Pathology Education Powered by Virtual and Digital Transformation: Now and the Future.

CONTEXT.­: Myriad forces are changing teaching and learning strategies throughout all stages and types of pathology education. Pathology educators and learners face the challenge of adapting to and adopting new methods and tools. The digital pathology transformation and the associated educational ecosystem are major factors in this setting of change. OBJECTIVE.­: To identify and collect resources, tools, and examples of educational innovations involving digital pathology that are valuable to pathology learners and teachers at each phase of professional development. DATA SOURCES.­: Sources were a literature review and the personal experience of authors and educators. CONCLUSIONS.­: High-quality digital pathology tools and resources have permeated all the major niches within anatomic pathology and are increasingly well applied to clinical pathology for learners at all levels. Coupled with other virtual tools, the training landscape in pathology is highly enriched and much more accessible than in the past. Digital pathology is well suited to the demands of peer-to-peer education, such as in the introduction of new testing, grading, or other standardized practices. We found that digital pathology was well adapted to apply our current understanding of optimal teaching strategies and was effective at the undergraduate, graduate, postgraduate, and peer-to-peer levels. We curated and tabulated many existing resources within some segments of pathology. We identified several best practices for each training or educational stage based on current materials and proposed high-priority areas for potential future development.

Intraventricular neurocysticercosis causing obstructing hydrocephalus.

Neurocysticercosis is a parasitic infection caused by the larval stage of the pork tapeworm Taenia solium. Diagnostic criteria for neurocysticercosis are based on clinical manifestations, neuroimaging findings, and epidemiologic exposure. Treatment is tailored to acute symptoms. If increased intracranial pressure is present, then surgical intervention and/or corticosteroids may be used. If seizures are present, then antiepileptic drugs are used for therapy. Antiparasitic therapy is warranted for patients with viable and/or degenerating cysts in the brain parenchyma on neuroimaging. We present a case report of neurocysticercosis causing obstructive hydrocephalus requiring a ventriculoperitoneal shunt.

An unusual myeloid sarcoma.

Myeloid sarcoma is a tumor mass of immature myeloid or monocytic cells (rarely erythroid or megakaryocytic) occurring in an extramedullary site. A de novo promyelocytic granulocytic sarcoma is a very rare tumor. We report a case of a young man presenting with a paraspinal myeloid sarcoma of promyelocytic origin.

Unraveling unique and common cell type-specific mechanisms in glioblastoma multiforme.

Glioblastoma multiforme persists to be an enigmatic distress in neuro-oncology. Its untethering capacity to thrive in a confined microenvironment, metastasize intracranially, and remain resistant to the systemic treatments, renders this tumour incurable. The glial cell type specificity in GBM remains exploratory. In our study, we aimed to address this problem by studying the GBM at the cell type level in the brain. The cellular makeup of this tumour is composed of genetically altered glial cells which include astrocyte, microglia, oligodendrocyte precursor cell, newly formed oligodendrocyte and myelinating oligodendrocyte. We extracted cell type-specific solid tumour as well as recurrent solid tumour glioma genes, and studied their functional networks and contribution towards gliomagenesis. We identified the principal transcription factors that are found to be regulating vital tumorigenic processes. We also assessed the protein-protein interaction networks at their domain level to get a more microscopic view of the structural and functional operations that transpire in these cells. This yielded the eminent protein regulators exhibiting their regulation in signaling pathways. Overall, our study unveiled regulatory mechanisms in glioma cell types that can be targeted for a more efficient glioma therapy.

Actinomyces causing a brain abscess.

Actinomycosis is an uncommon, chronic granulomatous disease caused by the filamentous, gram-positive bacterium Actinomyces israelii. It causes indolent, painful wound infections commonly presenting with oral-cervicofacial manifestations, but other infections of the chest wall and gastrointestinal and genital tract are also seen. A high level of suspicion is required for diagnosis, as it may be missed or mistaken for malignancy. Severe cases may involve the central nervous system and require surgical intervention. We present a case report of actinomycosis causing a brain abscess.

Bradycardia in Recent Heart Transplant: Will the Microscope Illuminate the True Answer?CME.

Transplant recipients are at risk of developing rejection that may cause significant morbidity and mortality following transplantation The clinical presentation of rejection may be atypical, leading to difficulties in diagnosis and management especially in cases with a nondiagnostic biopsy specimen. The emergence of artificial intelligence may aid in clinical decision making when traditional techniques are inconclusive.

Network Analysis Identifies Drug Targets and Small Molecules to Modulate Apoptosis Resistant Cancers.

Programed cell death or apoptosis fails to induce cell death in many recalcitrant cancers. Thus, there is an emerging need to activate the alternate cell death pathways in such cancers. In this study, we analyzed the apoptosis-resistant colon adenocarcinoma, glioblastoma multiforme, and small cell lung cancers transcriptome profiles. We extracted clusters of non-apoptotic cell death genes from each cancer to understand functional networks affected by these genes and their role in the induction of cell death when apoptosis fails. We identified transcription factors regulating cell death genes and protein-protein interaction networks to understand their role in regulating cell death mechanisms. Topological analysis of networks yielded FANCD2 (ferroptosis, negative regulator, down), NCOA4 (ferroptosis, up), IKBKB (alkaliptosis, down), and RHOA (entotic cell death, down) as potential drug targets in colon adenocarcinoma, glioblastoma multiforme, small cell lung cancer phenotypes respectively. We also assessed the miRNA association with the drug targets. We identified tumor growth-related interacting partners based on the pathway information of drug-target interaction networks. The protein-protein interaction binding site between the drug targets and their interacting proteins provided an opportunity to identify small molecules that can modulate the activity of functional cell death interactions in each cancer. Overall, our systematic screening of non-apoptotic cell death-related genes uncovered targets helpful for cancer therapy.

Histologic patterns of lung injury in patients using e-cigarettes.

In recent years, e-cigarette use has become more popular. Until recently, it was considered safer than smoking. We report two cases of acute pulmonary illness associated with vaping, focusing on their histologic patterns.

Sports-Injury Encephalopathy.

Sports-related encephalopathies are a growing concern among athletes who have experienced head trauma. Anxiety is heightened for the public and especially among parents of children playing contact sports. The most common neuropsychological conditions are concussions and traumatic encephalopathies. Concussions result from brain traumas that can be asymptomatic, but more serious concussions can include loss of consciousness, neurological abnormalities, and/or posttraumatic amnesias. Repetitive concussions lead to persistent brain pathology, known as chronic traumatic encephalopathies. This gradually progressive neurodegenerative disease frequently presents with cognitive and neurological deficits, which can result in significant parkinsonian features and dementia. Imaging studies may be noncontributory; however, diffusion tensor imaging, magnetic resonance spectroscopy, and functional magnetic resonance imaging can detect changes indicative of these encephalopathies. Progressive neuronal degeneration with tau proteins are documented on pathological examination. Prevention, early diagnosis, and proper treatment are the recommended approach to these conditions.

Comparison of Clinical and Morphologic Findings in Patients With Cardiac Sarcoidosis Severe Enough to Warrant Heart Transplantation in Those With -vs- Those Without Non-Caseating Granulomas in the Explanted Heart (Burnt-Out Sarcoid).

Can cardiac sarcoidosis with heart failure severe enough to warrant orthotopic heart transplantation (OHT) be present without non-caseating granulomas in the explanted heart? The objective is to compare clinical and morphological features in patients with cardiac sarcoidosis severe enough to warrant OHT with -vs-without non-caseating granulomas in the explanted heart. The study was conducted at Baylor University Medical Center in Dallas, Texas. From a total of 671 explanted hearts examined from 1993 to 2018, twenty-five (4%) had gross morphologic features characteristic of cardiac sarcoidosis. At the time of OHT, the patients ranged in age from 50 to 69 years [mean 57]. Cardiac sarcoidosis was diagnosed before OHT in 3 (12%) patients, by percutaneous biopsy of the heart in 2 patients and by histologic examination of the "left ventricular core" in 1 patient who had a left ventricular assist device inserted, and, by examination of the native heart after OHT in the remaining 22 (88%) patients. Of the 25 patients, 16 (64%) had typical sarcoid non-caseating granulomas in the explanted heart, and 9 (36%) had no granulomas in the explanted heart. Comparison of certain clinical and morphologic features in the group with -vs- the group without cardiac granulomas showed no significant differences. In conclusion, of patients with cardiac sarcoidosis severe enough to warrant OHT, some have typical non-caseating granulomas in the explanted heart and some do not. The clinical and gross morphologic features of those with and those without cardiac granulomas are similar.

The Mitral Valve 16 Months After Operative Insertion of the Alfieri Stitch.

We describe considerable fibrous thickening of the mitral leaflets 16 months after insertion of an Alfieri stitch in a previously anatomically normal but functionally regurgitant mitral valve. Whether this type of mitral thickening will occur after percutaneous insertion of the mitral clip for pure mitral regurgitation remains to be determined.

Effectiveness of continuous versus single injection femoral nerve block for total knee arthroplasty: A double blinded, randomized trial.

BACKGROUND: Effective analgesia following total knee arthroplasty (TKA) is important for maximizing patient satisfaction, early participation in physical therapy and reducing the hospital stay. This trial compared continuous catheter femoral nerve block (cFNB) to single injection femoral nerve block (sFNB) in terms of analgesia, opioid consumption, and participation in physical therapy and associated side effects. METHODS: This randomized, double blinded trial was conducted in a non-university hospital setting, without major changes to anesthesia or surgical clinical pathways. A total of 85 patients scheduled for primary TKA were randomized to receive either cFNB (n=44) or sFNB (n=41). All patients had FNB with 0.5% ropivacaine bolus followed by subarachnoid block for surgery. Postoperatively, 0.2% ropivacaine infusion was commenced in cFNB group and a sham catheter was taped to the skin in sFNB group. All patients received a structured multimodal analgesia regimen throughout hospital stay. The primary outcomes were peak resting visual analogue scale (VAS) scores and morphine consumption at 48h postoperatively. RESULTS: VAS scores (Mean difference 0.25, 95% Confidence Interval (CI) -0.56 to 1.06; [P=0.196]) and morphine consumption (Mean difference 0.95mg, 95% CI -9.99 to 11.89; [P=0.863]) were not significantly different among patients who received cFNB versus sFNB at 48h. There was no difference in hospital stay (P=0.517) or long-term functional recovery between the two groups (P=0.385). CONCLUSIONS: sFNB block provides equal pain relief compared with cFNB, after TKA with no significant difference in opioid consumption, hospital stay, physical therapy outcomes or associated side effects.

Clinical outcomes of current medical approaches for Middle East respiratory syndrome: A systematic review and meta-analysis.

Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus. Because of lack of vaccination, various studies investigated the therapeutic efficacy of antiviral drugs and supportive remedies. A systematic literature search from 10 databases was conducted and screened for relevant articles. Studies reporting information about the treatment of MERS coronavirus infection were extracted and analyzed. Despite receiving treatment with ribavirin plus IFN, the case fatality rate was as high as 71% in the IFN-treatment group and exactly the same in patients who received supportive treatment only. Having chronic renal disease, diabetes mellitus and hypertension increased the risk of mortality (P < .05), and chronic renal disease is the best parameter to predict the mortality. The mean of survival days from onset of illness to death was 46.6 (95% CI, 30.5-62.6) for the IFN group compared with 18.8 (95% CI, 10.3-27.4) for the supportive-only group (P = .001). Delay in starting treatment, older age group, and preexisting comorbidities are associated with worse outcomes. In conclusion, there is no difference between IFN treatment and supportive treatment for MERS patients in terms of mortality. However, ribavirin and IFN combination might have efficacious effects with timely administration and monitoring of adverse events. Large-scale prospective randomized studies are required to assess the role of antiviral drugs for the treatment of this high mortality infection.

Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo.

The Kelch-like erythroid-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) signaling pathway is the subject of several clinical trials evaluating the effects of Nrf2 activation on the prevention of cancer and diabetes and the treatment of chronic kidney disease and multiple sclerosis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two distinct series of Nrf2 chemical activators. Previous reports have described activator-specific effects on Nrf2-dependent gene regulation and physiologic outcomes. Here we used a robust chemical genomics approach to characterize expression profiles between D3T and CDDO-Im in livers from wild-type and Nrf2-null mice. At equally efficacious doses in wild-type mice, 406 genes show common RNA responses to both treatments. These genes enriched the Nrf2-regulated pathways of antioxidant defense and xenobiotic metabolism. In addition, 197 and 745 genes were regulated uniquely in response to either D3T or CDDO-Im, respectively. Functional analysis of the D3T-regulated set showed a significant enrichment of Nrf2-regulated enzymes involved in cholesterol biosynthesis. This result was supported by Nrf2-dependent increases in lanosterol synthase and CYP51 protein expression. CDDO-Im had no effect on cholesterol biosynthesis regardless of the dose tested. However, unlike D3T, CDDO-Im resulted in Nrf2-dependent elevation of peroxisome proliferator α and Kruppel-like factor 13, as well as the coactivator peroxisome proliferator γ coactivator 1ß, together indicating regulation of ß-oxidation and lipid metabolic pathways. These findings provide novel insights into the pharmacodynamic action of these two activators of Keap1-Nrf2 signaling. Although both compounds modify Keap1 to affect canonical cytoprotective gene expression, additional unique sets of Nrf2-dependent genes were regulated by each agent with enrichment of selective metabolic pathways.

Obesity Cardiometabolic Comorbidity Prevalence in Children in a Rural Weight-Management Program.

This descriptive study examines the prevalence of obesity-related cardiometabolic (CM) risk factors using CM laboratory metrics, in 3 to 19 year olds presenting to a rural American Academy of Pediatrics stage 3 multidisciplinary weight management clinic based on gender, age ranges, and obesity classes. From 2009 to 2016, 382 children (body mass index ≥85th percentile) enrolled. Multiple logistic regression determined the effects of age, gender, or obesity class on CM risk factors. Odds of elevated insulin were more significant in 15 to 19 year olds than in 3 to 5 year olds, or in 6 to 11 year olds. Obesity class III had higher odds than class II, class I, and overweight in having elevated insulin; twice likely than class II for having low high-density lipoprotein; and twice as likely than class I for high triglycerides. Adolescents and obesity class III categories have significant CM risk but the burden in younger and less severe obesity cohorts cannot be underestimated.

Establishment of the Pediatric Obesity Weight Evaluation Registry: A National Research Collaborative for Identifying the Optimal Assessment and Treatment of Pediatric Obesity.

BACKGROUND: Prospective patient registries have been successfully utilized in several disease states with a goal of improving treatment approaches through multi-institutional collaboration. The prevalence of youth with severe obesity is at a historic high in the United States, yet evidence to guide effective weight management is limited. The Pediatric Obesity Weight Evaluation Registry (POWER) was established in 2013 to identify and promote effective intervention strategies for pediatric obesity. METHODS: Sites in POWER provide multicomponent pediatric weight management (PWM) care for youth with obesity and collect a defined set of demographic and clinical parameters, which they regularly submit to the POWER Data Coordinating Center. A program profile survey was completed by sites to describe characteristics of the respective PWM programs. RESULTS: From January 2014 through December 2015, 26 US sites were enrolled in POWER and had submitted data on 3643 youth with obesity. Ninety-five percent were 6-18 years of age, 54% female, 32% nonwhite, 32% Hispanic, and 59% publicly insured. Over two-thirds had severe obesity. All sites included a medical provider and used weight status in their referral criteria. Other program characteristics varied widely between sites. CONCLUSION: POWER is an established national registry representing a diverse sample of youth with obesity participating in multicomponent PWM programs across the United States. Using high-quality data collection and a collaborative research infrastructure, POWER aims to contribute to the development of evidence-based guidelines for multicomponent PWM programs.

Using a Patient Portal to Transmit Patient Reported Health Information into the Electronic Record: Workflow Implications and User Experience.

INTRODUCTION: This project implemented an integrated patient self-reported screening tool in a patient portal and assessed clinical workflow and user experience in primary care practices. METHODS: An electronic health risk assessment based on the CMS Annual Wellness Visit (AWV) was developed to integrate self-reported health information into the patient's electronic health record (EHR). Patients enrolled in care coordination tested the implementation. The evaluation plan included quantitative and qualitative measures of patient adoption, provider adoption, workflow impact, financial impact, and technology impact. FINDINGS: Seventy-two patients completed the sample AWV, and 80% of the questionnaires had clinical findings that required provider follow-up. Patients expressed satisfaction with the portal, as it enabled them to view their health record and enter information. Implementation did not reduce office staff time. Providers and office staff agreed that an electronic system for adding information to their record would increase patient satisfaction, but they expressed concern with the need to promptly review the information and the time involved to accomplish this prior to an office visit. DISCUSSION: Despite satisfaction among patients, portal adoption is still low, due to technological limitations and to the lack of adaptability to primary care practice workflow. Notwithstanding those barriers, the use of the portal for completion of repetitive tasks, such as screening tools, should be encouraged. CONCLUSIONS: Patients can effectively use portals to complete the patient reported section of the CMS AWV. However, if the information is not completed during the same day of the office visit, the time required to address health findings outside of a regular office visit is uncompensated, and diminished the enthusiasm for this process among primary care practice staff.

Effects of tranexamic acid and bipolar sealer alone or in combination in primary total knee arthroplasty: a prospective, randomized, controlled trial.

BACKGROUND: The purpose of this study was to compare 2 blood management interventions, tranexamic acid (TXA) and bipolar sealer system (BSS) used independently or in combination with a control group during primary total knee arthroplasty (TKA). METHODS: A total of 127 TKA patients were enrolled and randomized into 4 groups: Intravenous TXA plus the BSS (N = 29, group 1); TXA only (N = 29, group 2); BSS only (N = 31, group 3); and intravenous normal saline as a control group (N = 32, group 4). RESULTS: Changes in hemoglobin from baseline to postoperative follow-up were significantly lower among patients who received TXA plus BSS and those receiving TXA only when compared with the control. BSS only did not differ significantly when compared to the control group. In addition, TXA plus BSS was as efficacious as TXA only in preserving postoperative hemoglobin. CONCLUSIONS: In other terms, using bipolar sealer did not add to the effect of TXA in reducing the postoperative hemoglobin drop in primary TKA.

Patient Portal as a Tool for Enhancing Patient Experience and Improving Quality of Care in Primary Care Practices.

INTRODUCTION: This study assessed whether patient portals influence patients' ability for self-management, improve their perception of health state, improve their experience with primary care practices, and reduce healthcare utilization. METHODS: Patients participating in a nurse-led care coordination program received personalized training to use the portal to communicate with the care team. Data analysis included pre-post comparison of self-efficacy (CDSES), health state (EQVAS), functional status (PROMIS®), experience with the provider/practice (CG-CAHPS), and healthcare utilization (admissions and ED visits). RESULTS: A total of 94 patients were enrolled, and 92 (Intent to Treat) were followed up for 7 months to assess their experience, and for 12 months to assess healthcare utilization. Seventy four (mean age 60+13 years) used the portal (Users). Comparison between baseline and 7-month follow-up showed no statistically significant improvements in self-efficacy, perception of health state or experience with the primary care practice. Only functional status improved significantly. ED visits/1000 patients were reduced by 26% and 21% in the Intent to Treat and Users groups, respectively. Hospital admissions/1000 patients were reduced by 46% in the Intent to Treat group and by 38% in the Users group. DISCUSSION: For patients in care coordination, having access to patient portals may improve access to providers and health data that lead to improvements in patients' functional status and reduce high-cost healthcare utilization, but it does not seem to improve self-efficacy, perception of health state, or experience with primary care practices. CONCLUSION: In this study, the use of patient portals improved functional status and reduced high-cost healthcare utilization in patients with chronic conditions.