Citations

Objectives: In the setting of ulnar collateral ligament (UCL) injury, surgical reconstruction of the UCL is not always selected, as it leads to a prolonged recovery time and return to play rates between 67-95%. To date, there is limited data on outcomes following nonoperative treatment in this population. Orthobiologics, such as platelet-rich plasma (PRP), have recently been used as an adjunct therapy for standard nonoperative treatment including rest and physical therapy for UCL injuries. The objective of this study was to determine if the addition of PRP injections in professional baseball players with UCL injuries reduces recovery time, lowers the likelihood of surgery, and increases the return to play rate compared to traditional nonoperative treatment. Methods: The Health and Injury Tracking System (HITS) database was searched from 2011-2015 for Major and Minor league baseball players with Grade I, II or III UCL injuries. Standard demographic, injury, and return to play data was obtained for all players. MRI’s for 353 athletes were reviewed by a musculoskeletal radiologist and graded accordingly. Outcomes were compared between players who received PRP injections in addition to traditional nonoperative treatment (PRP group) and players who received traditional nonoperative treatment alone (No PRP group). Statistical analysis was performed using Student’s T-test and Chi-square for parametric data. Kaplan Meier’s analysis was used for estimating longevity of the treatment. Results: A total of 544 Major and Minor League Baseball players with UCL tears underwent an initial course of nonoperative treatment (active rest & rehabilitation) for their injury between 2011-2015. Of these, 133 underwent PRP injections plus rehab and 411 underwent rehab alone. There was a significantly higher proportion of Major League Baseball players in the PRP group compared to the No PRP group (25.6% vs 9.0%, P<0.001). There was no difference between the two cohorts in regard to the grade of UCL tear (Figure 1). The players in the PRP group had a significantly longer time before returning to a throwing program compared to the No PRP group (64 days vs 51 days, P<0.001). The mean time from injury date to PRP injection was 14.5 days, which may explain the difference in time to return to throwing. The return to play rate in a live game without surgery was significantly lower in the PRP group compared to the No PRP group (46% vs 57%, P=0.03). There was no difference in the proportion of athletes requiring UCL reconstruction (58% vs 51%) or the time to surgery (154 days vs 178 days) between the two groups. Kaplan Meier survivor analysis showed no difference between the PRP and No PRP groups with regard to longevity of the native UCL (Figure 2). Conclusion: Among Major and Minor League Baseball players who were treated nonoperatively for a UCL injury between 2011-2015, 24% underwent PRP injections prior to rehab. Compared to traditional nonoperative rehab alone program, players who received PRP injections experienced a significantly longer time before returning to throwing, which may be in part due to the delay between the injury date and PRP injection. PRP injections did not appear to have a significant effect on the likelihood of surgical intervention.

SummaryWe evaluated the association of Human Pegivirus (HPgV) viraemia with risk of developing lymphoma, overall and by major subtypes. Because this virus has also been associated with better prognosis in the setting of co‐infection with human immunodeficiency virus, we further assessed the association of HPgV with prognosis. We used risk factor data and banked plasma samples from 2094 lymphoma cases newly diagnosed between 2002 and 2009 and 1572 frequency‐matched controls. Plasma samples were tested for HPgV RNA by reverse transcription polymerase chain reaction (RT‐PCR), and those with RNA concentrations <5000 genome equivalents/ml were confirmed using nested RT‐PCR methods. To assess the role of HPgV in lymphoma prognosis, we used 2948 cases from a cohort study of newly diagnosed lymphoma patients (included all cases from the case‐control study). There was a positive association of HPgV viraemia with risk of lymphoma overall (Odds ratio = 2·14; 95% confidence interval [CI] 1·63–2·80; P < 0·0001), and for all major subtypes except Hodgkin lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma, and this was not confounded by other lymphoma risk factors. In contrast, there was no association of HPgV viraemia with event‐free survival (Hazard ratio [HR] = 1·00; 95% CI 0·85–1·18) or overall survival (HR = 0·97; 95% CI 0·79–1·20) for lymphoma overall, or any of the subtypes. These data support the hypothesis for a role of HPgV in the aetiology of multiple lymphoma subtypes.

AbstractBackgroundBlepharospasm (BSP) is a type of focal dystonia characterized by involuntary orbicularis oculi spasms that are usually bilateral, synchronous, and symmetrical. Despite strong evidence for genetic contributions to BSP, progress in the field has been constrained by small cohorts, incomplete penetrance, and late age of onset. Although several genetic etiologies for dystonia have been identified through whole‐exome sequencing (WES), none of these are characteristically associated with BSP as a singular or predominant manifestation.MethodsWe performed WES on 31 subjects from 21 independent pedigrees with BSP. The strongest candidate sequence variants derived from in silico analyses were confirmed with bidirectional Sanger sequencing and subjected to cosegregation analysis.ResultsCosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. Deleterious variants in HS1BP3 (NM_022460.3: c.94C>A, p.Gly32Cys) and GNA14 (NM_004297.3: c.989_990del, p.Thr330ArgfsTer67) were identified in a father and son with segmental cranio‐cervical dystonia first manifest as BSP. Deleterious variants in DNAH17, TRPV4, CAPN11, VPS13C, UNC13B, SPTBN4, MYOD1, and MRPL15 were found in two or more independent pedigrees. To our knowledge, none of these genes have previously been associated with isolated BSP, although other CACNA1A mutations have been associated with both positive and negative motor disorders including ataxia, episodic ataxia, hemiplegic migraine, and dystonia.ConclusionsOur WES datasets provide a platform for future studies of BSP genetics which will demand careful consideration of incomplete penetrance, pleiotropy, population stratification, and oligogenic inheritance patterns.

Background: Although batters are frequently hit by pitch (HBP) in baseball, the effect of HBP injuries remains undefined in the literature. Purpose: To determine the effect of HBP injuries in terms of time out of play, injury patterns resulting in the greatest time out of play, and the value of protective gear such as helmets and elbow pads. Study Design: Descriptive laboratory study. Methods: Based on the Major League Baseball (MLB) Health and Injury Tracking System, all injuries to batters HBP during the 2011-2015 MLB and Minor League Baseball (MiLB) seasons were identified and analyzed. Video analysis was performed on all HBP events from the 2015 MLB season. Multivariate stepwise regression analysis was utilized to determine the predictive capacity of multiple variables (velocity, pitch type, location, etc) on injury status and severity. Results: A total of 2920 HBP injuries resulted in 24,624 days missed (DM) over the 5 seasons. MLB HBP injuries occurred at a rate of 1 per 2554 plate appearances (1 per 9780 pitches thrown). Mean DM per injury were 8.4 (11.7 for MLB vs 8.0 for MiLB, P < .001). Surgery was required for 3.1% of MLB injuries and 1.2% of MiLB injuries ( P = .005). The most common body regions injured were the hand/fingers (n = 638, 21.8%), head/face (n = 497, 17.0%), and elbow (n = 440, 15.7%), and there were 146 (5.0%) concussions. Injury rates and mean DM correlated with velocity in a near linear fashion. Players hit in the head/face (odds ratio, 28.7) or distal upper extremity (odds ratio, 6.4) were more likely to be injured than players HBP in other locations. Players with an unprotected elbow missed 1.7 more days (95% CI, –4.1 to 7.6) than those with an elbow protector ( P = .554) when injured after being HBP. Conclusion/Clinical Relevance: Although HBP injuries occur infrequently in the course of normal play, they collectively represent a significant source of time out of play. The most common body regions injured include the hands/fingers and head/face, and batters hit in these locations are significantly more likely to be injured. After contusions, concussions were the most common injury diagnosis.

Abstract Rationale Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. Objectives To determine whether computer-derived CT measures, specifically measures of pulmonary vessel–related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. Methods Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. Measurements and Main Results In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. Conclusions Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria—the VRS score—that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

Background: In recent years, there has been a dramatic rise in the annual number of ulnar collateral ligament (UCL) reconstructions performed in amateur baseball pitchers. Accordingly, increasing numbers of players are entering professional baseball having already undergone the procedure; however, the effect of prior UCL reconstruction on future success remains unknown. Purpose: (1) To provide an epidemiologic report on baseball players who undergo UCL reconstruction before being selected in the Major League Baseball (MLB) Draft, (2) to define the outcomes in terms of statistical performance, and (3) to compare these results with those of matched controls (ie, non–UCL reconstruction). Study Design: Cohort study; Level of evidence, 3. Methods: The MLB Amateur Draft Database was queried to identify all drafted pitchers who underwent UCL reconstruction before being drafted. For each pitcher drafted from 2005 to 2014 with prior UCL reconstruction, 3 healthy controls with no history of elbow surgery were randomly identified for matched analysis. A number of demographic and performance comparisons were made between these groups. Results: A total of 345 pitchers met inclusion criteria. The annual number of pitchers undergoing predraft UCL reconstructions rose steadily from 2005 to 2016 ( P < .001). For matched control analysis, 252 pitchers with a UCL reconstruction and a minimum 2-year follow-up (drafted between 2005 and 2014) were matched to 756 controls (non–UCL reconstruction). As compared with the non–UCL reconstruction group, pitchers who underwent predraft UCL reconstruction reached the MLB level with greater frequency (20% vs 12%, P = .003), and their MLB statistical performances were similar for all measures. Compared with all other pitchers drafted during that period, players who had a predraft UCL reconstruction demonstrated an increased likelihood of reaching progressive levels of play (Full Season A, AA, and MLB) within a given time frame ( P < .05 for all). Conclusion: The number of UCL reconstructions performed in amateur baseball players before the draft increased year over year for the entire study period. Professional pitchers who underwent UCL reconstruction as amateurs appear to perform at least as well as, if not better than, matched controls without elbow surgery.

Abstract Background: Abemaciclib is an orally administered, selective inhibitor of cyclin-dependent kinases 4 & 6 that is dosed on a twice daily continuous schedule. Abemaciclib has demonstrated clinical efficacy with a generally tolerable safety profile in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer in combination with fulvestrant in MONARCH 2 (NCT02107703) and in combination with non-steroidal aromatase inhibitors (NSAI) in MONARCH 3 (NCT02246621). These analyses were conducted to evaluate if patient and disease characteristics may better inform in whom and when abemaciclib should be initiated to define optimal treatment strategies. Methods: MONARCH 2 and 3 enrolled patients with HR+, HER2- advanced breast cancer. In MONARCH 2, patients whose disease had progressed while receiving endocrine therapy were treated with abemaciclib/placebo plus fulvestrant. In MONARCH 3, patients were treated with abemaciclib/placebo plus NSAI as initial therapy for advanced disease. An exploratory pooled analysis of the two studies was performed to determine significant prognostic factors. Efficacy results (progression-free survival [PFS] and objective response rate [ORR] in patients with measurable disease) were examined for patient subgroups corresponding to each of the identified significant prognostic factors. Subpopulation treatment effect pattern plot (STEPP) methodology was performed to examine the association between treatment-free interval (TFI) following adjuvant endocrine therapy and outcomes of endocrine therapy alone or in combination with abemaciclib in MONARCH 3. Results: Analyses of clinical factors in over 1000 patients confirmed the following to have prognostic value: bone-only disease, liver metastases, tumor grade, progesterone receptor (PgR) status, and ECOG performance status. Prognosis was poor in patients with liver metastases, PgR-negative tumors, and high-grade tumors. While all subpopulations benefited from the addition of abemaciclib to endocrine therapy regardless of prognosis, substantial benefit of abemaciclib was observed in poor prognosis subgroups, characterized by large increases in PFS (hazard ratios = 0.4 to 0.5) and ORR (over 30%). In addition, STEPP analysis of TFI on a subset of the MONARCH 3 population showed that patients with the shortest TFI appeared to have a poorer prognosis and received more benefit from the addition of abemaciclib compared to patients with longer TFI. Conclusions: This exploratory analysis has provided data that could help optimize treatment strategies by identifying that patients with poor prognostic factors may receive greater benefit from the addition of abemaciclib to endocrine therapy. Citation Format: Goetz MP, O'Shaughnessy J, Sledge Jr. GW, Martin M, Lin Y, Forrester T, Mockbee C, Smith IC, Di Leo A, Johnston S. The benefit of abemaciclib in prognostic subgroups: An exploratory analysis of combined data from the MONARCH 2 and 3 studies [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS6-02.

Purpose Abemaciclib, a cyclin-dependent kinase 4 and 6 inhibitor, demonstrated efficacy as monotherapy and in combination with fulvestrant in women with hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer previously treated with endocrine therapy. Methods MONARCH 3 is a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. Patients received abemaciclib or placebo (150 mg twice daily continuous schedule) plus either 1 mg anastrozole or 2.5 mg letrozole, daily. The primary objective was investigator-assessed progression-free survival. Secondary objectives included response evaluation and safety. A planned interim analysis occurred after 189 events. Results Median progression-free survival was significantly prolonged in the abemaciclib arm (hazard ratio, 0.54; 95% CI, 0.41 to 0.72; P = .000021; median: not reached in the abemaciclib arm, 14.7 months in the placebo arm). In patients with measurable disease, the objective response rate was 59% in the abemaciclib arm and 44% in the placebo arm ( P = .004). In the abemaciclib arm, diarrhea was the most frequent adverse effect (81.3%) but was mainly grade 1 (44.6%). Comparing abemaciclib and placebo, the most frequent grade 3 or 4 adverse events were neutropenia (21.1% v 1.2%), diarrhea (9.5% v 1.2%), and leukopenia (7.6% v 0.6%). Conclusion Abemaciclib plus a nonsteroidal aromatase inhibitor was effective as initial therapy, significantly improving progression-free survival and objective response rate and demonstrating a tolerable safety profile in women with HR-positive, HER2-negative advanced breast cancer.