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1.
Chin Clin Oncol ; 13(Suppl 1): AB088, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39295406

RESUMO

BACKGROUND: Spinal cord diffuse midline gliomas are rare, infiltrative entities with an extremely grim prognosis. Standard of care is limited and extrapolated from those for intracranial gliomas, focusing on maximal safe resection, chemotherapy and radiation therapy. These do not prolong survival significantly and while advances in molecular profiling and targeted therapy have been promising, further research still needs to be performed. Here, we present a case of a young lady with a cervical cord diffuse midline glioma, along with a literature review of the disease and treatment options. CASE DESCRIPTION: A 35-year-old female presented with progressive neck pain and left sided weakness. MRI revealed an intramedullary cervical spinal cord lesion. The lesion progressed rapidly to the medulla, resulting in lower cranial nerve palsies and left hemiplegia. Investigations for autoimmune and infective causes were negative. Cervical laminectomy and debulking was performed. Histological analysis showed high grade diffuse glioma, IDH-wildtype, loss of H3K27me3 staining and H3K27M positivity. The patient was treated with fractionated radiation and temozolamide, followed by lomustine and bevacizumab. A literature review was performed to better understand the molecular features, natural history and treatment options for spinal cord high grade gliomas. Our case highlights the importance of maintaining broad differentials for patients exhibiting features of cervical myelopathy. Malignant spinal cord tumours could be a differential. Molecular testing can aid in achieving an accurate diagnosis to better understand prognosis and determine treatment options. Early, function-preserving debulking with neuromonitoring is feasible. Adjuvant therapy with chemotherapy and radiation can prolong survival. CONCLUSIONS: Spinal cord diffuse midline gliomas H3 K27-altered demonstrate rapid progression and a poor prognosis. They should be considered as a differential in patients with cervical myelopathy. Molecular testing for H3 K27 alterations facilitates an accurate diagnosis. Surgical debulking and adjuvant therapy are viable treatment options.


Assuntos
Glioma , Neoplasias da Medula Espinal , Humanos , Feminino , Adulto , Glioma/terapia , Neoplasias da Medula Espinal/terapia
2.
Clin Geriatr Med ; 40(4): 669-683, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39349039

RESUMO

Hypertension is a major risk factor for cardiovascular disease, cognitive decline, and frailty. Given the increasing burden of hypertension in the aging population, it is imperative to improve hypertension management in that population. Apart from variations in treatment goals, challenges such as polypharmacy, medication side effects, and therapeutic inertia hinder adherence to guideline-directed medical therapies among older people. Effective public health messaging is essential for spreading evidence-based guidelines, raising awareness among clinicians, enhancing patient education and health literacy, and implementing community-based strategies to tackle hypertension. This review examines the current state of public messaging on hypertension in older adults.


Assuntos
Hipertensão , Saúde Pública , Humanos , Hipertensão/terapia , Idoso , Anti-Hipertensivos/uso terapêutico , Letramento em Saúde , Educação de Pacientes como Assunto
3.
J Am Heart Assoc ; 13(8): e032509, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38567660

RESUMO

BACKGROUND: Social determinants of health (SDOH) play a significant role in the development of cardiovascular risk factors. We investigated SDOH associations with cardiovascular risk factors among Asian American subgroups. METHODS AND RESULTS: We utilized the National Health Interview Survey, a nationally representative survey of US adults, years 2013 to 2018. SDOH variables were categorized into economic stability, neighborhood and social cohesion, food security, education, and health care utilization. SDOH score was created by categorizing 27 SDOH variables as 0 (favorable) or 1 (unfavorable). Self-reported cardiovascular risk factors included diabetes, high cholesterol, high blood pressure, obesity, insufficient physical activity, suboptimal sleep, and nicotine exposure. Among 6395 Asian adults aged ≥18 years, 22.1% self-identified as Filipino, 21.6% as Asian Indian, 21.0% as Chinese, and 35.3% as other Asian. From multivariable-adjusted logistic regression models, each SD increment of SDOH score was associated with higher odds of diabetes among Chinese (odds ratio [OR], 1.45; 95% CI, 1.04-2.03) and Filipino (OR, 1.24; 95% CI, 1.02-1.51) adults; high blood pressure among Filipino adults (OR, 1.28; 95% CI, 1.03-1.60); insufficient physical activity among Asian Indian (OR, 1.42; 95% CI, 1.22-1.65), Chinese (OR, 1.58; 95% CI, 1.33-1.88), and Filipino (OR, 1.24; 95% CI, 1.06-1.46) adults; suboptimal sleep among Asian Indian adults (OR, 1.20; 95% CI, 1.01-1.42); and nicotine exposure among Chinese (OR, 1.56; 95% CI, 1.15-2.11) and Filipino (OR, 1.50; 95% CI, 1.14-1.97) adults. CONCLUSIONS: Unfavorable SDOH are associated with higher odds of cardiovascular risk factors in Asian American subgroups. Culturally specific interventions addressing SDOH may help improve cardiovascular health among Asian Americans.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Hipertensão , Adulto , Humanos , Asiático , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco de Doenças Cardíacas , Nicotina , Fatores de Risco , Determinantes Sociais da Saúde
4.
Cureus ; 15(10): e46326, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916260

RESUMO

Compressive postoperative seromas in the cervical spine are a rare but significant complication following cervical laminectomy and instrumented fusion. There is a paucity of cases reported in the literature, with a majority of the reported cases attributing seroma formation to the use of recombinant human bone morphogenetic protein-2 (rhBMP-2). In this article, we report four cases of compressive postoperative seroma in the absence of rhBMP-2 use and highlight similarities in their clinical presentations. We postulate that seroma formation is a significant complication of the dead space that results following posterior instrumentation in the cervical spine, with or without the use of rhBMP-2. The typical presentation is one of the gradual delayed neurological deterioration several days following the index surgery and after drain removal. Neurological deterioration can be reversed rapidly with early recognition and drainage of the seroma.

5.
Am J Prev Cardiol ; 13: 100437, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36545389

RESUMO

Objective: This cross-sectional study aims to better understand the heterogeneous associations of acculturation level on CV risk factors among disaggregated Asian subgroups. We hypothesize that the association between acculturation level and CV risk factors will differ significantly by Asian subgroup. Methods: We used the National Health Interview Survey (NHIS), a nationally representative US survey, years 2014-18. Acculturation was defined using: (a) years in the US, (b) US citizenship status, and (c) level of English proficiency. We created an acculturation index, categorized into low vs. high (scores of 0-3 and 4, respectively). Self-reported CV risk factors included diabetes, high cholesterol, hypertension, obesity, tobacco use, and sufficient physical activity. Rao-Scott Chi Square was used to compare age-standardized, weighted prevalence of CV risk factors between Asian subgroups. We used logistic regression analysis to assess associations between acculturation and CV risk factors, stratified by Asian subgroup. Results: The study sample consisted of 6,051 adults ≥ 18 years of age (53.9% female; mean age 46.6 [SE 0.33]). The distribution by race/ethnicity was Asian Indian 26.9%, Chinese 22.8%, Filipino 18.1%, and other Asian 32.3%. The association between acculturation and CV risk factors differed by Asian subgroups. From multivariable adjusted models, high vs. low acculturation was associated with: high cholesterol amongst Asian Indian (OR=1.57, 95% CI: 1.11, 2.37) and other Asian (OR=1.48, 95% CI: 1.10, 2.01) adults, obesity amongst Filipino adults (OR= 1.62, 95% CI: 1.07, 2.45), and sufficient physical activity amongst Chinese (OR= 1.54, 95% CI: 1.09, 2.19) and Filipino adults (OR=1.58, 95% CI: 1.10, 2.27). Conclusion: This study demonstrates that acculturation is heterogeneously associated with higher prevalence of CV risk factors among Asian subgroups. More studies are needed to better understand these differences that can help to inform targeted, culturally specific interventions.

6.
Biomedicine (Taipei) ; 12(1): 16-20, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35836911

RESUMO

Introduction: The trauma patient has an increased susceptibility to postoperative surgical site infection (SSI). There is a lack of studies in the literature investigating the rates of SSI in minimally invasive spine (MIS) surgery for trauma patients with associated injuries, who also require surgical intervention for thoracolumbar fractures. We aim to investigate if MIS surgery for trauma patients reduces the incidence of SSI through a less invasive approach and smaller surgical incision. Methods: A case series of 30 trauma patients who underwent MIS surgery for thoracolumbar spine fractures at our center were followed up for a year. The primary outcome measured was the presence of a postoperative SSI. Subgroup analysis was performed to determine if there were specific factors that increase the risk of developing a SSI. Results: In total, 4 (13%) patients developed postoperative SSI out of which 1 was a deep infection (3%). Subgroup analysis of both patient and surgical factors did not demonstrate statistically significant results to suggest risk factors for SSI post-MIS surgery in our patient group. Conclusion: Our series of patients did not reflect a lower incidence of SSI with MIS surgery compared to incidences in the literature. This may suggest that the increased rates of SSI in the trauma patient may not be best addressed by a minimally invasive approach alone. A multidisciplinary approach that addresses other factors - such as prolonged recumbence and a compromised immunological state may yield improved results.

7.
J Clin Neurosci ; 89: 389-396, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34088580

RESUMO

BACKGROUND: The decision to resume antithrombotic therapy after surgical evacuation of chronic subdural hematoma (CSDH) requires judicious weighing of the risk of bleeding against that of thromboembolism. This study aimed to investigate the impact of time to resumption of antithrombotic therapy on outcomes of patients after CSDH drainage. METHODS: Data were obtained retrospectively from three tertiary hospitals in Singapore from 2010 to 2017. Outcome measures analyzed were CSDH recurrence and any thromboembolic events. Logistic and Cox regression tests were used to identify associations between time to resumption and outcomes. RESULTS: A total of 621 patients underwent 761 CSDH surgeries. Preoperative antithrombotic therapy was used in 139 patients. 110 (79.1%) were on antiplatelets and 35 (25.2%) were on anticoagulants, with six patients (4.3%) being on both antiplatelet and anticoagulant therapy. Antithrombotic therapy was resumed in 84 patients (60.4%) after the surgery. Median time to resumption was 71 days (IQR 29 - 201). Recurrence requiring reoperation occurred in 15 patients (10.8%), of which 12 had recurrence before and three after resumption. Median time to recurrence was 35 days (IQR 27 - 47, range 4 - 82 days). Recurrence rates were similar between patients that were restarted on antithrombotic therapy before and after 14, 21, 28, 42, 56, 70 and 84 days, respectively. Thromboembolic events occurred in 12 patients (8.6%), of which five had the event prior to restarting antithrombosis. CONCLUSIONS: Time to antithrombotic resumption did not significantly affect CSDH recurrence. Early resumption of antithrombotic therapy can be safe for patients with a high thromboembolic risk.


Assuntos
Anticoagulantes/administração & dosagem , Drenagem/métodos , Fibrinolíticos/administração & dosagem , Hematoma Subdural Crônico/cirurgia , Procedimentos Neurocirúrgicos/métodos , Complicações Pós-Operatórias/etiologia , Tromboembolia/epidemiologia , Adulto , Idoso , Anticoagulantes/uso terapêutico , Estudos de Coortes , Drenagem/efeitos adversos , Fibrinolíticos/uso terapêutico , Hematoma Subdural Crônico/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Tromboembolia/tratamento farmacológico
8.
Biomedicine (Taipei) ; 11(1): 51-55, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35223395

RESUMO

Revision anterior cervical spine surgery has a higher risk of recurrent laryngeal nerve palsy (RLNP). We describe a unique case of an isolated RLNP contralateral to the side of the surgical approach in a patient who underwent revision anterior cervical discectomy and fusion (ACDF) for cervical myelopathy, and in whom pre-operative laryngoscopic evaluation had excluded a pre-existing occult RLNP. Scarring around the recurrent laryngeal nerve at the previous surgical site may have rendered it less mobile, resulting in it being more susceptible to compression from an inflated endotracheal tube (ETT) cuff or traction from surgical retractors. This case illustrates that acute RLNP can rarely occur contralateral to the side of surgical approach in the setting of revision surgery. Surgeons performing revision ACDF can consider approaching from the same side as the index surgery or a posterior approach to reduce the risk of developing bilateral RLNP.

9.
Asian Spine J ; 15(3): 317-323, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33260284

RESUMO

STUDY DESIGN: Retrospective cohort study. PURPOSE: To identify the clinical significance of different patterns of intraoperative neuromonitoring (IONM) signal alerts. OVERVIEW OF LITERATURE: IONM is a long-established valuable adjunct to complex spine surgeries. IONM for cervical spine surgery is in the form of somatosensory evoked potential (SSEP) and motor evoked potential (MEP). The efficacy of both modalities (individually or in combination) to detect clinically significant neurological compromise is constantly being debated and requires conclusive suggestions. METHODS: Clinical and neuromonitoring data of 207 consecutive adult patients who underwent cervical spine surgeries at multiple surgical centers using bimodal IONM were analyzed. Signal changes were divided into three groups. Group 0 had transient signal changes in either MEPs or SSEPs, group 1 had sustained unimodal changes, and group 2 had sustained changes in both MEPs and SSEPs. The incidences of true neurological deficits in each group were recorded. RESULTS: A total of 25% (52/207) had IONM signal alerts. Out of these signal drops, 96% (50/52) were considered to be false positives. Groups 0 and 1 had no incidence of neurological deficits, while group 2 had a 29% (2/7) rate of true neurological deficits. The sensitivities of both MEP and SSEP were 100%. SSEP had a specificity of 96.6%, while MEP had a lower specificity at 76.6%. C5 palsy rate was 6%, and there was no correlation with IONM signal alerts (p=0.73). CONCLUSIONS: This study shows that we can better predict its clinical significance by dividing IONM signal drops into three groups. A sustained, bimodal (MEP and SSEP) signal drop had the highest risk of true neurological deficits and warrants a high level of caution. There were no clear risk factors for false-positive alerts but there was a trend toward patients with cervical myelopathy.

10.
J Clin Neurosci ; 78: 79-85, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32616352

RESUMO

Bilateral chronic subdural hematoma (bCSDH) is frequently drained unilaterally when the contralateral CSDH is small and asymptomatic. However, reoperation rates for contralateral CSDH growth can be high. We aimed to develop a prognostic scoring system to guide the selection of suitable patients for unilateral drainage of bCSDH. Data were collected retrospectively across three tertiary hospitals from 2010 to 2017 on all consecutive bCSDH patients aged 21 or above. Predictors of reoperation were identified using multivariable logistic regression. A prognostic score was developed and internally validated. 240 bCSDH patients were analyzed. 98 (40.8%) underwent unilateral and 142 (59.2%) underwent bilateral evacuation. Clinical outcomes were comparable between the unilateral and bilateral evacuation groups. Within the unilateral evacuation group, 4 (4.1%) had a reoperation for contralateral CSDH growth. Reoperation for contralateral CSDH was predicted by preoperative use of anticoagulants (OR = 15.0, 95% CI: 1.49-169.15, p = 0.017). Complete resolution of contralateral CSDH was predicted by its preoperative maximum width, with a cut-off of 9 mm producing the highest sensitivity and specificity (OR = 4.17 for ≤9 mm, 95% CI: 1.54-11.11, p = 0.004). Using our prognostic score, reoperation rate for contralateral CSDH was 1.6%, 3.6%, 16.7%, and 50.0% in low-risk, moderate-risk, high-risk and very high-risk patients, respectively. With each increase of 1 in the prognostic score, patients were 4 times as likely to undergo reoperation for contralateral CSDH (OR = 3.98, 95% CI: 1.36-13.53, p = 0.013). Our proposed risk score may be used as an adjunct in clinical decision making for bCSDH patients undergoing unilateral evacuation.


Assuntos
Hematoma Subdural Crônico/diagnóstico , Prognóstico , Reoperação/estatística & dados numéricos , Adulto , Idoso , Anticoagulantes , Tomada de Decisão Clínica , Drenagem , Feminino , Hematoma Subdural Crônico/cirurgia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Centros de Atenção Terciária , Adulto Jovem
11.
World Neurosurg ; 140: 56-59, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32437994

RESUMO

BACKGROUND: Xanthomas are benign lipomatous deposits that can be found systemically in various tissues including bones. Their presence in the skull remains a rare entity. Despite their benign characteristics, imaging modalities are often unable to distinguish them from malignant lesions. This leads to a diagnostic dilemma in patients with underlying malignancy. This case report highlights such a case where clinical history of prostate cancer and image findings were concordant with that of metastatic deposit in the parietal skull region. CASE DESCRIPTION: This 65-year-old gentleman was diagnosed with prostatic adenocarcinoma. During systemic workup for his tumor, he was found to have a right parietal skull lesion. Magnetic resonance imaging of the brain, as well as a bone scan, were consistent with that of a metastatic deposit. As treatment would be drastically affected by the diagnosis, an excision biopsy was performed. The histology was consistent with that of a bone xanthoma. CONCLUSIONS: Xanthomas are benign lesions that can be seen deposited in appendicular and axial skeleton. Skull lesions are rare with most case descriptions focusing on their presence in the frontoorbital regions and mandible and temporal bone. They usually have a benign course but may present with symptoms due to localized mass effect. Surgical intervention and histologic diagnosis may still be required in these lesions due to their lack of imaging characteristics that confirm their diagnosis through noninvasive methods.


Assuntos
Crânio/patologia , Xantomatose/patologia , Idoso , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Diagnóstico Diferencial , Humanos , Masculino , Metástase Neoplásica/diagnóstico , Metástase Neoplásica/patologia , Neoplasias da Próstata/patologia , Xantomatose/diagnóstico
12.
Biomedicine (Taipei) ; 10(2): 30-35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33854918

RESUMO

BACKGROUND: Even though pedicle screw application is a common procedure, and in-spite of spine surgeons being proficient with the technique, mal-positioning of pedicle screws can still occur. We intend to determine by postoperative CT analysis, the incidence of pedicle screw breach in the thoracolumbar spine despite satisfactory intraoperative placement confirmed by fluoroscopy. MATERIALS AND METHODS: Consecutive patients diagnosed with thoracolumbar fractures who underwent open or minimally invasive posterior stabilization under fluoroscopic guidance were retrospectively reviewed. Postoperative CT scans of patients were analysed to determine the incidence of pedicle breach despite satisfactory intraoperative placement, and also to determine the factors that can predict a breach during intraoperative assessment. RESULTS: A total of 61 patients with 513 thoracolumbar pedicle screws were available for analysis. Based on our postoperative CT assessment, 28 screws (5.5%; 18 thoracic screws; 10 lumbar screws) had breached the pedicle. There were 14 minor (<3 mm) and 14 major (≥3 mm) breaches. The minimally invasive technique had a significantly lower breach rate compared to open surgery (1.9% vs. 7.9%). By retrospectively analysing the intra-operative fluoroscopic images, we determined certain parameters that could predict a breach during surgery. CONCLUSION: Pedicle breaches can still be present despite satisfactory placement of screws visualized intra-operatively. A medial breach is most likely when the length of the pedicle screw spans only up to 50% of the vertebral body as seen on the lateral view but the pedicle screw tip has already transgressed the midline as seen on an AP view. A lateral breach is likely when the tip of the pedicle screw is overlapped by the screw head or is only minimally visualized on an AP view.

13.
J Med Chem ; 59(18): 8233-62, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27541357

RESUMO

Blockage of more than one oncoprotein or pathway is now a standard approach in modern cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is <100 nM potent against HDACs 2 and 10, submicromolar potent against HDACs 1, 8, and 11, and >50-fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Inibidores de Histona Desacetilases/química , Inibidores de Histona Desacetilases/farmacologia , Janus Quinase 2/antagonistas & inibidores , Pirimidinas/química , Pirimidinas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/metabolismo , Humanos , Modelos Moleculares , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos
14.
Sci Rep ; 6: 18658, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26791325

RESUMO

Contemporary chemotherapeutic treatments incorporate the use of several agents in combination. However, selecting the most appropriate drugs for such therapy is not necessarily an easy or straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our method employed single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells to delineate a drug resistance gene network using a synthetic lethality workflow. Using the results of a previous unbiased screen, we assessed the genetic overlap of doxorubicin with six other drugs harboring varied mechanisms of action. Using this fission yeast model, drug-specific ontological sub-classifications were identified through the computation of relative hypersensitivities. We found that human gastric adenocarcinoma cells can be sensitized to doxorubicin by concomitant treatment with cisplatin, an intra-DNA strand crosslinking agent, and suberoylanilide hydroxamic acid, a histone deacetylase inhibitor. Our findings point to the utility of fission yeast as a model and the differential targeting of a conserved gene interaction network when screening for successful chemotherapeutic drug combinations for human cells.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Schizosaccharomyces/efeitos dos fármacos , Schizosaccharomyces/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/farmacologia , Combinação de Medicamentos , Resistência a Múltiplos Medicamentos/genética , Ensaios de Seleção de Medicamentos Antitumorais , Perfilação da Expressão Gênica , Humanos , Mutação
15.
J Thromb Thrombolysis ; 39(3): 328-36, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25700561

RESUMO

Antiplatelet therapies play a central role in reducing the risk of cardiovascular events such as myocardial infarction and stroke. While aspirin, a cyclo-oxygenase-1 inhibitor has been the cornerstone of antithrombotic treatment for several decades, P2Y12 receptor inhibitors cangrelor, clopidogrel, prasugrel, and ticagrelor and protease-activated receptor-1 antagonist vorapaxar, have emerged as additional therapies to reduce the risk of recurrent cardiovascular events in high-risk patients. Recent clinical trials evaluating the role of these agents and major society guideline updates for use of antiplatelet therapies for secondary prevention of cardiovascular events will be examined. The latest studies regarding the appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention will be presented. The current state of genetic and platelet function testing will be reviewed.


Assuntos
Testes Genéticos , Lactonas/uso terapêutico , Infarto do Miocárdio , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Piridinas/uso terapêutico , Receptores Purinérgicos P2Y12 , Acidente Vascular Cerebral , Humanos , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/genética , Receptores Purinérgicos P2Y12/genética , Receptores Purinérgicos P2Y12/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética
16.
Tex Heart Inst J ; 41(5): 533-6, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25425990

RESUMO

Carcinoid tumors are rare neuroendocrine malignancies that typically originate from the gastrointestinal tract. Patients who are diagnosed with carcinoid heart disease generally have poor prognoses because of advanced metastases during staging and few therapeutic options. We present the case of a 61-year-old woman with right-sided heart failure, secondary to carcinoid heart disease caused by a primary ovarian carcinoid tumor. After undergoing surgical resection of the left ovary and fallopian tube, the patient experienced complete resolution of her heart failure symptoms. In addition to the patient's case, we discuss the diagnosis, nature, and treatment of this rare condition.


Assuntos
Doença Cardíaca Carcinoide/terapia , Tumor Carcinoide/cirurgia , Insuficiência Cardíaca/terapia , Neoplasias Ovarianas/cirurgia , Doença Cardíaca Carcinoide/etiologia , Tumor Carcinoide/complicações , Feminino , Insuficiência Cardíaca/etiologia , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/complicações
17.
Future Med Chem ; 6(12): 1439-71, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25329199

RESUMO

Consisting of four members, JAK1, JAK2, JAK3 and TYK2, the JAK kinases have emerged as important targets for proliferative and immune-inflammatory disorders. Recent progress in the discovery of selective inhibitors has been significant, with selective compounds now reported for each isoform. This article summarizes the current state-of-the-art with a discussion of the most recently described selective compounds. X-ray co-crystal structures reveal the molecular reasons for the observed biochemical selectivity. A concluding analysis of JAK inhibitors in the clinic highlights increased clinical trial activity and diversity of indications. Selective JAK inhibitors, as single agents or in combination regimens, have a very promising future in the treatment of oncology, immune and inflammatory diseases.


Assuntos
Janus Quinases/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Animais , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Conformação Molecular , Inibidores de Proteínas Quinases/química , Relação Estrutura-Atividade , Especificidade por Substrato
18.
Vasc Health Risk Manag ; 10: 507-22, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25187724

RESUMO

Over the past few years, three novel oral anticoagulants, dabigatran, rivaroxaban, and apixaban, have been approved in the USA and Europe to reduce the risk of stroke or systemic embolism in patients with nonvalvular atrial fibrillation, and the results of a Phase III trial for a fourth novel oral anticoagulant, edoxaban, have recently been published. The aim of this review is to examine this indication from a clinician's perspective, highlighting efficacy and safety results from the major trials with these novel oral agents. Clinical issues regarding bleeding, monitoring, and reversal are discussed, along with requirements to consider when interrupting treatment with a novel oral anticoagulant for the purpose of transitioning to another anticoagulant and prior to cardioversion, ablation, percutaneous coronary intervention, or emergency surgery. The cost-effectiveness of each of the approved novel oral anticoagulants is reviewed, and the author provides recommendations for selecting appropriate patients for these agents.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/economia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/economia , Análise Custo-Benefício , Esquema de Medicação , Custos de Medicamentos , Substituição de Medicamentos , Medicina Baseada em Evidências , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Assistência Perioperatória , Fatores de Risco , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do Tratamento
19.
Asian Spine J ; 8(6): 831-4, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25558328

RESUMO

A 44-year-old male presented with symptoms of spinal cord compression secondary to metastatic prostate cancer. An urgent decompression at the cervical-thoracic region was performed, and there were no complications intraoperatively. Three hours postoperatively, the patient developed acute bilateral lower-limb paralysis (motor grade 0). Clinically, he was in class 3 hypovolemic shock. An urgent magnetic resonance imaging (MRI) was performed, showing no epidural hematoma. He was managed aggressively with medical therapy to improve his spinal cord perfusion. The patient improved significantly, and after one week, he was able to regain most of his motor functions. Although not commonly reported, spinal cord ischemia post-surgery should be recognized early, especially in the presence of hypovolemic shock. MRI should be performed to exclude other potential causes of compression. Spinal cord ischemia needs to be managed aggressively with medical treatment to improve spinal cord perfusion. The prognosis depends on the severity of deficits, and is usually favorable.

20.
Mol Imaging Biol ; 13(6): 1061-6, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21057879

RESUMO

PURPOSE: Inflammation plays a critical role in atherosclerosis and is associated with upregulation of inducible nitric oxide synthase (iNOS). We studied bioluminescence imaging (BLI) to track iNOS gene expression in a murine model of vascular inflammation. PROCEDURES: Macrophage-rich vascular lesions were induced by carotid ligation plus high-fat diet and streptozotocin-induced diabetes in 18 iNOS-luc reporter mice. In vivo iNOS expression was imaged serially by BLI over 14 days, followed by in situ BLI and histology. RESULTS: BLI signal from ligated carotids increased over 14 days (9.7 ± 4.4 × 10(3 ) vs. 4.4 ± 1.7 × 10(3) photons/s/cm(2)/sr at baseline, p < 0.001 vs. baseline, p < 0.05 vs. sham controls). Histology confirmed substantial macrophage infiltration, with iNOS and luciferase expression, only in ligated left carotid arteries and not controls. CONCLUSIONS: BLI allows in vivo detection of iNOS expression in murine carotid lesions and may provide a valuable approach for monitoring vascular gene expression and inflammation in small animal models.


Assuntos
Artéria Carótida Primitiva/patologia , Regulação Enzimológica da Expressão Gênica , Imageamento Tridimensional/métodos , Inflamação/enzimologia , Inflamação/genética , Medições Luminescentes/métodos , Óxido Nítrico Sintase Tipo II/genética , Animais , Artéria Carótida Primitiva/enzimologia , Luciferases/metabolismo , Macrófagos , Camundongos , Óxido Nítrico Sintase Tipo II/metabolismo , Coloração e Rotulagem
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