Citations

Objectives: There is a paucity of literature regarding outcomes of anterior shoulder instability (ASI) in throwers and overhead athletes (OHA). The purpose of this study was to report the pathology, treatment strategies, and outcomes of ASI in throwers and overhead athletes utilizing an established US geographic population-based cohort. Methods: An established geographic database of more than 500,000 patients was used to identify athletes <40 years of age with ASI between 1994 and 2016. Medical records were reviewed to obtain demographics, type of sport, surgical details, and clinical outcomes. Patients were contacted after final clinical follow-up for patient reported outcomes (PRO). The Western Ontario Shoulder Instability (WOSI) score, return to sport at previous level of performance (RPP), rate of return to play (RTP) and time to RTP were recorded. Statistical analysis was performed comparing throwers to non-throwers and OHA to non-overhead athletes (NOHA). Results: The study population consisted of 171 patients, 114 NOHA and 57 OHA. Of the OHA, 40 were throwers. The mean follow-up was 14.7 ± 5.6 years for PRO’s and 11.7 ± 7.3 years for last clinical evaluation. No difference in overall instability events was seen in either group. Throwers were more likely to present with subluxations while non-throwers were more likely to present with frank dislocations. NOHA and non-throwers were more likely than OHA and throwers to have a history of trauma related to ASI, respectively ( P = <.001, P = .002). Throwers were more likely to undergo an open surgical procedure (45%) than non-throwers (15%) ( P = .038). The rate of recurrent instability between groups was similar. Throwers returned to sport at a lower rate than non-throwers, however this did not reach significance (64% vs 83%, P = .100). Throwers and OHA reported similar WOSI scores, RPP and time to RTP grouped by surgical or conservative management compared to non-throwers and NOHA, respectively. Conclusions: In a US cohort of patients, throwers and OHA had a similar number of instability events compared to non-throwers and NOHA, respectively. Non-throwers and NOHA were more likely to present with frank dislocation which is supported by the significantly higher rates of trauma in both groups. Notably, the WOSI score, RPP, rate of RTP and time to RTP showed no difference between throwers and OHA when compared to their non-throwing and NOHA counterparts.

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P &lt; .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P &lt; .001) and grade 3 to 4 aGVHD (HR, 1.97; P &lt; .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

PURPOSE This study sought to determine the prognostic significance of the WHO-defined glioma molecular subgroups along with additional alterations, including MGMT promoter methylation and mutations in ATRX, CIC, FUBP1, TERT, and TP53, in NRG/RTOG 0424 using long-term follow-up data. METHODS Mutations were determined using an Ion Torrent sequencing panel. 1p/19q co-deletion and MGMT promoter methylation were determined by Affymetrix OncoScan and Illumina 450K arrays. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios were calculated using the Cox proportional hazard model. Multivariable analyses (MVAs) included patient pretreatment characteristics. RESULTS We obtained complete molecular data to categorize 80/129 eligible patients within the WHO subgroups. Of these, 26 (32.5%) were IDHmutant/co-deleted, 28 (35%) were IDHmutant/non-co-deleted, and 26 (32.5%) were IDHwild-type. Upon single-marker MVA, both IDHmutant subgroups were associated with significantly better OS and PFS ( P values < .001), compared with the IDHwild-type subgroup. MGMT promoter methylation was obtained on 76 patients, where 58 (76%) were methylated and 18 (24%) were unmethylated. Single-marker MVAs demonstrated that MGMT promoter methylation was statistically significant for OS ( P value < .001) and PFS ( P value = .003). In a multimarker MVA, one WHO subgroup comparison ( IDHmutant/co-deleted v IDHwild-type) was significant for OS ( P value = .045), whereas MGMT methylation did not retain significance. CONCLUSION This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.

Abstract Normal brain aging is accompanied by patterns of functional and structural change. Alzheimer's disease (AD), a representative neurodegenerative disease, has been linked to accelerated brain aging at respective age ranges. Here, we developed a deep learning-based brain age prediction model using fluorodeoxyglucose (FDG) PET and structural MRI and tested how the brain age gap relates to degenerative cognitive syndromes including mild cognitive impairment, AD, frontotemporal dementia, and Lewy body dementia. Occlusion analysis, performed to facilitate interpretation of the model, revealed that the model learns an age- and modality-specific pattern of brain aging. The elevated brain age gap in dementia cohorts was highly correlated with the cognitive impairment and AD biomarker. However, regions generating brain age gaps were different for each diagnosis group of which the AD continuum showed similar patterns to normal aging in the CU.

Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage in brain tumors. Using simulations, we previously demonstrated that multi-echo DSC-MRI protocols provide improvements in contrast agent dosing, pulse sequence flexibility, and rCBV accuracy. The purpose of this study is to assess the in-vivo performance of dual-echo acquisitions in patients with brain tumors (n = 59). To verify pulse sequence flexibility, four single-dose dual-echo acquisitions were tested with variations in contrast agent dose, flip angle, and repetition time, and the resulting dual-echo rCBV was compared to standard single-echo rCBV obtained with preload (double-dose). Dual-echo rCBV was comparable to standard double-dose single-echo protocols (mean (standard deviation) tumor rCBV 2.17 (1.28) vs. 2.06 (1.20), respectively). High rCBV similarity was observed (CCC = 0.96), which was maintained across both flip angle (CCC = 0.98) and repetition time (CCC = 0.96) permutations, demonstrating that dual-echo acquisitions provide flexibility in acquisition parameters. Furthermore, a single dual-echo acquisition was shown to enable quantification of both perfusion and permeability metrics. In conclusion, single-dose dual-echo acquisitions provide similar rCBV to standard double-dose single-echo acquisitions, suggesting contrast agent dose can be reduced while providing significant pulse sequence flexibility and complementary tumor perfusion and permeability metrics.

Objective: To report the injury characteristics, radiographic findings, and long-term outcomes of nonoperative management for posterior shoulder instability (PSI). Design: A retrospective review of 143 patients with PSI using a large geographic database. Setting: Single county between January 1994 and July 2012. Patients: A clinical history and diagnosis of PSI, one confirmatory imaging study to support the diagnosis, and a minimum of 5 years follow-up were required for inclusion. Patients with seizure disorders, anterior-only instability, multidirectional instability, and superior labrum from anterior to posterior diagnosis were excluded. Interventions: Patients with PSI were managed nonoperatively or operatively. Main Outcome Measures: Pain, recurrent instability, and progression into glenohumeral osteoarthritis at long-term follow-up. Results: One hundred fifteen patients were identified. Thirty-seven (32%) underwent nonoperative management. Twenty (54%) patients were diagnosed with posterior subluxation, 3 (8%) with a single dislocation, and 7 (19%) with multiple dislocations. Symptomatic progression of glenohumeral arthritis was observed in 8% (3) of patients. Pain improved in 46% (17) of patients and worsened in 19% (7). Recurrent instability and progression to osteoarthritis occurred in 15% (3/20) of patients with a traumatic instability event compared with 0% of atraumatic patients after nonoperative management ( P = 0.234). Pain at follow-up was more common in nonoperative than operative patients ( P = 0.017). Conclusions: Nonoperative management is a viable option for many patients with posterior shoulder instability; however, many may continue to have posterior shoulder pain.

Abstract Background Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. Methods The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/− concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. Results Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations, and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. Conclusion Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification.

Purpose To define the success rate of initial nonoperative treatment for traumatic anterior shoulder instability in a defined U.S. geographic population, describe factors that predict conversion to surgery after initial nonoperative management, and describe the long‐term outcomes of nonoperative treatment after the index traumatic anterior instability event. Methods The Rochester Epidemiology Project database was used to identify patients aged 14 to 39 years treated for anterior shoulder instability between 1994 and 2016. Patient demographic characteristics, comorbidities, injury characteristics, and imaging were evaluated. Patients treated nonoperatively for the first 6 months after the index instability event were analyzed to determine long‐term outcomes (recurrence rate, pain at last follow‐up, radiographic outcomes), the success rate of continued nonoperative treatment (no conversion to surgery), and factors associated with conversion to surgery (patient and injury characteristics). Survivorship free of surgery was reported with a Kaplan‐Meier survival curve, and Cox proportional hazards models were used to evaluate association of variables with conversion to surgery. Results A total of 379 patients met the study criteria, with an average follow‐up period of 10.2 years (range, 0.53‐25.00 years). The average age was 23.9 years, the mean body mass index was 26.2, and 100% of instability events were due to trauma. Of the shoulders, 79 (20.1%) ultimately failed initial nonoperative treatment and progressed to surgery. At final follow‐up, the rate of recurrent instability was 52.3% in the group treated definitively without surgery, and the recurrence rate decreased from 92.4% to 10.1% in patients who underwent conversion to surgical treatment. Factors associated with conversion to surgery included 2 or more subluxations prior to the first evaluation (hazard ratio [HR], 1.82; P = .002), 2 or more dislocations prior to the first evaluation (HR, 1.76; P = .006), and recurrent instability at follow‐up (HR, 4.21; P < .001). Conclusions Most patients younger than 40 years with shoulder instability who were initially treated nonoperatively for 6 months were definitively treated without surgery. Ultimately, 35% of these patients experienced recurrent dislocations after 6 months of conservative treatment and 20% underwent surgical treatment. In most patients who underwent conversion to surgical treatment, surgery was performed within 12.5 years of their first instability event. Patients who experienced multiple instability events before or after consultation were more likely to undergo conversion to surgery after initial nonoperative management. Level of Evidence Level III, retrospective database review.

AbstractBackgroundMargins in transoral surgery for tonsil cancer can be limited by oropharyngeal wall thickness (OWT), but the normal range is not well established.MethodsIn 240 noncancer subjects, OWT was measured bilaterally in the vicinity of the tonsils with MRI. Statistical analysis was performed to assess for interaction of age, sex, location, and obesity.ResultsMean(SD) OWT measured 3.4(0.6) mm posteriorly, 3.7(2.0) mm between the styloglossus and stylopharyngeus, and 5.3(0.8) mm laterally. OWT was greater in men, correlated with obesity, decreased posteriorly and laterally in the 60–80 versus 40–59 year age groups, and increased when styloglossus/stylopharyngeus were closer. OWT was <5 mm in 36.7%–97.9% of locations, with the largest percentage below this threshold located posteriorly.ConclusionsOWT is frequently <5 mm, particularly in the posterior and intermuscular areas, suggesting that a smaller surgical margin may need to be accepted in transoral tonsil cancer surgery for anatomic reasons.