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1.
J Hand Surg Am ; 49(3): 212-221, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38069954

RESUMO

PURPOSE: Despite modern advancements in the treatment of late stages of wrist joint degeneration, few reliable options exist for patients requiring motion-preserving reconstruction of their radiocarpal and midcarpal joints. Vascularized composite allotransplantation (VCA) could be considered an option for wrist reconstruction in the future. The goal of this study was to describe the relevant anatomy and design a potential surgical technique for wrist VCA. METHODS: Anatomic studies were performed on 17 human upper extremities. The arterial system of each cadaver was injected with latex dye or radiographic contrast. After injecting a contrast medium visible on a computerized tomography (CT) scan, the initial three specimens were examined using microCT. This confirmed joint vascular patency and allowed for the dissection of the other specimens that were injected with latex for the study of joint vascularization and the design of the wrist VCA. We then outlined a donor and recipient surgical technique for transplant based on recipient CT scans. Customized cutting guides were designed for the transplant procedure. After the procedure, we performed angiography of the VCA to determine the vascularity of the transplant. RESULTS: Using a combined volar and dorsal approach, we were able to perform a complete wrist VCA procedure. After the completed transplant procedure, angiographic imaging of the specimens demonstrated that the flap dissection and transplantation preserved the nutrient endosteal supply to the distal end of the radius and ulna, as well as to the carpal bones and the metacarpal bases. CONCLUSIONS: The dissection of the donor, recipient, and the entire vascularized joint transplant procedure served to illustrate the anatomical feasibility of the cadaveric surgical technique. This establishes an anatomic basis for the possibility of future human clinical applications. CLINICAL RELEVANCE: This study helps investigate the anatomical feasibility of a wrist VCA.


Assuntos
Látex , Alotransplante de Tecidos Compostos Vascularizados , Humanos , Estudos de Viabilidade , Articulação do Punho/cirurgia , Meios de Contraste , Cadáver
2.
Ann Plast Surg ; 91(1): 109-116, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37450869

RESUMO

BACKGROUND: Neuroma-induced neuropathic pain is associated with loss of function and reduced quality of life. No consistently effective standard-of-care treatment has been defined. Neurocap, a bioresorbable nerve capping device, has been designed to isolate the nerve stump from surrounding tissues to reduce development of symptomatic end-neuromas. METHODS: Patients with peripheral symptomatic end-neuromas were included in a prospective, multicenter, single-arm design. Data were collected presurgery up till 24 months postsurgery. Eligible patients with neuromas were identified based on blocks using anesthetic. Intervention included surgical excision and capping of the transected proximal nerve end with the Neurocap. Main outcome measures were pain, function, recurrence of symptomatic neuroma, use of analgesics, and adverse events. RESULTS: In total, 73 patients with 50 upper-extremity and 23 lower-extremity end-neuromas were enrolled. End-neuromas were predominately located in the digits and lower leg. Statistical power of the study outcomes was preserved by 46 of 73 patients completing 24-month follow-up. The mean VAS-Pain score at baseline was 70.2 ± 17.8 (scale 0-100) and decreased significantly to 31 ± 32.5 (P < 0.001). Function significantly improved over time. The recurrence rate of confirmed symptomatic neuroma was low (2 of 98 capped nerves). Adverse event rate was low and included pain and infection; there were no unexpected device-related adverse events. Most patients reported lower use of nonsteroidal anti-inflammatory drugs, opioids, and antineuropathic medications at last follow-up compared with baseline. CONCLUSIONS: End-neuroma treatment with excision and capping resulted in long-term significant reduction in reported pain, disability, and analgesic medication use. Adverse event rate was low.


Assuntos
Neuralgia , Neuroma , Humanos , Estudos Prospectivos , Qualidade de Vida , Implantes Absorvíveis , Neuroma/cirurgia , Neuralgia/etiologia , Neuralgia/cirurgia
3.
J Reconstr Microsurg ; 36(6): 397-402, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32040964

RESUMO

BACKGROUND: Immunosuppression risks are a major concern with vascularized composite allotransplantation (VCA). As an emerging strategy, the antirejection role played by mesenchymal stem cells (MSCs) is receiving attention. However, the current literature reports are inconclusive regarding the robustness of the MSC monotherapy. Using a rat forelimb VCA model, this study tested the robustness of the immunomodulation efficacy of gingival-derived MSCs (GMSCs) and bone marrow-derived MSCs (BMMSCs). METHODS: Forelimbs were transplanted on pairs of major histocompatibility complex-incompatible rats (Wistar-Kyoto donor, Lewis [LEW] recipient). Twenty-four LEW rats were randomly divided into four groups, including control (no treatment) and three treatment groups: rapamycin (2 mg/kg/day for 28 days, postoperatively), BMMSC and GMSC, both of which received donor-derived stem cells administered intravenously on postoperative days (PODs) 0, 3, 7, and 14. Rejection was considered as 80% skin necrosis of the allograft. Microcomputed tomography (µCT) was performed to evaluate healing at osteosynthesis site. On POD 14, limbs from each group underwent histological analysis and rejection grading using the Banff system. RESULTS: Both BMMSC (15.0 days) and GMSC (14.7 days) treatment failed to prolong VCA survival in comparison with the control group (13.8 days; p > 0.050), while the rapamycin significantly delayed acute VCA rejection (24.5 days; p = 0.003). Micro-CT imaging revealed no gross visual difference across all groups. Histology revealed that the control group was most severely affected (grades III and IV) followed by MSC (grade II) and rapamycin (grade I). CONCLUSION: MSC monotherapy, both BMMSC and GMSC, did not inhibit rejection in our VCA model. Skin immunogenicity is an important issue in promoting rejection, and a concomitant immunosuppression regimen should be considered to prolong allograft survival.


Assuntos
Células-Tronco Mesenquimais , Alotransplante de Tecidos Compostos Vascularizados , Animais , Rejeição de Enxerto , Sobrevivência de Enxerto , Membro Posterior , Ratos , Ratos Endogâmicos Lew , Ratos Endogâmicos WKY , Microtomografia por Raio-X
4.
Am J Transplant ; 19(3): 865-875, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30091824

RESUMO

On July 3, 2014, the Organ Procurement and Transplantation Network/United Network for Organ Sharing was charged with the oversight of vascularized composite allograft (VCA) procurement and transplantation in the United States. As of December 31, 2017, 61 VCA programs at 27 centers were approved in the United States. Fifty candidates have been added to the waiting list at 15 centers. Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb, 10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7 pancreata). Six uterus transplants were performed from living donors. Fourteen candidates were still waiting at 9 centers on December 31, 2017. Two of the 10 uterus recipients had live births and 3 still had viable grafts. Seventeen of 18 nonuterus recipients had functioning grafts. At present, VCA is an emerging field with a small number of patients transplanted. Data on posttransplant survival and functional outcomes continue to be collected to further the understanding of this complex and evolving field. Further systematic data are important for policy refinement and assurance of patient safety.


Assuntos
Aloenxertos Compostos/transplante , Sobrevivência de Enxerto , Complicações Pós-Operatórias , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/normas , Alotransplante de Tecidos Compostos Vascularizados/normas , Listas de Espera/mortalidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Estados Unidos , Adulto Jovem
5.
Pediatr Transplant ; 23(5): e13466, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31081211

RESUMO

Listing the world's first pediatric bilateral hand transplant patient for a donor posed many challenges including matching the appropriate donor age, bone size, skin tone, and growth potential in an already limited donor population. This study describes the prevalence and distribution of potential pediatric VCA donors in the United States. We assessed the UNOS database from 2008 to 2015 to identify the prevalence of potential pediatric VCA donors. Standard VCA inclusion and exclusion criteria were applied to the dataset for all pediatric solid organ donors. Frequency analyses were performed of characteristics important for VCA matching. The dataset began with 57 300 brain-dead donors and after applying the inclusion and exclusion criteria including age <18, decreased to 4663 (8.1%). The number of pediatric potential VCA donors per UNOS region ranged from 11 to 112/year. The majority of pediatric potential VCA donors were blood type O Whites, with the least common profile being blood type AB of "other" ethnicity. The present study confirmed that pediatric VCA donors are rare and may require longer travel times for procurement and listing at multiple centers in order to find a suitable donor. This will be a limiting factor for the expansion of pediatric VCA.


Assuntos
Mãos/cirurgia , Doadores de Tecidos/provisão & distribuição , Alotransplante de Tecidos Compostos Vascularizados , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estados Unidos
6.
Pain Med ; 20(12): 2528-2538, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30657996

RESUMO

OBJECTIVES: To evaluate the prevention of opioid-induced nausea and vomiting (OINV) and the relief of moderate to severe acute pain by CL-108, a novel drug combining a low-dose antiemetic (rapid-release promethazine 12.5 mg) with hydrocodone 7.5 mg/acetaminophen 325 mg (HC/APAP) was used. METHODS: This was a multicenter, randomized, double-blind, placebo- and active-controlled multidose study. After surgical extraction of two or more impacted third molar teeth (including at least one mandibular impaction), 466 patients with moderate to severe pain (measured on a categorical pain intensity scale [PI-CAT]) were randomized to CL-108, HC/APAP, or placebo. Over the next 24 hours, patients used the PI-CAT to assess pain at regular intervals whereas nausea, vomiting, and other opioid-related side effects were also assessed prospectively. Study medications were taken every four to six hours as needed; supplemental rescue analgesic and antiemetic medications were permitted. Co-primary end points were the incidence of OINV and the time-weighted sum of pain intensity differences over 24 hours (SPID24). RESULTS: Relative to HC/APAP treatment alone, CL-108 treatment reduced OINV by 64% (P < 0.001). Treatment with CL-108 significantly reduced pain intensity compared with placebo (SPID24 = 16.2 vs 3.5, P < 0.001). There were no unexpected or serious adverse events. CONCLUSIONS: CL-108 is a safe and effective combination analgesic/antiemetic for the prevention of OINV during treatment of moderate to severe acute pain.


Assuntos
Acetaminofen/uso terapêutico , Dor Aguda/tratamento farmacológico , Analgésicos Opioides/uso terapêutico , Antieméticos/uso terapêutico , Hidrocodona/uso terapêutico , Náusea/prevenção & controle , Dor Pós-Operatória/tratamento farmacológico , Prometazina/uso terapêutico , Extração Dentária , Vômito/prevenção & controle , Adolescente , Adulto , Analgésicos Opioides/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Masculino , Dente Serotino/cirurgia , Náusea/induzido quimicamente , Medição da Dor , Dente Impactado/cirurgia , Resultado do Tratamento , Vômito/induzido quimicamente , Adulto Jovem
8.
Ann Plast Surg ; 80(4): 364-372, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29389704

RESUMO

BACKGROUND: The medial femoral condyle (MFC) flap has become a popular choice for treatment of small bony defects. We aim to describe outcomes after MFC flap treatment of upper and lower extremity osseous defects and test the null hypothesis that no factors influence risks for nonunion, increased time to union, and complications. METHODS: A retrospective chart review was performed on all patients undergoing MFC free vascularized bone flaps by the senior author between May 2010 and March 2016. Preoperative, intraoperative, and postoperative data were collected. RESULTS: We identified 29 patients for inclusion (22 upper and 7 lower extremity reconstructions) treated with the MFC flap for diagnoses including long bone nonunion, avascular necrosis (AVN), or AVN with nonunion. Mean postoperative follow-up was 56 weeks. The average patient was 38 years old (range = 17-61 years) and had undergone 1.5 previous failed surgeries. Union was achieved in 86% of patients at a mean of 15.8 weeks (83% at 17.9 weeks for the scaphoid). No patient with lunate AVN progressed. There were no intraoperative flap complications or bone flap loss, but 28% underwent additional unplanned surgical procedures. We identified previous surgery as a risk factor for delayed union but did not observe significant risk factors predictive of nonunion or complications requiring unplanned reoperation. CONCLUSIONS: Extremity reconstruction using the MFC corticocancellous flap results in a high rate of union yet minimal donor morbidity for a challenging patient cohort. Previous surgery was a risk factor for increased time to union.


Assuntos
Transplante Ósseo/métodos , Extremidades/cirurgia , Fêmur/transplante , Retalhos de Tecido Biológico/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Adulto , Extremidades/diagnóstico por imagem , Extremidades/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteonecrose , Estudos Retrospectivos , Resultado do Tratamento
9.
Microsurgery ; 38(6): 605-610, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28657669

RESUMO

INTRODUCTION: The use of arteriovenous (AV) loops in microsurgical lower extremity reconstruction is a controversial topic. The objective of the present study was to assess the impact of AV loops on complication rates following microsurgical reconstruction of posttraumatic lower extremity defects. PATIENTS AND METHODS: Patients who underwent free flap coverage of posttraumatic defects in combination with an AV loop (Group 1) were identified and matched for age, body mass index (BMI), tobacco use, defect location, and flap type with patients who underwent reconstruction without vein grafts (Group 2). Outcomes of interest included complication rate and flap loss rate. RESULTS: Groups 1 and 2 consisted of 10 patients each with a mean age of 51 years (range, 21-79 years) and 47.3 years (range, 22-69 years), respectively (P = 0.596). No differences were noted regarding flap loss (P = 1.0), intraoperative (P = 0.474) or postoperative complication rate [surgical site infection (P = 1.0), bleeding (P = 1.0), delayed wound healing (P = 0.23), dehiscence (P = 0.58), and osseous non-union (P = 1.0)]. Only one flap loss was noted in Group 1. The only differences were increased operative time (P = 0.03) and increased length of stay (P = 0.009) in Group 1. CONCLUSION: Our results suggest that utilization of vein grafts with creation of AV loops followed by single-stage division and free flap transfer for reconstruction of posttraumatic lower extremity defects achieve reconstructive outcomes similar to those obtained in patients in whom no vein grafts are necessary.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Retalhos de Tecido Biológico/irrigação sanguínea , Traumatismos da Perna/cirurgia , Microcirurgia/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Feminino , Humanos , Tempo de Internação , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Duração da Cirurgia , Adulto Jovem
10.
Microsurgery ; 36(8): 672-675, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26566967

RESUMO

In this report, we present a rat orthotopic forelimb allotransplantation model. Eight forelimbs were transplanted from Brown Norway rats to Lewis rats. Axillary vessels of transplant were used as the vascular pedicles, which were anastomosed to the external jugular vein and common carotid artery of the recipient rat. The ulnar, radial, and median nerves were also repaired. Among rats, a tapered dose of cyclosporine was administered in five rats. In other three rats, no immunosuppressive therapy was given. The viability and signs of rejection of transplanted forelimbs, sensation recovery, bone healing, and histology were assessed up to the 90th postoperative day. All of rats but one survived surgery. All of transplanted forelimbs survived. In the rats treated with cyclosporine the transplanted forelimbs achieved long-term survival with motion and sensation recovery. On 90th day after surgery, bone healing was achieved. There was no sign of rejection in histology. In the rats without cyclosporine treatment, the transplanted forelimbs experienced tissue necrosis started from day 12 postoperatively. This experimental study showed the feasibility of orthotopic forelimb allotransplantation in the rat model. © 2015 Wiley Periodicals, Inc. Microsurgery 36:672-675, 2016.


Assuntos
Membro Anterior/transplante , Alotransplante de Tecidos Compostos Vascularizados/métodos , Animais , Ciclosporina/uso terapêutico , Membro Anterior/irrigação sanguínea , Membro Anterior/inervação , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Imunossupressores/uso terapêutico , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Transplante Homólogo/métodos
11.
J Craniofac Surg ; 27(1): e102-5, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26703058

RESUMO

The purpose of this study was to compare overall patient satisfaction after orthognathic surgery with the following specific categories: appearance, functional ability, general health, sociability, and patient-clinician communication. A 16-question survey was developed and administered to include patients at either 6 or 12 months after orthognathic surgery between June 2013 and June 2014 at the University of Pennsylvania and Massachusetts General Hospital. The predictor variables included age, sex, type of procedure, medical comorbidities, intra- or postoperative complications, and presence of paresthesia. The outcome variable was patient satisfaction overall and in each category based on a Likert scale (0: not satisfied at all to 5: very satisfied).A total of 37 patients completed the survey and had a high overall rate of satisfaction (100% of responses were 4 or 5 on Likert scale). Overall satisfaction had the highest correlation with appearance (ρ=0.52, P=0.0009) followed by sociability (ρ=0.47, P=0.004), patient-clinician communication (ρ=0.38, P=0.02) functionality (ρ=0.19, P=0.26), and general health (ρ = -0.11, P = 0.51). Patients had high satisfaction scores for orthognathic surgery. Satisfaction with postoperative appearance had the strongest correlation with overall satisfaction.


Assuntos
Procedimentos Cirúrgicos Ortognáticos/psicologia , Satisfação do Paciente , Adolescente , Adulto , Comunicação , Deglutição/fisiologia , Oclusão Dentária , Relações Dentista-Paciente , Estética , Feminino , Seguimentos , Nível de Saúde , Humanos , Relações Interpessoais , Complicações Intraoperatórias/psicologia , Masculino , Mastigação/fisiologia , Osteotomia de Le Fort/psicologia , Osteotomia Sagital do Ramo Mandibular/psicologia , Parestesia/psicologia , Complicações Pós-Operatórias/psicologia , Respiração , Sono/fisiologia , Fala/fisiologia , Adulto Jovem
13.
J Arthroplasty ; 28(8 Suppl): 7-10, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23953964

RESUMO

In order to identify risk factors for readmissions following total hip arthroplasty (THA) and the causes and financial implications of such readmissions, we analyzed clinical and administrative data on 1583 consecutive primary THAs performed at a single institution. The 30-day readmission rate was 6.51%. Increased age, length of stay, and body mass index were associated with significantly higher readmission rates. The most common re-admitting diagnoses were deep infection, pain, and hematoma. Average profit was lower for episodes of care with readmissions ($1548 vs. $2872, P=0.028). If Medicare stops reimbursing for THA readmissions, the institution under review would sustain an average net loss of $11,494 for episodes of care with readmissions and would need to maintain readmission rates below 23.6% in order to remain profitable.


Assuntos
Artroplastia de Quadril/economia , Readmissão do Paciente/economia , Complicações Pós-Operatórias/economia , Fatores Etários , Idoso , Distinções e Prêmios , Índice de Massa Corporal , Centers for Medicare and Medicaid Services, U.S./economia , Estudos de Coortes , Controle de Custos/tendências , Feminino , Custos de Cuidados de Saúde/tendências , Hematoma/economia , História do Século XXI , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/economia , Estudos Retrospectivos , Fatores de Risco , Infecção da Ferida Cirúrgica/economia , Estados Unidos
14.
Plast Reconstr Surg Glob Open ; 11(8): e5212, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37593694

RESUMO

Free flap surgery for limb salvage has become the surgical standard for reconstruction of bone and soft tissue with success rates and flap survivals of 94%-95%. The soft tissue defect dictates the technique of coverage. In many cases, multiple techniques of soft tissue coverage are necessary, ranging from myocutaneous and fasciocutaneous free flaps to split-thickness skin grafts (STSGs). It has been shown that fasciocutaneous free flaps are not inferior to muscle flaps in treatment of lower leg limb salvage. Although a complete flap loss is rare, it is not uncommon to have partial flap necrosis, wound dehiscence, or secondary soft tissue defects, necessitating further minor reconstruction, which we call "touch up" skin grafts. In many of these secondary procedures, split thickness skin grafts are sufficient. We have been using the skin portion of the fasciocutaneous free flap as a donor site for harvesting STSGs for quite some time without disadvantages. We believe that minimizing additional donor site morbidity is of great importance. The free tissue transfer is insensate and readily available at the site of injury, making prepping and draping simple as well as cosmetically acceptable, as the transferred free tissue, unfortunately, is rarely a perfect fit. The associated pain, discomfort, and scar of an additional donor site can be avoided. In our case series, we did not experience any flap loss, infections, or complications. Thus, harvesting an STSG from a fasciocutaneous free flap seems to be a feasible option to be considered in limb salvage.

15.
Ann Plast Surg ; 69(4): 451-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22964666

RESUMO

PURPOSE: The purpose of this study was to assess the microsurgical training background of current members of the American Society for Surgery of the Hand (ASSH) and then determine the impact that prior training had on current microsurgical practice. METHODS: A 174-item anonymous Web-based survey was sent to all active ASSH members. Items addressed prior residency and fellowship training, practice setting, and training, comfort, and practice of specific microsurgical procedures. Data were analyzed using frequency tables, cross-tabulations, χ tests, and other established statistical methods. RESULTS: Surveys were received from 377 of 2019 ASSH members (18.7% response rate). Residency training was in orthopedics (n=249, 66.9%), plastic surgery (n=56, 15.1%), or general surgery (n=55, 14.8%). Fellowship training was in orthopedic (n=242, 65.1%), combined (n=65, 17.5%), and plastic surgery (n=15, 4%) programs. Microsurgical procedures involving nerves were performed by 96.6% of surgeons (n=337), with no significant differences between surgeons trained in plastic surgery versus orthopedic surgery residencies, and no differences between those who had completed orthopedic versus combined fellowships. Of the surgeons completing the survey, 56.1% (n=208) performed general microvascular procedures, 50% (n=179) performed replantations, and 30.6% (n=113) performed free flaps. Hand surgeons who completed plastic surgery residencies were more likely to perform general microvascular procedures, replantations, and free flaps than surgeons trained in orthopedic residencies. When comparing training in orthopedic and combined fellowships, there was no difference in performance of replantations, free flaps, general microvascular surgery, or microsurgical procedures involving nerves. CONCLUSIONS: Training backgrounds have a substantial impact on current microsurgical practice, with residency having the most significant effect. Specifically, hand surgeons trained in plastic surgery residency programs are more likely to perform replantations, free tissue transfer, and general microvascular surgery than those who completed orthopedic residencies. Fellowship training background does not significantly affect microsurgical practice.


Assuntos
Cirurgia Geral/educação , Mãos/cirurgia , Internato e Residência , Microcirurgia/estatística & dados numéricos , Ortopedia/educação , Padrões de Prática Médica/estatística & dados numéricos , Cirurgia Plástica/educação , Competência Clínica , Bolsas de Estudo , Retalhos de Tecido Biológico/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Humanos , Microcirurgia/educação , Transferência de Nervo/educação , Transferência de Nervo/estatística & dados numéricos , Reimplante/educação , Reimplante/estatística & dados numéricos , Sociedades Médicas , Estados Unidos
16.
Sci Transl Med ; 13(576)2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441426

RESUMO

Osteoarthritis (OA) is a widespread joint disease for which there are no disease-modifying treatments. Previously, we found that mice with cartilage-specific epidermal growth factor receptor (EGFR) deficiency developed accelerated knee OA. To test whether the EGFR pathway can be targeted as a potential OA therapy, we constructed two cartilage-specific EGFR overactivation models in mice by overexpressing heparin binding EGF-like growth factor (HBEGF), an EGFR ligand. Compared to wild type, Col2-Cre HBEGF-overexpressing mice had persistently enlarged articular cartilage from adolescence, due to an expanded pool of chondroprogenitors with elevated proliferation ability, survival rate, and lubricant production. Adult Col2-Cre HBEGF-overexpressing mice and Aggrecan-CreER HBEGF-overexpressing mice were resistant to cartilage degeneration and other signs of OA after surgical destabilization of the medial meniscus (DMM). Treating mice with gefitinib, an EGFR inhibitor, abolished the protective action against OA in HBEGF-overexpressing mice. Polymeric micellar nanoparticles (NPs) conjugated with transforming growth factor-α (TGFα), a potent EGFR ligand, were stable and nontoxic and had long joint retention, high cartilage uptake, and penetration capabilities. Intra-articular delivery of TGFα-NPs effectively attenuated surgery-induced OA cartilage degeneration, subchondral bone plate sclerosis, and joint pain. Genetic or pharmacologic activation of EGFR revealed no obvious side effects in knee joints and major vital organs in mice. Together, our studies demonstrate the feasibility of using nanotechnology to target EGFR signaling for OA treatment.


Assuntos
Cartilagem Articular , Osteoartrite , Animais , Modelos Animais de Doenças , Receptores ErbB , Articulação do Joelho , Camundongos , Osteoartrite/tratamento farmacológico
17.
Clin Orthop Relat Res ; 468(2): 590-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19701672

RESUMO

UNLABELLED: Skeletal reconstruction of large tumor resection defects is challenging. Free vascularized fibular transfer offers the potential for rapid autograft incorporation in limbs compromised by adjuvant chemotherapy or radiation. We retrospectively reviewed 30 patients treated with free vascularized fibular graft reconstruction of large skeletal defects after tumor resections (mean defect length, 14.8 cm). The minimum followup was 2 years (mean, 4.9 years; range, 2-15 years). One patient died with liver and lung metastases at 3 years postoperatively. Loss of limb occurred in one patient. Five patients either had metastatic disease (one patient) or had metastatic disease (four patients) develop after treatment, with a mean time to metastasis of 18 months. The overall complication rate was 16 of 30 (53%), with a reoperation rate of 12 of 30 (40%). Union was attained in all 30 grafts. Primary union was attained in 23 (77%) at a mean of 6 months. Secondary union was achieved in seven (23%) after revision fixation and bone grafting; the mean subsequent time to union was 9.2 months, with an index of 1.33 additional operations per patient. Graft fracture (20%) and infection (10%) were other common complications. Despite a high complication rate, free vascularized fibular graft reconstruction offers a reliable treatment of large skeletal defects after tumor resection without increased risk of limb loss, local recurrence, or tumor metastasis. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo , Fíbula/irrigação sanguínea , Fíbula/transplante , Adolescente , Adulto , Idoso , Amputação Cirúrgica , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Transplante Ósseo/efeitos adversos , Criança , Feminino , Fíbula/diagnóstico por imagem , Fraturas Ósseas/etiologia , Sobrevivência de Enxerto , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Osseointegração , Radiografia , Reoperação , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
18.
JBJS Case Connect ; 10(3): e19.00296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32910616

RESUMO

CASE: A 20-year-old man with congenital arthrogryposis presented for evaluation of biceps dysfunction. Although his left elbow was supple with 0° to 110° passive range of motion (ROM), he had no active ROM and was unable to perform basic activities of daily living such as bringing his hand to his mouth to feed himself. A bipolar latissimus transfer was performed to achieve functional active ROM. CONCLUSION: Bipolar latissimus transfer is a challenging, robust flap able to restore active elbow flexion in select groups of patients with biceps dysfunction, supple elbow, and functional latissimus dorsi.


Assuntos
Artrogripose/cirurgia , Músculos Superficiais do Dorso/transplante , Extremidade Superior/fisiologia , Artrogripose/fisiopatologia , Humanos , Masculino , Amplitude de Movimento Articular , Adulto Jovem
19.
Clin Pharmacol Ther ; 106(3): 632-641, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30929268

RESUMO

The mechanisms underlying interindividual variability in analgesic efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) are not well understood. Therefore, we performed pain phenotyping, functional neuroimaging, pharmacokinetic/pharmacodynamic assessments, inflammation biomarkers, and gene expression profiling in healthy subjects who underwent surgical extraction of bony impacted third molars and were treated with ibuprofen (400 mg; N = 19) or placebo (N = 10). Analgesic efficacy was not associated with demographic or clinical characteristics, ibuprofen pharmacokinetics, or the degree of cyclooxygenase inhibition by ibuprofen. Compared with partial responders to ibuprofen (N = 9, required rescue medication within the dosing interval), complete responders (N = 10, no rescue medication) exhibited greater induction of urinary prostaglandin metabolites and serum tumor necrosis factor-α and interleukin 8. Differentially expressed genes in peripheral blood mononuclear cells were enriched for inflammation-related pathways. These findings suggest that a less pronounced activation of the inflammatory prostanoid system is associated with insufficient pain relief on ibuprofen alone and the need for additional therapeutic intervention.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Ibuprofeno/farmacologia , Dor Pós-Operatória/tratamento farmacológico , Prostaglandina-Endoperóxido Sintases/efeitos dos fármacos , Adulto , Método Duplo-Cego , Feminino , Humanos , Ibuprofeno/uso terapêutico , Mediadores da Inflamação/metabolismo , Masculino , Fenótipo , Transcriptoma , Adulto Jovem
20.
Clin Oral Implants Res ; 19(11): 1197-201, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18983324

RESUMO

OBJECTIVES: Severe alveolar bone loss affects dental implant placement. Bone augmentation by grafting iliac crest bone rich in osteoprogenitor cells such as bone marrow stromal cells (BMSCs) requires a second surgical procedure in non-orofacial bone. Skeletal site-specific osteogenesis indicates maxilla and mandible BMSCs are highly proliferative and exhibit osteogenic properties superior to iliac crest BMSCs. Alveolar bone can be easily obtained during routine dental surgery, but it is unclear if titanium-attached alveolar BMSCs will retain their superior osteogenic properties. This study evaluated and compared in vitro osteogenic properties of titanium-attached maxilla and iliac crest BMSCs in same individuals. MATERIAL AND METHODS: Primary culture of maxilla and iliac crest BMSCs from four normal healthy volunteers was expanded in culture. In 24-well plates, first passage BMSCs were seeded directly (1 x 10(4) cells/well) on oxidized titanium disks (1.27 cm diameter and 2 mm thickness) or tissue culture plate. Each cell type was assessed for affinity for titanium, post-attachment survival and osteogenic differentiation based on alkaline phosphatase and osteopontin expressions. RESULTS: There was no difference in the affinity of maxilla and iliac crest BMSCs to titanium. However, titanium-attached maxilla BMSCs were apparently more osteogenically responsive than iliac crest cells based on calcium accumulation and gene expression of alkaline phosphatase and osteopontin. But these differences were not statistically significant in this small patient sample. CONCLUSION: Maxilla and iliac crest BMSCs have similar attachment affinity for titanium. This pilot study indicates that titanium-attached maxilla BMSCs are more osteogenically responsive and may be a viable and more readily available donor graft material in implant dentistry.


Assuntos
Células da Medula Óssea/fisiologia , Ílio/citologia , Maxila/citologia , Osteogênese , Fosfatase Alcalina/biossíntese , Calcificação Fisiológica , Adesão Celular , Proliferação de Células , Células Cultivadas , Ligas Dentárias , Humanos , Osteopontina/biossíntese , Projetos Piloto , Células Estromais/fisiologia , Alicerces Teciduais , Titânio
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