Association of platelet-to-lymphocyte ratio levels with the risk of cardiac adverse events in people with type 2 diabetes undergoing percutaneous coronary intervention: A large-scale prospective cohort study.

BACKGROUND: The platelet-to-lymphocyte ratio (PLR), a promising inflammatory biomarker, contributes to the development of atherosclerosis and type 2 diabetes (T2D). Therefore, this study aimed to elucidate the importance of PLR in predicting adverse events in people undergoing percutaneous coronary intervention (PCI) with T2D. METHODS: We consecutively enrolled 8831 people who underwent PCI and divided them into four groups according to PLR and glycemic metabolic status (PLR-Low/High without T2D, PLR-Low/High with T2D). The endpoints were major adverse cardiovascular and cerebrovascular events (MACCE) and stent thrombosis. A multivariate Cox regression analysis was performed to determine this association. RESULTS: During the 2.4-year follow-up, 663 (7.5%) MACCE and 75 (0.85%) stent thromboses were recorded. The risk of MACCE (hazard ratio [HR]: 1.30, 95% confidence interval [CI]: 1.10-1.53, P = 0.002) and stent thrombosis (HR: 2.32, 95% CI: 1.38-3.90, P = 0.002) was significantly higher in people with high PLR levels than in those with low PLR. Among people with T2D, the PLR-High group showed a significantly higher risk of MACCE (HR: 1.59, 95% CI: 1.21-2.09, P = 0.001) and stent thrombosis (HR: 3.15, 95% CI: 1.32-7.52, P = 0.010). However, these associations were not significant in people without T2D. CONCLUSIONS: PLR has been originally documented as a significant predictor of poor prognosis and a high incidence of stent thrombosis in people undergoing PCI, especially in those with T2D.

High triglyceride-glucose index predicts cardiovascular events in patients with coronary bifurcation lesions: a large-scale cohort study.

BACKGROUND: Coronary bifurcation lesion, as a complex coronary lesion, is associated with higher risk of long-term poor prognosis than non-bifurcation lesions. The triglyceride-glucose (TyG) index has been shown to predict cardiovascular (CV) events in patients with coronary artery disease (CAD). However, the prognostic value of the TyG index in patients with bifurcation lesions who are at high risk of CV events remains undetermined. Therefore, this study aimed to investigate the association between the TyG index and CV events in patients with bifurcation lesions. METHODS: A total of 4530 consecutive patients with angiography-proven CAD and bifurcation lesions were included in this study from January 2017 to December 2018. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Patients were assigned into 3 groups according to TyG tertiles (T) (T1: <8.633; T2: 8.633-9.096 and T3: ≥9.096). The primary endpoint was CV events, including CV death, nonfatal myocardial infarction and nonfatal stroke at 3-year follow-up. Restricted cubic spline (RCS) analysis, Kaplan-Meier curves and Cox proportional hazard models were used to investigate the associations between the TyG index and study endpoints. RESULTS: During a median follow-up of 3.1 years, 141 (3.1%) CV events occurred. RCS analysis demonstrated a linear relationship between the TyG index and events after adjusting for age and male sex (non-linear P = 0.262). After multivariable adjustments, elevated TyG index (both T2 and T3) was significantly associated with the risk of CV events (hazard ratio [HR], 1.68; 95% confidence interval [CI],1.06-2.65; HR, 2.10; 95%CI, 1.28-3.47, respectively). When study patients were further stratified according to glycemic status, higher TyG index was associated with significantly higher risk of CV events in diabetic patients after adjusting for confounding factors (T3 vs. T1; HR, 2.68; 95%CI, 1.17-6.11). In addition, subgroup analysis revealed consistent associations of the TyG index with 3-year CV events across various subgroups. Furthermore, adding the TyG index to the original model significantly improved the predictive performance. CONCLUSIONS: High TyG index was associated with CV events in patients with bifurcation lesions, suggesting the TyG index could help in risk stratification and prognosis in this population.

Social isolation, loneliness, and incident type 2 diabetes mellitus: results from two large prospective cohorts in Europe and East Asia and Mendelian randomization.

Background: Social isolation and loneliness pose significant public health challenges globally. The objective of this study is to investigate the association between social isolation, loneliness, and the risk of type 2 diabetes mellitus (T2DM). Methods: 423,503 UK adults from the UK Biobank (UKB) and 13,800 Chinese adults from the China Health and Retirement Longitudinal Study (CHARLS) were analyzed. The exposures of interest were social isolation and loneliness. Social isolation was evaluated based on the number of household members, frequency of social activities, contact with others, and marriage status (CHARLS only). Loneliness was evaluated by the subjective feeling of loneliness and the willingness to confide in others (UKB only). The primary endpoint was incident T2DM. The two-sample Mendelian randomization (MR) analysis was based on the genome-wide association studies of UKB (n = 463,010) and the European Bioinformatics Institute (n = 655,666). Findings: The UKB cohort study documented 15,072 T2DM cases during a mean follow-up of 13.5 years, and the CHARLS cohort study recorded 1,249 T2DM cases during a mean follow-up of 5.8 years. Social isolation and loneliness showed significant associations with an elevated risk of T2DM in both UKB (social isolation [most vs least]: HR 1.17, 95% CI 1.11-1.23; loneliness [yes vs no]: HR 1.21, 95% CI 1.13-1.30) and CHARLS cohorts (social isolation [yes vs no]: HR 1.22, 95% CI 1.06-1.40; loneliness [yes vs no]: HR 1.21, 95% CI 1.07-1.36). These associations remained significant after accounting for baseline glucose status and genetic susceptibility to T2DM. Two-sample MR analyses determined that feeling lonely (OR 1.04, 95% CI 1.02-1.06) and engaging in fewer leisure/social activities (OR 1.03, 95% CI 1.02-1.05) were associated with increased T2DM risk, whereas more contact with friends or family (OR 0.99, 95% CI 0.98-0.99) was associated with reduced T2DM risk. Interpretation: Social isolation and loneliness are each associated with an elevated risk of T2DM, with MR analyses suggesting potential causal links. These associations remain significant after considering genetic susceptibility to T2DM. The findings highlight the importance of promoting initiatives to address social isolation and loneliness as part of T2DM prevention strategies. Funding: CAMS Innovation Fund for Medical Sciences (No. 2021-I2M-1-008) and National Natural Science Foundation of China (No. 72103187).

The impact of sleep quality and its change on the long-term risk of stroke in middle-aged and elderly people: Findings from the English Longitudinal Study of Ageing.

OBJECTIVE: This study focused on middle-aged and elderly adults (mean age ≥60 years) in England and aimed to evaluate the impact of sleep quality and change in sleep quality on the long-term risk of stroke. PATIENTS/METHODS: The current prospective study enrolled 6214 participants without stroke from wave 4 (2008-2009) of the English Longitudinal Study Aging (ELSA) dataset. From the ELSA questionnaires, sleep quality scores were calculated and used to evaluate the sleep quality of each participant. Cox proportional hazards regression models were used to assess the association between sleep status and stroke risk. Restricted cubic spline (RCS) was employed for the relationship between sleep quality score and the risk of stroke. RESULTS: During the 8-year follow-up, 130 (2.1%) cases of stroke were recorded. Participants with poor baseline sleep quality had a significantly higher long-term risk of stroke compared with those with good sleep quality (hazard ratio [HR] 2.37, 95% confidence intervals [CI] 1.44, 3.91). For the influence of change in sleep quality on stroke risk, worsened sleep quality was associated with a significant increase in the risk of stroke in the good (HR 2.08, 95% CI, 1.02, 4.26) and intermediate sleep quality groups (HR 2.15, 95% CI, 1.16, 3.98). Moreover, improved sleep quality decreased stroke risk among subjects with poor sleep quality (HR 0.31, 95% CI, 0.15, 0.61). CONCLUSIONS: Poor and worsened sleep quality is associated with an increased risk of stroke. Emphasis should be placed on improving sleep quality in middle-aged and elderly individuals.

High-Grade Desmoplastic Foamy Gland Prostatic Adenocarcinoma.

CONTEXT.­: It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and death. OBJECTIVE.­: To review the morphology, immunohistochemistry, and prognosis for this rare subtype of prostate adenocarcinoma. DESIGN.­: Twenty-four cases received for consultation from 2010 to 2021 were analyzed including needle biopsy (n = 21), transurethral resection (n = 2), and a cystoprostatectomy (n = 1). RESULTS.­: Patients ranged in age from 40 to 89 years (mean, 67 years). On average, 8 cores per case were involved (mean 67% core involvement). Extraprostatic extension and seminal vesicle invasion were observed in 6 of 21 (29%) and 3 of 21 (14%) needle biopsy cases, respectively. Twenty of the 24 cases (83%) were Grade Group (GG) 5 with 4 of 24 (17%) being GG4. Tumor necrosis as a component of Gleason pattern 5 was observed in 21 of 24 cases (88%). Associated intraductal adenocarcinoma (IDC) was observed in 22 of 24 cases (92%), with 4 of 24 cases (17%) demonstrating extensive IDC. Diagnostic challenges were as follows: (1) sparse isolated cancer glands embedded in the dense desmoplastic stroma; (2) fragmented glands; and (3) aberrant staining for high-molecular-weight cytokeratin in a nonbasal cell pattern in all cases. PTEN loss was observed in 9 cases, and p53 nuclear accumulation was observed in 8 cases. Three patients were lost to follow-up. Overall, of the 16 patients with meaningful follow-up, 12 (75%) either had metastases or died from prostate cancer. CONCLUSIONS.­: High-grade desmoplastic foamy gland adenocarcinoma is difficult to diagnose and grade and has a poor prognosis.

Value of 5-Hydroxymethylcytosine in HBV-Carrying High-Risk Hepatocellular Carcinoma Population: An Evaluation Based on Differential Analysis.

Objective: To clarify the application value of 5-hydroxymethylcytosine (5hmC) in evaluating the progression of chronic hepatitis B (CHB) to hepatocellular carcinoma (HCC) based on difference analysis. Methods: A total of 180 patients were enrolled. Among them, 84 patients with chronic hepatitis B virus (HBV) infection while no progression to hepatocellular carcinoma (HCC) were included in the control group (CG), and 96 patients with HCC developed from HBV infection were included in the research group (RG). Two-thirds of the samples were used in the training set and 1/3 samples in the validation set to detect the level of 5hmC in both groups based on the modified nano-hmC-Seal technique. The expression levels of 5hmC-related genes TET2 and TET3 were quantified by qPCR, and the correlation between TET3 and 5hmC was analyzed by Pearson's correlation coefficients. Receiver operating characteristic (ROC) curves were drawn to evaluate the application value of the TET3-based 5hmC prediction model in the early diagnosis of HCC. Results: (i) The expression of 5hmC in RG was lower than that in CG, no matter in the training set or the validation set. (ii) 5hmC was significantly enriched in the region between the transcription initiation site and the transcription end site but was depleted in the flanking region. (iii) 5hmC-related genes TET2 and TET3 were significantly downregulated in HCC patients, whether in the training set or the validation set. (iv) In both the training and validation sets, TET3 showed a positive association with 5hmC. (v) ROC analysis results showed that the 5hmC prediction model could be used to predict the progression of CHB to HCC (training set: AUC = 0.81, 0.729-0.893; validation set: AUC = 0.84, 0.739-0.936). Conclusions: TET3 expression based on 5hmC sequencing is a landmark molecule for evaluating the progression of HCC in CHB patients, which is worthy of further study and promotion.

Jailed Balloon Technique Is Superior to Jailed Wire Technique in Reducing the Rate of Side Branch Occlusion: Subgroup Analysis of the Conventional Versus Intentional StraTegy in Patients With High Risk PrEdiction of Side Branch OccLusion in Coronary Bifurcation InterVEntion Trial.

Objective: Jailed balloon technique (JBT) is an active side branch (SB) protection strategy and is considered to be superior to the jailed wire technique (JWT) in reducing SB occlusion. However, no randomized trials have proved that. We aim to investigate whether JBT could decrease the SB occlusion rate. Methods: Conventional versus Intentional straTegy in patients with high Risk prEdiction of Side branch OccLusion in coronary bifurcation interVEntion (CIT-RESOLVE) (NCT02644434, registered on December 31, 2015) (https://clinicaltrials.gov) is a randomized trial that assessed the effects of different strategies on SB occlusion rate in patients with a high risk of SB occlusion. The present subgroup analysis enrolled bifurcation lesions (2 mm ≤ reference vessel diameter of SB < 2.5 mm) with Visual estimation for Risk prEdiction of Side branch OccLusion in coronary bifurcation intervention (V-RESOLVE) score ≥ 12 points. The primary endpoint is SB occlusion. One-year clinical events were compared. Results: A total of 284 subjects at 16 sites were randomly assigned to the JBT group (n = 143) or the JWT group (n = 141). The rate of SB occlusion (9.1 vs. 19.9%, p = 0.02) and periprocedural myocardial infarction (defined by WHO, 7 vs. 14.9%, p = 0.03) is significantly lower in the JBT group than in the JWT group. The JBT and JWT groups showed no significant differences in cardiac death (0.7 vs. 0.7%, p = 1), myocardial infarction (MI, 6.3 vs. 7.1%, p = 0.79), target lesion revascularization (TLR, 1.4 vs. 2.1%, p = 0.68), and major cardiac adverse events (MACE, a composite of all-cause death, MI, or TLR, 8.4 vs. 10.6%, p = 0.52) during a 1-year follow-up. Conclusion: In patients with a high risk of SB occlusion (V-RESOLVE score ≥ 12 points), JBT is superior to JWT in reducing SB occlusion. However, no significant differences were detected in 1-year MACE.

The Predictive Value of Baseline Target Lesion SYNTAX Score for No-Reflow during Urgent Percutaneous Coronary Intervention in Acute Myocardial Infarction.

OBJECTIVES: To evaluate the predictive value of target lesion SYNTAX score (TL-SS) for no-reflow in the patients with acute myocardial infarction undergoing urgent percutaneous coronary intervention (PCI). BACKGROUND: Risk assessment, prevention, and prompt management of no-reflow in urgent PCI are crucial but remain challenging. SYNTAX score emerged as a tool for prediction, but may contain redundant information. METHODS: After screening of consecutive patients who underwent urgent PCI in Fuwai Hospital from January 2013 to December 2013, 487 patients with 528 lesions were involved. The endpoint was no-reflow during the PCI procedure. RESULTS: No-reflow occurred in 52 patients (10.7%) and 53 lesions (10.0%). High TL-SS levels were strongly associated with increased risks of no-reflow in the urgent PCI procedure (all adjusted P < 0.05). TL-SS displayed good discrimination ability for no-reflow (C-statistics = 0.76, 95% CI 0.72-0.80), which was better than that of SYNTAX score (P=0.016). Following categorizing the lesions into two groups according to the Youden Index, the high-risk group (TL-SS ≥8) showed significantly higher no-reflow rate compared with the low-risk group (TL-SS <8) (20.6% vs. 3.6%, odds ratio 6.86, 95% confidence interval 3.50-13.41, P < 0.001). In the target lesions that underwent balloon predilation, maximum predilation pressure >10 atm was associated with higher rate of no-reflow in the high-risk group (odds ratio 3.81, 95% confidence interval 1.10-13.17). CONCLUSIONS: TL-SS is a potential predictor for risk stratification of no-reflow in urgent PCI. In the high TL-SS lesions that underwent balloon predilation, maximum predilation pressure >10 atm was associated with higher risk of no-reflow.

In Silico Multi-Compartment Detection Based on Multiplex Immunohistochemical Staining in Renal Pathology.

With the rapid advancement in multiplex tissue staining, computer hardware, and machine learning, computationally-based tools are becoming indispensable for the evaluation of digital histopathology. Historically, standard histochemical staining methods such as hematoxylin and eosin, periodic acid-Schiff, and trichrome have been the gold standard for microscopic tissue evaluation by pathologists, and therefore brightfield microscopy images derived from such stains are primarily used for developing computational pathology tools. However, these histochemical stains are nonspecific in terms of highlighting structures and cell types. In contrast, immunohistochemical stains use antibodies to specifically detect and quantify proteins, which can be used to specifically highlight structures and cell types of interest. Traditionally, such immunofluorescence-based methods are only able to simultaneously stain a limited number of target proteins/antigens, typically up to three channels. Fluorescence-based multiplex immunohistochemistry (mIHC) is a new technology that enables simultaneous localization and quantification of numerous proteins/antigens, allowing for the possibility to detect a wide range of histologic structures and cell types within tissue. However, this method is limited by cost, specialized equipment, technical expertise, and time. In this study, we implemented a deep learning-based pipeline to synthetically generate in silico mIHC images from brightfield images of tissue slides-stained with routinely used histochemical stains, in particular PAS. Our tool was trained using fluorescence-based mIHC images as the ground-truth. The proposed pipeline offers high contrast detection of structures in brightfield imaged tissue sections stained with standard histochemical stains. We demonstrate the performance of our pipeline by computationally detecting multiple compartments in kidney biopsies, including cell nuclei, collagen/fibrosis, distal tubules, proximal tubules, endothelial cells, and leukocytes, from PAS-stained tissue sections. Our work can be extended for other histologic structures and tissue types and can be used as a basis for future automated annotation of histologic structures and cell types without the added cost of actually generating mIHC slides.

A pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) (NET and undifferentiated carcinoma of the pancreas with osteoclast-like giant cells) with metastatic neuroendocrine component to the liver.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGCs) is an extremely rare morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC), exhibiting a characteristic component of reactive osteoclast-like giant cells admixed with neoplastic mononuclear cells. Sommers and Meissner first described it in 1954 as an "unusual carcinoma of the pancreas". Later it acquired many different names. In 2010, the WHO classified these tumors as a variant of PDAC under the heading of "undifferentiated carcinoma with osteoclast-like giant cells". Here we describe the first case of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) composed of UCOGC and pancreatic neuroendocrine tumor (NET), which occurred in a 78-year-old man with biliary colic and pancreatitis. The mass did not respond to the chemotherapy, and he soon developed liver metastasis from the NET component, and unfortunately, the patient passed away 10 months later. Since UCOGC is extremely rare, and its association with NET has not been reported yet, our case expands the knowledge regarding its unusual presentation and poor prognosis.

A Scoring System to Predict No-Reflow Phenomenon in Elective Percutaneous Coronary Intervention: The RECOVER Score.

The RECOVER score system aimed to stratify the risk of no-reflow phenomenon in patients undergoing elective percutaneous coronary intervention. A total of 3967 patients with 5340 lesions were used for the construction and validating of the risk model and score system. In multivariable analyses, 3 variables were independently associated with the risk of no-reflow phenomenon (model C-statistic=0.746 (95% confidence interval [CI]: 0.690 to 0.803) with good calibration). No-reflow phenomenon rates in both construction and validation cohort increased significantly across different risk groups. The RECOVER score can help identify patients at risk for phenomenon during percutaneous coronary intervention.

Validation of the DAPT score in large-scale consecutive and contemporary patients population in the real world.

Dual antiplatelet therapy (DAPT) score emerged as a tool for quantification of ischemia and bleeding risks. However, there was discrepancy of the prediction ability of DAPT score in previous studies. We aimed to assess the utility of DAPT score in a large-scale cohort of consecutive percutaneous coronary intervention (PCI) patients. This study enrolled 9,114 patients who had undergone PCI at Fuwai Hospital in 2013, adhered to DAPT and were event-free within the first 12 months following PCI. The endpoints included primary ischemic endpoints (major adverse cardiovascular and cerebrovascular events, and myocardial infarction and/or stent thrombosis), and bleeding endpoint from 12 through 24 months after PCI. Patients were classified into low (score <2, n = 3,989) and high (score ≥2, n = 5,125) DAPT score groups. The incidence rates of primary ischemic endpoints and bleeding endpoint were similar between the two groups. Multivariable analysis demonstrated DAPT score not to be an independent predictor of primary ischemic endpoints or bleeding endpoint. Based on receiver operating characteristic curves analysis, the C-statistic of DAPT score for primary ischemic endpoints or bleeding endpoint did not achieve a significant extent. In this large-scale cohort of PCI patients, DAPT score did not discriminate the risks of ischemic and bleeding events.

A pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) (NET and undifferentiated carcinoma of the pancreas with osteoclast-like giant cells) with metastatic neuroendocrine component to the liver

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGCs) is an extremely rare morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC), exhibiting a characteristic component of reactive osteoclast-like giant cells admixed with neoplastic mononuclear cells. Sommers and Meissner first described it in 1954 as an "unusual carcinoma of the pancreas". Later it acquired many different names. In 2010, the WHO classified these tumors as a variant of PDAC under the heading of "undifferentiated carcinoma with osteoclast-like giant cells". Here we describe the first case of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) composed of UCOGC and pancreatic neuroendocrine tumor (NET), which occurred in a 78-year-old man with biliary colic and pancreatitis. The mass did not respond to the chemotherapy, and he soon developed liver metastasis from the NET component, and unfortunately, the patient passed away 10 months later. Since UCOGC is extremely rare, and its association with NET has not been reported yet, our case expands the knowledge regarding its unusual presentation and poor prognosis.

Polyclonal CD5+/CD19+ B1a lymphocytes after allogeneic stem cell transplantation: a potential diagnostic pitfall.

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Improving the accuracy of gastrointestinal neuroendocrine tumor grading with deep learning.

The Ki-67 index is an established prognostic factor in gastrointestinal neuroendocrine tumors (GI-NETs) and defines tumor grade. It is currently estimated by microscopically examining tumor tissue single-immunostained (SS) for Ki-67 and counting the number of Ki-67-positive and Ki-67-negative tumor cells within a subjectively picked hot-spot. Intraobserver variability in this procedure as well as difficulty in distinguishing tumor from non-tumor cells can lead to inaccurate Ki-67 indices and possibly incorrect tumor grades. We introduce two computational tools that utilize Ki-67 and synaptophysin double-immunostained (DS) slides to improve the accuracy of Ki-67 index quantitation in GI-NETs: (1) Synaptophysin-KI-Estimator (SKIE), a pipeline automating Ki-67 index quantitation via whole-slide image (WSI) analysis and (2) deep-SKIE, a deep learner-based approach where a Ki-67 index heatmap is generated throughout the tumor. Ki-67 indices for 50 GI-NETs were quantitated using SKIE and compared with DS slide assessments by three pathologists using a microscope and a fourth pathologist via manually ticking off each cell, the latter of which was deemed the gold standard (GS). Compared to the GS, SKIE achieved a grading accuracy of 90% and substantial agreement (linear-weighted Cohen's kappa 0.62). Using DS WSIs, deep-SKIE displayed a training, validation, and testing accuracy of 98.4%, 90.9%, and 91.0%, respectively, significantly higher than using SS WSIs. Since DS slides are not standard clinical practice, we also integrated a cycle generative adversarial network into our pipeline to transform SS into DS WSIs. The proposed methods can improve accuracy and potentially save a significant amount of time if implemented into clinical practice.

Polyclonal CD5+/CD19+ B1a lymphocytes after allogeneic stem cell transplantation: a potential diagnostic pitfall

In adults, B-lymphocytes comprise approximately 10% of circulating lymphocytes. The majority of peripheral B cells are B2 cells ("Mature" B-cells), which function as part of the humoral adaptive immune system. B1 cells ("Innate-like" B cells) are another sub-class of B lymphocytes, considered as innate immune cells with a characteristic phenotype (CD20+, CD27+, CD43+, CD70-, CD11b+, sIgM++, sIgD+) which can be divided into two subtypes; B1a (CD5+): spontaneously produce broadly reactive natural IgM, and B1b (CD5-): can generate T-cell independent, long-lasting IgM. There is very limited data available, indicating a correlation between allogeneic bone marrow transplantation and an increase in B1a cells. Here we present a case of a 17-year-old female with homozygous sickle cell disease (HbSS disease) who underwent hematopoietic stem cell transplant (HSCT). Approximately seven months post-transplant, she was found to have 16% immature mononuclear cells on complete blood count (CBC)-differential report. A follow-up peripheral blood flow cytometry showed that these cells were polyclonal CD5+/CD20+ B-cells, and comprised 66% of lymphocytes. Further workup and follow up failed to reveal any lymphoproliferative disorders. It is important not to misdiagnose these cells as an atypical CD5+ lymphoproliferative disorder. The presence of B1a cells has not been widely reported in non-neoplastic post-stem cell transplanted patients. This case also adds to and expands our knowledge regarding the presence of increased circulating B1a cells after stem cell transplant in a patient with no history of hematological malignancy.

Acetaminophen interference with Nova StatStrip® Glucose Meter: case report with bench top confirmation.

Context: Point-of-care glucose meters are an integral part in the assessment of patients with altered mental status. For this reason, glucose meters are checked for interference from commonly encountered substances, including acetaminophen. The Nova StatStrip® glucose meter has previously been reported to be resistant to interference. We report a case of a very high acetaminophen concentration causing interference with this point-of-care glucose meter.Case report: A 25-year-old female presented after an overdose of acetaminophen and diphenhydramine combination product. Patient was minimally responsive, so a point-of-care glucose check was attempted using the Nova StatStrip® glucose meter. Five different meters were attempted, and each showed an error message. Laboratory analysis using Beckman Coulter® Unicel DxC 800 revealed a glucose of 180 mg/dL and an acetaminophen concentration of 465 mg/L. Serum spiked with acetaminophen at different concentrations revealed interference with the Nova StatStrip® glucose meter at a concentration of 399 mg/L and above. To our knowledge, this interference with the Nova StatStrip® glucose meter has not been reported in the medical literature.Conclusion: Very high levels of acetaminophen can interfere with point-of-care glucose meters, even those that have previously been reported to be robust such as the Nova StatStrip® glucose meter. Clinicians should be aware of this possible interference when treating patients with acetaminophen overdose.

Gleason pattern 4 with cribriform morphology on biopsy is associated with adverse clinicopathological findings in a prospective radical prostatectomy cohort.

The prognostic significance of the Gleason grading system has been well established. However, individual Gleason patterns comprise heterogeneous morphologies which might add additional prognostic information. Recent evidence suggests that Gleason pattern 4 with cribriform growth pattern is associated with an adverse prognosis. To determine the association between cribriform pattern on biopsies and pathological findings on subsequent prostatectomies, we evaluated the presence of cribriform architecture in a prospective cohort of 367 men from 2014 to 2018 treated at a single institution. Cribriform architecture was present in 63.5% of all biopsies and was correlated with the overall extent of Gleason pattern 4. In addition, cribriform morphology on biopsy showed a statistically significant association with higher Gleason grade and increased pathological stage and nodal metastasis. In a subset analysis of cases with Grade Group 2 (Gleason score 3 + 4, n = 208), these associations did not reach statistical significance, but the presence of cribriform growth in this subgroup showed a trend toward increased upgrading to Grade Group 5 (Gleason score 9/10) (1 [0.5%] vs. 5 [2.4%], P = 0.06). This large prospective study comparing biopsy and prostatectomy finding of cribriform architecture demonstrates that cribriform pattern 4 is associated with adverse prognostic features and highlights the relevance for recognizing specific morphologies with distinct biological and clinical features.

Integrating the residual SYNTAX score to improve the predictive ability of the age, creatinine, and ejection fraction (ACEF) score for cardiac mortality in percutaneous coronary intervention patients.

OBJECTIVES: To improve the prognostic value of the age, creatinine, and ejection fraction (ACEF) score following percutaneous coronary intervention (PCI) by integrating the residual SYNTAX score (rSS). BACKGROUND: ACEF score was proposed for predicting the operative mortality risk in elective cardiac operations and has been validated in numerous studies. However, it does not incorporate coronary lesion-based variables for risk assessment of patients who undergo PCI. METHODS: Overall, 10,072 patients who underwent PCI at our hospital in 2013 were enrolled. The endpoint was 2-year cardiac death after PCI, defined as death that was not attributed to a non-cardiac cause. ACEF-rSS was constructed with incremental weights attributed to the ACEF score and rSS according to their estimated coefficients. RESULTS: 2-year cardiac death occurred in 63 patients (0.63%). In multivariable analyses, the ACEF score and rSS > 8 were independently associated with the risk of cardiac death. ACEF-rSS was computed as age (years)/ejection fraction (%) + 1 (if creatinine ≥2.0 mg/dl) + 1 (if rSS >8). The discrimination of ACEF-rSS was significantly better than that of the ACEF score based on receiver operating characteristic (ROC) curve analysis and integrated discrimination improvement (IDI) (C-statistics = 0.835 vs. 0.776 for ACEF-rSS and ACEF score, respectively, p = .029; IDI = 0.014, p < .001). Compared with all other SYNTAX-derived risk scores, ACEF-rSS had significantly better discrimination ability based on ROC curve analysis, net reclassification improvement, and IDI. CONCLUSIONS: Combining the ACEF score with rSS to produce the ACEF-rSS enhanced the predictive ability for long-term cardiac mortality.