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1.
J Hand Microsurg ; 14(1): 25-30, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35256825

RESUMO

Introduction The purpose of this study was to evaluate the early outcomes of thumb metacarpophalangeal (MCP) joint ulnar collateral ligament (UCL) repair using suture anchors with suture tape augmentation. Materials and Methods Six patients underwent thumb UCL repair or reconstruction with suture tape augmentation and six patients underwent thumb UCL repair with intraosseous suture anchors between January 2013 and January 2018. The main outcome measures were range of motion, strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and complications. Results At final follow-up for patients who had suture tape augmentation, the average thumb MCP joint and interphalangeal (IP) joint flexion were 65 and 73 degrees, respectively. The average DASH score was 4.3. At final follow-up for patients who had intraosseous suture anchor repair, the average thumb MCP joint and IP joint flexion were 50 and 60 degrees, respectively. The average DASH score was 38. There were no complications or secondary procedures in either group. Conclusion The use of suture anchor repair with suture tape augmentation for thumb UCL injuries is a treatment option that allows for early range of motion with satisfactory early outcomes that are comparable to intraosseous suture anchor repair. Level of Evidence This is a level IV, case series article.

2.
Haematologica ; 106(6): 1608-1615, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32414849

RESUMO

Mutations of the IGH variable region in patients with chronic lymphocytic leukemia (CLL) are associated with a favorable prognosis. Cytogenetic complexity (>3 unrelated aberrations) and translocations have been associated with an unfavorable prognosis. While mutational status of IGHV is stable, cytogenetic aberrations frequently evolve. However, the relationships of these features as prognosticators at diagnosis are unknown. We examined the CpG-stimulated metaphase cytogenetic features detected within one year of diagnosis of CLL and correlated these features with outcome and other clinical features including IGHV. Of 329 untreated patients, 53 (16.1%) had a complex karyotype (16.1%), and 85 (25.8%) had a translocation. Median time to first treatment (TFT) was 47 months. In univariable analyses, significant risk factors for shorter TFT (p3.5, log-transformed WBC, unmutated IGHV, complex karyotype, translocation, and FISH for trisomy 8, del(11q) and del(17p). In multivariable analysis, there was significant effect modification of IGHV status on the relationship between translocation and TFT (p=0.002). In IGHV mutated patients, those with a translocation had over 3.5 times higher risk of starting treatment than those without a translocation (p.


Assuntos
Leucemia Linfocítica Crônica de Células B , Análise Citogenética , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Prognóstico
3.
Cureus ; 12(9): e10256, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-33042694

RESUMO

Meningiomas arise from arachnoid cap cells and are the most common heavily researched intracranial tumors. Most of these neoplasms are benign and are classified as World Health Organization (WHO) grade I. They are often found in parasagittal and falx regions, over cerebral convexities, and in the sphenoid ridges. Spheno-orbital meningiomas (SOMs) occupy the cranium and the orbit and are less commonly encountered. Nonetheless, in this case study, a 9.5 cm × 5 cm SOM occurring in a 93-year-old female cadaver was identified and examined. The tumor spanned from the left middle cranial fossa, through the anterior fossa and invaded the orbit. It caused proptosis of the left eye, compression of the temporal lobe, and damage to the optic nerve. Histological examination of the tumor revealed characteristics of a WHO grade I meningothelial meningioma.

4.
J Neurosurg Spine ; : 1-5, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30660112

RESUMO

OBJECTIVE: The aim of this study was to determine the inter-rater reliability of the modified Medical Research Council (MRC) scale for grading motor function in patients with chronic incomplete spinal cord injury (SCI). METHODS: Two neurosurgical residents and 2 faculty members performed motor examinations in 6 chronic incomplete SCI patients for a total of 156 muscle groups. Examinations were performed using the modified MRC grading scale during routine clinic visits for each patient. Informed consent was obtained prior to enrollment. Patients with American Spinal Injury Association (ASIA) Impairment Scale grade A (ASIA A) injuries were excluded. Inter-rater reliability coefficients were calculated using Kendall's coefficient of concordance (W) and intraclass correlation coefficients (ICCs). RESULTS: Sixty-four percent of the tested variables demonstrated extremely strong (W 0.71-0.9) or strong (0.51-0.7) inter-rater reliability using Kendall's coefficient of concordance and an ICC corresponding to excellent (ICC > 0.75) or fair to good (ICC 0.4-0.75) inter-rater reliability. An additional 7% showed poor inter-rater reliability (ICC < 0.4). The remaining variables tested did not reach statistical significance. CONCLUSIONS: The inter-rater reliability of the modified MRC scale was found to be high in the majority of tested variables, but the results suggest that discrepancy among trained observers does exist. Reliability was greatest in the lower-extremity muscle groups and least in the upper-extremity muscle groups in patients with chronic incomplete SCI.

5.
Neurosurgery ; 84(5): 993-999, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30544216

RESUMO

BACKGROUND: Confusion exists among neurosurgeons when choosing and implementing an appropriate study design and statistical methods when conducting research. We noticed particular difficulty with mislabeled and inappropriate case-control studies in the neurosurgical literature. OBJECTIVE: To quantify and to rigorously review this issue for appropriateness in publication and to establish quality of the manuscripts using a rigorous technique. METHODS: Following a literature search, pairs drawn from 5 independent reviewers evaluated a complete sample of 125 manuscripts claiming to be case-control studies with respect to basic case-control criteria. Seventy-five papers were then subjected to a more rigorous appraisal for quality using the SIGN Methodology Checklist for case-control studies. RESULTS: Fifty publications were rejected based on basic criteria used to identify case-control design. Of the 75 subjected to quality analysis, 46 were felt to be acceptable for publication. Only 11 papers (9%) achieved the designation of high quality. Of the original 125 papers evaluated, 79 (63%) were inappropriately labeled case-control studies. CONCLUSION: Mislabeling and use of inappropriate study design are common in the neurosurgical literature. Manuscripts should be evaluated rigorously by reviewers and readers, and neurosurgical training programs should include instruction on choice of appropriate study design and critical appraisal of the literature.


Assuntos
Estudos de Casos e Controles , Neurocirurgia/normas , Projetos de Pesquisa/normas , Relatório de Pesquisa/normas , Humanos , Editoração
6.
Neurosurgery ; 84(4): 819-826, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30535401

RESUMO

Case-control (case-control, case-controlled) studies are beginning to appear more frequently in the neurosurgical literature. They can be more robust, if well designed, than the typical case series or even cohort study to determine or refine treatment algorithms. The purpose of this review is to define and explore the differences between case-control studies and other so-called nonexperimental, quasiexperimental, or observational studies in determining preferred treatments for neurosurgical patients.


Assuntos
Estudos de Casos e Controles , Pesquisa Biomédica , Humanos , Projetos de Pesquisa
7.
Haematologica ; 103(8): 1288-1297, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29773600

RESUMO

Diseases with clonal hematopoiesis such as myelodysplastic syndrome and acute myeloid leukemia have high rates of relapse. Only a small subset of acute myeloid leukemia patients are cured with chemotherapy alone. Relapse in these diseases occurs at least in part due to the failure to eradicate leukemic stem cells or hematopoietic stem cells in myelodysplastic syndrome. CD123, the alpha chain of the interleukin-3 receptor heterodimer, is expressed on the majority of leukemic stem cells and myelodysplastic syndrome hematopoietic stem cells and in 80% of acute myeloid leukemia. Here, we report indiscriminate killing of CD123+ normal and acute myeloid leukemia / myelodysplastic syndrome cells by SL-401, a diphtheria toxin interleukin-3 fusion protein. SL-401 induced cytotoxicity of CD123+ primary cells/blasts from acute myeloid leukemia and myelodysplastic syndrome patients but not CD123- lymphoid cells. Importantly, SL-401 was highly active even in cells expressing low levels of CD123, with minimal effect on modulation of the CD123 target in acute myeloid leukemia. SL-401 significantly prolonged survival of leukemic mice in acute myeloid leukemia patient-derived xenograft mouse models. In addition to primary samples, studies on normal cord blood and healthy marrow show that SL-401 has activity against normal hematopoietic progenitors. These findings indicate potential use of SL-401 as a "bridge-to-transplant" before allogeneic hematopoietic cell transplantation in acute myeloid leukemia / myelodysplastic syndrome patients.


Assuntos
Linfócitos T CD4-Positivos/efeitos dos fármacos , Subunidade alfa de Receptor de Interleucina-3/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Subunidade alfa de Receptor de Interleucina-3/análise , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/patologia , Proteínas Recombinantes de Fusão/uso terapêutico , Células Tumorais Cultivadas
8.
J Neurosurg Spine ; 28(2): 140-148, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29171791

RESUMO

OBJECTIVE Dysphagia and vocal cord palsy (VCP) are common complications after anterior cervical discectomy and fusion (ACDF). The reported incidence rates for dysphagia and VCP are variable. When videolaryngostroboscopy (VLS) is performed to assess vocal cord function after ACDF procedures, the incidence of VCP is reported to be as high as 22%. The incidence of dysphagia ranges widely, with estimates up to 71%. However, to the authors' knowledge, there are no prospective studies that demonstrate the rates of VCP and dysphagia for reoperative ACDF. This study aimed to investigate the incidence of voice and swallowing disturbances before and after reoperative ACDF using a 2-team operative approach with comprehensive pre- and postoperative assessment of swallowing, direct vocal cord visualization, and clinical neurosurgical outcomes. METHODS A convenience sample of sequential patients who were identified as requiring reoperative ACDF by the senior spinal neurosurgeon at the University of Alabama at Birmingham were enrolled in a prospective, nonrandomized study during the period from May 2010 until July 2014. Sixty-seven patients undergoing revision ACDF were enrolled using a 2-team approach with neurosurgery and otolaryngology. Dysphagia was assessed both preoperatively and postoperatively using the MD Anderson Dysphagia Inventory (MDADI) and fiberoptic endoscopic evaluation of swallowing (FEES), whereas VCP was assessed using direct visualization with VLS. RESULTS Five patients (7.5%) developed a new postoperative temporary VCP after reoperative ACDF. All of these cases resolved by 2 months postoperatively. There were no new instances of permanent VCP. Twenty-five patients had a new swallowing disturbance detected on FEES compared with their baseline assessment, with most being mild and requiring no intervention. Nearly 60% of patients showed a decrease in their postoperative MDADI scores, particularly within the physical subset. CONCLUSIONS A 2-team approach to reoperative ACDF was safe and effective, with no new cases of VCP on postoperative VLS. Dysphagia rates as assessed through the MDADI scale and FEES were consistent with other published reports.


Assuntos
Vértebras Cervicais/cirurgia , Transtornos de Deglutição/etiologia , Discotomia , Complicações Pós-Operatórias , Fusão Vertebral , Disfunção da Prega Vocal/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Deglutição , Transtornos de Deglutição/diagnóstico por imagem , Endoscopia Gastrointestinal , Feminino , Tecnologia de Fibra Óptica , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Reoperação , Fatores de Risco , Resultado do Tratamento , Disfunção da Prega Vocal/epidemiologia
9.
J Clin Invest ; 127(8): 3052-3064, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28714866

RESUMO

BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially. T cell phenotype, immune function, and CLL cell immunosuppressive capacity were evaluated. RESULTS: Ibrutinib markedly increased CD4+ and CD8+ T cell numbers in CLL patients. This effect was more prominent in effector/effector memory subsets and was not observed with acalabrutinib. Ex vivo studies demonstrated that this may be due to diminished activation-induced cell death through ITK inhibition. PD-1 and CTLA-4 expression was significantly markedly reduced in T cells by both agents. While the number of Treg cells remained unchanged, the ratio of these to conventional CD4+ T cells was reduced with ibrutinib, but not acalabrutinib. Both agents reduced expression of the immunosuppressive molecules CD200 and BTLA as well as IL-10 production by CLL cells. CONCLUSIONS: Ibrutinib treatment increased the in vivo persistence of activated T cells, decreased the Treg/CD4+ T cell ratio, and diminished the immune-suppressive properties of CLL cells through BTK-dependent and -independent mechanisms. These features provide a strong rationale for combination immunotherapy approaches with ibrutinib in CLL and other cancers. TRIAL REGISTRATION: ClinicalTrials.gov NCT01589302 and NCT02029443. Samples described here were collected per OSU-0025. FUNDING: The National Cancer Institute.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/metabolismo , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Linfócitos T/metabolismo , Adenina/análogos & derivados , Tirosina Quinase da Agamaglobulinemia , Idoso , Animais , Antígenos CD/metabolismo , Benzamidas/uso terapêutico , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Antígeno CTLA-4/metabolismo , Estudos de Coortes , Feminino , Humanos , Imunossupressores/uso terapêutico , Imunoterapia , Interleucina-10/metabolismo , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Pessoa de Meia-Idade , Piperidinas , Receptor de Morte Celular Programada 1/metabolismo , Proteínas Tirosina Quinases/metabolismo , Pirazinas/uso terapêutico , Receptores Imunológicos/metabolismo , Linfócitos T/citologia
10.
J Clin Oncol ; 35(13): 1437-1443, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28418267

RESUMO

Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can cause relapse, but data regarding the prevalence and natural history of these mutations are limited. Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses. Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospectively on a screening population. Results With a median follow-up time of 3.4 years, the estimated cumulative incidence of progression at 4 years is 19% (95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1), and age less than 65 years were risk factors for progression. Among patients who experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95% CI, 71% to 94%), and these mutations were detected an estimated median of 9.3 months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients examined prospectively, eight patients have experienced relapse, and all of these patients had acquired resistance mutations before relapse. A resistance mutation was detected in an additional eight patients who have not yet met criteria for clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance. We show that mutations in BTK and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.


Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/enzimologia , Proteínas Tirosina Quinases/genética , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Adulto , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Masculino , Pessoa de Meia-Idade , Fosfolipase C gama/genética , Piperidinas , Proteínas Tirosina Quinases/metabolismo , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia
11.
Blood Adv ; 1(19): 1584-1588, 2017 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-29296799

RESUMO

Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described. Using fluorescence in situ hybridization, we detected near-tetraploidy in 9 of 297 patients with CLL prior to beginning ibrutinib treatment on 1 of 4 clinical trials (3.0%; 95% confidence interval [CI], 1.4%-5.7%). Near-tetraploidy was associated with aggressive disease characteristics: Rai stage 3/4 (P = .03), deletion 17p (P = .03), and complex karyotype (P = .01). Near-tetraploidy was also associated with ibrutinib discontinuation due to Richter transformation (P < .0001), but not due to progressive CLL (P = .41). Of the 9 patients with near-tetraploidy, 6 had Richter transformation with diffuse large B-cell lymphoma. In a multivariable model, near-tetraploidy (hazard ratio [HR], 8.66; 95% CI, 3.83-19.59; P < .0001) and complex karyotype (HR, 4.77; 95% CI, 1.42-15.94; P = .01) were independent risk factors for discontinuing ibrutinib due to transformation. Our results suggest that near-tetraploidy is a potential prognostic marker for Richter transformation to assess in patients going on ibrutinib.

12.
J Neurosurg Spine ; 25(2): 198-204, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27015129

RESUMO

OBJECTIVE Recurrent laryngeal nerve (RLN) injury is one of the most frequent complications of anterior cervical discectomy and fusion (ACDF) procedures. The frequency of RLN is reported as 1%-11% in the literature. (4 , 15) The rate of palsy after reoperative ACDF surgery is not well defined. This meta-analysis was performed to review the current medical evidence on RLN injury after ACDF surgery and to determine a relative rate of RLN injury after reoperative ACDF. METHODS MEDLINE, PubMed, and Google Scholar searches were performed using several key words and phrases related to ACDF surgery. Included studies were written in English, addressed revisionary ACDF surgery, and studied outcomes of RLN injury. Statistical analysis was then performed using a random-effects model to calculate a pooled rate of RLN injury. The heterogeneity of the studies was assessed using Cochran's Q statistic and I(2) statistic, and a funnel plot was constructed to evaluate publication bias. RESULTS The search initially identified 345 articles on this topic. Eight clinical articles that met all inclusion criteria were included in the meta-analysis. A total of 238 patients were found to have undergone reoperative ACDF. Thirty-three of those patients experienced an RLN injury. This analysis identified a rate of RLN injury in the literature after reoperative ACDF of 14.1% (95% confidence interval [CI] 9.8%-19.1%). CONCLUSIONS The rate of RLN palsy of 14.1% was greater than any published rate of RLN injury after primary ACDF operations, suggesting that there is a greater risk of hoarseness and dysphagia with reoperative ACDF surgeries than with primary procedures as reported in these studies.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/efeitos adversos , Complicações Pós-Operatórias , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Reoperação/efeitos adversos , Fusão Vertebral/efeitos adversos , Discotomia/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Traumatismos do Nervo Laríngeo Recorrente/epidemiologia , Reoperação/métodos , Risco , Fusão Vertebral/métodos
13.
JAMA Oncol ; 1(1): 80-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26182309

RESUMO

IMPORTANCE: The Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in patients with chronic lymphocytic leukemia (CLL). Reasons for discontinuing therapy with this drug and outcomes following discontinuation have not been evaluated outside of clinical trials with relatively short follow-up. OBJECTIVE: To determine features associated with discontinuation of ibrutinib therapy and outcomes. DESIGN, SETTING, AND PARTICIPANTS: A total of 308 patients participating in 4 sequential trials of ibrutinib at The Ohio State University Comprehensive Cancer Center were included. These clinical trials accrued patients included in this analysis from May 2010 until April 2014, and data were locked in June 2014. MAIN OUTCOMES AND MEASURES: Patients were evaluated for time to therapy discontinuation, reasons for discontinuation, and survival following discontinuation. For patients who discontinued therapy because of disease progression, targeted deep sequencing was performed in samples at baseline and time of relapse. RESULTS: With a median follow-up of 20 months, 232 patients remained on therapy, 31 had discontinued because of disease progression, and 45 had discontinued for other reasons. Disease progression includes Richter's transformation (RT) or progressive CLL. Richter's transformation appeared to occur early and CLL progressions later (cumulative incidence at 12 months, 4.5% [95% CI, 2.0%-7.0%] and 0.3% [95% CI, 0%-1.0%], respectively). Median survival following RT was 3.5 months (95% CI, 0.3-6.0 months) and 17.6 months (95% CI, 4.7 months-"not reached") following CLL progression. Sequencing on peripheral blood from 8 patients with RT revealed 2 with mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCG2. Deep sequencing on 11 patients with CLL progression revealed BTK or PLCG2 mutations in all. These mutations were not identified before treatment in any patient. CONCLUSIONS AND RELEVANCE: This single-institution experience with ibrutinib confirms it to be an effective therapy and identifies, for the first time, baseline factors associated with ibrutinib therapy discontinuation. Outcomes data show poor prognosis after discontinuation, especially for those patients with RT. Finally, sequencing data confirm initial reports associating mutations in BTK and PLCG2 with progression and clearly show that CLL progressions are associated with these mutations, while RT is likely not. TRIAL REGISTRATIONS: clinicaltrials.gov Identifiers:NCT01105247, NCT01217749, NCT01589302, and NCT01578707.


Assuntos
Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Adulto , Tirosina Quinase da Agamaglobulinemia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ensaios Clínicos como Assunto , Análise Mutacional de DNA/métodos , Progressão da Doença , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/enzimologia , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Mutação , Ohio , Fosfolipase C gama/genética , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos , Recidiva , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Childs Nerv Syst ; 30(9): 1589-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24798479

RESUMO

PURPOSE: Penetrating gunshot wounds to the head (GSWH) have notoriously poor outcomes with extremely high mortality. Long-term follow-up data of affected children is scant in the medical literature. This report summarizes clinical presentation, management, and long-term outcomes from three children who survived "execution style" frontal, bihemispheric gunshot wounds with no or minimal surgical intervention. METHODS: A retrospective chart review of available medical records and outcomes from standardized, validated psychological instruments was undertaken, summarized, and evaluated. RESULTS: Despite bihemispheric injuries in each patient, no patient required operative intervention. Each child survived without readily evident neurologic impairment; however, the extent of impaired executive function varied widely, and severe disinhibition remains profoundly disabling in one survivor. CONCLUSIONS: Bihemispheric penetrating gunshot injuries are not uniformly fatal and can occasionally be associated with long-term favorable survival; however, impaired executive function has significant potential to be profoundly disabling in these injuries.


Assuntos
Transtornos Cognitivos/etiologia , Ferimentos por Arma de Fogo/complicações , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Estudos Retrospectivos , Irmãos , Sobrevida , Tomógrafos Computadorizados
15.
PLoS One ; 8(4): e61035, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23593382

RESUMO

Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%), and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs.


Assuntos
Neoplasias Encefálicas/enzimologia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Glioblastoma/enzimologia , Sequência de Bases , Metilação de DNA , Primers do DNA , Humanos , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
16.
J Neurosurg Pediatr ; 11(4): 478-84, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23350678

RESUMO

The authors report on an infant with a bifrontal encephalocele that was associated with multisuture craniosynostosis, spasticity, and a progressively severe epilepsy. They describe the initial presentation, genetic screening results, staged multidisciplinary operative plans, clinical course, complications, and long-term surgical and developmental follow-up. To their knowledge, the comprehensive surgical management of this type of complicated congenital cranial anomaly has not been previously described. Surgical management was staged and multidisciplinary and required careful attention to all 3 components of the condition: 1) hydrocephalus, 2) frontal meningoencephalocele, and 3) epilepsy.


Assuntos
Craniossinostoses/cirurgia , Encefalocele/cirurgia , Meningocele/cirurgia , Craniossinostoses/complicações , Craniossinostoses/diagnóstico , Encefalocele/complicações , Encefalocele/diagnóstico , Epilepsia/diagnóstico , Epilepsia/etiologia , Epilepsia/prevenção & controle , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/etiologia , Hidrocefalia/prevenção & controle , Recém-Nascido , Masculino , Meningocele/complicações , Meningocele/diagnóstico
17.
J Neurosurg ; 117(5): 860-3, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22957527

RESUMO

OBJECT: This study was undertaken to assess the reliability of observations of postoperative photographs in assigning House-Brackmann scores as outcome measures for patients following resection of vestibular schwannomas. METHODS: Forty pictures of differing facial expressions typically elicited from patients for assigning House-Brackmann scores were individually evaluated by neurosurgery residents and faculty members at the University of Alabama at Birmingham; a score was assigned to each picture by the individual raters. The interrater reliability was measured using the Spearman correlation coefficient, Kendall coefficient of concordance, and kappa statistic; internal consistency was calculated using the Cronbach alpha reliability estimate. RESULTS: The Spearman correlation coefficients showed strong positive association among raters, with a range of values of 0.66 to 0.90. Internal consistency measured by the Cronbach alpha coefficient was excellent (α = 0.97). The Kendall coefficient of concordance for the ordinal grades suggested a substantial degree of agreement among the raters (w = 0.76, p < 0.001). CONCLUSIONS: Static postoperative photographs are a reliable outcome measure for determining facial nerve function after vestibular schwannoma resection and may serve as a surrogate for the dynamic patient interview.


Assuntos
Traumatismos do Nervo Facial/diagnóstico , Neuroma Acústico/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Fotografação , Complicações Pós-Operatórias/diagnóstico , Interpretação Estatística de Dados , Expressão Facial , Traumatismos do Nervo Facial/fisiopatologia , Paralisia Facial/fisiopatologia , Humanos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Resultado do Tratamento
18.
Leuk Lymphoma ; 53(9): 1743-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22369572

RESUMO

The impact of mutation of the ATM (ataxia telangiectasia mutated) gene in chronic lymphocytic leukemia (CLL) treatment outcome has not been examined. We studied ATM mutations in 73 patients treated with fludarabine and rituximab. ATM gene mutation analysis was performed using temperature gradient capillary electrophoresis. The impact of detected variants on overall survival (OS) and progression-free survival (PFS) was tested with proportional hazards models. None of the 73 patients demonstrated truncating ATM mutations; 17 (23%, 95% confidence interval 14-35%) had non-silent variants (ATM-NSVs), including 13 known ATM polymorphisms and four missense variants. ATM-NSVs were not significantly associated with any baseline characteristics including immunoglobulin heavy chain variable gene (IGVH) status. In multivariable models, no significant differences in complete response (p =0.70), PFS (p =0.59) or OS (p =0.13) were observed. Our data indicate that truncating ATM mutations are rare in patients with CLL. Furthermore, in this dataset, these non-silent variants had limited impact on PFS and OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Proteínas Serina-Treonina Quinases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Proteínas Mutadas de Ataxia Telangiectasia , Análise Mutacional de DNA , Intervalo Livre de Doença , Feminino , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Polimorfismo de Nucleotídeo Único , Modelos de Riscos Proporcionais , Rituximab , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
19.
Childs Nerv Syst ; 28(4): 575-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22258754

RESUMO

INTRODUCTION: The care of patients with pseudotumor cerebri (idiopathic intracranial hypertension) involves ophthalmologists, neurologists and neurosurgeons. Its clinical characteristics in the pediatric population are distinct from those in adult patients. PATIENTS AND METHODS: Fifty-nine patients diagnosed with pseudotumor cerebri were identified from the neurosurgery and neurology databases at Children's Hospital, Birmingham, AL, USA. Clinical data were collected from the ophthalmology, neurology and neurosurgery departments. RESULTS: The average age of patients at diagnosis was 11.4 years (range 3-17). The average opening pressure of lumbar puncture (LP) was 37 cm of water. Most of the patients responded well to therapeutic LPs and medical management. Neurosurgical interventions included intracranial pressure monitoring and shunt insertion in nine patients. In three patients who presented with acute visual decline, two recovered and one remains legally blind. CONCLUSIONS: The care of patients with pseudotumor cerebri requires a multiple-disciplinary approach. Neurosurgical interventions are sometimes needed for diagnostic and treatment purpose. Prompt and accurate communication among specialists is necessary to ensure timely treatment and optimal outcomes.


Assuntos
Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/terapia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Gerenciamento Clínico , Feminino , Seguimentos , Humanos , Masculino
20.
J Neurosurg Pediatr ; 8(1): 1-5, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21721881

RESUMO

OBJECT: In 1998 the authors identified 5 patients with syringomyelia and no evidence of Chiari malformation Type I (CM-I). Magnetic resonance imaging of the entire neuraxis ruled out other causes of a syrinx. Ultimately, abnormal CSF flow at the foramen magnum was the suspected cause. The label "Chiari 0" was used to categorize these unique cases with no tonsillar ectopia. All of the patients underwent posterior fossa decompression and duraplasty identical to the technique used to treat patients with CM-I. Significant syrinx and symptom resolution occurred in these patients. Herein, the authors report on a follow-up study of patients with CM-0 who were derived from over 400 operative cases of pediatric CM-I decompression. METHODS: The authors present their 12-year experience with this group of patients. RESULTS: Fifteen patients (3.7%) were identified. At surgery, many were found to have physical barriers to CSF flow near the foramen magnum. In most of them, the syringomyelia was greatly diminished postoperatively. CONCLUSIONS: The authors stress that this subgroup represents a very small cohort among patients with Chiari malformations. They emphasize that careful patient selection is critical when diagnosing CM-0. Without an obvious CM-I, other etiologies of a spinal syrinx must be conclusively ruled out. Only then can one reasonably expect to ameliorate the clinical course of these patients via posterior fossa decompression.


Assuntos
Malformação de Arnold-Chiari/diagnóstico , Malformação de Arnold-Chiari/cirurgia , Descompressão Cirúrgica/métodos , Siringomielia/diagnóstico , Siringomielia/cirurgia , Adolescente , Malformação de Arnold-Chiari/classificação , Vértebras Cervicais/cirurgia , Criança , Pré-Escolar , Craniotomia , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Siringomielia/classificação
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