Molecular pathology quality control in Southeast Asia: Results of a multiregional quality assurance study from MASTER KEY Asia

Tissue specimen quality assurance is a major issue of precision medicine for rare cancers. However, the laboratory standards and quality of pathological specimens prepared in Asian hospitals remain unknown. To understand the methods in Southeast Asian oncology hospitals and to clarify how pre-analytics affect the quality of formalin-fixed paraffin-embedded (FFPE) specimens, a questionnaire surveying pre-analytical procedures (Part I) was administered, quality assessment of immunohistochemistry (IHC) staining and DNA/RNA extracted from the representative FFPE specimens from each hospital (Part II) was conducted, and the quality of DNA/RNA extracted from FFPE of rare-cancer patients for genomic sequencing (Part III) was examined. Quality measurements for DNA/RNA included ΔΔCt, DV200, and cDNA yield. Six major cancer hospitals from Malaysia, Philippines, and Vietnam participated. One hospital showed unacceptable quality for the DNA/RNA assessment, but improved by revising laboratory procedures. Only 57% (n = 73) of the 128 rare-cancer patients' specimens met both DNA and RNA quality criteria for next-generation sequencing. Median DV200 was 80.7% and 64.3% for qualified and failed RNA, respectively. Median ΔΔCt was 1.25 for qualified and 4.89 for failed DNA. Longer storage period was significantly associated with poor DNA (fail to qualify ratio = 1579:321 days, p < 0.001) and RNA (fail to qualify ratio = 1070:280 days, p < 0.001). After improvement of pre-analytical factors, the qualification rate increased for hospitals A and E from 41.5% to 70.5% and 62.5% to 86%, respectively. This is the first report to elucidate the pre-analytical laboratory procedures of main Southeast Asian oncology hospitals. An external quality assessment program may improve factors associated with tumor FFPE specimen quality.     

Evaluation of microalbuminuria after non-ionic radiocontrast medium exposure in patients undergoing coronary angiography

We described a massive non compaction cardiomyopathy associated with Antiphospholipid syndrome in a 53-year-old male with many episodes of ischemic cerebral stroke complicated by functional disability, cognitive decline and vascular dementia. In our case, the association of massive non compaction cardiomyopathy and severe left ventricular dysfunction added to Antiphospholipid syndrome has showed a dramatic thromboembolic manifestation.     

Biases in the Explore–Exploit Tradeoff in Addictions: The Role of Avoidance of Uncertainty

We focus on exploratory decisions across disorders of compulsivity, a potential dimensional construct for the classification of mental disorders. Behaviors associated with the pathological use of alcohol or food, in alcohol use disorders (AUD) or binge-eating disorder (BED), suggest a disturbance in explore–exploit decision-making, whereby strategic exploratory decisions in an attempt to improve long-term outcomes may diminish in favor of more repetitive or exploitatory choices. We compare exploration vs exploitation across disorders of natural (obesity with and without BED) and drug rewards (AUD). We separately acquired resting state functional MRI data using a novel multi-echo planar imaging sequence and independent components analysis from healthy individuals to assess the neural correlates underlying exploration. Participants with AUD showed reduced exploratory behavior across gain and loss environments, leading to lower-yielding exploitatory choices. Obese subjects with and without BED did not differ from healthy volunteers but when compared with each other or to AUD subjects, BED had enhanced exploratory behaviors particularly in the loss domain. All subject groups had decreased exploration or greater uncertainty avoidance to losses compared with rewards. More exploratory decisions in the context of reward were associated with frontal polar and ventral striatal connectivity. For losses, exploration was associated with frontal polar and precuneus connectivity. We further implicate the relevance and dimensionality of constructs of compulsivity across disorders of both natural and drug rewards.     

Osimertinib versus Standard of Care EGFR TKI as First-Line Treatment in Patients with EGFRm Advanced NSCLC: FLAURA Asian Subset

Introduction

Here we report efficacy and safety data of an Asian subset of the phase III FLAURA trial (NCT02296125), which compares osimertinib with standard of care (SoC) EGFR tyrosine kinase inhibitors (TKIs) in patients with previously untreated advanced NSCLC with tumors harboring exon 19 deletion (Ex19del)/L858R EGFR TKI–sensitizing mutations.

Treatment of aberrant facial nerve regeneration with botulinum toxin A

purpose To assess the effect and efficacy of botulinum toxin type A (BTX-A) at reducing and maintaining eyelid synkinesia in aberrant facial nerve regeneration, while concurrently observing for the presence of side effects to differing treatment doses. methods A prospective interventional study of five patients with eyelid synkinesia resulting from aberrant regeneration of the facial nerve. Patients were treated with injections of either 120, 80 or 40 units of BTX-A (Dysport) into the orbicularis oculi. Objective and subjective reduction in synkinesia, maintenance of response and presence of side effects were recorded. results All five patients had improvement of the synkinesia with BTX-A treatment. Lower doses were found to be as effective as higher doses. Mean duration of abolished synkinesia was three months. Two patients developed a ptosis which resolved spontaneously. None of the patients treated with the lowest dose of 40 units developed a ptosis. conclusion Low-dose BTX-A has a lower incidence of ptosis and is effective in the treatment of aberrant facial nerve regeneration.