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2.
J Cardiovasc Surg (Torino) ; 63(1): 37-43, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34014056

RESUMO

BACKGROUND: This study aimed to investigate the impact of segmental artery reimplantation and its patency on spinal cord ischemia (SCI) in thoracoabdominal aorta replacement. METHODS: For 193 patients who underwent early postoperative computed tomographic (CT) angiography after thoracoabdominal aorta replacement, the technique of segmental artery reimplantation, their patency, and postoperative SCI were retrospectively investigated. RESULTS: The early patency rate of reimplanted segmental artery was 83.3% (210 of 252), as 13 were taken down intraoperatively and 42 were not visualized in the postoperative CT angiography. The patency rate differed according to the reimplantation technique: 93.6% (131/140) for en bloc patch, 95.6% (43/45) for small individual patch, and 53.7% (36/67) for graft interposition. SCI occurred in 13 (6.3%) patients, 4 of whom (2.0%) remained paraplegic permanently. SCI was significantly more frequent (P=0.044) in the patients in whom segmental artery reimplantation was not successful (take-down or occlusion, 6/37=16.2%) than in those who had all segmental arteries sacrificed intentionally (2/64=3.1%) and those who showed patency of all reimplanted segmental arteries (5/92=5.4%). Especially, there was no permanent paraplegia in the last group. Failure of intended segmental artery reimplantation was a significant risk factor of postoperative SCI in logistic regression analysis (P=0.012; odds ratio 4.65, 95% confidence interval 1.41-15.36). CONCLUSIONS: During thoracoabdominal aorta replacement, attention should be paid to the segmental artery reimplantation technique, which affects the risk of occlusion or intraoperative take-down and thereby may have impact on postoperative SCI.


Assuntos
Aorta Abdominal/cirurgia , Aorta Torácica/cirurgia , Implante de Prótese Vascular/efeitos adversos , Isquemia do Cordão Espinal/epidemiologia , Grau de Desobstrução Vascular , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/fisiopatologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aortografia , Angiografia por Tomografia Computadorizada , Humanos , Incidência , Reimplante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
3.
JSES Int ; 4(4): 875-881, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33345228

RESUMO

BACKGROUND: Superior labrum lesion from anterior to posterior (SLAP) often presents together with other shoulder pathologies such as rotator cuff tear (RCT), but it is uncertain if repairing both SLAP and RCT has superior clinical outcomes over isolated repairs of SLAP and RCT. MATERIALS AND METHODS: This was a retrospective cohort study with prospectively collected data, reviewing 157 patients who underwent arthroscopic repair of either RCT, SLAP (type II lesion), or both. Before surgery and after 6 weeks, 12 weeks, and 24 weeks, shoulder objective range of motion and strength were measured, patient-reported function and pain was assessed by the modified L'Insalata questionnaire with a Likert scale, and complications after each repair were examined. RESULTS: At 24 weeks after surgery, the combined group (n = 22) and SLAP group (n = 47) had significantly higher forward flexion (165° ± 4° and 167° ± 4° vs. 154° ± 3°, P = .01 and P = .01), external rotation strength (82 ± 6 N, 81 ± 6 N vs. 61 ± 3 N, P = .01 and P = .01), and abduction strength (94 ± 14 N, 78 ± 8 N vs. 53 ± 3 N, P = .001 and P = .02) compared with the rotator cuff tear repair (RCR) group (n = 88). The combined group also had stronger internal rotation than the RCR group (107 ± 12 N vs. 72 ± 4 N, P = .02). Function and pain improved from "severe-moderate" to "moderate-mild" in all groups after surgery. CONCLUSION: Repairing RCT and SLAP tears together results in significant clinical benefits compared to repairing just RCT and analogous results against SLAP-only repair.

4.
J Surg Oncol ; 122(3): 469-479, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32424895

RESUMO

BACKGROUND: Surgery for perihilar cholangiocarcinoma (PHCC) is associated with high morbidity. This study aimed to investigate the clinical value of the future liver remnant volume-to-body weight (FLRV/BW) and propose a risk score for predicting the risk of patients with PHCC developing posthepatectomy liver failure (PHLF). METHODS: This study included 348 patients who underwent major hepatectomy with bile duct resection for PHCC during 2008-2015 at a single center in Korea and they were retrospectively analyzed. RESULTS: Clinically relevant PHLF was noted in 40 patients (11.4%). The area under the curve (AUC) for FLRV/BW was not significantly different from that for FLRV/total liver volume (P = .803) or indocyanine green clearance of the future liver remnant (P = .629) in terms of predicting PHLF. On multivariate analysis, predictors of PHLF (P < .05) were male sex, albumin less than 3.5 g/dL, preoperative cholangitis, portal vein resection, FLRV/BW less than 0.5%, and FLRV/BW 0.5% to 0.75%. These variables were included in the risk score that showed good discrimination (AUC, 0.853; 95% CI, 0.802-0.904). It will help rank patients into three risk subgroups with a predicted liver failure incidence of 4.75%, 18.73%, and 51.58%, respectively. CONCLUSIONS: FLRV/BW is a comparable risk prediction factor of PHLF and the proposed risk score can help to predict the risk of planned surgery in PHCC.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Hepatectomia/efeitos adversos , Tumor de Klatskin/cirurgia , Falência Hepática/etiologia , Idoso , Ductos Biliares/cirurgia , Peso Corporal , Feminino , Hepatectomia/métodos , Humanos , Fígado/anatomia & histologia , Fígado/cirurgia , Masculino , Curva ROC , Estudos Retrospectivos , Fatores de Risco
5.
J Immunol ; 203(7): 1961-1972, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31451675

RESUMO

Human mesenchymal stem cell (MSC) extracellular vesicles (EV) can reduce the severity of bacterial pneumonia, but little is known about the mechanisms underlying their antimicrobial activity. In the current study, we found that bacterial clearance induced by MSC EV in Escherichia coli pneumonia in C57BL/6 mice was associated with high levels of leukotriene (LT) B4 in the injured alveolus. More importantly, the antimicrobial effect of MSC EV was abrogated by cotreatment with a LTB4 BLT1 antagonist. To determine the role of MSC EV on LT metabolism, we measured the effect of MSC EV on a known ATP-binding cassette transporter, multidrug resistance-associated protein 1 (MRP1), and found that MSC EV suppressed MRP1 mRNA, protein, and pump function in LPS-stimulated Raw264.7 cells in vitro. The synthesis of LTB4 and LTC4 from LTA4 are competitive, and MRP1 is the efflux pump for LTC4 Inhibition of MRP1 will increase LTB4 production. In addition, administration of a nonspecific MRP1 inhibitor (MK-571) reduced LTC4 and subsequently increased LTB4 levels in C57BL/6 mice with acute lung injury, increasing overall antimicrobial activity. We previously found that the biological effects of MSC EV were through the transfer of its content, such as mRNA, microRNA, and proteins, to target cells. In the current study, miR-145 knockdown abolished the effect of MSC EV on the inhibition of MRP1 in vitro and the antimicrobial effect in vivo. In summary, MSC EV suppressed MRP1 activity through transfer of miR-145, thereby resulting in enhanced LTB4 production and antimicrobial activity through LTB4/BLT1 signaling.


Assuntos
Lesão Pulmonar Aguda , Infecções por Escherichia coli , Escherichia coli/imunologia , Vesículas Extracelulares , Células-Tronco Mesenquimais/imunologia , Pneumonia Bacteriana , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Lesão Pulmonar Aguda/terapia , Animais , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/terapia , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/patologia , Vesículas Extracelulares/transplante , Humanos , Leucotrieno B4/imunologia , Leucotrieno C4/imunologia , Pulmão/imunologia , Pulmão/patologia , Masculino , Células-Tronco Mesenquimais/patologia , Camundongos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores , Proteínas Associadas à Resistência a Múltiplos Medicamentos/imunologia , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/terapia , Propionatos/farmacologia , Quinolinas/farmacologia , Células RAW 264.7
6.
Eur J Anaesthesiol ; 35(8): 598-604, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28857785

RESUMO

BACKGROUND: The laryngeal mask airway supreme (LMA-S) and i-gel are both popular second-generation supraglottic airway devices that have been widely studied in surgical patients, but their differences in clinical performance in the elderly are not clear. OBJECTIVE: We compared the efficacy and safety of the LMA-S and i-gel in anaesthetised and paralysed elderly patients. DESIGN: A randomised study. SETTING: Single-centre trial, study period January 2014 from to October 2016. PATIENTS: One hundred and six elderly patients who underwent urological or orthopaedic surgery with an expected duration less than 2 h. INTERVENTION: Patients were allocated to either the LMA-S (n = 53) or i-gel (n = 53) group. All insertions were performed in a standardised manner according to the manufacturers' instructions. MAIN OUTCOME MEASURES: Our primary endpoint was the rate of successful insertion at the first attempt. The adequacy of positive pressure ventilation and airway sealing, fibreoptic laryngoscopy grades and stability of airway maintenance during anaesthesia were also assessed. RESULTS: Although the rate of successful insertion at the first attempt was similar between the two groups (94.3 vs. 82.7%, P = 0.072), more patients required device manipulation during insertion with the LMA-S than the i-gel (42.3 vs. 18.9%, P = 0.011). Good fibreoptic laryngoscopy grades were significantly more common with the i-gel than the LMA-S (79.3 vs. 55.8%, P = 0.042), and peak inspiratory pressures were lower in the i-gel group both immediately after insertion and at the end of surgery. Leak pressures were significantly higher in the i-gel group than the LMA-S group, both immediately after insertion and at the end of surgery (25.8 vs. 23.0, P = 0.036; and 28.1 vs. 23.7, P < 0.001, respectively). CONCLUSION: Both the LMA-S and i-gel were used successfully and safely in elderly patients. However, the i-gel demonstrated better airway sealing than the LMA-S at insertion and during maintenance of anaesthesia. TRIAL REGISTRATION: NCT02026791 at clinicaltrial.gov.


Assuntos
Anestesia Geral/instrumentação , Anestesia Geral/métodos , Desenho de Equipamento/normas , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Paralisia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Máscaras Laríngeas/normas , Masculino , Paralisia/induzido quimicamente , Paralisia/cirurgia , Estudos Prospectivos
7.
Br J Haematol ; 176(5): 743-749, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28106903

RESUMO

The phase 3 FIRST (Frontline Investigation of REVLIMID + Dexamethasone Versus Standard Thalidomide) trial demonstrated that lenalidomide plus low-dose dexamethasone (Rd) until disease progression (Rd continuous) is an effective treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). Given genetic differences between Asian and Western populations, this subanalysis of the FIRST trial examined the safety and efficacy of Rd (given continuously or for 18 cycles [Rd18]) and MPT (melphalan, prednisone, thalidomide) in 114 Asian patients from Mainland China, South Korea and Taiwan. Efficacy and safety with Rd continuous in Asian patients were consistent with those in the overall study population. The overall response rates were 77·8% for Rd continuous, 57·5% for MPT and 65·8% for Rd18. The risk of progression or death was reduced by 39% with Rd continuous versus MPT and by 35% with Rd continuous versus Rd18. Rd continuous improved the 3-year survival rate compared with MPT (70·2% vs. 56·4%) and Rd18 (58·1%). Common grade 3/4 adverse events in the Rd continuous and MPT arms were neutropenia (25·0% vs. 43·6%), infection (19·4% vs. 28·2%) and anaemia (19·4% vs. 15·4%), respectively. Thromboembolic event rates were low, and no second primary malignancies were observed. Rd continuous is safe and effective in transplant-ineligible Asian patients with NDMM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ásia , Povo Asiático , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Infecções/induzido quimicamente , Lenalidomida , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Neutropenia/induzido quimicamente , Prednisona/uso terapêutico , Indução de Remissão , Talidomida/administração & dosagem , Talidomida/uso terapêutico , Resultado do Tratamento
8.
Lancet Haematol ; 3(11): e506-e515, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27751707

RESUMO

BACKGROUND: Panobinostat plus bortezomib and dexamethasone significantly increased median progression-free survival compared with placebo plus bortezomib and dexamethasone in the phase 3 PANORAMA 1 trial. Here, we present the final overall survival analysis for this trial. METHODS: PANORAMA 1 is a randomised, placebo-controlled, double-blind, phase 3 trial of patients with relapsed or relapsed and refractory multiple myeloma with one to three previous treatments. Patients were randomly assigned (1:1) to receive panobinostat (20 mg orally) or placebo, with bortezomib (1·3 mg/m2 intravenously) and dexamethasone (20 mg orally), over two distinct treatment phases. In treatment phase 1 (eight 3-week cycles), patients received: panobinostat or placebo on days 1, 3, 5, 8, 10, and 12; bortezomib on days 1, 4, 8, and 11; and dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. During treatment phase 2 (four 6-week cycles with a 2 weeks on, 1 week off schedule), panobinostat or placebo was given three times a week, bortezomib was administered once a week, and dexamethasone was given on the days of and following bortezomib administration. The primary endpoint was progression-free survival; overall survival was a key secondary endpoint. This study is registered at ClinicalTrials.gov, NCT01023308. FINDINGS: Between Jan 21, 2010, and Feb 29, 2012, 768 patients were enrolled into the study and randomly assigned to receive either panobinostat (n=387) or placebo (n=381), plus bortezomib and dexamethasone. At data cutoff (June 29, 2015), 415 patients had died. Median overall survival was 40·3 months (95% CI 35·0-44·8) in those who received panobinostat, bortezomib, and dexamethasone versus 35·8 months (29·0-40·6) in those who received placebo, bortezomib, and dexamethasone (hazard ratio [HR] 0·94, 95% CI 0·78-1·14; p=0·54). Of patients who had received at least two previous regimens including bortezomib and an immunomodulatory drug, median overall survival was 25·5 months (95% CI 19·6-34·3) in 73 patients who received panobinostat, bortezomib, and dexamethasone versus 19·5 months (14·1-32·5) in 74 who received placebo (HR 1·01, 95% CI 0·68-1·50). INTERPRETATION: The overall survival benefit with panobinostat over placebo with bortezomib and dexamethasone was modest. However, optimisation of the regimen could potentially prolong treatment duration and improve patients' outcomes, although further trials will be required to confirm this. FUNDING: Novartis Pharmaceuticals.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/efeitos adversos , Bortezomib/farmacologia , Bortezomib/uso terapêutico , Dexametasona/efeitos adversos , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ácidos Hidroxâmicos/efeitos adversos , Ácidos Hidroxâmicos/farmacologia , Ácidos Hidroxâmicos/uso terapêutico , Indóis/efeitos adversos , Indóis/farmacologia , Indóis/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Atividades Cotidianas/classificação , Adulto , Fatores Etários , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Povo Asiático/etnologia , Astenia/induzido quimicamente , Contagem de Células Sanguíneas/estatística & dados numéricos , Bortezomib/farmacocinética , Aberrações Cromossômicas/efeitos dos fármacos , Aberrações Cromossômicas/estatística & dados numéricos , Creatinina/sangue , Diarreia/induzido quimicamente , Progressão da Doença , Intervalo Livre de Doença , Método Duplo-Cego , Fadiga/induzido quimicamente , Feminino , Geografia/estatística & dados numéricos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Ácidos Hidroxâmicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Indóis/farmacocinética , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/etnologia , Estadiamento de Neoplasias , Panobinostat , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Qualidade de Vida , Insuficiência Renal/complicações , Fatores Sexuais , Esteroides/uso terapêutico , Análise de Sobrevida , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento
9.
Minerva Anestesiol ; 82(6): 649-56, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26576858

RESUMO

BACKGROUND: Patients undergoing laparoscopic gynecological surgery are at high risk of postoperative nausea and vomiting (PONV). We compared the antiemetic efficacy of ondansetron plus betahistine with that of ondansetron alone in this patient population. METHODS: In this randomized, double-blinded study, 168 patients were randomly allocated to receive placebo (O group) or betahistine 18 mg (OB group) orally 3 hours before surgery and 24 hours thereafter. In both groups, ondansetron 4 mg was administered at the end of surgery and 8 mg were added to an intravenous patient-controlled analgesia (IV-PCA) fentanyl solution. The primary outcome was complete response (no PONV and no rescue antiemetics) during the first 48 hours after surgery. The severity of nausea, pain score, and adverse events were assessed. RESULTS: The incidence of complete response was significantly higher in OB group than in O group (69% vs. 46%, P=0.004). The severity of nausea was lower in OB group than in O group during 30 minutes to 6 hours and 6 to 24 hours after surgery (P=0.001 and P<0.001). Pain score was similar between the groups. The incidence of dizziness was lower in OB group than in O group (13% vs. 40%, P < 0.001). Six patients (7%) in OB group and 15 patients (18%) in O group required early IV-PCA discontinuation, primarily because of PONV and/or dizziness (P=0.038). CONCLUSIONS: Compared to ondansetron alone, ondansetron plus betahistine was more effective to prevent PONV and dizziness in high-risk patients undergoing laparoscopic gynecological surgery.


Assuntos
Antieméticos/uso terapêutico , beta-Histina/uso terapêutico , Laparoscopia/efeitos adversos , Ondansetron/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Adulto , Idoso , Antieméticos/efeitos adversos , beta-Histina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/métodos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Ondansetron/efeitos adversos , Medição da Dor , Estudos Prospectivos , Índice de Gravidade de Doença , Adulto Jovem
10.
J Biomed Opt ; 20(2): 26004, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25700233

RESUMO

Tumor collagen characteristics influence tumor malignancy, invasion, and metastasis. This study investigates the effects of trastuzumab (Tz) on the collagen of Tz-responsive (BT474) and Tz-resistant (HR6) breast cancer xenografts. Collagen content was assessed by in vivo second harmonic generation (SHG) imaging and histological trichrome staining of tumor sections. Collagen SHG imaging of control BT474 and HR6 tumors demonstrated increased collagen density after 14 days of treatment (p < 0.05). Trichrome staining revealed decreased collagen in Tz-treated BT474 and HR6 tumors at 2, 5, and 14 days of treatment, suggesting that Tz affects the tumor microenvironment independent of epithelial cell response. Additionally, collagen alignment analysis revealed significantly less aligned collagen in the Tz-treated BT474 tumors at day 14 compared with control BT474 tumors. There was no correlation between SHG endpoints (collagen density and alignment) and trichrome staining (p > 0.05), consistent with the physically distinctive nature of these measurements. There was also no correlation between tumor size and collagen endpoints (p > 0.05). These results identify changes within the collagen compartment of the tumor microenvironment following Tz treatment, which are independent from the tumor cell response to Tz, and demonstrate that intravital collagen SHG imaging is capable of measuring dynamic changes in tumor microenvironment following treatment that complements trichrome staining.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Colágeno/química , Resistencia a Medicamentos Antineoplásicos , Animais , Linhagem Celular Tumoral , Feminino , Camundongos , Camundongos Nus , Microscopia de Fluorescência por Excitação Multifotônica , Trastuzumab , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Clin Anesth ; 26(6): 432-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25172503

RESUMO

STUDY OBJECTIVE: To investigate whether Type O blood group status is associated with increased intraoperative blood loss and requirement of blood transfusion in extensive spine surgery. DESIGN: Retrospective comparative study. SETTING: University-affiliated, non-profit teaching hospital. MEASUREMENTS: Data from 1,050 ASA physical status 1, 2, 3, 4, and 5 patients who underwent spine surgeries involving 4 or more vertebral levels were analyzed. Patients with Type O blood were matched to similar patients with other blood types using propensity scores, which were estimated via demographic and morphometric data, medical history variables, and extent of surgery. Intraoperative estimated blood loss (EBL) was compared among matched patients using a linear regression model; intraoperative transfusion requirement in volume of red blood cells, fresh frozen plasma, platelet, cryoprecipitate, cell salvaged blood, volume of intraoperative infusion of hetastarch, 5% albumin, crystalloids, and hospital length of hospital (LOS) were compared using Wilcoxon rank-sum tests. MAIN RESULTS: Intraoperative EBL and requirement of blood product transfusion were similar in patients with Type O blood group and those with other blood groups. CONCLUSION: There was no association between Type O blood and increased intraoperative blood loss or blood transfusion requirement during extensive spine surgery, with similar hospital LOS in Type O and non-O patients.


Assuntos
Sistema ABO de Grupos Sanguíneos , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Coluna Vertebral/cirurgia , Adulto , Idoso , Transfusão de Componentes Sanguíneos/métodos , Suscetibilidade a Doenças/sangue , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco
12.
PLoS One ; 8(11): e78765, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24223849

RESUMO

High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (α-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited.


Assuntos
Dieta Cetogênica , Membro Anterior/fisiopatologia , Atividade Motora/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Ácido 3-Hidroxibutírico/sangue , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Ácidos Cumáricos/farmacologia , Modelos Animais de Doenças , Expressão Gênica , Transportador de Glucose Tipo 1/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/sangue , Simportadores/antagonistas & inibidores , Simportadores/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética
13.
Anesthesiology ; 119(4): 932-40, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23681143

RESUMO

BACKGROUND: The authors tested the primary hypothesis that perioperative IV lidocaine administration during spine surgery (and in the postanesthesia care unit for no more than 8 h) decreases pain and/or opioid requirements in the initial 48 postoperative hours. Secondary outcomes included major complications, postoperative nausea and vomiting, duration of hospitalization, and quality of life. METHODS: One hundred sixteen adults having complex spine surgery were randomly assigned to perioperative IV lidocaine (2 mg·kg·h) or placebo during surgery and in the postanesthesia care unit. Pain was evaluated with a verbal response scale. Quality of life at 1 and 3 months was assessed using the Acute Short-form (SF) 12 health survey. The authors initially evaluated multivariable bidirectional noninferiority on both outcomes; superiority on either outcome was then evaluated only if noninferiority was established. RESULTS: Lidocaine was significantly superior to placebo on mean verbal response scale pain scores (P < 0.001; adjusted mean [95% CI] of 4.4 [4.2-4.7] and 5.3 [5.0-5.5] points, respectively) and significantly noninferior on mean morphine equivalent dosage (P = 0.011; 55 [36-84] and 74 [49-111] mg, respectively). Postoperative nausea and vomiting and the duration of hospitalization did not differ significantly. Patients given lidocaine had slightly fewer 30-day complications than patients given placebo (odds ratio [95% CI] of 0.91 [0.84-1.00]; P = 0.049). Patients given lidocaine had significantly greater SF-12 physical composite scores than placebo at 1 (38 [31-47] vs. 33 [27-42]; P = 0.002) and 3 (39 [31-49] vs. 34 [28-44]; P = 0.04) months, postoperatively. CONCLUSION: IV lidocaine significantly improves postoperative pain after complex spine surgery.


Assuntos
Analgésicos Opioides/uso terapêutico , Lidocaína/uso terapêutico , Dor/tratamento farmacológico , Assistência Perioperatória/métodos , Qualidade de Vida , Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Anestésicos Locais/administração & dosagem , Anestésicos Locais/uso terapêutico , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Tempo de Internação/estatística & dados numéricos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Morfina/uso terapêutico , Razão de Chances , Medição da Dor/métodos , Cuidados Pós-Operatórios/métodos , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Adulto Jovem
14.
Anesthesiology ; 119(1): 61-70, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23619173

RESUMO

BACKGROUND: Volatile anesthetic prices differ substantially. But differences in drug-acquisition cost would be inconsequential if hospitalization were prolonged by more soluble anesthetics. The authors tested the hypothesis that the duration of hospitalization is prolonged with isoflurane anesthesia. METHODS: Initially, the authors queried their electronic records and used propensity matching to generate homogeneous sets of adults having inpatient noncardiac surgery who were given desflurane, sevoflurane, and isoflurane. The authors then conducted a prospective alternating intervention trial in which adults (mostly having colorectal surgery) were assigned to isoflurane or sevoflurane, based on protocol. RESULTS: In the retrospective analysis, 2,898 matched triplets were identified among 43,352 adults, each containing one patient receiving isoflurane, desflurane, and sevoflurane, respectively. The adjusted geometric mean (95% CI) hospital length-of-stay for the isoflurane cases was 2.85 days (2.78-2.93); this was longer than that observed for both desflurane (2.64 [2.57-2.72]; P<0.001) and sevoflurane (2.55 [2.48-2.62]; P<0.001). In the prospective trial (N=1,584 operations), no difference was found; the adjusted ratio of means (95% CI) of hospital length-of-stay in patients receiving isoflurane versus sevoflurane was 0.98 (0.88-1.10), P=0.77, with adjusted geometric means (95% CI) estimated at 4.1 (3.8-4.4) and 4.2 days (3.8-4.5), respectively. CONCLUSIONS: Results of the propensity-matched retrospective analysis suggested that avoiding isoflurane significantly reduced the duration of hospitalization. In contrast, length-of-stay was comparable in our prospective trial. Volatile anesthetic choice should not be based on concerns about the duration of hospitalization. These studies illustrate the importance of following even the best retrospective analysis with a prospective trial.


Assuntos
Anestésicos Inalatórios , Tempo de Internação/estatística & dados numéricos , Adulto , Idoso , Analgésicos Opioides/uso terapêutico , Período de Recuperação da Anestesia , Feminino , Humanos , Período Intraoperatório , Isoflurano , Modelos Logísticos , Masculino , Éteres Metílicos , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Medição de Risco , Tamanho da Amostra , Sevoflurano , Resultado do Tratamento
15.
Spine (Phila Pa 1976) ; 37(23): E1422-31, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22869059

RESUMO

STUDY DESIGN: In vivo large animal (pig) model study of cerebrospinal fluid (CSF) pressures after acute experimental spinal cord injury (SCI). OBJECTIVE: To determine how the CSF pressure (CSFP) and CSF pulse pressure amplitude (CSFPPA) cranial and caudal to the injury site change after an acute SCI with subsequent thecal occlusion and decompression. SUMMARY OF BACKGROUND DATA: Lowering intrathecal pressure via CSF drainage is currently instituted to prevent ischemia-induced SCI during thoracoabdominal aortic aneurysm surgery and was recently investigated as a potential intervention for acute traumatic SCI. However, in SCI patients, persistent extradural compression commonly occludes the subarachnoid space. This may generate a CSFP differential across the injury site, which cannot be appreciated with lumbar catheter pressure measurements. METHODS: Anesthetized pigs were subjected to an acute contusive SCI at T11 and 8 hours of sustained compression (n = 12), or sham surgery (n = 2). CSFP was measured cranial and caudal to the injury site, using miniature pressure transducers, during compression and for 6 hours after decompression. RESULTS: The cranial-caudal CSFP differential increased (mean, 0.39 mm Hg/h), predominantly due to increased cranial pressure. On decompression, cranial CSFP decreased (mean, -1.16 mm Hg) and caudal CSFP increased (mean, 0.65 mm Hg). The CSFP differential did not change significantly after decompression. Cranial CSFPPA was greater than caudal CSFPPA, but this differential did not change during compression. On decompression, the caudal CSFPPA increased in some but not all animals. CONCLUSION: Although extradural compression exists at the site of injury, lumbar CSFP may not accurately indicate CSFP cranial to the injury. Decompression may provide immediate, though perhaps partial, resolution of the pressure differential. CSFPPA was not a consistent indicator of decompression in this animal model. These findings may have implications for the design of future clinical protocols in which CSFP is monitored after acute SCI.


Assuntos
Pressão do Líquido Cefalorraquidiano , Descompressão Cirúrgica/métodos , Drenagem , Compressão da Medula Espinal/cirurgia , Traumatismos da Medula Espinal/cirurgia , Doença Aguda , Animais , Pressão Arterial , Modelos Animais de Doenças , Feminino , Pressão Intracraniana , Monitorização Fisiológica/instrumentação , Compressão da Medula Espinal/líquido cefalorraquidiano , Compressão da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Traumatismos da Medula Espinal/fisiopatologia , Suínos , Porco Miniatura , Fatores de Tempo , Transdutores de Pressão , Pressão Venosa
16.
PLoS One ; 6(4): e19247, 2011 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-21559420

RESUMO

One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.


Assuntos
Biomarcadores/líquido cefalorraquidiano , Traumatismos da Medula Espinal/líquido cefalorraquidiano , Traumatismos da Medula Espinal/diagnóstico , Animais , Biomarcadores/metabolismo , Western Blotting , Cromatografia Líquida/métodos , Masculino , Espectrometria de Massas/métodos , Peptídeos/química , Prognóstico , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Medula Espinal/patologia , Fatores de Tempo
18.
Leuk Lymphoma ; 48(4): 716-22, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17454629

RESUMO

The objective of this retrospective study was to investigate clinical features and treatment outcomes in patients with angioimmunoblastic T-cell lymphoma (AITL), data of which were collected over a 15-year period. Sixty-five patients diagnosed with AITL were included in the study. About half of the patients (46.2%) presented with poor performance status (ECOG > or = 2); 72.3% of patients belonged to high intermediate or high-risk of IPI and same proportion belonged to Class 2 of PIT (Prognostic index for PTCL-U), and most patients (95.4%) were diagnosed at an advanced stage. At diagnosis, 27 patients (41.5%) presented with malignant pleural effusion, and 22 patients (33.8%) had skin involvement. Most of the initial chemotherapy regimens were anthracycline-based (88.2%). Overall response rate to initial chemotherapy was 86.2% (64.7% of complete response, 21.5% of partial response). The median progression-free survival and overall survival of all patients was 7.1 months (95% CI, 2.8 - 11.4) and 15.1 months (95% CI, 6.7 - 23.5), respectively. Age, performance status, and PIT scores were predictive prognostic factors for survival. In conclusion, although AITLs showed a good response to the initial chemotherapy, their response durations were short; therefore, chemotherapy for AITL should be modified or intensified as in high-dose chemotherapy.


Assuntos
Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Neovascularização Patológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antraciclinas/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Resultado do Tratamento
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