Citations

AbstractBackgroundHuman pegivirus (HPgV) is a single-strand RNA virus belonging to the Flaviviridae. Although no definitive association between HPgV infection and disease has been identified, previous studies have suggested an association of HPgV viremia with risk of lymphomas.MethodsWe conducted a systematic review and meta-analysis, including 1 cohort study and 14 case-control studies, assessing the association of HPgV viremia with adult lymphomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model, overall and by geographic region and lymphoma subtype.ResultsThe overall OR for lymphoma was 2.85 (95% CI, 1.98–4.11), with statistically significantly elevated ORs observed in 8 of 15 studies. There was a small amount of heterogeneity among studies (I2 = 28.9%; Q = 18.27, P = .16), and the funnel plot provided no evidence for publication bias. The strongest association with lymphoma risk was observed for studies from Southern Europe (OR, 5.68 [95% CI, 1.98–16.3]), whereas weaker ORs (with 95% CIs) were observed for studies from North America (2.24 [1.76–2.85]), Northern Europe (2.90 [.45–18.7), and the Middle East (2.51 [.87–7.27]), but all of similar magnitude. Participants with HPgV viremia had statistically significantly increased risks (OR [95% CI]) for developing diffuse large B-cell (3.29 [1.63–6.62]), follicular (3.01 [1.95–4.63]), marginal zone (1.90 [1.13–3.18]), and T-cell (2.11 [1.17–3.89]) lymphomas, while the risk for Hodgkin lymphoma (3.53 [.48–25.9]) and chronic lymphocytic leukemia (1.45 [.45–4.66]) were increased but did not achieve statistical significance.ConclusionsThis meta-analysis supports a positive association of HPgV viremia with lymphoma risk, overall and for the major lymphoma subtypes.

Background: The variability of throwing metrics, particularly elbow torque and ball velocity, during structured long-toss programs is unknown. Hypotheses: (1) Elbow torque and ball velocity would increase as throwers progressed through a structured long-toss program and (2) intrathrower reliability would be high while interthrower reliability would be variable. Study Design: Descriptive laboratory study. Level of Evidence: Level 3. Methods: Sixty healthy high school and collegiate pitchers participated in a structured long-toss program while wearing a validated inertial measurement unit, which measured arm slot, arm velocity, shoulder rotation, and elbow varus torque. Ball velocity was assessed by radar gun. These metrics were compared within and between all pitchers at 90, 120, 150, and 180 ft and maximum effort mound pitching. Intra- and interthrower reliabilities were calculated for each metric at every stage of the program. Results: Ball velocity significantly changed at each progressive throwing distance, but elbow torque did not. Pitching from the mound did not place more torque on the elbow than long-toss throwing from 120 ft and beyond. Intrathrower reliability was excellent (intraclass correlation coefficient >0.75) throughout the progressive long-toss program, especially on the mound. Ninety-one percent of throwers had acceptable interthrower reliability (coefficient of variation <5%) for ball velocity, whereas only 79% of throwers had acceptable interthrower reliability for elbow torque. Conclusion: Based on trends in elbow torque, it may be practical to incorporate pitching from the mound earlier in the program (once a player is comfortable throwing from 120 ft). Ball velocity and elbow torque do not necessarily correlate with one another, so a degree of caution should be exercised when using radar guns to estimate elbow torque. Given the variability in elbow torque between throwers, some athletes would likely benefit from an individualized throwing program. Clinical Relevance: Increased ball velocity does not necessarily equate to increased elbow torque in long-toss. Some individuals would likely benefit from individualized long-toss programs for rehabilitation.

Background: Ulnar collateral ligament (UCL) reconstruction of the elbow is commonly performed on professional baseball pitchers. Recent reports have suggested that revision rates are on the rise and may be higher than previously thought. Purpose: To provide a comprehensive report on current trends, surgical techniques, and outcomes of revision UCL reconstructions performed on professional baseball pitchers between 2010 and 2016. Study Design: Case series; Level of evidence, 4. Methods: The Major League Baseball Health and Injury Tracking System (HITS) was used to compile records of all revision UCL reconstructions performed on professional baseball pitchers between 2010 and 2016. Player data and outcomes were obtained from HITS, and surgical details were obtained from operative reports. Descriptive statistical analysis was performed on epidemiologic data. Outcomes (return to play [RTP] rates, RTP times, subsequent injuries, and subsequent surgeries) were compared across the most common surgical techniques (docking vs modified Jobe) and graft sources (palmaris longus autograft vs hamstring autograft). Results: A total of 69 professional baseball pitchers underwent revision UCL reconstruction from 2010 to 2016 at an average of 1424 days (47 months) after their primary surgery. A trend was seen toward increasing numbers of revision surgeries over time ( R 2 = 0.441; P = .104). The most commonly used tunnel configuration was the modified Jobe technique (n = 41; 59.4%), and the most commonly used graft was hamstring autograft (n = 34; 49.3%). A majority (76.6%) of pitchers achieved RTP, and 55.3% were able to return to the same level of play. Mean time to RTP was 436 days (14.5 months) for players with a palmaris longus autograft versus 540 days (18 months) for those with a hamstring autograft ( P = .108). Further, the mean time to RTP was 423 days (14 months) for the docking technique versus 519 days (17 months) for the modified Jobe technique ( P = .296). Similar rates of subsequent injuries and surgeries were noted between the 2 revision techniques and 2 most commonly used graft constructs. Conclusion: Revision UCL reconstruction showed relatively high RTP rates (77%), but only 55% of players returned to their same level of play. Mean time to RTP was shorter than that found in other, smaller investigations. Although general trends were seen toward decreased time to RTP for the docking technique and palmaris longus autograft, these differences did not reach statistical significance.

AbstractBackgroundRacial disparities in breast cancer (BC) outcomes persist where non-Hispanic black (NHB) women are more likely to die from BC than non-Hispanic white (NHW) women, and the extent of this disparity varies geographically. We evaluated tumor, treatment, and patient characteristics that contribute to racial differences in BC mortality in Atlanta, Georgia, where the disparity was previously characterized as especially large.MethodsWe identified 4943 NHW and 3580 NHB women in the Georgia Cancer Registry with stage I–IV BC diagnoses in Atlanta (2010–2014). We used Cox proportional hazard regression to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) comparing NHB vs NHW BC mortality by tumor, treatment, and patient characteristics on the additive and multiplicative scales. We additionally estimated the mediating effects of these characteristics on the association between race and BC mortality.ResultsAt diagnosis, NHB women were younger—with higher stage, node-positive, and triple-negative tumors relative to NHW women. In age-adjusted models, NHB women with luminal A disease had a 2.43 times higher rate of BC mortality compared to their NHW counterparts (95% CI = 1.99 to 2.97). High socioeconomic status (SES) NHB women had more than twice the mortality rates than their white counterparts (HR = 2.67, 95% CI = 1.65 to 4.33). Racial disparities among women without insurance, in the lowest SES index, or diagnosed with triple-negative BC were less pronounced.ConclusionsIn Atlanta, the largest racial disparities are observed in luminal tumors and most pronounced among women of high SES. More research is needed to understand drivers of disparities within these treatable features.

Objectives: The variability of throwing metrics, particularly elbow torque and ball velocity, during structured long-toss programs is yet to be fully elucidated. The primary aims of this study were to assess various throwing metrics through a structured long-toss program using wearable technology and to quantify the intra and inter thrower variability of these metrics at each stage of throwing. Methods: This was a descriptive laboratory study in which 60 high school and collegiate pitchers participated in a predetermined, structured, progressive long-toss program. All players wore a motusBASEBALL sleeve (Motus Global, Inc.; Rockville Centre, NY), which measured arm slot, arm velocity, shoulder rotation, and elbow varus torque. Radar guns were used to measure ball velocity. These metrics were compared within and between all pitchers at each of the following throwing distances: 90 ft, 120 ft, 150 ft, 180 ft, and maximum effort mound pitching. Intra- and inter- thrower reliabilities were calculated for each throwing metric at every stage of the program. Excellent intra-thrower reliability was defined by an Intra-class coefficient (ICC) >0.750. Acceptable inter-thrower reliability was defined by a Coefficient of Variation (CV) <5%. Results: Ball velocity significantly changed at each progressive throwing distance, but this did not consistently correlate with an increase in elbow torque. Pitching from the mound did not place more torque on the elbow than throwing from 120 ft and beyond. Intra-thrower reliability was excellent throughout the progressive long-toss program for each throwing metric. Ninety-one percent of throwers had acceptable inter-thrower reliability for ball velocity, whereas only 79% of throwers had acceptable inter-thrower reliability for elbow torque. Conclusion: Based on trends in elbow torque, it may be practical to incorporate pitching from the mound earlier in the program (once a player is comfortable throwing from 120 ft). Ball velocity and elbow torque do not necessarily correlate with one another, so a degree of caution should be exercised when using radar guns to estimate elbow torque. Given the variability in elbow torque between throwers, some athletes would likely benefit from an individualized throwing program.

Objectives: Progressive throwing programs are a mainstay of rehabilitating the throwing athlete after injury or surgery. Athletes are commonly asked to throw at reduced levels of effort (i.e. “50% effort”, ”75%,” etc) to minimize stress to healing tissues. However, it is unknown whether players’ perceived exertion matches actual exertion. The purpose of this study was to determine whether decreased effort correlates with decreased throwing metrics, whether metrics decrease to a predictable degree, and to quantify variability of these metrics within a given athlete when attempting to throw at sub-maximal effort. Methods: Sixty healthy, high school and collegiate baseball pitchers participated in a structured throwing program. After warming up, each pitcher was asked to throw five, max effort long toss throws at a distance of 120 feet. Afterwards, they were asked to give 5 throws at both 75% effort and 50% effort from the same distance. A motusBASEBALL sleeve (Motus Global, Inc.; Massapequa, NY) was worn by all players, which measured arm slot, velocity, shoulder rotation, and elbow varus torque (Nm). Ball velocity was measured in miles per hour (MPH) using a radar gun. The observed changes in throwing metrics were compared to one another across each of the throwing scenarios using a general estimating equation to control for multiple comparisons. They were also compared to the expected change to see if a decrease from 100% effort to 75%, and then to 50% resulted in proportional decreases in elbow torque and ball velocity. Intra-thrower variability was determined for each throwing metric at each degree of effort, and these results are reported using intra-class correlation coefficients (ICC) where an ICC > 0.75 was considered to represent excellent agreement. Results: Mean elbow torque decreased as players decreased their perceived effort from 100% (72.7 Nm) to 75% (67.3 Nm) to 50% (62.s Nm) (p<0.001). Mean ball velocity also decreased as they progressed from 100% effort (77.8 MPH) to 75% effort (66.5) to 50% effort (60.3 MPH) throws (p<0.001). However, these observed decreases in torque and velocity were much smaller in magnitude than the decreases in perceived effort. During the 75% effort throws, torque and velocity were not reduced to 75% of max. Instead, elbow torque was only reduced to 93.3% of max, and velocity dropped to 86.1% of max. Similarly, for the 50% effort throws, torque remained 86.5% of max effort torque, while velocity remained 78.1% of max. Accordingly, for every 25% decrease in perceived effort, torque only decreased 7%, and velocity only decreased 11%. These observed differences were all significantly different than the expected differences (p<0.001 for all). Intra-thrower reliability was considered excellent for all metrics within each throwing scenario: max effort, 75% effort, and 50% effort (ICC>0.75 for all). Conclusion: Measured effort was significantly greater than perceived effort during this standardized throwing program for all metrics tested. This is especially true for ball velocity and varus elbow torque. Ultimately, when players throw at what they perceive to be “reduced effort,” their actual throwing metrics do not decrease at the same rate as their perceived exertion. This has significant implications for throwers during the rehabilitation process as their elbows are likely experiencing more stress than desired. Clinicians and coaches must be aware and may want to consider transitioning to more objective measures of effort during rehabilition.

Objectives: Ulnar collateral ligament (UCL) reconstruction of the elbow is a commonly performed surgery on professional baseball pitchers. Recent reports have suggested that revision rates are on the rise and may be higher than previously thought. The purpose of this study is to provide a comprehensive report on current trends, surgical techniques, and outcomes of revision UCL reconstructions performed on professional baseball pitchers between 2010 and 2016. Methods: The Major League Baseball (MLB) Health and Injury Tracking System (HITS) was used to compile records of all revision UCL reconstructions performed on professional baseball pitchers between 2010 and 2016. Player data and outcomes were obtained from HITS while surgical details were obtained from operative reports. Descriptive statistical analysis was performed on epidemiologic data. Outcomes (return to play rates, return to play times, subsequent injuries, and subsequent surgeries) were compared across the most common surgical techniques (Docking vs. Modified Jobe) and graft sources (palmaris longus autograft vs. hamstring autograft). Results: A total of 69 professional baseball pitchers underwent revision UCL reconstruction from 2010 to 2016 at an average of 1,424 days (47 months) after their primary surgery. There was a trend toward increasing numbers of revision surgeries over time (R2=0.441; p=0.104). The most commonly used tunnel configuration was the Modified Jobe technique (n=41, 59.4%) and the most common graft utilized was hamstring autograft (n=34, 49.3%). 76.6% of pitchers were able to return to play (RTP) and 55.3% were able to return to the same level of play. Mean time to RTP in players with a palmaris longus autograft was 436 days versus 540 days for hamstring autograft (p=0.108) and the mean time to RTP in players was 423 days for the Docking technique versus 519 days for the Modified Jobe technique (p=0.296). Similar rates of subsequent injuries and surgeries were noted between the two revision techniques and two most commonly used graft constructs. Conclusion: This report detailing revision UCL reconstruction amongst professional baseball pitchers showed a trend towards increasing numbers of revisions being performed, a finding consistent with other recent studies. The overall return to play percentage was higher than previously reported (76.6%); however, significantly fewer (55.3%) players returned to the same level of play. This work also demonstrated decreased return to play times (n=484 days, SD: 117.3) compared to other investigations. The Modified Jobe was the most commonly used surgical technique and the two most commonly used graft constructs were hamstring autograft and palmaris longus autograft. Although this analysis did not reveal any statistically significant comparative differences between surgical techniques or graft constructs, future studies involving head-to-head comparisons of these surgical variables, specific to revision UCL reconstruction, may be helpful in improving player outcomes and career performance.

Background: Professional baseball players are at risk of acute and chronic injuries to their upper extremities. Methods: Major League Baseball’s Health and Injury Tracking System, a prospective injury surveillance system, was used to identify and characterize all hand and wrist injuries sustained by all Major League Baseball (MLB) and Minor League Baseball (MiLB) players during the pre-, regular, and postseason throughout 2011-2016. Injuries were included if they resulted in at least 1 day out of play and were sustained during standard baseball activities. Days missed were defined as the time between injury and the first time in which a player was cleared to return to play. Results: During the study period, there were 4478 hand and 1748 wrist injuries throughout MLB and MiLB, which resulted in a total of 105 246 days out of play. This was equivalent to the length of 575 individual MLB player seasons, and the mean days missed per injury was 17 days. Most injuries were traumatic in nature, with 43% (n = 2672) of players injured after being hit by a baseball that mainly occurred during batting (n = 2521; 40%). Injuries that most frequently required surgical intervention were hook of hamate fractures (72%) and scaphoid fractures (60%). Conclusions: Understanding the epidemiology and impact of hand and wrist injuries in MLB and MiLB players may lead to improved management of these injuries and reduce time away from play. Most importantly, preventive measures and/or enhanced protective gear may be developed to minimize these types of injuries in MLB and MiLB.

26 Background: NKTR-262 is a novel intratumoral prodrug designed to promote tumor antigen release, an immune stimulatory environment, and antigen presentation. NKTR-214 increases CD8+ T cells and NK cells in the tumor microenvironment. The combination of NKTR-262 with NKTR-214 accesses innate and adaptive immunity to provide an abscopal response and systemic tumor immunity. The Phase 1b/2 REVEAL trial is enrolling. Methods: In a 3+3 Phase 1 design, pts who are relapsed/refractory to ≥1 CPI receive escalating doses of intratumoral (IT) NKTR-262 followed by combined q3w treatment of IT NKTR-262 and fixed-dose intravenous (IV) NKTR-214 (0.006 mg/kg). Phase 1 will evaluate PK, safety, efficacy, and determine recommended Phase 2 dose. Scans are conducted every 9 wks (± 1 wk). Peripheral blood (PB) and tumor tissue are collected to measure biomarkers of immune activation. In Phase 2 expansion, NKTR-262 + NKTR-214 ± IV nivolumab (360 mg) will be assessed in specific tumor cohorts of IO-naïve and experienced pts. Results: As of 06 Nov 2018, 11 pts had received at least one cycle of NKTR-262 + NKTR-214 therapy. 7/11 pts were efficacy evaluable with at least one on-treatment scan (4 MEL, 2 SARC, 1 CRC). 2/4 R/R melanoma pts had uPRs with 100% (scan 2) and 40% (scan 1) reductions in target lesions per RECIST 1.1, respectively. Both patients remain on treatment. Two SARC pts had stable disease at scan 1. No pts experienced G3 or higher TRAEs or immune-related adverse events (AEs). Most common G1-2 AEs were transient flu-like symptoms. Gene expression analysis of tumor and PB show dose-dependent induction (4 to 16-fold) of TLR target genes. Consistent with the mechanism of action for NKTR-214, PB flow cytometry shows an average 13-fold increase from baseline in Ki67+ CD8+T cells in 6 pts. Conclusions: NKTR-262 + NKTR-214 engage the immune activation cascade from local tumor antigen production to anti-tumor T cell response. Initial dose levels of NKTR-262 with fixed-dose NKTR-214 were well-tolerated with early evidence of clinical activity. These data support continued evaluation of the combination +/- nivolumab. Clinical trial information: NCT03435640.

Background: During rehabilitation throwing programs, baseball players are commonly asked to throw at reduced levels of effort (ie, 50% effort, 75% effort, etc) to moderate stress to healing tissues. It is currently unknown how changes in players’ perceived exertion compares with changes in actual exertion during structured long-toss programs. Purpose: To determine whether decreased effort correlates with decreased throwing metrics, whether metrics decrease proportionally with reductions in perceived effort, and to quantify intrathrower variability. Study Design: Descriptive laboratory study. Methods: Sixty male high school and collegiate baseball pitchers participated in a structured throwing program. A motusBASEBALL sleeve was worn by all players, which measured elbow varus torque, arm velocity, arm slot, and shoulder rotation. Ball velocity was measured with a radar gun. Each pitcher threw 5 throws a distance of 120 ft with 3 efforts: maximum effort, 75% effort, and 50% effort. Throwing metrics were compared among the 3 levels of effort to see if each 25% decrease resulted in proportional decreases in elbow varus torque and ball velocity. Intrathrower variability was determined for each throwing metric at each degree of effort. Results: All throwing metrics decreased as players decreased their perceived effort ( P < .001). However, these observed decreases were much smaller in magnitude than the decreases in perceived effort. During the 75% effort throws, elbow varus torque was only reduced to 93% of maximum and velocity dropped to 86% of maximum. Similarly, for the 50% effort throws, elbow varus torque remained 87% of max effort torque, while velocity remained 78% of max. Intrathrower reliability was considered excellent for most metrics (intraclass correlation coefficient, >0.75). Conclusion: For every 25% decrease in perceived effort, elbow varus torque only decreased 7% and velocity only decreased 11%. Thus, when players throw at what they perceive to be reduced effort, their actual throwing metrics do not decrease at the same rate as their perceived exertion. Clinical Relevance: Measured effort decreased with decreasing perceived effort, but these were not proportional. This has significant implications for physical therapists, physicians, trainers, coaches, and athletes to understand and monitor elbow stress during the rehabilitation process.