Balloon‐occluded retrograde transvenous obliteration for recurrent fundal gastric variceal bleeding in an adolescent

Gastric variceal bleeding is associated with high morbidity and mortality. Balloon‐occluded retrograde transvenous obliteration is a relatively new treatment used to control bleeding gastric varices that involves transvenous sclerosis of gastric varices through a spontaneous gastrorenal shunt. Here, we report on a 14‐yr‐old patient that underwent balloon‐occluded retrograde transvenous obliteration for refractory bleeding fundal varices in the setting of esophageal varices and cirrhosis, which did not respond to medical management or endoscopic injection. This case report serves as a reminder that balloon‐occluded retrograde transvenous obliteration can successfully control fundal variceal bleeding in pediatric patients and may serve as a bridge to liver transplantation.     

Normalization of serum lactic dehydrogenase in β-thalassemia patients following bone marrow transplantation

Serum lactic dehydrogenase (LDH) levels are mildly elevated in β-thalassemia major due to ineffective erythropoiesis. We reviewed the charts of 15 consecutive thalassemic children who underwent allogeneic, T-cell-depleted bone marrow transplantation (BMT) in our department during the last 3 years. Eleven patients had successful engraftment and are alive and well without evidence of disease, according to physical examinations, blood counts, and polymerase chain reaction (PCR) tests, with a median follow-up of 2 years. Two patients died due to transplantation-related complications, and two rejected the graft and received their backup autologous marrow. The LDH levels in the transplanted patients gradually decreased from an average of 952 ± 155 IU/L 10 days pre-transplant (N = 300–620) to 426 ± 56 IU/L at the day of transplantation, and stayed at approximately the same level post-transplant (489 ± 55 IU/L). By contrast, the LDH levels reverted to the pre-transplant value in those patients who rejected their marrow. The significance of this clinical observation for the pathophysiologic mechanism of intramedullary hemolysis and ineffective erythropoiesis in β-thalassemia major is discussed. © 1996 Wiley-Liss, Inc.     

A wearable sensor identifies alterations in community ambulation in multiple sclerosis: contributors to real-world gait quality and physical activity

Journal of Neurology - People with multiple sclerosis (pwMS) often suffer from gait impairments. These changes in gait have been well studied in laboratory and clinical settings. A thorough...     

Enhanced Survival and Neurite Network Formation of Human Umbilical Cord Blood Neuronal Progenitors in Three-Dimensional Collagen Constructs

Umbilical cord blood (CB) stem cells have been proposed for cell-based therapeutic applications for diverse diseases of the CNS. We hypothesized that tissue-engineering strategies may extend the efficacy of these approaches by improving the long-term viability and function of stem cell-derived neuronal progenitors. To test our hypothesis, we explored the survival and differentiation of human CB-derived neuronal progenitors (HUCBNP) in a three-dimensional (3D) collagen construct. In contrast to two-dimensional culture conditions, the cells survived in 3D for an extended period of time of more than 2 months. Under 3D conditions, HUCBNP underwent spontaneous neuronal differentiation, which was further enhanced by treatment with neuronal conditioned medium (CM) and nerve growth factor (NGF). Neurite outgrowth, quantified by assessing the fractal dimension (D _f) of the complex neuronal networks, was significantly enhanced under 3D conditions in the presence of CM/NGF, concomitant with a reduced expression of the early neuronal marker nestin (1.9-fold), and increased levels of mature neuronal markers such as MAP-2 (3.6-fold), β-tubulin (1.5-fold), and neuronal specific enolase (6.6-fold) and the appearance of the synaptic marker synaptophysin. To assess the feasibility for clinical usage, HUCBNP were also isolated from frozen CB samples and cultured under 3D conditions. The data indicate the essential complete preservation of neurotrophic (survival) and neurotropic (neurite outgrowth) properties. In conclusion, 3D culture conditions are proposed as an essential step for both maintenance of CB neuronal progenitors in vitro and for investigating specific features of neuronal differentiation towards future use in regenerative therapy.     

Relatively favorable outcome after allogeneic stem cell transplantation for BCR‐ABL1‐positive AML: A survey from the acute leukemia working party of the European Society for blood and marrow transplantation (EBMT)

The aim of the study was to assess the role of allogeneic stem cell transplantation (SCT) in patients diagnosed with BCR‐ABL1‐positive acute myeloid leukemia (AML). Fifty‐seven patients (median age, 48 years, range: 19‐67) with BCR‐ABL1 positive AML undergoing SCT were identified. The majority of the patients (70%) received a TKI before the transplant. At SCT 48 patients were in CR (45 in CR1), while 9 patients were transplanted in a more advanced stage of the disease. MRD was negative (BCR‐ABL1/ABL < 10⁴) at time of SCT in 36.1% (14/40). After SCT, 16 (61.5%) out of 26 patients with MRD positive at transplantation reached MRD negativity. After a median follow‐up of 6.3 years (0.7–14.2), NRM, RI, LFS, OS, and GRFS at 5 years were 18.1%, 37%, 44.2%, 53.8%, and 32.1%, respectively. The cumulative incidence of acute GvHD grade II‐IV was 16.4%, incidence of chronic GvHD 24.9%, and of extensive cGvHD 21.4%, respectively. In patients who received SCT in CR1, 5‐yr NRM, RI, LFS, OS, and GRFS were 15.9%, 36.4%, 46.5%, 59.4%, and 34.9%, respectively. Univariate analysis showed that age (<50 vs. ≥50 years) was associated with RI (5‐yr: 22.7 vs. 50%), LFS (5‐yr: 61.9 vs. 31.8%), and GRFS (5‐yr: 52.4 vs. 18.2%), whereas MRD‐negative status before SCT was associated with an improved GRFS (38.9 vs. 16.7%). We conclude that the outcome of patients <50 years of age with BCR‐ABL1‐positive AML receiving allogeneic SCT in CR is relatively favorable, possibly reflecting the beneficial effect of the use of TKI.     

MicroRNA expression differentiates between primary lung tumors and metastases to the lung

For surgical pathologists, distinguishing whether a pulmonary neoplasm is primary or metastatic can be challenging, and current biomarkers do not always aid lung tumor classification. The tissue-associated expression of microRNA likely explains the remarkable finding that many tumors can be classified based solely on their microRNA expression signature. Here we show that microRNAs can serve as biomarkers for lung tumor classification. Using microRNA microarray data generated from 76 formalin-fixed, paraffin-embedded (FFPE) samples of either primary lung cancer or metastatic tumors to the lung, we have identified a set of microRNAs expressed differentially between these two groups. This set includes hsa-miR-182, which was most strongly over-expressed in the lung primary tumors, and hsa-miR-126, which was over-expressed in the metastatic tumors. The differential expression of this set of microRNAs was confirmed using qRT-PCR on a set of 54 samples. In light of our data, microRNA expression should be considered as a potential clinical biomarker for surgical pathologists faced with discerning the tumor type of an inscrutable lung neoplasm.     

The role of stress in the mosaic of autoimmunity: An overlooked association

Stress is defined as the pscyophysiological reaction in which the steady state is disturbed or threatened. Stress is not always perceived as a negative response. Stress results when environmental demands exceed an individuals' adaptive capacities. Autoimmune diseases are heterogeneous group of chronic diseases which occur secondary to loss of self antigen tolerance. The etiopathogenesis of autoimmune disease is uncertain. Genetic factors as well as environmental factors appear to interplay, leading to a cascade of events resulting in disease onset. Stress has been postulated to play a role in disease onset in the genetically susceptible patients. During the stress response, catecholamines and glucocorticoids are released from locus coeruleus and adrenal gland. These biomolecules exert control over various immune cells in the innate and adaptive arms of the immune system, thereby altering the cytokine profile released. The increase of IL-4 promotes T-helper 2 (T_h2) cell differentiation, while the decrease in IL-12 and the increased IL-10 production reduce the number of T-helper 1 (T_h1) cells. The relationship between stress and autoimmune diseases is intricate. Stress has been shown to be associated with disease onset, and disease exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune conditions. In certain conditions such as psoriasis, stress has been implicated in delaying lesion clearance upon the application of standard treatment regimes. Finally, psychological therapy and cognitive behavioral therapy aimed to reduce stress levels was shown to be effective in influencing better outcomes in many autoimmune diseases. The purpose of this paper is to closer inspect the clinical evidence regarding the role of stress on influencing the various aspects of disease entities.