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1.
J Clin Med ; 13(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38592250

RESUMO

Background: The management of acromioclavicular joint injuries requires a thorough understanding of the anatomy and biomechanics of the joint, as well as knowledge of the pertinent physical exam findings and classification to determine an appropriate treatment approach, whether operative or nonoperative. In this article, we present a narrative review of the current state of understanding surrounding these issues. Although there are a large number of options for operative intervention, we additionally present our experience with anatomic coracoclavicular ligament reconstruction (ACCR) with imbrication of the deltoid fascia. Methods: A retrospective review of prospectively collected data on a total of 45 patients who had undergone ACCR between 2003 and 2016 were collected. Results: We found that improvements were seen in American Shoulder and Elbow Surgeons Score (ASES) (53 ± 19 to 81 ± 23), Simple Shoulder Test (SST) (6 ± 3 to 12 ± 13), Constant-Murley (CM) (60 ± 18 to 92 ± 8), and Rowe (67 ± 14 to 89 ± 11) and the mean post-operative SANE score was 86 ± 17. Conclusions: ACCR has the advantage of addressing both horizontal and vertical stability with good outcomes.

2.
Biologics ; 18: 29-59, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38299120

RESUMO

Despite significant advances in the understanding and delivery of osteosynthesis, fracture non-union remains a challenging clinical problem in orthopaedic surgery. To bridge the gap, basic science characterization of fracture healing provides a platform to identify and target biological strategies to enhance fracture healing. Of immense interest, Platelet-rich plasma (PRP) is a point of care orthobiologic that has been extensively studied in bone and soft tissue healing given its relative ease of translation from the benchtop to the clinic. The aim of this narrative review is to describe and relate pre-clinical in-vitro and in-vivo findings to clinical observations investigating the efficacy of PRP to enhance bone healing for primary fracture management and non-union treatment. A particular emphasis is placed on the heterogeneity of PRP preparation techniques, composition, activation strategies, and delivery. In the context of existing data, the routine use of PRP to enhance primary fracture healing and non-union management cannot be supported. However, it is acknowledged that extensive heterogeneity of PRP treatments in clinical studies adds obscurity; ultimately, refinement (and consensus) of PRP treatments for specific clinical indications, including repetition studies are warranted.

3.
Arthroscopy ; 40(3): 1006-1008, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38219106

RESUMO

The Fragility Index (FI) provides the number of patients whose outcome would need to have changed for the results of a clinical trial to no longer be statistically significant. Although it's a well-intended and easily interpreted metric, its calculation is based on reversing a significant finding and therefore its interpretation is only relevant in the domain of statistical significance. Its interpretation is only relevant in the domain of statistical significance. A well-designed clinical trial includes an a priori sample size calculation that aims to find the bare minimum of patients needed to obtain statistical significance. Such trials are fragile by design! Examining the robustness of clinical trials requires an estimation of uncertainty, rather than a misconstrued, dichotomous focus on statistical significance. Confidence intervals (CIs) provide a range of values that are compatible with a study's data and help determine the precision of results and the compatibility of the data with different hypotheses. The width of the CI speaks to the precision of the results, and the extent to which the values contained within have potential to be clinically important. Finally, one should not assume that a large FI indicates robust findings. Poorly executed trials are prone to bias, leading to large effects, and therefore, small P values, and a large FI. Let's move our future focus from the FI toward the CI.


Assuntos
Ensaios Clínicos como Assunto , Intervalos de Confiança , Humanos , Viés , Tamanho da Amostra
4.
Clin Shoulder Elb ; 26(4): 380-389, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37957884

RESUMO

BACKGROUND: Total shoulder arthroplasty (TSA) with a nonspherical humeral head component and inlay glenoid is a successful bone-preserving treatment for glenohumeral arthritis. This study aimed to describe the 90-day complication profile of TSA with this prosthesis and compare major and minor complication and readmission rates between inpatient- and outpatient-procedure patients. METHODS: A retrospective review was performed of a consecutive cohort of patients undergoing TSA with a nonspherical humeral head and inlay glenoid in the inpatient and outpatient settings by a single surgeon between 2017 and 2022. Age, sex, body mass index, American Society of Anesthesiologists (ASA) score, Charlson Comorbidity Index (CCI), and 90-day complication and readmission rates were compared between inpatient and outpatient groups. RESULTS: One hundred eighteen TSAs in 111 patients were identified. Mean age was 64.9 years (range, 39-90) and 65% of patients were male. Ninety-four (80%) and 24 (20%) patients underwent outpatient and inpatient procedures, respectively. Four complications (3.4%) were recorded: axillary nerve stretch injury, isolated ipsilateral arm deep venous thrombosis (DVT), ipsilateral arm DVT with pulmonary embolism requiring readmission, and gastrointestinal bleed requiring readmission. There were no reoperations or other complications. Outpatients were younger with lower ASA and CCI scores than inpatients; however, there was no difference in complications (1/24 vs. 3/94, P=1.00) or readmissions (1/24 vs. 1/94, P=0.37) between these two groups. CONCLUSIONS: TSA with a nonspherical humeral head and inlay glenoid can be performed safely in both inpatient and outpatient settings. Rates of early complications and readmissions were low with no difference according to surgical setting. Level of evidence: IV.

5.
J Shoulder Elbow Surg ; 32(6S): S17-S22, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36822500

RESUMO

BACKGROUND: The concordance between preoperative synovial fluid cultures and intraoperative tissue cultures for identifying pathogenic microorganisms in shoulder periprosthetic joint infection (PJI) remains poorly understood. The purpose of our study was to examine the diagnostic accuracy of positive synovial fluid culture results in early pathogen identification for shoulder PJI. METHODS: A total of 35 patients who met the Musculoskeletal Infection Society criteria for PJI following primary anatomic or reverse arthroplasty and the study inclusion criteria were identified retrospectively from a single institution (multiple surgeons) from January 2011 to June 2021. The inclusion criteria required a positive preoperative intra-articular synovial fluid sample within 90 days analyzed within the same institution and intraoperative tissue cultures at the time of arthrotomy. Concordance was determined when the organism(s) identified from the aspirate correlated with the intraoperative specimens. RESULTS: Overall concordance was identified in 28 of 35 patients (80%), with similar concordance for anatomic (21 of 24, 88%) and reverse (7 of 11, 64%) shoulder arthroplasties (P = .171). Culture discordance occurred in 7 of 35 patients (20%): of these, 5 (14%) had no corresponding intraoperative culture growth whereas 2 (6%) had polymicrobial intraoperative cultures. Monomicrobial Cutibacterium acnes PJI cases were the most common (24 of 35, 69%) and had an overall concordance rate of 79%. Of 5 discordant C acnes patients, 2 had polymicrobial intraoperative cultures and 3 had negative intraoperative culture results; all the patients with negative intraoperative culture results had received antibiotics between the time of aspiration and surgery. Considered separately, concordance in patients who had a positive aspirate finding for C acnes and did not receive antibiotics prior to surgery was 19 of 21 (90%), with a sensitivity of 100% (95% confidence interval, 82%-100%) and a corresponding positive predictive value of 0.91 (95% confidence interval, 58%-93%). CONCLUSION: Preoperative positive aspiration culture results demonstrated favorable sensitivity and specificity when compared with intraoperative tissue cultures in identifying pathogenic microorganisms in shoulder PJI patients. These findings are congruent with literature from hip and knee arthroplasty. Ultimately, confidence in the accuracy of positive preoperative aspiration culture results in shoulder PJI may facilitate the development of early, targeted treatment strategies while directing patient expectations and risk.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Articulação do Ombro , Humanos , Ombro/cirurgia , Estudos Retrospectivos , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/cirurgia , Infecções Relacionadas à Prótese/microbiologia , Articulação do Ombro/patologia , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/cirurgia , Sensibilidade e Especificidade , Líquido Sinovial
6.
Clin Cancer Res ; 29(6): 1086-1101, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36355054

RESUMO

PURPOSE: We evaluated the activity of AZD8205, a B7-H4-directed antibody-drug conjugate (ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination with the PARP1-selective inhibitor AZD5305, in preclinical models. EXPERIMENTAL DESIGN: IHC and deep-learning-based image analysis algorithms were used to assess prevalence and intratumoral heterogeneity of B7-H4 expression in human tumors. Several TOP1i-ADCs, prepared with Val-Ala or Gly-Gly-Phe-Gly peptide linkers, with or without a PEG8 spacer, were compared in biophysical, in vivo efficacy, and rat toxicology studies. AZD8205 mechanism of action and efficacy studies were conducted in human cancer cell line and patient-derived xenograft (PDX) models. RESULTS: Evaluation of IHC-staining density on a per-cell basis revealed a range of heterogeneous B7-H4 expression across patient tumors. This informed selection of bystander-capable Val-Ala-PEG8-TOP1i payload AZ14170133 and development of AZD8205, which demonstrated improved stability, efficacy, and safety compared with other linker-payload ADCs. In a study of 26 PDX tumors, single administration of 3.5 mg/kg AZD8205 provided a 69% overall response rate, according to modified RECIST criteria, which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models. Addition of AZD5305 sensitized very low B7-H4-expressing tumors to AZD8205 treatment, independent of HRD status and in models representing clinically relevant mechanisms of PARPi resistance. CONCLUSIONS: These data provide evidence for the potential utility of AZD8205 for treatment of B7-H4-expressing tumors and support the rationale for an ongoing phase 1 clinical study (NCT05123482). See related commentary by Pommier and Thomas, p. 991.


Assuntos
Imunoconjugados , Neoplasias , Ratos , Humanos , Animais , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Inibidores da Topoisomerase I , Neoplasias/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerase-1/genética
7.
Pediatr Surg Int ; 38(9): 1297-1302, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35794495

RESUMO

BACKGROUND: Pediatric mediastinal masses may be resected using an open or video-assisted thoracoscopic surgery (VATS) approach. We sought to define the preoperative imaging findings predicting amenability to VATS. METHODS: This multicenter retrospective study of pediatric patients undergoing either VATS or open surgical mediastinal mass resection between 2008 and 2018 evaluated the preoperative imaging descriptors associated with VATS. Postoperative endpoints included length of stay (LOS), 30-day readmission, 90-day mortality and complication rates. RESULTS: Mediastinal mass resection was performed in 33 patients. Median tumor size was 6 cm, and 51.5% had anterior mediastinal tumors. The 23 (69.7%) patients who underwent VATS were significantly older (144 months vs 32, P = 0.01) and larger (33.6 kg vs 13.8 P = 0.03). Preoperative imaging characteristics in VATS included "well circumscribed", "smooth margins" and "cystic", while the open surgery group were "heterogeneous" and "coarse calcification". The open group had more germ cell tumors (60.0% vs 13.0%, P = 0.16) but no difference in malignancy. VATS patients had shorter LOS (2 days vs 6.5, P = 0.24). Readmission, complication and mortality rates were similar. CONCLUSIONS: Pediatric patients with apparent malignancy frequently underwent open resection compared with the thoracoscopic group, although final malignant pathology was similar. Equivalent outcomes and shorter LOS should favor a minimally invasive approach. LEVEL OF EVIDENCE: Level III.


Assuntos
Neoplasias do Mediastino , Toracotomia , Criança , Humanos , Neoplasias do Mediastino/diagnóstico por imagem , Neoplasias do Mediastino/cirurgia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
8.
Mol Cancer Ther ; 21(9): 1439-1448, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-35793464

RESUMO

Antibody-drug conjugate (ADC) research has typically focused on the release of highly potent cytotoxic agents to achieve antitumor efficacy. However, recently approved ADCs trastuzumab deruxtecan and sacituzumab govitecan release lower-potency topoisomerase inhibitors. This has prompted interest in ADCs that release lower-potency cytotoxic drugs to potentially enhance therapeutic index and reduce unwanted toxicity. Pyrrolobenzodiazepine (PBD) dimer ADCs have been widely investigated in human clinical trials, which have focused on high-potency PBDs. In this study, we evaluated five ADCs that release the low-potency PBD dimer SG3650. The relatively low clogD for this agent facilitated higher drug-to-antibody ratio (DAR) conjugation without the need for antibody engineering or functionalization of the drug. The rank order of potency for DAR 2 site-specific ADCs (conjugated at the C239i position) matched the order for the corresponding free drugs in vitro. Despite free drug SG3650 being inactive in vivo, the DAR 2 ADCs derived from the corresponding drug-linker SG3584 showed antitumor efficacy in solid (anti-HER2) and hematologic (anti-CD22) xenograft models. Antitumor activity could be enhanced by conjugating SG3584 to trastuzumab at higher DARs of 4 and 8 and by adjusting dosing and schedule. Higher-DAR conjugates were stable and displayed good rat pharmacokinetic profiles as measured by ELISA and LC/MS-MS. A single intravenous dose of isotype control SG3584 DAR 2 ADC resulted in no mortality in rats or monkeys at doses of up to 25 and 30 mg/kg, respectively. These findings suggest that further investigations of low-potency PBD dimers in ADCs that target hematologic and solid tumors are warranted.


Assuntos
Antineoplásicos , Imunoconjugados , Animais , Antineoplásicos/farmacologia , Benzodiazepinas/farmacologia , Linhagem Celular Tumoral , Humanos , Imunoconjugados/uso terapêutico , Pirróis , Ratos , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Curr Rev Musculoskelet Med ; 15(6): 456-464, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35881326

RESUMO

PURPOSE OF REVIEW: There is little doubt that the consensus has changed to favor preservation of meniscal function where possible. Accordingly, the indications for meniscal repair strategies have been refocused on the long-term interest of knee joint health. The development and refinements in surgical technique have been complemented by biological augmentation strategies to address intrinsic challenges in healing capacity of meniscal tissue, with variable effects. RECENT FINDINGS: A contemporary approach to meniscal healing includes adequate surgical fixation, meniscal and synovial tissue stimulation, and management of the intraarticular milieu. Overall, evidence supporting the use of autogenous or allogeneic cell sources remains limited. The use of FDA-approved medications to effect biologically favorable mechanisms during meniscal healing holds promise. Development and characterization of biologics continue to advance with translational research focused on specific growth factors, cell and tissue behaviors in meniscal healing, and joint homeostasis. Although significant strides have been made in laboratory and pre-clinical studies, translation to clinical application remains challenging. Finally, expert consensus and standardization of nomenclature related to orthobiologics for meniscal preservation will be important for the advancement of this field.

10.
Astrobiology ; 22(9): 1081-1098, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35704291

RESUMO

On Earth, the circulation of Fe-rich fluids in hydrothermal environments leads to characteristic iron mineral deposits, reflecting the pH and redox chemical conditions of the hydrothermal system, and is often associated with chemotroph microorganisms capable of deriving energy from chemical gradients. On Mars, iron-rich hydrothermal sites are considered to be potentially important astrobiological targets for searching evidence of life during exploration missions, such as the Mars 2020 and the ExoMars 2022 missions. In this study, an extinct hydrothermal chimney from the Jaroso hydrothermal system (SE Spain), considered an interesting geodynamic and mineralogical terrestrial analog for Mars, was analyzed using Raman spectroscopy, X-ray diffraction, and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy. The sample consists of a fossil vent in a Miocene shallow-marine sedimentary deposit composed of a marl substrate, an iron-rich chimney pipe, and a central space filled with backfilling deposits and vent condensates. The iron crust is particularly striking due to the combined presence of molecular and morphological indications of a microbial colonization, including mineral microstructures (e.g., stalks, filaments), iron oxyhydroxide phases (altered goethite, ferrihydrite), and organic signatures (carotenoids, organopolymers). The clear identification of pigments by resonance Raman spectroscopy and the preservation of organics in association with iron oxyhydroxides by Raman microimaging demonstrate that the iron crust was indeed colonized by microbial communities. These analyses confirm that Raman spectroscopy is a powerful tool for documenting the habitability of such historical hydrothermal environments. Finally, based on the results obtained, we propose that the ancient iron-rich hydrothermal pipes should be recognized as singular terrestrial Mars analog specimens to support the preparatory work for robotic in situ exploration missions to Mars, as well as during the subsequent interpretation of data returned by those missions.


Assuntos
Fósseis , Marte , Exobiologia , Sedimentos Geológicos/química , Ferro/análise , Microscopia Eletrônica de Varredura , Minerais/análise , Espectrometria por Raios X , Análise Espectral Raman/métodos , Difração de Raios X
11.
Clin Orthop Relat Res ; 480(4): 735-744, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34779790

RESUMO

BACKGROUND: Metformin, an oral drug used to treat patients with diabetes, has been associated with prolonged survival in patients with various visceral carcinomas. Although the exact mechanisms are unknown, preclinical translational studies demonstrate that metformin may impair tumor cellular metabolism, alter matrix turnover, and suppress oncogenic signaling pathways. Currently used chemotherapeutic agents have not been very successful in the adjuvant setting or for treating patients with metastatic sarcomas. We wanted to know whether metformin might be associated with improved survival in patients with a soft tissue sarcoma. QUESTIONS/PURPOSES: In patients treated for a soft tissue sarcoma, we asked: (1) Is there an association between metformin use and longer survival? (2) How does this association differ, if at all, among patients with and without the diagnosis of diabetes? METHODS: The Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database was used to identify patients with a diagnosis of soft tissue sarcoma from 2007 to 2016. Concomitant medication use was identified using National Drug Codes using the Medicare Part D event files. This database was chosen because of the large number of captured sarcoma patients, availability of tumor characteristics, and longitudinal linkage of Medicare data. A total of 14,650 patients were screened for inclusion. Patients with multiple malignancies, diagnosis at autopsy, or discrepant linkage to the Medicare database were excluded. Overall, 4606 patients were eligible for the study: 598 patients taking metformin and 4008 patients not taking metformin. A hazard of mortality (hazard ratio) was analyzed comparing patients taking metformin with those patient groups not taking metformin and expressed in terms of a 95% confidence interval. Cox regression analysis was used to control for patient-specific, disease-specific, and treatment-specific covariates. RESULTS: Having adjusted for disease-, treatment-, and patient-specific characteristics, patients taking metformin experienced prolonged survival compared with all patients not taking metformin (HR 0.76 [95% CI 0.66 to 0.87]). Associated prolonged survival was also seen when patients taking metformin were compared with those patients not on metformin irrespective of a diabetes diagnosis (HR 0.79 [95% CI 0.66 to 0.94] compared with patients with a diagnosis of diabetes and HR 0.77 [95% CI 0.67 to 0.89] compared with patients who did not have a diagnosis of diabetes). CONCLUSION: Without suggesting causation, we found that even after controlling for confounding variables such as Charlson comorbidity index, tumor grade, size, stage, and surgical/radiation treatment modalities, there was an association between metformin use and increased survival in patients with soft tissue sarcoma. When considered separately, this association persisted in patients not on metformin with and without a diabetes diagnosis. Although metformin is not normally prescribed to patients who do not have a diabetes diagnosis, these data support further study, and if these findings are substantiated, it might lead to the performance of multicenter, prospective clinical trials about the use of metformin as an adjuvant therapy for the treatment of soft tissue sarcoma in patients with and without a preexisting diabetes diagnosis. LEVEL OF EVIDENCE: Level III, therapeutic study.


Assuntos
Metformina , Sarcoma , Neoplasias de Tecidos Moles , Idoso , Humanos , Medicare , Metformina/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Programa de SEER , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Estados Unidos/epidemiologia
12.
Phys Rev Lett ; 127(16): 165101, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34723586

RESUMO

We present Magnetospheric Multiscale observations showing large numbers of slow electron holes with speeds clustered near the local minimum of double-humped velocity distribution functions of background ions. Theoretical computations show that slow electron holes can avoid the acceleration that otherwise prevents their remaining slow only under these same circumstances. Although the origin of the slow electron holes is still elusive, the agreement between observation and theory about the conditions for their existence is remarkable.

14.
Arthrosc Tech ; 10(6): e1447-e1453, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34258189

RESUMO

Transverse patella fractures with loss of knee extensor mechanism function are a common orthopaedic injury requiring operative fixation. Current accepted surgical options for noncomminuted transverse fractures include open reduction with tension band wiring. Although these procedures result in good clinical outcomes and fracture healing, symptomatic hardware from the historically used metal implants is very common. The purpose of this Technical Note is to describe a technique for treatment of transverse patellar fractures using cannulated compression screws with tensioned high-resistance suture tape functioning as the tension band. This technique provides effective, reproducible fracture fixation while minimizing symptomatic hardware, failure, and reoperation.

15.
N Am Spine Soc J ; 6: 100067, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35141632

RESUMO

BACKGROUND: Spinal epidural abscess (SEA) in children is a rare condition with dangerous sequelae, and with only 22 other cases reported in the literature, treatment algorithms are poorly understood. Quick identification of the classic tried of sepsis, back pain and neurological deficit is critical. Source identification difficult and often cannot be identified. Reported pathogens include varicella-zoster virus, S. aureus, and S pyogenes. CASE DESCRIPTION: We report a case of spontaneous pediatric SEA in a 22-month old female without obvious neurologic deficit, who underwent a T10-11 decompressive laminotomy and evacuation of abscess and subsequent 3-week course of intravenous ceftriaxone for culture positive S. pyogenes. OUTCOME: The patient showed marked improvement in symptoms after decompression. 5 weeks postoperatively after transitioning from intravenous ceftriaxone to oral ceftin, the patient redeveloped a deep space infection and was taken back for a repeat debridement. The cultures from this procedure were negative and the patient was discharged on oral clindamycin. CONCLUSIONS: Pediatric spontaneous SEA is a rare condition and early diagnosis and surgical intervention if indicated can prevent dangerous sequelae. Further studies into the surgical indications for decompression will aid in algorithmic decision making.

16.
Arthroscopy ; 37(3): 953-960, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33130059

RESUMO

PURPOSE: To evaluate the effect of soaking of anterior cruciate ligament (ACL) grafts in vancomycin solution on graft biomechanical properties at the time of implantation. METHODS: The central third of patellar tendons was harvested from mature bovine knees and prepared as a tendon-only graft or a bone-tendon-bone (BTB) graft. Tendons were wrapped in gauze soaked in vancomycin solution (VS) (5 mg/mL) or normal saline (NS) and left to stand for 30 minutes at room temperature, simulating graft exposure times in the operating room during ACL reconstruction. Tensile testing was carried out on a materials testing system with (1) low-magnitude loading (60 N at 3 mm/s) with repeated testing of tendon-only grafts; and (2) high-magnitude loading (600 N at 10 mm/min) of BTB grafts. For tendon-only grafts, specimens were first wrapped in NS-soaked gauze and underwent testing, with repeated testing performed after wrapping in gauze soaked in VS or buffered VS (pH 7.0). For BTB grafts, specimens were randomly assigned to treatment with VS or NS. RESULTS: For tendon-only grafts, there was no difference in Young's modulus (YM) after soaking with VS soaking (baseline, 12.69 MPa; treatment, 16.07 ± 4.44 MPa; P = .99) or buffered VS (baseline, 12.45 ± 4.55 MPa; treatment, 15.56 ± 2.83 MPa; P = .99). For BTB grafts, there were no differences in elongation strain (VS, 46.8% ± 7.0%; NS, 31.5% ± 13.5%, P = .19) or YM (VS, 158.4 ± 15.8 MPa; NS, 158.5 ± 23.3 MPa, P = .99). CONCLUSIONS: According to controlled biomechanical tests, vancomycin soaking of patellar tendon grafts does not adversely affect time-zero material properties. CLINICAL RELEVANCE: This study suggests that vancomycin wrapping has no immediate adverse effects on the biomechanical properties of ACL grafts. Randomized controlled trials are warranted to validate the widespread use of vancomycin soaking of tendon grafts for infection prophylaxis during ACL reconstruction.


Assuntos
Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Antibacterianos/uso terapêutico , Ligamento Patelar/transplante , Vancomicina/uso terapêutico , Animais , Fenômenos Biomecânicos , Cadáver , Bovinos , Estresse Mecânico
17.
Arthroscopy ; 36(5): 1431-1440, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31862290

RESUMO

PURPOSE: To determine whether (1) human leukocyte-platelet-rich plasma (L-PRP) or (2) leukocyte-platelet-rich fibrin (L-PRF) delivered on a hyaluronic acid (HA) scaffold at a bovine chondral defect, a simulated cartilage tear interface, in vitro would improve tissue formation based on biomechanical, histologic, and biochemical measures. METHODS: L-PRF and L-PRP were prepared from 3 healthy volunteer donors and delivered in conjunction with HA scaffolds to defects created in full-thickness bovine cartilage plugs harvested from bovine femoral condyle and trochlea. Specimens were cultured in vitro for up to 42 days. Treatment groups included an HA scaffold alone and scaffolds containing L-PRF or L-PRP. Cartilage repair was assessed using biomechanical testing, histology, DNA quantification, and measurement of sulfated glycosaminoglycan and collagen content at 28 and 42 days. RESULTS: L-PRF elicited the greatest degree of defect filling and improvement in other histologic measures. L-PRF-treated specimens also had the greatest cellularity when compared with L-PRP and control at day 28 (560.4 µg vs 191.4 µg vs 124.2 µg, P = .15); at day 48, there remained a difference, although not significant, between L-PRF versus L-PRP (761.1 µg vs 589.3 µg, P = .219) . L-PRF had greater collagen deposition when compared with L-PRP at day 42 (40.1 µg vs 16.3 µg, P < .0001). L-PRF had significantly greater maximum interfacial strength compared with the control at day 42 (10.92 N vs 0.66 N, P = .015) but had no significant difference compared with L-PRP (10.92 N vs 6.58 N, P = .536). L-PRP facilitated a greater amount of sulfated glycosaminoglycan production at day 42 when compared with L-PRF (15.9 µg vs 4.3 µg, P = .009). CONCLUSIONS: Delivery of leukocyte-rich platelet concentrates in conjunction with a HA scaffold may allow for improvements in cartilage healing through different pathways. L-PRF was not superior to L-PRP in its biomechanical strength, suggesting that both treatments may be effective in improving biomechanical strength of healing cartilage through different pathways. CLINICAL RELEVANCE: The delivery of platelet-rich concentrates in conjunction HA scaffolds may augment healing cartilaginous injuries.


Assuntos
Cartilagem Articular/metabolismo , Colágeno/metabolismo , Ácido Hialurônico/administração & dosagem , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Artropatias/terapia , Articulação do Joelho/metabolismo , Fibrina Rica em Plaquetas , Alicerces Teciduais , Animais , Bovinos , Humanos , Artropatias/metabolismo
18.
Cells Tissues Organs ; 207(2): 97-113, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655811

RESUMO

Bone grafting is the second most common tissue transplantation procedure worldwide. One of the alternative methods for bone repair under investigation is a tissue-engineered bone substitute. An ideal property of tissue-engineered bone substitutes is osteoinductivity, defined as the ability to stimulate primitive cells to differentiate into a bone-forming lineage. In the current study, we use a decellularization and oxidation protocol to produce a porcine bone scaffold and examine whether it possesses osteoinductive potential and can be used to create a tissue-engineered bone microenvironment. The decellularization protocol was patented by our lab and consists of chemical decellularization and oxidation steps using combinations of deionized water, trypsin, antimicrobials, peracetic acid, and triton-X100. To test if the bone scaffold was a viable host, preosteoblasts were seeded and analyzed for markers of osteogenic differentiation. The osteoinductive potential was observed in vitro with similar osteogenic markers being expressed in preosteoblasts seeded on the scaffolds and demineralized bone matrix. To assess these properties in vivo, scaffolds with and without preosteoblasts preseeded were subcutaneously implanted in mice for 4 weeks. MicroCT scanning revealed 1.6-fold increased bone volume to total volume ratio and 1.4-fold increase in trabecular thickness in scaffolds after implantation. The histological analysis demonstrates new bone formation and blood vessel formation with pentachrome staining demonstrating osteogenesis and angiogenesis, respectively, within the scaffold. Furthermore, CD31+ staining confirmed the endothelial lining of the blood vessels. These results demonstrate that porcine bone maintains its osteoinductive properties after the application of a patented decellularization and oxidation protocol developed in our laboratory. Future work must be performed to definitively prove osteogenesis of human mesenchymal stem cells, biocompatibility in large animal models, and osteoinduction/osseointegration in a relevant clinical model in vivo. The ability to create a functional bone microenvironment using decellularized xenografts will impact regenerative medicine, orthopedic reconstruction, and could be used in the research of multiple diseases.


Assuntos
Xenoenxertos/transplante , Células-Tronco Mesenquimais/metabolismo , Alicerces Teciduais/química , Transplante Heterólogo , Animais , Substitutos Ósseos/química , Diferenciação Celular , Linhagem Celular , Xenoenxertos/química , Camundongos , Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Osteoblastos , Osteogênese , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Suínos , Engenharia Tecidual/métodos
19.
Phys Sportsmed ; 47(4): 375-386, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30977691

RESUMO

A Type II SLAP (superior labrum anterior posterior) lesion is a tear of the superior glenoid labrum with involvement of the long head of the biceps tendon insertion. In patients that do not improve with conservative treatment, there is a great deal of variability in the surgical management of these injuries that includes arthroscopic SLAP repair, arthroscopic SLAP repair with biceps tenodesis, biceps tenodesis alone and biceps tenotomy. Each surgical technique has specific effects on a patient's postoperative course and functional recovery. Rehabilitation strategies may be best formulated on an individual basis with an open line of communication between the operating surgeon and the physical therapist. Despite an increased incidence in treatment, there is currently no consensus on the optimal surgical procedure or treatment algorithm for Type II SLAP injuries. However, in middle-aged or older patients (>35) with Type II SLAP tears, either arthroscopic suprapectoral or mini-open subpectoral biceps tenodesis is recommended due to the higher failure rates observed with arthroscopic SLAP repair in this patient group. Although more patients present with a 'Popeye' sign after biceps tenotomy, long-term functional outcome is similar between biceps tenodesis compared to tenotomy. However, more patients will experience biceps fatigue or cramping after the tenotomy procedure. Biceps tenodesis is preferred in younger, more active patients, while tenotomy is preferred in the middle-aged or older and lower demand patients. The aim of this paper is to provide a brief description of the different surgical techniques employed to address Type II SLAP lesions (arthroscopic repair, biceps tenodesis, and biceps tenotomy) and provide a review of available literature regarding outcomes and prognostic factors associated with each technique.


Assuntos
Músculo Esquelético/lesões , Procedimentos de Cirurgia Plástica/métodos , Ruptura/cirurgia , Lesões do Ombro , Traumatismos dos Tendões/cirurgia , Tendões/cirurgia , Artroscopia/métodos , Humanos , Músculo Esquelético/cirurgia , Prognóstico , Articulação do Ombro/cirurgia , Traumatismos dos Tendões/diagnóstico , Tenodese , Tenotomia
20.
Orthop Res Rev ; 11: 1-7, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30774465

RESUMO

Plantar fibromatosis (Ledderhose disease) is a rare, benign, hyperproliferative fibrous tissue disorder resulting in the formation of nodules along the plantar fascia. This condition can be locally aggressive, and often results in pain, functional disability, and decreased quality of life. Diagnosis is primarily clinical, but MRI and ultrasound are useful confirmatory adjuncts. Given the benign nature of this condition, treatment has historically involved symptomatic management. A multitude of conservative treatment strategies supported by varying levels of evidence have been described mostly in small-scale trials. These therapies include steroid injections, verapamil, radiation therapy, extracorporeal shock wave therapy, tamoxifen, and collagenase. When conservative measures fail, surgical removal of fibromas and adjacent plantar fascia is often done, although recurrence is common. This review aims to provide a broad overview of the clinical features of this disease as well as the current treatment strategies being employed in the management of this condition.

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