Performance Differences in Elite National Basketball Association and Women's National Basketball Association Players Based Upon Whether the Dominant or Non-dominant Achilles Tendon Was Ruptured.

Background National Basketball Association (NBA) and Women's National Basketball Association (WNBA) players with Achilles tendon ruptures have previously been noted to have a significant decline in performance post-injury. There has been recent anecdotal evidence that elite players with dominant Achilles tendon ruptures may be able to return at a higher level of play post-rupture. Objective This study aimed to evaluate for any differences in performance in higher-performing NBA and WNBA players with dominant versus non-dominant Achilles tendon ruptures pre- and post-injury. Methods This study was conducted at the University of Pennsylvania, Department of Physical Medicine and Rehabilitation. NBA and WNBA players with an Achilles tendon rupture from 1990 to 2020 were identified. Only elite players, indicated by an average player efficiency rating (PER) of >15 in either of the three seasons pre/post-injury, were included. The average PER, offensive rating, defensive rating, and usage percentage were compared in the three seasons pre- and post-injury. Results Eighteen players met the inclusion criteria, and nine each were classified as dominant and non-dominant Achilles tendon ruptures based on their primary shooting hand. There was no significant difference between the dominant and non-dominant rupture groups in any outcomes pre-injury, including age. The non-dominant cohort had a significant decline in PER (20.04 vs. 14.16; p < 0.001) and offensive rating (110.33 vs. 101.56; p = 0.004) post-injury. There was no significant difference observed post-injury in defensive rating or usage percentage. The dominant cohort had no significant difference in any outcomes post-injury, returning to the same level of play as pre-injury. Despite no difference existing between the groups at baseline, the dominant group performed significantly better post-rupture with regard to PER (19.56 vs. 14.16; p < 0.001) and offensive rating (114.00 vs. 101.56; p < 0.001) versus the non-dominant group. Conclusion Elite NBA and WNBA players with dominant Achilles tendon ruptures had no change in performance post-injury, returning to the same level of production as pre-injury. Post-rupture, they demonstrated notably superior outcomes versus the non-dominant group with regard to PER and offensive rating. The non-dominant rupture group experienced the same decline in PER and offensive rating post-injury observed in previous studies. The data indicate that elite NBA and WNBA players with a dominant Achilles tendon rupture have a much more favorable recovery post-injury and are able to return to the same level of performance.

Adhesive Capsulitis Following Improper Tetanus-Diphtheria (Td) Booster Administration.

Adhesive capsulitis following vaccination is a rare complication secondary to improper intramuscular (IM) deltoid vaccine administration. It is considered a subset of the broad category known as shoulder injury related to vaccine administration (SIRVA). SIRVA typically results from improper shoulder anatomic localization prior to injection, leading to erroneous placement of the needle into the glenohumeral joint capsule or subacromial space. This can trigger a wide array of pathologies, including adhesive capsulitis. We present the first known case of adhesive capsulitis following improper tetanus-diphtheria (Td) vaccine administration. The patient, a previously healthy middle-aged female, began experiencing significant anterior left shoulder pain the day following a Td booster vaccination. She remarked receiving the injection "higher up" in the shoulder than normal. Over the next two weeks, she began noting significant shoulder stiffness, which was followed by a progressive loss of shoulder range of motion. Her symptoms persisted for four months without definitive diagnosis or treatment. After four months of symptoms, the patient visited an outpatient sports medicine clinic where the diagnosis of adhesive capsulitis was made. Although the patient was referred for physical therapy, focusing on gentle range of motion (ROM) and stretches, followed by a planned isometric strengthening program once ROM improved, she was eventually lost to follow-up, and her recovery is unclear. Given the rarity of the diagnosis, it is unclear if adhesive capsulitis, secondary to improper IM vaccination, follows the same temporal course as "classic" adhesive capsulitis or results in a different timeframe of recovery. Further studies are needed on this subject.

Improvement in "Jumping Stump" Syndrome Following Diagnostic Sciatic Nerve Block and Home Exercise Program in a Transtibial Amputee.

"Jumping Stump" syndrome is a rare postoperative complication seen in the residual limb of amputees, with only a few cases documented in the literature. It has been defined as a peripherally induced movement disorder leading to either dystonia, myoclonus, tremors, or choreiform movements in the amputated residual limb. It is often associated with significant discomfort and an inability to ambulate with a prosthetic limb. Treatment options remain inconclusive at this time. We present a case of "Jumping Stump" syndrome in a young female transtibial amputee following revision transtibial amputation (TTA) with myodesis and targeted muscle reinnervation. About six weeks after revision surgery, the patient started experiencing significant myoclonus of the right residual limb when extending the knee. She was trialed on various oral pharmacologic agents over six months and had multiple prosthetic adjustments without any symptomatic relief. Moreover, the patient was also prescribed a daily knee range of motion (ROM) and stretching program. Six months after symptom onset, she underwent a diagnostic right sciatic nerve block and right biceps femoris point block with immediate and significant improvement in symptoms. She had a greater ROM in the affected limb without myoclonus and was able to ambulate once again with her prosthetic limb. Our patient's response to a diagnostic nerve and motor point block, as well as her marked improvement of symptoms with a consistent home exercise (stretching) program, suggests that desensitization of a muscle-tendon stretch response likely accounted for the improvement of symptoms. It is hypothesized that chemodenervation via botulinum toxin, in addition to the consistent home stretching program, would have accelerated the improvement of symptoms and should be further explored as a potential treatment modality for "Jumping Stump" syndrome.

Self-reporting of Conflicts of Interest by Ophthalmology Researchers Compared with the Open Payments Database Industry Reports.

PURPOSE: To evaluate the completeness of conflict-of-interest self-reporting by ophthalmology researchers and to assess factors associated with self-reporting. DESIGN: Cross-sectional observational study. PARTICIPANTS: We evaluated articles published between January and June 2017 in Ophthalmology, JAMA Ophthalmology, the American Journal of Ophthalmology, and Investigative Ophthalmology and Visual Science. To assess more accurately the cases in which an author published multiple articles, we defined a unit of analysis, authorship, for which each author of each article is a unique data point. To enable comparison with the Open Payments Database (OPD), we only included United States physician authorships. METHODS: For each authorship, we defined self-reported relationships as the companies listed in the article's conflict-of-interest disclosures. Based on journal policies, we defined OPD-reported relationships as the list of companies that reported payments to the author within 36 months before submission. MAIN OUTCOME MEASURES: For each authorship, we assessed the proportion of OPD-reported relationships that were self-reported. The primary measurement was the proportion of authorships reporting none of their OPD-reported relationships. RESULTS: Of the 660 total authorships (486 unique authors), 413 authorships (63%) reported none of their OPD-reported relationships, 112 (17%) reported some of them, 9 (1%) reported all of them, and 126 (19%) had 0 relationships. The proportion of authorships reporting none of their relationships did not differ significantly between journals that required reporting of all relationships compared with journals that required reporting only of relevant relationships (adjusted percentage, 61.4% vs. 64.3%; P = 0.46). Authorships with more dollars received during the reporting period showed higher rates of self-reporting (P < 0.001). CONCLUSIONS: Even among journals that required complete reporting, self-reporting was low compared with an industry-maintained database of financial relationships. Deficiencies in reporting may undermine confidence in self-reporting and may compromise the transparency that is needed to interpret research results fairly. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Integrating primary care, shared decision making, and community engagement to facilitate equitable access to multi-cancer early detection clinical trials.

Effective implementation of cancer screening programs can reduce disease-specific incidence and mortality. Screening is currently recommended for breast, cervical, colorectal and lung cancer. However, initial and repeat adherence to screening tests in accordance with current guidelines is sub-optimal, with the lowest rates observed in historically underserved groups. If used in concert with recommended cancer screening tests, new biospecimen-based multi-cancer early detection (MCED) tests could help to identify more cancers that may be amendable to effective treatment. Clinical trials designed to assess the safety and efficacy of MCED tests to assess their potential for reducing cancer mortality are needed and many are underway. In the conduct of MCED test trials, it is crucial that participant recruitment efforts successfully engage participants from diverse populations experiencing cancer disparities. Strategic partnerships involving health systems, clinical practices, and communities can increase the reach of MCED trial recruitment efforts among populations experiencing disparities. This goal can be achieved by developing health system-based learning communities that build understanding of and trust in biomedical research; and by applying innovative methods for identifying eligible trial patients, educating potential participants about research trials, and engaging eligible individuals in shared decision making (SDM) about trial participation. This article describes how a developing consortium of health systems has used this approach to encourage the uptake of cancer screening in a wide range of populations and how such a strategy can facilitate the enrollment of persons from diverse patient and community populations in MCED trials.

How Would You Screen This Patient for Colorectal Cancer? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Colorectal cancer (CRC) is the third leading cause of cancer death for men and women in the United States, with an estimated 52 580 people expected to die in 2022. Most frequently, CRC is diagnosed among persons aged 65 to 74 years. However, among persons younger than 50 years, incidence rates have been increasing since the mid-1990s. In 2021, partially because of the rising incidence, the U.S. Preventive Services Task Force (USPSTF) recommended CRC screening for adults aged 45 to 49 years (Grade B recommendation). Options for CRC screening include stool-based and direct visualization tests. The USPSTF did not recommend a specific screening test; rather, its guidance was to select a test after a discussion with the patient. Here, a primary care physician and a gastroenterologist discuss the recommendation to begin CRC screening at age 45, review options for CRC screening, and discuss how to choose among the available options.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Reevaluating the Evidence for Intensive Postoperative Extracolonic Surveillance for Nonmetastatic Colorectal Cancer.

OBJECTIVES: The FACS, GILDA, and COLOFOL trials have cast doubt on the value of intensive extracolonic surveillance for resected nonmetastatic colorectal cancer and by extension metastasectomy. We reexamined this pessimistic interpretation. We evaluate an alternative explanation: insufficient power to detect a realistically sized survival benefit that may be clinically meaningful. METHODS: A microsimulation model of postdiagnosis colorectal cancer was constructed assuming an empirically plausible efficacy for metastasectomy and thus surveillance. The model was used to predict the large-sample mortality reduction expected for each trial and the implied statistical power. A potential recurrence imbalance in the FACS trial was investigated. Goodness of fit between model predictions and trial results were evaluated. Downstream life expectancy was estimated and power calculations performed for future trials evaluating surveillance and metastasectomy. RESULTS: For all 3 trials, the model predicted a mortality reduction of ≤5% and power of <10%. The FACS recurrence imbalance likely led to a large relative bias (>2.5) in the hazard ratio for overall survival favoring control. After adjustment, both COLOFOL and FACS results were consistent with model predictions (P>.5). A 2.6 (95% credible interval 0.5-5.1) and 3.6 (95% credible interval 0.8-7.0) month increase in life expectancy is predicted comparing intensive extracolonic surveillance-routine computed tomography scans and carcinoembryonic antigen assays-with 1 computed tomography scan at 12 months or no surveillance, respectively. An adequately sized surveillance trial is not feasible. A metastasectomy trial should randomize at least 200 to 300 patients. CONCLUSIONS: Recent trial results do not warrant de novo skepticism of metastasectomy nor targeted extracolonic surveillance. Given the potential for clinically meaningful life-expectancy gain and significant uncertainty, a trial of metastasectomy is needed.

Phase I double-blind, placebo-controlled trial of dolcanatide (SP-333) 27 mg to explore colorectal bioactivity in healthy volunteers.

Guanylyl cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of the luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Previous studies revealed that linaclotide, an oral GUCY2C agonist formulated for gastric release, did not persist to activate guanylyl cyclase signaling in the distal rectum. Dolcanatide is an investigational oral uroguanylin analog, substituted with select D amino acids, for enhanced stability and extended persistence to activate GUCY2C in small and large intestine. However, the ability of oral dolcanatide to induce a pharmacodynamic (PD) response by activating GUCY2C in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of oral dolcanatide 27 mg daily for 7 d to healthy volunteers did not activate GUCY2C, quantified as accumulation of its product cyclic GMP, in epithelial cells of the distal rectum. These data reveal that the enhanced stability of dolcanatide, with persistence along the rostral-caudal axis of the small and large intestine, is inadequate to regulate GUCY2C across the colorectum to prevent tumorigenesis. These results highlight the importance of developing a GUCY2C agonist for cancer prevention formulated for release and activity targeted to the colorectum.

miCLIP-MaPseq Identifies Substrates of Radical SAM RNA-Methylating Enzyme Using Mechanistic Cross-Linking and Mismatch Profiling.

The family of radical SAM RNA-methylating enzymes comprises a large group of proteins that contains only a few functionally characterized members. Several enzymes in this family have been implicated in the regulation of translation and antibiotic susceptibility, emphasizing their significance in bacterial physiology and their relevance to human health. While few characterized enzymes have been shown to modify diverse RNA substrates, highlighting potentially broad substrate scope within the family, many enzymes in this class have no known substrates. The precise knowledge of RNA substrates and modification sites for uncharacterized family members is important for unraveling their biological function. Here, we describe a strategy for substrate identification that takes advantage of mechanism-based cross-linking between the enzyme and its RNA substrates, which we named individual-nucleotide-resolution cross-linking and immunoprecipitation combined with mutational profiling with sequencing (miCLIP-MaPseq). Identification of the position of the modification site is achieved using thermostable group II intron reverse transcriptase (TGIRT), which introduces a mismatch at the site of the cross-link.

Thyroid eye disease with choroidal folds.

Purpose: To determine the clinical course of patients with chorioretinal folds (CRF) in thyroid eye disease (TED).Methods: A multi-center retrospective case series of patients with TED who developed CRF.Results: Ten patients (17 eyes) with CRF related to TED were identified. The mean age of presentation was 59.3 ± 8.3 years old. The majority of patients were male (70%), hyperthyroid (70%), hyperopic (53%), had a history of radioactive iodine (60%), and currently on methimazole treatment (30%). Three patients (3 eyes) had unilateral involvement of CRF with bilateral TED. The average clinical activity score was 3.6 ± 2.1 at the time of presentation. The most commonly enlarged extraocular muscles were medial (76%), inferior (64%), superior (64%) and lateral rectus (35%). Compressive optic neuropathy was seen in 47% of eyes. Treatment included oral prednisone (70%), orbital decompression (59%), thyroidectomy (20%) and tocilizumab (10%). The CRF did not resolve over a follow up period of 24.7 ± 23.7 months in 70% of eyes. There was no significant difference in average axial length (25.7 ± 4.9 mm) and optic nerve to optic strut distance (37.8 ± 3.9 mm) between patients with CRF and the eight age-and sex-matched TED control patients without CRF (p = 0.81 and 0.65 respectively). A univariable and multivariable analysis found an enlarged inferior rectus as a factor in TED patients with persistent CRF.Conclusions: CRF are often an indicator of visually threatening situations and often do not resolve despite treatment of TED.

Real-time Assessment of the Development and Function of the Placenta Across Gestation to Support Therapeutics in Pregnancy.

The placenta is vital to the health and development of the fetus, serving to deliver oxygen and nutrients, facilitate the removal of waste products, and provide a barrier to pathogens and other harmful substances present in the maternal circulation. When these processes fail to operate normally, they can lead to complications of pregnancy such as preeclampsia or fetal growth restriction. The development of novel therapeutics for the mother, fetus, or placenta requires a mechanistic understanding of the development and functions of the placenta. For the obstetric clinician, being able to monitor the placenta throughout the pregnancy and to measure the impact of any treatment modality on the mother and the developing fetus are essential for providing the best possible care. The Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health has been a longtime supporter of research on the placenta. In 2014, the Human Placenta Project was initiated to help to drive an understanding of the biology of the human placenta and to facilitate the development of novel tools and approaches to allow for safe, noninvasive, real-time assessment of the placenta across pregnancy. Those efforts, along with others from around the globe, are showing promise. Although not yet ready for clinical application, these advances are moving the field forward and are certain to have a tremendous impact on the development and assessment of therapeutics designed for treating conditions of pregnancy.