Laser microdissection and mass spectrometry-based proteomics aids the diagnosis and typing of renal amyloidosis

Accurate diagnosis and typing of renal amyloidosis is critical for prognosis, genetic counseling, and treatment. Laser microdissection and mass spectrometry are emerging techniques for the analysis and diagnosis of many renal diseases. Here we present the results of laser microdissection and mass spectrometry performed on 127 cases of renal amyloidosis during 2008-2010. We found the following proteins in the amyloid deposits: immunoglobulin light and heavy chains, secondary reactive serum amyloid A protein, leukocyte cell-derived chemotaxin-2, fibrinogen-α chain, transthyretin, apolipoprotein A-I and A-IV, gelsolin, and β-2 microglobulin. Thus, laser microdissection of affected areas within the kidney followed by mass spectrometry provides a direct test of the composition of the deposit and forms a useful ancillary technique for the accurate diagnosis and typing of renal amyloidosis in a single procedure.     

A rare anatomical variation of the brachial plexus: single cord anomaly

Anatomical variations of the brachial plexus may be important in regional anesthesia and upper limb procedures. A fused single cord of the brachial plexus, although considered rare, was discovered in 4 Indian male cadavers during the dissection of 90 brachial plexuses. All 4 cases demonstrated deviation from the usual pattern starting at the division of trunks continuing to the formation of cords. The location of these single cords was lateral to the axillary artery instead of the typical perivascular relationship. A fused single cord of brachial plexus might be more common than previously thought. The impact on the performance or success of blockade remains unknown.     

Analysis & commentary: The US Preventive Services Task Force should consider a broader evidence base in updating its diabetes screening guidelines

Diabetes, especially type 2 diabetes, is on the rise throughout the United States. Several national health organizations and professional medical societies advocate screening people in high-risk groups for diabetes. However, the US Preventive Services Task Force recommends screening only adults with hypertension. We examined evidence supporting screening high-risk adults, including studies using intermediate outcomes and modeling studies. We found a broad range of evidence of practical relevance to diabetes screening that merits consideration in developing new screening guidelines. This evidence could inform recommendations to expand coverage to screening of other high-risk groups and could facilitate the prevention and early treatment of diabetes. We recommend that the US Preventive Services Task Force consider these expanded sources of evidence and revise its recommendations accordingly.     

Ultrasonography for masseter muscle cysticercosis

Solitary cheek swellings can present a diagnostic dilemma. We managed two children 10 y and 8 y presenting with pain and swelling on one side of cheek for over 15 d and no constitutional symptoms. Sonography showed cysticercosis in both of them. We treated both with steroids and albendazole, with good response.     

Longitudinal liver sampling in patients with chronic hepatitis B starting antiviral therapy reveals hepatotoxic CD8+ T cells

Accumulation of activated immune cells results in nonspecific hepatocyte killing in chronic hepatitis B (CHB), leading to fibrosis and cirrhosis. This study aims to understand the underlying mechanisms in humans and to define whether these are driven by widespread activation or a subpopulation of immune cells. We enrolled CHB patients with active liver damage to receive antiviral therapy and performed longitudinal liver sampling using fine-needle aspiration to investigate mechanisms of CHB pathogenesis in the human liver. Single-cell sequencing of total liver cells revealed a distinct liver-resident, polyclonal CD8⁺ T cell population that was enriched at baseline and displayed a highly activated immune signature during liver damage. Cytokine combinations, identified by in silico prediction of ligand-receptor interaction, induced the activated phenotype in healthy liver CD8⁺ T cells, resulting in nonspecific Fas ligand–mediated killing of target cells. These results define a CD8⁺ T cell population in the human liver that can drive pathogenesis and a key pathway involved in their function in CHB patients.