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Abstract Context Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia. Objectives The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT’s role for dystonia. Methods A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review. Results Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson’s disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia. Conclusions Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.

Study Design. Literature review and institutional analysis. Objective. This review examines the potential advantages of awake spinal surgery under neuroaxial anesthesia in minimizing positioning-related complications compared with traditional general anesthesia. Summary of Background Data. Spinal surgeries performed in the prone position under general anesthesia are associated with perioperative complications, such as ocular injury and vision loss, nerve damage, and pressure ulcers. Materials and Methods. A comprehensive literature search was conducted for articles published from 1986 to 2023 focusing on awake spinal surgery and positioning-related complications. In addition, insights from the Mayo Clinic team were incorporated to assess the potential benefits of awake spine surgery. Results. The review identified several positioning-related complications associated with prone positioning during spine surgery, including perioperative visual loss, neuropathies, pressure ulcers, and intra-abdominal hypertension leading to systemic cardiovascular effects and potential organ dysfunction. Advances at the Mayo Clinic have enabled the use of awake spinal surgery under neuroaxial anesthesia for complex procedures such as robotic transforaminal lumbar interbody fusion. The use of awake lumbar spine surgery has demonstrated advantages, including reduced positioning-related complications, immediate patient feedback to avoid harmful maneuvers, shorter operating room times, and improved hemodynamic stability. Conclusions. Awake lumbar spine surgery offers notable advantages in reducing positioning-related complications and presents a promising alternative to general anesthesia.

Background: Abdominal musculature injuries comprise the third most prevalent time-loss injury across professional baseball. Despite increased awareness and prevention attempts in the recent decade, the trends of these abdominal injury numbers in Major League Baseball (MLB) are not fully understood. Purposes: To update the trends in oblique and intercostal injuries, analyze the impact of these injuries based on time out of play, and identify factors that correlate with increased injury severity to help with recovery time prognostication for the sports medicine community. Study Design: Descriptive epidemiology study. Methods: Using the MLB Health and Injury Tracking System, the authors identified all abdominal and core musculature injuries that resulted in time out of play in MLB and Minor League Baseball (MiLB) between the 2011 and 2021 seasons. These were filtered for injuries that resulted in ≥1 days missed (DM) during spring training, the regular season, and postseason. A Student t test was utilized to assess for significant differences for all normally distributed values. Regression analysis was utilized for determining change over time. For all statistical comparisons, the threshold for alpha was set to P < .05. Results: During the study period between 2011 and 2021, there were 4560 total abdominal injuries among 3401 athletes. When filtered for in-season, time-loss injuries defined as spring training, regular season, and postseason, there were 2890 injuries. Of these, 1928 were oblique injuries, 453 were intercostal injuries, and 115 were rectus injuries. The number of oblique injuries each season increased for all of baseball ( P < .001), as well as for MLB ( P = .009) and MiLB ( P = .012) individually. Of the 1928 oblique injuries, 498 (26%) oblique injuries occurred at the MLB level and 1430 (74%) occurred at the MiLB level. Batting and pitching-related injuries comprised 860 (45%) and 729 (38%) oblique injuries, with a total of 18,455 DM and 20,891 DM, respectively. This corresponded to a mean of 22 DM for batting injuries and 29 DM for pitching injuries (mean difference, 7.2; 95% CI, 5.27-9.13; P < .001). Conclusion: This decade-long study on professional baseball revealed a significant increase in abdominal oblique injuries across MLB and MiLB, with the largest number of injuries observed in the 2021 season. Meanwhile, there was a significant decrease in intercostal injuries across professional baseball during these years. Such injuries continue to pose challenges, leading to substantial DM per injury and affecting players from various positions.

BACKGROUND Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP. METHODS In this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples. RESULTS An early and sustained clinical response was seen, with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8 + , and CXCL13 + cytotoxic T cell population in LP skin and demonstrated a rapid decrease in IFN signature within 2 weeks of treatment, most prominently in the basal layer of the epidermis. CONCLUSION This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. TRIAL REGISTRATION NCT05188521 FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell–engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Abstract INTRODUCTION Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within non‐Hispanic White (NHW) populations. Here we provide an extensive survey of the proteomic landscape of AD across diverse racial/ethnic groups. METHODS Two cortical regions, from multiple centers, were harmonized by uniform neuropathological diagnosis. Among 998 unique donors, 273 donors self‐identified as African American, 229 as Latino American, and 434 as NHW. RESULTS While amyloid precursor protein and the microtubule‐associated protein tau demonstrated higher abundance in AD brains, no significant race‐related differences were observed. Further proteome‐wide and focused analyses (specific amyloid beta [Aβ] species and the tau domains) supported the absence of racial differences in these AD pathologies within the brain proteome. DISCUSSION Our findings indicate that the racial differences in AD risk and clinical presentation are not underpinned by dramatically divergent patterns in the brain proteome, suggesting that other determinants account for these clinical disparities. Highlights We present a large‐scale proteome (∼10,000 proteins) of DLPFC (998) and STG (244) across AD cases. About 50% of samples were from racially and ethnically diverse brain donors. Key AD proteins (amyloid and tau) correlated with CERAD and Braak stages. No significant race‐related differences in amyloid and tau protein levels were observed in AD brains. AD‐associated protein changes showed a strong correlation between the brain proteomes of African American and White individuals. This dataset advances understanding of ethnoracial‐specific AD pathways and potential therapies.

Background and Aims: Sarcopenia is highly prevalent in patients with liver cirrhosis and is associated with adverse clinical outcomes, including HE. Androgen receptor agonists, androgen receptor agonists, can address these conditions through multimodal mechanisms of action; however, their safety and efficacy in patients with cirrhosis have not been well established. Approach and Results: In this multicenter, double-blind, phase 2 trial, men with sarcopenia and cirrhosis awaiting liver transplant were randomized 1:1 to receive either oral Androgen Receptor Agonist LPCN 1148 or placebo for 24 weeks (NCT04874350). The primary end point was the change from baseline to 24 weeks in skeletal muscle index measured by a CT scan of the L3 region, analyzed with a prespecified modified intent-to-treat population. The secondary end point was the number of overt HE events. Twenty-nine participants (mean age=59 y, MELD=17) received at least 1 dose of LPCN 1148 (n=15) or placebo (n=14). Baseline characteristics were similar between groups. Primary end point analysis demonstrated an increase in L3-skeletal muscle index measured by a CT scan of the L3 region in the LPCN 1148 group (n=15) compared to placebo (n=10), with a mean group difference of 4.4 cm2/m2 (95% CI: 1.3–7.4 cm2/m2, p=0.007). Participants in LPCN 1148 experienced fewer episodes of overt HE (Common Terminology Criteria for Adverse Events grade ≥2; p=0.02) than placebo. The number and severity of treatment-emergent adverse events were similar between arms. Conclusions: LPCN 1148 treatment improved sarcopenia and reduced the number of overt HE episodes in men with cirrhosis and sarcopenia awaiting liver transplant. These findings support additional research on the efficacy of LPCN 1148 in treating sarcopenia and preventing HE recurrence.

Background: Patients with persistent symptomatic iliopsoas tendonitis following total hip arthroplasty may benefit from iliopsoas fractional lengthening. We present an arthroscopic approach utilizing an air bursogram that provides safe and predictable access to the iliopsoas tendon for efficient tendon lengthening without violating the capsule or unintentional instrumentation of the nearby medial neurovascular bundle. Indications: Arthroscopic iliopsoas fractional lengthening is indicated for patients with clinical evidence of symptomatic iliopsoas tendonitis following total hip arthroplasty and have no radiographic evidence of frank acetabular malpositioning. A diagnosis of iliopsoas tendinitis amenable to surgical management can be established with substantial but nondurable relief following image-guided anesthetic injection to the iliopsoas bursa. Technique Description: Under fluoroscopic guidance, an air bursogram is employed in the anatomic plane of the iliopsoas tendon to accurately identify its course. This allows for hip portal placement with precise subsequent instrumentation. This technique is preferred in the setting of postarthroplasty anatomy because it avoids capsular violation and the challenge of working in an altered anatomic space with a nearby, medially based neurovascular bundle. Results: Arthroscopic and endoscopic approaches to iliopsoas release have been shown to provide excellent functional and patient-reported outcomes in >85% of patients, and several studies have shown that an arthroscopic approach not only provides a less invasive technique but also results in comparable or improved clinical outcomes with lower revision rates compared to open release or acetabular cup revision. Our technique for arthroscopic iliopsoas fractional lengthening using the air bursogram is both safe and reproducible and offers distinct advantages, including maintenance of an intact capsule, visual confirmation of the correct anatomic structure to be released, and percutaneous access with standard arthroscopic access cannulas without the need for hip distraction. Conclusions: Arthroscopic fractional iliopsoas lengthening is a minimally invasive and successful treatment option for patients with persistent groin pain after total hip arthroplasty, especially without substantial acetabular component malpositioning. This technique includes using an air bursogram to safely identify and navigate to the iliopsoas tendon without violating the hip capsule, thereby reducing the risk of inadvertent instrumentation of adjacent critical neurovascular structures. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

Abstract Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi is critical to avoid unnecessary increased risk of normal tissue toxicity. In this study, we used GBM patient-derived xenografts (PDX) in orthotopic murine models to study the relationship between molecular features, pharmacokinetics, and the radiosensitizing potential of the DNA-PKi peposertib. We show that peposertib radiosensitizes established and PDX GBM lines in vitro at 300 nmol/L and above, with a significant increase in radiosensitization by maintaining post-IR exposure for &gt;12 hours. Radiosensitization by peposertib is mediated by catalytic inhibition of DNA-PK, and knockdown of DNA-PK by short hairpin RNA (shRNA) largely abolished the radiosensitizing effect. Peposertib decreased auto-phosphorylation of DNA-PKcs after IR in a dose-dependent manner with a delay in resolution of γH2AX foci at 24 hours. The addition of peposertib to IR significantly increased survival in GBM120 orthotopic xenografts, but not in GBM10. There was no difference in plasma or average tumor concentrations of peposertib in the two cohorts. Although the mechanism underpinning this discordant effect in vitro versus in vivo is not clear, there was an association for greater sensitization in TP53 mutant lines. Transfection of a dominant-negative TP53 mutant in baseline TP53 wild-type GBM lines significantly delayed growth and decreased nonhomologous end joining efficiency (but not homologous recombination), after peposertib exposure. See related commentary by Buchsbaum, p. 840

Abstract One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed 10 principles that could be translated to controlling cancers: (i) prevent onset, (ii) monitor continuously, (iii) identify thresholds below which there will be no intervention, (iv) change interventions in response to burden, (v) preferentially select nonchemical control methods, (vi) use target-specific drugs, (vii) use the lowest effective dose, (viii) reduce cross-resistance, (ix) evaluate success based on long-term management, and (x) forecast growth and response. These principles are general to all cancers and cancer drugs and so could be employed broadly to improve oncology. Here, we review the parallel difficulties in controlling drug resistance in pests and cancer cells. We show how the principles of resistance management in pests might be applied to cancer. Integrated pest management inspired the development of adaptive therapy in oncology to increase progression-free survival and quality of life in patients with cancers where cures are unlikely. These pest management principles have the potential to inform clinical trial design.