Molecular Diagnostic Review of Diffuse Large B-Cell Lymphoma and Its Tumor Microenvironment.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma. It is a clinically and morphologically heterogeneous entity that has continued to resist complete subtyping. Molecular subtyping efforts emerged in earnest with the advent of gene expression profiling (GEP). This molecular subtyping approach has continued to evolve simultaneously with others including immunohistochemistry and more modern genomic approaches. Recently, the veritable explosion of genomic data availability and evolving computational methodologies have provided additional avenues, by which further understanding and subclassification of DBLCLs is possible. The goal of this review is to provide a historical overview of the major classification timepoints in the molecular subtyping of DLBCL, from gene expression profiling to present day understanding.

Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations.

Diagnosis in the early stages of hereditary transthyretin (ATTR) amyloidosis is imperative to support timely treatment to prevent or delay disease progression. Genetic testing in the setting of genetic counselling enables identification of carriers of a TTR gene mutation who are therefore at risk of developing TTR-associated disease. Knowledge of different genotypes and how they manifest in symptomatic disease should facilitate development of a structured and targeted approach to enable diagnosis of symptomatic disease in ATTR amyloidosis mutation carriers on the first manifestation of the earliest detectable sign or symptom. A group of experts from across Europe, Israel and Japan met to reach a consensus on such an approach. The proposed approach involves establishing a baseline for key clinical parameters, determination of the timing and frequency of follow-up in TTR mutation carriers based on a predicted age of disease onset, and recognition of the likely initial clinical signs and symptoms aligned with the phenotype of the specific TTR gene mutation and family history. Minimum criteria for diagnosis of symptomatic disease have been agreed, which it is hoped will ensure diagnosis of ATTR amyloidosis at the earliest possible stage in people with a known TTR mutation.

Difficulty in determining the association of a single nucleotide polymorphism in the ZNF512B gene with the risk and prognosis of amyotrophic lateral sclerosis.

The advent of next-generation sequencing technology is expected to accelerate the identification of novel genes, and this technology will likely supersede Sanger sequencing. Thus, genome-wide association studies (GWASs) are performed more routinely in an effort to identify disease-susceptibility genes for sporadic amyotrophic lateral sclerosis (ALS). Previously, a Japanese team conducted a large-scale GWAS with 1,305 Japanese ALS patients and discovered a new single nucleotide polymorphism (SNP) rs2275294 associated with susceptibility to sporadic ALS (sALS) in the ZNF512B gene on chromosome 20q13.33. Ju et al. recently performed a case-control study to examine the possible association of rs2275294 with the risk of sALS. Their results, however, indicated that the SNP in ZNF512B is not associated with sALS susceptibility in the Chinese population. A precise diagnosis of neurodegenerative diseases, especially ALS, is highly challenging. For GWASs and other clinical research studies that require a large sample size, if true ALS patients are not selected initially, then all subsequent research is futile. Here, I evaluate the factors that are likely responsible for the inconsistent results obtained by GWASs and propose the development of a new classification system and diagnostic criteria for ALS as the first step towards conducting better clinical studies on ALS. I have attempted to explain the reasons for the inconsistent association between rs2275294 and ALS progression by listing the gene-gene/gene-environment interactions, age of onset, sample size, odds ratio, and inappropriate ALS diagnosis criteria for stratifying this heterogeneous disease in this review.

Anaphylaxis: Unique aspects of clinical diagnosis and management in infants (birth to age 2 years).

In this rostrum we aim to increase awareness of anaphylaxis in infancy in order to improve clinical diagnosis, management, and prevention of recurrences. Anaphylaxis is increasingly reported in this age group. Foods are the most common triggers. Presentation typically involves the skin (generalized urticaria), the respiratory tract (cough, wheeze, stridor, and dyspnea), and/or the gastrointestinal tract (persistent vomiting). Tryptase levels are seldom increased because of infant anaphylaxis, although baseline tryptase levels can be increased in the first few months of life, reflecting mast cell burden in the developing immune system. The differential diagnosis of infant anaphylaxis includes consideration of age-unique entities, such as food protein-induced enterocolitis syndrome with acute presentation. Epinephrine (adrenaline) treatment is underused in health care and community settings. No epinephrine autoinjectors contain an optimal dose for infants weighing 10 kg or less. After treatment of an anaphylactic episode, follow-up with a physician, preferably an allergy/immunology specialist, is important for confirmation of anaphylaxis triggers and prevention of recurrences through avoidance of confirmed specific triggers. Natural desensitization to milk and egg can occur. Future research should include validation of the clinical criteria for anaphylaxis diagnosis in infants, prospective longitudinal monitoring of baseline serum tryptase levels in healthy and atopic infants during the first year of life, studies of infant comorbidities and cofactors that increase the risk of severe anaphylaxis, development of autoinjectors containing a 0.1-mg epinephrine dose suitable for infants, and inclusion of infants in prospective studies of immune modulation to prevent anaphylaxis recurrences.

Key points summarization of 《Guidelines for the diagnosis and management of aplastic anemia (2009)》 / 中华实用儿科临床杂志

Aplastic anemia (AA) is one of serious hematopoietic diseases,clinical diagnosis and treatment is difficult.The guidelines for the diagnosis and management of aplastic anemia recommended (Guideline) by British Society for Haematology Committee in 2009,is made up of many experts based on experiences,used the method of evidence-based medicine,and collected all the reports of diagnosis and treatment of AA published in recent years,after strict screening screening and sums up the writing complete guidance document represented the principle and clinical methodology of diagnosis and treatment of AA in the mainstream view of world.The Guideline is comprehensive,on the basis of fully,opinionated,detailed,clinical maneuverability is strong,has a very high refe-rence value.In this paper,that selected and summarized of the contents closely related to the clinical diagnosis and treatment of AA from the guideline,in order to provide reference well to the colleague.