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Structural elucidation of Gram-negative bacterial lipid A traditionally requires chemical extraction followed by tandem MS data in the negative ion mode. Previously, we reported FLAT and FLATn as methods to rapidly determine the structure of lipid A without chromatographic techniques. In this work, we extend the capability and effectiveness of these techniques to elucidate the chemical structure in a de novo manner by including the use of positive ion mode (FLAT+ and FLATn+) spectral approaches. Advantages of positive mode analysis of lipid A include the generation of more interpretable and informative fragmentation patterns that include the identification of diagnostic fragments, including selective dissociation of a glycosidic bond between two glucosamine units and the selective dissociation at the secondary acyl chain in 2'-N, allowing for the determination of the composition of fatty acids. As a proof of principle, we present here two previously uncharacterized structures of lipid A from Roseomonas mucosa (R. mucosa) and Moraxella canis (M. canis). In R. mucosa, we determined the lipid A structure with a nonconventional backbone of-ß-1,6 linked 2,3-dideoxy-2,3-diamno-d-glucopyranose further modified with galacturonic acid in the place of typical 1-phosphate, and in M. canis, we assigned a single discrete structure using the specific fragmentation patterns of terminal phosphate groups present in lipid A. Therefore, FLATn+, in combination with FLAT and FLATn, provides a multimodal structural platform for rapid structure characterization of unusual and complex lipid A structures from a single colony.
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PURPOSE: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. PATIENTS AND METHODS: This first-in-human, multicenter, open-label, phase 1/2 study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase 2 dose (RP2D), and characterize the pharmacokinetics (PK); exploratory objectives included pharmacodynamics and efficacy. RESULTS: Vimseltinib was well tolerated; the majority of non-laboratory treatment-emergent adverse events were grade 1/2. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The RP2D was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7 to 46.9), and the objective response rate as assessed by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 was 72%. CONCLUSIONS: Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT whose disease is not amenable to surgery.
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Shigella spp. infection contributes significantly to the global disease burden, primarily affecting young children in developing countries. Currently, there are no FDA-approved vaccines against Shigella, and the prevalence of antibiotic resistance is increasing, making therapeutic options limited. Live-attenuated vaccine strains WRSs2 (S. sonnei) and WRSf2G12 (S. flexneri 2a) are highly immunogenic, making them promising vaccine candidates, but possess an inflammatory lipid A structure on their lipopolysaccharide (LPS; also known as endotoxin). Here, we utilized bacterial enzymatic combinatorial chemistry (BECC) to ectopically express lipid A modifying enzymes in WRSs2 and WRSf2G12, as well as their respective wild-type strains, generating targeted lipid A modifications across the Shigella backgrounds. Dephosphorylation of lipid A, rather than deacylation, reduced LPS-induced TLR4 signaling in vitro and dampened endotoxic effects in vivo. These BECC-modified vaccine strains retained the phenotypic traits of their parental strains, such as invasion of epithelial cells and immunogenicity in mice without adverse endotoxicity. Overall, our observations suggest that BECC-engineered live attenuated vaccines are a promising approach to safe and effective Shigella vaccines.
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BACKGROUND: Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. METHODS: MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov, NCT05059262, and enrolment is complete. FINDINGS: Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group vs 0% (none of 40) in the placebo group (difference 40% [95% CI 29-51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. INTERPRETATION: Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. FUNDING: Deciphera Pharmaceuticals.
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Tumor de Células Gigantes de las Vainas Tendinosas , Humanos , Método Doble Ciego , Masculino , Femenino , Persona de Mediana Edad , Adulto , Tumor de Células Gigantes de las Vainas Tendinosas/tratamiento farmacológico , Anciano , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Resultado del Tratamiento , Anilidas , QuinolinasRESUMEN
OBJECTIVE: The objective was to develop consensus treatment plans (CTPs) for patients with refractory moderately severe juvenile dermatomyositis (JDM) treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: The Biologics Workgroup of the Childhood Arthritis and Rheumatology Research Alliance JDM Research Committee used case-based surveys, consensus framework, and nominal group technique to produce bDMARD CTPs for patients with refractory moderately severe JDM. RESULTS: Four bDMARD CTPs were proposed: tumor necrosis factor α (TNFα) inhibitor (adalimumab or infliximab), abatacept, rituximab, and tocilizumab. Each CTP has different options for dosing and/or route. Among 76 respondents, consensus was achieved for the proposed CTPs (93% [67 of 72]) as well as for patient characteristics, assessments, outcome measures, and follow-up. By weighted average, respondents indicated that they would most likely administer rituximab, followed by abatacept, TNFα inhibitor, and tocilizumab. CONCLUSION: CTPs for the administration of bDMARDs in refractory moderately severe JDM were developed using consensus methodology. The implementation of the bDMARD CTPs will lay the groundwork for registry-based prospective comparative effectiveness studies.
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Background: Although several studies have noted that patients are routinely overprescribed opioids, few have reported usage after arthroscopic surgery. Purpose: To determine opioid consumption and allocation for unused opioids after common arthroscopic surgeries. Study Design: Case series; Level of evidence, 4. Methods: Patients between the ages of 15 and 40 years who were scheduled to undergo anterior cruciate ligament reconstruction (ACLR), labral repair of the hip or shoulder, meniscectomy, or meniscal repair were prospectively enrolled. Patients were prescribed either 5 mg hydrocodone-325 mg acetaminophen or 5 mg oxycodone-325 mg acetaminophen based on surgeon preference. Patients completed a daily opioid usage survey during the 2-week postoperative period. In addition, patients completed a survey on postoperative day 21 inquiring about continued opioid use and medication disposal, if applicable. Opioid medication consumption was converted to morphine milligram equivalents (MMEs). Results: Of the 200 patients who were enrolled in the study, 176 patients had sufficient follow-up after undergoing 85 (48%) ACLR, 26 (14.8%) hip labral repair, 34 (19.3%) shoulder labral repair, 18 (10.2%) meniscectomy, and 13 (7.4%) meniscal repair procedures. Mean age was 26.1 years (SD, 7.38); surgeons prescribed a mean of 26.6 pills whereas patients reported consuming a mean of 15.5 pills. The mean MME consumption in the 14 days after each procedure was calculated: ACLR (95.7; 44% of prescription), hip labral repair (84.8; 37%), shoulder labral repair (57.2; 35%), meniscectomy (18.4; 27%), and meniscal repair (32.1; 42%). This corresponded to approximately 39% of the total opioid prescription being utilized across all procedures. Mean MME consumption was greatest on postoperative day 1 in hip, shoulder, and meniscal procedures and on postoperative day 2 in ACLR. Only 7.04% of patients reported continued opioid use in the third postoperative week. Patients had a mean of 11 unused pills or 77.7 MMEs remaining. Of the patients with remaining medication, 24.7% intended to keep their medication for future use. Conclusion: The results of our study indicate that patients who undergo the aforementioned arthroscopic procedures consume <75 MMEs in the 2-week postoperative period, translating into a mean of 10 to 15 pills consumed. Approximately 60% of total opioids prescribed went unused, and one-fourth of patients intended to keep their remaining medication for future usage. We have provided general prescribing guidelines and recommend that surgeons carefully consider customizing their opioid prescriptions on the basis of procedure site to balance optimal postoperative analgesia with avoidance of dissemination of excess opioids.
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INTRODUCTION: Stoma site incisional hernias (SSIHs) are associated with substantial long-term morbidity, and the rate can be as high as 30% to 40%. Recent efforts using prophylactic mesh reinforcement (PMR) to reduce the development of hernias have shown encouraging outcomes. The objective of this study was to assess the use of prophylactic biosynthetic mesh at the time of stoma reversal on the overall SSIH rate. METHODS: This is an observational retrospective cohort study. A review of 101 consecutive patients who underwent PMR in the retrorectus plane from 2015 to 2020 was compared to 73 consecutive patients who underwent primary stoma closure without mesh from 2011 to 2014. The primary endpoint was the presence of SSIH on clinical examination or computed tomography after ostomy takedown. RESULTS: In total, 174 cases were analyzed with 101 patients in the treatment group (median follow-up 45.2 months) and 73 patients in the control group (median follow-up 43.2 months). There were no major differences in preoperative characteristics between the groups. Fourteen patients developed SSIHs with 1 (1.0%) in the treatment arm and 13 (17.8%) in the control arm (p = 0.001). The majority of stomas were loop ileostomies and end colostomies, and stoma type did not affect hernia rates. On univariate analysis, body mass index (p = 0.029) and chronic kidney disease < 3 (p = 0.003) were independent predictors of hernia formation, while mesh was significantly protective (p = 0.000057). DISCUSSION: PMR with biosynthetic mesh at the time of stoma reversal and closure is an effective procedure to reduce the incidence of SSIHs and does not seem to be associated with an increased risk of complications.
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Hernia Incisional , Mallas Quirúrgicas , Estomas Quirúrgicos , Humanos , Hernia Incisional/prevención & control , Hernia Incisional/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Estomas Quirúrgicos/efectos adversosRESUMEN
Background: The ulnar collateral ligament (UCL) is the primary soft tissue stabilizer to valgus stress in the elbow and is placed under this valgus stress during the throwing motion. Although there are known risk factors for UCL injury, it is unknown whether the UCL undergoes adaptive changes in athletes from different climates. Purpose: To compare elbow stress ultrasound (SUS) findings between professional baseball pitchers from warm climates versus cold climates and assess significant differences in adaptive and morphologic changes in the UCL. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Dynamic SUS evaluations were performed over 18 years on the dominant and nondominant arms of 643 professional pitchers from warm and cold climates as determined by the player's country/state of origin. Studies were compared with respect to relative UCL thickness (dominant arm vs nondominant arm), relative glenohumeral joint laxity (joint space distance under stress vs joint space distance at rest), and the presence of morphologic changes such as tears or calcifications. In addition, a subgroup analysis was performed to compare the progression of SUS findings over 3 years in players with sequential yearly data. Results: Players from warmer climates had significantly greater relative UCL thicknesses than players from colder climates (1.75 vs 1.50 mm, respectively; P = .047). There were no differences between these 2 groups in terms of relative ulnohumeral joint laxity (P = .201), presence of morphologic changes (P = .433), 3-year progression of relative UCL thickness (P = .748), or relative joint laxity (P = .904). Conclusion: Professional pitchers from warm climates had a greater side-to-side difference in UCL thickness between the dominant and nondominant arms. This may be due to the potential for year-round throwing among baseball players from warm climates. There was no difference in laxity, thickness progression, laxity progression, or the presence of additional morphologic changes.
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Introduction: Given the increasing incidence of traumatic thoracolumbar injuries in recent years, studies have sought to investigate potential risk factors for outcomes in these patients. Research question: The aim of this study was to investigate trends and risk factors for in-hospital mortality after fusion for traumatic thoracolumbar injury. Materials and methods: Patients undergoing thoracolumbar fusion after traumatic injury were queried from the National Inpatient Sample (NIS) from 2012 to 2017. Analysis was performed to identify risk factors for inpatient mortality after surgery. Results: Patients in 2017 were on average older (51.0 vs. 48.5, P = 0.004), had more admitting diagnoses (15.5 vs. 10.7, p < 0.001), were less likely to be White (75.8% vs. 81.2%, p = 0.006), were from a ZIP code with a higher median income quartile (Quartile 1: 31.4% vs. 28.6%, p = 0.011), and were more likely to have Medicare as a primary payer (22.9% vs. 30.1%, p < 0.001). Bivariate analysis of demographics and surgical characteristics demonstrated that patients in the in-hospital mortality group (n = 90) were older (70.2 vs. 49.6, p < 0.001), more likely to be male (74.4% vs. 62.8%, p = 0.031), had a great number of admitted diagnoses (21.3 vs. 12.7, p < 0.001), and were more likely to be insured by Medicare (70.0% vs. 27.0%, p < 0.001). Multivariate regression analysis found age (OR 1.06, p < 0.001) and Black race (OR 3.71, p = 0.007) were independently associated with in-hospital mortality. Conclusion: Our study of nationwide, traumatic thoracolumbar fusion procedures from 2012 to 2017 in the NIS database found older, black patients were at increased risk for in-hospital mortality after surgery.
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Introduction: As the population of elderly patients continues to rise, the number of these individuals presenting with thoracolumbar trauma is expected to increase. Research question: To investigate thoracolumbar fusion outcomes for patients with vertebral fractures as stratified by decade. Secondarily, we examined the variability of cost across age groups by identifying drivers of cost of care. Materials and methods: We queried the United States Nationwide Inpatient Sample(NIS) for adult patients undergoing spinal fusion for thoracolumbar fractures between 2012 and 2017. Patients were stratified by decade 60-69(sexagenarians), 70-79(septuagenarians) and 80-89(octogenarians). Bivariable analysis followed by multivariable regression was performed to assess independent predictors of length of stay(LOS), hospital cost, and discharge disposition. Results: A total of 2767 patients were included, of which 46%(N = 1268) were sexagenarians, 36% septuagenarians and 18%(N = 502) octogenarians. Septuagenarians and octogenarians had shorter LOS compared to sexagenarians(ß = -0.88 days; p = 0.012) and(ß = -1.78; p < 0.001), respectively. LOS was reduced with posterior approach(-2.46 days[95% CI: 3.73-1.19]; p < 0.001), while Hispanic patients had longer LOS(+1.97 [95% CI: 0.81-3.13]; p < 0.001). Septuagenarians had lower total charges $12,185.70(p = 0.040), while the decrease in charges in octogenarians was more significant, with a decrease of $26,016.30(p < 0.001) as compared to sexagenarians. Posterior approach was associated with a decrease of $24,337.90 in total charges(p = 0.026). Septuagenarians and octogenarians had 1.72 higher odds(p < 0.001) and 4.16 higher odds(p < 0.001), respectively, of discharge to a skilled nursing facility. Discussion and conclusions: Healthcare utilization in geriatric thoracolumbar trauma is complex. Cost reductions in the acute hospital setting may be offset by unaccounted costs after discharge. Further research into this phenomenon and observed racial/ethnic disparities must be pursued.
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BACKGROUND: Data on sports/physical activity participation following unicompartmental knee arthroplasty (UKA) and patello-femoral arthroplasty (PFA) is variable and limited. The purpose of this study was to assess participations, outcomes, and limitations in sports following UKA and PFA. METHODS: Patients who underwent UKA and PFA at a single institution from 2015 to 2020 were surveyed on sports participation before and after surgery. Data was correlated with perioperative patient characteristics and outcome scores. Among 776 patients surveyed, 356 (50%) patients responded. Of respondents, 296 (83.1%) underwent UKA, 44 (12.6%) underwent PFA, and 16 (4.5%) underwent both UKA/PFA. RESULTS: Activity participation rates were 86.5, 77.3, and 87.5% five years prior, and 70.9, 61.4, and 75% at one year prior to UKA, PFA, and UKA/PFA, respectively. Return to sports rates were 81.6, 64.7, and 62.3% at mean 4.6 years postoperatively, respectively. The most common activities were recreational walking, swimming, cycling, and golf. Patients returned to a similar participation level for low-impact activities, whereas participation decreased for intermediate- and high-impact activities. Patients participating in activities had higher postoperative Knee Injury and Osteoarthritis Outcome Score Joint Replacement (P < .001), 12-Item Short Form Physical Component Score (P = .045) and Mental Component Score (P = .012). Activity restrictions were reported among 25, 36.4, and 25% of UKA, PFA, and UKA/PFA patients, respectively, and were more commonly self-imposed than surgeon-directed. CONCLUSIONS: Though UKA patients' postoperative sports participation may improve compared to one year preoperatively, participation for patients surgically treated for isolated osteoarthritis is decreased compared to 5 years preoperatively and varies among patient subsets.
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Artroplastia de Reemplazo de Rodilla , Volver al Deporte , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Volver al Deporte/estadística & datos numéricos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/cirugía , Deportes , Recuperación de la Función , Resultado del Tratamiento , Articulación Patelofemoral/cirugía , Articulación de la Rodilla/cirugía , Encuestas y CuestionariosRESUMEN
STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate how preoperative Oswestry Disability Index (ODI) thresholds might affect minimal clinically important difference (MCID) achievement following lumbar fusion. SUMMARY OF BACKGROUND DATA: As payers invest in alternative payment models, some are suggesting threshold cutoffs of patient-reported outcomes (PROMs) in reimbursement approvals for orthopedic procedures. The feasibility of this has not been investigated in spine surgery. MATERIALS/METHODS: We included all adult patients undergoing one to three-level primary lumbar fusion at a single urban tertiary academic center from 2014 to 2020. ODI was collected preoperatively and one year postoperatively. We implemented theoretical threshold cutoffs at increments of 10. MCID was set at 14.3. The percent of patients meeting MCID were determined among patients "approved" or "denied" at each threshold. At each threshold, the positive predictive value (PPV) for MCID attainment was calculated. RESULTS: A total 1368 patients were included and 62.4% (N=364) achieved MCID. As the ODI thresholds increased, a greater percent of patients in each group reached the MCID. At the lowest ODI threshold, 6.58% (N=90) of patients would be denied, rising to 20.2%, 39.5%, 58.4%, 79.9%, and 91.4% at ODI thresholds of 30, 40, 50, 60, and 70, respectively. The PPV increased from 0.072 among patients with ODI>20 to 0.919 at ODI>70. The number of patients denied a clinical improvement in the denied category per patient achieving the MCID increased at each threshold (ODI>20: 1.96; ODI>30: 2.40; ODI>40: 2.75; ODI>50: 3.03; ODI>60: 3.54; ODI>70: 3.75). CONCLUSION: Patients with poorer preoperative ODI are significantly more likely to achieve MCID following lumbar spine fusion at all ODI thresholds. Setting a preoperative ODI threshold for surgical eligibility will restrict access to patients who may benefit from spine fusion despite ODI>20 demonstrating the lowest predictive value for MCID achievement. LEVEL OF EVIDENCE: 3.
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Evaluación de la Discapacidad , Vértebras Lumbares , Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Vértebras Lumbares/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Degeneración del Disco Intervertebral/cirugía , Adulto , Diferencia Mínima Clínicamente Importante , Medición de Resultados Informados por el PacienteRESUMEN
INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N = 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing-based assay. ctDNA was detected in 280/362 (77%) samples with KIT mutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KIT exon 11 + 13/14 mutations (ripretinib, n = 21; sunitinib, n = 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KIT exon 11 + 17/18 mutations (ripretinib, n = 27; sunitinib, n = 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.
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Antineoplásicos , Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Naftiridinas , Urea/análogos & derivados , Adulto , Humanos , Sunitinib/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/genética , Tumores del Estroma Gastrointestinal/patología , Mesilato de Imatinib/uso terapéutico , Resistencia a Antineoplásicos/genética , Biomarcadores , Mutación/genética , Antineoplásicos/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patologíaRESUMEN
BACKGROUND: The severity of degenerative changes of the hip is known to adversely impact the outcomes of the treatment of femoroacetabular impingement (FAI). Although the operative indications for FAI have expanded to include patients with moderate degrees of hip osteoarthritis, the exact stage of hip osteoarthritis at which surgery for FAI can offer clinical benefits is still uncertain. QUESTIONS/PURPOSES: (1) How does the survivorship free from conversion to THA and survivorship free from revision differ between patients with preexisting Tönnis Grades 2 or 3 changes and those without advanced degenerative changes (Tönnis Grade 0 or 1) after mini-open femoroacetabular osteoplasty? (2) What are the differences in hip-specific and general-health outcome scores between the two groups after mini-open femoroacetabular osteoplasty? METHODS: From December 2003 to April 2019, we treated 901 patients for FAI, and their clinical data were systematically recorded in a longitudinally maintained database. Mini-open femoroacetabular osteoplasty was our preferred surgical approach because of the surgeon's extensive experience with the technique. Among the entire dataset, 6% of patients (51 individuals) had Tönnis Grade 2 or higher hip osteoarthritis, while the remaining 94% (850 patients) had no or mild degenerative changes (Tönnis Grade 0 or 1). In the Tönnis Grade 2 or 3 group, three patients were lost before the minimum 2-year follow-up duration, leaving 4% (48 patients) who qualified for inclusion in the study. For the matched group with Tönnis Grade 0 or 1, 5% (45 patients) were excluded because of incomplete data, and a further 7% (58 patients) were excluded because they did not have 2 years of follow-up, leaving 83% (747 patients) who were eligible for the matching process. Matching was based on patient age (within 1 year), gender, and BMI (within one unit). Matching resulted in the inclusion of 144 randomly selected control patients in this retrospective, comparative study. General indications for femoroacetabular osteoplasty included symptoms of pain and restricted hip motion in young, active patients with signs of FAI evident on physical examination and radiographs. Patient demographics, medical history, radiographic parameters, and intraoperative findings were compared between the two groups to establish baseline differences and identify potential confounding variables. There was no difference in the mean ± standard deviation age between the cohort of interest and control group (39 ± 10 years and 38 ± 11 years, respectively; p = 0.67). There was no difference in the mean follow-up duration (7 ± 3 years versus 8 ± 2 years; p = 0.25) or the preoperative symptomatic period between the study and control groups (2 ± 2 years versus 3 ± 6 years; p = 0.09). There was no difference in the prevalence of dysplasia, slipped capital femoral epiphysis, Perthes disease, or avascular necrosis of the hip between the two groups. Intraoperatively, the groups did not differ in terms of labral repair (65% [31 of 48] versus 78% [113 of 144]; p = 0.08) and labral transplantation (2%; p > 0.99 for both); however, labral resection was performed more frequently in the study group (63% [30 of 48] versus 42% [60 of 144]; p = 0.002). At a minimum of 2 years of follow-up, survivorship free from conversion to THA and survivorship free from revision surgeries, as well as the latest clinical and functional outcome scores (SF-36, Hip Disability and Osteoarthritis Outcome Score, and modified Harris hip score), were compared between groups. RESULTS: Survivorship free from conversion to THA at 5 years was lower among patients with preexisting Tönnis Grades 2 or 3 changes than it was among patients matched for age, gender, and BMI who did not have advanced degenerative changes (Tönnis Grade 0 or 1) after mini-open femoroacetabular osteoplasty (75% [95% confidence interval 64% to 88%] versus 92% [95% CI 87% to 96%]; p < 0.001). No patients in either group underwent reoperation other than conversion to THA. Although the groups did not differ at baseline in terms of their outcomes scores, the group with more visible arthritis had lower postoperative Hip Disability and Osteoarthritis Outcome Scores than the control group (60 ± 21 points versus 86 ± 11 points, mean difference 26 points [95% CI 10 to 41]; p =0.004). There were no other between-group differences in outcome scores after surgery. CONCLUSION: In our study, approximately 25% of patients undergoing mini-open femoroacetabular osteoplasty with Tönnis Grade 2 or higher osteoarthritis underwent conversion to THA within 5 years. Some postoperative functional scores were lower in patients with advanced arthritis than in matched patients with no or mild arthritis. We emphasize the importance of exercising caution when considering femoroacetabular osteoplasty in patients in whom advanced arthritis is already evident at the time of presentation. LEVEL OF EVIDENCE: Level III, therapeutic study.
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BACKGROUND: The Major League Baseball (MLB) draft is a common route for players to enter professional baseball in the United States. Players taken in earlier rounds are typically higher-performing players. When looking at pitchers specifically, higher performance at the amateur level may be associated with an increased frequency of adaptive change in the throwing elbow. PURPOSE: To determine whether pitchers taken in earlier rounds of the MLB draft have a greater frequency or extent of pathological change in the elbow, as measured by dynamic stress ultrasound. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Dynamic stress ultrasounds (SUSs) were performed over 18 years on the dominant and nondominant arms of 651 professional pitchers. The 383 drafted players were grouped according to the round in which they were drafted (rounds 1-5, 6-10, 11-20, 21+). Groups were compared with respect to "relative" ulnar collateral ligament (UCL) thickness (dominant-nondominant), relative ulnohumeral joint laxity (joint space distance under stress minus joint space at rest), and the presence of pathology (calcifications, tears, hypoechoic foci, osteophytes). In addition, a subgroup analysis was done to compare the progression of SUS findings over 3 years in players for which data were available. RESULTS: Draft round groups did not differ by age, number of previous spring training, or handedness. Comparing baseline measurements, there was no significant relationship between draft round and relative UCL thickness (P = .932), relative laxity (P = .996), or presence of pathology detectable on SUS (P = .642). However, increased relative UCL thickness was significantly associated with the presence of pathology on SUS (odds ratio, 1.45; 95% CI, 1.26-1.69; P < .001). Longitudinally, there was no significant relationship between draft round and 3-year progression of relative laxity, relative UCL thickness, or clinical progression of pathology. CONCLUSION: Higher-performing pitchers are drafted earlier in the MLB draft. This may be attributable to peak pitch velocity, in-game performance, visibility gained during player showcases, or any number of other sport-specific variables. However, despite this, there was no significant relationship between draft round and adaptive changes to the elbow or specific properties of the UCL on stress ultrasound.
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Béisbol , Ligamento Colateral Cubital , Ligamentos Colaterales , Articulación del Codo , Reconstrucción del Ligamento Colateral Cubital , Humanos , Codo/diagnóstico por imagen , Ligamento Colateral Cubital/diagnóstico por imagen , Estudios Transversales , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Ligamentos Colaterales/diagnóstico por imagen , Ligamentos Colaterales/cirugíaRESUMEN
OBJECTIVE: Myositis-associated autoantibodies (MAAs) have been associated with overlap myositis, certain disease manifestations such as interstitial lung disease (ILD), and worse prognosis in the idiopathic inflammatory myopathies. MAAs overall remain largely uncharacterized in patients with juvenile-onset myositis. Moreover, it is unknown whether the number of MAAs is associated with disease severity. METHODS: Patients with juvenile myositis in cross-sectional natural history studies who underwent testing for myositis autoantibodies were included. Demographics, myositis autoantibodies, clinical characteristics, medications received, and outcomes of those with and without MAAs were compared. Multivariable logistic regression was performed to determine whether the number of MAAs detected was associated with severe disease features. RESULTS: Among 551 patients, 36% had an MAA and 13% had more than one MAA. Among those who were MAA positive, there was a higher frequency of overlap myositis (18% vs 5.9%, P < 0.001). MAA positivity was associated with certain clinical features, including Raynaud phenomenon (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.41-4.28) and ILD (OR 3.43, 95% CI 1.75-6.96), as well as a chronic disease course (OR 1.72, 95% CI 1.10-2.72) and mortality (OR 3.76, 95% CI 1.72-8.43). The number of MAAs was also associated with mortality (OR 1.83, 95% CI 1.16-2.86). CONCLUSION: MAAs were prevalent in a large cohort of patients with juvenile myositis. ILD, refractory disease, and mortality were associated with MAA positivity. Prospective studies are needed to determine whether early detection of MAAs may lead to improved outcomes for patients with juvenile myositis.
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Autoanticuerpos , Miositis , Humanos , Autoanticuerpos/inmunología , Autoanticuerpos/sangre , Masculino , Femenino , Niño , Adolescente , Estudios Transversales , Miositis/inmunología , Miositis/mortalidad , Dermatomiositis/inmunología , Dermatomiositis/complicaciones , Dermatomiositis/mortalidad , Índice de Severidad de la Enfermedad , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/mortalidad , Enfermedades Pulmonares Intersticiales/etiología , Modelos Logísticos , Preescolar , Enfermedad de Raynaud/inmunologíaRESUMEN
INTRODUCTION: Patients presenting with spinal cord injury (SCI) often times have notable deficits or polytrauma and may require urgent decision making for early management. However, their presentation may affect decision-making ability. Although advance care planning (ACP) may help guide spine surgeons as to patient preferences, the rate at which they are available and disparities in ACP completion are still not understood. The objective of this study was to evaluate disparities in the completion of ACP among patients with acute SCI. METHODS: All patients presenting with cervical SCI to the emergency department at an urban, tertiary level I trauma center from 2010 to 2021 were identified from a prospective database of all consults evaluated by the spine service. Each patient's medical record was reviewed to assess for the presence of ACP documents such as living will, power of attorney, or advance directive. Community-level socioeconomic status was assessed using the Distressed Communities Index. Bivariable and multivariable analyses were performed. RESULTS: We identified 424 patients: 104 (24.5%) of whom had ACP. Patients with ACP were older (64.8 versus 56.5 years, P = 0.001), more likely White (78.8% versus 71.9%, P = 0.057), and present with ASIA Impairment Scale grade A SCI (21.2% versus 12.8%, P = 0.054), although the latter two did not reach statistical significance. On multivariable logistic regression, patients residing in at-risk communities were significantly less likely to have ACP documents compared with those in prosperous communities (odds ratio [OR]: 0.29, P = 0.03). Although patients living in distressed communities were less likely to complete ACP compared with those in prosperous communities (OR 0.50, P = 0.066), this did not meet statistical significance. Female patients were also less likely to have ACP (OR: 0.43, P = 0.005). CONCLUSION: Female patients and those from at-risk communities are markedly less likely to complete ACP. Attention to possible disparities during admission and ACP discussions may help ensure that patients of all backgrounds have treatment goals documented.
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Planificación Anticipada de Atención , Médula Cervical , Traumatismos de la Médula Espinal , Humanos , Femenino , Directivas Anticipadas , Clase Social , Traumatismos de la Médula Espinal/terapiaRESUMEN
STUDY DESIGN: Retrospective single-institution cohort. OBJECTIVE: To evaluate the implementation of a commercial bundled payment model in patients undergoing lumbar spinal fusion. SUMMARY OF BACKGROUND DATA: BPCI-A caused significant losses for many physician practices, prompting private payers to establish their own bundled payment models. The feasibility of these private bundles has yet to be evaluated in spine fusion. METHODS: Patients undergoing lumbar fusion from October to December 2018 in BPCI-A before our institution's departure were included for BPCI-A analysis. Private bundle data was collected from 2018 to 2020. Analysis of the transition was conducted among Medicare-aged beneficiaries. Private bundles were grouped by calendar year (Y1, Y2, Y3). Stepwise multivariate linear regression was performed to measure independent predictors of net deficit. RESULTS: The net surplus was the lowest in Y1 ($2,395, P =0.03) but did not differ between our final year in BPCI-A and subsequent years in private bundles (all, P >0.05). AIR and SNF patient discharges decreased significantly in all private bundle years compared with BPCI. Readmissions fell from 10.7% (N=37) in BPCI-A to 4.4% (N=6) in Y2 and 4.5% (N=3) Y3 of private bundles ( P <0.001). Being in Y2 or Y3 was independently associated with a net surplus in comparison to the Y1 (ß: $11,728, P =0.001; ß: $11,643, P =0.002). Postoperatively, length of stay in days (ß: $-2,982, P <0.001), any readmission (ß: -$18,825, P =0.001), and discharge to AIR (ß: $-61,256, P <0.001) or SNF (ß: $-10,497, P =0.058) were all associated with a net deficit. CONCLUSIONS: Nongovernmental bundled payment models can be successfully implemented in lumbar spinal fusion patients. Constant price adjustment is necessary so bundled payments remain financially beneficial to both parties and systems overcome early losses. Private insurers who have more competition than the government may be more willing to provide mutually beneficial situations where cost is reduced for payers and health systems. LEVEL OF EVIDENCE: 3.
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Medicare , Fusión Vertebral , Humanos , Anciano , Estados Unidos , Estudios Retrospectivos , Alta del PacienteRESUMEN
Meta-analyses represent the best available medical evidence. Although a powerful tool, they are not without criticisms since any bias in the original studies are then compounded when they are pooled together for the meta-analysis. Funnel plots provide a useful graphical representation of the presence of bias, and forest plots represent the heterogeneity of findings within studies included in a meta-analysis. The purpose of this review is to help readers interpret these statistical tools to better understand the findings of a meta-analysis.
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Sesgo de Publicación , Humanos , SesgoRESUMEN
PURPOSE: Joint line (JL) position change in total knee arthroplasty (TKA) may alter knee biomechanics and impact function. The purpose of this study was to compare the change in JL position between robotic-assisted TKA (RA-TKA) and conventional TKA (C-TKA). METHODS: A retrospective, radiographic analysis was conducted of patients who underwent RA-TKA and C-TKA to compare JL position change. JL position was measured in consecutive RA-TKAs and C-TKAs performed by four fellowship-trained arthroplasty surgeons. Statistical analysis was done utilizing t-tests and Mann Whitney U tests, with statistical significance being defined as a p value < 0.05. RESULTS: Six hundred total RA-TKAs and 400 total C-TKAs were included in the analysis. There were no significant differences in patient baseline characteristics such as body mass index, range of motion, and tibiofemoral coronal alignment. RA-TKAs were associated with an average of 0.04 (2.2) mm JL position change, and C-TKAs were associated with an average 0.5 (3.2) mm JL position change (p = 0.030). There were inter-surgeon differences when comparing the change in JL position for RA-TKAs and C-TKAs between the four participating surgeons. CONCLUSION: RA-TKA leads to better preservation of the JL position than C-TKA, and this seems to be dependent on the arthroplasty surgeon's preferences and techniques during TKA. Whether this statistically significant difference is clinically relevant needs to be further investigated.