Citations

AbstractIntroductionMethemoglobin (MetHb) and sulfhemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. Methemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfhemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M‐Hemoglobin variants (M‐Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well.MethodsHerein, we report 53 hemoglobin variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn‐Malloy laboratory assay method.ResultsOur data indicate M‐Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular variant. In particular, α globin chain M‐Hbs can mimic acquired sulfhemoglobinemia due to an isolated increased SHb value.ConclusionIf the patient appears clinically well other than cyanosis, M‐Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.

The accurate diagnosis of chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) subtypes with monocytic differentiation relies on the proper identification and quantitation of blast cells and blast-equivalent cells, including promonocytes. This distinction can be quite challenging given the cytomorphologic and immunophenotypic similarities among the monocytic cell precursors. The aim of this study was to assess the performance of convolutional neural networks (CNN) in separating monocytes from their precursors (i.e., promonocytes and monoblasts). We collected digital images of 935 monocytic cells that were blindly reviewed by five experienced morphologists and assigned into three subtypes: monocyte, promonocyte, and blast. The consensus between reviewers was considered as a ground truth reference label for each cell. In order to assess the performance of CNN models, we divided our data into training (70%), validation (10%), and test (20%) datasets, as well as applied fivefold cross validation. The CNN models did not perform well for predicting three monocytic subtypes, but their performance was significantly improved for two subtypes (monocyte vs. promonocytes + blasts). Our findings (1) support the concept that morphologic distinction between monocytic cells of various differentiation level is difficult; (2) suggest that combining blasts and promonocytes into a single category is desirable for improved accuracy; and (3) show that CNN models can reach accuracy comparable to human reviewers (0.78 ± 0.10 vs. 0.86 ± 0.05). As far as we know, this is the first study to separate monocytes from their precursors using CNN.

Background: Human induced pluripotent stem cells with normal (wild-type) or upregulated (overexpressed) levels of CCND2 (cyclin D2) expression were differentiated into cardiomyocytes (CCND2 WT CMs or CCND2 OE CMs, respectively) and injected into infarcted pig hearts. Methods: Acute myocardial infarction was induced by a 60-minute occlusion of the left anterior descending coronary artery. Immediately after reperfusion, CCND2 WT CMs or CCND2 OE CMs (3×10 7 cells each) or an equivalent volume of the delivery vehicle was injected around the infarct border zone area. Results: The number of the engrafted CCND2 OE CMs exceeded that of the engrafted CCND2 WT CMs from 6- to 8-fold, rising from 1 week to 4 weeks after implantation. In contrast to the treatment with the CCND2 WT CMs or the delivery vehicle, the administration of CCND2 OE CM was associated with significantly improved left ventricular function, as revealed by magnetic resonance imaging. This correlated with reduction of infarct size, fibrosis, ventricular hypertrophy, and cardiomyocyte apoptosis, and increase of vascular density and arterial density, as per histologic analysis of the treated hearts. Expression of cell proliferation markers (eg, Ki67, phosphorylated histone 3, and Aurora B kinase) was also significantly upregulated in the recipient cardiomyocytes from the CCND2 OE CM-treated than from the CCND2 WT CM-treated pigs. The cell proliferation rate and the hypoxia tolerance measured in cultured human induced pluripotent stem cell cardiomyocytes were significantly greater after treatment with exosomes isolated from the CCND2 OE CMs (CCND2 OE Exos) than from the CCND2 WT CMs (CCND2 WT Exos). As demonstrated by our study, CCND2 OE Exos can also promote the proliferation activity of postnatal rat and adult mouse cardiomyocytes. A bulk miRNA sequencing analysis of CCND2 OE Exos versus CCND2 WT Exos identified 206 and 91 miRNAs that were significantly upregulated and downregulated, respectively. Gene ontology enrichment analysis identified significant differences in the expression profiles of miRNAs from various functional categories and pathways, including miRNAs implicated in cell-cycle checkpoints (G2/M and G1/S transitions), or the mechanism of cytokinesis. Conclusions: We demonstrated that enhanced potency of CCND2 OE CMs promoted myocyte proliferation in both grafts and recipient tissue in a large mammal acute myocardial infarction model. These results suggest that CCND2 OE CMs transplantation may be a potential therapeutic strategy for the repair of infarcted hearts.

Objective Effective medical therapy and validated trial outcomes are lacking for small bowel Crohn’s disease (CD) strictures. Histopathology of surgically resected specimens is the gold standard for correlation with imaging techniques. However, no validated histopathological scoring systems are currently available for small bowel stricturing disease. We convened an expert panel to evaluate the appropriateness of histopathology scoring systems and items generated based on panel opinion. Design Modified RAND/University of California Los Angeles methodology was used to determine the appropriateness of 313 candidate items related to assessment of CD small bowel strictures. Results In this exercise, diagnosis of naïve and anastomotic strictures required increased bowel wall thickness, decreased luminal diameter or internal circumference, and fibrosis of the submucosa. Specific definitions for stricture features and technical sampling parameters were also identified. Histopathologically, a stricture was defined as increased thickness of all layers of the bowel wall, fibrosis of the submucosa and bowel wall, and muscularisation of the submucosa. Active mucosal inflammatory disease was defined as neutrophilic inflammation in the lamina propria and any crypt or intact surface epithelium, erosion, ulcer and fistula. Chronic mucosal inflammatory disease was defined as crypt architectural distortion and loss, pyloric gland metaplasia, Paneth cell hyperplasia, basal lymphoplasmacytosis, plasmacytosis and fibrosis, or prominent lymphoid aggregates at the mucosa/submucosa interface. None of the scoring systems used to assess CD strictures were considered appropriate for clinical trials. Conclusion Standardised assessment of gross pathology and histopathology of CD small bowel strictures will improve clinical trial efficiency and aid drug development.

Aims The purpose of this study was to report bone adaptive changes after anatomical total shoulder arthroplasty (TSA) using a standard-length hydroxyapatite (HA)-coated humeral component, and to report on a computer-based analysis of radiographs to determine changes in peri-implant bone density objectively. Methods A total of 44 TSAs, performed between 2011 and 2014 using a cementless standard-length humeral component proximally coated with HA, were included. There were 23 males and 21 females with a mean age of 65 years (17 to 65). All shoulders had good quality radiographs at six weeks and five years postoperatively. Three observers graded bone adaptive changes. All radiographs were uploaded into a commercially available photographic software program. The grey value density of humeral radiological areas was corrected to the grey value density of the humeral component and compared over time. Results Stress shielding was graded as mild in 14 shoulders and moderate in three; the greater tuberosity was the predominant site for stress shielding. The mean metaphyseal and diaphyseal fill-fit ratios were 0.56 (SD 0.1) and 0.5 (SD 0.07), respectively. For shoulders with no radiologically visible stress shielding, the mean decrease in grey value in zones 1 and 7 was 20%, compared with 38% in shoulders with radiologically visible stress shielding. Conclusion The rate of moderate stress shielding was 7%, five years after implantation of a cementless standard-length HA-coated humeral component. Clinical observation of stress shielding identified on radiographs seems to represent a decrease in grey value of 25% or more. Cite this article: Bone Joint J 2021;103-B(5):958–963.

The optimal training of the highly specialized congenital heart surgeon is a long and complex process, which is a significant challenge in most parts of the world. The World Society for Pediatric and Congenital Heart Surgery (WSPCHS) has established the Global Council on Education for Congenital Heart Surgery as a nonprofit organization with the goal of assessing current training and certification and ultimately establishing standardized criteria for the training, evaluation, and certification of congenital heart surgeons around the world. The Global Council and the WSPCHS have reviewed the present status of training and certification for congenital cardiac surgery around the world. There is currently lack of consensus and standardized criteria for training in congenital heart surgery, with significant disparity between continents and countries. This represents significant obstacles to international job mobility of competent congenital heart surgeons and to the efforts to improve the quality of care for patients with Congenital Heart Disease worldwide. The purpose of this article is to summarize and document the present state of training and certification in congenital heart surgery around the world.