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2.
J Orthop Sci ; 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37903677

RESUMO

BACKGROUND: Surgical site infections are common in spinal surgeries. It is uncertain whether outcomes in spine surgery patients with vs. without surgical site infection are equivalent. Therefore, we assessed the effects of surgical site infection on postoperative patient-reported outcomes. METHODS: We enrolled patients who underwent elective spine surgery at 12 hospitals between April 2017 and February 2020. We collected data regarding the patients' backgrounds, operative factors, and incidence of surgical site infection. Data for patient-reported outcomes, namely numerical rating scale, Neck Disability Index/Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 1 year postoperatively. We divided the patients into with and without surgical site infection groups. Multivariate logistic regression analyses were performed to identify the risk factors for surgical site infection. Using propensity score matching, we obtained matched surgical site infection-negative and -positive groups. Student's t-test was used for comparisons of continuous variables, and Pearson's chi-square test was used to compare categorical variables between the two matched groups and two unmatched groups. RESULTS: We enrolled 8861 patients in this study; 74 (0.8 %) developed surgical site infections. Cervical spine surgery and American Society of Anesthesiologists physical status classification ≥3 were identified as risk factors; microendoscopy was identified as a protective factor. Using propensity score matching, we compared surgical site infection-positive and -negative groups (74 in each group). No significant difference was found in postoperative pain or dysesthesia of the lower back, buttock, leg, and plantar area between the groups. When comparing preoperative with postoperative pain and dysesthesia, statistically significant improvement was observed for both variables in both groups (p < 0.01 for all variables). No significant differences were observed in postoperative outcomes between the matched surgical site infection-positive and -negative groups. CONCLUSIONS: Patients with surgical site infections had comparable postoperative outcomes to those without surgical site infections.

3.
BMC Musculoskelet Disord ; 23(1): 902, 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209211

RESUMO

BACKGROUND: Whether lumbar decompression with fusion surgery is effective against Meyerding grade 2 degenerative spondylolisthesis (DS) is unknown. Therefore, the current study aimed to compare the surgical outcomes between posterior decompression alone and posterior decompression with fusion surgery among patients with grade 2 DS with central canal stenosis. METHODS: This retrospective cohort study included prospectively registered patients (n = 3863) who underwent surgery for degenerative lumbar spinal canal stenosis at nine high-volume spine centers from April 2017 to July 2019. Patients with grade 2 DS and central canal stenosis were included in the analysis. Patients with radiculopathy, including foraminal stenosis, degenerative scoliosis, and concomitant anterior spinal fusion, and those with a previous history of lumbar surgery were excluded. The participants were divided into the decompression alone group (group D) and decompression with fusion surgery group (group F). Data about patient-reported outcomes, including Numeric Rating Scale (low back pain, leg pain, leg numbness, and foot numbness), Oswestry Disability Index, EuroQol Five-Dimensional questionnaire, and 12-Item Short-Form Health Survey scores, were obtained preoperatively and 2 years postoperatively. RESULTS: In total, 2354 (61%) patients, including 42 (1.8%) with grade 2 DS (n = 18 in group D and n = 24 in group F), completed the 2-year follow-up. Group D had a higher proportion of female patients than group F. However, the two groups did not significantly differ in terms of other baseline demographic characteristics. Group D had a significantly shorter surgical time and lower volume of intraoperative blood loss than group F. Postoperative patient-reported outcomes did not significantly differ between the two groups, although the preoperative degree of low back pain was higher in group F than in group D. The slip degree of group D did not worsen during the follow-up period. CONCLUSION: The surgical outcomes were similar regardless of the addition of fusion surgery among patients with grade 2 DS. Decompression alone was superior to decompression with fusion surgery as it was associated with a lower volume of intraoperative blood loss and shorter surgical time.


Assuntos
Dor Lombar , Fusão Vertebral , Estenose Espinal , Espondilolistese , Perda Sanguínea Cirúrgica , Estudos de Coortes , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Feminino , Humanos , Hipestesia/cirurgia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Estenose Espinal/complicações , Estenose Espinal/cirurgia , Espondilolistese/complicações , Espondilolistese/cirurgia , Resultado do Tratamento
4.
J Neurosurg Spine ; 36(6): 892-899, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34996037

RESUMO

OBJECTIVE: The aim of this study was to compare perioperative complications and postoperative outcomes between patients with lumbar recurrent stenosis without lumbar instability and radiculopathy who underwent decompression surgery and those who underwent decompression with fusion surgery. METHODS: For this retrospective study, the authors identified 2606 consecutive patients who underwent posterior surgery for lumbar spinal canal stenosis at eight affiliated hospitals between April 2017 and June 2019. Among these patients, those with a history of prior decompression surgery and central canal restenosis with cauda equina syndrome were included in the study. Those patients with instability or radiculopathy were excluded. The patients were divided between the decompression group and decompression with fusion group. The demographic characteristics, numerical rating scale score for low-back pain, incidence rates of lower-extremity pain and lower-extremity numbness, Oswestry Disability Index score, 3-level EQ-5D score, and patient satisfaction rate were compared between the two groups using the Fisher's exact probability test for nominal variables and the Student t-test for continuous variables, with p < 0.05 as the level of statistical significance. RESULTS: Forty-six patients met the inclusion criteria (35 males and 11 females; 19 patients underwent decompression and 27 decompression and fusion; mean ± SD age 72.5 ± 8.8 years; mean ± SD follow-up 18.8 ± 6.0 months). Demographic data and perioperative complication rates were similar. The percentages of patients who achieved the minimal clinically important differences for patient-reported outcomes or satisfaction rate at 1 year were similar. CONCLUSIONS: Among patients with central canal stenosis who underwent revision, the short-term outcomes of the patients who underwent decompression were comparable to those of the patients who underwent decompression and fusion. Decompression surgery may be effective for patients without instability or radiculopathy.


Assuntos
Dor Lombar , Radiculopatia , Fusão Vertebral , Estenose Espinal , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Constrição Patológica/cirurgia , Estudos Retrospectivos , Radiculopatia/cirurgia , Radiculopatia/etiologia , Descompressão Cirúrgica/efeitos adversos , Vértebras Lombares/cirurgia , Estenose Espinal/complicações , Dor Lombar/cirurgia , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
5.
World Neurosurg ; 153: e265-e274, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34175484

RESUMO

OBJECTIVE: To compare the clinical and radiographic outcomes and complications in patients undergoing multilevel posterior cervical fusion surgery, ending at C7 or crossing the cervicothoracic junction (CTJ). METHODS: A total of 96 patients undergoing multilevel posterior cervical fusion surgery ending at C7, T1, or T2 were screened. The patients who fulfilled the inclusion criteria were divided into 2 groups based on the lower instrumented vertebra (LIV) level: group C7 (ending at C7) and group T1-T2 (crossing the CTJ). The radiographic and clinical outcomes were compared between the 2 groups, and the risk factors for instrument failure at LIV were investigated. RESULTS: In total, 73 patients (76%) completed at least 1 year follow-up and divided into group C7 (n = 43) and group T1-T2 (n = 30). Preoperative and postoperative radiographic parameters, the Japanese Orthopaedic Association score, and patient-reported outcomes were not significantly different between the 2 groups. Significantly longer surgical time, increased blood loss, and higher incidence rates of perioperative or postoperative complications were noted in group T1-T2. On the other hand, the incidence of instrument failures at LIV was significantly higher in group C7. Multivariate analysis showed that ending at C7, skipping screw insertion at the proximal vertebra adjacent to LIV, and a large postoperative cervical sagittal vertical axis (>40 mm) were risk factors for instrument failure at LIV. CONCLUSIONS: Crossing the CTJ during multilevel posterior cervical fusion surgery reduced instrument failures at LIV, but increased the surgical invasiveness and perioperative and postoperative complications.


Assuntos
Perda Sanguínea Cirúrgica , Vértebras Cervicais/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Falha de Prótese , Compressão da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Medição de Risco
6.
Commun Biol ; 4(1): 374, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33742110

RESUMO

Oncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear. Here we use Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. These findings suggest that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients.


Assuntos
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Genes ras , Neoplasias Pulmonares/metabolismo , Tolerância a Radiação , Fatores de Transcrição STAT/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Células A549 , Animais , Animais Geneticamente Modificados , Proliferação de Células/efeitos da radiação , Citocinas/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinases/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Camundongos Nus , Camundongos Transgênicos , Comunicação Parácrina , Tolerância a Radiação/genética , Fatores de Transcrição STAT/genética , Transdução de Sinais , Carga Tumoral/efeitos da radiação , Proteína Supressora de Tumor p53/genética , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Cell ; 183(5): 1219-1233.e18, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33242418

RESUMO

Cancer therapies kill tumors either directly or indirectly by evoking immune responses and have been combined with varying levels of success. Here, we describe a paradigm to control cancer growth that is based on both direct tumor killing and the triggering of protective immunity. Genetic ablation of serine protease inhibitor SerpinB9 (Sb9) results in the death of tumor cells in a granzyme B (GrB)-dependent manner. Sb9-deficient mice exhibited protective T cell-based host immunity to tumors in association with a decline in GrB-expressing immunosuppressive cells within the tumor microenvironment (TME). Maximal protection against tumor development was observed when the tumor and host were deficient in Sb9. The therapeutic utility of Sb9 inhibition was demonstrated by the control of tumor growth, resulting in increased survival times in mice. Our studies describe a molecular target that permits a combination of tumor ablation, interference within the TME, and immunotherapy in one potential modality.


Assuntos
Citotoxicidade Imunológica , Imunoterapia , Proteínas de Membrana/metabolismo , Neoplasias/imunologia , Neoplasias/terapia , Serpinas/metabolismo , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxicidade Imunológica/efeitos dos fármacos , Progressão da Doença , Feminino , Deleção de Genes , Granzimas/metabolismo , Imunidade/efeitos dos fármacos , Melanoma/patologia , Camundongos Endogâmicos C57BL , Neoplasias/prevenção & controle , Bibliotecas de Moléculas Pequenas/farmacologia , Células Estromais/efeitos dos fármacos , Células Estromais/patologia , Microambiente Tumoral/efeitos dos fármacos
8.
Curr Probl Cancer ; 42(5): 457-465, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30064936

RESUMO

Cervical cancer is the fourth most common cancer among women globally. The burden faced by low- and middle-income countries is significantly greater than high-income countries. The disparity is a direct result of the differences in resources. Developed nations have organized vaccination and screening programs that have decreased their cervical cancer incidence. More readily available personnel and technology exists to implement appropriate treatment modalities. However, for many underdeveloped nations, the scarcity of resources and infrastructure make such preventative and treatment programs limited or even nonexistent.


Assuntos
Detecção Precoce de Câncer , Saúde Global , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Países em Desenvolvimento , Feminino , Humanos
9.
Anal Bioanal Chem ; 403(2): 583-91, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22367332

RESUMO

A sensitive yet robust analytical method is presented for the simultaneous determination of 12 human pharmaceuticals (valproic acid, phenytoin, ibuprofen, gabapentin, acetaminophen, gemfibrozil, naproxen, ketoprofen, secobarbital, phenobarbital, 5-fluorouracil, and diclofenac) and 6 antiseptics (biosol, biphenylol, p-chloro-m-cresol, p-chloro-m-xylenol, chlorophene, and triclosan). The method employs solid-phase extraction (SPE) followed by a novel pentafluorobenzylation using a mixture of acetontrile/water (1/1, v/v). The method is simple to perform (derivatization can be completed in a single test tube) and eliminates the need for any solvent/SPE cartridge drying or blow-down. It affords excellent resolution, high sensitivity and reproducibility, and freedom from interference even for matrices as complex as untreated sewage. The method was applied to the analysis of sewage samples using 15 isotopically labeled surrogates, which resulted in the detection of 10 of the 12 pharmaceuticals and all of the antiseptics sought. Ten of 15 surrogates were synthesized from pure analytes by a simple H-D exchange reaction employing D(2)O and D(2)SO(4). Measured recoveries were sensitive to matrix effects and varied substantially among analytes, indicative of the limitations associated with using a single surrogate standard.


Assuntos
Anti-Infecciosos Locais/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Anti-Infecciosos Locais/isolamento & purificação , Fluorbenzenos/química , Técnicas de Diluição do Indicador , Preparações Farmacêuticas/isolamento & purificação , Esgotos/química , Poluentes Químicos da Água/isolamento & purificação
10.
J Chromatogr A ; 1217(4): 558-64, 2010 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-20015510

RESUMO

The presence of pharmaceuticals and other wastewater-derived micropollutants in surface and groundwaters is receiving intense public and scientific attention. Yet simple GC/MS methods that would enable measurement of a wide range of such compounds are scarce. This paper describes a GC/MS method for the simultaneous determination of 13 pharmaceuticals (acetaminophen, albuterol, allopurinol, amitriptyline, brompheniramine, carbamazepine, carisoprodol, ciclopirox, diazepam, fenofibrate, metoprolol, primidone, and terbinafine) and 5 wastewater-derived contaminants (caffeine, diethyltoluamide, n-butylbenzene sulfonamide, n-nonylphenol, and n-octylphenol) by solid phase extraction (SPE) and derivatization with BSTFA. The method was applied to the analysis of raw and treated sewage samples obtained from a wastewater treatment plant located in the mid-Atlantic United States. All analytes were detected in untreated sewage, and 14 of the 18 analytes were detected in treated sewage.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Esgotos/análise , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Preparações Farmacêuticas/isolamento & purificação , Sensibilidade e Especificidade , Solventes , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/isolamento & purificação
11.
Biodegradation ; 20(4): 441-66, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19112598

RESUMO

Pharmaceuticals and personal care products (PPCPs) have been the focus of much recent research as concerns rise about their occurrence in bodies of water worldwide. In an effort to characterize the risk and determine the prevalence of these micropollutants in lakes and rivers, many researchers are examining PPCP removal from impaired water during wastewater treatment and water recycling (soil passage) processes. Biodegradation studies and projects considering combinations of biodegradation and other removal processes have been conducted over a wide range of compound categories and therapeutic classes, as well as across different systems and scales of study. This review summarizes the extent of PPCP removal observed in these various systems.


Assuntos
Cosméticos/metabolismo , Preparações Farmacêuticas/metabolismo , Poluentes Químicos da Água/metabolismo , Cosméticos/isolamento & purificação , Preparações Farmacêuticas/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação
12.
Hum Pathol ; 36(3): 275-81, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15791572

RESUMO

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995. The population representativeness of the TMA was evaluated by comparing patient and clinical characteristics of TMA cases to that of all cases of colorectal carcinoma diagnosed statewide in 1995. Cytokeratin 20 (CK20) and cytokeratin 7 (CK7) immunohistochemistry was used to validate the utility of the TMA, and the expression of these proteins was correlated with patient and tumor characteristics. The TMA comprised tissue specimens from 286 patients representing 47% of all invasive cases diagnosed statewide in 1995. TMA cases were comparable to all invasive colorectal cases statewide with respect to age, sex, race/ethnicity, anatomic site, and survival. There were some differences between TMA cases and all cases with respect to tumor stage, histological classification, and treatment. There were significant differences in the relative expression of CK20 and CK7 proteins between malignant and normal tissues and by tumor stage. Advanced cancers were more likely to have CK20+/cytokeratin 7+ (CK7+) profiles than early-stage cancers, which were predominantly CK20+/cytokeratin 7- (CK7-). CK7+ expression was not correlated with anatomic location of carcinomas. This well-characterized TMA offers a powerful tool for testing hypotheses regarding colorectal carcinogenesis, including the identification of potential markers of neoplastic development and progression.


Assuntos
Neoplasias Colorretais/química , Proteínas de Filamentos Intermediários/análise , Queratinas/análise , Adenocarcinoma/química , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Queratina-20 , Queratina-7 , Masculino , Pessoa de Meia-Idade , Mortalidade , Invasividade Neoplásica , Estadiamento de Neoplasias , Análise Serial de Proteínas , Taxa de Sobrevida
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