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1.
J Orthop Surg (Hong Kong) ; 31(1): 10225536231155749, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36815584

RESUMO

PURPOSE: Joint arthroplasty has become increasingly more common in the United States, and it is important to examine the patient-based risk factors and surgical variables associated with hospital readmissions. The purpose of this study was to identify stratified rates and risk factors for readmission after upper extremity (shoulder, elbow, and wrist) and lower extremity (hip, knee, and ankle) arthroplasty. METHODS: All patients undergoing upper and lower extremity arthroplasty from 2008-2018 were identified using the National Surgical Quality Improvement Program dataset. Patient demographics, medical comorbidities and surgical characteristics were examined utilizing uni- and multi-variate analysis for significant predictors of 30-days hospital readmission. RESULTS: A total of 523,523 lower and 25,215 upper extremity arthroplasty patients were included in this study. A number of 22,183 (4.2%) lower and 1072 (4.4%) upper extremity arthroplasty patients were readmitted within 30 days of discharge. Significant risk factors for 30-days readmission after lower extremity arthroplasty included age, Body Mass Index (BMI), operative time, dependent functional status, American Society of Anesthesiologists (ASA) score ≥3, increased length of stay, and various medical comorbidities such as diabetes, tobacco dependency, and chronic obstructive pulmonary disease (COPD). An overweight BMI was associated with a lower odds of 30-days readmission when compared to a normal BMI for lower extremity arthroplasty. Analysis for upper extremity arthroplasty revealed similar findings of significant risk factors for 30-days hospital readmission, although diabetes mellitus was not found to be a significant risk factor. CONCLUSION: Nearly one in 25 patients undergoing upper and lower extremity arthroplasty experiences hospital readmission within 30-days of index surgery. There are several modifiable risk factors for 30-days hospital readmission shared by both lower and upper extremity arthroplasty, including tobacco smoking, COPD, and hypertension. Optimization of these medical comorbidities may mitigate the risk short-term readmission following joint arthroplasty procedures and improve overall cost effectiveness of perioperative surgical care.


Assuntos
Artroplastia de Quadril , Doença Pulmonar Obstrutiva Crônica , Humanos , Complicações Pós-Operatórias/etiologia , Readmissão do Paciente , Fatores de Risco , Artroplastia de Quadril/efeitos adversos , Extremidade Inferior/cirurgia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/cirurgia , Estudos Retrospectivos
2.
Arthroscopy ; 38(10): 2887-2896.e4, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35662668

RESUMO

PURPOSE: To use an expected-value decision analysis to determine the optimal treatment decision between repair and biceps tenodesis (BT) for an isolated type II SLAP injury. METHODS: An expected-value decision analysis with sensitivity analysis was performed to systematically quantify the clinical decision. To determine outcome probabilities, a decision tree was constructed (repair vs BT) and a meta-analysis was conducted. To determine outcome utilities, we evaluated 70 patients with a chief complaint of shoulder pain regarding age, sex, Shoulder Activity Level, and visual analog scale score in terms of potential outcome preferences. Statistical fold-back analysis was performed to determine the optimal treatment. One-way sensitivity analysis determined the effect of changing the reinjury rate on the expected value of BT. RESULTS: The overall expected value was 8.66 for BT versus 7.19 for SLAP repair. One-way sensitivity analysis showed that BT was the superior choice if reinjury rates were expected to be lower than 28%. Meta-analysis of 23 studies and 908 patients revealed that the probability of a "well" outcome was significantly greater for BT (87.8%; 95% confidence interval [CI], 74.9%-94.6%; I2 = 0.0%) than for SLAP repair (62.9%; 95% CI, 55.9%-69.3%; I2 = 65.9%; P = .0023). The rate of reinjury was 1.5% for BT (95% CI, 0.05%-33.8%; I2 = 0.0%) and 6.4% for repair (95% CI, 4.2%-9.6%; I2 = 24%), which was not statistically significantly different (P = .411). A total of 50 participants (mean age, 25.4 years [standard deviation, 8.9 years]; 76% male patients; 50% overhead athletes) met the inclusion criteria. Forty-six percent of participants had a high Shoulder Activity Level score. CONCLUSIONS: Decision analysis showed that BT is preferred over repair for an isolated type II SLAP tear based on greater expected value of BT versus repair. Meta-analysis showed more frequent favorable outcomes with BT. Surgeons can use this information to tailor discussions with patients. LEVEL OF EVIDENCE: Level IV, meta-analysis of Level I-IV studies.


Assuntos
Relesões , Lesões do Ombro , Articulação do Ombro , Tenodese , Adulto , Artroscopia , Técnicas de Apoio para a Decisão , Humanos , Lesões do Ombro/cirurgia , Articulação do Ombro/cirurgia
3.
Curr Rev Musculoskelet Med ; 14(5): 297-303, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34581990

RESUMO

PURPOSE OF REVIEW: Reverse total shoulder arthroplasty (rTSA) has emerged as an effective treatment option for patients with rotator cuff arthropathy resulting from irreparable rotator cuff tears. However, patients with combined loss of abduction and external rotation may still experience functional deficits after rTSA. One option to address this has been the latissimus dorsi tendon transfer (LDTT), or modified L'Episcopo procedure. The purpose of this review is to describe the role of LDTT with rTSA and to critically evaluate the evidence on whether a supplemental LDTT ultimately improves patient function. RECENT FINDINGS: Patients with an intact rotator cuff demonstrated a significant increase in active external rotation following rTSA compared to those with a deficient rotator cuff following rTSA. Compared to their pre-operative baseline assessments, patients who undergo rTSA with LDTT report significant improvements in active external rotation. However, a randomized trial comparing rTSA patients with and without LDTT failed to demonstrate a significant difference in active external rotation or patient-reported outcomes between groups. Observational studies have shown that patients experience significant improvements in active range of motion and various patient-reported outcome measures following rTSA with latissimus dorsi tendon transfer. When directly comparing rTSA with LDTT to rTSA alone, the current literature fails to demonstrate a statistically significant difference in active external rotation or patient-reported outcomes at short-term follow-up. Further randomized controlled trials are required to fully understand the potential benefits of added tendon transfer in the rTSA patient population.

4.
J Burn Care Res ; 42(6): 1210-1214, 2021 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-33608722

RESUMO

Nucleated red blood cells (NRBCs) have been studied in critically ill and injured patients as a predictor of increased in-hospital mortality and poor clinical outcomes. While prior studies have demonstrated the prognostic power of NRBCs in the critical patient, there has been a paucity of literature available describing their value as a prognostic indicator in the severely burned patient. This retrospective observational study was conducted from 2012 to 2017. Inclusion criteria for this study included all burn patients with total body surface area > 10% who were aged ≥ 15 years. Demographic and clinical data were collected from the electronic medical record system. Data analysis consisted of descriptive and comparative analysis using SPSS. Two hundred and nineteen patients (17.5%) met inclusion criteria with 51 (23.3%) patients positive for NRBCs. The presence of NRBCs had an increased mortality rate with an odds ratio of 6.0 (P = .001; 2.5, 14.5); was more likely to appear in older patients (P < .001); and was associated with increased hospital length of stay (P < .001), injury severity scores (P < .001), and complications. The presence of NRBCs even at the low concentrations reported in our study showed a 6-fold increase in the rate of mortality. With the current improvements in burn care leading to higher survival rates, the need to improve upon the numerous models that have been developed to predict mortality in severe burn patients is clear given the significantly increased risk of death that the presence of NRBCs portends.


Assuntos
Queimaduras/metabolismo , Contagem de Eritrócitos , Eritrócitos Anormais/metabolismo , Adolescente , Adulto , Idoso , Plaquetas/metabolismo , Queimaduras/mortalidade , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Estudos Retrospectivos , Fatores de Risco
5.
J Burn Care Res ; 42(2): 182-185, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33200770

RESUMO

The increasing trend of admissions due to recreational fires prompted a 5-year review. The retrospective chart review of pediatric burn injuries from campfires or bonfires treated at a single medical center's burn unit. The study included children within the ages of 0 to 15 admitted or transferred from January 2012 to December 2016 with first, second, and/or third degree burns by bonfires. These patients accrued burns due to active fires as well as postfire ember contact. Two hundred-eighty nine (289) were pediatric admissions out of which 66 (22.8%) were pediatric admissions associated with recreational fires. The mean annual admission for campfire or bonfire burns was 13 ± .98. The mean age was 4 ± 2.47 years. Gender distribution revealed 21 female and 45 male pediatric patients under the age of 15. From the available data, 8 (12%) of these burns occurred at home in the backyard and 16 (24%) at a public camp or park. Injury mechanisms were more commonly a result of direct contact with hot coals and embers (65%). Falls into open flame accounted for 23% (n = 15) of injuries, and flash flames accounted for 12% of injuries (n = 8). The presence of supervision was unknown in 56%; however, lack of supervision was a factor in 14% of our study population. By gaining a better understanding of the type of injury, mechanism of injury, and the demographic of recreational fire burn victims, policy, and awareness campaigns were instituted in an effort to reduce the incidence of recreational fire burns.


Assuntos
Acidentes/estatística & dados numéricos , Queimaduras/epidemiologia , Queimaduras/terapia , Acampamento/estatística & dados numéricos , Incêndios/estatística & dados numéricos , Adolescente , Unidades de Queimados , Criança , Pré-Escolar , Feminino , Traumatismos do Pé/epidemiologia , Traumatismos do Pé/terapia , Traumatismos da Mão/epidemiologia , Traumatismos da Mão/terapia , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Fatores de Risco
6.
Arthrosc Sports Med Rehabil ; 2(4): e399-e415, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32875305

RESUMO

PURPOSE: To systematically review the operative versus nonoperative methods for management of iliotibial band syndrome (ITBS) with comparison of the respective clinical outcomes. METHODS: By adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, 3 databases (Medline, Scopus, Web of Science) searched from inception to October 2019 for randomized clinical trials (RCTs) and observational studies on humans that reported the outcomes following operative or nonoperative management of ITBS. Excluded were case reports, case series with <5 participants, review articles, non-English articles, and non-peer-reviewed articles. The Methodological Index for Non-Randomized Studies (MINORS) criteria for observational studies and the Cochrane Risk of Bias Tool for RCTs were used for quality control. RESULTS: There were 15 eligible studies (9 for operative,6 for nonoperative treatment) examining 179 athletes (mean age 27.3 years, range: 17-53) who received conservative therapy for ITBS and 200 athletes (mean age 30.1 years, range: 14-63) who underwent surgical treatment. Most athletes were runners (65%). The mean follow-up time was significantly longer in studies reporting the outcomes following operative compared with nonoperative ITBS treatment (33.5 vs 2 months, respectively, P < .05). Significant variability in the methods used to assess the clinical outcomes precluded meta-analysis. The most commonly reported (7/9 studies, 77.7%) variable for postoperative evaluation in athletes was the return to sport rate (range: 81%-100%). Significant reduction in pain was consistently (6/6 studies,100%) found among the studies reporting the results of conservative ITBS treatment. The included RCTs were of good (1/5, 20%), fair (2/5, 40%), or poor (2/5, 40%) quality, whereas the average MINORS score was 7.4 (range: 3-13) for observational studies. The level of evidence ranged from Level II (6/15 studies) to IV (9/15 studies). CONCLUSIONS: Based on the current literature and at a maximum follow-up time of 6 months, conservative therapy can effectively reduce ITBS symptoms in athletes. Multiple surgical options exist for athletes who do not respond to nonoperative measures, with a reported return to sport rate between 81% and 100%. LEVEL OF EVIDENCE: Systematic review of Level II and IV studies.

7.
Arch Osteoporos ; 15(1): 80, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32468516

RESUMO

In this retrospective study, approximately 77% of patients who attended their osteoporosis clinic follow-up appointments following a fragility fracture were started on medical treatment. Approximately 82% of those patients were adherent with their treatment, and 1% of patients sustained a secondary fragility fracture while on treatment. PURPOSE: To assess the effects of implementation of a fracture liaison service at a tertiary care academic medical center on osteoporosis treatment adherence and secondary fracture rates. METHODS: We retrospectively reviewed over 6000 patients age 50 years or greater during a 5-year time period (2013-2018). Patients were identified as having a fragility fracture on presentation to the emergency department at the Wake Forest Baptist Medical Center and referred to our osteoporosis clinic using the electronic medical record. Data were collected regarding those patients who were recommended treatment, started treatment, maintained adherent to treatment, and those who sustained a secondary fracture. RESULTS: 6178 patients were identified as having a fragility fracture and referred to the osteoporosis clinic. 2631 of these patients successfully had a scheduled outpatient appointment at the osteoporosis clinic, of which 1937 attended their initial appointment and 1840 of these patients were prescribed treatment. Of the 1840 patients who were initially prescribed medication, 1416 (76.96%) initiated their treatment, and 1156 (81.64%) remained adherent to treatment. Fifteen patients (1.05%) on treatment sustained a secondary fracture after initiation of therapy. CONCLUSION: Implementation of a fracture liaison service at a tertiary care academic medical center is feasible and is associated with high rates of treatment implementation/adherence and low incidence of secondary fracture.


Assuntos
Osteoporose , Fraturas por Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Humanos , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Estudos Retrospectivos , Prevenção Secundária , Atenção Terciária à Saúde , Cooperação e Adesão ao Tratamento
8.
Arthroscopy ; 36(2): 397-399, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32014172

RESUMO

The advent of modern suture anchor technology has not only revolutionized arthroscopic treatment options for management of complex shoulder pathology, but also engendered a materials science quest to identify the ultimate composition and design. What began as an open procedure with transosseous suture fixation has evolved dramatically with the widespread adoption of an arthroscopic, anchor-based technique for rotator cuff repair. Currently, a litany of commercially available "hard" and "soft" anchors are flooding the market, with limited qualitative comparisons to suggest superiority of one type. Ideally, suture anchor design should permit preservation of native glenohumeral bone stock with gradual osseointegration, limit disruption of local tissue homeostasis, and maintain time-zero mechanical strength until soft-tissue healing has occurred. At present, a vented, open-anchor architecture may facilitate better biologic incorporation with increased bony ingrowth through access to marrow elements, although these radiographic advantages have not conferred any clinically meaningful differences for our rotator cuff repair patients. For anchor composition, the jury is still out, and we need to continue to critically evaluate for perianchor cyst formation and longer term remodeling. In fact, the true merits of increased bony ingrowth and limited osteolysis may only be realized at the time of revision rotator cuff repair, during which prior implant position or secondary cystic change may further dictate suture anchor design, size, and placement.


Assuntos
Lesões do Manguito Rotador , Âncoras de Sutura , Artroscopia , Benzofenonas , Humanos , Cetonas , Polietilenoglicóis , Polímeros , Estudos Prospectivos , Manguito Rotador
9.
Trauma Surg Acute Care Open ; 1(1): e000016, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-29766060

RESUMO

BACKGROUND: Owing to the potential risks associated with missed injury, many blunt trauma patients with suspected cervical spine injury undergo some form of imaging technique which has progressed from primarily using plain radiography to relying on CT. Recently, studies have shown that in certain situations, adding MRI may improve the diagnostic accuracy over solely relying on CT. METHODS: Retrospective study of 3468 adult blunt trauma patients at a level I trauma center of which 94 with an initial negative CT scan underwent subsequent MRI. These 94 patients were classified as reliable or unreliable for examination; coded as either having a positive or negative MRI result; and assessed for a change in management. RESULTS: Of the 94 patients in the study population, 69 (73.4%) were deemed reliable and 25 (26.6%) deemed unreliable for examination. Overall, 65 (69.1%) patients had a positive MRI result-49 (71.0%) reliable and 16 (64.0%) unreliable-with some patients testing positive for more than one finding. There was no significant difference in positive MRI rates between reliable and unreliable patients. None of the 29 patients who had negative MRI had a change in management, while 31 of the 65 (47.7%) patients with positive MRI did have a change in management of either continued cervical collar immobilization or neck surgery. CONCLUSIONS: The use of CT scans should be continued as the primary imaging technique for patients with suspected cervical spine injuries. In cases where obtundation or clinical suspicion exists for a false-negative CT scan, MRI should be considered as a supplement and should not be rejected solely based on the negative result of the CT. LEVEL OF EVIDENCE: Level IV.

10.
J Transl Med ; 13: 110, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-25889105

RESUMO

BACKGROUND: Osteosarcoma (OS) is the most common type of solid bone cancer, with latent metastasis being a typical mode of disease progression and a major contributor to poor prognosis. For this to occur, cells must resist anoikis and be able to recapitulate tumorigenesis in a foreign microenvironment. Finding novel approaches to treat osteosarcoma and target those cell subpopulations that possess the ability to resist anoikis and contribute to metastatic disease is imperative. Here we investigate anchorage-independent (AI) cell growth as a model to better characterize anoikis resistance in human osteosarcoma while using an expression profiling approach to identify and test targetable signaling pathways. METHODS: Established human OS cell lines and patient-derived human OS cell isolates were subjected to growth in either adherent or AI conditions using Ultra-Low Attachment plates in identical media conditions. Growth rate was assessed using cell doubling times and chemoresistance was assessed by determining cell viability in response to a serial dilution of either doxorubicin or cisplatin. Gene expression differences were examined using quantitative reverse-transcription PCR and microarray with principal component and pathway analysis. In-vivo OS xenografts were generated by either subcutaneous or intratibial injection of adherent or AI human OS cells into athymic nude mice. Statistical significance was determined using student's t-tests with significance set at α=0.05. RESULTS: We show that AI growth results in a global gene expression profile change accompanied by significant chemoresistance (up to 75 fold, p<0.05). AI cells demonstrate alteration of key mediators of mesenchymal differentiation (ß-catenin, Runx2), stemness (Sox2), proliferation (c-myc, Akt), and epigenetic regulation (HDAC class 1). AI cells were equally tumorigenic as their adherent counterparts, but showed a significantly decreased rate of growth in-vitro and in-vivo (p<0.05). Treatment with the pan-histone deacetylase inhibitor vorinostat and the DNA methyltransferase inhibitor 5-azacytidine mitigated AI growth, while 5-azacytidine sensitized anoikis-resistant cells to doxorubicin (p<0.05). CONCLUSIONS: These data demonstrate remarkable plasticity in anoikis-resistant human osteosarcoma subpopulations accompanied by a rapid development of chemoresistance and altered growth rates mirroring the early stages of latent metastasis. Targeting epigenetic regulation of this process may be a viable therapeutic strategy.


Assuntos
Anoikis , Neoplasias Ósseas/genética , Epigênese Genética , Perfilação da Expressão Gênica , Osteossarcoma/genética , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Osteossarcoma/tratamento farmacológico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
Int J Surg Case Rep ; 10: 134-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25839433

RESUMO

INTRODUCTION: Adult intussusception is rare. Lipoma is the second most common benign tumor of the colon and most common to cause colonic intussusception in adults, but rare. PRESENTATION OF CASE: A 35-years-old male presented with a history of intermittent abdominal pain and bright red rectal bleeding, with symptoms waxing and waning for one month. On physical examination, the abdomen was distended with tenderness over the periumbilical, suprapubic, and left lower quadrant regions with guarding. CT demonstrated colo-colonic intussusception of the sigmoid colon with a 2.3cm×2.6cm intra-mural lipoma of the rectosigmoid region. The patient underwent an exploratory laparotomy with partial reduction of the intussusception, sigmoid colon resection and end colostomy. Histopathology confirmed a 2.5cm sub-mucosal lipoma without evidence of malignancy. DISCUSSION: Sixty-sixty five percent of cases with intussusception of the large bowel in adults are related to a malignant etiology and most cases of sigmoidorectal intussusception reported in the literature are secondary to underlying malignancy. Colo-colic intussusception is the most common type of intussusception in adults. The incidence of lipomas of the large intestine is reported to range from 0.035% to 4.4%. Ninety percent of colonic lipomas are submuscosal and are mostly located in the right hemicolon. Only 25% of patients with colonic lipoma develop symptoms. Colonic lipomas of the rectosigmoid region represent a very rare occurrence and subsequent etiology for sigmoidorectal intussusceptions in adults. CONCLUSION: Colonic lipoma should be considered in the differential diagnosis of adults with intussusception, with reduction and resection leading to excellent results.

12.
Am J Med Genet A ; 167(7): 1429-35, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25808193

RESUMO

Oculoectodermal syndrome (OES) is a rare disease characterized by a combination of congenital scalp lesions and ocular dermoids, with additional manifestations including non-ossifying fibromas and giant cell granulomas of the jaw occurring during the first decade of life. To identify the genetic etiology of OES, we conducted whole-genome sequencing of several tissues in an affected individual. Comparison of DNA from a non-ossifying fibroma to blood-derived DNA allowed identification of a somatic missense alteration in KRAS NM_033360.3(KRAS):c.38G>A, resulting in p.Gly13Asp. This alteration was also observed in the patient's other affected tissues including the skin and muscle. Targeted sequencing in a second, unrelated OES patient identified an NM_033360.3(KRAS):c.57G>C, p.Leu19Phe alteration. Allelic frequencies fell below 40% in all tissues examined in both patients, suggesting that OES is a mosaic RAS-related disorder, or RASopathy. The characteristic findings in OES, including scalp lesions, ocular dermoids, and benign tumors, are found in other mosaic and germline RASopathies. This discovery also broadens our understanding of the spectrum of phenotypes resulting from KRAS alterations. Future research into disease progression with regard to malignancy risk and investigation of RAS-targeted therapies in OES is warranted. KRAS sequencing is clinically available and may also now improve OES diagnostic criteria.


Assuntos
Cisto Dermoide/genética , Cisto Dermoide/patologia , Displasia Ectodérmica/genética , Displasia Ectodérmica/patologia , Genoma Humano/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Sequência de Bases , Criança , Pré-Escolar , Coristoma/patologia , Doenças da Córnea/patologia , Feminino , Frequência do Gene , Transtornos do Crescimento/patologia , Humanos , Masculino , Dados de Sequência Molecular , Mutação de Sentido Incorreto/genética , Couro Cabeludo/patologia , Análise de Sequência de DNA
13.
Am Surg ; 80(12): 1250-5, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25513925

RESUMO

Acute care surgery (ACS) programs have emerged mainly at academic medical centers to provide timely care for emergency general surgery and trauma patients. We hypothesized that the development of an ACS program in a multispecialty group practice would improve outcomes for patients with acute appendicitis. A retrospective analysis of patients with acute appendicitis was performed in two time periods: 18 months of private practice and the following 12 months with ACS coverage. Length of stay was the primary outcome measure. A total of 871 patients were studied (526 private practice, 345 ACS). The ACS group had a greater proportion of laparoscopic appendectomies (P < 0.001) and more transitions in care between surgeons (P < 0.001). Length of stay was shorter in the ACS group (1.6 ± 1.5 [mean ± standard deviation] vs 1.9 ± 2.4 days, P = 0.01) and a greater proportion of surgeries were performed during the daytime (44.9 vs 36.6%, P = 0.02). Multivariate analysis demonstrated length of stay was related to appendicitis grade (P < 0.001), American Society of Anesthesiologists class (P < 0.001), symptom duration (P = 0.001), and laparoscopic approach (P < 0.001). The initial transition from private practice to ACS resulted in decreased length of stay with no increase in morbidity related to transitions of surgical care in patients with appendicitis.


Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Cuidados Críticos/organização & administração , Prática de Grupo/organização & administração , Prática Privada/organização & administração , Adulto , Apendicite/diagnóstico , Estudos de Coortes , Feminino , Seguimentos , Humanos , Comunicação Interdisciplinar , Laparoscopia/métodos , Laparotomia/métodos , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Avaliação de Programas e Projetos de Saúde , Estudos Retrospectivos , Medição de Risco , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
14.
PLoS One ; 9(12): e112454, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25474689

RESUMO

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.


Assuntos
Degeneração do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Técnicas de Cultura de Órgãos , Animais , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Interleucina-1beta/administração & dosagem , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/genética , Deslocamento do Disco Intervertebral/metabolismo , Camundongos , Microscopia de Fluorescência , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/genética , Transcriptoma
15.
PLoS One ; 9(10): e111431, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25347326

RESUMO

Osteosarcoma (OS) is the most common type of solid bone cancer and remains the second leading cause of cancer-related death for children and young adults. Hypoxia is an element intrinsic to most solid-tumor microenvironments, including that of OS, and is associated with resistance to therapy, poor survival, and a malignant phenotype. Cells respond to hypoxia through alterations in gene expression, mediated most notably through the hypoxia-inducible factor (HIF) class of transcription factors. Here we investigate hypoxia-induced changes in the Wnt/ß-catenin signaling pathway, a key signaling cascade involved in OS pathogenesis. We show that hypoxia results in increased expression and signaling activation of HIF proteins in human osteosarcoma cells. Wnt/ß-catenin signaling is down-regulated by hypoxia in human OS cells, as demonstrated by decreased active ß-catenin protein levels and axin2 mRNA expression (p<0.05). This down-regulation appears to rely on both HIF-independent and HIF-dependent mechanisms, with HIF-1α standing out as an important regulator. Finally, we show that hypoxia results in resistance of human OS cells to doxorubicin-mediated toxicity (6-13 fold increase, p<0.01). These hypoxic OS cells can be sensitized to doxorubicin treatment by further inhibition of the Wnt/ß-catenin signaling pathway (p<0.05). These data support the conclusion that Wnt/ß-catenin signaling is down-regulated in human OS cells under hypoxia and that this signaling alteration may represent a viable target to combat chemoresistant OS subpopulations in a hypoxic niche.


Assuntos
Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Osteossarcoma/metabolismo , Oxigênio/metabolismo , Via de Sinalização Wnt , Hipóxia Celular , Linhagem Celular Tumoral , Doxorrubicina/toxicidade , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
16.
Transl Res ; 164(2): 139-48, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24726460

RESUMO

Aneurysmal bone cyst (ABC) is a benign tumor of bone presenting as a cystic, expansile lesion in both the axial and appendicular skeleton. Axial lesions demand special consideration, because treatment-related morbidity can be devastating. In similar lesions, such as giant cell tumor of bone (GCTB), the receptor-activator of nuclear kappaB ligand (RANKL)-receptor-activator of nuclear kappaB (RANK) signaling axis is essential to tumor progression. Although ABC and GCTB are distinct entities, they both contain abundant multinucleated giant cells and are osteolytic characteristically. We hypothesize that ABCs express both RANKL and RANK similarly in a cell-type specific manner, and that targeted RANKL therapy will mitigate ABC tumor progression. Cellular expression of RANKL and RANK was determined in freshly harvested ABC samples using laser confocal microscopy. A consistent cell-type-specific pattern was observed: fibroblastlike stromal cells expressed RANKL strongly whereas monocyte/macrophage precursor and multinucleated giant cells expressed RANK. Relative RANKL expression was determined by quantitative real-time polymerase chain reaction in ABC and GCTB tissue samples; no difference in relative expression was observed (P > 0.05). In addition, we review the case of a 5-year-old boy with a large, aggressive sacral ABC. After 3 months of targeted RANKL inhibition with denosumab, magnetic resonance imaging demonstrated tumor shrinkage, bone reconstitution, and healing of a pathologic fracture. Ambulation, and bowel and bladder function were restored at 6 months. Denosumab treatment was well tolerated. Post hoc analysis demonstrated strong RANKL expression in the pretreatment tumor sample. These findings demonstrate that RANKL-RANK signal activation is essential to ABC tumor progression. RANKL-targeted therapy may be an effective alternative to surgery in select ABC presentations.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , Cistos Ósseos Aneurismáticos/diagnóstico , Cistos Ósseos Aneurismáticos/tratamento farmacológico , Ligante RANK/antagonistas & inibidores , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Cistos Ósseos Aneurismáticos/metabolismo , Pré-Escolar , Denosumab , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/genética , Fator de Transcrição STAT1
17.
J Trauma ; 68(3): 560-3, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20065871

RESUMO

BACKGROUND: : As the population continues to age, the number of patients undergoing traumatic injury while on antiplatelet or anticoagulation therapies is increasing. Mortality has been shown to increase in traumatic brain injury patients on warfarin therapy. Whether this increased mortality is seen in trauma patients without traumatic brain injury remains controversial. We investigated whether patients on antiplatelet and/or anticoagulation therapy were at increased risk of death from blunt traumatic injury in the absence of head injury. METHODS: : A retrospective review of our Level I trauma center database was performed from 2002 to 2007. Inclusion criteria included all patients older than 60 years admitted to the trauma service. Only patients with a computed tomography scan negative for intracranial injury were analyzed. RESULTS: : Two hundred twelve patients were found, of which 67 were found to be taking aspirin, warfarin, clopidogrel, or a combination of the three. Injury Severity Score (21 vs. 21), length of stay (11 days vs. 9 days), intensive care unit days (5 days vs. 4 days), and deaths (13% vs. 10%) were similar between those patients on antiplatelet/anticoagulation therapy and those who were not. CONCLUSION: : In the absence of traumatic brain injury, the use of preinjury antiplatelet and/or anticoagulation therapy does not significantly increase the risk of mortality in the trauma patient. As the number of active seniors rises, this patient population will continue to present to the trauma service. To the best of our knowledge, this study is one of the largest addressing this question, and the only study examining the addition of antiplatelet therapy.


Assuntos
Anticoagulantes/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Ferimentos não Penetrantes/mortalidade , Idoso , Lesões Encefálicas , Estudos de Coortes , Cuidados Críticos , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Índices de Gravidade do Trauma , Ferimentos não Penetrantes/diagnóstico , Ferimentos não Penetrantes/terapia
19.
Obes Surg ; 12(1): 19-24, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11868291

RESUMO

BACKGROUND: Deep venous thrombosis (DVT) is a significant risk in patients undergoing surgery for morbid obesity and may be associated with significant morbidity and mortality. In a consecutive group of patients in one bariatric surgery practice, the initial group of patients who received prophylaxis for DVT was given enoxaparin 30 mg q12h while the later group was given enoxaparin 40 mg q12h. METHODS: 481 patients who underwent primary and revisional bariatric surgery over 38 months (October 1997-December 2000) were evaluated. All patients received a multi-modality DVT prophylaxis protocol that included: early ambulation, graduated compression stockings, intermittent pneumatic compression, and enoxaparin (LMWH) in two dosage groups. The first 92 patients (19%) in the series (Group I) received LMWH 30 mg q12h while the subsequent 389 patients (81%) (Group II) received LMWH 40 mg q12h. RESULTS: Group I patients were not different from Group II patients in body mass index (BMI) (51.7 vs 50.3 kg/m2), age (43.7 vs 44.3 yrs), sex (men 20.2% vs 15.8%) or history of previous DVT (3.2% vs 3.9%). Group I patients did have significantly longer procedure times (213 vs 175 min, p < 0.05) and hospital stays (5.67 d vs 3.81 d, p < 0.05) than Group II. There were a total of 7 (1.4%) postoperative DVT complications. 5 DVT complications occurred in Group I (5.4%) compared with 2 DVT complications in Group II (0.6%) (p < 0.01 by Fisher Exact Test two-tailed). One patient in each group required treatment for hemorrhage. CONCLUSION: A multi-modality prophylaxis treatment protocol in patients undergoing bariatric surgery is feasible and achieves a low incidence of postoperative DVT complications. The use of a higher dose of enoxaparin, 40 mg q12h, may reduce the incidence of DVT complications in patients following bariatric surgery without an increase in bleeding complications.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Obesidade Mórbida/cirurgia , Trombose Venosa/prevenção & controle , Adulto , Feminino , Humanos , Masculino , Fatores de Risco
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