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1.
JAMA Netw Open ; 4(8): e2120456, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34379123

RESUMO

Importance: Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. Objective: To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. Design, Setting, and Participants: This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. Exposures: The presence of a COVID-19 diagnosis using ICD-10. Main Outcomes and Measures: Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2. Results: Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non-COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25]; P < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P < .001), and in-hospital mortality (24 women [0.1%] vs 71 [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001). Conclusions and Relevance: This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.


Assuntos
COVID-19/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Nascimento Prematuro/epidemiologia , Centros Médicos Acadêmicos/estatística & dados numéricos , Adolescente , Adulto , COVID-19/terapia , Estudos de Casos e Controles , Cesárea/estatística & dados numéricos , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Intubação Intratraqueal/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Pandemias , Gravidez , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/terapia , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiologia , Adulto Jovem
2.
J Gastrointest Surg ; 25(1): 201-210, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32030602

RESUMO

BACKGROUND: Non-elective cholecystectomies can lead to severe postoperative complications and mortality. Existing risk prediction tools do not meet the need to reliably predict these complications. METHODS: Using the 2011-2016 American College of Surgeons National Surgical Quality Improvement Program datasets, we identified patients undergoing non-elective cholecystectomy with primary ICD 9/10 codes indicating the following diagnoses: symptomatic cholelithiasis, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and cholangitis. We randomly allocated patients to derivation and validation cohorts (80/20 split). Severe complications (Clavien-Dindo grades IV and V) included unplanned intubation, prolonged mechanical ventilation, pulmonary embolism, acute renal failure requiring dialysis, stroke, myocardial infarction, cardiac arrest, septic shock, and mortality. Logistic regression using backward selection identified predictors of severe complications and a risk score was generated based on this model. RESULTS: Of 68,953 patients in the derivation cohort, 1.7% (N = 1157) suffered severe complications. The final multivariable risk score model included the following predictors: age (0-12 points), preoperative sepsis (5 points), planned open procedure (5 points), estimated glomerular filtration rate (0-13 points), and preoperative albumin level (0-8 points). The associated risk-score model yielded scores from 0 to 43 with 0.1-59.4% predicted probability of severe complications and had a C-statistic of 0.845 (95% CI 0.834, 0.857) in the derivation cohort and 0.870 (95% CI 0.851, 0.889) in the validation cohort. CONCLUSION: A simple risk-score model predicts severe complications in patients undergoing unplanned cholecystectomy for common indications encountered in an acute care surgery service and identifies high-risk patients.


Assuntos
Colecistectomia , Colelitíase , Humanos , Modelos Logísticos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
3.
Gynecol Oncol Rep ; 33: 100592, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32529020

RESUMO

CIC-rearranged round cell sarcoma (CRS) is a rare entity that presents in various anatomical locations and involves deep soft-tissue structures and skin. Although commonly confused with and clinically similar to Ewing sarcoma (ES), investigators have recently shown that this unique condition maintains morphologic and pathologic features that are distinct from ES. In this report, we present and discuss a case of CRS of the uterus, the first of its kind to be reported in the English-language literature. We urge the scientific community to continue its investigations in elucidating the features of this entity, as young women who suffer from this condition have dismal prognoses and currently do not have access to therapeutic options for cure.

4.
Childs Nerv Syst ; 36(3): 559-568, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31863148

RESUMO

PURPOSE: Endoscopic third ventriculostomy (ETV) has gained traction as a method for treating post-hemorrhagic hydrocephalus of prematurity (PHHP) in an effort to obviate lifelong shunt dependence in neonates. However, data remains limited regarding inpatient failures. METHODS: A retrospective analysis of the NIS between 1998 and 2014 was performed. Discharges with age < 1 year and ICD-9-CM codes indicating intraventricular hemorrhage of prematurity (772.1x) and ETV/shunt (02.22 and 02.3x) were included. Patients with ICD-9-CM codes for ventricular drain/reservoir (02.21) were excluded to prevent confounding. Time trend series plots were created. Yearly trends were quantified using logarithmic regression analysis. Kaplan-Meier curves were utilized to analyze time to treatment failure. Time to failure for each treatment was compared using log-rank. RESULTS: A total of 11,017 discharges were identified. ETV was more likely to be utilized at < 29 weeks gestational age (p = 0.0039) and birth weight < 1000 g (p = 0.0039). Shunts were less likely to fail in older and heavier newborns (OR 0.836 p = 0.00456, OR 0.828 p = 0.0001, respectively). Those initially shunted had lower failure rates compared with ETV (OR 0.44, p < 0.0001) but time to failure was longer with ETV (p = 0.04562). 79.5% of ETVs that failed were shunted after the first failure. Shunts were much less likely to undergo ETV if they failed (OR 0.21, p < 0.0001). Higher grade IVH was predictive of shunt failure but not ETV (OR 2.36, p = 0.0129). CONCLUSIONS: Although ETV can be effective in PHHP, it has a much higher initial failure rate than shunting and should thus be chosen based on a multifactorial approach.


Assuntos
Hidrocefalia , Neuroendoscopia , Terceiro Ventrículo , Idoso , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Lactente , Recém-Nascido , Pacientes Internados , Estudos Retrospectivos , Terceiro Ventrículo/cirurgia , Resultado do Tratamento , Ventriculostomia
5.
J Neurosurg Pediatr ; : 1-9, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628286

RESUMO

OBJECTIVE: Cerebral palsy (CP) is the most common childhood physical disability. Historically, children with hypertonia who are nonambulatory (Gross Motor Function Classification System [GMFCS] level IV or V) were considered candidates for intrathecal baclofen (ITB) therapy to facilitate care and mitigate discomfort. Selective dorsal rhizotomy (SDR) was often reserved for ambulant children to improve gait. Recently, case series have suggested SDR as an alternative to ITB in selected children functioning at GMFCS level IV/V. The objective for this study was to systematically review the evidence for ITB and SDR in GMFCS level IV or V children. METHODS: Medline, Embase, Web of Science, and Cochrane databases were systematically searched. Articles were screened using the following inclusion criteria: 1) peer-reviewed articles reporting outcomes after SDR or ITB; 2) outcomes reported using a quantifiable scale or standardized outcome measure; 3) patients were < 19 years old at the time of operation; 4) patients had a diagnosis of CP; 5) patients were GMFCS level IV/V or results were reported based on GMFCS status and included some GMFCS level IV/V patients; 6) article and/or abstract in English; and 7) primary indication for surgery was hypertonia. Included studies were assessed with the Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) tool. RESULTS: Twenty-seven studies met inclusion criteria. The most commonly reported outcomes were spasticity (on the Mean Ashworth Scale) and gross motor function (using the Gross Motor Function Measure), although other outcomes including frequency of orthopedic procedures and complications were also reported. There is evidence from case series that suggests that both ITB and SDR can lower spasticity and improve gross motor function in this nonambulatory population. Complication rates are decidedly higher after ITB due in part to the ongoing risk of device-related complications. The heterogeneity among study design, patient selection, outcome selection, and follow-up periods was extremely high, preventing meta-analysis. There are no comparative studies, and meaningful health-related quality of life outcomes such as care and comfort are lacking. This review is limited by the high risk of bias among included studies. Studies of SDR or ITB that did not clearly describe patients as being GMFCS level IV/V or nonambulatory were excluded. CONCLUSIONS: There is a lack of evidence comparing the outcomes of ITB and SDR in the nonambulatory CP population. This could be overcome with standardized prospective studies using more robust methodology and relevant outcome measures.

6.
Surg Neurol Int ; 10: 70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31528408

RESUMO

Background: The Currarino syndrome (CS), defined by the triad of anorectal malformations, sacral bone deformities, and presacral masses, is rare. There are few surgical series that discuss conservative management versus the surgical approaches to these lesions. Here, we describe utilizing a combined anterior and posterior approach for resecting these lesions in four patients. Methods: Four patients with CS were treated with two-stage approaches performed by a multidisciplinary team, including pediatric neurosurgery and general surgery. The first anterior laparoscopic approach mobilized the presacral mass from its ventral attachments. The second posterior procedure detethered the spinal cord, repaired the dural defect, and facilitated removal of the presacral mass. Results: Gross total resection of all four presacral masses was accomplished without intraoperative complication; all patients clinically improved. Conclusion: The CS is characterized by a large presacral mass. Here, one must rule out malignancy and also consider diagnosis/resection due to the risks for malignant transformation. The operative approach we described in four patients utilized standard anterior mobilization of the mass, followed by posterior detethering, dural repair, and ultimate resection.

7.
J Clin Neurosci ; 64: 98-100, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30952556

RESUMO

Vasculitis of the central nervous system is a rare and poorly understood disease of the brain and spinal cord. Cerebral angiography is the radiological gold standard for diagnosis in patients with compatible clinical findings. However, advances in the quality of noninvasive neuroimaging techniques of cerebral and spinal vasculature such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA) may obviate the need for invasive catheter angiography. We reviewed our institutional experience at Jackson Memorial Hospital between 2011 and 2016 to assess the utility of performing a cerebral digital subtraction angiogram (DSA) in the management of suspected vasculitis. In 16 (59%) of the 27 patients who underwent both noninvasive imaging and DSA, neither imaging studies showed any evidence of vasculitis. Despite these negative studies, 2 patients were treated empirically with immunosuppressants based on clinical symptoms and laboratory findings. 10 (37%) patients demonstrated irregularities on MRA and findings were confirmed by DSA in 6 of these patients. All 6 of these patients were treated, however, 2 of the 4 patients with abnormal MRA and normal DSA were also started on immunosuppressive therapy despite negative DSA. In conclusion, invasive catheter-based angiography may be of limited benefit in the diagnosis and management of PCNSV when considered in the context of clinical and laboratory findings and MRA or CTA results. Further large studies are necessary to determine whether non-invasive imaging can replace DSA.


Assuntos
Angiografia Digital/métodos , Angiografia Cerebral/métodos , Neuroimagem/métodos , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Adulto , Idoso , Angiografia por Tomografia Computadorizada/métodos , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade
8.
Clin Cancer Res ; 25(6): 1913-1922, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30498094

RESUMO

PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.Experimental Design: In this study, we examined the immune landscape and function of PD-1 expression by T cells from tumor and peripheral blood in patients with malignant glioma. RESULTS: We found several differences between PD-1+ tumor-infiltrating lymphocytes (TIL) and patient-matched PD-1+ peripheral blood T lymphocytes. Phenotypically, PD-1+ TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1+ T cells, which instead had increased markers of memory. A comparison of the T-cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1+ T cells had a significantly increased proliferative capacity upon activation compared with PD-1- T cells. CONCLUSIONS: Our evidence suggests that PD-1 expression in patients with glioma reflects chronically activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomic location. The decreased diversity in PD-1+ T cells suggests that the PD-1-expressing population has a narrower range of cognate antigen targets compared with the PD-1 nonexpression population. This information can be used to inform how we interpret immune responses to PD-1-blocking therapies or other immunotherapies.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Linfócitos do Interstício Tumoral/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Citotóxicos/imunologia , Adulto , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/imunologia , Encéfalo/citologia , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/cirurgia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/cirurgia , Feminino , Perfilação da Expressão Gênica , Glioblastoma/sangue , Glioblastoma/tratamento farmacológico , Glioblastoma/cirurgia , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T Citotóxicos/metabolismo
9.
Seizure ; 61: 89-93, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30118930

RESUMO

PURPOSE: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT) is an emerging minimally-invasive alternative to resective surgery for medically-intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies opportunities to glean insights into epileptogenic regions and their interactions with functional brain networks. In this exploratory analysis, we sought to characterize associations between MRgLITT ablation zones and large-scale brain networks that portended seizure outcome using resting-state fMRI. METHODS: Presurgical fMRI and intraoperatively volumetric structural imaging were obtained, from which the ablation volume was segmented. The network properties of the ablation volume within the brain's large-scale brain networks were characterized using graph theory and compared between children who were and were not rendered seizure-free. RESULTS: Of the seventeen included children, five achieved seizure freedom following MRgLITT. Greater functional connectivity of the ablation volume to canonical resting-state networks was associated with seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who subsequently became seizure-free following MRgLITT had significantly greater strength, and eigenvector centrality within the large-scale brain network. CONCLUSIONS: These findings provide novel insights into the interaction between epileptogenic cortex and large-scale brain networks. The association between ablation volume and resting-state networks may supply novel avenues for presurgical planning and patient stratification.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Terapia a Laser/métodos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Adolescente , Criança , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Monitorização Intraoperatória , Vias Neurais/cirurgia , Procedimentos Neurocirúrgicos , Descanso , Resultado do Tratamento , Adulto Jovem
10.
Surg Neurol Int ; 9: 93, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29770253

RESUMO

Background: Ependymomas are relatively uncommon tumors that constitute about 7% of all primary intracranial neoplasms. Among these, high-grade ependymomas are locally aggressive and recur most commonly at the primary site following resection. Ependymomas are also known to be the one glial neoplasm that tends to frequently metastasize inside and outside the central nervous system (CNS) that complicates workup and management. Metastasis due to surgical manipulation is common and neurosurgeons should be well-versed in the most effective methods to remove these tumors in order to avoid such metastases. Case Description: Here, we report a case of a 28-year-old female who initially presented with a parenchymal World Health Organization (WHO) grade III anaplastic ependymoma of the occipital lobe without metastasis. After multiple resections, the patient showed no evidence of disease recurrence for 2 years. During follow-up, new metastasis to the frontal lobe as well as to the lung were discovered 2 years after the initial surgery, without recurrence at the tumor's primary site. Conclusions: While uncommon, this case demonstrates the possibility for ependymomas to metastasize via cerebrospinal fluid to other locations within the CNS and hematologically to extraneural locations without recurring locally.

11.
Cureus ; 10(1): e2115, 2018 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-29593945

RESUMO

When deciding on a surgical route to reach subcortical brain tumors and colloid cysts, many surgeons advocate the use of transcallosal, transsulcal, or skull base approaches over transcortical approaches due to a high reported incidence of postoperative seizures. We have retrospectively analyzed all patients operated upon by a senior neurosurgeon (Ricardo J. Komotar) who undertook transcortical approaches for the resection of subcortical brain tumors and colloid cysts. We have also performed a comprehensive review of the literature to estimate postoperative seizure risk after transcortical approaches for the resection of deep tumors and colloid cysts. Of 27 patients who underwent transcortical approaches for the resection of subcortical brain tumors and colloid cysts, zero had postoperative seizures. A comprehensive review of the literature shows an 8.3% postoperative risk of seizures after the transcortical approach. Our institution has never experienced a postoperative seizure following the transcortical approach for the resection of deep tumors and colloid cysts. For this reason, we advocate selecting a surgical approach that obtains adequate lesion exposure and minimizes the violation and retraction of eloquent cortex, venous structures, and white matter tracts, rather than on presumed postoperative seizure risk.

12.
Neuro Oncol ; 19(6): 796-807, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28115578

RESUMO

Background: Adaptive immune resistance in the tumor microenvironment appears to attenuate the immunotherapeutic targeting of glioblastoma (GBM). In this study, we identified a tumor-infiltrating myeloid cell (TIM) population that expands in response to dendritic cell (DC) vaccine treatment. The aim of this study was to understand how this programmed death ligand 1 (PD-L1)-expressing population restricts activation and tumor-cytolytic function of vaccine-induced tumor-infiltrating lymphocytes (TILs). Methods: To test this hypothesis in our in vivo preclinical model, we treated mice bearing intracranial gliomas with DC vaccination ± murine anti-PD-1 monoclonal antibody (mAb) blockade or a colony stimulating factor 1 receptor inhibitor (CSF-1Ri) (PLX3397) and measured overall survival. We then harvested and characterized the PD-L1+ TIM population and its role in TIL activation and tumor cytolysis in vitro. Results: Our data indicated that the majority of PD-L1 expression in the GBM environment is contributed by TIMs rather than by tumor cells themselves. While PD-1 blockade partially reversed the TIL dysfunction, targeting TIMs directly with CSF-1Ri altered TIM expression of key chemotactic factors associated with promoting increased TIL infiltration after vaccination. Neither PD-1 mAb nor CSF-1Ri had a demonstrable therapeutic benefit alone, but when combined with DC vaccination, a significant survival benefit was observed. When the tripartite regimen was given (DC vaccine, PD-1 mAb, PLX3397), long-term survival was noted together with an increase in the number of TILs and TIL activation. Conclusion: Together, these studies elucidate the role that TIMs play in mediating adaptive immune resistance in the GBM microenvironment and provide evidence that they can be manipulated pharmacologically with agents that are clinically available. Development of immune resistance in response to active vaccination in GBM can be reversed with dual administration of CSF-1Ri and PD-1 mAb.


Assuntos
Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Vacinas Anticâncer/administração & dosagem , Glioblastoma/imunologia , Linfócitos do Interstício Tumoral/imunologia , Células Mieloides/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Glioblastoma/prevenção & controle , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Fator Estimulador de Colônias de Macrófagos/antagonistas & inibidores , Receptor de Fator Estimulador de Colônias de Macrófagos/imunologia , Receptor de Fator Estimulador de Colônias de Macrófagos/metabolismo , Células Tumorais Cultivadas , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Surg Neurol Int ; 7(Suppl 28): S756-S758, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27904756

RESUMO

BACKGROUND: Isolated acute foot drop due to traumatic brain injury is exceedingly rare and is often misdiagnosed during initial evaluation. Here, we present the case of a patient who presented with left foot drop after falling off a bicycle. CASE DESCRIPTION: The patient is a 55-year-old male who was mountain biking when he fell, hit his head, and lost consciousness. Neurologic examination of the left leg revealed foot drop, no sensory deficits, and 3+ reflexes at the knee and ankle with clonus. Electroencephalography, computed tomography (CT) of the head, magnetic resonance imaging (MRI) of the lumbar spine, and CT of the lower extremities were all negative. Only MRI of the brain with a gradient echo sequence revealed microhemorrhages focused around the right precentral gyrus. The patient underwent physical therapy, and by 3 months had regained full strength in his left leg. CONCLUSION: Central causes of foot drop are exceptionally rare, however, they should be considered in all cases of post-traumatic dorsiflexion paresis. The key to the accurate diagnosis is a high index of suspicion as well as thorough and careful physical examination including reflex and sensory testing. Selective imaging modalities such as MRI or CT can then be used to verify the diagnosis.

14.
JCI Insight ; 1(10)2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27453950

RESUMO

DC vaccination with autologous tumor lysate has demonstrated promising results for the treatment of glioblastoma (GBM) in preclinical and clinical studies. While the vaccine appears capable of inducing T cell infiltration into tumors, the effectiveness of active vaccination in progressively growing tumors is less profound. In parallel, a number of studies have identified negative costimulatory pathways, such as programmed death 1/programmed death ligand 1 (PD-1/PD-L1), as relevant mediators of the intratumoral immune responses. Clinical responses to PD-1 pathway inhibition, however, have also been varied. To evaluate the relevance to established glioma, the effects of PD-1 blockade following DC vaccination were tested in intracranial (i.c.) glioma tumor- bearing mice. Treatment with both DC vaccination and PD-1 mAb blockade resulted in long-term survival, while neither agent alone induced a survival benefit in animals with larger, established tumors. This survival benefit was completely dependent on CD8+ T cells. Additionally, DC vaccine plus PD-1 mAb blockade resulted in the upregulation of integrin homing and immunologic memory markers on tumor-infiltrating lymphocytes (TILs). In clinical samples, DC vaccination in GBM patients was associated with upregulation of PD-1 expression in vivo, while ex vivo blockade of PD-1 on freshly isolated TILs dramatically enhanced autologous tumor cell cytolysis. These findings strongly suggest that the PD-1/PD-L1 pathway plays an important role in the adaptive immune resistance of established GBM in response to antitumor active vaccination and provide us with a rationale for the clinical translation of this combination therapy.

15.
Cancer Immunol Res ; 4(5): 412-418, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26968205

RESUMO

Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate-pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412-8. ©2016 AACR.


Assuntos
Neoplasias Encefálicas/terapia , Células Dendríticas/transplante , Glioblastoma/terapia , Linfócitos do Interstício Tumoral/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Neoplasias Encefálicas/imunologia , Progressão da Doença , Glioblastoma/imunologia , Humanos , Imunoterapia Adotiva/métodos , Receptores de Antígenos de Linfócitos T/sangue , Análise de Sobrevida , Vacinação/métodos
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