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1.
Am J Sports Med ; : 3635465241263595, 2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39101607

RÉSUMÉ

BACKGROUND: The indications for hip arthroscopy in patients aged ≥40 years remain controversial, as observational studies have suggested that advanced age portends poor functional outcomes, poor durability of improvement, and high rates of conversion to total hip arthroplasty. PURPOSE: To compare hip arthroscopy versus nonoperative management for symptomatic labral tears in patients aged ≥40 years with limited radiographic osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This single-surgeon, parallel randomized controlled trial included patients aged ≥40 years with limited osteoarthritis (Tönnis grades 0-2) who were randomized 1:1 to arthroscopic surgery with postoperative physical therapy (SPT) or physical therapy alone (PTA). Patients who received PTA and achieved unsatisfactory improvement were permitted to cross over to SPT after completing ≥14 weeks of physical therapy (CO). The primary outcomes were the International Hip Outcome Tool-33 score and modified Harris Hip Score at 24 months after surgery, and secondary outcomes included other patient-reported outcome measures and the visual analog scale for pain. The primary analysis was performed on an intention-to-treat basis using linear mixed-effects models. Sensitivity analyses included modified as-treated and treatment-failure analyses. RESULTS: A total of 97 patients were included, with 52 (53.6%) patients in the SPT group and 45 (46.4%) patients in the PTA group. Of the patients who underwent PTA, 32 (71.1%) patients crossed over to arthroscopy at a mean of 5.10 months (SD, 3.3 months) after physical therapy initiation. In both intention-to-treat and modified as-treated analyses, the SPT group displayed superior mean patient-reported outcome measure and pain scores across the study period for nearly all metrics relative to the PTA group. In the treatment-failure analysis, the SPT and CO groups showed greater improvement across all metrics compared with PTA; however, post hoc analyses revealed no significant differences in improvement between the SPT and CO groups. No significant differences were observed between groups in rates of total hip arthroplasty conversion. CONCLUSION: In patients ≥40 years of age with limited osteoarthritis, hip arthroscopy with postoperative physical therapy led to better outcomes than PTA at a 24-month follow-up. However, additional preoperative physical therapy did not compromise surgical outcomes and allowed some patients to avoid surgery. When surgery is indicated, age ≥40 years should not be considered an independent contraindication to arthroscopic acetabular labral repair. REGISTRATION: NCT03909178 (ClinicalTrials.gov identifier).

2.
JSES Int ; 8(4): 828-836, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39035668

RÉSUMÉ

Background: While studies have assessed comparative rates of restoration of shoulder function and alleviation of symptoms, comparative systemic postoperative complication rates between biceps tenotomy and tenodesis have yet to be assessed. The purpose of the present study was to use a national administrative database to perform a comprehensive investigation into 30-day complication rates after biceps tenotomy versus tenodesis, thus providing valuable insights for informed decision-making by clinicians and patients regarding the optimal surgical approach for pathologies of the long head of the biceps tendon. Methods: The National Surgical Quality Improvement Program database was queried to analyze postoperative complication rates and metrics associated with biceps tenotomy and tenodesis. Patient data spanning from 2012 to 2021 was extracted, with relevant variables assessed to identify and compare these two surgical approaches. Adjusted and unadjusted analyses were utilized to analyze patient demographics, comorbidities, operative times, lengths of stay, readmissions, adverse events, and yearly surgical volume, along with trends in usage, across cohorts. Results: Of 11,527 total patients, 264 (2.29%), 6826 (59.22%), and 4437 (38.49%) underwent tenotomy, tenodesis with open repair, and tenodesis with arthroscopic repair, respectively. Tenotomy operative times ([mean ± SD]: 66.25 ± 44.76 minutes) were shorter than those for open tenodesis (78.83 ± 41.82) and arthroscopic tenodesis (75.98 ± 40.16). Conversely, tenotomy patients had longer hospital days (0.88 ± 4.86 days) relative to open tenodesis (.08 ± 1.55) and arthroscopic tenodesis (.12 ± 2.70). Multivariable logistic regression controlling for demographics and comorbidities demonstrated that patients undergoing tenodesis were less likely to be readmitted (adjusted odds ratio [AOR]: 0.42, 95% confidence interval [CI]: 0.17-0.98, P = .050) or sustain serious adverse events (AOR: 0.27, 95% CI: 0.13-0.57, P < .001), but equally likely to sustain minor adverse events (AOR: 0.87, CI: 0.21-3.68, P = .850), compared with patients undergoing tenotomy. Lastly, comparing utilization rates from 2012 to 2021 revealed a significant decrease in the proportion of tenotomy (from 6.2% to 1.0%) compared to open tenodesis (from 41.0% to 57.3%) and arthroscopic tenodesis (52.8% to 41.64%; P trend = .001). Conclusion: To our knowledge, this is the first large national database study investigating postoperative complication rates between the various surgical treatments for pathologies of the long head of the biceps tendon. Our results suggest that tenodesis yields fewer serious adverse events and lower readmission rates than tenotomy. We also found a shorter operative time for tenotomy. These findings support the increased utilization of tenodesis relative to tenotomy in recent years.

3.
JSES Int ; 8(4): 776-784, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39035669

RÉSUMÉ

Background: Patients with partial thickness rotator cuff tears (PTRCTs) often present with concurrent pathology of the long head of the biceps tendon (LHBT). To address both conditions simultaneously, long head of the biceps (LHB) tenotomy or tenodesis can be performed at the time of arthroscopic rotator cuff repair (RCR). This study aims to compare postoperative shoulder active range of motion (AROM) and complications following transtendinous RCR with concurrent LHB tenodesis or tenotomy. Methods: A total of 90 patients with PTRCTs met inclusion criteria for this study. Patients who underwent tear-completion-and-repair, revision surgery, or open repair of the LHB tendon were excluded. Patients were stratified into tenotomy, arthroscopic suprapectoral tenodesis, or no biceps operation cohorts and were propensity matched 1:1:1 on age, sex, body mass index, and smoking status. Primary outcome measures included AROM in forward flexion, abduction, external rotation, and internal rotation at 6 weeks, 3 months, and 6 months postoperatively. The development of severe stiffness and rates of rotator cuff retear at final follow-up were recorded as secondary outcomes. Results: When comparing the tenotomy and tenodesis cohorts, tenotomy patients were found to have increased AROM at 3 months in forward flexion (153.2° vs. 130.1°, P = .004), abduction (138.6° vs. 114.2°, P = .019), and external rotation (60.4° vs. 43.8°, P = .014), with differences in forward flexion remaining significant at 6 months (162.4° vs. 149.4°, P = .009). There were no significant differences in interval rates of recovery in any plane between cohorts. Additionally, there were no significant differences in rates of symptomatic retears between groups (P = .458). Rates of severe postoperative stiffness approached but did not achieve statistical significance between tenotomy (4.2%) and tenodesis (29.2%) cohorts (P = .066). Smoking status was a significant predictor of severe stiffness (odds ratio, 13.69; P = .010). Conclusion: Despite significant differences in absolute AROM between cohorts, the decision to perform tenotomy or tenodesis was not found to differentially affect rates of AROM recovery for patients undergoing arthroscopic transtendinous RCR for PTRCT. Notably, however, transient stiffness complications were more commonly observed in smokers, and data trends suggested an increased risk of stiffness for patients undergoing LHB tenodesis. Overall, postoperative stiffness is likely multifactorial and attributable to both patient- and procedure-specific factors, and LHB tenotomy may be more appropriate for patients with risk factors for developing stiffness postoperatively.

4.
Article de Anglais | MEDLINE | ID: mdl-38903605

RÉSUMÉ

Background: A number of techniques have been described to enter the capsule and gain access to the hip joint during hip arthroscopy1,2. Among these, the interportal and T-capsulotomies are the most commonly utilized; however, these approaches transect the iliofemoral ligament, which normally resists anterior subluxation and stabilizes extension3. Thus, these approaches may introduce capsuloligamentous instability1,4-7 and have been associated with complications such as dislocation, postoperative pain, microinstability, seroma, and heterotopic ossification5,8-12. Although prior literature has demonstrated durable mid-term results for patients undergoing capsulotomies with capsular closure6,13, avoidance of iatrogenic injury to the hip capsule altogether is preferable. Thus, the puncture capsulotomy technique we present is minimally invasive, preserves the biomechanics of the hip joint and capsule without disrupting the iliofemoral ligament, and allows for appropriate visualization of the joint through placement of multiple small portals. Description: Following induction of anesthesia and with the patient supine on a hip traction table, the nonoperative leg is positioned at 45° abduction with support of a well-padded perineal post, and the operative hip is placed into valgus against the post14. Intra-articular fluid distention with normal saline solution is utilized to achieve approximately 9 mm of inferior migration of the femoral head and decrease risk of iatrogenic nerve injury15. Then, under fluoroscopic guidance, an anterolateral portal is created 1 cm anterior and 1 cm superior to the greater trochanter at an approximately 15° to 20° angle. Second, via arthroscopic visualization, the anterior portal is created 1 cm distal and 1 cm lateral to the intersection of a vertical line drawn at the anterior superior iliac spine and a horizontal line at the level of the anterolateral portal. Third, equidistant between the anterior and anterolateral portals, the mid-anterior portal is created distally. Finally, at one-third of the distance between the anterior superior iliac spine and the anterolateral portal, the Dienst portal is created. Thus, these 4 portals form a quadrilateral arrangement through which puncture capsulotomy can be performed5. Alternatives: Alternative approaches to the hip capsule include interportal and T-capsulotomies, with or without capsular closure1,2,4,6,7,16. Although the most frequently utilized, these approaches transect the iliofemoral ligament and thus may introduce capsuloligamentous instability1,4-7,17. Rationale: The puncture capsulotomy technique has the advantage of maintaining the integrity of the capsule through the placement of 4 small portals. The technique does not transect the iliofemoral ligament and thus does not introduce capsuloligamentous instability. Furthermore, although good mid-term outcomes have been reported with capsular closure6,13,18, the present technique avoids creating unnecessary injury to the capsule and complications of an unrepaired capsule or, conversely, of plication. Expected Outcomes: Patients who underwent the puncture capsulotomy technique showed significant improvements in multiple functional outcome scores at a mean follow-up of 30.4 months, including the International Hip Outcome Tool (iHOT-33) (39.6 preoperatively to 76.1 postoperatively), Hip Outcome Score-Activities of Daily Living subscale (HOS-ADL) (70.0 to 89.3), HOS Sport-Specific Subscale (HOS-SSS) (41.8 to 75.7), and modified Harris hip score (mHHS) (60.1 to 84.9). At 2 years postoperatively with respect to iHOT-33, 81.0% of patients achieved the minimal clinically important difference, 62.0% achieved the patient acceptable symptom state, and 58.9% achieved substantial clinical benefit. In addition, mean visual analog scale pain scores improved significantly over the follow-up period (6.3 to 2.2; p < 0.001). Finally, there were zero occurrences of infection, osteonecrosis of the femoral head, dislocation or instability, or femoral neck fracture in patients treated with puncture capsulotomy19,20. Important Tips: Anterolateral portal placement should be performed using the intra-articular fluid distention technique with fluoroscopy to avoid risk of iatrogenic labral damage and distraction-induced neurapraxia. Subsequent portals must then be placed under direct arthroscopic visualization.On establishment of the anterolateral portal, the scope should be switched to the anterior portal to ensure that the anterolateral portal has not been placed through the labrum and to adjust its placement to better access pathology. This portal, as well as all others, may be subsequently modified by adjusting the angle of the cannula, without making a new skin incision.If a cam lesion is located more anteromedially or posterolaterally, an additional accessory portal may be made distal or proximal to the anterolateral portal, respectively, in order to enhance visualization.Intermittent traction is utilized throughout the surgery. No traction is utilized during preparing and draping, suture tensioning and tie-down, and femoroplasty, with minimal traction during acetabuloplasty; these precautions serve to prevent iatrogenic superficial peroneal nerve injury.There can be a steep learning curve for this technique. In particular, greater surgical experience is required to perform adequate femoral osteoplasty for large cam lesions with this approach21.Instrument maneuverability and visualization can be somewhat constrained with this approach.It is more difficult to perform certain procedures with this technique, including segmental and circumferential labral reconstructions, particularly with remote grafts5. Acronyms and Abbreviations: iHOT-33 = International Hip Outcome Tool-33HOS-ADL = Hip Outcome Score-Activities of Daily Living subscaleHOS-SSS = Hip Outcome Score-Sport-Specific SubscaleAP = anteroposteriorMRA = magnetic resonance arthrogramMRI = magnetic resonance imagingCT = computed tomographyASIS = anterior superior iliac spinemHHS = modified Harris hip score.

5.
Am J Sports Med ; 52(9): 2295-2305, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38872427

RÉSUMÉ

BACKGROUND: Despite focus on surgical preservation of the chondrolabral junction (CLJ), the transition zone between the acetabular cartilage and labrum, the association between severity of CLJ breakdown and functional outcomes after hip arthroscopy remains unexplored. PURPOSE: To assess the influence of CLJ breakdown on patient-reported outcome measures (PROMs) at a 24-month follow-up after hip arthroscopy for symptomatic labral tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective review of prospectively collected data was conducted to identify patients ≥18 years of age with a minimum 24-month follow-up who underwent hip arthroscopy by a single surgeon for the treatment of symptomatic labral tears secondary to femoroacetabular impingement. The Beck classification of transition zone cartilage was used to grade CLJ damage; patients with grades 0 to 2 were stratified into the mild CLJ damage cohort, and those with grades 3 and 4 were stratified into the severe CLJ damage cohort. PROMs were collected at baseline and at 3, 6, 12 months, and annually thereafter postoperatively. Linear mixed-effects models were used to compare PROMs. Rates of achieving clinically meaningful thresholds and subsequent surgery rates were also compared. RESULTS: In total, 198 patients met the inclusion criteria, with a mean follow-up of 3.54 ± 1.26 years. A total of 95 patients with severe CLJ damage (mean age, 34.9 ± 10.5 years) were compared with 103 patients with mild CLJ damage (mean age, 38.2 ± 11.9 years). Hip Outcome Score-Activities of Daily Living (HOS-ADL), Non-Arthritic Hip Score (NAHS), and visual analog score for pain were inferior in the severe CLJ group at enrollment and all follow-up time points (P≤ .05). However, patients with severe CLJ breakdown exhibited greater improvements in HOS-ADL and NAHS at the 24-month follow-up and achieved clinically meaningful thresholds at equivalent rates to patients with mild CLJ breakdown. Subsequent surgery rates were 6.8% and 12.6% in patients with mild versus severe CLJ damage, respectively (P = .250). CONCLUSION: Severe CLJ breakdown is associated with increased pain and decreased functional level preoperatively and up to 24 months after hip arthroscopy. Despite this, patients with severe CLJ breakdown experienced greater improvements in functional outcomes at a 24-month follow-up and achieved clinical thresholds at similar rates to patients with mild CLJ damage. Thus, while worse baseline pain and functional levels may indicate severe CLJ breakdown, these patients still benefit substantially from hip arthroscopy.


Sujet(s)
Acétabulum , Arthroscopie , Cartilage articulaire , Conflit fémoro-acétabulaire , Mesures des résultats rapportés par les patients , Humains , Mâle , Femelle , Adulte , Études rétrospectives , Acétabulum/chirurgie , Acétabulum/traumatismes , Conflit fémoro-acétabulaire/chirurgie , Cartilage articulaire/chirurgie , Cartilage articulaire/traumatismes , Adulte d'âge moyen , Jeune adulte , Articulation de la hanche/chirurgie , Articulation de la hanche/physiopathologie , Indice de gravité de la maladie , Résultat thérapeutique
6.
J Bone Joint Surg Am ; 2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38781316

RÉSUMÉ

BACKGROUND: Despite growing interest in delivering high-value orthopaedic care, the costs associated with hip arthroscopy remain poorly understood. By employing time-driven activity-based costing (TDABC), we aimed to characterize the cost composition of hip arthroscopy for labral pathological conditions and to identify factors that drive variation in cost. METHODS: Using TDABC, we measured the costs of 890 outpatient hip arthroscopy procedures for labral pathological conditions across 5 surgeons at 4 surgery centers from 2015 to 2022. All patients were ≥18 years old and were treated by surgeons who each performed ≥20 surgeries during the study period. Costs were normalized to protect the confidentiality of internal hospital cost data. Descriptive analyses and multivariable linear regression were performed to identify factors underlying cost variation. RESULTS: The study sample consisted of 515 women (57.9%) and 375 men (42.1%), with a mean age (and standard deviation) of 37.1 ± 12.7 years. Most of the procedures were performed in patients who were White (90.6%) or not Hispanic (93.4%). The normalized total cost of hip arthroscopy per procedure ranged from 43.4 to 203.7 (mean, 100 ± 24.2). Of the 3 phases of the care cycle, the intraoperative phase was identified as the largest generator of cost (>90%). On average, supply costs accounted for 48.8% of total costs, whereas labor costs accounted for 51.2%. A 2.5-fold variation between the 10th and 90th percentiles for total cost was attributed to supplies, which was greater than the 1.8-fold variation attributed to labor. Variation in total costs was most effectively explained by the labral management method (partial R2 = 0.332), operating surgeon (partial R2 = 0.326), osteoplasty type (partial R2 = 0.087), and surgery center (partial R2 = 0.086). Male gender (p < 0.001) and younger age (p = 0.032) were also associated with significantly increased costs. Finally, data trends revealed a shift toward labral preservation techniques over debridement during the study period (with the rate of such techniques increasing from 77.8% to 93.2%; Ptrend = 0.0039) and a strong correlation between later operative year and increased supply costs, labor costs, and operative time (p < 0.001 for each). CONCLUSIONS: By applying TDABC to outpatient hip arthroscopy, we identified wide patient-to-patient cost variation that was most effectively explained by the method of labral management, the operating surgeon, the osteoplasty type, and the surgery center. Given current procedural coding trends, declining reimbursements, and rising health-care costs, these insights may enable stakeholders to design bundled payment structures that better align reimbursements with costs. LEVEL OF EVIDENCE: Economic and Decision Analysis Level IV. See Instructions for Authors for a complete description of levels of evidence.

7.
Commun Biol ; 7(1): 563, 2024 May 13.
Article de Anglais | MEDLINE | ID: mdl-38740899

RÉSUMÉ

Targeting the estrogen receptor alpha (ERα) pathway is validated in the clinic as an effective means to treat ER+ breast cancers. Here we present the development of a VHL-targeting and orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of ERα. In vitro studies with this PROTAC demonstrate excellent ERα degradation and ER antagonism in ER+ breast cancer cell lines. However, upon dosing the compound in vivo we observe an in vitro-in vivo disconnect. ERα degradation is lower in vivo than expected based on the in vitro data. Investigation into potential causes for the reduced maximal degradation reveals that metabolic instability of the PROTAC linker generates metabolites that compete for binding to ERα with the full PROTAC, limiting degradation. This observation highlights the requirement for metabolically stable PROTACs to ensure maximal efficacy and thus optimisation of the linker should be a key consideration when designing PROTACs.


Sujet(s)
Récepteur alpha des oestrogènes , Protéolyse , Protéine Von Hippel-Lindau supresseur de tumeur , Humains , Récepteur alpha des oestrogènes/métabolisme , Protéine Von Hippel-Lindau supresseur de tumeur/métabolisme , Protéine Von Hippel-Lindau supresseur de tumeur/génétique , Femelle , Protéolyse/effets des médicaments et des substances chimiques , Animaux , Administration par voie orale , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/métabolisme , Tumeurs du sein/anatomopathologie , Lignée cellulaire tumorale , Souris , Antinéoplasiques/pharmacologie , Antinéoplasiques/administration et posologie
8.
Exp Clin Transplant ; 22(4): 258-266, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38742315

RÉSUMÉ

OBJECTIVES: The demographic disparities among surgeons in academic leadership positions is well documented. We aimed to characterize the present demographic details of abdominal transplant surgeons who have achieved academic and clinical leadership positions. MATERIALS AND METHODS: We reviewed the 2022-2023 American Society of Transplant Surgeons membership registry to identify 1007 active abdominal transplant surgeons. Demographic details (academic and clinical titles) were collected and analyzed using the chi-square test, the Fisher exact test, and t tests. Multinomial logistic regressions were conducted. RESULTS: Female surgeons (P < .001) and surgeons from racial-ethnic minorities (P = .027) were more likely to be assistants or associates rather than full professors. White male surgeons were more likely to be full professors than were White female (P < .001), Asian female (P = .008), and Asian male surgeons (P = .005). There were no Black female surgeons who were full professors. The frequency of full professorship increased with surgeon age (P < .001). Male surgeons were more likely to hold no academic titles (P < .001). Female surgeons were less likely to be chief of transplant(P = .025), chief of livertransplant (P = .001), chief of pancreas transplant (P = .037), or chair of surgery (P = .087, significance at 10%). Chief of kidney transplant was the most common clinical position held by a surgeon from a racial or ethnic minority group. Female surgeons were more likely to hold no clinical titles (P = .001). CONCLUSIONS: The underrepresentation of women and people from racial and ethnic minority groups in academic and clinical leadership positions in the field of abdominal transplant surgery remains evident. White male physicians are more likely to obtain full professorship, and they comprise most of the clinical leadership positions overall. A continued push for representative leadership is needed.


Sujet(s)
Minorités ethniques et raciales , Leadership , Transplantation d'organe , Femmes médecins , Chirurgiens , Humains , Femelle , Mâle , Femmes médecins/tendances , Chirurgiens/tendances , Transplantation d'organe/tendances , Minorités ethniques et raciales/statistiques et données numériques , Diversité culturelle , Facteurs raciaux , Corps enseignant et administratif en médecine/statistiques et données numériques , Adulte , Mobilité de carrière , États-Unis , Adulte d'âge moyen , Facteurs sexuels , Enregistrements , Minorités/statistiques et données numériques
9.
Drug Metab Dispos ; 52(7): 626-633, 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38684371

RÉSUMÉ

In vitro metabolism studies of the spleen tyrosine kinase inhibitors AZ-A and AZ-B identified four unusual metabolites. M1 (mass-to-charge ratio 411) was formed by both molecules and was common to several analogs (AZ-C to AZ-H) sharing the same core structure, appearing to derive from the complete loss of a pendent 3,4-diaminotetrahydropyran ring and pyrazole ring cleavage resulting in a nonobvious metabolite. M2-M4 were formed by AZ-A and a subset of the other compounds only and apparently resulted from a sequential loss of H2 from parent. Initial attempts to isolate M3 for identification were unsuccessful due to sample degradation, and it was subsequently found that M2 and M3 underwent sequential chemical degradation steps to M4. M4 was successfully isolated and shown by mass spectrometry and NMR spectroscopy to be a tricyclic species incorporating the pyrazole and the 3,4-diaminotetrahydropyran groups. We propose that this arises from an intramolecular reaction between the primary amine on the tetrahydropyran and a putative epoxide intermediate on the adjacent pyrazole ring, evidence for which was generated in a ß-mercaptoethanol-trapping experiment. The loss of the tetrahydropyran moiety observed in M1 was found to be enhanced in an analog that was unable to undergo the intramolecular reaction step, leading us to propose two possible reaction pathways originating from the reactive intermediate. Ultimately, we conclude that the apparently complex and unusual metabolism of this series of compounds likely resulted from a single metabolic activation step forming an epoxide intermediate, which subsequently underwent intramolecular rearrangement and/or chemical degradation to form the final observed products. SIGNIFICANCE STATEMENT: The current work provides an unusual biotransformation example showing the potential for intramolecular reactions and chemical degradation to give the appearance of complex metabolism arising from a single primary route of metabolism.


Sujet(s)
Biotransformation , Protein-tyrosine kinases , Syk kinase , Syk kinase/métabolisme , Syk kinase/antagonistes et inhibiteurs , Humains , Protein-tyrosine kinases/antagonistes et inhibiteurs , Protein-tyrosine kinases/métabolisme , Inhibiteurs de protéines kinases/métabolisme , Microsomes du foie/métabolisme , Protéines et peptides de signalisation intracellulaire/métabolisme , Protéines et peptides de signalisation intracellulaire/antagonistes et inhibiteurs , Pyrazoles/métabolisme
10.
Am J Sports Med ; 52(5): 1153-1164, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38476016

RÉSUMÉ

BACKGROUND: Arthroscopic treatment of femoroacetabular impingement (FAI) and symptomatic labral tears confers short- to midterm benefits, yet further long-term evidence is needed. Moreover, despite the physiological and biomechanical significance of the chondrolabral junction (CLJ), the clinical implications of damage to this transition zone remain understudied. PURPOSE: To (1) report minimum 8-year survivorship and patient-reported outcome measures after hip arthroscopy for FAI and (2) characterize associations between outcomes and patient characteristics (age, body mass index, sex), pathological parameters (Tönnis angle, alpha angle, type of FAI, CLJ breakdown), and procedures performed (labral management, FAI treatment, microfracture). STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This retrospective cohort study included patients who underwent primary hip arthroscopy for symptomatic labral tears secondary to FAI by a single surgeon between 2002 and 2013. All patients were ≥18 years of age with minimum 8-year follow-up and available preoperative radiographs. The primary outcome was conversion to total hip arthroplasty (THA), and secondary outcomes included revision arthroscopy, patient-reported outcome measures, and patient satisfaction. CLJ breakdown was assessed using the Beck classification. Kaplan-Meier estimates and weighted Cox regression were used to estimate 10-year survivorship (no conversion to THA) and identify risk factors associated with THA conversion. RESULTS: In this study of 174 hips (50.6% female; mean age, 37.8 ± 11.2 years) with mean follow-up of 11.1 ± 2.5 years, the 10-year survivorship rate was 81.6% (95% CI, 75.9%-87.7%). Conversion to THA occurred at a mean 4.7 ± 3.8 years postoperatively. Unadjusted analyses revealed several variables significantly associated with THA conversion, including older age; higher body mass index; higher Tönnis grade; labral debridement; and advanced breakdown of the CLJ, labrum, or articular cartilage. Survivorship at 10 years was inferior in patients exhibiting severe (43.6%; 95% CI, 31.9%-59.7%) versus mild (97.9%; 95% CI, 95.1%-100%) breakdown of the CLJ (P < .001). Multivariable analysis identified worsening CLJ breakdown (weighted hazard ratio per 1-unit increase, 6.41; 95% CI, 3.11-13.24), older age (1.09; 95% CI, 1.04-1.14), and higher Tönnis grade (4.59; 95% CI, 2.13-9.90) as independent negative prognosticators (P < .001 for all). CONCLUSION: Although most patients achieved favorable minimum 8-year outcomes, several pre- and intraoperative factors were associated with THA conversion; of these, worse CLJ breakdown, higher Tönnis grade, and older age were the strongest predictors.


Sujet(s)
Arthroplastie prothétique de hanche , Conflit fémoro-acétabulaire , Humains , Femelle , Adulte , Adulte d'âge moyen , Mâle , Arthroplastie prothétique de hanche/méthodes , Articulation de la hanche/chirurgie , Études de suivi , Études de cohortes , Études rétrospectives , Arthroscopie/méthodes , Résultat thérapeutique , Conflit fémoro-acétabulaire/imagerie diagnostique , Conflit fémoro-acétabulaire/chirurgie , Conflit fémoro-acétabulaire/complications
11.
Am J Obstet Gynecol MFM ; 6(4): 101331, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38447678

RÉSUMÉ

BACKGROUND: Abdominoplasty surgery is a common body contouring surgery to remove excess fat and skin and restore weakened or separated abdominal muscles caused by aging, pregnancy, or weight fluctuations. There is limited literature regarding patient and pregnancy outcomes after abdominoplasty. OBJECTIVE: This study aimed to determine whether there was a correlation between adverse pregnancy outcomes and history of abdominoplasty. STUDY DESIGN: Our study used a large federated deidentified national health research network with data sourced from 68 healthcare organizations within the United States (TriNetX; data accessed on August 19, 2022). All patients with a record of pregnancy were identified using the International Classification of Diseases, Ninth Revision and Tenth Revision, codes and were grouped into those with a history of abdominoplasty and those without. This study evaluated the perinatal outcomes of fetal growth restriction, abnormal umbilical artery Dopplers, gestational hypertension, preeclampsia, preterm delivery, preterm premature rupture of membranes, gestational diabetes mellitus, macrosomia, stillbirth, abnormal placentation, and wound disruption or infection occurring during a patient's pregnancy after abdominoplasty. Propensity matching was performed to account for potential confounders. An alpha level of <.05 was considered statistically significant. RESULTS: Of the 44,737 patients meeting our criteria, 304 had a history of abdominoplasty, whereas 44,433 did not (control). Our study found that patients with a history of abdominoplasty had significantly higher gravidity, were largely located in the Southern and Midwest region, and had higher counts of vaginal deliveries and cesarean deliveries than the control cohort (Table 1). After propensity score matching, our study found a lower risk of preeclampsia and preterm premature rupture of membranes in patients with abdominoplasty (odds ratio, 0.46; 95% confidence interval, 0.32-0.67; P<.0001) (Table 2). Furthermore, abdominoplasty was associated with an increased risk of preterm delivery (odds ratio, 2.15; 95% confidence interval, 1.48-3.13; P=.0002) (Table 2). Lastly, this study did not find significant differences in the other perinatal outcomes (Table 2). CONCLUSION: Our data suggest that abdominoplasty may be associated with a relative increase in the rates of preterm delivery and cesarean delivery and that other perinatal outcomes are not increased. This provides evidence that future desire for pregnancy need not be a relative contraindication to abdominoplasty.


Sujet(s)
Abdominoplastie , Issue de la grossesse , Humains , Grossesse , Femelle , Abdominoplastie/méthodes , Abdominoplastie/effets indésirables , Études rétrospectives , Adulte , Issue de la grossesse/épidémiologie , Complications de la grossesse/épidémiologie , États-Unis/épidémiologie , Naissance prématurée/épidémiologie , Naissance prématurée/étiologie , Nouveau-né
12.
Cancer Immunol Res ; 12(6): 663-672, 2024 Jun 04.
Article de Anglais | MEDLINE | ID: mdl-38489753

RÉSUMÉ

The DNA exonuclease three-prime repair exonuclease 1 (TREX1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. As tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here, we show that in tumor cells, TREX1 restricts spontaneous activation of the cGAS/STING pathway, and the subsequent induction of a type I IFN response. As a result, TREX1 deficiency compromised in vivo tumor growth in mice. This delay in tumor growth depended on a functional immune system, systemic type I IFN signaling, and tumor-intrinsic cGAS expression. Mechanistically, we show that tumor TREX1 loss drove activation of CD8+ T cells and NK cells, prevented CD8+ T-cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Consequently, TREX1 deficiency combined with T-cell-directed immune checkpoint blockade. Collectively, we conclude that TREX1 is essential to limit tumor immunogenicity, and that targeting this innate immune checkpoint remodels the tumor microenvironment and enhances antitumor immunity by itself and in combination with T-cell-targeted therapies. See related article by Toufektchan et al., p. 673.


Sujet(s)
Exodeoxyribonucleases , Immunité innée , Protéines membranaires , Nucleotidyltransferases , Phosphoprotéines , Exodeoxyribonucleases/génétique , Exodeoxyribonucleases/métabolisme , Animaux , Nucleotidyltransferases/métabolisme , Nucleotidyltransferases/génétique , Phosphoprotéines/métabolisme , Phosphoprotéines/génétique , Souris , Protéines membranaires/métabolisme , Protéines membranaires/génétique , Humains , Tumeurs/immunologie , Tumeurs/métabolisme , Tumeurs/génétique , Interféron de type I/métabolisme , Souris knockout , Souris de lignée C57BL , Lymphocytes T CD8+/immunologie , Lymphocytes T CD8+/métabolisme , Lignée cellulaire tumorale , Transduction du signal , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique
13.
Am J Sports Med ; 52(3): 631-642, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38369972

RÉSUMÉ

BACKGROUND: In the setting of femoroacetabular impingement (FAI), decompression osteoplasties reconcile deleterious loading patterns caused by cam and pincer lesions. However, native variations of spinopelvic sagittal alignment may continue to perpetuate detrimental effects on the labrum, chondrolabral junction, and articular cartilage after hip arthroscopy. PURPOSE: To evaluate the effect of pelvic incidence (PI) on postoperative outcomes after hip arthroscopy for acetabular labral tears in the setting of FAI. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A retrospective query of prospectively collected data identified patients ≥18 years of age who underwent primary hip arthroscopy for FAI and acetabular labral tears between February 2014 and January 2022, with 3-, 6-, 12-, and 24-month follow-ups. Measurements for PI, pelvic tilt (PT), sacral slope (SS), and acetabular version were obtained via advanced diagnostic imaging. Patients were stratified into low-PI (<45°), moderate-PI (45°≤ PI ≤ 60°), and high-PI (>60°) cohorts. Patient-reported outcome measures (PROMs), clinically meaningful outcomes (ie, minimal clinically important difference, Patient Acceptable Symptom State, substantial clinical benefit, and maximal outcome improvement), visual analog scale (VAS) pain scores, and patient satisfaction were compared across cohorts. RESULTS: A total of 74 patients met eligibility criteria and were stratified into low-PI (n = 28), moderate-PI (n = 31), and high-PI (n = 15) cohorts. Correspondingly, patients with high PI displayed significantly greater values for PT (P = .001), SS (P < .001), acetabular version (P < .001), and acetabular inclination (P = .049). By the 12- and 24-month follow-ups, the high-PI cohort was found to have significantly inferior PROMs, VAS pain scores, rates of clinically meaningful outcome achievement, and satisfaction relative to patients with moderate and/or low PI. No significant differences were found between cohorts regarding rates of revision arthroscopy, subsequent spine surgery, or conversion to total hip arthroplasty. CONCLUSION: After hip arthroscopy, patients with a high PI (>60°) exhibited inferior PROMs, rates of achieving clinically meaningful thresholds, and satisfaction at 12 and 24 months relative to patients with low or moderate PI. Conversely, the outcomes of patients with low PI (<45°) were found to match the trajectory of those with a neutral spinopelvic alignment (45°≤ PI ≤ 60°). These findings highlight the importance of analyzing spinopelvic parameters preoperatively to prognosticate outcomes before hip arthroscopy for acetabular labral tears and FAI.


Sujet(s)
Conflit fémoro-acétabulaire , Humains , Conflit fémoro-acétabulaire/chirurgie , Arthroscopie , Études de cohortes , Études rétrospectives , Douleur
16.
Surg Obes Relat Dis ; 20(1): 40-45, 2024 Jan.
Article de Anglais | MEDLINE | ID: mdl-37722939

RÉSUMÉ

BACKGROUND: Bariatric surgery is an effective treatment for obesity and may decrease the morbidity and mortality of obesity-associated cancers. OBJECTIVE: We investigated the risk of a new diagnosis of Barrett esophagus (BE) following bariatric surgery compared to screening colonoscopy controls. SETTING: Large national database including patients who received care in inpatient, outpatient, and specialty care services. METHODS: A national healthcare database (TriNetX, LLC) was used for this analysis. Cases included adults (aged ≥18 yr) who had undergone either sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Controls included adults undergoing screening colonoscopy and an esophagoduodenoscopy on the same day and had never undergone bariatric surgery. Cases and controls were propensity-matched for confounders. The risk of de novo diagnosis of BE at least 1 year after bariatric surgery was compared between cases and controls. Secondary analyses examined the effect of bariatric surgery on metabolic outcomes such as weight loss and body mass index (BMI). The risk of de novo diagnosis of BE in SG was compared with RYGB. Odds ratios (OR) and 95% CI were used to report on these associations. RESULTS: In the propensity-matched analysis, patients who had undergone a bariatric surgical procedure showed a significantly reduced risk of de novo BE when compared with screening colonoscopy controls (.67 [.48, .94]). There was substantial reduction in weight and BMI in the bariatric surgery group when compared with baseline. There was no significant difference in de novo BE diagnosis between the propensity-matched SG and RYGB groups (.77 [.5, 1.2]). CONCLUSION: Patients who underwent bariatric surgery (RYGB or SG) had a lower risk of being diagnosed with BE compared with screening colonoscopy controls who did not receive bariatric surgery. This effect appears to be largely mediated by reduction in weight and BMI.


Sujet(s)
Chirurgie bariatrique , Oesophage de Barrett , Dérivation gastrique , Obésité morbide , Adulte , Humains , Obésité morbide/complications , Obésité morbide/chirurgie , Oesophage de Barrett/diagnostic , Oesophage de Barrett/épidémiologie , Oesophage de Barrett/étiologie , Chirurgie bariatrique/effets indésirables , Chirurgie bariatrique/méthodes , Dérivation gastrique/méthodes , Résultat thérapeutique , Obésité/chirurgie , Gastrectomie/effets indésirables , Gastrectomie/méthodes , Études rétrospectives
17.
Clin Gastroenterol Hepatol ; 22(3): 523-531.e3, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-37716614

RÉSUMÉ

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.


Sujet(s)
Oesophage de Barrett , Tumeurs de l'oesophage , Reflux gastro-oesophagien , Humains , Oesophage de Barrett/diagnostic , Oesophage de Barrett/épidémiologie , Oesophage de Barrett/anatomopathologie , Prévalence , Tumeurs de l'oesophage/diagnostic , Tumeurs de l'oesophage/épidémiologie , Endoscopie gastrointestinale , Reflux gastro-oesophagien/épidémiologie , Endoscopie digestive
18.
J Surg Res ; 295: 350-356, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-38064975

RÉSUMÉ

INTRODUCTION: Postoperative atrial fibrillation (POAF) is a common complication following lung lobectomy and is associated with increased risk of stroke, mortality, and prolonged hospital length of stay. The purpose of this study was to define the risk factors for POAF after lobectomy, hypothesizing that operative approach would be associated with risk of chronic POAF. METHODS: The TriNetX database was used to identify adult patients with no history of arrythmia receiving elective lung lobectomy for cancer from 7/6/2003-7/6/2023. Patients were categorized by approach: video-assisted thoracoscopic surgery (VATS) or open. The outcome of interest was the presence of POAF occurring at 1-3 months ("early") and 12-24 months postop ("chronic"). Propensity matching was performed to reduce bias between cohorts. RESULTS: We identified 22,998 patients: 8472 (36.8%) who received open and 14,526 (63.2%) VATS lobectomy. The rate of early POAF was 3.7% of VATS and 5.3% of open patients. The rate of chronic POAF was 5.5 % of VATS patients and 6.2% of open lobectomy patients. Propensity matching decreased bias between the approach groups, creating 7942 pairs for analysis. After matching, the risk of early POAF was greater in the open approach (5.5% open vs 3.4% VATS, risk ratio 1.607 (95% confidence interval 1.385-1.865), P < 0.001). Chronic POAF was (also) higher in the open approach (6.3% open vs 5.2% VATS, Risk Ratio 1.211 (95%CI 1.067-1.374), P = 0.003). CONCLUSIONS: Postoperative atrial fibrillation (POAF) occurs more commonly after open lobectomy, both acutely and chronically. Providers should counsel patients about the risk of chronic arrythmia after lung resection.


Sujet(s)
Fibrillation auriculaire , Tumeurs du poumon , Adulte , Humains , Tumeurs du poumon/chirurgie , Pneumonectomie/effets indésirables , Fibrillation auriculaire/épidémiologie , Fibrillation auriculaire/étiologie , Fibrillation auriculaire/chirurgie , Durée du séjour , Complications postopératoires/épidémiologie , Complications postopératoires/étiologie , Études rétrospectives , Chirurgie thoracique vidéoassistée/effets indésirables , Facteurs de risque , Poumon
19.
Am Surg ; 90(3): 393-398, 2024 Mar.
Article de Anglais | MEDLINE | ID: mdl-37658717

RÉSUMÉ

BACKGROUND: It is unclear how patients with anal fissures are treated in real-world settings, particularly since patients may not see colorectal surgeons. This study describes trends in treatment with medical therapies (calcium-channel blockers [CCBs], nitroglycerin [NTG], and narcotics) and surgical treatments. METHODS: Cohorts were created within the TriNetX database platform using codes for anal fissures and surgical interventions. Demographics were compared between patients that received surgical intervention within 1 year of diagnosis, CCB or NTG within 1 year (or preoperatively), or narcotics within 30 days or postoperatively vs those who did not. RESULTS: 121,213 patients were included of which 4.0% had surgical intervention. Factors associated with surgical intervention were male sex (OR 1.40), White race (OR 1.17), and Hispanic ethnicity (OR 1.11). Male patients were more likely to undergo sphincterotomy (OR 1.49). Female (OR 1.27), non-Hispanic (OR 1.34), and White patients (OR 1.41) were more likely to have chemodenervation. Regarding nonoperatively managed patients, non-Hispanic (OR .91) and White patients (OR .89) were less likely to receive CCB/NTG. Male (OR 1.21), non-Hispanic (OR 1.08), and Black patients (OR 1.20) were more likely to receive narcotics. Male patients that required surgery were more likely to be prescribed CCB/NTG preoperatively (OR 1.27). Non-Hispanic surgical patients were more likely to receive narcotics (OR 1.84). DISCUSSION: Male fissure patients were more likely to undergo surgical intervention other than chemodenervation. Differences in the rates of surgery and medical therapy (especially narcotics) between races and ethnicities require exploration to enhance the care of patients with anal fissures.


Sujet(s)
Fissure anale , Humains , Mâle , Femelle , Fissure anale/chirurgie , Canal anal/chirurgie , Nitroglycérine/usage thérapeutique , Administration par voie topique , Maladie chronique , Stupéfiants/usage thérapeutique
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