Selective Laser Sintering 3-Dimensional Printing as a Single Step Process to Prepare Amorphous Solid Dispersion Dosage Forms for Improved Solubility and Dissolution Rate

This study reports the development of ritonavir-copovidone amorphous solid dispersions (ASDs) and dosage forms thereof using selective laser sintering (SLS) 3-dimensional (3-D) printing in a single step, circumventing the post-processing steps required in common techniques employed to make ASDs. For this study, different drug loads of ritonavir with copovidone were processed at varying processing conditions to understand the impact, range, and correlation of these parameters for successful ASD formation. Further, ASDs characterized using conventional and advanced solid-state techniques including wide-angle X-ray scattering (WAXS), solid-state nuclear magnetic resonance (ssNMR), revealed the full conversion of the crystalline drug to its amorphous form as a function of laser-assisted selective fusion in a layer-by-layer manner. It was observed that an optimum combination of the powder flow properties, surface temperature, chamber temperature, laser speed, and hatch spacing was crucial for successful ASD formation, any deviations resulted in print failures or only partial amorphous conversion. Moreover, a 21-fold increase in solubility was demonstrated by the SLS 3-D printed tablets. The results confirmed that SLS 3-D printing can be used as a single-step platform for creating ASD-based pharmaceutical dosage forms with a solubility advantage.     

Right‐Sided Endomyocardial Fibrosis with a Right Atrial Thrombus: Three‐Dimensional Transthoracic Echocardiographic Evaluation

Endomyocardial fibrosis is a form of restrictive cardiomyopathy mainly affecting poor children and young adults in geographically restricted areas of Latin America, Africa, and Southeast Asia. The pathophysiological hallmark of the disease is focal or diffuse endocardial thickening involving mainly the inflow, the apices, and the subvalvular region leading to valvular regurgitation, diastolic dysfunction and obliteration of the ventricular apex. Advanced right‐sided disease has slow flow of blood through chambers with propensity of thrombus formation especially in the right atria. Although two‐dimensional transthoracic echocardiography remains the cornerstone for the diagnosis of this disease, the case presented here shows how three‐dimensional transthoracic echocardiography can add substantial information regarding the region of involvement of the right ventricle as well as the various characteristics of the right atrial thrombus.     

Who Should Receive a Transplant for Acute Lymphoblastic Leukaemia?

Allogeneic haematopoietic cell transplantation continues to be an important curative therapy for acute lymphoblastic leukaemia (ALL). Traditionally accepted indications for allografting adult ALL patients need reevaluation in light of outcomes with paediatric-like intensive regimens. Minimal residual disease status and oncogenetics can be used for restratification of standard risk patients. A greater body of data on haematopoietic cell transplantation (HCT) outcomes from haploidentical and cord blood donor sources has been generated in recent years. In this review, we describe the indications for allografting adult ALL patients in first complete remission (CR1). Role of minimal residual disease (MRD) in optimising HCT for ALL is delineated. We also discuss how alternative donors, haploidentical and cord blood and reduced intensity conditioning make allografts more accessible to patients with high-risk ALL. Recent data on use of monoclonal antibodies and chimeric antigen receptor (CAR)-modified T cells in adult ALL patients are also reviewed.     

Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney injury

Severe sepsis often leads to multiple organ dysfunction syndromes (MODS) with acute kidney injury (AKI). AKI affects approximately, 35% of Intensive Care Unit patients, and most of these are due to sepsis. Mortality rate of sepsis-induced AKI is high. Inappropriate use of antimicrobials may be responsible for higher therapeutic failure, mortality rates, costs and toxicity as well as the emergence of resistance. Antimicrobial treatment is particularly difficult due to altered pharmacokinetic profile, dynamic changes in patient''s clinical status and, in many cases, need for renal replacement therapy. This article aims to describe the appropriate antimicrobial dosing and reviews the factors contributing to the difficulties in establishing precise guidelines for antimicrobial dosing in sepsis-induced AKI patients. Search strategy: Text material was collected by systematic search in PubMed, Google (1978–2013) for original articles.     

Macular buckle without vitrectomy for myopic macular schisis: a Canadian case series

Objective

To determine the effectiveness of a macular buckle procedure without vitrectomy for the treatment of symptomatic myopic macular schisis.