Inflammatory Characteristics of Stenotic Aortic Valves: A Comparison between Rheumatic and Nonrheumatic Aortic Stenosis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Background. Although our comprehension of nonrheumatic aortic stenosis (NRAS) has increased substantially during the last decade, less is known about the histopathology of rheumatic aortic stenosis (RAS). The aim of this study was to investigate rheumatic aortic stenosis by means of analyses previously used in nonrheumatic stenosis. Material and Methods. Valve specimens were obtained from 39 patients referred to hospital due to significant aortic stenosis. According to established macroscopic criteria the valves were divided into two groups consisting of 29 NRAS and 10 RAS valves. Mononuclear inflammatory cells and apolipoproteins were investigated using immunohistochemical analyses. Results. The localisation of calcification differed in tricuspid nonrheumatic valves when compared to bicuspid nonrheumatic and rheumatic valves. The RAS valves revealed a lower degree of T lymphocyte infiltration compared with the NRAS valves. Infiltration of macrophages was seen in all valves and there were no differences regarding deposition of apolipoprotein. Conclusion. Rheumatic and nonrheumatic aortic stenotic valves show a similar and significant chronic inflammation. The similarities regarding the localisation of calcification indicate that the valve anomaly/morphology can influence the pathogenesis of aortic stenosis. Finally, our findings highlight the question of a postinflammatory valvular disease of other causes than rheumatic fever.Swedish Heart-Lung Foundation, Östergötland County Council, Linköping University Hospital

Reversed halo sign on CT as a presentation of lymphocytic interstitial pneumonia.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.A 52 year-old African American female with a past medical history of symptomatic uterine fibroids and increasing abdominal circumference underwent abdominal computed tomography (CT) as part of her workup. Because of an abnormality in the left lower lobe, CT of the chest was subsequently performed and showed a focal region of discontinuous crescentic consolidation with central ground glass opacification in the right lower lobe, suggestive of the reversed halo sign. The patient underwent percutaneous CT-guided core biopsy of the lesion, which demonstrated lymphocytic interstitial pneumonia, a benign lymphoproliferative disease characterized histologically by small lymphocytes and plasma cells. This case report describes the first histologically confirmed presentation of lymphocytic interstitial pneumonia with the reversed halo sign on CT

Population-level deficit of homozygosity unveils CPSF3 as an intellectual disability syndrome gene.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPredicting the pathogenicity of biallelic missense variants can be challenging. Here, we use a deficit of observed homozygous carriers of missense variants, versus an expected number in a set of 153,054 chip-genotyped Icelanders, to identify potentially pathogenic genotypes. We follow three missense variants with a complete deficit of homozygosity and find that their pathogenic effect in homozygous state ranges from severe childhood disease to early embryonic lethality. One of these variants is in CPSF3, a gene not previously linked to disease. From a set of clinically sequenced Icelanders, and by sequencing archival samples targeted through the Icelandic genealogy, we find four homozygous carriers. Additionally, we find two homozygous carriers of Mexican descent of another missense variant in CPSF3. All six homozygous carriers of missense variants in CPSF3 show severe intellectual disability, seizures, microcephaly, and abnormal muscle tone. Here, we show how the absence of certain homozygous genotypes from a large population set can elucidate causes of previously unexplained recessive diseases and early miscarriage.Sacchi Foundatio

Clinicopathologic conference: multiple fetal demises, lactic acidosis and hepatic iron accumulation

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldABSTRACT A case of a premature infant with lactic acidosis and hepatic iron accumulation, born to a mother with multiple fetal demises, is presented and discussed by both clinician and pathologist, in this traditional clinico-pathologic conference. The discussion includes the differential diagnoses of lactic acidosis and hepatic iron accumulation in infants