Citations

AbstractPurposeOvernight admission following anterior cruciate ligament reconstruction has implications on clinical outcomes as well as cost benefit, yet there are few validated risk calculators for reliable identification of appropriate candidates. The purpose of this study is to develop and validate a machine learning algorithm that can effectively identify patients requiring admission following elective anterior cruciate ligament (ACL) reconstruction. MethodsA retrospective review of a national surgical outcomes database was performed to identify patients who underwent elective ACL reconstruction from 2006 to 2018. Patients admitted overnight postoperatively were identified as those with length of stay of 1 or more days. Models were generated using random forest (RF), extreme gradient boosting (XGBoost), linear discriminant classifier (LDA), and adaptive boosting algorithms (AdaBoost), and an additional model was produced as a weighted ensemble of the four final algorithms.ResultsOverall, of the 4,709 patients included, 531 patients (11.3%) required at least one overnight stay following ACL reconstruction. The factors determined most important for identification of candidates for inpatient admission were operative time, anesthesia type, age, gender, and BMI. Smoking history, history of COPD, and history of coagulopathy were identified as less important variables. The following factors supported overnight admission: operative time > 200 min, age < 35.8 or > 53.5 years, male gender, BMI < 25 or > 31.2 kg/m2, positive smoking history, history of COPD and the presence of preoperative coagulopathy. The ensemble model achieved the best performance based on discrimination assessed via internal validation (AUC = 0.76), calibration, and decision curve analysis. The model was integrated into a web‐based open‐access application able to provide both predictions and explanations.ConclusionModifiable risk factors identified by the model such as increased BMI, operative time, anesthesia type, and comorbidities can help clinicians optimize preoperative status to prevent costs associated with unnecessary admissions. If externally validated in independent populations, this algorithm could use these inputs to guide preoperative screening and risk stratification to identify patients requiring overnight admission for observation following ACL reconstruction.Level of evidenceIV.

PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing—initial testing of priority genes followed by expanded testing—was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Purpose The purpose of this study is to define the impact of preoperative opioid use on postoperative opioid use, patient‐reported outcomes, and revision rates in a cohort of patients receiving arthroscopic shoulder surgery. Methods Patients who underwent shoulder arthroscopy were identified from an institutional database. Inclusion criteria were completion of preoperative and postoperative patient‐reported outcome measures (PROMs) at 1‐year follow‐up and completion of a questionnaire on use of opioids and number of pills per day. Outcomes assessed included postoperative PROM scores, postoperative opioid use, persistent pain, and achievement of the patient acceptable symptomatic state. A matched cohort analysis was performed to evaluate the impact of opioid use on achievement of postoperative outcomes, whereas a multivariate regression was performed to determine additional risk factors. Receiver operating characteristic curves were used to establish threshold values in oral morphine equivalents (OMEs) that predicted each outcome. Results A total of 184 (16.3%) patients were included in the opioid use (OU) group and 1,058 in the no opioid use (NOU) group. The OU and NOU groups showed statistically significant differences in both preoperative and postoperative scores across all PROMs ( P < .001). Multivariate logistic regression identified preoperative opioid use as a significant predictor of reduced achievement of the patient acceptable symptomatic state (odds ratio [OR], 0.69, 95% confidence interval [CI], 0.29‐0.83, P = .008), increased likelihood of endorsing persistent pain (OR, 1.73, 95% CI, 1.17‐2.56, P = .006), and increased opioid use at 1 year (OR, 21.3, 95% CI, 12.2‐37.2, P < .001). Consuming a high dosage during the perioperative period increased risk of revision surgery (OR, 8.59, 95% CI, 2.12‐34.78, P < .003). Results were confirmed by matched cohort analysis. Receiver operating characteristic analysis found that total OME >1430 mg/d in the perioperative period (area under the curve, 0.76) and perioperative daily OME >32.5 predicted postoperative opioid consumption (area under the curve, 0.79). Conclusions Patients with a history of preoperative opioid use can achieve significant improvements in patient‐reported outcomes after arthroscopic shoulder surgery. However, preoperative opioid use negatively impacts patients’ level of satisfaction and is a significant predictor of pain and continued opioid usage. Level of evidence Level III, retrospective cohort study

Abstract BACKGROUND Degenerative cervical myelopathy (DCM) is a progressive disease resulting from cervical cord compression. The modified Japanese Orthopaedic Association (mJOA) is commonly used to grade myelopathic symptoms, but its persistent postoperative improvement has not been previously explored. OBJECTIVE To utilize the Quality Outcomes Database (QOD) to evaluate the trajectory of outcomes in those operatively treated for DCM. METHODS This study is a retrospective analysis of prospectively collected data. The QOD was queried for patients undergoing elective surgery for DCM. Patients were divided into mild (≥14), moderate (9-13), or severe (<9) categories for their baseline severity of myelopathic symptoms (mJOA scores). A parsimonious multivariable logistic regression model was fitted with 2 points improvement on mJOA from 3- to 12-mo follow-up as the outcome of interest. RESULTS A total of 2156 patients who underwent elective surgery for DCM and had complete 3- and 12-mo follow-up were included in our analysis. Patients improved significantly from baseline to 3-mo on their mJOA scores, regardless of their baseline mJOA severity. After adjusting for the relevant preoperative characteristics, the baseline mJOA categories had significant impact on outcome of whether a patient keeps improving in mJOA score from 3 to 12 mo postsurgery. Patient with severe mJOA score at baseline had a higher likelihood of improvement in their myelopathic symptoms, compared to patients with mild mJOA score in. CONCLUSION Most patients achieve improvement on a shorter follow-up; however, patients with severe symptoms keep on improving until after a longer follow-up. Preoperative identification of such patients helps the clinician settling realistic expectations for each follow-up timepoint.

Introduction: Aneurysm rupture is associated with high mortality and morbidity, including both intracranial aneurysms (IA) and abdominal aortic aneurysms (AAA). Despite potential preemptive treatment in those identified prior to IA or AAA rupture, the evidence for whom to screen remains limited. IA and AAA share both environmental and genetic risk, and prior cost-effectiveness models suggest the potential efficacy of screening in these high-risk individuals. We hypothesized that reciprocal screening in those presenting with IA for AAA would yield positive results. Methods: The BAAS study sought to establish the co-prevalence of IA and AAA. In this arm of BAAS, we recruited patients presenting with IA and screened them for AAA using abdominal ultrasound (aU/S) at two sites: Mayo Clinic and the University of Virginia (UVA). All participants underwent a detailed interview to collect demographic, radiographic, and clinical data. At UVA, participants also received genetic counseling. Results: At Mayo Clinic, we enrolled and screened 81 consecutive patients with aSAH (3 patients with known AAA were excluded) with 3 (3.7%) positive aU/S for AAA. At UVA, we recruited 195 consecutive patients presenting with ruptured or unruptured IA and completed screening aU/S in 178 (93%). Only one (0.6%) had an AAA. Conclusion: The lower positive screening at UVA (0.6%) which enrolled both ruptured and unruptured IA compared to the 3.7% positive results at Mayo suggests that future efforts to identify who with IA might benefit from AAA screening should focus on those with aneurysmal subarachnoid hemorrhage (aSAH).

Introduction: Abdominal aortic aneurysm (AAA) rupture has a mortality rate of 64% and intracranial aneurysm (IA) rupture has a mortality rate of 50%. Despite the high mortality rates, early detection and treatment of these vascular lesions prior to rupture can prevent devastating clinical outcomes, underscoring the need to identify high-risk populations for screening. Current evidence demonstrates shared genetic and environmental risk factors for both AAA and IA. Methods: The BAAS study sought to establish the co-prevalence of AAA and IA. In one arm of BAAS, we recruited patients presenting with AAA and screened them for IA. All participants underwent a detailed interview to collect demographic, radiographic, and clinical data and also had genetic counseling. Results: Of the 126 individuals with an AAA enrolled, 65% (82/126) completed the MRA. Difficulty with logistics of obtaining the research MRA with long distance travel to clinic was the principal reason for failure to obtain MRA. We identified 20.7% (17/82) with one or more IA, including 21 aneurysms found during systematic screening. IA ranged in size from 1.5-14 mm (height) x 1.4-7 mm (width) and varied in location. 9.5% (2/21) had a maximum diameter of 7 mm or more. One participant with a positive MRA underwent early coil embolization with the remainder undergoing continued clinical surveillance. Of the 15 individuals completing the genetic counseling screening, two underwent recommended clinical genetic testing, revealing one negative screen and one variant of unknown significance in the MYH11 gene. Conclusion: Consistent with our prior cost effectiveness models, these prospective data support the clinical utility of routine screening for IA in patients presenting with AAA.

Purpose Selection bias in clinical trials has consequences for scientific validity and applicability of study results to the general population. There is concern that patients with clinically aggressive disease may not have enrolled in recent diffuse large B-cell lymphoma (DLBCL) trials due to the consent process and the inability to delay therapy for eligibility evaluation. We have examined the diagnosis-to-treatment interval (DTI) and its association with clinical factors and outcome in a clinic-based observational cohort of patients with DLBCL from the United States. Validation of results was performed in an independent, clinical trial-based cohort from Europe. Patients and Methods Patients were prospectively enrolled in the University of Iowa and Mayo Clinic Specialized Programs of Research Excellence Molecular Epidemiology Resource (MER; N = 986) or the Lymphoma Study Association (LYSA) LNH-2003 clinical trials program (N = 1,444). All patients received anthracycline-based immunochemotherapy at initial diagnosis. Associations of DTI with clinical factors and outcome were examined. Outcome was assessed using event-free survival at 24 months from diagnosis (EFS24). Results Median (range) DTI was 15 days (0 to 155 days in the MER and 23 days (0 to 215 days) in LYSA. Shorter DTI was strongly associated with adverse clinical factors, including elevated lactate dehydrogenase levels, poor performance status, B symptoms, and higher International Prognostic Index in both cohorts (all P < .001). Longer DTI was associated with improved EFS24 in both the MER (per-week odds ratio, 0.80; 95% CI, 0.74 to .0.87) and LYSA (per-week odds ratio, 0.90; 95% CI, 0.86 to 0.94); association with EFS24 remained significant after adjustment for International Prognostic Index. Conclusion DTI is strongly associated with prognostic clinical factors and outcome in newly diagnosed DLBCL. DTI should be reported in all clinical trials of newly diagnosed DLBCL and future trials should take steps to avoid selection bias due to treatment delay.

Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL.

Akt is a downstream target of B cell receptor signaling and is a central regulator of CLL cell survival. We aim to investigate the safety and efficacy of the Akt inhibitor MK‐2206 in combination with bendamustine and rituximab (BR) in relapsed and/or refractory CLL in a phase I/II study. A standard phase I design was used with cohorts of three plus three patients to determine the maximum tolerated dose (MTD) of MK‐2206 in combination with BR in relapsed CLL. Single‐agent MK‐2206 (weekly dosed) was administered one‐week in advance before BR on cycle 1 and subsequently was given with BR at the same time for cycle 2‐6. Phase II employed the MTD of MK‐2206 with BR to evaluate safety and efficacy of this study combination. Thirteen relapsed/refractory CLL were treated for maximal 6‐cycle of therapy. The maximum tolerated dose of MK‐2206 was 90 mg by mouth once weekly. The most common grade 3/4 adverse events were neutropenia (46%), febrile neutropenia (23%), rash (15%), diarrhea (15%), and thrombocytopenia (15%). Overall response rate was 92% with a median progression free survival and treatment free survival of 16 and 24 months, respectively. Five patients (38%) achieved complete remission or complete remission with incomplete count recovery, two of whom were MRD negative. The efficacy and tolerability of this combination indicates that Akt inhibition combined with chemoimmunotherapy is a promising novel treatment combination in CLL and deserves further prospective clinical trial.