Citations

Case: Acute medial collateral ligament (MCL) tears of the great toe metatarsophalangeal joint are rare, leading to sparse literature regarding their management. Suture anchor repair with suture tape augmentation is an effective treatment of thumb ulnar collateral ligament tears, a close analog. This case report presents a 23-year-old professional surfer with an acute hallux MCL avulsion. Management included repair with suture anchor and suture tape augmentation. The patient returned to sport quickly and had no pain or complications at 1-year follow-up. Conclusion: In this case of acute MCL tear of the great toe, suture anchor repair with suture tape augmentation facilitated early mobilization, rapid rehabilitation, return to competitive sport, and sustained good outcome. Level of Evidence: Level V

BACKGROUND AND OBJECTIVES: Sacrectomy is often the treatment of choice to provide the greatest chance of progression-free and overall survival for patients with primary malignant bone tumors of the sacrum. After midsacrectomy, the stability of the sacropelvic interface is diminished, resulting in insufficiency fractures. Traditional stabilization involves lumbopelvic fixation but subjects normal mobile segments to fusion. The purpose of this study was to determine whether standalone intrapelvic fixation is a safe adjunct to midsacrectomy, avoiding both sacral insufficiency fractures and the morbidity of instrumenting into the mobile spine. METHODS: A retrospective study identified all patients who underwent resection of sacral tumors at 2 comprehensive cancer centers between June 2020 and July 2022. Demographic, tumor-specific, operative characteristics and outcome data were collected. The primary outcome was presence of sacral insufficiency fractures. A retrospective data set of patients undergoing midsacrectomy without hardware placement was collected as a control. RESULTS: Nine patients (5 male, 4 female), median age 59 years, underwent midsacrectomy with concomitant placement of standalone pelvic fixation. No patients developed insufficiency fractures during the 216 days of clinical and 207 days of radiographic follow-up. There were no adverse events attributable to the addition of standalone pelvic fixation. In our historical cohort of partial sacrectomies without stabilization, there were 4/25 patients (16%) with sacral insufficiency fractures. These fractures appeared between 0 and 5 months postoperatively. CONCLUSION: A novel standalone intrapelvic fixation after partial sacrectomy is a safe adjunct to prevent postoperative sacral insufficiency fractures in patients undergoing midsacrectomy for tumor. Such a technique may allow for long-term sacropelvic stability without sacrificing mobile lumbar segments.

Background Immune checkpoint inhibitors (ICIs) are now a first-line treatment option for patients with pleural mesothelioma with the recent approval of ipilimumab and nivolumab. Mesothelioma has a low tumor mutation burden and no robust predictors of survival with ICI. Since ICIs enable adaptive antitumor immune responses, we investigated T-cell receptor (TCR) associations with survival in participants from two clinical trials treated with ICI. Methods We included patients with pleural mesothelioma who were treated with nivolumab (NivoMes, NCT02497508) or nivolumab and ipilimumab (INITIATE, NCT03048474) after first-line therapy. TCR sequencing was performed with the ImmunoSEQ assay in 49 and 39 pretreatment and post-treatment patient peripheral blood mononuclear cell (PBMC) samples. These data were integrated with TCR sequences found in bulk RNAseq data by TRUST4 program in 45 and 35 pretreatment and post-treatment tumor biopsy samples and TCR sequences from over 600 healthy controls. The TCR sequences were clustered into groups of shared antigen specificity using GIANA. Associations of TCR clusters with overall survival were determined by cox proportional hazard analysis. Results We identified 4.2 million and 12 thousand complementarity-determining region 3 (CDR3) sequences from PBMCs and tumors, respectively, in patients treated with ICI. These CDR3 sequences were integrated with 2.1 million publically available CDR3 sequences from healthy controls and clustered. ICI-enhanced T-cell infiltration and expanded T cell diversity in tumors. Cases with TCR clones in the top tertile in the pretreatment tissue or in circulation had significantly better survival than the bottom two tertiles (p<0.04). Furthermore, a high number of shared TCR clones between pretreatment tissue and in circulation was associated with improved survival (p=0.01). To potentially select antitumor clusters, we filtered for clusters that were (1) not found in healthy controls, (2) recurrent in multiple patients with mesothelioma, and (3) more prevalent in post-treatment than pretreatment samples. The detection of two-specific TCR clusters provided significant survival benefit compared with detection of 1 cluster (HR<0.001, p=0.026) or the detection of no TCR clusters (HR=0.10, p=0.002). These two clusters were not found in bulk tissue RNA-seq data and have not been reported in public CDR3 databases. Conclusions We identified two unique TCR clusters that were associated with survival on treatment with ICI in patients with pleural mesothelioma. These clusters may enable approaches for antigen discovery and inform future targets for design of adoptive T cell therapies.

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.

Levamisole is an anti-helminthic drug with immunomodulatory properties that is added to cocaine to increase its potency and weight. Levamisole-adulterated cocaine (LAC) may cause an antineutrophil cytoplasmic antibody (ANCA)-associated systemic small vessel vasculitis (AAV). We aimed to characterize the phenotype of persons developing pulmonary-renal syndrome (PRS) in LAC-induced AAV and summarize its treatment and outcomes. Pubmed and Web of Science were searched (until September 2022). Reports that described co-existing diffuse alveolar hemorrhage and glomerulonephritis in an adult (age ≥ 18) with confirmed or suspected LAC exposure were included. Reports, demographics, clinical and serologic features, treatment and outcome characteristics were extracted. Of the 280 records identified, eight met the inclusion criteria, including eight unique cases. Persons were aged 22–58 years, and 50% were women. Cutaneous involvement occurred in only half of the cases. Other associated vasculitis findings and serologies were heterogeneous. All patients received immunosuppression with steroids, with cyclophosphamide and rituximab commonly added. We concluded that PRS could occur from LAC-induced AAV. Distinguishing LAC-induced AAV from primary AAV is challenging as clinical and serologic presentations overlap. Asking about cocaine use is requisite in persons presenting with PRS to guide diagnosis and appropriately counsel on cocaine cessation in conjunction with immunosuppression as treatment.

AbstractObjectivesThe aim of this study was to describe the use pattern and outcomes of protamine administration for heparin reversal among sites performing percutaneous left atrial appendage occlusion (LAAO).MethodsWe identified 45,135 patients who underwent LAAO at 243 hospitals participating in Vizient® Clinical Database between January 1, 2016 and December 31, 2021. Patients were stratified according to protamine administration after the procedure. Outcomes of interest included vascular complications, major bleeding, ischemic events, and same‐day discharge.ResultsA total of 40,278 patients were included in the propensity‐matched comparison, of whom 50% received protamine after the LAAO procedure. The use of protamine varied across hospitals, with 88 hospitals (36.2%) using protamine in >75% of cases and 32 hospitals (13.1%) not using protamine at all. Major bleeding occurred less frequently in the protamine group compared with the control group (2.4% vs. 2.8%, p = 0.03). Major vascular complications and pericardial tamponade were rare but slightly higher in the protamine group (0.8% vs. 0.6%, p = 0.04) and (1.0% vs. 0.8%, p = 0.01), respectively. There were no differences in the rates of ischemic or hemorrhagic stroke, all‐cause mortality, or the rate of any major adverse event between the two groups. Same‐day discharge was more frequent in the protamine group (12.3% vs 9.4%, p ≤ 0.001).ConclusionsProtamine is used in approximately 50% of LAAO procedures and is associated with lower bleeding events and higher rates of same‐day discharge. The higher vascular complication and tamponade is likely due to its ad‐hoc use as a reversal agent in these patients.

Background: The N-MOmentum trial investigated safety and efficacy of inebilizumab in participants with neuromyelitis optica spectrum disorder (NMOSD). Objective: Evaluate the attack identification process and adjudication committee (AC) performance in N-MOmentum. Methods: Adults ( n = 230) with NMOSD and Expanded Disability Status Scale score ⩽8 were randomized (3:1) to inebilizumab 300 mg or placebo. The randomized controlled period was 28 weeks or until adjudicated attack. Attacks were adjudicated according to 18 predefined criteria. Magnetic resonance imaging (MRI) and biomarker (serum glial fibrillary acidic protein [sGFAP]) analyses were performed. Results: A total of 64 participant-reported neurological events occurred; 51 (80%) were investigator-determined to be attacks. The AC confirmed 43 of the investigator-determined attacks (84%). There was high inter- and intra-AC-member agreement. In 25/64 events (39%) and 14/43 AC-adjudicated attacks (33%), MRI was reviewed during adjudication. Retrospective analysis revealed new domain-specific T1 and T2 MRI lesions in 90% of adjudicated attacks. Increased mean sGFAP concentrations (>2-fold change) from baseline were observed in 56% of adjudicated attacks versus 14% of investigator-determined attacks rejected by the AC and 31% of participant-reported events determined not to be attacks. Conclusion: AC adjudication of NMOSD attacks according to predefined criteria appears robust. MRI lesion correlates and sGFAP elevations were found in most adjudicated attacks.

Objective To describe the development, implementation, and validation of a radiology-administered protocol to obtain magnetic resonance imaging (MRI) in patients with cochlear implants and auditory brainstem implants without magnet removal. Study Design Retrospective review and description of novel care pathway. Methods A radiology-administered protocol was designed based on careful input from the radiology safety committee and neurotology. Radiology technologist training modules, consent instructions, patient educational material, clinical audits, and other safeguards were implemented, with samples provided in this report. The primary outcomes measured included instances of magnet displacement during MRI and premature termination of MRI studies secondary to pain. Results Between June 19, 2018, and October 12, 2021, 301 implanted ears underwent MRI without magnet removal, including 153 devices housing diametric MRI-conditional magnets, and 148 implants with conventional axial (i.e., nondiametric) magnets. Among cases with diametric MRI-conditional magnets, all studies were completed without magnet dislodgement or need to terminate imaging early due to pain. Among cases with conventional axial (nondiametric) magnets, 29 (19.6%) MRI studies were stopped prematurely secondary to pain or discomfort; the overall rate of this event was 9.6% (29 of 301) among the entire study cohort. In addition, 6.1% (9 of 148) experienced confirmed magnet displacement despite headwrap placement; the overall rate among all cases was 3.0% (9 of 301). Eight of these patients received successful external magnet reseating through manual pressure on the external scalp without surgery, and one required surgical replacement of the magnet in the operating room. There were no documented instances of hematoma, infection, device or magnet extrusion, internal device movement (i.e., gross receiver-stimulator migration), or device malfunction in this cohort related to MRI. Conclusions We present the successful implementation of a radiology-administered protocol designed to streamline care for cochlear implant and auditory brainstem implant recipients who require MRI and ease clinical demands for otolaryngology providers. Examples of resources developed, including a process map, radiology training modules, consent instructions, patient educational materials, clinical audit, and other procedural safety measures are provided so interested groups may consider adapting and implementing related measures according to need.