Quantitative susceptibility mapping for detection of kidney stones, hemorrhage differentiation, and cyst classification in ADPKD.

BACKGROUND AND PURPOSE: The objective is to demonstrate feasibility of quantitative susceptibility mapping (QSM) in autosomal dominant polycystic kidney disease (ADPKD) patients and to compare imaging findings with traditional T1/T2w magnetic resonance imaging (MRI). METHODS: Thirty-three consecutive patients (11 male, 22 female) diagnosed with ADPKD were initially selected. QSM images were reconstructed from the multiecho gradient echo data and compared to co-registered T2w, T1w, and CT images. Complex cysts were identified and classified into distinct subclasses based on their imaging features. Prevalence of each subclass was estimated. RESULTS: QSM visualized two renal calcifications measuring 9 and 10 mm and three pelvic phleboliths measuring 2 mm but missed 24 calcifications measuring 1 mm or less and 1 larger calcification at the edge of the field of view. A total of 121 complex T1 hyperintense/T2 hypointense renal cysts were detected. 52 (43%) Cysts appeared hyperintense on QSM consistent with hemorrhage; 60 (49%) cysts were isointense with respect to simple cysts and normal kidney parenchyma, while the remaining 9 (7%) were hypointense. The presentation of the latter two complex cyst subtypes is likely indicative of proteinaceous composition without hemorrhage. CONCLUSION: Our results indicate that QSM of ADPKD kidneys is possible and uniquely suited to detect large renal calculi without ionizing radiation and able to identify properties of complex cysts unattainable with traditional approaches.

Evaluation of a Zoonotic Orthopoxvirus PCR Assay for the Detection of Mpox Virus Infection.

An epidemic caused by an outbreak of mpox (formerly monkeypox) in May 2022 rapidly spread internationally, requiring an urgent response from the clinical diagnostics community. A detailed description of the clinical validation and implementation of a laboratory-developed real-time PCR test for detecting nonvariola Orthopoxvirus-specific DNA based on the newly designed RealStar Zoonotic Orthopoxvirus assay is presented. The validation was performed using an accuracy panel (n = 97) comprising skin lesion swabs in universal transport media and from mpox virus genomic DNA spiked into pooled mpox virus-negative remnant universal transport media of lesion specimens submitted for routine clinical testing in the NewYork-Presbyterian Hospital clinical laboratory system. Accuracy testing demonstrated excellent assay agreement between expected and observed results and comparable diagnostic performance to three different reference tests. Analytical sensitivity with 95% detection probability was 126 copies/mL, and analytical specificity, clinical sensitivity, and clinical specificity were 100%. In summary, the RealStar Zoonotic Orthopoxvirus assay provides a sensitive and reliable method for routine diagnosis of mpox infections.

Pleural Effusions on MRI in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) has cystic fluid accumulations in the kidneys, liver, pancreas, arachnoid spaces as well as non-cystic fluid accumulations including pericardial effusions, dural ectasia and free fluid in the male pelvis. Here, we investigate the possible association of ADPKD with pleural effusion. ADPKD subjects (n = 268) and age-gender matched controls without ADPKD (n = 268) undergoing body magnetic resonance imaging from mid-thorax down into the pelvis were independently evaluated for pleural effusion by 3 blinded expert observers. Subjects with conditions associated with pleural effusion were excluded from both populations. Clinical and laboratory data as well as kidney, liver and spleen volume, pleural fluid volume, free pelvic fluid and polycystic kidney disease genotype were evaluated. Pleural effusions were observed in 56 of 268 (21%) ADPKD subjects compared with 21 of 268 (8%) in controls (p < 0.0001). In a subpopulation controlling for renal function by matching estimated glomerular filtration rate (eGFR), 28 of 110 (25%) ADPKD subjects had pleural effusions compared to 5 of 110 (5%) controls (p < 0.001). Pleural effusions in ADPKD subjects were more prevalent in females (37/141; 26%) than males (19/127,15%; p = 0.02) and in males were weakly correlated with the presence of free pelvic fluid (r = 0.24, p = 0.02). ADPKD subjects with pleural effusions were younger (48 ± 14 years old vs. 43 ± 14 years old) and weighed less (77 vs. 70 kg; p ≤ 0.02) than those without pleural effusions. For ADPKD subjects with pleural effusions, the mean volume of fluid layering dependently in the posterior−inferior thorax was 19 mL and was not considered to be clinically significant. Pleural effusion is associated with ADPKD, but its role in the pathogenesis of ADPKD requires further evaluation.

Rapid detection of SARS-CoV-2 variants of concern by single nucleotide polymorphism genotyping using TaqMan assays.

We evaluated the performance of SARS-CoV-2 TaqMan real-time reverse-transcription PCR (RT-qPCR) assays (ThermoFisher) for detecting 2 nonsynonymous spike protein mutations, E484K and N501Y. Assay accuracy was evaluated by whole genome sequencing (WGS). Residual nasopharyngeal SARS-CoV-2 positive samples (N = 510) from a diverse patient population in New York City submitted for routine SARS-CoV-2 testing during January-April 2020 were used. We detected 91 (18%) N501Y and 101 (20%) E484K variants. Four samples (0.8%) were positive for both variants. The assay had nearly perfect concordance with WGS in the validation subset, detecting B.1.1.7 and B.1.526 variants among others. Sensitivity and specificity ranged from 0.95 to 1.00. Positive and negative predictive values were 0.98-1.00. TaqMan genotyping successfully predicted the presence of B.1.1.7, but had significantly lower sensitivity, 62% (95% CI, 0.53, 0.71), for predicting B.1.526 sub-lineages lacking E484K. This approach is rapid and accurate for detecting SARS-CoV-2 variants and can be rapidly implemented in routine clinical setting.

A common intronic single nucleotide variant modifies PKD1 expression level.

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1 and PKD2 (PKD1/2), has unexplained phenotypic variability likely affected by environmental and other genetic factors. Approximately 10% of individuals with ADPKD phenotype have no causal mutation detected, possibly due to unrecognized risk variants of PKD1/2. This study was designed to identify risk variants of PKD genes through population genetic analyses. We used Wright's F-statistics (Fst) to evaluate common single nucleotide variants (SNVs) potentially favored by positive natural selection in PKD1 from 1000 Genomes Project (1KG) and genotyped 388 subjects from the Rogosin Institute ADPKD Data Repository. The variants with >90th percentile Fst scores underwent further investigation by in silico analysis and molecular genetics analyses. We identified a deep intronic SNV, rs3874648G> A, located in a conserved binding site of the splicing regulator Tra2-ß in PKD1 intron 30. Reverse-transcription PCR (RT-PCR) of peripheral blood leukocytes (PBL) from an ADPKD patient homozygous for rs3874648-A identified an atypical PKD1 splice form. Functional analyses demonstrated that rs3874648-A allele increased Tra2-ß binding affinity and activated a cryptic acceptor splice-site, causing a frameshift that introduced a premature stop codon in mRNA, thereby decreasing PKD1 full-length transcript level. PKD1 transcript levels were lower in PBL from rs3874648-G/A carriers than in rs3874648-G/G homozygotes in a small cohort of normal individuals and patients with PKD2 inactivating mutations. Our findings indicate that rs3874648G > A is a PKD1 expression modifier attenuating PKD1 expression through Tra2-ß, while the derived G allele advantageously maintains PKD1 expression and is predominant in all subpopulations.

Deployed Deep Learning Kidney Segmentation for Polycystic Kidney Disease MRI.

This study develops, validates, and deploys deep learning for automated total kidney volume (TKV) measurement (a marker of disease severity) on T2-weighted MRI studies of autosomal dominant polycystic kidney disease (ADPKD). The model was based on the U-Net architecture with an EfficientNet encoder, developed using 213 abdominal MRI studies in 129 patients with ADPKD. Patients were randomly divided into 70% training, 15% validation, and 15% test sets for model development. Model performance was assessed using Dice similarity coefficient (DSC) and Bland-Altman analysis. External validation in 20 patients from outside institutions demonstrated a DSC of 0.98 (IQR, 0.97-0.99) and a Bland-Altman difference of 2.6% (95% CI: 1.0%, 4.1%). Prospective validation in 53 patients demonstrated a DSC of 0.97 (IQR, 0.94-0.98) and a Bland-Altman difference of 3.6% (95% CI: 2.0%, 5.2%). Last, the efficiency of model-assisted annotation was evaluated on the first 50% of prospective cases (n = 28), with a 51% mean reduction in contouring time (P < .001), from 1724 seconds (95% CI: 1373, 2075) to 723 seconds (95% CI: 555, 892). In conclusion, our deployed artificial intelligence pipeline accurately performs automated segmentation for TKV estimation of polycystic kidneys and reduces expert contouring time. Keywords: Convolutional Neural Network (CNN), Segmentation, Kidney ClinicalTrials.gov identification no.: NCT00792155 Supplemental material is available for this article. © RSNA, 2022.

System-wide transcriptome damage and tissue identity loss in COVID-19 patients.

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections.

Pericardial Effusion on MRI in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) has been associated with cardiac abnormalities including mitral valve prolapse and aneurysmal dilatation of the aortic root. Herein, we investigated the potential association of pericardial effusion with ADPKD. Subjects with ADPKD (n = 117) and control subjects without ADPKD matched for age, gender and renal function (n = 117) undergoing MRI including ECG-gated cine MRI of the aorta and heart were evaluated for pericardial effusion independently by three observers measuring the maximum pericardial effusion thickness in diastole using electronic calipers. Pericardial effusion thickness was larger in ADPKD subjects compared to matched controls (Mann-Whitney p = 0.001) with pericardial effusion thickness >5 mm observed in 24 of 117 (21%) ADPKD subjects compared to 4 of 117 (3%) controls (p = 0.00006). Pericardial effusion thickness in ADPKD was associated with female gender patients (1.2 mm greater than in males, p = 0.03) and pleural effusion thickness (p < 0.001) in multivariate analyses. No subjects exhibited symptoms related to pericardial effusion or required pericardiocentesis. In conclusion, pericardial effusion appears to be more prevalent in ADPKD compared to controls. Although in this retrospective cross-sectional study we did not identify clinical significance, future investigations of pericardial effusion in ADPKD subjects may help to more fully understand its role in this disease.

Combining molecular testing and the Bethesda category III:VI ratio for thyroid fine-needle aspirates: A quality-assurance metric for evaluating diagnostic performance in a cytopathology laboratory.

BACKGROUND: Molecular testing (MT) of thyroid fine-needle aspiration (FNA)-derived genetic material is commonly used to assess malignancy risk for indeterminate cases. The Bethesda System for Reporting Thyroid Cytopathology (TBS) provides limited guidance for the appropriate use of category III (atypia of undetermined significance [AUS]). The authors combined MT with cytomorphology to monitor AUS diagnoses in a cytopathology laboratory. METHODS: Neoplasia-associated genetic alterations (NGAs) were determined by MT of preoperative FNA biopsies or resected malignancies and were categorized as BRAF V600E mutations, RAS-like mutations (HRAS, NRAS, or KRAS mutations or non-V600E BRAF mutations), or other mutations. RESULTS: Among 7382 thyroid FNA biopsies, the AUS rate was 9.3% overall and ranged from 4.3% to 24.2% among 6 cytopathologists (CPs) who evaluated >150 cases. The ratio of specimens falling into TBS category III to specimens falling into category VI (malignant) (the III:VI ratio) was 2.4 overall (range, 1.1-8.1), and the ratio of specimens falling into TBS categories III and IV (follicular neoplasm or suspicious for follicular neoplasm) combined (III+IV) to specimens falling into category VI (the [III+IV]:VI ratio) was 2.9 overall (range, 1.4-9.5). MT was performed on 588 cases from 560 patients (79% women) with a median age of 56 years (range, 8-89 years). BRAF V600E mutation was the most common (76% of cases) in TBS category VI and was rare (3%) in category III. RAS-like mutations were most common in TBS categories III (13%), IV (25%), and V (suspicious for malignancy) (17.5%). The NGA rate in AUS cases fell between 5% and 20% for 5 of 6 CPs and did not correlate with the III:VI ratio or the (III+IV):VI ratio. CONCLUSIONS: Lack of correlation between the NGA rate and easily calculable diagnostic ratios enables the calibration of diagnostic thresholds, even for CPs who have normal metrics. Specifically, calculation of the NGA rate and the III:VI ratio may allow individual CPs to determine whether they are overcalling or undercalling cases that other CPs might otherwise recategorize.

Adenovirus viremia after in vivo T-cell depleted allo-transplant in adults: low lymphocyte counts are associated with uncontrolled viremia and fatal outcomes.

The incidence of adenovirus viremia and the role of screening in preventing adenovirus disease in adult transplant recipients are not well defined. Between January 2017 and May 2020, 262 allogeneic transplants were performed using in vivo T-cell depletion. Adenovirus viremia was found in 59 patients for a cumulative incidence of 10% by one hundred days and 23% (95% CI 20-26%) by one year. There was a higher incidence of viremia associated with cord blood transplant (p = .04). No other patient, donor or transplant characteristics were identified that predicted for viremia. In 47 patients (80%), viremia remained well below 200,000 copies/mL and resolved. Twelve patients developed high level viremia. Treatment with antivirals and in some cases adoptive cell therapy, was often ineffective and only two survived. Low lymphocyte count at initial detection of adenovirus viremia was the best predictor of uncontrolled disease.

Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). METHODS: To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. RESULTS: Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic "second hit" alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2 ; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 17% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another 18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14% of these cysts harbored copy number neutral LOH events, while the other 3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic "second hit" alterations occurred at the same germline mutated PKD1/2 gene. CONCLUSIONS: These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.

Performance Evaluation of the MatMaCorp COVID-19 2SF Assay for the Detection of SARS-CoV-2 from Nasopharyngeal Swabs.

The coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on clinical diagnostic testing, and the need for PCR-based testing remains to be met. Nucleic acid amplification testing (NAAT) is the recommended method for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to the inherent advantages in sensitivity and specificity. In this study, we evaluated the performance of the MatMaCorp COVID-19 2SF test, a reverse transcription-PCR (RT-PCR) assay for the qualitative detection of SARS-CoV-2 from nasopharyngeal (NP) swabs, run on the Solas 8 instrument (MatMaCorp, Lincoln, NE). The Solas 8 device is portable, and the kit is a lab-in-a-box design which provides reagents in a shelf-stable lyophilized powder format. A total of 78 remnant clinical specimens were used to evaluate the COVID-19 2SF test. Sixty-two clinical specimens originally tested by the Xpert Xpress SARS-CoV-2 assay (Cepheid, Inc., Sunnyvale, CA) were used to evaluate the clinical accuracy of the COVID-19 2SF test. The negative percent agreement (NPA) was 100% (95% confidence interval [CI], 83.9% to 100%), and the positive percent agreement (PPA) was 85.4% (95% CI, 70.8% to 94.4%). Sixteen remnant specimens positive for other common respiratory pathogens (FilmArray respiratory panel 2.0; BioFire, Salt Lake City, UT) were assayed on the Solas 8 device to evaluate specificity. No cross-reactivity with other respiratory pathogens was identified. The unique lab-in-a-box design and shelf-stable reagents of the MatMaCorp COVID-19 2SF test offer laboratories a rapid option for a diagnostic NAAT for SARS-CoV-2 that can help meet diagnostic needs. IMPORTANCE The demand for molecular testing for COVID-19 remains to be met. This study of the MatMaCorp Solas 8 device and COVID-19 test provides the first evaluation of this platform.

Next-Generation Sequencing of Cell-Free DNA Extracted From Pleural Effusion Supernatant: Applications and Challenges.

Cell-free DNA (cfDNA) extracted from diverse specimen types has emerged as a high quality substrate for molecular tumor profiling. Analytical and pre-analytical challenges in the utilization of cfDNA extracted from pleural effusion supernatant (PES) are herein characterized in patients with metastatic non-small cell lung carcinoma (NSCLC). Pleural effusion specimens containing metastatic NSCLC were collected prospectively. After ThinPrep® (TP) and cell block (CB) preparation, DNA was extracted from residual PES and analyzed by gel electrophoresis for quality and quantity. Libraries were prepared and sequenced with a targeted next-generation sequencing (NGS) platform and panel clinically validated for plasma specimens. Results were compared with DNA extracted from corresponding FFPE samples that were sequenced using institutional targeted NGS assays clinically validated for solid tumor FFPE samples. Tumor (TC) and overall cellularity (OC) were evaluated. Fourteen specimens were collected from 13 patients. Median specimen volume was 180 mL (range, 35-1,400 mL). Median TC and OC on TP slides and CB sections were comparable. Median extracted DNA concentration was 7.4 ng/µL (range, 0.1-58.0 ng/µL), with >5 ng/µL DNA extracted from 10/14 specimens (71%). Mutations were identified in 10/14 specimens, including 1/3 specimens with median molecular coverage <1,000 reads. The minimal detected allelic fraction was 0.6%. NGS was falsely negative for the presence of one driver mutation. No correlation was identified between sample volume or OC, quality or quantity of extracted DNA, or mutation detection. Despite analytical and pre-analytical challenges, PES represents a robust source of DNA for NGS.

A Curriculum for Genomic Education of Molecular Genetic Pathology Fellows: A Report of the Association for Molecular Pathology Training and Education Committee.

Molecular genetic pathology (MGP) is a subspecialty of pathology and medical genetics and genomics. Genomic testing, which is defined as that which generates large data sets and interrogates large segments of the genome in a single assay, is increasingly recognized as essential for optimal patient care through precision medicine. The most common genomic testing technologies in clinical laboratories are next-generation sequencing and microarray. It is essential to train in these methods and to consider the data generated in the context of the diagnosis, medical history, and other clinical findings of individual patients. Accordingly, updating the MGP fellowship curriculum to include genomics is timely, important, and challenging. At the completion of training, an MGP fellow should be capable of independently interpreting and signing out results of a wide range of genomic assays and, given the appropriate context and institutional support, of developing and validating new assays in compliance with applicable regulations. The Genomics Task Force of the MGP Program Directors, a working group of the Association for Molecular Pathology Training and Education Committee, has developed a genomics curriculum framework and recommendations specific to the MGP fellowship. These recommendations are presented for consideration and implementation by MGP fellowship programs with the understanding that MGP programs exist in a diversity of clinical practice environments with a spectrum of available resources.

Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2,500 COVID-19 cases associated with this variant have been detected in the United States (US) since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight that the primary ports of entry for B.1.1.7 in the US were in New York, California, and Florida. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid- to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus has infected over 115 million people and caused over 2.5 million deaths worldwide. Yet, the molecular mechanisms underlying the clinical manifestations of COVID-19, as well as what distinguishes them from common seasonal influenza virus and other lung injury states such as Acute Respiratory Distress Syndrome (ARDS), remains poorly understood. To address these challenges, we combined transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues, matched with spatial protein and expression profiling (GeoMx) across 357 tissue sections. These results define both body-wide and tissue-specific (heart, liver, lung, kidney, and lymph nodes) damage wrought by the SARS-CoV-2 infection, evident as a function of varying viral load (high vs. low) during the course of infection and specific, transcriptional dysregulation in splicing isoforms, T cell receptor expression, and cellular expression states. In particular, cardiac and lung tissues revealed the largest degree of splicing isoform switching and cell expression state loss. Overall, these findings reveal a systemic disruption of cellular and transcriptional pathways from COVID-19 across all tissues, which can inform subsequent studies to combat the mortality of COVID-19, as well to better understand the molecular dynamics of lethal SARS-CoV-2 infection and other viruses.

Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States.

The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response.

Prevalence of Inferior Vena Cava Compression in ADPKD.

INTRODUCTION: Kidney and liver cysts in autosomal dominant polycystic kidney disease (ADPKD) can compress the inferior vena cava (IVC), but IVC compression prevalence and its risk factors are unknown. METHODS: Patients who have ADPKD (n = 216) with abdominal magnetic resonance imaging (MRI) studies and age-/sex-matched controls (n = 216) were evaluated for IVC compression as well as azygous vein diameter (a marker of collateral blood flow) and IVC aspect ratio (left-to-right dimension divided by anterior-to-posterior dimension with a value of 1 corresponding to a circular (high pressure) IVC caudal to compression. RESULTS: Severe IVC compression (≥70%) was observed in 33 (15%) ADPKD subjects and mild compression (≥50% to <70%) was observed in 33 (15%) subjects; whereas controls had no IVC compression (P < 0.001). Severe IVC compression was associated with larger azygous vein (4.0 ± 1.3 mm versus 2.3 ± 0.8 mm without IVC compression; P < 0.001) and a more circular IVC cross-section upstream (mean IVC aspect ratio: 1.16 ± 0.27 vs. 1.69 ± 0.67, P < 0.001), suggesting higher pressure upstream from the compression. IVC compression was associated with older age, lower estimated glomerular filtration rate (eGFR), greater height-adjusted total kidney volumes, greater height-adjusted liver volume (ht-LV), and greater liver and renal cyst fractions (P < 0.001). No subject younger than 30 years had IVC compression, but ADPKD subjects ≥40 years old had 12-fold higher risk of IVC compression (95% confidence interval [CI]: 4.2-42.4), with highest predicted probability for Mayo Clinic classes 1D (59%; 95% CI: 39%-76%) and 1E (74%; 95% CI: 49%-90%) after adjustment (P < 0.001). Women with ht-LV ≥ 2000 ml/m had 83% (95% CI: 59%-95%) prevalence of IVC compression. Complications of IVC compression included deep vein thrombosis (DVT) and symptomatic hypotension. CONCLUSIONS: IVC compression is common in ADPKD patients >40 years old, with Mayo Clinic class 1D/E, and in females with ht-LV > 2000 ml/m.

Hemorrhagic Cysts and Other MR Biomarkers for Predicting Renal Dysfunction Progression in Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Screening for rapidly progressing autosomal dominant polycystic kidney disease (ADPKD) is necessary for assigning and monitoring therapies. Height-adjusted total kidney volume (ht-TKV) is an accepted biomarker for clinical prognostication, but represents only a small fraction of information on abdominal MRI. PURPOSE: To investigate the utility of other MR features of ADPKD to predict progression. STUDY TYPE: Single-center retrospective. POPULATION: Longitudinal data from 186 ADPKD subjects with baseline serum creatinine, PKD gene testing, abdominal MRI measurements, and ≥2 follow-up serum creatinine were reviewed. FIELD STRENGTH/SEQUENCE: 1.5T, T2 -weighted single-shot fast spin echo, T1 -weighted 3D spoiled gradient echo (liver accelerated volume acquisition) and 2D cine velocity encoded gradient echo (phase contrast MRA). ASSESSMENT: Ht-TKV, renal blood flow (RBF), number and fraction of renal and hepatic cysts, bright T1 hemorrhagic renal cysts, and liver and spleen volumes were independently assessed by three observers blinded to estimated glomerular filtration rate (eGFR) data. STATISTICAL TESTS: Linear mixed-effect models were applied to predict eGFR over time using MRI features at baseline adjusted for confounders. Validation was performed in 158 patients who had follow-up MRI using receiver operator characteristic, sensitivity, and specificity. RESULTS: Hemorrhagic cysts, fraction of renal and hepatic cysts, height-adjusted liver and spleen volumes were significant independent predictors of future eGFR (final prediction model R2 = 0.88 P < 0.05). The number of hemorrhagic cysts significantly improved the prediction compared to ht-TKV in predicting future eGFR (area under the curve [AUC] = 0.94, 95% confidence interval [CI]: 0.9-0.94 vs. R2 = 0.9, 95% CI: 0.85-0.9, P = 0.045). For baseline eGFR ≥60 ml/min/1.73m2 , sensitivity for predicting eGFR<45 ml/min/1.73m2 by ht-TKV alone was 29%. Sensitivity increased to 72% with all MRI variables in the model (P < 0.05 = 0.019), whereas specificity was unchanged, 100% vs. 99%. DATA CONCLUSION: Combining multiple MR features including hemorrhagic renal cysts, renal cyst fraction, liver and spleen volume, hepatic cyst fraction, and renal blood flow enhanced sensitivity for predicting eGFR decline in ADPKD compared to the standard model including only ht-TKV. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:564-576.

Rapid Implementation of Severe Acute Respiratory Syndrome Coronavirus 2 Emergency Use Authorization RT-PCR Testing and Experience at an Academic Medical Institution.

An epidemic caused by an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019 has since rapidly spread internationally, requiring urgent response from the clinical diagnostics community. We present a detailed overview of the clinical validation and implementation of the first laboratory-developed real-time RT-PCR test offered in the NewYork-Presbyterian Hospital system following the Emergency Use Authorization issued by the US Food and Drug Administration. Nasopharyngeal and sputum specimens (n = 174) were validated using newly designed dual-target real-time RT-PCR (altona RealStar SARS-CoV-2 Reagent) for detecting SARS-CoV-2 in upper respiratory tract and lower respiratory tract specimens. Accuracy testing demonstrated excellent assay agreement between expected and observed values and comparable diagnostic performance to reference tests. The limit of detection was 2.7 and 23.0 gene copies per reaction for nasopharyngeal and sputum specimens, respectively. Retrospective analysis of 1694 upper respiratory tract specimens from 1571 patients revealed increased positivity in older patients and males compared with females, and an increasing positivity rate from approximately 20% at the start of testing to 50% at the end of testing 3 weeks later. Herein, we demonstrate that the assay accurately and sensitively identifies SARS-CoV-2 in multiple specimen types in the clinical setting and summarize clinical data from early in the epidemic in New York City.