refractory

Pure red cell aplasia (PRCS) is a well-recognized complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many therapeutic options are available to treat this condition, including erythropoietin, rituximab, bortezomib, plasma exchange, immunoadsorption, donor lymphocyte infusion, mesenchymal stem cells, anti-thymocyte globulin and high-dose steroids; however treatment outcomes are often variable and can sometimes lead to disappointing results. In this brief article we report our experience with two patients with PRCA after major AB0-incompatible HSCT who were resistant to multiple therapeutic interventions and who eventually benefited from treatment with eltrombopag, a thrombopoietin mimetic approved by the Food and Drug Administration for the treatment of patients with immune thrombocytopenic purpura or severe aplastic anemia (SAA), refractory to immunosuppressive agents or not eligible to HSCT...

Cryoballoon ablation is a recently introduced treatment option for patients with symptomatic, drug-refractory atrial fibrillation. The rate of complications is low and comprises mainly vascular-access-site complications and phrenic nerve palsy. We report a case of life-threatening pulmonary haemorrhage occurring during the procedure.

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment...

Thrombocytopenia, a serious complication of myelosuppressive chemotherapy in cancer patients, is managed with platelet transfusions until recovery of platelet counts. However, children receiving chemotherapy can rarely develop immune thrombocytopenia (ITP) that is refractory to transfused platelets. This limits the ability to achieve adequate platelet counts and administer further myelosuppressive chemotherapy safely, especially if first-line ITP therapy is ineffective. We report 2 cases of intravenous immunoglobulin refractory ITP in children receiving chemotherapy for high-risk neuroblastoma...

Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle)...

A frequent observation in dual-task studies is the backward crosstalk effect (BCE), meaning that aspects of a secondary Task 2 influence Task 1 performance. Up to this point, 2 major types of the BCE were investigated: a BCE based on dimensional overlap between both stimuli and/or responses (the compatibility-based BCE), and a BCE based on whether Task 2 is a go or no-go task (the no-go BCE). Recent evidence suggests that the compatibility-based BCE has its locus inside the response selection stage. The available evidence for the locus of the no-go BCE is still mixed, however...

Accumulating evidence shows a key function for astrocytic connexin43 (Cx43) signaling in epilepsy. However, the lack of experimental distinction between Cx43 gap junction channels (GJCs) and hemichannels (HCs) has impeded the identification of the exact contribution of either channel configurations to epilepsy. We therefore investigated whether TAT-Gap19, a Cx mimetic peptide that inhibits Cx43 HCs but not the corresponding Cx43 GJCs, influences experimentally induced seizures in rodents. Dye uptake experiments in acute hippocampal slices of mice demonstrated that astroglial Cx43 HCs open in response to the chemoconvulsant pilocarpine and this was inhibited by TAT-Gap19...

BACKGROUND: Morbidly obese patients with respiratory failure who do not improve on conventional mechanical ventilation (CMV) often undergo rescue therapy with extracorporeal membrane oxygenation (ECMO). We describe our experience with high-frequency percussive ventilation (HFPV) as a rescue modality. METHODS: In a retrospective analysis from 2009 to 2016, 12 morbidly obese patients underwent HFPV after failing to wean from CMV. Data were collected regarding demographics, cause of respiratory failure, ventilation settings, and hospital course outcomes...

Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs...

We report our experience of two cases of refractory cellulitis caused by peripheral micro-arteriovenous fistulas (AVFs) in the lower extremity. The micro-AVFs were so small that they could not be located accurately; further, the patients' symptoms differed markedly from those previously reported for AVF. AVF is known to cause ischemic symptoms. In contrast, micro-AVF causes congestive symptoms and remains undetected in the majority of patients. Identification of this pathology is crucial to enable effective treatment by the ligation of the incompetent perforator vein that increases venous hypertension, leading to congestive symptoms...

The past few years have seen increasing support for gross total resection in the management of low-grade gliomas (LGGs), with a greater extent of resection correlated with better overall survival, progression-free survival, and time to malignant transformation. There is consistent evidence in literature supporting extent of safe resection as a good prognostic indicator as well as positively affecting seizure control, symptomatic relief in pressure symptoms, and longer progression-free and total survival. The operative goal in most LGG cases is to maximize the extent of resection for these benefits while avoiding postoperative neurologic deficits...

Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an effective treatment for refractory epilepsy. Due to the unique location of ANT in the thalamus facing the lateral and third ventricles, transventricular DBS lead placement is an essential part of ANT DBS. However, there is no report regarding hardware problems including impedance variability in transventricular ANT DBS due to limited experience. A 45-year-old male patient with previously effective, bilateral ANT DBS presented with increasing seizure frequency and a shortened battery longevity within 2 years...

Brain abscesses are associated with high morbidity and mortality rates. In particular, patients with intraventricular rupture of brain abscess (IVROBA) exhibit mortality rates up to 85%. Treatment options are lacking for IVROBA, once patients become refractory to intravenous antibiotics and surgical drainage. Limited data exist regarding the risks and benefits of intraventricular therapy in such a scenario. We report a patient with IVROBA, who deteriorated while on systemic antibiotics; once intraventricular vancomycin was employed, the patient demonstrated remarkable improvement without perceivable side effects...

Context: High intracranial pressure is the most frequent cause of mortality and disability after severe traumatic brain injury (TBI) which is treated by first-line therapeutic measures. When these measures fail, second-line therapies are started. Among second-line therapies, decompressive craniectomy (DC) has been used. It improves the functional outcome in these patients. Aim: This study aims to analyze the clinicoradiological factors associated with the prognosis of severe TBI in patients undergoing DC...

Introduction: Coccygodynia refers to a pathological condition in which pain occurs in the coccyx or its immediate vicinity. The pain is usually provoked by sitting or rising from sitting. Several studies have reported good or excellent results after coccygectomy especially in patients who are refractory to conservative treatment. Aims and Objectives: This study aims to evaluate the role and effectiveness of coccygectomy in chronic refractory coccygodynia. Materials and Methods: Between January 2011 and January 2015, 16 consecutive patients (4 males and 12 females) who underwent surgical coccygectomy were enrolled prospectively in the study...

Introduction: Significant impairment of left ventricular function causes low cardiac output syndrome in the immediate postoperative period in 3-14% of patients undergoing surgery, increasing the mortality 15-fold. Aim: To assess the use of levosimendan in patients undergoing cardiac surgery in 2016. Material and methods: The analysis included 14 patients: 3 (21.4%) women and 11 (78.6%) men aged 65.4 ±11.8 years. The mean value of left ventricular ejection fraction amounted to 20 ±6...

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration characterised by an abnormal branching vascular network with aneurysmal polypoidal choroidal vascular lesions. PCV is more prevalent in Asian populations than in Caucasians, which may explain its underdiagnosis in Western countries. Evidence regarding the efficacy of different anti-vascular endothelial growth factor (anti-VEGF) agents on PCV is scarce, with most of these studies being conducted in Asian treatment-naïve patients...

OBJECTIVE: Heartburn is the most specific symptom of reflux disease and is highly responsive to proton pump inhibitor (PPI) therapy. Some patients do not respond to PPIs, but mechanisms of refractoriness have not yet been fully elucidated. Impedance-pH monitoring, allowing comprehensive on-therapy assessment of reflux, represents a valuable test to investigate PPI refractoriness. METHODS: Prospective multicenter study comparing endoscopy-negative patients with PPI-refractory and PPI-responsive heartburn...

Lipoic acid is an essential cofactor for the mitochondrial 2-ketoacid dehydrogenase complexes and the glycine cleavage system. Lipoyltransferase 1 catalyzes the covalent attachment of lipoate to these enzyme systems. Pathogenic variants in LIPT1 gene have recently been described in four patients from three families, commonly presenting with severe lactic acidosis resulting in neonatal death and/or poor neurocognitive outcomes. We report a 2-month-old male with severe lactic acidosis, refractory status epilepticus, and brain imaging suggestive of Leigh disease...

BACKGROUND: Catheter ablation is proven to be an effective strategy for drug refractory ventricular tachycardia (VT) in ischemic cardiomyopathy. However, the appropriate timing of VT ablation and identifying the group of patients that may receive the greatest benefit remains uncertain. There is limited data on the effect on prophylactic catheter ablation (PCA) in the prevention of implantable cardioverter defibrillator (ICD) therapy, electrical storm, and mortality. METHODS: We performed a comprehensive literature search through November 1, 2017, for all eligible studies comparing PCA + ICD versus ICD only in eligible patients with ischemic cardiomyopathy...