Esophageal squamous cell carcinoma with pagetoid spread: a clinicopathologic study.

Pagetoid spread in esophageal squamous epithelium associated with underlying esophageal adenocarcinoma (EAC) has been well studied. Case reports describing pagetoid spread of esophageal squamous cell carcinomas (ESCC) also exist in the literature. The latter, however, has not been systematically studied. In this study, we report seven cases of pagetoid spread associated with ESCC. The clinical, morphologic, and immunophenotypic profiles of pagetoid spread in the context of ESCC and EAC are compared. Cases of pagetoid spread of ESCC were identified through computerized search of pathology archives at five institutions. Additional cases were identified through manual review of surgical resection cases of treatment naive ESCC in Mass General Brigham (MGB) pathology archive. Clinical history was collected via chart review. Immunohistochemistry for CK7, CK20, CDX2, p53, p63, and p40 was performed on selected cases. A computerized search of pathology archives of five institutions revealed only two cases. A manual review of 76 resected untreated ESCC revealed five additional cases with unequivocal pagetoid spread of ESCC, indicating the condition was not uncommon but rarely reported. Patient age ranged from 54 to 78 years (median, 65). There were six women and one man. One case had in situ disease, five had pT1 (1 pT1a and 4 pT1b), and one had pT3 disease. One of the patients with pT1 tumor had a positive lymph node, while the remaining six patients were all N0. Four tumors were in the proximal to mid esophagus, and three in the distal esophagus. Patient survival ranged from 25 months to more than 288 months. The pagetoid tumor cells demonstrated enlarged, hyperchromatic nuclei with variable amounts of eosinophilic cytoplasm. The cytoplasm was often condensed to the perinuclear area, creating peripheral clearing. By immunohistochemistry, the pagetoid cells were positive for p40 (6/6) and p63 (7/7) and negative for CDX2 (7/7). The tumor cells showed mutant-type staining for p53 in five of seven cases. One of the patients had pagetoid tumor cells at the resection margin and subsequently had recurrent disease 2 years later. All other patients had negative resection margins and did not have local recurrence. Four cases of pagetoid spread in the context of EAC were used as a comparison group. Previously published studies were also analyzed. These tumors were all located in the distal esophagus or gastroesophageal junction. All cases were associated with underlying invasive EAC. Pagetoid spread associated with EAC often had cytoplasmic vacuoles or mucin. They were more frequently positive for CK7 than pagetoid ESCC (p = 0.01). Both ESCC and EAC may give rise to pagetoid spread of tumor cells within surface squamous epithelium. Pagetoid spread from ESCC and EAC have overlapping morphologic features. P40 and p63 immunostains can facilitate the distinction between ESCC and EAC. P53 immunostain can aid in confirmation of malignancy. Understanding their overlapping pathologic features will help pathologists avoid pitfalls and diagnose these lesions correctly on biopsy specimens.

Development and Clinical Evaluation of a Rapid Point of Care Test for Ebola Virus Infection in Humans.

The genus Ebolavirus contains multiple species of viruses that are highly contagious and lethal, often causing severe hemorrhagic fever. To minimize the global threat from Ebola virus disease (EVD), sustainable, field-appropriate tools are needed to quickly screen and triage symptomatic patients and conduct rapid screening of cadavers to ensure proper handling of human remains. The OraQuick® Ebola Rapid Antigen Test is an in vitro diagnostic single-use immunoassay for the qualitative detection of Ebola virus antigens that detects all known species within the genus Ebolavirus. Here, we report the performance of the OraQuick® Ebola Rapid Antigen Test and provide a comparison of its performance with other rapid diagnostic tests (RDTs) for EVD. OraQuick® Ebola demonstrated clinical sensitivity of 84.0% in archived EVD patient venous whole-blood (WB) samples, 90.9% in Ebola virus-infected monkey fingerstick samples, and 97.1% in EVD patient cadaver buccal swabs, as well as clinical specificity of 98.0-100% in venous WB samples and 99.1-100% in contrived saliva samples. It is the only 510(k)-cleared Ebola rapid test, has analytical sensitivity as good as or better than all RDT comparators for EVD, and can detect the Sudan virus. Our data demonstrate that the OraQuick® Ebola Rapid Antigen Test is a sensitive and specific assay that can be used for rapid detection of EBOV in humans and could support efforts for EVD-specific interventions and control over outbreaks.

Development and Clinical Performance of InteliSwab® COVID-19 Rapid Test: Evaluation of Antigen Test for the Diagnosis of SARS-CoV-2 and Analytical Sensitivity to Detect Variants of Concern Including Omicron and Subvariants.

BACKGROUND AND OBJECTIVES: Timely detection of SARS-CoV-2 infection with subsequent contact tracing and rapid isolation are considered critical to containing the pandemic, which continues with the emergence of new variants. Hence, there is an ongoing need for reliable point-of-care antigen rapid diagnostic tests (Ag-RDT). This report describes the development, evaluation, and analytical sensitivity of the diagnostic performance of the InteliSwab® COVID-19 Rapid Test. Methods: Samples from 165 symptomatic subjects were tested with InteliSwab® and the results were compared to RT-PCR to determine the antigen test performance. The analytical sensitivity of InteliSwab® for the detection of different variants was assessed by limit of detection (LOD) determination using recombinant nucleocapsid proteins (NPs) and testing with virus isolates. Western immunoblot independently confirmed that each monoclonal Ab is capable of binding to all variants tested thus far. RESULTS: The overall positivity rate by RT-PCR was 37% for the 165 symptomatic subjects. Based on RT-PCR results as the reference standard, InteliSwab® showed clinical sensitivity and specificity of 85.2% (95% CI, 74.3-92.0%) and 98.1% (95% CI, 93.3-99.7%), respectively. The overall agreement was 93.3% (Kappa index value 0.85; 95% CI, 0.77-0.74) between RT-PCR and InteliSwab® test results. Furthermore, the evaluation of analytical sensitivity for different SARS-CoV-2 variants by InteliSwab® was comparable in the detection of all the variants tested, including Omicron subvariants, BA.4, BA.5, and BQ.1. CONCLUSIONS: Due to the surge of infections caused by different variants from time to time, there is a critical need to evaluate the sensitivity of rapid antigen-detecting tests for new variants. The study findings showed the robust diagnostic performance of InteliSwab® and analytical sensitivity in detecting different SARS-CoV-2 variants, including the Omicron subvariants. With the integrated swab and excellent sensitivity and variant detection, this test has high potential as a point-of-care Ag-RDT in various settings when molecular assays are in limited supply and rapid diagnosis of SARS-CoV-2 is necessary.

Photoplethysmography behind the Ear Outperforms Electrocardiogram for Cardiovascular Monitoring in Dynamic Environments.

An increasing proportion of occupational mishaps in dynamic, high-risk operational environments have been attributed to human error, yet there are currently no devices to routinely provide accurate physiological data for insights into underlying contributing factors. This is most commonly due to limitations of commercial and clinical devices for collecting physiological data in environments of high motion. Herein, a novel Photoplethysmography (PPG) sensor device was tested, called SPYDR (Standalone Performance Yielding Deliberate Risk), reading from a behind-the-ear location, specifically designed for high-fidelity data collection in highly dynamic high-motion, high-pressure, low-oxygen, and high-G-force environments. For this study, SPYDR was installed as a functional ear-cup replacement in flight helmets worn by rated US Navy aircrew. Subjects were exposed to reduced atmospheric pressure using a hypobaric chamber to simulated altitudes of 25,000 feet and high G-forces in a human-rated centrifuge up to 9 G acceleration. Data were compared to control devices, finger and forehead PPG sensors, and a chest-mounted 12-lead ECG. SPYDR produced high-fidelity data compared to controls with little motion-artifact controls in the no-motion environment of the hypobaric chamber. However, in the high-motion, high-force environment of the centrifuge, SPYDR recorded consistent, accurate data, whereas PPG controls and ECG data were unusable due to a high-degree-motion artifacts. The data demonstrate that SPYDR provides an accurate and reliable system for continuous physiological monitoring in high-motion, high-risk environments, yielding a novel method for collecting low-artifact cardiovascular assessment data important for investigating currently inaccessible parameters of human physiology.

Evaluation of a pharmacy technician-based medication prior authorization program.

BACKGROUND: The roles of pharmacy technicians in clinical practice are being explored. Medication prior authorizations (PAs) from insurers can lead to delays in pharmacotherapy. OBJECTIVE: To assess the efficiency of our clinical pharmacy technicians in processing PAs for medications. PRACTICE DESCRIPTION: Outpatient clinics in a comprehensive health care provider group. PRACTICE INNOVATION: PA requests are routed to technicians for initial data collection. Clinical pharmacists can review their work before submission. EVALUATION METHODS: Clinical pharmacy staff in 4 clinics recorded information about PA requests from January 21, 2020, to April 21, 2020. In 3 of the clinics, PA requests were primarily processed by clinical pharmacy technicians. In another clinic, requests were processed by a clinical pharmacist. Information collected included the date the request was received, outcomes (e.g., approval, therapy change, or nonapproval), and the date of final outcome. Descriptive statistics were prepared, including number of requests that were approved, number of business days between request and decision, and final outcome. RESULTS: Overall, 720 PA requests were received. Of these, 88.6% were approved with first response, and 673 (93.5%) were eventually approved. Median time to first response was 0 business days, regardless of clinic. In 75% of cases, first response was within 1 business day. PA characteristics varied across clinics; however, PA approval percentages were comparable (91.2%-94.3%). CONCLUSION: In an assessment of clinical pharmacy technicians' efficiency in responding to pharmacy plan PA requests, more than 90% were approved, often within one business day. Our results must be interpreted in light of local factors and a virus pandemic during the study. However, results of requests handled by technicians were similar to results when the requests were handled by a clinical pharmacist. Clinical pharmacy technicians can be efficient and cost-effective in this role.

Electronic Nose With Detection Method for Alcohol, Acetone, and Carbon Monoxide in Coronavirus Disease 2019 Breath Simulation Model.

Electronic nose technology may have the potential to substantially slow the spread of contagious diseases with rapid signal indication. As our understanding of infectious diseases such as Corona Virus Disease 2019 improves, we expect electronic nose technology to detect changes associated with pathogenesis of the disease such as biomarkers of immune response for respiratory symptoms, central nervous system injury, and/or peripheral nervous system injury in the breath and/or odor of an individual. In this paper, a design of an electronic nose was configured to detect the concentration of a COVID-19 breath simulation sample of alcohol, acetone, and carbon monoxide mixture. After preheating for 24 hours, the sample was carried into an internal bladder of the collection vessel for analysis and data was collected from three sensors to determine suitability of these sensors for the application of exhaled breath analysis. Test results show a detection range in parts-per-million within the sensor detection range of at least 10-300 ppm. The output response of an MQ-2 and an MQ-135 sensor to a diverse environment of target gasses show the MQ-2 taking a greater length of time to normalize baseline drift compared to an MQ-135 sensor due to cross interferences with other gasses. The COVID-19 breath simulation sample was established and validated based on preliminary data obtained from parallel COVID-19 breath studies based in Edinburgh and Dortmund. This detection method provides a non-invasive, rapid, and selective detection of gasses in a variety of applications in virus detection as well as agricultural and homeland security.

Educational Case: Group B Streptococcus Meningitis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

The effects of embryonic hypoxic programming on cardiovascular function and autonomic regulation in the American alligator (Alligator mississippiensis) at rest and during swimming.

Reptilian embryos naturally experience fluctuating oxygen levels in ovo, and developmental hypoxia has been established to have long-term impacts on cardiovascular function in vertebrates. In the present study, we investigated the impact of developmental 21% (normoxia) and 10% O2 (hypoxia) on juvenile (4-year-old) American alligator cardiovascular function in animals at rest and during swimming. In both experimental groups, combined right aortic and right subclavian blood flow approximately doubled during swimming. Carotid blood flow increased during swimming in the hypoxia-programmed animals only, and both carotid and left aortic blood flow reached higher values in swimming hypoxic-programmed animals compared to the normoxic group. However, pulmonary blood flow, which increased two to threefold during swimming (in both groups), was higher in normoxic-programmed animals at both rest and swimming. The differences between programming groups were preserved after cholinergic blockade (atropine), but reduced by adrenergic receptor antagonists (propranolol and phentolamine). Propranolol and phentolamine also blunted the incremental increases in blood flows during swimming, which was especially clear in the hypoxia-programmed animals. Alteration in adrenergic control and relative cardiac size (which was increased in hypoxic-programmed alligators) may account for the differences between the experimental groups.

An understanding of enhanced osteoblast adhesion on various nanostructured polymeric and metallic materials prepared by ionic plasma deposition.

The development of new materials through novel surface modification techniques to enhance orthopedic implant lifetimes (hence, decreasing the need for revision surgery) is of great interest to the medical community. The purpose of this in vitro study was to treat common metallic implant materials [such as titanium (Ti) and a titanium alloy (Ti6Al4V)] and traditional polymeric materials (like polyethylene terephthalate, polyvinyl chloride, polyurethane, polytetrafluoroethylene, ultra-high molecular weight polyethylene (UHMWPE) and nylon) with either nanoparticulate alumina or titanium using novel (i) ionic plasma deposition (IPD) and (ii) nitrogen ion immersion plasma deposition (NIIPD) techniques. The treated surfaces were characterized by scanning electron microscopy, atomic force microscopy and surface energy, demonstrating greater nanoscale roughness on the modified surfaces regardless of the underlying material or coating applied. These surface-modified substrates were also tested for cytocompatibility properties with osteoblasts (or bone-forming cells). Results showed increased osteoblast adhesion on modified compared to control (traditional or untreated) materials. Since the adhesion of osteoblasts is the first crucial step for new bone synthesis, these results are very promising and suggest that the plasma deposition processes used in this study should be further investigated to improve the longevity of orthopedic implants.

Increased endothelial cell adhesion on plasma modified nanostructured polymeric and metallic surfaces for vascular stent applications.

Techniques to regenerate the vasculature have risen considerably over the last few decades due to the increased clinical diagnosis of artery narrowing and blood vessel blockage. Although initially re-establishing blood flow, current small diameter vascular regenerative materials often eventually cause thrombosis and restenosis due to a lack of initial endothelial cell coverage on such materials. The objective of this in vitro study was to evaluate commonly used vascular materials (specifically, polyethylene terephthalate, polytetrafluoroethylene, polyvinyl chloride, polyurethane, nylon, commercially pure titanium, and a titanium alloy (Ti6Al4V)) modified using an ionic plasma deposition (IPD) process and a nitrogen ion implantation plasma deposition (NIIPD) process. Such surface modifications have been previously shown to create nanostructured surface features which mimic the natural nanostructured surface features of blood vessels. The modified and unmodified surfaces were characterized by scanning electron microscopy, atomic force microscopy and surface energy measurements. Furthermore, in vitro endothelial cell adhesion tests (a key first step for vascular material endothelialization) demonstrated increased endothelial cell adhesion on many modified (with IPD and NIIPD + IPD) compared to unmodified samples. In general, endothelial cell adhesion increased with nanoroughness and surface energy but demonstrated a decreased endothelial cell adhesion trend after an optimal coating surface energy value was reached. Thus, results from this study provided materials and a versatile surface modification process that can potentially increase endothelialization faster than current unmodified (conventional) polymer and metallic vascular materials.

Insulin acutely decreases hepatic fatty acid synthase activity.

Insulin is viewed as a positive regulator of fatty acid synthesis by increasing fatty acid synthase (FAS) mRNA transcription. We uncover a new mechanism by which insulin acutely reduces hepatic FAS activity by inducing phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its interaction with FAS. Ceacam1 null mice (Cc1(-/-)) show loss of insulin's ability to acutely decrease hepatic FAS activity. Moreover, adenoviral delivery of wild-type, but not the phosphorylation-defective Ceacam1 mutant, restores the acute effect of insulin on FAS activity in Cc1(-/-) primary hepatocytes. Failure of insulin to acutely reduce hepatic FAS activity in hyperinsulinemic mice, including L-SACC1 transgenics with liver inactivation of CEACAM1, and Ob/Ob obese mice, suggests that the acute effect of insulin on FAS activity depends on the prior insulinemic state. We propose that this mechanism acts to reduce hepatic lipogenesis incurred by insulin pulses during refeeding.

H2O absorption spectroscopy for determination of temperature and H2O mole fraction in high-temperature particle synthesis systems.

Water absorption spectroscopy has been successfully demonstrated as a sensitive and accurate means for in situ determination of temperature and H2O mole fraction in silica (SiO2) particle-forming flames. Frequency modulation of near-infrared emission from a semiconductor diode laser was used to obtain multiple line-shape profiles of H2O rovibrational (v1 + v3) transitions in the 7170-7185-cm(-1) region. Temperature was determined by the relative peak height ratios, and XH2O was determined by use of the line-shape profiles. Measurements were made in the multiphase regions of silane/hydrogen/oxygen/ argon flames to verify the applicability of the diagnostic approach to combustion synthesis systems with high particle loadings. A range of equivalence ratios was studied (phi = 0.47 - 2.15). The results were compared with flames where no silane was present and with adiabatic equilibrium calculations. The spectroscopic results for temperature were in good agreement with thermocouple measurements, and the qualitative trends as a function of the equivalence ratio were in good agreement with the equilibrium predictions. The determinations for water mole fraction were in good agreement with theoretical predictions but were sensitive to the spectroscopic model parameters used to describe collisional broadening. Water absorption spectroscopy has substantial potential as a valuable and practical technology for both research and production combustion synthesis facilities.

Practice management: a third-year clerkship experience.

BACKGROUND AND OBJECTIVES: This report describes a curricular experience that introduces the basics of practice management to third-year family medicine students. The curriculum includes evidence-based medicine, managed care concepts and terminology, financial management terms and concepts, laws and legal issues, and insurance and coding. METHODS: In 1999-2000, a three-session practice management curriculum was implemented in five family medicine third-year clerkship rotations at the University of North Carolina at Chapel Hill, Wilmington site. The learning activities included readings, a "quiz show" game, and a patient practice-centered project. RESULTS: Students reported greater knowledge and confidence in the selected topics. The practice management curriculum was positively evaluated overall. CONCLUSIONS: This interactive learning module for the family medicine students begins the process of incorporating practice management skills and knowledge.