refractory

OBJECTIVES: Coarctation of the aorta is known to present with hypertension in older patients; we reviewed our experience and assessed the outcome of hypertension following surgical correction. METHODS: From April 2004 to date, 43 patients above the age of 12 underwent coarctation of the aorta repair. The mean age was 20.4 + 9.7 years (maximum 56 years); 21 (48.8%) were older than 18 years and 28 (65.1%) were men. Thirty (69.8%) patients had hypertension...

Functional magnetic resonance imaging (fMRI) is an important tool for pre-surgical evaluation of eloquent cortex. Classic task-based paradigms require patient participation and individual imaging sequence acquisitions for each functional domain that is being assessed. Resting state fMRI (rs-fMRI), however, enables functional localization without patient participation and can evaluate numerous functional domains with a single imaging session. To date, post-processing of this resting state data has been resource intensive, which limits its widespread application for routine clinical use...

BACKGROUND: Susac syndrome (SS) classically presents with the clinical triad of retinal artery occlusion, sensorineural hearing loss, and encephalopathy and the neuroimaging triad of white matter lesions, deep gray matter lesions, and leptomeningeal disease. However, patients can present with an incomplete clinical or neuroimaging triads making diagnosis difficult in certain situations. A standard treatment paradigm also is lacking in this illness. It is important for neuro-ophthalmologists to recognize clinical and radiographic findings that are pathognomonic for this syndrome and have a basic understanding of the available treatment options...

Hepatocellular carcinoma (HCC) is highly refractory to current therapeutics used in the clinic. DX-2647, a recombinant human antibody, potently neutralizes the action of insulin-like growth factor-II (IGF-II), a ligand for three cell-surface receptors (IGF-IR, insulin receptor A and B isoforms, and the cation-independent mannose-6-phosphate receptor) which is overexpressed in primary human HCC. DX-2647 impaired the growth of tumor xenografts of the HCC cell line, Hep3B; however, xenografts of the HCC cell line, HepG2, were largely unresponsive to DX-2647 treatment...

Multiple myeloma (MM) is a neoplastic plasma cell disorder with high disease recurrence rates. Novel therapeutic approaches capable of improving outcomes in patients with MM are urgently required. The AKT signalling plays a critical regulatory role in MM pathophysiology, including survival, proliferation, metabolism, and has emerged as a key therapeutic target. Here, we identified a novel AKT inhibitor, HS1793, and defined its mechanism of action and clinical significance in MM. HS1793 disrupted the interaction between AKT and heat shock protein 90, resulting in protein phosphatase 2A-modulated phosphorylated-AKT (p-AKT) reduction...

Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis...

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In multiple myeloma (MM), maintenance therapy is a longer and less intensive treatment course than initial therapy that is administered after induction to delay disease progression. Maintenance and continuous therapy have been shown to suppress minimal residual disease and deepen and prolong responses, with the goal of improving progression-free survival and overall survival. Areas covered: In this review, we have summarized current clinical trial data on maintenance and continuous therapy in newly-diagnosed MM and relapsed/refractory MM (RRMM), focusing on lenalidomide and bortezomib...

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1...

Aplastic anemia (AA) is characterized by multilineage cytopenias and bone marrow hypocellularity. Severe AA can be treated with immunosuppressive therapy (IST) and/or allogeneic hematopoietic stem cell transplantation. The thrombopoietin agonist eltrombopag has been shown to induce hematopoietic recovery and transfusion independence in adults with refractory and relapsed AA. Recently, upfront eltrombopag therapy in patients with AA in combination with IST has shown efficacy. Data for its use without concurrent IST in pediatric patients with AA remain sparse...

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that has been associated with EWSR1-CREB1 gene fusion. Outcome in patients with unresectable distant metastases is generally fatal. Interleukin-6 (IL-6) secretion has been described in tumors with EWSR1-CREB1 fusion, and may promote tumor growth due to autocrine stimulation. Tocilizumab is an IL-6 receptor antibody that has potential benefit as a targeted therapy in refractory neoplasms with IL-6 secretion. We describe a child with metastatic AFH with EWSR1-CREB1 fusion and elevated IL-6 whose disease progressed during treatment with traditional chemotherapeutic agents, but improved after targeted therapy with tocilizumab...

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the clinical features, diagnosis, pathogenesis, epidemiology, and treatment of the rare primary headache disorders short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA). Together these entities are known as short-lasting unilateral neuralgiform headache attacks (SUNHA). RECENT FINDINGS: Recent case reports of secondary SUNCT and SUNA due to medullary infarcts support the theory that the trigeminohypothalamic pathway is involved in the pathophysiology of SUNHA...

DNA in nucleosomes has restricted nucleosome dynamics and is refractory to DNA-templated processes. Histone post-translational modifications play important roles in regulating DNA accessibility in nucleosomes. Whereas most histone modifications function either by mitigating the electrostatic shielding of histone tails or by recruiting 'reader' proteins, we show that ubiquitylation of H2B K34, which is located in a tight space protected by two coils of DNA superhelix, is able to directly influence the canonical nucleosome conformation via steric hindrances by ubiquitin groups...

Burn injuries generate multisystem physiological derangements. The authors present a case series of three patients developing acute coronary syndrome (ACS) stemming from coronary vasospasm (CVS) over a course of 5 months. This etiology of ACS is significant as it has previously not been described in burn patients and requires a different management algorithm than vaso-occlusive disease. All patients were admitted to a single accredited burn unit. Burn mechanisms were flash burn, chemical fire, and house fire...

Purpose: To investigate the pain relief effect and safety of percutaneous radiofrequency ablation (RFA) with a multitined electrode combined with cement injection in patients with painful metastatic bone tumors. Materials and methods: Sixteen patients with 34 osteolytic metastatic lesions were treated with RFA including 4 males and 12 females (age range 54-84). Thirteen patients with spinal metastases received additional cement injection. Medical imaging, a visual analog scale (VAS) and the EORTC QLQ-C30 were performed to evaluate the metastatic lesion, pain and quality of life, respectively, before and after RFA and at follow-ups...

Bacterial transcription termination proceeds via two main mechanisms triggered either by simple, well-conserved (intrinsic) nucleic acid motifs or by the motor protein Rho. Although bacterial genomes can harbor hundreds of termination signals of either type, only intrinsic terminators are reliably predicted. Computational tools to detect the more complex and diversiform Rho-dependent terminators are lacking. To tackle this issue, we devised a prediction method based on Orthogonal Projections to Latent Structures Discriminant Analysis [OPLS-DA] of a large set of in vitro termination data...

Background: Considering the effect of statins on the regulation of dopamine neurotransmitters and glutamates and importance of the treatment of obsessive-compulsive disorder (OCD) due to its relatively high prevalence and disability of available drugs in treatment of many patients, we came to the point to examine effectiveness of statins in patients with OCD. Materials and Methods: This study is a double-blind randomized clinical trial, which is done in OCD clinic of Isfahan Shariati in 2014 for 1 year...

Sin Nombre virus (SNV) causes hantavirus cardiopulmonary pulmonary syndrome (HCPS) with the loss of pulmonary vascular endothelial integrity, and pulmonary edema without causing cytopathic effects on the vascular endothelium. HCPS is associated primarily with a dysregulated immune response. We previously found occult signs of hemostatic imbalance in the form of a sharp >30-100 fold increase in the expression of plasminogen activator inhibitor type 1 (PAI-1), in serial blood plasma draws of terminal stage-patients...

We have reviewed the English literature published in the last 70 years on Diseases of the Vertebral Basilar Circulation, or Posterior Circulation Disease (PCD). We have found that errors have been made in the conduct and interpretation of these studies that have led to incorrect approaches to the management of PCD. Because of the difficulty in evaluating the PC, the management of PCD has been incorrectly applied from anterior circulation disease (ACD) experience to PCD. PCD is a common form of stroke affecting 20-40% patients with stroke...

The biologic antitumor necrosis factor alpha (anti-TNFα) agents have revolutionised the treatment of inflammatory bowel disease (IBD). However, some patients experience primary nonresponse, loss of response, or intolerance. Therefore, introducing a newer class of therapy with a mechanism of action that acts on different inflammatory pathways involved in IBD pathogenesis is appealing. Vedolizumab is a fully humanised monoclonal antibody that selectively targets α4β7 integrin. Based on the results of the pivotal clinical GEMINI trials, vedolizumab was approved for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) refractory or intolerant to either conventional therapy or TNFα inhibitors...