Results of Randomized Controlled Trials of Platelet-Rich Plasma in Lower Extremity Tendinopathy Are Not Influenced By Industry Sponsorship.

PURPOSE: To determine whether industry affiliation influences the results of randomized controlled trials (RCTs) studying the use of platelet-rich plasma (PRP) for the treatment of patellar or Achilles tendinopathy. METHODS: PubMed, Scopus, Cochrane, and Medline databases were searched in July 2023 for RCTs published between 2009 and July 2023 investigating PRP for treatment of patellar or Achilles tendinopathy. Industry affiliation (IA) was determined by analyzing each study's funding or conflict of interest section. Author disclosures were searched on The American Academy of Orthopaedic Surgeons (AAOS) disclosure database and the Centers for Medicare & Medicaid Services open payments database. An IA designation was given if an author had a relevant disclosure or if the company funding the study manufactured PRP. Otherwise, a non-industry affiliated (NIA) designation was given. Fisher exact analysis was used to determine if PRP had a favorable, no significant, or unfavorable effect on outcome. RESULTS: Analysis was done on 22 studies (10 IA and 12 NIA), with 17 (77.3%) studies reporting a conflict of interest or funding for the research, 4 (18.2%) reporting no conflict of interest, and 1 (4.5%) with no reporting. Of the 22 included studies, 8 (36.4%) reported favorable outcomes regarding PRP utilization and 14 (63.6%) reported no significant effect. Favorable outcomes were found in 4 (40.0%) of the 10 IA studies and no significant effect was reported in 6 (60.0%). The 12 NIA studies included 4 (33.3%) with favorable results and 8 (66.7%) with no significant effect. The comparison between industry affiliation and results reported was not statistically significant (p = 1). CONCLUSION: Results of RCTs evaluating use of PRP on lower extremity tendinopathy were not influenced by industry sponsorship. CLINICAL RELEVANCE: The majority of biomedical research is funded through industry sponsorship. While this relationship is necessary as technologies are developed, it is important to scrutinize studies for evidence of industry bias to understand how this bias may be affecting study results published in the literature.

Most Major Hospitals Fail to Comply with Federal Price Transparency Regulations.

PURPOSE: This study aims to present hospital compliance with federal price transparency regulations for sports medicine procedures. METHODS: Online price estimator and machine-readable files were recovered for U.S. News and World Report's (USNWR) top 100 orthopedic hospitals. From June to November 2023, compliance and monetary values were recorded for each of Centers for Medicare and Medicaid Services (CMS) price transparency regulations. Price estimator data was assessed based on hospital placement in the bottom and top 50 of the 100 institutions under review, as well as by region (Northeast, South, Midwest, West). Statistical analyses included two-sample t-tests and Kruskal Wallis tests. RESULTS: 95% of hospitals had a price estimator tool for both subacromial decompression (Current Procedural Terminology (CPT): 29826) and meniscectomy (CPT: 29881). Only 38% were compliant with all regulations for subacromial decompression and 39% for meniscectomy; the remaining did not list minimum or maximum procedure charges. Higher ranked hospitals were significantly more likely to charge a higher cash price for subacromial decompression and meniscectomy (p = 0.040 and p = 0.009 respectively). Compliance with machine-readable file reporting was poor with less than 20% meeting requirements for each CPT code. Reported prices varied greatly by hospital. CONCLUSIONS: This study demonstrates that USNWR top 100 orthopedic hospitals exhibit poor overall compliance with federal price transparency regulations for sports medicine procedures. Most often they lack full compliance by not reporting minimum or maximum charges as part of their price estimator tool or do not report procedure prices in their machine-readable files. Hospitals also exhibit wide variation in prices reported for specific procedures. CLINICAL RELEVANCE: Consumer price transparency continues to be an important goal in healthcare as it allows patients to make informed decisions when selecting appropriate treatment options and providers. To realize the full benefits of price transparency hospitals should address areas of improvement.

Perioperative Intravenous Dexamethasone Use Is Not Associated with Periprosthetic Joint Infection or Wound Healing Complications Following Shoulder Arthroplasty.

BACKGROUND: Perioperative intravenous (IV) dexamethasone is commonly used in lower extremity total joint arthroplasty to manage postoperative pain and nausea/vomiting, and recent studies have demonstrated that its use may lower rates of acute postoperative medical complications. However, there is limited information regarding the safety and efficacy of IV dexamethasone in patients undergoing total shoulder arthroplasty (TSA). Additionally, there is concern surrounding corticosteroid use prior to surgery as preoperative corticosteroid injections have been associated with adverse outcomes after TSA, including periprosthetic joint infection (PJI) and revision surgery. Thus, the purpose of this study was to evaluate the effect of perioperative IV dexamethasone on 90-day rates of PJI, wound complications, and medical complications after TSA. METHODS: The Premiere national hospital database was used to identify adult patients undergoing elective TSA between 2016 and 2020; patients were excluded if they were under 18 years old, were undergoing revision TSA, or had a prior proximal humerus open reduction internal fixation (ORIF) procedure. Patients who did and did not receive perioperative IV dexamethasone were then compared in both univariate and multivariate analyses. A Bonferroni correction was utilized to adjust for multiple comparisons. The primary endpoint was risk of acute infectious complications within 90 days of surgery, including PJI and wound infection/dehiscence. Secondary endpoints included acute pulmonary, renal, and thromboembolic complications. RESULTS: A total of 135,333 patients underwent TSA during the study period; 61.2% underwent reverse total shoulder arthroplasty (RTSA), 33.8% underwent anatomic total shoulder arthroplasty (ATSA), and 5.0% underwent hemiarthroplasty (HA). From 2016 to 2020, perioperative IV dexamethasone use increased by 135%. Multivariate analysis revealed that patients who received perioperative IV dexamethasone did not have increased odds of PJI, superficial wound infection, or wound dehiscence (p = 0.15 - 0.47) but did have decreased odds of sepsis (OR 0.67, 95% CI 0.55-0.81) and other medical complications such as urinary tract infection (UTI) and acute kidney injury (AKI). Additionally, there was a trend towards decreased 90-day hospital readmission (OR 0.88, 95% CI 0.81-0.96, p=0.003). CONCLUSIONS: Perioperative IV dexamethasone was not associated with increased risk of acute infectious and wound healing complications. Moreover, patients who received perioperative IV dexamethasone had decreased odds of medical complications and trended towards lower rates of 90-day hospital readmission. The results of this study support the safety of perioperative IV dexamethasone use in patients undergoing elective TSA.

Final phase I substudy results of ivosidenib in patients with mutant IDH1 relapsed/refractory myelodysplastic syndrome.

Ivosidenib is a first-in-class mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor and has shown efficacy and tolerability in patients with advanced mIDH1 hematologic malignancies, leading to approval in front-line and relapsed/refractory (R/R) mIDH1 AML populations. We report final data from a phase I single-arm substudy (NCT02074839) of patients with R/R mIDH1 MDS following failure of standard-of-care therapies. Oral ivosidenib was taken once daily on days 1-28 in 28-day cycles. Primary objectives were to determine safety, tolerability, and clinical activity. The primary efficacy endpoint was the complete remission + partial remission (CR+PR) rate. Nineteen patients were enrolled; 18 were included in the efficacy analysis. Treatment-related adverse events occurred in eight (42.1%) patients, including a grade 1 QT interval prolongation in one (5.3%) patient and grade 2 differentiation syndrome in two (10.5%) patients. Rates of CR+PR and objective response (CR +PR+marrow CR) were 38.9% (95% confidence interval [CI]: 17.3, 64.3) and 83.3% (95% CI: 58.6, 96.4), respectively. Kaplan-Meier estimates showed a 68.6% probability of patients in CR achieving a remission duration of >=5 years, and a median OS of 35.7 months. Of note, 71.4% and 75.0% baseline red blood cell (RBC) and platelet transfusion-dependent patients, respectively, became transfusion independent (TI; no transfusion >=56 days); 81.8% and 100% of baseline RBC and platelet TI patients, respectively, remained TI. One (5.3%) patient proceeded to a hematopoietic stem cell transplant by data cut-off. In conclusion, ivosidenib is clinically active, with durable remissions and a manageable safety profile observed in patients with mIDH1 R/R MDS.

Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML.

Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this large R/R AML patient cohort, targeted next-generation sequencing at baseline (screening) revealed distinct co-mutation patterns and mutational burden between subgroups bearing different IDH2 variants: variant IDH2-R140 was associated with greater mutational burden and was enriched predominantly with poor-risk mutations, including FLT3, RUNX1, and NRAS, while variant IDH2-R172 was associated with lower mutational burden and was preferentially co-mutated with DNMT3A. In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.

ASCT2-Targeting Antibody-Drug Conjugate MEDI7247 in Adult Patients with Relapsed/Refractory Hematological Malignancies: A First-in-Human, Phase 1 Study.

BACKGROUND: MEDI7247 is a first-in-class antibody-drug conjugate (ADC) consisting of an anti-sodium-dependent alanine-serine-cysteine transporter 2 antibody-conjugated to a pyrrolobenzodiazepine dimer. OBJECTIVE: This first-in-human phase 1 trial evaluated MEDI7247 in patients with hematological malignancies. PATIENTS AND METHODS: Adults with acute myeloid leukemia (AML), multiple myeloma (MM), or diffuse large B-cell lymphoma (DLBCL) relapsed or refractory (R/R) to standard therapies, or for whom no standard therapy exists, were eligible. Primary endpoints were safety and determination of the maximum tolerated dose (MTD). Secondary endpoints included assessments of antitumor activity, pharmacokinetics (PK), and immunogenicity. RESULTS: As of 26 March 2020, 67 patients were treated (AML: n = 27; MM: n = 18; DLBCL: n = 22). The most common MEDI7247-related adverse events (AEs) were thrombocytopenia (41.8%), neutropenia (35.8%), and anemia (28.4%). The most common treatment-related grade 3/4 AEs were thrombocytopenia (38.8%), neutropenia (34.3%), and anemia (22.4%). Anticancer activity (number of responders/total patients evaluated) was observed in 11/67 (16.4%) patients. No correlation was observed between ASCT2 expression and clinical response. Between-patient variability of systemic exposure of MEDI7247 ADC and total antibody were high (AUCinf geometric CV%: 62.3-134.2, and 74.8-126.1, respectively). SG3199 (PBD dimer) plasma concentrations were below the limit of quantification for all patients after Study Day 8. Anti-drug antibody (ADA) prevalence was 7.7%, ADA incidence was 1.9%, and persistent-positive ADA was 5.8%. CONCLUSIONS: Thrombocytopenia and neutropenia limited repeat dosing. Although limited clinical activity was detected, the dose-escalation phase was stopped early without establishing an MTD. The study was registered with ClinicalTrials.gov (NCT03106428).

A phase 1 study of the irreversible FLT3 inhibitor FF-10101 in relapsed or refractory acute myeloid leukemia.

ABSTRACT: FLT3 tyrosine kinase inhibitors (TKIs) have clinical efficacy for patients with FLT3-mutated AML (acute myeloid leukemia), but their impact is limited by resistance in the setting of monotherapy and by tolerability problems when used in combination therapies. FF-10101 is a novel compound that covalently binds to a cysteine residue near the active site of FLT3, irreversibly inhibiting receptor signaling. It is effective against most FLT3 activating mutations, and, unlike other inhibitors, is minimally vulnerable to resistance induced by FLT3 ligand. We conducted a phase 1 dose escalation study of oral FF-10101 in patients with relapsed and/or refractory AML, the majority of whom harbored FLT3-activating mutations and/or had prior exposure to FLT3 inhibitors. Fifty-four participants enrolled in cohorts receiving doses ranging from 10 to 225 mg per day and 50 to 100 mg twice daily (BID). The dose limiting toxicities were diarrhea and QT prolongation. Among 40 response-evaluable participants, the composite complete response rate was 10%, and the overall response rate (including partial responses) was 12.5%, including patients who had progressed on gilteritinib. Overall, 56% of participants had prior exposure to FLT3 inhibitors. The recommended phase 2 dose was 75 mg BID. FF-10101 potentially represents a next-generation advance in the management of FLT3-mutated AML. This trial was registered at www.ClinicalTrials.gov as #NCT03194685.

Evidence Guiding Commercial Payer Coverage Criteria for Total Ankle Arthroplasty.

Background: Total ankle arthroplasty (TAA), first developed as an alternative to ankle arthrodesis, has become an increasingly popular management option for end-stage ankle arthritis. Prior studies have shown commercial insurance payers base their coverage criteria on limited and low level of evidence research. This study aims to quantify and describe the evidence insurance companies use to support TAA coverage policies. Methods: The top 11 national commercial health insurance payers for TAA were identified. A google search was performed to identify payer coverage policies. Policy documents were examined and cited references were classified by type of reference as well as reviewed for level of evidence (LOE). Specific coverage criteria for each individual payer were then extracted. Criteria were compared to assess for similarities among commercial payers. Finally, all references cited by each payer were examined to determine whether they mentioned the specific payer criteria. Results: Six of the 11 payers had accessible coverage policies. The majority of cited references were primary journal articles (145, 60.9%) and the majority of references cited (179, 75.2%) were level III or level IV evidence. We found significant homogeneity in coverage criteria among payers. In addition, cited sources inconsistently mentioned specific payer coverage criteria. Conclusion: This study demonstrates that commercial insurance payers rely on the relatively low level of currently available scientific evidence when formulating coverage policies for TAA use and adopt criteria that have not been thoroughly analyzed in the literature. More high level of evidence research is needed to help clinicians and insurance companies further refine indications for TAA so that patients who might benefit from the procedure are adequately covered. Level of Evidence: Level IV, review.

Differentiation syndrome associated with treatment with IDH2 inhibitor enasidenib: pooled analysis from clinical trials.

ABSTRACT: Treatment with enasidenib, a selective mutant isocitrate dehydrogenase isoform 2 (IDH2) inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging because of nonspecific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy. Across the total AML population, 67 of 643 (10.4%) had ≥1 any-grade DS event, with highest incidence in patients who received enasidenib plus azacitidine and lowest incidence in patients who received enasidenib plus chemotherapy (13/74 [17.6%] and 2/93 [2.2%]). The most common symptoms of DS were dyspnea/hypoxia (80.6%) and pulmonary infiltrate (73.1%). Median time to onset of first DS event across all studies was 32 days (range, 4-129). Most patients (88.1%) received systemic steroids for treatment of DS. Evaluation of baseline risk factors for DS identified higher levels of bone marrow blasts and lactate dehydrogenase as independent factors associated with increased grade 3 to 5 DS risk. Overall, these results suggest that DS associated with IDH inhibition is manageable, given the benefits of enasidenib treatment in IDH2-mutated AML. We further characterized enasidenib-related DS in these patients and identified risk factors, which could be used for DS management in clinical practice. These trials were registered at www.ClinicalTrials.gov as # NCT01915498, NCT02577406, NCT02677922, and NCT02632708.

Delayed duodenal/gastric fistula resulting in persistent perihepatic abscesses as a late complication of laparoscopic cholecystectomy.

Since the early 1990's, laparoscopic cholecystectomy has become the gold standard for the treatment of symptomatic gallbladder disease. Although the incidence of postoperative complications is generally lower with this approach, gallbladder perforation represents a serious risk that is among the most common complications of laparoscopic cholecystectomy. The sequalae that can follow iatrogenic perforation have not been well documented and only a few case reports exist in the current literature. In this paper we discuss two case reports of delayed perihepatic abscesses following prior laparoscopic cholecystectomy, ultimately resulting in fistulous tracts. The course of the disease is discussed along with the diagnostic workup and eventual successful management of the aforementioned complications. Treating enteric fistulae requires a systematic approach and is carried out in phases. Enteric fistula formation following laparoscopic cholecystectomy is a rare complication of retained gallstones that can present months to years following the index operation. Significant care should be taken to avoid perforation and all efforts should be made to retrieve stones if spillage occurs.

NCAA football players are at higher risk of upper extremity injury after first-time concussion.

BACKGROUND: Previous research has demonstrated that concussions increase the risk of subsequent lower extremity musculoskeletal injury in athletes. However, the risk of upper extremity injury in athletes' post-concussion is poorly understood. METHODS: All concussed football players within a National Collegiate Athletic Association (NCAA) Division I conference athletic database were identified between 2017 and 2021. After exclusions, each athlete experiencing their first concussion was then retrospectively reviewed for upper extremity injuries in the year prior to their concussion and in the year beginning at 90 days after their concussion. All upper extremity injuries were identified and the odds ratio, 95% confidence interval, and statistical significance between groups were calculated in Microsoft Excel. RESULTS: 160 de-identified football players from a single conference who were first diagnosed with concussions in the seasons from 2017 through 2021 met inclusion criteria. In these athletes the odds of upper extremity injury in year following first diagnosed concussion were 2.36 times higher than in the year prior (95% CI 1.13-4.95, p = 0.02). Shoulder was the most common site of injury with 57.7% of injuries compared to 19.2% in the hand, 15.4% in the elbow, 7.7% in the forearm, and 0% in the wrist. CONCLUSION: This study demonstrates that collegiate football players are at a 2.36 times greater risk of upper extremity injury in the year following their first diagnosed concussion compared to the year preceding it. The most common site of upper extremity injury after concussion was the shoulder. LEVEL OF EVIDENCE: III.

Randomized controlled trials in the shoulder arthroplasty literature rarely include key demographic and socioeconomic patient data.

BACKGROUND: It is well known that socioeconomic and demographic variables can greatly affect health outcomes. Previous studies across medical and surgical subspecialties have demonstrated that these variables are frequently under-reported in randomized controlled trials (RCTs). No such study currently exists that examines rates of reporting of sociodemographic variables in shoulder arthroplasty RCTs. This study aims to present these rates and explore the impact of failing to report socioeconomic variables in shoulder arthroplasty RCTs. METHODS: The PubMed database was queried for the term shoulder arthroplasty. Sixty-five RCTs from the past 10 years were identified for inclusion from 5 high-impact orthopedic surgery journals. Each RCT was analyzed for patient age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, work status, and education. It was also noted whether each of the above variable was mentioned in the results section of the article. Data were presented in a descriptive fashion as well as analyzed using χ2 and Fisher exact tests where appropriate. RESULTS: From 2014 to 2023, the 65 shoulder arthroplasty RCTs published reported age in 40 of 65 (61.5%) in their results sections and 61 of 65 (93.8%) in any section. Sex or gender was reported in 27 of 65 (41.5%) in their results sections and 61 of 65 (93.8%) in any section. No articles included any sociodemographic variables in the results section. Reporting rates for sociodemographic variables in any section were as follows: race, 6 of 65 (9.2%); ethnicity, 5 of 65 (7.7%); work status, 4 of 65 (6.2%); and insurance status, 1 of 65 (1.5%). No studies included income or education of the enrolled patients. There was no difference in reporting sociodemographic variables by journal (P = .45) or by year of publication (P = .57). However, no study prior to 2020 included any sociodemographic variable (0 of 27, 0%), whereas from 2020 onward 6 studies included at least 1 (6 of 38, 15.8%). Sociodemographic variables were reported significantly less frequently than age and sex or gender (P = .001). DISCUSSION: Our study found sociodemographic variables are rarely reported in shoulder arthroplasty RCTs, whereas age and sex or gender are reported with great frequency. In order to understand the results of shoulder arthroplasty RCTs, apply their findings to the care of our patients, and address health disparities, we must ensure these studies include patient sociodemographic data.

Demographic and Socioeconomic Patient Data Are Rarely Included in Randomized Controlled Trials for Femoral Acetabular Impingement and Hip Arthroscopy: A Systematic Review.

Purpose: To determine the rate of reporting for sociodemographic variables in randomized controlled trials (RCTs) investigating femoral acetabular impingement (FAI) and hip arthroscopy. Methods: PubMed, Scopus, and Web of Science were queried for articles relating to FAI and hip arthroscopy. Articles included in final analysis were RCTs investigating operative management of FAI. Included RCTs were analyzed for reporting of age and sex or gender as well as the following sociodemographic variables: race, ethnicity, insurance status, income, housing status, work status, and education level in the results section or any section of the paper. Data was analyzed using χ2 and Fisher exact tests with significance defined as P < .05. Results: Forty-eight RCTs were identified from 2011 to 2023. Age was reported in 48 of 48 (100%) of included papers; sex or gender was reported in 47 of 48 (97.9%). Reporting of sociodemographic variables in any section respectively was: race (7/48, 14.6%), ethnicity (4/48, 8.33%), insurance status (0/48, 0%), income (1/48, 2.08%), housing status (0/48, 0%), work status (3/48, 6.25%), and education (2/48, 4.17%). There was no significant difference for reporting demographic variables with respect to journal or year of publication (P = .666 and P = .761, respectively). Sociodemographic variables (9/48) were reported significantly less frequently than age and sex or gender (48/48) (P < .001). Conclusions: This study found that sociodemographic variables in FAI and hip arthroscopy RCTs are reported with much lower frequency than age and sex or gender. These findings may demonstrate the need to include patient sociodemographic data in RCTs so that their results can be better generalized and applied to the appropriate patient population. Level of Evidence: Level II, systematic review of level I and II evidence.

Patient Reported Clinical Outcomes Following PCL Suture Augmentation in Patients with Multiligamentous Knee Injury: A Retrospective Observational Study.

Purpose: To compare the patient-reported outcomes between patients with posterior cruciate ligament (PCL) reconstruction or repair alone versus PCL reconstruction or repair with internal bracing (IB) in the context of multi-ligament knee injuries (MLKI). Methods: All patients who underwent surgical management of MLKI at two institutions between 2006 and 2020 were retrospectively identified and offered participation in the study. Patient reported outcomes were measured via three instruments: Lysholm Knee score, Multiligament Quality of Life (ML-QOL), and the Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT). The postoperative outcomes and reoperation rates were compared between the internal bracing and non-internal bracing groups. Results: Fifty-two patients were analyzed; 34 were included in the IB group (17.6% female; age 33.1 ±1.60 years), and 18 were included in the non-IB group (11.1% female; age 34.1 ±3.72 years). Mean follow-up time of the entire cohort was 1.44 ± 0.22 years (IB: 1.21 ± 0.18; non-IB: 2.1 ±0.65). There were no significant differences between PROMIS CAT [PROMIS Pain (54.4 ±1.78 vs 51.7 ±1.70, p=0.319), Physical Function (44.3 ±2.27 vs 47.9 ±1.52, p=0.294), Mobility (44.0 ±1.71 vs 46.1 ±2.10, p=0.463)], ML-QOL [ML-QOL Physical Impairment (40.7 ±4.21 vs 41.7±5.10, p=0.884), Emotional Impairment (49.2 ±4.88 vs 44.7±5.87, p=0.579), Activity Limitation (43.5 ±4.56 vs 31.5±3.62, p=0.087), Societal Involvement (44.9 ±4.96 vs 37.5 ±5.30, p=0.345)] and Lysholm knee score (61.8 ±4.55 vs 61.0 ±4.95, p=0.916) postoperatively compared to the non-IB group. Conclusion: In this group of patients, function and patient-reported outcomes between patients treated with PCL reconstruction and repair without internal brace versus those with additional internal brace augmentation were not significantly different. Further research encompassing a larger patient sample is necessary to investigate the efficacy of the internal brace for PCL injury in the context of MLKI injuries.

Results from phase 1 of the MANIFEST clinical trial to evaluate the safety and tolerability of pelabresib in patients with myeloid malignancies.

Pelabresib (CPI-0610), a BET protein inhibitor, is in clinical development for hematologic malignancies, given its ability to target NF-κB gene expression. The MANIFEST phase 1 study assessed pelabresib in patients with acute leukemia, high-risk myelodysplastic (MDS) syndrome, or MDS/myeloproliferative neoplasms (MDS/MPNs) (NCT02158858). Forty-four patients received pelabresib orally once daily (QD) at various doses (24-400 mg capsule or 225-275 mg tablet) on cycles of 14 d on and 7 d off. The most frequent drug-related adverse events were nausea, decreased appetite, and fatigue. The maximum tolerated dose (MTD) was 225 mg tablet QD. One patient with chronic myelomonocytic leukemia (CMML) showed partial remission. In total, 25.8% of acute myeloid leukemia (AML) patients and 38.5% of high-risk MDS patients had stable disease. One AML patient and one CMML patient showed peripheral hematologic response. The favorable safety profile supports the ongoing pivotal study of pelabresib in patients with myelofibrosis using the recommended phase 2 dose of 125 mg tablet QD.CLINICAL TRIAL REGISTRATION: NCT02158858.

Outcomes of multiligament knee injury treated with versus without internal brace suture augmentation.

PURPOSE: To compare the postoperative outcomes between Internal Brace (IB) and non-IB patients who underwent surgical management of multiple-ligament knee injuries (MLKI). METHODS: Patients who underwent surgical management of MLKI at two institutions between 2010 and 2020 were identified and offered participation in the study via the collection of postoperative functional outcomes for MLKI; Lysholm Knee score, Multiligament Quality of Life (ML-QOL), Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT), Pain Interference (PI), Physical Function (PF), and Mobility instruments (MI). The postoperative outcomes and reoperation rates were compared between the IB group and non-IB group. RESULTS: One hundred and twenty-six patients were analyzed; 89 were included in the IB group (31.5% female; age 35.6 ± 1.4 years), and 37 were included in the non-IB group (25.7% female; age 38.8 ± 2.4 years). Mean follow-up time of the entire cohort was 37.9 ± 4.7 months [IB: 21.8 + 1.63; non-IB: 76.4 ± 6.2, p < 0.001). The IB group achieved similar PROMIS CAT [PROMIS Pain (51.8 + 1.1 vs. 52.1 + 1.6, p = 0.8736), Physical Function (46.6 + 1.2 vs. 46.4 + 1.8, p = 0.9168), Mobility (46.0 + 1.0 vs. 43.7 + 1.6, p = 0.2185)], ML-QOL [ML-QOL Physical Impairment (36.6 + 2.5 vs. 43.5 ± 4.2, p = 0.1485), Emotional Impairment (42.5 + 2.9 vs. 48.6 ± 4.6, p = 0.2695), Activity Limitation (34.5 + 2.8 vs. 36.2 ± 4.3, p = 0.7384), Societal Involvement (39.1 + 3.0 vs. 41.7 + 4.2, p = 0.6434)] and Lysholm knee score (64.9 + 2.5 vs. 60.4 + 4.0, p = 0.3397) postoperatively compared the non-IB group, but the differences were not significant. CONCLUSION: In this cohort of patients with MLKI treated with versus without IB, outcomes and reoperation rates trended toward favoring IB, but the study was not sufficiently powered to reach statistical significance. Internal bracing could be useful in the management of MLKI. In the future, matched patient cohorts with more patients are warranted to further evaluate the clinical impact of the internal brace in MLKI.

Traditional Medicare or Medicare Advantage? The Leukemia and Cancer Perspective.

Today, approximately 50% of patients eligible for Medicare have opted for Medicare Advantage as their primary coverage. Whereas Medicare Advantage is a reasonable option for healthy senior Americans, issues arise once they have serious or chronic medical problems, which are prevalent among older Americans. This review details the pros and cons of standard Medicare vs Medicare Advantage. The authors recommend considering standard Medicare as a better form of insurance coverage. In addition, patients should also enroll in Medicare Part D to get prescription drug coverage; buy a supplemental MediGap policy; and buy additional coverage for hearing, vision, and dental care. Although this is a more complicated process, it is also a better one until Medicare Advantage revises its plans to address the current issues facing Americans on such plans who have serious illnesses.

Evaluation of spin in reviews of biodegradable balloon spacers for massive irreparable rotator cuff tears.

HYPOTHESIS: Clinical studies are often at risk of spin, a form of bias where beneficial claims are overstated while negative findings are minimized or dismissed. Spin is often more problematic in abstracts given their brevity and can result in the misrepresentation of a study's actual findings. The goal of this study is to aggregate primary and secondary studies reporting the clinical outcomes of the use of subacromial balloon spacers in the treatment of massive irreparable rotator cuff tears to identify the incidence of spin and find any significant association with study design parameters. MATERIALS AND METHODS: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Independent searches were completed on 2 databases (PubMed and Embase) for primary studies, systematic and current concepts reviews, and meta-analyses and the results were compiled. Two authors independently screened the studies using a predetermined inclusion criteria and aggregated data including titles, publication journals and years, authors, study design, etc. Each study was independently assessed for the presence of 15 different types of spin. Statistical analysis was conducted to identify associations between study characteristics and spin. RESULTS: Twenty-nine studies met the inclusion criteria for our analysis, of which 10 were reviews or meta-analyses and 19 were primary studies. Spin was identified in every study except for 2 (27/29, 93.1%). Type 3 spin, "Selective reporting of or overemphasis on efficacy outcomes or analysis favoring the beneficial effect of the experimental intervention" and type 9 spin, "Conclusion claims the beneficial effect of the experimental treatment despite reporting bias" were most frequently noted in our study, both observed in 12/29 studies (41.4%). Date of publication, and adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses or "The International Prospective Register of Systematic Reviews" were study characteristics associated with a higher rate of certain types of spin. There was a statistically significant association between disclosure of external study funding source and the presence of spin type 4, but none of the other forms of spin. CONCLUSION: Spin is highly prevalent in the abstracts of primary studies, systematic reviews, and meta-analyses discussing the use of subacromial balloon spacer technology in the treatment of massive irreparable rotator cuff tears. Our findings revealed that spin in the abstract tended to favor the balloon spacer intervention. Further efforts are required in the future to mitigate spin within the abstracts of published manuscripts.

Tissue Augmentation Techniques in the Management of Ligamentous Knee Injuries.

Despite early reports of high failure rates in knee ligament repair techniques resulting in favor of reconstruction, newer advances in surgical technology have shifted the attention back to repair with the addition of various tissue augmentation techniques. Ligament repair preserves proprioceptors in the native ligament and avoids autograft tendon harvest, minimizing the complications associated with donor site ruptures in reconstruction techniques. Tissue augmentation has been successfully used in knee ligamentous and tendon repair procedures, as well as in some upper extremity procedures. This study provides a clinical update on the surgical techniques, biomechanics, and outcomes with the application of various tissue augmentation techniques in the ligaments surrounding the knee joint.