboprophylaxis.RéSUMé: OBJECTIF: À l’heure actuelle, il n’existe pas de consensus concernant la prophylaxie périopératoire en cas de thromboembolie veineuse (TEV) pour les patients subissant une chirurgie du rachis. En l’absence d’études de grande envergure, nous avons cherché à utiliser des données nationales afin d’étudier l’association entre l’anticoagulothérapie et la TEV chez les patients de chirurgie du rachis. Nos critères d’évaluation secondaires étaient la présence d’hématome et les transfusions sanguines. MéTHODE: Nous avons inclus les chirurgies de discectomie cervicale antérieure avec fusion (DCAF) et de fusion lombaire postérieure (FLP) réalisées entre 2006 et 2016 et enregistrées dans la base de données Premier Healthcare. L’anticoagulothérapie a été catégorisée en aspirine, héparine normale, et héparine de bas poids moléculaire, donnée le jour de la chirurgie. Les modèles à effets mixtes ont mesuré l’association entre les catégories d’anticoagulation et les critères d’évaluation. Les cohortes ont été ajustées afin de réduire le risque de « confusion par indication » et de distinguer une utilisation prophylactique d’une utilisation thérapeutique des anticoagulants. Nous rapportons les rapports de cotes (RC) et les intervalles de confiance (IC) corrigés par Bonferroni. RéSULTATS: Parmi les 83 839 personnes ayant subi une DCAF ou une FLP, 0,45 % (n = 374) ont développé un hématome, 8,1 % (n = 6769) ont reçu une transfusion sanguine et 0,13 % (n = 113) ont souffert d’une TEV. Après ajustement pour tenir compte des covariables pertinentes, l’aspirine prophylactique (RC, 1,48; IC, 1,17 à 1,86) et l’héparine normale (RC, 2,01; IC, 1,81 à 2,24) ont été associées à des probabilités accrues de transfusion sanguine. Aucune différence détectable dans les risques d’hématome ou de TEV n’a été observée, indépendamment de l’anticoagulant utilisé. CONCLUSION: Bien que l’héparine de bas poids moléculaire ait été utilisée bien moins fréquemment que l’héparine normale, elle était associée à une incidence plus faible de transfusion par rapport à l’aspirine et à l’héparine normale. Les trois anticoagulants ont été associés à une incidence comparable de TEV et d’hématome. Les variations en matière de risque de TEV spécifiques aux sous-groupes pourraient orienter les études futures afin de tenter d’identifier les patients qui pourraient bénéficier le plus d’une thromboprophylaxie pharmaceutique.

BACKGROUND: The use of regional anesthesia (RA) in pediatric patients remains understudied, although evidence suggests benefits over general anesthesia. QUESTIONS/PURPOSES: We sought to identify factors associated with RA use in patients under the age of 21 years undergoing ambulatory orthopedic surgery. METHODS: Patients under the age of 21 who underwent anterior cruciate ligament (ACL) repair or reconstruction, knee arthroscopy (KA), or shoulder arthroscopy (SA) were identified from the NY Statewide Planning and Research Cooperative System (SPARCS) database (2005–2015). Frequencies of RA use (defined by femoral nerve block, spinal, epidural, caudal, or brachial plexus anesthesia) were calculated. Multivariable regression analysis identified patient- and healthcare system–related factors associated with the use of RA. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: We identified 87,273 patients who underwent the procedures of interest (ACL n = 28,226; SA n = 18,155; KA n = 40,892). In our primary analysis, 14.4% (n = 1404) had RA as their primary anesthetic; this percentage increased for patients who had ACL or KA. When adjusting for covariates, Hispanic ethnicity (OR 0.78; CI 0.65–0.94) and Medicaid insurance (OR 0.75; CI 0.65–0.87) were associated with decreased odds for the provision of RA. Further, we identified increasing age (OR 1.10; CI 1.08–1.11), ACL versus SA (OR 1.91; CI 1.74–2.10), and sports injuries (OR 1.20; CI 1.10–1.31) as factors associated with increased odds of RA use. CONCLUSION: In this analysis, RA was used in a minority of patients under the age of 21 undergoing ambulatory orthopedic surgery. Older age was associated with increased use while Hispanic ethnicity and lower socioeconomic status were associated with lower use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-020-09805-0) contains supplementary material, which is available to authorized users.

Study design Retrospective cohort study. Objective We sought to determine if there was an association between enhanced recovery after surgery (ERAS) implementation level and complication risk, length of stay, and cost of hospitalization. Summary of background data ERAS protocols aim to minimize the stress response of surgery by promoting early mobilization, oral intake, as well as improvement of analgesia. Implementation of ERAS protocols in spine surgeries has been limited to mostly single-institution studies, and no population-based data exist on the impact of the level of implementation of various ERAS components on outcomes. Methods In this study we identified 265,576 posterior lumbar fusion surgeries from 2006 to 2016. The main effect was the application of eight ERAS-related practices: (1) multimodal analgesia, (2) tranexamic acid, (3) antiemetics, (4) steroids, (5) early physical therapy, (6) avoidance of urinary catheters, (7) avoidance of patient-controlled analgesia, (8) avoidance of wound drains. Patients were classified by levels of ERAS implementation: "High," "Medium," and "Low" ERAS implementation if they received more than five, three to five, or less than three ERAS components, respectively. Mixed-effects models measured associations between ERAS implementation categories and complications, length and cost of hospitalization; odds ratios (OR, or average ratios for continuous outcomes), and 99.4% confidence intervals (CI) were reported. Results Overall, 13.3%, 62.8%, and 24.4% of cases were categorized as "High," "Medium," and "Low" ERAS implementation, respectively. After adjusting for study variables, "Medium" and "High" (compared with "Low") ERAS implementation levels were significantly associated with incrementally improved outcomes regarding "any complication" (OR 0.84 CI 0.80-0.88 and OR 0.77 CI 0.71-0.84), cardiopulmonary complications (OR 0.75 CI 0.68-0.73 and OR 0.69 CI 0.59-0.80), length of stay (average ratio 0. 94 CI 0.93-0.94 and average ratio 0.91 CI 0.90-0.91), and hospitalization cost (average ratio 0.99 CI 0.98-0.99 and average ratio OR 0.95 0.95-0.96). Conclusion In a cohort undergoing posterior lumbar spine fusion the level of utilization of ERAS protocol components was independently associated with incrementally improved complication odds as well as reduced length of stay and a small decrease in overall hospitalization cost. Level of evidence 3.

BackgroundGiven the steep learning curve for neuraxial and peripheral nerve blocks, utilization of general anesthesia may increase as new house staff begin their residency programs. We sought to determine whether “July effect” affects the utilization of neuraxial anesthesia, peripheral nerve blocks, and opioid prescribing for lower extremity total joint arthroplasties (TJA) in July compared with June in teaching and non-teaching hospitals.MethodsNeuraxial anesthesia, peripheral nerve block use, and opioid prescribing trends were assessed using the Premier database (2006–2016). Analyses were conducted separately for teaching and non-teaching hospitals. Differences in proportions were evaluated via χ2 test, while differences in opioid prescribing were analyzed via Wilcoxon rank-sum tests.ResultsA total of 1 723 256 TJA procedures were identified. The overall proportion of neuraxial anesthesia use in teaching hospitals was 14.4% in both June and July (p=0.940). No significant changes in neuraxial use were seen in non-teaching hospitals (24.5% vs 24.9%; p=0.052). Peripheral nerve block utilization rates did not differ in both teaching (15.4% vs 15.3%; p=0.714) and non-teaching hospitals (10.7% vs 10.5%; p=0.323). Overall median opioid prescribing at teaching hospitals changed modestly from 262.5 oral morphine equivalents (OME) in June to 260 in July (p=0.026) while median opioid prescribing remained at a constant value of 255 OME at non-teaching hospitals (p=0.893).ConclusionUtilization of neuraxial and regional anesthesia techniques was not affected during the initial transition period of new house staff in US teaching institutions. It is feasible that enough resources are available in the system to accommodate periods of turnover and maintain levels of regional anesthetic care including additional attending anesthesiologist oversight.

There is paucity of data regarding opioid dispension in patients undergoing bilateral total knee arthroplasty (BTKA). Our aim is to compare in-hospital opioid dispension between BTKA and unilateral TKA (UTKA) and to identify other factors associated with opioid dispension in the BTKA and UTKA cohorts.Patients receiving elective TKA from 2006 to 2016 were retrospectively extracted from the Premier Healthcare Database. The effect of interest was bilateral TKA. Our primary outcome was in-hospital opioid dispension in oral morphine equivalents. Univariable statistics between study variables and TKA type were obtained. A multilevel logistic regression model was run for the outcome of high opioid dispension.A total of 1,029,120 patients were included. Among these, 14,469 (1.4%) underwent a BTKA. Within the 10-year period studied, there was a decrease in opioid dispension in both groups. Logistic regression analysis showed that patients treated with BTKA had 1.68 times higher odds for high opioid dispension compared to UTKA patients (odds ratio = 1.68; 95.5% confidence interval = 1.62, 1.75; P.0001). White race, longer length of stay, Charlson/Deyo index, type of insurance, rural location, general anesthesia, peripheral nerve block use, and patient-controlled analgesia were also associated with high opioid dispension. Conversely, a more recent year of surgery, female gender, older age, and administration of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors were associated with lower odds for high opioid dispension.BTKA patients have increased odds for higher in-hospital opioid dispension compared to UTKA recipients. Utilization and prescribing habits should be examined to determine the optimal approach to opioid prescription in BTKA patients compared to UTKA.

Background We report preclinical and first-in-human-brain-cancer data using a targeted poly (ADP-ribose) polymerase 1 (PARP1) binding PET tracer, [18F]PARPi, as a diagnostic tool to differentiate between brain cancers and treatment-related changes. Methods We applied a glioma model in p53-deficient nestin/tv-a mice, which were injected with [18F]PARPi and then sacrificed 1 h post-injection for brain examination. We also prospectively enrolled patients with brain cancers to undergo dynamic [18F]PARPi acquisition on a dedicated positron emission tomography/magnetic resonance (PET/MR) scanner. Lesion diagnosis was established by pathology when available or by Response Assessment in Neuro-Oncology (RANO) or RANO-BM response criteria. Resected tissue also underwent PARPi-FL staining and PARP1 immunohistochemistry. Results In a preclinical mouse model, we illustrated that [18F]PARPi crossed the blood–brain barrier and specifically bound to PARP1 overexpressed in cancer cell nuclei. In humans, we demonstrated high [18F]PARPi uptake on PET/MR in active brain cancers and low uptake in treatment-related changes independent of blood–brain barrier disruption. Immunohistochemistry results confirmed higher PARP1 expression in cancerous than in noncancerous tissue. Specificity was also corroborated by blocking fluorescent tracer uptake with an excess unlabeled PARP inhibitor in patient cancer biospecimen. Conclusions Although larger studies are necessary to confirm and further explore this tracer, we describe the promising performance of [18F]PARPi as a diagnostic tool to evaluate patients with brain cancers and possible treatment-related changes.

Background Severe gastrointestinal (GI) complications after elective hip and knee arthroplasty (THA/TKA) are rare. Some of them can be life-threatening and/or require emergency abdominal surgery. We studied the epidemiology of severe GI complications after THA/TKA and associations with anesthesia- and/or analgesia-related factors. Methods We included 591,865 THA and 1,139,616 TKA cases (Premier Healthcare claims database; 2006-2016). Main outcomes were GI complications and related emergency surgeries within 30 days after THA/TKA. Anesthesia- and analgesia-related factors were anesthesia type (neuraxial, general), use of peripheral nerve block, patient-controlled analgesia, nonopioid analgesics (acetaminophen, gabapentin/pregabalin, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, ketamine), and opioids (in oral morphine equivalents, categorized into low, medium, and high use based on the interquartile range). Mixed-effects models measured associations between anesthesia- and analgesia-related factors and outcomes, which were reported using odds ratios (ORs) and 95% confidence intervals (CIs). Results Among THA patients, GI complications were observed in 1.03% (n = 6103), with 0.08% (n = 450) requiring emergency surgery; this was 0.79% (n = 8971) and 0.05% (n = 540), respectively, for TKA patients. After adjustment for relevant covariates (including opioid use), almost all anesthesia-/analgesia-related factors were associated with significantly decreased odds of GI complications, specifically use of cyclooxygenase-2 inhibitors (OR 0.72 CI 0.67-0.76/OR 0.82 CI 0.78-0.86), nonsteroidal anti-inflammatory drugs (OR 0.81 CI 0.77-0.85/OR 0.90 CI 0.86-0.94), and peripheral nerve blocks (OR 0.77 CI 0.69-0.87/OR 0.91 CI 0.85-0.97); all for THA and TKA, respectively (all P Conclusion Rare, but devastating, acute GI complications (requiring surgery) after THA/TKA may be positively impacted by a variety of modifiable anesthesia-/analgesia-related interventions.

Background: With the incorporation of positron emission tomography (PET) imaging as part of the standard staging evaluation of follicular lymphoma (FL), it is generally recommended to obtain the diagnostic biopsy from a lesion with the highest standardized uptake value (SUV) to rule out de novo histologic transformation (HT). In some cases such an approach might be impractical, while in other cases a biopsy from a diseased area with a high SUV may still demonstrate an indolent histology. To date, there is no data to guide treatment choices in patients (pts) with FL with high SUVmax but with no documented evidence of HT. Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, provide a better outcome than R-Bendamustine (BR). Furthermore, it is unknown whether rituximab (R) maintenance is beneficial in this setting. Therefore, we aimed to compare the efficacy of R-CHOP vs BR in newly diagnosed FL pts with high SUVmax at baseline PET and to clarify the role of maintenance. Patients and Methods: We retrospectively identified 261 consecutive pts with newly diagnosed biopsy-proven FL1-3A and a SUVmax≥13 on baseline PET, who were treated with frontline R-CHOP (n=183) or BR (n=78) at 7 US cancer centers based on the physician's choice. Progression-free survival (PFS) was calculated from starting treatment until progression, relapse or death. Cut-offs of SUVmax ≥13≤18 and SUVmax>18 were used for sub-analysis (Haematologica;2020;105:1907-1913). Results: Median age was 59 years. The baseline characteristics of the two groups differed significantly for a younger age (58 vs 62 years, p=0.009), a higher rate of B-symptoms (26% vs 10%, p=0.005) and baseline SUVmax>18 (49% vs 36%, p=0.04) in the R-CHOP group. A diagnostic biopsy was obtained from the site at the highest SUV in 129 (71%) and 43 (55%) pts, respectively (p=0.01). These suggest a potential selection of R-CHOP in pts with adverse features. At the end of therapy (EoT), R-CHOP treated pts achieved higher PET-CT complete response rates (CR 82% vs 69%, p=0.02). This superiority held in pts with diagnostic biopsy at the highest SUV site (CR 83% vs 67%, p=0.03), but not in the others (CR 80% vs 71%, p=0.37). Progression occurred at EoT in 11 and 14 pts receiving R-CHOP and BR (6% vs 18%, p=0.02), with a higher rate of HT in the BR group (13% vs 4%, p=0.006). After a median follow-up of 76 months (range, 4-208 months), there was no significant difference in PFS between R-CHOP and BR treated pts (hazard ratio [HR] 1.22, p=0.34). PFS was strongly associated with FLIPI 2 (HR 2.32, p=0.01) and 3-5 (HR 2.69, p=0.003) in the univariate as well as in the multivariate analysis (FLIPI 2 HR 2.19, p=0.02; FLIPI 3-5 HR 2.51, p=0.01). There was a trend toward overall survival (OS) benefit in the R-CHOP group (Fig.1A). In the univariate analysis for OS, BR regimen (HR 2.12, p=0.03), age >60 (HR 2.54, p=0.006), FLIPI 3-5 (HR 5.13, p=0.03) and biopsy at the highest SUV site (HR 0.44, p=0.01) were prognostic, however none of those remained significant in the multivariate analysis (BR regimen HR 1.84, p=0.09; age >60 HR 1.92, p=0.08; FLIPI 3-5 HR 3.11, p=0.14; biopsy at the highest SUV site HR 0.60, p=0.13; SUVmax>18 HR 1.87, p=0.055). Among pts with EoT response after R-CHOP or BR (n=170 and n=64, respectively), one third in each group (36% vs 41%, respectively) received R-maintenance for a median of 8 administrations (range, 2-12). A significant PFS advantage (landmark analysis) was observed with R-maintenance (Fig.1B; HR 0.53, p=0.02); however, this did not translate in survival benefit (HR 0.67, p=0.49). In a multivariable model, R-maintenance (HR 0.53, p=0.02), FLIPI 2 (HR 2.47, p=0.03) and 3-5 (HR 2.79, p=0.01) remained independent prognosticators of PFS, while no parameters significantly affected OS. The 2-year HT rate (10% vs 17%) and cumulative incidence did not statistically differ between R-CHOP and BR groups (Fig.1C, p=0.159). Early progression (POD24) occurred in 43 and 22 pts who received R-CHOP and BR, respectively (24% vs 28%) and resulted in a significantly higher risk of death (HR 4.12, p=0.006). Conclusion: In newly diagnosed FL pts with SUVmax≥13 at baseline PET, R-CHOP was more effective in achieving CR and reducing the risk of early HT compared with BR, and it was associated with a trend toward survival advantage. Rituximab maintenance significantly prolonged PFS. A prospective evaluation with a larger population will be needed to confirm our findings. Disclosures Joffe: Epizyme: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Ruella:Abclon, BMS, NanoString: Consultancy; Abclon: Consultancy, Research Funding; UPenn/Novartis: Patents & Royalties. Svoboda:Adaptive: Consultancy; Astra-Zeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Imbrium: Consultancy; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Research Funding; TG: Research Funding; Genmab: Consultancy; Atara: Consultancy. Witzig:Immune Design: Research Funding; Spectrum: Consultancy; Karyopharm Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Consultancy, Research Funding; AbbVie: Consultancy; MorphSys: Consultancy; Incyte: Consultancy. Smith:TG Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding; Pharmacyclics: Research Funding; Karyopharm: Consultancy, Research Funding; FortySeven: Research Funding; Acerta: Research Funding; Genentech/Roche: Consultancy, Other: Support of parent study and funding of editorial support, Research Funding. Armand:Affimed: Consultancy, Research Funding; Otsuka: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; IGM: Research Funding; Infinity: Consultancy; Genentech: Research Funding; Sigma Tau: Research Funding; Celgene: Consultancy; Adaptive: Consultancy, Research Funding; Tensha: Research Funding; Roche: Research Funding; Merck & Co., Inc.: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy. Nastoupil:Janssen: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Gilead/KITE: Honoraria; Gamida Cell: Honoraria; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Celgene: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Ansell:Takeda: Research Funding; Regeneron: Research Funding; Bristol Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; AI Therapeutics: Research Funding; ADC Therapeutics: Research Funding. Zelenetz:Novartis: Consultancy; Adaptive Biotechnology: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy; Gilead: Research Funding; Celgene: Consultancy; Roche: Research Funding; Amgen: Consultancy; BeiGene: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Sandoz: Research Funding; Celgene: Research Funding; MorphoSys: Research Funding; MEI Pharma: Research Funding. Younes:BioPath, Xynomic, Epizyme, and F. Hoffmann-La Roche: Consultancy; Janssen, Curis, Merck, Bristol-Myers Squibb, Syndax Pharmaceuticals, F. Hoffmann-La Roche, Curis (Inst), Johnson & Johnson (Inst), Novartis (Inst): Research Funding; Janssen, AbbVie, Merck, Curis, Epizyme, F. Hoffmann-La Roche, Takeda, Bristol-Myers Squibb, Bayer HealthCare Pharmaceuticals, Celgene, Incyte, Janssen Pharmaceuticals, Merck, Sanofi, Seattle Genetics, Takeda Millennium: Honoraria; AstraZeneca: Current Employment; MSKCC: Ended employment in the past 24 months.

Importance Surgical resection has been considered the only curative option for patients with pancreatic cancer. Nonoperative local treatment options that can provide a similar benefit are needed. Emerging radiation techniques that address organ motion have enabled curative radiation doses to be given in patients with inoperable disease. Objective To determine the association of hypofractionated ablative radiation therapy (A-RT) with survival for patients with locally advanced pancreatic cancer (LAPC) treated with a novel radiation planning and delivery technique. Design, setting, and participants This cohort study included 119 consecutive patients treated with A-RT between June 2016 and February 2019 and enrolled in a prospectively maintained database. Patients were treated with a standardized technique within a large academic cancer center regional network. All patients with localized, unresectable, or medically inoperable pancreatic cancer with tumors of any size and less than 5 cm luminal abutment with the primary tumor were eligible. Interventions Ablative RT (98 Gy biologically effective dose) was delivered using standard equipment. Respiratory gating, soft tissue image guidance, and selective adaptive planning were used to address organ motion and limit the dose to surrounding luminal organs. Main outcomes and measures The primary outcome was overall survival (OS). Secondary outcomes included incidence of local progression and progression-free survival. Results Between 2016 and 2019, 119 patients (59 men, median age 67 years) received A-RT, including 99 with T3/T4 and 53 with node-positive disease, with a median carbohydrate antigen 19-9 (CA19-9) level greater than 167 U/mL. Most (116 [97.5%]) received induction chemotherapy for a median of 4 months (0.5-18.4). Median OS from diagnosis and A-RT were 26.8 and 18.4 months, respectively. Respective 12- and 24-month OS from A-RT were 74% (95% CI, 66%-83%) and 38% (95% CI, 27%-52%). Twelve- and 24-month cumulative incidence of locoregional failure were 17.6% (95% CI, 10.4%-24.9%) and 32.8% (95% CI, 21.6%-44.1%), respectively. Postinduction CA19-9 decline was associated with improved locoregional control and survival. Grade 3 upper gastrointestinal bleeding occurred in 10 patients (8%) with no grade 4 to 5 events. Conclusions and relevance This cohort study of patients with inoperable LAPC found that A-RT following multiagent induction therapy for LAPC was associated with durable locoregional tumor control and favorable survival. Prospective randomized trials in patients with LAPC are warranted.

BackgroundSeveral studies have evaluated the impact of preoperative depression on outcomes following total joint arthroplasty (TJA), however few have studied new-onset depression or anxiety after TJA. We aimed to identify the incidence of and risk factors for new-onset depression/anxiety after TJA, specifically focusing on the role of chronic opioid use.MethodsPatients who underwent total hip (THA) or total knee (TKA) arthroplasty from 2012 to 2015 were identified from the Truven MarketScan database. The main outcomes were new-onset depression or anxiety. The main risk factor of interest was chronic opioid use as a proxy for chronic pain; this was classified into three groups: isolated preoperative use, isolated postoperative use, and preoperative use that continued postoperatively. Multivariable logistic regression models were used to obtain ORs and 95% CIs.ResultsOverall, 106 260 TJA procedures were included (34.3% THA/65.7% TKA); new-onset depression and anxiety were observed in 3.6% and 4.8% of patients, respectively. Preoperative chronic opioid use (6.3%; OR 1.88, 95% CI 1.47 to 2.40), isolated postoperative use (10%; OR 2.61, 95% CI 2.08 to 3.28), and continued postoperative use (7.8%; OR 2.08, 95% CI 1.74 to 2.49) were all associated with significantly increased odds of new-onset depression. Additional risk factors included female gender, younger age, comorbid psychological conditions, and hospital readmission within 6 months of surgery. Similar patterns were seen for new-onset anxiety.DiscussionGiven the observed relationship between chronic opioid use and adverse psychological outcomes following TJA, the relationship between these two entities requires further evaluation, specifically to identify if there is a causal relationship.

244 Background: Subgroup analysis of trials data suggested a favorable prognostic role for microsatellite instability high (MSI-high) status in resectable gastric cancer, but a lack of survival benefit from neoadjuvant/adjuvant chemotherapy; questioning current standard of care for MSI-high locally advanced gastric cancer. To help guide treatment decision making, we retrospectively studied the interaction between MSI status and chemotherapy on survival in a single institution. Methods: All clinically advanced (tumor stage 3-4 or positive lymph nodes) gastric cancer patients that underwent gastrectomy between 2000-2018 with MSI status available from immunohistochemistry (IHC, deficient mismatch repair protein expression (dMMR) vs proficient (pMMR)) or DNA next generation sequencing testing (NGS, MSI-high vs low/stable (MSS)) were included. Clinicopathological characteristics and overall survival (OS) was compared between patients with neoadjuvant/adjuvant chemotherapy and without, stratified for MSI status, by Kaplan-Meier and Cox regression analysis. Results: From a total of 1,844 clinically advanced patients with resection, MSI status was available in 559 as determined by IHC in 420, NGS in 88, and both in 51 with a concordance rate of 50/51 (98%). Tumors were dMMR/MSI-high in 84 (15%) and pMMR/MSS in 475 (85%). Patients with dMMR/MSI-high tumors were more often older, female, and had distal tumors with intestinal subtype. Neoadjuvant and/or adjuvant chemotherapy was administered in 53 (63%) in the dMMR/MSI-high group and 367 (77%) in the pMMR/MSS (p = 0.006). Median (interquartile range) time of follow-up was 32 (19-57) months. In the total cohort, OS after 3 years was 82% in the dMMR/MSI-high and 59% in pMMR/MSS (p < 0.001). In the patients with neoadjuvant/adjuvant chemotherapy only, the dMMR/MSI-high had improved OS (3-years OS: 80% vs 60%, p = 0.001), and after adjustment for age and clinical tumor stage in multivariable analysis, dMMR/MSI-high status was associated with improved OS (HR 0.38 95%CI 0.22-0.68). In the dMMR/MSI-high group only, 3-year OS was 80% with chemotherapy vs 86% without (p = 0.374), and chemotherapy was not associated with a difference in OS after multivariable analysis (HR 1.03 95%CI 0.40-2.66). In case of neoadjuvant chemotherapy, grade 1 pathological response ( > 90%) was observed in 1/41 (2.4%) of the dMMR/MSI-high tumors vs 43/278 (16%) of the pMMR/MSS tumors respectively (p = 0.026). Conclusions: The incidence of MSI-high tumors in our cohort of clinically locally advanced, resectable, gastric cancers was 15%. Patients with MSI-high tumors had worse pathological treatment response to neoadjuvant chemotherapy, but better OS, compared to microsatellite stable tumors. However, in patients with MSI-high tumors, OS was not altered by neoadjuvant/adjuvant chemotherapy. We recommend assessing MSI status in locally advanced gastric cancer.

Background Investigations suggest a relationship between increased resource utilization with disease burden and advanced age. However, it remains unknown the degree increased resource utilization is associated with pre-existing conditions, before complications occur. Methods This retrospective study identified total hip/knee arthroplasty cases in the Premier Database from 2006 to 2016 (N = 1,613,744), with hospitalization cost as the primary outcome. With a variable combining the conditions and complication, generalized linear models measured associations between condition/complication interaction groups and hospitalization cost. Estimates of percent cost increase by variable were obtained. Results Across all conditions, an increase in cost ranging from 0.38% to 4.28% was found in the absence of a complication. The “Condition = No, Complication = Yes” group was associated with a range of 11.50%-12.40% increase in average hospitalization cost, and the range was 14.43%-30.85% for the “Condition = Yes, Complication = Yes” group. Conclusion We found that having a high-risk condition without a complication accounted only for a modest hospitalization cost increase.