Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

The highly transmissible B.1.1.7 variant of SARS-CoV-2, first identified in the United Kingdom, has gained a foothold across the world. Using S gene target failure (SGTF) and SARS-CoV-2 genomic sequencing, we investigated the prevalence and dynamics of this variant in the United States (US), tracking it back to its early emergence. We found that, while the fraction of B.1.1.7 varied by state, the variant increased at a logistic rate with a roughly weekly doubling rate and an increased transmission of 40%-50%. We revealed several independent introductions of B.1.1.7 into the US as early as late November 2020, with community transmission spreading it to most states within months. We show that the US is on a similar trajectory as other countries where B.1.1.7 became dominant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Implementation and Performance of a Point-of-Care COVID-19 Test Program in 4,000 California Schools.

OBJECTIVE: To evaluate the feasibility and accuracy of an unprecedented COVID-19 antigen testing program in schools, which required a healthcare provider order, laboratory director, a Clinical Laboratory Improvement Amendments (CLIA) certificate of waiver, as well as training of school personnel. STUDY DESIGN: Descriptive report of a point-of-care, school-based antigen testing program in California from 8/1/2021 through 5/30/2022, in which participants grades K-12 self-swabbed and school personnel performed testing. Participants included 944,009 students, personnel, and community members from 4,022 California K-12 schools. Outcomes measured include sensitivity and specificity (with polymerase chain reaction [PCR] as comparator), of the Abbott BinaxNOW™ antigen test, number of tests performed, and active infections identified. RESULTS: Of 102,022 paired PCR/antigen tests, the overall sensitivity and specificity for the antigen test was 81.2% (95%CI:80.5%-81.8%) and 99.6% (95%CI:99.5%-99.6%), respectively using cycle threshold (Ct) values <30. During January through March 2022, the highest prevalence period, the positive predictive value (PPV) of antigen testing was 94.7% and the negative predictive value was 94.2%. Overall, 4,022 school sites were enrolled and 3,987,840 million antigen tests were performed on 944,009 individuals. A total of 162,927 positive antigen tests were reported in 135,163 individuals (14.3% of persons tested). CONCLUSIONS: Rapidly implementing a school-based testing program in thousands of schools is feasible. Self-swabbing and testing by school personnel can yield accurate results. On-site COVID-19 testing is no longer necessary in schools, but this model provides a framework for future infectious disease threats.

Pathology of Breast Cancer: Subtypes, Receptors, Biologic Markers, and Staging.

Although the normal anatomy of the breast is relatively simple, a myriad of hyperplastic, atypical, and frankly malignant processes exist. Though a histologic continuum exists, the natural progression of breast disease is not always on a continuum. Moreover, the distinction between hyperplastic, atypical, and frankly malignant processes rests on subtle qualitative and sometimes quantitative features. The treatment of breast-related lesions has always been, and continues to be, a multidisciplinary task. A general understanding of histopathologic features of breast disease will allow clinicians to identify scenarios that are potentially inconsistent with the working diagnosis.

Point prevalence survey to evaluate the seropositivity for coronavirus disease 2019 (COVID-19) among high-risk healthcare workers.

Among 1,770 healthcare workers serving in high-risk care areas for coronavirus disease 2019 (COVID-19), 39 (2.2%) were seropositive. Exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in the community was associated with being seropositive. Job or unit type and percentage of time working with COVID-19 patients were not associated with positive antibody tests.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States.

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Digital Whole Slide Imaging Compared With Light Microscopy for Primary Diagnosis in Surgical Pathology.

CONTEXT.­: The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. OBJECTIVE.­: To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. DESIGN.­: The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. RESULTS.­: The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, -0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. CONCLUSIONS.­: WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology.

Resting brain glucose uptake in headache-free migraineurs.

BACKGROUND AND OBJECTIVE: To compare metabolism in the brains of migraineurs during headache-free periods with those obtained from healthy volunteers. METHODS: Eleven migraineurs (defined by the International Headache Society's criteria) presented during spontaneous headache-free intervals to undergo (18)FDG PET brain imaging of glucose metabolism. The control group consisted of 14 healthy volunteers. Comparison of images was done using Statistical Parametric Mapping to detect significant (P < .05) differences in brain glucose metabolism between the 2 groups. RESULTS: Two regions of significant increase in glucose uptake were identified in migraineurs relative to the control population. The 2 regions were mapped predominantly to the posterior white matter of the cerebrum and cerebellum. CONCLUSIONS: Our study demonstrates the presence of what may be a primary metabolic disturbance in the posterior white matter of the brain in migraineurs.

Tissue preparation for MOHS' frozen sections: a comparison of three techniques.

Accurate, efficient frozen section analysis is important for tumor control. A few studies address the technical issues. More are needed, especially as new technologies become available. The objective of this study is to compare the efficiency of three techniques of flattening tissue for microscopically oriented histologic surgery (MOHS): conventional frozen sectioning, Cryocup, and CryoHist. Conventional chuck/heat sink-frozen section preparation were compared with Cryocup and CryoHist to determine the most efficient technique to examine 100% of the surgical margin of 4-cm diameter, full thickness, fresh autopsy cylinders of anterior abdominal skin, which were marked on their deep and peripheral margins. The specimens were frozen sectioned at 5 microm until all the marking dye was gone from the deep surface, and 95% of the perimeter epidermis could be seen. The conventional chuck required an average of 304 micrometers to clear the deep margin and four fifths did not contain 95% of the epidermal margin. The Cryocup required an average of 284 microm to examine the deep margin and 95% of the epidermal margin. The CryoHist required an average of 104 microm to examine the deep margin and 95% of the epidermal border. The new techniques improve the efficiency and presumably the accuracy of tumor margin analysis.

Manual urine microscopy versus automated urine analyzer microscopy in patients with acute kidney injury.

OBJECTIVE: To examine whether a significant difference exists between the reported ranges of granular and muddy brown casts in urine specimens using manual microscopy compared with an automated urine analyzer in a cohort of patients with acute kidney injury (AKI). METHODS: Freshly voided urine specimens from 25 consecutive patients who were under evaluation by the Department of Nephrology for AKI were simultaneously examined using the iQ200 automated microscopy system and manual microscopy performed by a trained observer. We coded the results according to the number of pathological casts identified and performed a 3 × 2 Freeman-Halton extension of the Fisher exact probability test. RESULTS: Overall, the number of casts identified via manual microscopy differed significantly (P <.001) from the number identified via the automated microscopy system. CONCLUSIONS: This study provides evidence of the importance of performing a manual microscopic examination of urine sediment in patients with AKI. Further studies are needed to assess whether manual microscopy provides prognostic implications regarding renal recovery, hemodialysis dependency, and mortality.

Relationship of resistant hypertension and treatment outcomes with total arterial compliance in a predominantly African American hypertensive cohort.

Resistant hypertension (RH) affects 8% to 30% of hypertensive patients. Blood pressure (BP) reflects the interaction between vascular compliance, resistance to flow, intravascular volume, and cardiac contractility. The relationship of RH with total arterial compliance index (TACI) has not been adequately explored. The RH period prevalence (RH at baseline or follow-up) was determined in a hypertensive cohort (N=156) and compared across quartiles of TACI. Age- and sex-adjusted systolic BP, diastolic BP, and antihypertensive therapeutic intensity score (TIS) were also determined at the time of first BP control. The cohort was 85.3% African American and 67.3% female. Median follow-up was 7 months. The prevalence of RH at baseline was 14.7% while the period prevalence was 43.6%. The period prevalence of RH by ascending quartile for TACI was 66%, 36.8%, 40%, and 30.8% (P=.008). The average BP and antihypertensive TIS at first BP control across TACI quartiles was 122.3/73.4 mm Hg (2.26), 120.7/72.5 mm Hg (1.88), 122.4/75.3 mm Hg (1.71), and 120.0/79.4 mm Hg (1.64) (P=.62, P=.03, P=.13). Low TACI was linked to higher RH prevalence and antihypertensive TIS at first attainment of goal BP according to the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. TACI provides prognostic information that is clinically and perhaps pathophysiologically relevant in RH.

Transcranial Doppler measurements in migraine and nitroglycerin headache.

The objective of this study was to examine the cerebral circulation during spontaneous migraine attacks and to compare changes to an experimental headache model induced by nitroglycerin (NTG) infusion. This prospective study was carried out in a tertiary care hospital on migraineurs with or without aura. Healthy volunteers served as controls. There were no interventions. Flow velocity (FV) and pulsatility index (PI) were measured in migraineurs between and during headache attacks. In controls, FV and PI of the middle cerebral arteries were performed at baseline and after each IV infusion of 0.125, 0.25 and 0.5 microg/kg/min of NTG. In migraineurs, a significant increase in the mean flow velocity (MFV) in the left vertebral artery (VA) and the PI of the right VA during spontaneous migraine headache was found. In controls, all FV significantly decreased after infusion of NTG. The NTG model produces expected and substantially different vascular effects than those seen with spontaneous migraine headache.

Sirenomelia of an intracytoplasmic sperm injection conceptus: a case report and review of mechanism.

Postmortem dissection of the 18-week male conceptus, product of intracytoplasmic sperm injection (ICSI), demonstrated the hallmark findings of sirenomelia. The lower legs were fused and the left knee was rotated medially. Internal organs showed hypoplastic lungs, a multicystic kidney, and unilateral ureteral hypoplasia. The vitelline artery was absorbed, in a classic fashion, into the umbilical artery and communicated with the aorta at a point proximal to the iliac arteries. The tributaries distal to this point were hypoplastic. This finding is consistent with previously documented cases of sirenomelia and is thought to be the pathogenetic mechanism resulting in a vascular steal from the lower extremities. A rare finding was the presence of a penis on the dorsal side just below a perforate anus. In this case report, we discuss the pertinent clinical history and autopsy findings. A brief review of the mechanism thought to give rise to sirenomelia is provided. To our knowledge, this is the first reported case of sirenomelia in an ICSI conceptus.