Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia.

PURPOSE: The toxicity of allogeneic stem-cell transplantation can be substantially reduced using a reduced-intensity conditioning (RIC) regimen. This has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) has not yet been defined, and consequently, the role of RIC allografts in the management of these diseases remains conjectural. PATIENTS AND METHODS: Seventy-six patients with high-risk AML or MDS received an allograft using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range, 18 to 71 years). RESULTS: The 100-day transplantation-related mortality rate was 9%, and no patient developed greater than grade 2 graft-versus-host disease. With a median follow-up of 36 months (range, 13 to 70 months), 27 patients were alive and in remission, with 3-year actuarial overall survival (OS) and disease-free survival (DFS) rates of 41% and 37%, respectively. The 3-year OS and DFS rates of patients with AML in complete remission at the time of transplantation were 48% and 42%, respectively. Disease relapse was the most common cause of treatment failure and occurred at a median time of 6 months after transplantation. All but one patient destined to relapse did so within 24 months of transplantation. CONCLUSION: The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts can produce sustained DFS in a significant number of patients with AML who would be ineligible for allogeneic transplantation with myeloablative conditioning.     

A Novel Supervised Approach for Segmentation of Lung Parenchyma from Chest CT for Computer-Aided Diagnosis

Segmentation of lung parenchyma from the chest computed tomography is an important task in analysis of chest computed tomography for diagnosis of lung disorders. It is a challenging task especially in the presence of peripherally placed pathology bearing regions. In this work, we propose a segmentation approach to segment lung parenchyma from chest. The first step is to segment the lungs using iterative thresholding followed by morphological operations. If the two lungs are not separated, the lung junction and its neighborhood are identified and local thresholding is applied. The second step is to extract shape features of the two lungs. The third step is to use a multilayer feed forward neural network to determine if the segmented lung parenchyma is complete, based on the extracted features. The final step is to reconstruct the two lungs in case of incomplete segmentation, by exploiting the fact that in majority of the cases, at least one of the two lungs would have been segmented correctly by the first step. Hence, the complete lung is determined based on the shape and region properties and the incomplete lung is reconstructed by applying graphical methods, namely, reflection and translation. The proposed approach has been tested in a computer-aided diagnosis system for diagnosis of lung disorders, namely, bronchiectasis, tuberculosis, and pneumonia. An accuracy of 97.37 % has been achieved by the proposed approach whereas the conventional thresholding approach was unable to detect peripheral pathology-bearing regions. The results obtained prove to be better than that achieved using conventional thresholding and morphological operations.     

Serum IgG Profiling of Toddlers Reveals a Subgroup with Elevated Seropositive Antibodies to Viruses Correlating with Increased Vaccine and Autoantigen Responses

Purpose

The human antibody repertoire forms in response to infections, the microbiome, vaccinations, and environmental exposures. The specificity of such antibody responses was compared among a cohort of toddlers to identify differences between seropositive versus seronegative responses.

Methods

An assessment of the serum IgM and IgG antibody reactivities in 197 toddlers of 1- and 2-years of age was performed with a microfluidic array containing 110 distinct antigens. Longitudinal profiling was done from years 1 to 2. Seropositivity to RNA and DNA viruses; bacteria; live attenuated, inactive, and subunit vaccines; and autoantigens was compared. A stratification was developed based on quantitative variations in the IgG responses. Clinical presentations and previously known genetic risk alleles for various immune system conditions were investigated in relation to IgG responses.

Results

IgG reactivities stratified toddlers into low, moderate, and high responder groups. The high group (17%) had elevated IgG responses to multiple RNA and DNA viruses (e.g., respiratory syncytial virus, Epstein-Barr virus, adenovirus, Coxsackievirus) and this correlated with increased responses to live attenuated viral vaccines and certain autoantigens. This high group was more likely to be associated with gestational diabetes and an older age. Genetic analyses identified polymorphisms in the IL2RB, TNFSF4, and INS genes in two high responder individuals that were associated with their elevated cytokine levels and clinical history of eczema and asthma.

Conclusion

Serum IgG profiling of toddlers reveals correlations between the magnitude of the antibody responses towards viruses, live attenuated vaccines, and certain autoantigens. A low responder group had much weaker responses overall, including against vaccines. The serum antibody screen also identifies individuals with IgG responses to less common infections (West Nile virus, parvovirus, tuberculosis). The characterization of the antibody responses in combination with the identification of genetic risk alleles provides an opportunity to identify children with increased risk of clinical disease.

     

Left Main Coronary Artery Thrombosis With Acute Myocardial Infarction: A Management Dilemma

Left main coronary artery (LMCA) thrombosis with acute myocardial infarction is a rare condition with very high mortality. The low incidence of this condition and exclusion of patients with LMCA thrombosis from clinical trials prevent the development of optimal management strategy in these patients. Therefore, there are no clear-cut guidelines describing an evidence-based approach for this condition. We describe a patient with LMCA thrombosis presenting with acute myocardial infarction, who was found to have hypercoagulable state related to homocysteinemia on further work-up. This case highlights the challenges faced during the management of this rare condition due to lack of clear-cut guidelines describing an evidence-based approach.     

In vitro antibacterial potential of metal oxide nanoparticles against antibiotic resistant bacterial pathogens

ObjectiveTo investigate the antibacterial potential of 5 different metal oxide nanoparticles against antibiotic resistant bacterial pathogens viz., Pseudomonas aeruginosa, Klebsiella sp. Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus sp.MethodsThe antibacterial activity of the five different nanoparticles was assessed by well diffusion method. Different concentrations of the nanoparticles were analyzed by MIC and MBC techniques. Finally the potential MgO nanoparticle was also subjected for the time kill assay method.ResultsThe results reveal that, the MgO nanoparticle showed maximum sensitivity [(16.00±0.53) mm dia] against Streptococcus pneumoniae and showed minimum sensitivity against Klebsiella sp. [(9.00±0.31) mm dia]. None of the nanoparticles showed sensitivity against the Streptococcus sp. The MIC result reveals that, the MgO nanoparticle showed maximum inhibition at a concentration of 10 μ g against Streptococcus pneumoniae. Moreover, the time kill assay reveals that, the bacterial growth was inhibited from the 2nd h onwards at a concentration of 10μ g.ConclusionsIt is concluded from the present findings that, the MgO nanoparticle could be used as an alternative antibacterial agent after completing successful in vivo trials.     

The Story of the Texas Pain Society: Formation and Function of a Regional Pain Society

Abstract: The idea of forming a Texas Pain Society came to the Founders in 1987 due to disparity and deficiencies in the practice of pain management in the United States and, in particular, the State of Texas. The Founders considered very carefully the implication of forming such a society. They diligently mapped out the mission and goals of the Texas Pain Society in those early formative years. This report is the history of Texas Pain Society as the activities unfolded from 1989 to 2011. The reader may question why there is a need to tell such a story. We believe strongly that, with disparities of standards of practice in pain medicine and poor recognition of advances in pain management, this scenario is quite common in many states and countries. The practitioners of pain management in these regions certainly must have considered getting together and forming a consensus on the standards of practice in their communities. This historical report of the Texas Pain Society provides the relevant information necessary and the efforts to be made for a society’s mission to achieve its goals and have an ongoing impact in its own region. We hope that we have shed some light on a process for the formation of a regional pain society such as ours. ?