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1.
Arch Bone Jt Surg ; 10(10): 863-870, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36452422

RESUMO

Background: The purpose of this study is to compare the incidence of complications associated with tension band wiring (TBW) versus plate osteosynthesis (POS) in the treatment of olecranon fractures. Methods: We performed a retrospective cohort study of operatively treated adult olecranon fractures from an integrated healthcare system by multiple surgeons from January 2008 to December 2011. Patients were divided into two cohorts: fractures fixed using the tension band technique and fractures fixed using plate osteosynthesis. The study was limited to the Orthopedic Trauma Association classification of olecranon fracture type 21-B1, with subtypes 1-3. Outcome measures were loss of fracture fixation requiring revision, postoperative infection, stiffness requiring surgery, and symptomatic hardware removal (HWR). Univariate and multivariable logistic regressions were performed to test the associations between the type of internal fixation and outcomes. Results: A total of 321 olecranon fractures were included (median age: 61 years old, 57 % female); 153 participants were treated with TBW, and 168 patients with POS. There was one failure in the TBW group and two in the POS group (P=0.62). There were no significant differences in the infection rates (TBW 5%, POS 9%, P=0.20) and no reoperations for stiffness. The HWR occurred significantly more often in TBW (29%) than in POS (14%) (OR=0.39, P=0.001). The association between POS and decreased HWR remained highly significant (OR=0.40, P=0.003) after adjusting for clinical variables. Conclusion: In this large study comparing POS and TBW for 21-B1 olecranon fractures, no difference in fixation failure, infection, or postoperative stiffness was noted. A significantly greater risk of symptomatic hardware occurred in TBW. These findings may assist surgeons and patients in considering the risks and benefits of TBW and POS as treatment options for displaced olecranon fractures.

2.
Anesth Analg ; 135(6): 1189-1197, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36155546

RESUMO

BACKGROUND: We examined the incidence, postoperative outcomes, and patient-related factors associated with preincision cardiac arrest in patients undergoing cardiac surgery. METHODS: We retrospectively examined adult patients undergoing elective or urgent cardiac surgery at the Cleveland Clinic between 2008 and 2019. The incidence of preincision cardiac arrest, defined as arrest between induction of general anesthesia and surgical incision, was reported. In a secondary analysis, we assessed the association between preincision cardiac arrest and major postoperative outcomes. In a tertiary analysis, we used adjusted linear regression models to explore the association between preincision cardiac arrest and prespecified patient risk factors, including severe left main coronary artery stenosis, left ventricular ejection fraction, moderate/severe right ventricular dysfunction, low-flow low-gradient aortic stenosis, and moderate/severe pulmonary hypertension. RESULTS: Preincision cardiac arrests occurred in 75 of 41,238 (incidence of 0.18%; 95% CI, 0.17-0.26) patients who had elective or urgent cardiac surgery. Successful cardiopulmonary resuscitation with return of spontaneous circulation or bridge to cardiopulmonary bypass occurred in 74 of 75 (98.6%) patients. Patients who experienced preincision cardiac arrest had significantly higher in-hospital mortality than those who did not (11% vs 2%; odds ratio [OR] (95% CI), 4.14 (1.94-8.84); P < .001). They were also more likely to suffer postoperative respiratory failure (46% vs 13%; OR [95% CI], 3.94 [2.40-6.47]; P < .001), requirement for renal replacement therapy (11% vs 2%; OR [95% CI], 3.90 [1.82-8.35]; P < .001), neurologic deficit (7% vs 2%; OR [95% CI], 2.49 (1.00-6.21); P = .05), and longer median hospital stay (15 vs 8 days; hazard ratio (HR) [95% CI], 0.68 [0.55-0.85]; P < .001). Reduced left ventricular ejection fraction (per 5% decrease) (OR [95% CI], 1.13 [1.03-1.22]; P = .006) and moderate/severe pulmonary hypertension (OR [95% CI], 3.40 [1.95-5.90]; P < .001) were identified as independent risk factors for cardiac arrest. CONCLUSIONS: Cardiac arrest after anesthetic induction is rare in cardiac surgical patients in our investigation. Though most patients are rescued, morbidity and mortality remain higher. Reduced left ventricular ejection fraction and moderate/severe pulmonary hypertension are associated with greater risk for preincision cardiac arrest.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Parada Cardíaca , Hipertensão Pulmonar , Adulto , Humanos , Incidência , Volume Sistólico , Estudos Retrospectivos , Função Ventricular Esquerda , Parada Cardíaca/diagnóstico , Parada Cardíaca/epidemiologia , Parada Cardíaca/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Fatores de Risco , Resultado do Tratamento
3.
J Mol Biol ; 434(9): 167533, 2022 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-35314146

RESUMO

The neutrophil NADPH oxidase produces both intracellular and extracellular reactive oxygen species (ROS). Although oxidase activity is essential for microbial killing, and ROS can act as signaling molecules in the inflammatory process, excessive extracellular ROS directly contributes to inflammatory tissue damage, as well as to cancer progression and immune dysregulation in the tumor microenvironment. How specific signaling pathways contribute to ROS localization is unclear. Here we used a systems pharmacology approach to identify the specific Class I PI3-K isoform p110ß, and PLD1, but not PLD2, as critical regulators of extracellular, but not intracellular ROS production in primary neutrophils. Combined crystallographic and molecular dynamics analysis of the PX domain of the oxidase component p47phox, which binds the lipid products of PI 3-K and PLD, was used to clarify the membrane-binding mechanism and guide the design of mutant mice whose p47phox is unable to bind 3-phosphorylated inositol phospholipids. Neutrophils from these K43A mutant animals were specifically deficient in extracellular, but not intracellular, ROS production, and showed increased dependency on signaling through the remaining PLD1 arm. These findings identify the PX domain of p47phox as a critical integrator of PLD1 and p110ß signaling for extracellular ROS production, and as a potential therapeutic target for modulating tissue damage and extracellular signaling during inflammation.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases , NADPH Oxidases , Neutrófilos , Espécies Reativas de Oxigênio , Animais , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Ativação Enzimática , Inflamação , Camundongos , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neutrófilos/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
4.
Clin Infect Dis ; 74(3): 467-471, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35148386

RESUMO

BACKGROUND: Pregnancy has been reported to be a risk factor for severe COVID-19. We evaluated the impact of pregnancy on severe COVID-19 and mortality in an electronic medical record (EMR) database that enabled exclusion of labor and delivery (L&D) encounters. METHODS: In this retrospective cohort study, EMRs from 82 healthcare facilities in the Cerner COVID-19 Datamart were analyzed. The study comprised 38 106 individuals aged 18-45 years old with COVID-19 who had emergency department, urgent care, or inpatient encounters from December 2019 to September 2020. Subgroups were balanced through propensity score weights for age, race, smoking status, and number of comorbidities. The primary outcome was COVID-19-related mortality; secondary outcomes were markers of severe COVID-19: intubations, mechanical ventilation, use of vasopressors, diagnosis of sepsis, and diagnosis of acute respiratory distress syndrome. RESULTS: In comparing pregnant and nonpregnant women, no statistical differences were found for markers of severe COVID-19, after adjusting for age, smoking, race, and comorbidities. The adjusted odds of an inpatient encounter were higher for pregnant vs nonpregnant women (adjusted odds ratio [aOR], 13.2; 95% confidence interval [CI], 11.6-15.3; P < .001), but notably lower after excluding L&D encounters (aOR, 2.3; 95% CI, 1.89-2.88; P < .001). In comparison to women without L&D encounters, hospitalization was significantly more likely for men. CONCLUSIONS: We did not find an increased risk of severe COVID-19 or mortality in pregnancy. Hospitalization does not necessarily indicate severe COVID-19 in pregnancy, as half of pregnant patients with COVID-19 were admitted for L&D encounters in this study.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Adolescente , Adulto , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto Jovem
5.
J Immunother Cancer ; 9(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33883258

RESUMO

BACKGROUND: Full application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8+ lymphocytes and natural killer (NK) cells. To ease rhIL-15 administration, we shortened time of infusion. Treatment with rhIL-15 at a dose of 3-5 µg/kg as a 5-day continuous intravenous infusion (CIV-5) had no dose-limiting toxicities while effector cell stimulation was comparable to the CIV-10 regimen. METHODS: Eleven patients with metastatic cancers were treated with rhIL-15 CIV-5, 3 µg (n=4), 4 µg (n=3), and 5 µg/kg/day (n=4) in a phase I dose-escalation study (April 6, 2012). RESULTS: Impressive expansions of NK cells were seen at all dose levels (mean 34-fold), including CD56bright NK cells (mean 144-fold for 4 µg/kg), as well as an increase in CD8+ T cells (mean 3.38-fold). At 5 µg/kg/day, there were no dose-limiting toxicities but pulmonary capillary leak and slower patient recovery. This led to our choice of the 4 µg/kg as CIV-5 dose for further testing. Cytolytic capacity of CD56bright and CD56dim NK cells was increased by interleukin-15 assayed by antibody-dependent cellular cytotoxicity (ADCC), natural cytotoxicity and natural killer group 2D-mediated cytotoxicity. The best response was stable disease. CONCLUSIONS: IL-15 administered as CIV-5 substantially expanded NK cells with increased cytotoxic functions. Tumor-targeting monoclonal antibodies dependent on ADCC as their mechanism of action including alemtuzumab, obinutuzumab, avelumab, and mogamulizumab could benefit from those NK cell expansions and provide a promising therapeutic strategy. TRIAL REGISTRATION NUMBERS: NCT01572493, NCT03759184, NCT03905135, NCT04185220 and NCT02689453.


Assuntos
Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Interleucina-15/administração & dosagem , Células Matadoras Naturais/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Técnicas de Cocultura , Citocinas/metabolismo , Citotoxicidade Imunológica/efeitos dos fármacos , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Interleucina-15/efeitos adversos , Células K562 , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Contagem de Linfócitos , Masculino , Maryland , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/imunologia , Neoplasias/metabolismo , Fatores de Tempo , Resultado do Tratamento
6.
Trauma Surg Acute Care Open ; 5(1): e000528, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381653

RESUMO

BACKGROUND: Cervical spinal cord injury (CSCI) is devastating and costly. Previous research has demonstrated that diaphragm pacing (DPS) is safe and improves respiratory mechanics. This may decrease hospital stays, vent days, and costs. We hypothesized DPS implantation would facilitate liberation from ventilation and would impact hospital charges. METHODS: We performed a retrospective review of patients with acute CSCI between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity matching based on age, injury severity score, ventilator days, hospital length of stay, and need for tracheostomy. We then adjusted total hospital charges by year using US Bureau of Labor Statistics annual adjusted Medical Care Prices. Bivariate and multivariate linear regression statistics were performed using STATA V.15. RESULTS: Between July 2011 and May 2017, all patients with acute CSCI were evaluated for DPS implantation. 40 patients who had laparoscopic DPS implantation (DPS) were matched to 61 who did not (NO DPS). Following DPS implantation, there was a statistically significant increase in spontaneous Vt compared with NO DPS (+88 mL vs -13 mL; 95% CI 46 to 131 vs -78 to 51 mL, respectively; p=0.004). Median time to liberation after DPS was significantly shorter (10 vs 29 days; 95% CI 6.5 to 13.6 vs 23.1 to 35.3 days; p<0.001). Adjusted hospital charges were significantly lower for DPS on multivariate linear regression models controlling for year of injury, sex, race, injury severity, and age (p=0.003). DISCUSSION: DPS implantation in patients with acute CSCI produces significant improvements in spontaneous Vt and reduces time to liberation, which translated into reduced hospital charges on a risk-adjusted, inflation-adjusted model. DPS implantation for patients with acute CSCI should be considered. LEVEL OF EVIDENCE: Level III.

7.
Trauma Surg Acute Care Open ; 5(1): e000446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32432171

RESUMO

BACKGROUND: Patients who sustain blunt solid organ injury to the liver, spleen, or kidney and are treated nonoperatively frequently undergo serial monitoring of their hemoglobin (Hb). We hypothesized that among initially hemodynamically stable patients with blunt splenic, hepatic, or renal injuries treated without an operation, scheduled monitoring of serum Hb values may be unnecessary as hemodynamic instability, not merely Hb drop, would prompt intervention. METHODS: We performed a retrospective review of patients admitted to our urban Level 1 trauma center following blunt trauma with any grade III, IV, or V liver, spleen, or kidney injury from January 1, 2016 to December 31, 2016. Patients who were hemodynamically unstable and went directly to the operating room or interventional radiology were excluded. Patients who required any urgent or unplanned operative or angiographic intervention were compared with patients who did not require an intervention. Routine demographic and outcome variables were obtained and bivariate and multivariate regression statistics were performed using Stata V.10. RESULTS: A total of 138 patients were included in the study. Age (39.3 vs 41.4, p=0.51), mean injury severity score (26.7 vs 22.1, p=0.12), and admission Hb (11.9 vs 12.8, p=0.06) did not differ significantly between the two groups. The number of Hb draws (9.2 vs 10, p=0.69) and the associated change in Hb (3.7 vs 3.5, p=0.71) did not differ significantly between the two groups. Only splenic grade predicted need for urgent intervention (3.5 vs 2, p<0.001). All patients who required an operative or radiologic intervention did so based on change in hemodynamics or severity of splenic grade, per our institutional protocol, and not Hb trend. DISCUSSION: Among patients with blunt solid organ injury, a need for emergent intervention in the form of laparotomy or angioembolization occurs within the first hours of injury. Routine scheduled Hb measurements did not change management in our cohort. LEVEL OF EVIDENCE: Level III.

8.
J Trauma Acute Care Surg ; 89(3): 423-428, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32467474

RESUMO

BACKGROUND: Cervical spinal cord injury (CSCI) is devastating with ventilator-associated pneumonia being a main driver of morbidity and mortality. Laparoscopic diaphragm pacing implantation (DPS) has been used for earlier liberation from mechanical ventilation. We hypothesized that DPS would improve respiratory mechanics and facilitate liberation. METHODS: We performed a retrospective review of acute CSCI patients between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity score matching based on age, Injury Severity Score, ventilator days, hospital length of stay, and need for tracheostomy. Patients with complete respiratory mechanics data were analyzed and compared. Those who did not have DPS (NO DPS) had spontaneous tidal volume (Vt) recorded at time of intensive care unit admission, at day 7, and at day 14, and patients who had DPS had spontaneous Vt recorded before and after DPS. Time to ventilator liberation and changes in size of spontaneous Vt for patients while on the ventilator were analyzed. Bivariate and multivariate logistic and linear regression statistics were performed using STATA v10. RESULTS: Between July 2011 and May 2017, 37 patients that had DPS were matched to 34 who did not (NO DPS). Following DPS, there was a statistically significant increase in spontaneous Vt compared with NO DPS (+88 mL vs. -13 mL; 95% confidence interval, 46-131 mL vs. -78 to 51 mL, respectively; p = 0.004). Median time to liberation after DPS was significantly shorter (10 days vs. 29 days; 95% CI, 6.5-13.6 days vs. 23.1-35.3 days; p < 0.001). Liberation prior to hospital discharge was not different between the two groups. The DPS placement was found to be associated with a statistically significant decrease in days to liberation and an increase in spontaneous Vt in multivariate linear regression models. CONCLUSION: The DPS implantation in acute CSCI patients produces significant improvements in spontaneous Vt and reduces time to liberation from mechanical ventilation. Prospective comparative studies are needed to define the clinical benefits and potential cost savings of DPS implantation. LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Diafragma , Terapia por Estimulação Elétrica , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Insuficiência Respiratória/terapia , Traumatismos da Medula Espinal/complicações , Doença Aguda , Adulto , Vértebras Cervicais , Eletrodos Implantados , Feminino , Humanos , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/etiologia , Respiração , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/etiologia , Mecânica Respiratória , Estudos Retrospectivos , Adulto Jovem
9.
Am J Surg ; 218(2): 255-260, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30558803

RESUMO

INTRODUCTION: The aim of our study is to analyze the 5 years' trends, mortality rate, and factors that influence mortality after civilian penetrating traumatic brain injury (pTBI). METHODS: We performed a 5-year-analysis of all trauma patients diagnosed with pTBI in the TQIP. Our outcome measures were trends of pTBI. RESULTS: A total of 26,871 had penetrating brain injury over the 5-year period. Mean age was 36.2 ±â€¯18 years. Overall 55% of the patients had severe TBI and mortality rate was 43.8%. There was an increase in the rate of pTBI from 3042/100,000 (2010) to 7578/100,000 trauma admissions (2014) (p < 0.001). The mortality rate has increased from 35% (2010) to 48% (2011) (p < 0.001) followed by a linear decrease in mortality to 40% (2014). Independent predictors of mortality were age, pre-hospital intubation, suicide attempt, and craniotomy/craniectomy. CONCLUSIONS: Incidence and mortality for patients who are brought to hospitals following pTBI have gradually increased over the five-year period. Self-inflicted injury and prehospital intubation were the two most significant predictors of mortality.


Assuntos
Lesões Encefálicas Traumáticas/epidemiologia , Traumatismos Cranianos Penetrantes/epidemiologia , Adolescente , Adulto , Lesões Encefálicas Traumáticas/mortalidade , Feminino , Traumatismos Cranianos Penetrantes/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
10.
Trauma Surg Acute Care Open ; 3(1): e000132, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30023432

RESUMO

BACKGROUND: Recent legislation repealing the Sustainable Growth Rate mandates gradual replacement of fee for service with alternative payment models (APMs), which will include service bundling. We analyzed the 2 years' experience at our state-designated level I trauma center to determine the feasibility of such an approach for trauma care. METHODS: De-identified data from all injured patients treated by the trauma service during 2014 and 2015 were reviewed to determine individual patient injury profiles. Using these injury profiles we created the 'trauma bundle' by concatenating the highest Abbreviated Injury Scale score for each of the six body regions to produce a single 'signature' of injury by region for every patient. These trauma bundles were analyzed by frequency over 2 years and by each year. The impacts of physiology and resource consumption were evaluated by determination of the correlation of the mean and SD of calculated survival probability (Ps) and intensive care unit length of stay (ICU LOS) for each profile group occurring more than 12 times in 2 years. RESULTS: The 5813 patients treated over 2 years produced 858 distinct injury profiles, only 8% (71) of which occurred more than 12 times in 2 years. Comparison of 2014 and 2015 profiles demonstrated high frequency variation among profiles between the 2 years. Analysis of injury patterns occurring >12 times in 2 years demonstrated an inverse correlation between the mean and SD for Ps (R2=0.68) and a direct correlation for ICU LOS (R2=0.84). DISCUSSION: These data indicate that the disease of injury is too inconsistent a mix of injury pattern and physiologic response to be predictably bundled for an APM. The inverse correlation of increasing SD with increasing ICU LOS and decreasing Ps suggests an opportunity for measurable process improvement. LEVEL OF EVIDENCE: Economic and value-based evaluations, level IV. STUDY TYPE: Economic/decision.

11.
J Trauma Acute Care Surg ; 85(5): 928-931, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29985232

RESUMO

BACKGROUND: Cervical spinal cord injury (CSCI) is devastating. Respiratory failure, ventilator-associated pneumonia (VAP), sepsis, and death frequently occur. Case reports of diaphragm pacing system (DPS) have suggested earlier liberation from mechanical ventilation in acute CSCI patients. We hypothesized DPS implantation would decrease VAP and facilitate liberation from ventilation. METHODS: We performed a retrospective review of patients with acute CSCI managed at a single Level 1 trauma center between January 2005 and May 2017. Routine demographics were collected. Patients underwent propensity matching based on age, injury severity score, ventilator days, hospital length of stay, and need for tracheostomy. Outcome measures included hospital length of stay, intensive care unit length of stay, ventilator days (vent days), incidence of VAP, and mortality. Bivariate and multivariate logistic and linear regression statistics were performed using STATA Version 10. RESULTS: Between July 2011 and May 2017, all patients with acute CSCI were evaluated for DPS implantation. Forty patients who had laparoscopic DPS implantation (DPS) were matched to 61 who did not (NO DPS). Median time to liberation after DPS implantation was 7 days. Hospital length of stay and mortality were significantly lower on bivariate analysis in DPS patients. Diaphragm pacing system placement was not found to be associated with statistically significant differences in these outcomes on risk-adjusted multivariate models that included admission year. CONCLUSIONS: Diaphragm pacing system implantation in patients with acute CSCI can be one part of a comprehensive critical care program to improve outcomes. However, the association of DPS with the marked improved mortality seen on bivariate analysis may be due solely to improvements in critical care throughout the study period. Further studies to define the benefits of DPS implantation are needed. LEVEL OF EVIDENCE: Therapeutic, level IV.


Assuntos
Diafragma , Terapia por Estimulação Elétrica , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Insuficiência Respiratória/terapia , Traumatismos da Medula Espinal/complicações , Doença Aguda , Adulto , Vértebras Cervicais , Eletrodos Implantados , Feminino , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia Associada à Ventilação Mecânica/etiologia , Respiração , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
12.
Cartilage ; 9(3): 248-254, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-28530120

RESUMO

Objective To evaluate the outcome of patients who have undergone simultaneous osteotomy and osteochondral allograft (OCA) transplantation. Our hypothesis is that use of high tibial osteotomy and fresh OCA in a combined procedure is safe and effective without increasing morbidity in comparison to OCA alone. Design A case series of 17 patients underwent tibial osteotomy and simultaneous OCA during a single surgery. Osteotomy was indicated when axial alignment was within the affected compartment. Patients had a minimum of 2 years of follow-up after surgery. The mean graft size was 8.7 cm2, with 82% located on the medial femoral condyle alone and 18% involving the medial femoral condyle and one or more other sites. Data collection included demographics, osteotomy correction, graft site(s) and area, and clinical evaluation. Failure was defined as conversion to arthroplasty. Results Two of 17 patients (12%) failed at a mean of 9.3 years. The remaining 15 patients (88%) had intact allografts with mean survival of 8.1 years (SD 3.3). Five patients (29%) had an additional procedure, all undergoing osteotomy hardware removal. Of those with surviving allografts, mean pain and function scores improved significantly from the preoperative to postoperative assessment and International Knee Documentation Committee total scores improved significantly from 40.9 ± 15.4 preoperative to 75.5 ± 24.0 at latest follow-up ( P = 0.003); 92% of patients were satisfied with the results of the surgery. No postoperative complications occurred. Conclusion Combining high tibial osteotomy and OCA in properly selected patients is safe and effective.


Assuntos
Articulação do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Transplante Homólogo/métodos , Adulto , Aloenxertos/transplante , Cartilagem Articular/cirurgia , Terapia Combinada/métodos , Feminino , Fêmur/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Cancer Immunol Res ; 5(10): 929-938, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28842470

RESUMO

The cytokine IL15 is required for survival and activation of natural killer (NK) cells as well as expansion of NK-cell populations. Here, we compare the effects of continuous IL15 infusions on NK-cell subpopulations in cancer patients. Infusions affected the CD56bright NK-cell subpopulation in that the expansion rates exceeded those of CD56dim NK-cell populations with a 350-fold increase in their total cell numbers compared with 20-fold expansion for the CD56dim subset. CD56bright NK cells responded with increased cytokine release to various stimuli, as expected given their immunoregulatory functions. Moreover, CD56bright NK cells gained the ability to kill various target cells at levels that are typical for CD56dim NK cells. Some increased cytotoxic activities were also observed for CD56dim NK cells. IL15 infusions induced expression changes on the surface of both NK-cell subsets, resulting in a previously undescribed and similar phenotype. These data suggest that IL15 infusions expand and arm CD56bright NK cells that alone or in combination with tumor-targeting antibodies may be useful in the treatment of cancer. Cancer Immunol Res; 5(10); 929-38. ©2017 AACR.


Assuntos
Citocinas/biossíntese , Citotoxicidade Imunológica/efeitos dos fármacos , Interleucina-15/administração & dosagem , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Antígeno CD56/metabolismo , Humanos , Imunofenotipagem , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia
14.
Shock ; 44(2): 128-36, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26009816

RESUMO

Primed neutrophils that are capable of releasing matrix metalloproteinases (MMPs) into the circulation are thought to play a significant role in the pathophysiology of acute respiratory distress syndrome (ARDS). We hypothesized that direct measurement of plasma MMP-9 activity may be a predictor of incipient tissue damage and subsequent lung injury, which was investigated in both an animal model of ARDS and a small cohort of 38 critically ill human patients. In a mouse model of ARDS involving instillation of intratracheal lipopolysaccharide (LPS) to induce lung inflammation, we measured neutrophil-mediated inflammation, along with MMP-9 activity in the airways and lung tissue and MMP-9 expression in the plasma. Neutrophil recruitment, inflammation, and MMP-9 activity in the airways and lung tissue increased throughout the 72 h after LPS instillation, whereas plasma MMP-9 expression was greatest at 12 to 24 h after LPS instillation. The results suggest that the peak in plasma MMP-9 activity may precede the peak of neutrophil inflammation in the airways and lung tissue in the setting of ARDS. Based on this animal study, a retrospective observational cohort study involving 38 patients admitted to a surgical intensive care unit at a tertiary care university hospital with acute respiratory failure requiring intubation and mechanical ventilation was conducted. Plasma samples were collected daily, and MMP-9 activity was compared with lung function as determined by the PaO2/FiO2 ratio. In patients who developed ARDS, a notable increase in plasma MMP-9 activity on a particular day correlated with a decrease in the PaO2/FiO2 ratio on the following day (r = -0.503, P < 0.006). Taken together, these results suggest that plasma MMP-9 activity changes, as a surrogate for primed neutrophils may have predictive value for the development of ARDS in a selected subset of critically ill patients.


Assuntos
Lesão Pulmonar Aguda/enzimologia , Regulação Enzimológica da Expressão Gênica , Metaloproteinase 9 da Matriz/sangue , Síndrome do Desconforto Respiratório/enzimologia , Lesão Pulmonar Aguda/sangue , Adulto , Idoso , Animais , Medula Óssea/metabolismo , Estado Terminal , Modelos Animais de Doenças , Feminino , Humanos , Inflamação , Unidades de Terapia Intensiva , Cinética , Lipopolissacarídeos/química , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Oxigênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Síndrome do Desconforto Respiratório/sangue , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo
15.
J Trauma Acute Care Surg ; 78(3): 580-5, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25710430

RESUMO

BACKGROUND: There are many benefits of repair over ligation of major venous injuries (MVIs) following penetrating trauma, but the risk of pulmonary embolism (PE) is not well defined. We hypothesized that rates of PE are comparable between repair and ligation of MVI. METHODS: All penetrating trauma patients with MVI requiring an operation from 2003 to 2012 (n = 158) were retrospectively reviewed. Propensity scores were based on a logistic regression model using patient and injury characteristics. A 1:1 fixed ratio nearest neighbor matching was performed to compare outcomes of the repair and ligation cohorts. Data are reported as mean ± SD if parametric, or median (interquartile range) if not, and compared using a t test, Mann-Whitney U-test, χ2, or Fisher's exact test, as appropriate. RESULTS: The population was 89% male, age 32 ± 12 years, 74% gunshot wound, Injury Severity Score of 19 ± 13, length of stay of 9 (18) days, 3.8% PE, and a mortality of 21.5%. Repair was performed in 37% (n = 59), ligation was performed in 60% (n = 94), and 3% required both. With ligation versus repair, ligation patients were generally more critically injured; 48-hour survival was 78% versus 93% (p = 0.0083), initial Glasgow Coma Scale (GCS) score was 12 ± 5 versus 14 ± 3 (p = 0.003), initial base excess was -9 ± 8 versus -5 ± 5 mEq/L (p = 0.003), more packed red blood cells were transfused (12 (14) U vs. 9 (12) U; p = 0.032), and major arterial injury was more likely (86% vs. 42%, p < 0.001), but the PE rate was identical (5.9%) in propensity-matched cohorts. In those who developed a PE, all were receiving standard thromboprophylaxis. CONCLUSION: Following penetrating trauma, the risk of PE between repair and ligation of MVI is comparable. LEVEL OF EVIDENCE: Epidemiologic study, level III.


Assuntos
Embolia Pulmonar/etiologia , Lesões do Sistema Vascular/complicações , Lesões do Sistema Vascular/cirurgia , Veias/lesões , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/cirurgia , Adulto , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Florida/epidemiologia , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Ligadura , Masculino , Pontuação de Propensão , Embolia Pulmonar/mortalidade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Lesões do Sistema Vascular/mortalidade , Ferimentos Penetrantes/mortalidade
16.
Fertil Steril ; 103(2): 347-52.e1, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25516080

RESUMO

OBJECTIVE: To determine whether endometriosis is associated with mitochondrial dysfunction in cumulus (granulosa [GC]) cells of subjects undergoing IVF-intracytoplasmic sperm injection (ICSI). DESIGN: Prospective cohort study. SETTING: An IVF clinic in a tertiary academic care center. PATIENT(S): Eleven women with endometriosis and 39 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Cumulus cell adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA), and genomic DNA (gDNA) number. RESULT(S): Cumulus cell ATP content was 65% lower in subjects with surgically proven endometriosis (median 312.5 attomoles/ng total DNA, interquartile range = 116.0-667.8) compared with controls (median 892.4 attomoles/ng total DNA, interquartile range = 403.0-1,412.2). There was no significant difference in mtDNA:gDNA ratio. There were no significant differences in age, body mass index (BMI), basal serum FSH level, total oocyte number, metaphase II (M2) oocyte number, metaphase I oocyte number, percentage of M2 oocytes, fertilization rate, implantation rate, or pregnancy rate (PR). Multivariate regression analysis showed significant positive correlations between ATP and [1] M2 oocyte number (r = 0.307) and [2] pregnancy (r = 0.332). There were also trends toward positive correlations between ATP and [3] age (r = 0.283), [4] total number of oocytes (r = 0.271), [5] percentage of M2 oocytes (r = 0.249), and [6] implantation rate (r = 0.293). There were no statistically significant correlations between mtDNA:gDNA ratio and any demographic factors or clinical outcomes measured. CONCLUSION(S): Surgically confirmed endometriosis may be associated with cumulus cell mitochondrial dysfunction in subjects undergoing IVF-ICSI for infertility, as reflected by decreased ATP production.


Assuntos
Trifosfato de Adenosina/biossíntese , Células do Cúmulo/metabolismo , Endometriose/metabolismo , Mitocôndrias/metabolismo , Injeções de Esperma Intracitoplásmicas , Adulto , Estudos de Coortes , DNA Mitocondrial/metabolismo , Endometriose/diagnóstico , Feminino , Fertilização in vitro/métodos , Humanos , Masculino , Gravidez , Taxa de Gravidez/tendências , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas/métodos
17.
Int J Surg Case Rep ; 5(10): 662-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25194599

RESUMO

INTRODUCTION: de Garengeot's hernia is very rare. Richter's hernia is responsible for 10% of acute strangulated hernias. PRESENTATION OF CASE: A 91-year-old woman with three days of abdominal distention was found on computed tomogram to have an incarcerated femoral hernia. Operation revealed a de Garengeot's hernia combined with a Richter's hernia of small bowel. Primary repair was performed along with appendectomy. DISCUSSION: We discuss these rare hernias, not previously reported in combination, and options for management. CONCLUSION: Combined de Garengeot's and Richter's hernias are rare, represent a significant diagnostic challenge, and should be repaired urgently to prevent ischemic bowel, or limit contamination if ischemia is already present. Use of computed tomography will likely lead to increased pre-operative diagnosis of this rare entity.

18.
Obstet Gynecol ; 118(2 Pt 1): 223-230, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21775836

RESUMO

OBJECTIVE: To study whether pain location is related to lesion location in women with chronic pelvic pain and biopsy-proven endometriosis. METHODS: A secondary analysis was performed to compare self-reported pain location with recorded laparoscopy findings for location and characteristics of all visible lesions. All lesions were excised. Endometriosis was diagnosed using histopathology criteria. The pelvic area was divided into three anterior and two posterior regions. Lesion depth, number of lesions or endometriomas, and disease burden (defined as sum of lesion sizes, or single compared with multiple lesions) were determined for each region. Data were analyzed using t tests, Fisher exact tests, and logistic regression modeling, with P values corrected for multiple comparisons using the step-down Bonferroni method. RESULTS: Women with endometriosis (n = 96) had lower body mass indexes, were more likely to be white, had more previous surgeries, and had more frequent menstrual pain and incapacitation than did chronic pain patients without endometriosis (n = 37). Overall, few patients had deeply infiltrating lesions (n = 38). Dysuria was associated with superficial bladder peritoneal lesions. Other lesions or endometriomas were not associated with pain in the same anatomic locations. Lesion depth, disease burden, and number of lesions or endometriomas were not associated with pain. CONCLUSION: In this group of women with biopsy-proven endometriosis, few had deeply infiltrating lesions or endometriomas. Dysuria and midline anterior pain were the only symptoms associated with the location of superficial endometriosis lesions. The lack of relationship between pain and superficial lesion location raises questions about how these lesions relate to pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00001848. LEVEL OF EVIDENCE: : II.


Assuntos
Endometriose/complicações , Dor Pélvica/etiologia , Adolescente , Adulto , Biópsia , Conservadores da Densidade Óssea/uso terapêutico , Doença Crônica , Endometriose/patologia , Endometriose/cirurgia , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Dor Pélvica/tratamento farmacológico , Cloridrato de Raloxifeno/uso terapêutico , Adulto Jovem
19.
Clin Obstet Gynecol ; 53(2): 413-9, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20436318

RESUMO

Endometriosis has been associated with pain and infertility. The gold standard for the diagnosis of endometriosis has been visual inspection by laparoscopy, preferably with histologic confirmation. Because there is no good noninvasive test for endometriosis, there is often a significant delay in diagnosis of this disease. Imaging that confirms an endometriotic cyst or deep infiltrating endometriosis may help guide surgical therapeutic approaches. No serum marker has been found to diagnose endometriosis with adequate sensitivity and specificity. There has been a recent focus on the presence of nerve fibers in the eutopic endometrium of patients with endometriosis.


Assuntos
Endometriose/diagnóstico , Endométrio/diagnóstico por imagem , Laparoscopia , Biomarcadores , Biópsia , Endometriose/classificação , Endossonografia/métodos , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Gravidez , Vagina/diagnóstico por imagem
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