Citations

Background: Although the monitoring of a pitcher’s throwing arm workload has become a hot topic in both research and the pitching world, the impact of mound height and distance still remains unclear. Purpose: To compare the kinetics and kinematics between pitches from a mound and flat ground at 2 different distances. Study Design: Descriptive laboratory study. Methods: A total of 21 healthy high school varsity baseball pitchers (age, 16.2 ± 1.3 years; weight, 73.6 ± 11.0 kg; height, 181.3 ± 6.4 cm) participated in this study. Players were fitted with a motusBASEBALL sensor and sleeve. Each pitcher was instructed to pitch 5 fastballs under 4 conditions: mound at 60.5 ft (regulation distance), flat ground at 60.5 ft, mound at 50.5 ft, and flat ground at 50.5 ft. Linear mixed-effects models were used to account for both intra- and interplayer variability. A multivariable model was used to evaluate the association of mound pitching, flat-ground pitching, and their distances (50.5 ft and 60.5 ft), and their interaction to arm speed, arm slot, arm rotation, elbow varus torque, and ball velocity. Results: There were no statistically significant effects of mound, flat-ground, or distance variation on arm speed or shoulder rotation. Arm slot was significantly higher (+3.0°; P = .02) on pitches from the mound at 60.5 ft compared with 50.5 ft. Elbow varus torque was lower (–1.5 N·m; P = .02) on mound pitches at 60.5 ft compared with 50.5 ft. Pitches thrown from the mound displayed significantly faster ball velocity compared with flat-ground pitches at both distances ( P < .01 for both), with pitches at 60.5 ft having higher velocity (+0.7 m/s; P < .01). Conclusion: Contrary to long-standing notions, the study results suggest that pitching from the mound does not significantly increase stress on the elbow compared with flat-ground pitching. Lower elbow varus torque and faster ball velocity at the regulation distance compared with the reduced distance indicate that elbow stress and ball velocity may not correlate perfectly, and radar guns may not be an appropriate surrogate measure of elbow varus torque. Clinical Relevance: A better understanding of the kinetic and kinematic implications of various throwing programs will allow for the designing of programs that are driven by objective data with aims directed toward injury prevention and rehabilitation in baseball pitchers.

AbstractBackgroundDigital pathology and machine learning (ML) workflows have paradigm shifting potential especially in the field of Alzheimer’s disease and related disorders. However, many institutions/centers may not have access to these technologies. To provide benchmark data, a survey was developed and distributed to National Institutes of Health’s Alzheimer’s Disease Centers (ADCs) in the United States.MethodSurvey questions covered topics such as: infrastructure (i.e. type of digital slide scanners used), funding sources (i.e. how the scanner was funded), and data management/storage (i.e. size of digital files). After development, review, and approval by the ADC digital pathology working group, the survey was distributed via email to 35 past and current ADC directors and/or ADC neuropathology core leaders. Participation in the survey was completely voluntary and answers did not contain any personal data.ResultThe survey generated over a 90% response rate, and the majority of those who completed the survey were neuropathology core leaders; 81% stated their ADC had access to a digital slide scanner, most common brand being Aperio/Leica. One third of respondents stated there was a fee for service to utilize the scanner. For digital pathology and/or ML resources, 40% of respondents stated none are supported in any way by their ADC. To cover the purchase and operation of the scanner, 50% stated they had institutional support. Many were unsure of the approximate average scanned file size of digital images (37%) and total amount of storage space that files occupied (50%). Many (75%) were aware of other departments at their institution working with digital pathology and/or ML, but a similar percentage was unaware of multi‐university or industry partnerships.ConclusionThese results demonstrate many ADCs have access to a digital slide scanner and had institutional support to cover the purchase. However, further investigation is needed to understand hurdles and barriers for implementing both digital pathology and ML workflows aiding in standardized methods across ADCs.

Abstract BACKGROUND CC-115 is an oral, CNS-penetrant, selective inhibitor of mammalian target of rapamycin kinase (mTOR) and deoxyribonucleic acid-dependent protein kinase (DNA-PK). Both targets are important in glioblastoma; PI3K/Akt/mTOR signaling is hyperactive in most glioblastomas, and DNA-PK is integral to repair of radiotherapy-mediated DNA damage. To investigate CC-115 in newly diagnosed glioblastoma and explore potential genomic biomarker associations, CC-115 was evaluated in the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial, an adaptive platform trial designed to efficiently test experimental agents. METHODS Adults with newly diagnosed MGMT-unmethylated glioblastoma, with genomic data available, are eligible for this ongoing trial. Patients are adaptively randomized to one of several experimental arms or the control arm: standard radiotherapy with concurrent and adjuvant temozolomide. The primary endpoint is overall survival (OS). Patients randomized to CC-115 (10mg po BID) received it concurrently with radiotherapy and as adjuvant monotherapy. As the first in-human use of CC-115 with radiation, a safety lead-in 3 + 3 design was used. RESULTS Twelve patients were randomized to CC-115; seven patients had possible treatment-related CTCAE grade &gt; 3 toxicity, including four pre-specified dose-limiting toxicities: liver function abnormality (n=1), hyperlipidemia (n=1), lipase elevation (n=1) and cerebral edema (n=1). There was no significant difference in progression-free survival (PFS, median 4.2 months [CC-115] vs. 5.2 months, p=0.9) or OS (median 10.1 months [CC-115] vs. 14.5 months, p=0.9) compared to the 50 patients randomized to the control arm. Based on early PFS results, randomization probability to CC-115 decreased from 25% to &lt; 10% at time of the trial arm closure. CONCLUSION Concurrent and adjuvant CC-115 was associated with toxicity and failed to improve PFS or OS. The INSIGhT trial design allowed for more efficient testing of CC-115, decreasing patients and resources allocated to a therapy that was discontinued due to concerns about toxicity and unfavorable risk-to-benefit ratio.

Abstract BACKGROUND The cyclin D-CDK4/6-Rb pathway is activated in most glioblastomas. Abemaciclib is a potent CDK4/6 inhibitor with good brain penetration approved for ER/PR/HER2- breast cancer. In order to efficiently evaluate the potential impact of abemaciclib on overall survival (OS) in newly diagnosed glioblastoma and to simultaneously develop information regarding potential genomic biomarker associations, abemaciclib was included as an arm on the Individualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT) trial. INSIGhT is a phase II platform trial using response adaptive randomization and deep genomic profiling to more efficiently test experimental agents in MGMT unmethylated glioblastoma and potentially accelerate identification of novel therapies for phase III testing. Initial randomization was equal between abemaciclib, control, and two other experimental arms but subsequent randomization was adapted based on efficacy as determined by progression-free survival (PFS). Ineffective arms were discontinued and new arms added by protocol amendment. We report preliminary results for the abemaciclib arm which has completed accrual. METHODS Patients with newly diagnosed MGMT-unmethylated glioblastoma were randomized to receive either radiotherapy with concomitant and adjuvant temozolomide at standard doses or standard radiochemotherapy followed by adjuvant abemaciclib (150–200 mg orally BID) without temozolomide. Treatment continued until progression or development of unacceptable toxicities. The primary endpoint was OS. Association between abemaciclib efficacy and cyclin D-CDK4/6-Rb pathway genomic alterations was also investigated. RESULTS There were 123 patients (50 control; 73 treated with abemaciclib). Abemaciclib was generally well-tolerated with no new toxicity signals identified. PFS was significantly longer (p=0.03, logrank test) with abemaciclib (median 6.31 months 95% CI [5.29, 8.18]) compared to the control arm (5.16 months 95% CI [4.37, 6.28]). 28/50 control and 36/73 abemaciclib patients remain alive. CONCLUSION Preliminary analysis suggests that abemaciclib increases PFS compared to control. Updated toxicity, PFS and survival data and potential genomic biomarker associations will be presented.

Background The purpose of this study is to evaluate how prior breast augmentation impacts rates of complications and risk for reoperation after mastectomy with concurrent breast reconstruction. Methods Patients undergoing nipple-sparing, skin-sparing, or simple mastectomy with implant-based reconstruction from 2008 to 2018 were identified in a prospective database. Postoperative complications and reoperations were then analyzed comparing patients with prior augmentation to patients without history of previous breast surgery. Results A total of 468 patients were identified with a median follow-up of 4 years. Of these, 72 had prior augmentation mammoplasty. These patients underwent nipple-sparing (52, 72%), skin-sparing (15, 21%), or simple (5, 7%) mastectomy with immediate direct-to-implant (46, 61%) or tissue expander (26, 35%) reconstruction. On univariate analysis, this cohort had a lower body mass index (23.3 vs 25.3, P = 0.003), a higher rate of nipple-sparing mastectomy (72% vs 54%, P = 0.01), and a higher prevalence of stage I disease (44% vs 33%, P = 0.04). Differences in age, comorbidities, reconstructive techniques, tumor size, and neoadjuvant/adjuvant therapies were not significant. Overall complication rate between patients with or without prior augmentation did not significantly differ (51% vs 50%, P = 0.83); no significant differences in rates of surgical site infection, hematoma, mastectomy skin flap/wound necrosis, nipple complications, implant loss, or capsular contracture were found. Analysis of reoperations between patients with and without prior augmentation revealed no significant differences in average number of subsequent planned, unplanned, or total reoperations. On multivariate analysis, prior breast augmentation was found to be associated with significantly increased risk for undergoing ≥1 unplanned reoperation (odds ratio, 2.28; 95% confidence interval, 1.28–4.05, P = 0.005). Conclusions Prior augmentation mammoplasty does not significantly affect rates of postoperative complications after mastectomy with concurrent reconstruction. Although prior augmentation does not affect number of subsequent reoperations on average, it does increase the risk of experiencing 1 or more unplanned reoperation after mastectomy with reconstruction.

AbstractObjectivesMatrix differences among serum samples from non-pregnant and pregnant patients could bias measurements. Standard Reference Material 1949, Frozen Human Prenatal Serum, was developed to provide a quality assurance material for the measurement of hormones and nutritional elements throughout pregnancy.MethodsSerum from non-pregnant women and women in each trimester were bottled into four levels based on pregnancy status and trimester. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods were developed and applied to the measurement of thyroid hormones, vitamin D metabolites, and vitamin D-binding protein (VDBP). Copper, selenium, and zinc measurements were conducted by inductively coupled plasma dynamic reaction cell MS. Thyroid stimulating hormone (TSH), thyroglobulin (Tg), and thyroglobulin antibody concentrations were analyzed using immunoassays and LC-MS/MS (Tg only).ResultsCertified values for thyroxine and triiodothyronine, reference values for vitamin D metabolites, VDBP, selenium, copper, and zinc, and information values for reverse triiodothyronine, TSH, Tg, and Tg antibodies were assigned. Significant differences in serum concentrations were evident for all analytes across the four levels (p≤0.003).TSH measurements were significantly different (p<0.0001) among research-only immunoassays. Tg concentrations were elevated in research-only immunoassays vs. Federal Drug Administration-approved automated immunoassay and LC-MS/MS. Presence of Tg antibodies increased differences between automated immunoassay and LC-MS/MS.ConclusionsThe analyte concentrations’ changes consistent with the literature and the demonstration of matrix interferences in immunoassay Tg measurements indicate the functionality of this material by providing a relevant matrix-matched reference material for the different stages of pregnancy.

AbstractBackgroundThe aim of the study was to describe a novel technique for reinforcement of salvage laryngectomy closure using a bipedicled musculofascial submental flap.MethodsA retrospective cohort study design identified patients who underwent salvage laryngectomy reinforcement with a bipedicled submental hammock flap between January 2008 and December 2016 were compared to salvage laryngectomy patients treated with primary closure of the neopharynx during the same time period. Pharyngocutaneous fistula rates were compared between groups.ResultsPharyngocutaneous fistula rate in the submental hammock group (2/31, 6.5%) was significantly lower compared to the primary closure group (14/45, 31%, P < .05).ConclusionThe bipedicled musculofascial submental hammock flap is a viable method for reinforcement of salvage laryngectomy defects. It has a favorable pharyngocutaneous fistula rate compared to primary closure alone and has unique advantages over conventional methods of reinforcement.

Abstract The use of diced cartilage grafting is a powerful tool during rhinoplasty for dorsal augmentation; however, its application to nasal structural reconstruction has rarely been reported. Here we present a unique technique for Mohs defect reconstruction combining diced cartilage graft for dorsal augmentation and a folded paramedian forehead flap for soft tissue. A 54-year-old female presented with recurrent basal cell carcinoma of the nose that had been previously resected 3 times in the past. This was treated with Mohs surgery resulting in a through and through nasal defect. This was reconstructed with a staged folded paramedian forehead flap with staged. Due to a loss of dorsal volume and definition creating an excess supratip break, a diced cartilage graft with fibrin glue and temporalis fascia was used for dorsal augmentation. The use of diced cartilage has regained popularity over the last 2 decades with multiple techniques utilizing diced cartilage alone, wrapped in fascia, covered in fascia, wrapped in oxidized methylcellulose, or solidified with fibrin glue. Literature describing the use of fibrin glue suggests that it improves wound healing by promoting cartilage growth, stabilization, and diffusion of nutrients to the graft. Its malleable nature allows for adjustments after the initial placement. This report demonstrates the viability of diced cartilage graft for dorsal augmentation with a paramedian forehead flap for nasal reconstruction. This technique can serve as a powerful tool for the nasal reconstructive surgeon needing scaffolding to rebuild and define the nasal dorsum.

Abstract Background: Elastomeric respirators are reusable and reliable protection from infectious aerosol particles such as SARS-CoV-2. There is a lack of safety data for use in sterile fields limiting application to operating room settings where high-risk aerosol generating procedures are performed. We hypothesized an equivalent reduction in sterile field contamination would be achieved using an elastomeric respirator covered by a surgical mask as compared to a standard surgical mask or N95.Methods: Randomized controlled crossover experiment with repeat measurement comparing microbial and aerosol contamination of operating room surfaces for elastomeric respirators, elastomeric respirators covered by a surgical mask, N95, surgical mask, and no mask. 80 experiments were performed by participants with randomized order and balanced crossover to all masking groups (n=16 per masking group). Participants executed droplet and aerosol generating procedures while wearing: (Group 1) elastomeric respirator with mask, (Group 2) elastomeric respirator only, (Group 3) N95, and (Group 4) surgical mask. Positive control was established with the participant unmasked (Group 5). Contamination was measured by microbial growth on settling plates and optical particle counters (0.2+ and 2 um+ particles).Results: There was a reduction in microbial contamination at the sterile field (p<0.001) for all masks (Groups 1-4) compared to unmasked (Group 5). The mean colony forming units (CFU) at the sterile field was 0 CFUs for elastomeric respirator (+/- mask), N95, and surgical mask versus unmasked growing 1.875 CFUs. Compared to the unmasked control, the elastomeric respirator (+/- mask), N95, and surgical masks all resulted in a -0.75 difference in contamination (95% CI -0.91 to -0.48, p < 0.001). No significant difference in contamination between the elastomeric respirator (+/- mask) and a surgical mask was detected. No significant difference in particle counts (0.2 µm+ and 2.0 µm+) between the elastomeric respirator (+/- mask) and a standard surgical mask.Conclusion and Relevance: Elastomeric respirators with or without mitigation are as effective as a surgical mask and N95 for reducing contamination at the sterile field in an operating room. Consideration should be given to expanding the use of elastomeric respirators to operating rooms during high-risk aerosol generating procedures.