Post-Treatment surveillance intensity and overall survival in prostate cancer survivors (AFT-30).

BACKGROUND: Post-treatment surveillance affects millions of cancer survivors, but empiric data to guide clinical practice is lacking. This study assessed whether the intensity of surveillance testing after radical prostatectomy (RP) or radiation therapy (RT) for localized prostate cancer is associated with overall survival. METHODS: Men diagnosed with localized prostate cancer between 2005 and 2010 who underwent RP or RT at a Commission on Cancer-accredited facility were randomly sampled. Primary data collected of 10,147 patients sampled across 1007 facilities were linked with existing data from the National Cancer Database. Analysis examined whether intensity of surveillance measured as the number of PSA tests in the first year after primary treatment [categorized as 0-1 (low intensity), 2 (medium) or ≥ 3 (high intensity) PSA tests] was associated with overall survival. Secondary outcomes included recurrence-free survival (RFS) and subsequent use of imaging tests, biopsy procedures, and salvage treatment. RESULTS: Median follow-up exceeded 8 years from prostate cancer diagnosis. OS was not statistically significantly different across surveillance intensity groups among RT (P = .59) or RP (P = .29) patients. RFS was not statistically significantly different across surveillance intensity groups for RT (P = .13) patients, but was for RP (P = .01) patients with high intensity associated with the worse RFS. In both treatments, higher surveillance intensity was associated with more procedures and salvage treatments. CONCLUSIONS: In patients with localized prostate cancer, more frequent PSA surveillance testing after radical prostatectomy or radiation therapy was associated with increased procedures and salvage treatments but not overall survival.

Self-Reported Financial Difficulties Among Patients with Multiple Myeloma and Chronic Lymphocytic Leukemia Treated at U.S. Community Oncology Clinics (Alliance A231602CD).

Objectives: To estimate the proportion and correlates of self-reported financial difficulty among patients with multiple myeloma (MM) or chronic lymphocytic leukemia (CLL). Setting: 23 U.S. community and minority oncology practice sites affiliated with the National Cancer Institute Community Oncology Research Program (NCORP). Participants: 521 patients (≥18 years) with MM or CLL were consented and 416 responded to a survey (completion rate=79.8%). Respondents had a MM diagnosis (74.0%), an associate degree or higher (53.4%), were White (89.2%), insured (100%) and treated with clinician-administered drugs (68.0%). Interventions: Observational, prospective, protocol-based survey administered in 2019-2020. Primary and secondary outcome measures: Financial difficulty was assessed using a single-item standard measure, the EORTC QLQC30: "Has your physical condition or medical treatment caused you financial difficulties in the past year?" and using an 'any-or-none' composite measure of 22 items assessing financial difficulty, worries and the use of cost-coping strategies. Multivariable logistic regression models assessed the association between financial difficulty, diagnosis, and socioeconomic and treatment characteristics. Results: 16.8% reported experiencing financial difficulty using the single-item measure and 60.3% using the composite measure. Most frequently endorsed items in the composite measure were financial worry about having to pay large medical bills related to cancer and difficulty paying medical bills. Financial difficulty using the single-item measure was associated with having MM versus CLL (adjusted odds ratio [aOR], 0.34; 95% CI, 0.13-0.84; P=.02), having insurance other than Medicare (aOR, 2.53; 95% CI, 1.37-4.66; P=.003), being non-White (aOR, 2.21; 95% CI, 1.04-4.72; P=.04), and having a high school education or below (aOR, 0.36; 95% CI, 0.21-0.64; P=.001). Financial difficulty using the composite measure was associated with having a high school education or below (aOR, 0.62; 95% CI, 0.41-0.94; P=.03). Conclusions: U.S. patients with blood cancer report financial difficulty, especially those with low socio-economic status. Evidence-based and targeted interventions are needed.

A Bioengineered Cathepsin B-sensitive Gas Vesicle Nanosystem That Responds With Increased Gray-level Intensity of Ultrasound Biomicroscopic Images.

OBJECTIVE: This work aimed to promote the interaction of a modified gas vesicle (GV) with cathepsin B (CTSB) protease and analysed their backscattered signal by ultrasound (US). METHODS: We modified the sequence of the gene coding for GvpC to contain a CTSB cleavage and expressed the protein in an Escherichia coli recombinant system. The protein was purified and added to GVs preparations in which the original GvpC was removed (ΔGV), constituting the modified GV (GV*). Western blot testing was used to compare GVs with GvpC and engineered GvpC at starting (T0) and after 24 h (T24) reacting with CTSB. A 21 MHz US B-mode and non-linear contrast mode (5% total power) imaged US phantoms having samples of GVwt, ΔGV (stripped GV), GV* and CTSB + GV*. Also, a 21 MHz US B-mode imaged US phantoms having a tumour cell line extracellular fraction (TCEF) and the TCEF + GV* sample. A 100% total US power was applied to collapse the GV structure. RESULTS: On Western blotting, we detected a decrease in engineered GvpC levels 24 h after the incubation of GV* with CTSB, compared with the concentration at T0, suggesting that CTSB cleaved the engineered GvpC. Regions-of-interest over image of phantom cross-sections were determined and the B-mode image mean grey-level intensity resulted in a significant (p < 0.05) increase comparing CTSB + GV* with PBS (control), GVwt, ΔGV and GV*. Non-linear mode image grey-level intensity from CTSB + GV* increased by 11.79, 7.86 and 14.75 dB from samples containing GVwt, ΔGV and GV*, respectively. GV preparations incubated with TCEF and the TCEF + GV* sample showed an increase of 81% in signal compared with TCEF + GVwt. CONCLUSION: The increased US backscattered signal intensity suggests GVs as a potential biosensor for protease activity, possibly aiding the detection of protease-rich tissue regions.

The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Serous Atrophy of Bone Marrow in the Feet Diagnosed via Magnetic Resonance Imaging: A Case Report.

Serous atrophy of bone marrow (SABM) is characterized by focal replacement of bone marrow elements with extracellular gelatinous substances. It has been associated with a wide range of chronic conditions, including anorexia nervosa, malignancy, chronic kidney disease, and certain chronic infections. Previous literature has reported the disorder as primarily diagnosed via bone marrow biopsy and occurring outside of the distal extremities. Herein we describe a case of SABM occurring in the feet diagnosed via magnetic resonance imaging (MRI), a phenomenon that is rarely reported. The patient is a 45-year-old woman with a history of end-stage renal disease, congestive heart failure, type 2 diabetes, and peripheral arterial disease who initially presented with nonhealing, bilateral foot ulcers. She subsequently underwent several podiatric medical surgeries due to persistent foot infections and poor wound healing. During her most recent hospitalization, MRIs of her feet were obtained, and findings of abnormal bone marrow signal were attributed to technical malfunction of the MRI coil or scanner. After troubleshooting sources of malfunction, a repeated MRI of the foot was obtained and again demonstrated the same bone marrow signal abnormalities; at this time, SABM was diagnosed. Knowledge of this condition can prevent the misinterpretation of SABM on MRI and prevent the waste of time and medical resources.

Elucidating the assembly of gas vesicles by systematic protein-protein interaction analysis.

Gas vesicles (GVs) are gas-filled microbial organelles formed by unique 3-nm thick, amphipathic, force-bearing protein shells, which can withstand multiple atmospheric pressures and maintain a physically stable air bubble with megapascal surface tension. However, the molecular process of GV assembly remains elusive. To begin understanding this process, we have devised a high-throughput in vivo assay to determine the interactions of all 11 proteins in the pNL29 GV operon. Complete or partial deletions of the operon establish interdependent relationships among GV proteins during assembly. We also examine the tolerance of the GV assembly process to protein mutations and the cellular burdens caused by GV proteins. Clusters of GV protein interactions are revealed, proposing plausible protein complexes that are important for GV assembly. We anticipate our findings will set the stage for designing GVs that efficiently assemble in heterologous hosts during biomedical applications.

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model.

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

Leveraging oncology collaborative networks and biomedical informatics data resources to rapidly recruit and enroll rural residents into oncology quality of life clinical trials.

Purpose: This study assesses the feasibility of biomedical informatics resources for efficient recruitment of rural residents with cancer to a clinical trial of a quality-of-life (QOL) mobile app. These resources have the potential to reduce costly, time-consuming, in-person recruitment methods. Methods: A cohort was identified from the electronic health record data repository and cross-referenced with patients who consented to additional research contact. Rural-urban commuting area codes were computed to identify rurality. Potential participants were emailed study details, screening questions, and an e-consent link via REDCap. Consented individuals received baseline questionnaires automatically. A sample minimum of n = 80 [n = 40 care as usual (CAU) n = 40 mobile app intervention] was needed. Results: N = 1298 potential participants (n = 365 CAU; n = 833 intervention) were screened for eligibility. For CAU, 68 consented, 67 completed baseline questionnaires, and 54 completed follow-up questionnaires. For intervention, 100 consented, 97 completed baseline questionnaires, and 58 completed follow-up questionnaires. The CAU/intervention reached 82.5%/122.5% of the enrollment target within 2 days. Recruitment and retention rates were 15.3% and 57.5%, respectively. The mean age was 59.5 ± 13.5 years. The sample was 65% women, 20% racial/ethnic minority, and 35% resided in rural areas. Conclusion: These results demonstrate that biomedical informatics resources can be highly effective in recruiting for cancer QOL research. Precisely identifying individuals likely to meet inclusion criteria who previously indicated interest in research participation expedited recruitment. Participants completed the consent and baseline questionnaires with zero follow-up contacts from the research team. This low-touch, repeatable process may be highly effective for multisite clinical trials research seeking to include rural residents.

Freeze-dried porous collagen scaffolds for the repair of volumetric muscle loss injuries.

Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a 3D aligned collagen-glycosaminoglycan (CG) scaffold platform that supported in vitro myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either non-conductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks post-injury by in vivo electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than non-treated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that was not observed in non-repaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in non-treated tissues. Finally, only tissues treated with non-conductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.

Genetic findings in people with schwannomas who do not meet clinical diagnostic criteria for NF2-related schwannomatosis.

BACKGROUND: Most schwannomas are isolated tumours occurring in otherwise healthy people. However, bilateral vestibular schwannomas (BVS) or multiple non-vestibular schwannomas indicate an underlying genetic predisposition. This is most commonly NF2-related schwannomatosis (SWN), but when BVS are absent, this can also indicate SMARCB1-related or LZTR1-related SWN. METHODS: We assessed the variant detection rates for the three major SWN genes (NF2, LZTR1 and SMARCB1) in 154 people, from 150 families, who had at least one non-vestibular schwannoma, but who did not meet clinical criteria for NF2-related SWN at the time of genetic testing. RESULTS: We found that 17 (11%) people from 13 families had a germline SMARCB1 variant and 19 (12%) unrelated individuals had a germline LZTR1 variant. 19 people had an NF2 variant, but 18 of these were mosaic and 17 were only detected when 2 tumours were available for testing. The overall detection rate was 25% using blood alone, but increased to 36% when tumour analysis was included. Another 12 people had a germline variant of uncertain significance (VUS). CONCLUSIONS: There were similar proportions of LZTR1, SMARCB1 or mosaic NF2. However, since an NF2 variant was detected in tumours from 103 people, it is likely that further cases of mosaicism would be detected if more people had additional tumours available for analysis. In addition, if further evidence becomes available to show that the VUSs are pathogenic, this would significantly increase the proportion of people with a genetic diagnosis. Our results indicate the importance of comprehensive genetic testing and improved variant classification.

Phase 1 study of concomitant tumor treating fields and temozolomide chemoradiation for newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) is the most common and aggressive primary brain tumor and has limited effective therapies. Tumor treating fields (TTF; Optune Gio®) is an FDA-approved device with data supporting a significant survival benefit and minimal toxicity when added to maintenance chemotherapy. Uptake in clinical practice is not universal and might improve if a shorter duration of treatment is feasible. This phase 1 trial was designed to determine the safety and preliminary efficacy of TTF concomitant to chemoradiation. Methods: Patients with newly diagnosed, histologically confirmed GBM were eligible. Following surgery, patients were treated with TTF concomitant to standard chemoradiation. The device continued through 2 monthly cycles of maintenance temozolomide with imaging and clinical assessments at regular intervals to assess toxicity and response. The primary endpoint was the safety and tolerability of combined modality treatment based upon the incidence and severity of adverse events. Secondary endpoints were overall survival (OS) and progression-free survival (PFS). Results: Thirteen patients were enrolled. Dermatologic adverse events were frequent but limited to grade 1/2. There was only 1 serious adverse event possibly related to TTF and no patients were unable to complete the prescribed course of multimodality treatment due to TTF-associated toxicity. Twelve patients were evaluable for median and 6-month progression-free survival which were 8.5 months (mo) and 66.7%, respectively. Median and 12 mo overall survival were 16.0 mo and 83.3%, respectively. Conclusions: TTF can be safely delivered in conjunction with chemoradiation. The potential for a finite TTF course merits further evaluation.

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.

BACKGROUND: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. OBJECTIVE: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. METHODS: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. RESULTS: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. CONCLUSIONS: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.

Clinical and Radiographic results of a Retrograde Nail - Washer Combination Versus Lateral Locked Plating for Distal Femur Fractures.

OBJECTIVES: The objective of this study was to report outcomes of the Retrograde Femoral Nail-Advanced with Lateral Attachment Washer (RFNA-LAW) (Synthes; Paoli, PA) compared to laterally locked plates (LLP) when treating AO/OTA type 33 distal femoral fractures. METHODS: Design: Retrospective chart review. SETTING: Single, academic, Level-1 Trauma Center. PATIENT SELECTION CRITERIA: All adult patients who had fixation of an AO/OTA type 33 distal femoral fracture with the RFNA-LAW combination or LLP from 2018-2023 with follow-up to union or a minimum of one year. immediately post-operatively and at final follow-up. OUTCOME MEASURES AND COMPARISONS: The main outcome measure was union. Secondary outcomes included implant failure, infection, and alignment immediately post-operatively and at final follow-up. Patients were followed for a minimum of 1-year or to skeletal healing. RESULTS: Forty-eight patients (19 female) with a mean age of 56 years (range 19-94 years) were in the RFNA-LAW group. Fifty-three patients (29 female) with a mean age of 66 years (24-91 years) were in the LLP group. There were no significant differences when comparing Body Mass Index, diabetes, smoking status, mechanism of injury, or fracture classification between groups (p>0.05). There was no difference in immediate, post-operative alignment (p = 0.49). When comparing aLDFA measurements at final follow-up, there was significantly more malalignment in the LLP group (p = 0.005). There were 8 implant failures (15%) in the LLP group compared to 1 in the RFNA-LAW group (2%) (p = 0.02). There were 14 reoperations (26%) in the LLP group compared to 4 (8%) in the RFNA-LAW group (p = 0.02). CONCLUSIONS: The Retrograde Nail Advanced - Lateral Attachment Washer combination demonstrated a high union rate when treating complex fractures of the distal femur. When compared to lateral locked plating, this implant combination demonstrated significantly lower rates of nonunion and reoperation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Extended panel testing in ovarian cancer reveals BRIP1 as the third most important predisposition gene.

PURPOSE: The prevalence of germline pathogenic variants (PVs) in homologous recombination repair (HRR) and Lynch syndrome (LS) genes in ovarian cancer (OC) is uncertain. METHODS: An observational study reporting the detection rate of germline PVs in HRR and LS genes in all OC cases tested in the North West Genomic Laboratory Hub between September 1996 and May 2024. Effect sizes are reported using odds ratios (ORs) and 95% confidence intervals (95% CI) for unselected cases tested between April 2021 and May 2024 versus 50,703 controls from the Breast Cancer Risk after Diagnostic Gene Sequencing study. RESULTS: 2934 women were tested for BRCA1/2 and 433 (14.8%) had a PV. In up to 1572 women tested for PVs in non-BRCA1/2 HRR genes, detection rates were PALB2 = 0.8%, BRIP1 = 1.1%, RAD51C = 0.4% and RAD51D = 0.4%. In 940 unselected cases, BRIP1 (OR = 8.7, 95% CI 4.6-15.8) was the third most common OC predisposition gene followed by RAD51C (OR = 8.3, 95% CI 3.1-23.1), RAD51D (OR = 6.5, 95% CI 2.1-19.7), and PALB2 (OR = 3.9, 95% CI 1.5-10.3). No PVs in LS genes were detected in unselected cases. CONCLUSION: Panel testing in OC resulted in a detection rate of 2% to 3% for germline PVs in non-BRCA1/2 HRR genes, with the largest contributor being BRIP1. Screening for LS in unselected cases of OC is unnecessary.

A Fibroblast-Derived Secretome Stimulates the Growth and Invasiveness of 3D Plexiform Neurofibroma Spheroids.

Plexiform neurofibromas (PNs) occur in about a half of neurofibromatosis type 1 (NF1) patients and have garnered significant research attention due to their capacity for growth and potential for malignant transformation. NF1 plexiform neurofibroma (pNF1) is a complex tumor composed of Schwann cell-derived tumor cells (Nf1-/-) and the tumor microenvironment (TME). Although it has been widely demonstrated that the TME is involved in the formation of neurofibromas, little is known about the effects of the TME on the subsequent progression of human pNF1. Elucidating the molecular interactions between tumor cells and the TME may provide new therapeutic targets to reduce the progression of pNF1. In the present study, we focused on the contributions of fibroblasts, the most abundant cell types in the TME, to the growth of pNF1. To simulate the TME, we used a three-dimensional (3D) coculture model of immortalized pNF1 tumor cells (Nf1-/-) and primary fibroblasts (Nf1+/-) derived from pNF1 patients. We performed live-cell imaging of 3D/4D (3D in real-time) cultures through confocal microscopy followed by 3D quantitative analyses using advanced imaging software. The growth of pNF1 spheroids in 3D cocultures with fibroblasts was significantly greater than that of pNF1 spheroids in 3D monocultures. An increase in the growth of pNF1 spheroids also occurred when they were cultured with conditioned media (CM) from fibroblasts. Moreover, fibroblast-derived CM increased the invasive outgrowth and further local invasion of pNF1 spheroids. Interestingly, when small extracellular vesicles (sEVs) were depleted from the fibroblast-derived CM, the stimulation of the growth of pNF1 spheroids was lost. Our results suggest that fibroblast-derived sEVs are a therapeutic target for reducing the growth of pNF1.

Clinical and Radiographic Results After Treatment of Traumatic Syndesmotic Instability Using a Novel Screw-Suture Syndesmotic Fixation Device.

OBJECTIVES: The objective of this study was to report early outcomes of a novel screw-suture syndesmotic device compared with suture button fixation devices when treating traumatic syndesmotic instability. DESIGN: Retrospective chart review. SETTING: Single academic Level 1 Trauma Center. PATIENT SELECTION CRITERIA: All adult patients who had syndesmotic fixation with the novel device [novel syndesmotic repair implant (NSRI) group] compared with a suture button device (SB group) between January 2018 and December 2022. OUTCOME MEASURES AND COMPARISONS: Medial clear space and tibiofibular overlap measurements were compared immediately postoperatively and at the final follow-up. Patients were followed for a minimum of 1 year or skeletal healing. RESULTS: Fifty-nine patients (25 female) with an average age of 47 years (range 19-78 years) were in the NSRI group compared with 52 patients (20 female) with an average age of 41 years (range 18-73 years) in the SB group. There were no significant differences when comparing body mass index, diabetes, or smoking status between groups (P > 0.05). There was no difference when comparing the postoperative and final medial clear space measurements in the NSRI group compared with the SB group (P = 0.86; 95% confidence interval, -0.32 to 0.27). There was no difference when comparing the postoperative and final tibiofibular overlap measurements in the NSRI group compared with the SB group (P = 0.79; 95% confidence interval, -0.072 to 0.09). There were 3 cases of implant removal in the NSRI group compared with 2 in the SB group (P = 0.77). There was 1 failure in the NSRI group and none in the SB group. The remaining patients were all fully ambulatory at the final follow-up (P = 0.35). CONCLUSIONS: A novel screw-suture syndesmotic implant provides the fixation of a screw, and the flexibility of a suture had similar radiographic outcomes compared with suture button fixation devices in treating ankle syndesmotic instability. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Estimated Financial Impact of 2021 Office-Visit Work Relative Unit Updates on Surgical Global Periods.

This cross-sectional study assesses the impact of changes to medical billing and coding work relative value units in 2021.