High-output heart failure due to a giant left circumflex coronary aneurysm with a left atrial fistula and atrial septal defect: a case report.

Background: A coronary artery aneurysm is a rare cardiac anomaly that may be incidentally detected on echocardiography. When associated with a coronary cameral fistula, an aneurysm can become symptomatic. We present a unique case of a giant left circumflex coronary aneurysm with a fistula to the left atrium and a large atrial septal defect causing acute heart failure in a young woman during the peripartum period. Case summary: A 32 year-old woman who presented with hypoxia after the delivery of her fourth child was found to have heart failure with severe mitral regurgitation and multiple abnormal intracardiac shunts. Echocardiography showed a large circular structure with Doppler color flow into the left atrium and between the atria. Cardiac computed tomography showed multiple dilated coronary arteries including a left circumflex coronary artery aneurysm measuring >10 cm in diameter with fistulous communication to the left atrium and a large atrial septal defect. A right heart catheterization was performed, and the patient was diagnosed with high-output heart failure. Surgical closure of the coronary cameral fistula was deferred due to the risk of worsening pressure in the coronary aneurysm, and the patient was referred for cardiac transplantation. Discussion: This case illustrates severe heart failure as a complication of a giant coronary artery aneurysm with fistulization to the left atrium and subsequent shunting through a large atrial defect. Echocardiography allows for the detection of a coronary aneurysm and shunting, and cardiac computed tomography provides detailed visualization of a coronary cameral fistula.

Demographic and Socioeconomic Risk Factors for Granulomatous Mastitis in the United States: A Case-Control Study.

OBJECTIVE: Granulomatous mastitis (GM) is a benign breast disease that can have an extended clinical course impacting quality of life and causing breast disfigurement. Granulomatous mastitis has been studied throughout the world; however, less is known about GM patients in the United States. We aim to identify demographic and socioeconomic factors associated with GM in the United States. METHODS: An IRB-approved retrospective case-control study was performed of 92 patients with biopsy-proven GM at two institutions in Los Angeles, California: a safety-net hospital and an academic institution. Age-matched controls were selected from patients presenting for diagnostic breast imaging. Demographic and socioeconomic characteristics were collected. Data were analyzed using univariable test for odds ratios (ORs) with 95% confidence intervals (CIs) and multivariable conditional logistic regression. RESULTS: Patients with GM were more likely to prefer Spanish language (OR 6.20, 95% CI: 2.71%-14.18%), identify as Hispanic/Latina (OR 5.18, 95% CI: 2.38%-11.30%), and be born in Mexico (OR 3.85, 95% CI: 1.23%-12.02%). Cases were more likely to have no primary care provider (OR 3.76, 95% CI: 1.97%-7.14%) and use California Medicaid for undocumented adults (OR 3.65, 95% CI: 1.89%-7.08%). In the multivariable analysis, participants who preferred Spanish language had four times higher odds of GM versus those who preferred English language (OR 4.32, 95% CI: 1.38%-13.54%). CONCLUSION: Patients with GM may have barriers to health care access, such as preferring Spanish language, being an undocumented immigrant, and not having a primary care provider. Given these health care disparities, further research is needed to identify risk factors, etiologies, and treatments for this subset of GM patients.

Postmortem CT in decedents with SARS-CoV-2 infection. A single institution experience.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 produced a global pandemic with significant mortality. As autopsies are not routinely performed on all decedents with SARS-CoV-2 infection, postmortem CT (PMCT) may be valuable to provide additional information on the cause of death and risk factors known to be associated with an increased mortality in COVID-19. The purpose of this manuscript is to review the PMCT findings in a series of 42 decedents with SARS-CoV-2 infection from our institution. Retrospective analysis of 42 decedents who had a positive postmortem nasopharyngeal swab for SARS-CoV-2 and had a PMCT were included in this study. Images were reviewed for pulmonary findings seen in COVID-19 and other organ involvement. Of the 42 decedents, although the majority had imaging findings in the lungs that would be consistent with COVID-19 and acute respiratory distress syndrome, in 14% of the decedents the SARS-CoV-2 infection was likely coincidental and the PMCT findings suggested that they died from other pathology. Over half of the decedents that died from COVID-19 had PMCT findings of vascular disease. PMCT is useful to identify pulmonary and extra pulmonary findings in decedents with SARS-CoV-2 infection that can provide additional information, which may be useful for the forensic pathologist to help determine the underlying cause of death. Supplemental data for this article are available online at.

Quantitative Analysis of Contrast-enhanced Mammography for Risk Stratification of Benign Versus Malignant Disease and Molecular Subtype.

OBJECTIVE: To assess quantitative enhancement of benign, high-risk, and malignant lesions and differences in molecular subtype and grade of malignant lesions on contrast-enhanced mammography (CEM). METHODS: This IRB-approved retrospective study included women who underwent CEM for diagnostic work-up of a breast lesion between 2014 and 2020. Inclusion criteria were women who had diagnostic work-up with CEM and had BI-RADS 1 or 2 with one year follow-up, BI-RADS 3 with tissue diagnosis or stability for 2 years, or BI-RADS 4 or 5 with tissue diagnosis. An enhancement ratio was calculated for all lesions. This was obtained by drawing a region of interest within the lesion and a second region of interest in the nonenhancing background tissue using a program developed with MATLAB. Descriptive statistics were evaluated using chi-squared tests, Fisher exact tests, and analysis of variance. A logistic regression model was used to predict cancer outcome using the enhancement ratio. Statistical significance was defined as P < 0.05. RESULTS: There were 332 lesions in 210 women that met study criteria. Of the 332 lesions, 50.9% (169/332) were malignant, 5.7% (19/332) were high-risk, and 43.4% (144/332) were benign. Enhancement intensity of malignant lesions was higher than benign lesions. Odds ratio for quantitative enhancement of malignant lesions was 30.15 (P < 0.0001). Enhancement ratio above 1.49 had an 84.0% sensitivity and 84.0% specificity for malignancy. HER2-enriched breast cancers had significantly higher mean enhancement ratios (P = 0.0062). CONCLUSION: Quantitative enhancement on CEM demonstrated that malignant breast lesions had higher mean enhancement intensity than benign lesions.

111In-Labeled White Blood Cell Uptake in the Urinary Bladder in Occult Urinary Tract Infection.

ABSTRACT: A 55-year-old woman with multiple medical problems, including anuric, dialysis-dependent, end-stage renal disease, presented with persistent fever of unknown origin. Despite extensive workup with cross-sectional imaging and panculture, the etiology was not found. Eventually, an 111In-labeled WBC scan was performed to evaluate for occult infection, which revealed intense heterogeneous uptake in the urinary bladder. Subsequent bladder catheterization showed pus and blood, which grew Klebsiella pneumoniae. The fevers resolved with adjustment of the therapy. Although urinary analysis and culture are standard practice in the workup of fever of unknown origin, anuria may obscure this common source of infection.

Caval Aortic Index: A Novel Tool for Fluid Assessment in Obstetric Emergencies.

BACKGROUND: Uncorrected maternal hypotension occurring during obstetric emergencies may result in maternal and fetal morbidity. Fluid status of the pregnant mother is a major variable which affects the maternal hemodynamics during patient management, and there is no objective assessment tool for the same. A relatively new sonographic parameter, the inferior vena cava aorta (IVC/Ao) diameter index or caval aortic index, showed promise in this regard, and its application was studied in obstetric patients. METHODOLOGY: A prospective analytical study was conducted involving 50 pregnant and 50 nonpregnant women of reproductive age group. Using both subxiphoid and transhepatic views, their normal fasting caval aortic indices were determined from the ratio of mean IVC diameter to the mean aortic diameter. Descriptive and inferential statistical analyses were carried out accordingly. RESULTS: Normal IVC/Ao diameter index for nonpregnant healthy women of reproductive age was 1.11 ± 0.29 in the subxiphoid view and 1.21 ± 0.33 in the transhepatic view. The difference between the two views was not statistically significant. IVC/Ao diameter index for a normal term pregnant woman was 1.03 ± 0.26, and term pregnancy does not significantly cause variation in the index. CONCLUSIONS: Caval aortic index is a useful noninvasive tool to assess volume status and guide fluid management in pregnant women presenting to the emergency department, and the transhepatic view is comparable to the traditional subxiphoid view for the measurement of the same.

Efficacy of Baska mask and Laryngeal mask airway supreme during positive pressure ventilation - A comparative study.

BACKGROUND AND AIMS: Supraglottic airway devices have several roles including maintenance of a clear upper airway during general anesthesia. We primarily compared the efficacy of Baska mask (BM) and laryngeal mask airway supreme (LMAS) for the rate of first time successful placement and the seal pressure. The secondary outcome measures included laryngopharyngeal morbidity and the correct positioning of the gastric port. MATERIAL AND METHODS: A sample size of 30 was calculated in each study group. A total of 70 study participants were included in the statistical analysis of which 36 patients were in the BM group and 34 patients were in the LMAS group. RESULTS: The BM was successfully inserted in 28 patients (77.8%), whereas LMAS was successfully inserted in 33 patients (97.1%) in the first attempt (P = 0.028). The mean oropharyngeal seal pressure in the BM group was higher (33.28 ± 6.80 cm H2O) than compared to the LMAS group (27.47 ± 2.34 cm H2O) with a P value <0.001. There was no significant difference between the two groups in the incidence of postoperative laryngopharyngeal morbidity both in the immediate postoperative period (P = 0.479) and that seen 24 hours post operatively (P = 0.660). The nasogastric tube could easily be inserted in the entire study population. CONCLUSION: From the present study, it is concluded that the BM creates a higher oropharyngeal seal pressure than the LMAS. However, the BM is more difficult to insert. The incidence of postoperative laryngopharyngeal morbidity is similar in both groups.

Assessing the Diagnostic Yield of Targeted Next-Generation Sequencing for Melanoma and Gastrointestinal Tumors.

A common rationale in molecular diagnostic laboratories is that implementation of next-generation sequencing (NGS) enables simultaneous multigene testing, allowing increased information benefit compared with non-NGS assays. However, minimal published data exist to support this justification. The current study compared clinical diagnostic yield of TruSight Tumor 26 Sequencing Panel (TST26) in melanoma, colorectal (CRC), and gastrointestinal stromal (GIST) tumors with non-NGS assays. A total of 1041 formalin-fixed, paraffin-embedded tumors, of melanoma, CRC, and GIST, were profiled. NGS results were compared with non-NGS single-gene or single-variant assays with respect to variant output and diagnostic yield. A total of 79% melanoma and 94% CRC tumors were variant positive by panel testing. TST26 panel improved serine/threonine-protein kinase B-raf (BRAF) variant detection in melanoma compared with single-variant BRAF Val600Glu/Lys (V600E/K) routine tests by 24% and detected variants in genes other than BRAF, NRAS, and KIT, which could impact patient management in 20% additional cases. NGS enhanced diagnostic yield in CRC by 36% when compared with routine single-gene assays. In contrast, no added benefit of NGS-based testing for GIST tumors was observed. TST26 panel either missed or inaccurately called complex insertion/deletion variants in KIT exon 11, which were accurately identified by non-NGS methods. Findings of this study demonstrate the differential impact of cancer site and variant type on diagnostic test information yield from NGS assays.

Latency and interval therapy affect the evolution in metastatic colorectal cancer.

While comparison of primary tumor and metastases has highlighted genomic heterogeneity in colorectal cancer (CRC), previous studies have focused on a single metastatic site or limited genomic testing. Combining data from whole exome and ultra-deep targeted sequencing, we explored possible evolutionary trajectories beyond the status of these mutations, particularly among patient-matched metastatic tumors. Our findings confirm the persistence of known clinically-relevant mutations (e.g., those of RAS family of oncogenes) in CRC primary and metastases, yet reveal that latency and interval systemic therapy affect the course of evolutionary events within metastatic lesions. Specifically, our analysis of patient-matched primary and multiple metastatic lesions, developed over time, showed a similar genetic composition for liver metastatic tumors, which were 21-months apart. This genetic makeup was different from those identified in lung metastases developed before manifestation of the second liver metastasis. These results underscore the role of latency in the evolutionary path of metastatic CRC and may have implications for future treatment options.

Intercomparison of the Radio-Chronometric Ages of Plutonium-Certified Reference Materials with Distinct Isotopic Compositions.

An intercomparison of the radio-chronometric ages of four distinct plutonium-certified reference materials varying in chemical form, isotopic composition, and period of production are presented. The cross-comparison of the different 234U/238Pu, 235U/239Pu, 236U/240Pu, and 241Am/241Pu model purification ages obtained at four independent analytical facilities covering a range of laboratory environments from bulk sample processing to clean facilities dedicated to nuclear forensic investigation of environmental samples enables a true assessment of the state-of-practice in "age dating capabilities" for nuclear materials. The analytical techniques evaluated used modern mass spectrometer instrumentation including thermal ionization mass spectrometers and inductively coupled plasma mass spectrometers for isotopic abundance measurements. Both multicollector and single collector instruments were utilized to generate the data presented here. Consensus values established in this study make it possible to use these isotopic standards as quality control standards for radio-chronometry applications. Results highlight the need for plutonium isotopic standards that are certified for 234U/238Pu, 235U/239Pu, 236U/240Pu, and 241Am/241Pu model purification ages as well as other multigenerational radio-chronometers such as 237Np/241Pu. Due to the capabilities of modern analytical instrumentation, analytical laboratories that focus on trace level analyses can obtain model ages with marginally larger uncertainties than laboratories that handle bulk samples. When isotope ratio measurement techniques like thermal ionization mass spectrometry and inductively coupled plasma mass spectrometry with comparable precision are utilized, model purification ages with similar uncertainties are obtained.

Somatic Tumor Variant Filtration Strategies to Optimize Tumor-Only Molecular Profiling Using Targeted Next-Generation Sequencing Panels.

A common approach in clinical diagnostic laboratories to variant assessment from tumor molecular profiling is sequencing of genomic DNA extracted from both tumor (somatic) and normal (germline) tissue, with subsequent variant comparison to identify true somatic variants with potential impact on patient treatment or prognosis. However, challenges exist in paired tumor-normal testing, including increased cost of dual sample testing and identification of germline cancer predisposing variants. Alternatively, somatic variants can be identified by in silico tumor-only variant filtration precluding the need for matched normal testing. The barrier to tumor-only variant filtration is defining a reliable approach, with high sensitivity and specificity to identify somatic variants. In this study, we used retrospective data sets from paired tumor-normal samples tested on small (48 gene) and large (555 gene) targeted next-generation sequencing panels, to model algorithms for tumor-only variants classification. The optimal algorithm required an ordinal filtering approach using information from variant population databases (1000 Genomes Phase 3, ESP6500, ExAC), clinical mutation databases (ClinVar), and information on recurring clinically relevant somatic variants. Overall the tumor-only variant filtration strategy described in this study can define clinically relevant somatic variants from tumor-only analysis with sensitivity of 97% to 99% and specificity of 87% to 94%, and with significant potential utility for clinical laboratories implementing tumor-only molecular profiling.

Clinical Utility of Next-generation Sequencing in the Management of Myeloproliferative Neoplasms: A Single-Center Experience.

Although next-generation sequencing (NGS) has helped characterize the complex genomic landscape of myeloid malignancies, its clinical utility remains undefined. This has resulted in variable funding for NGS testing, limiting its accessibility. At our center, targeted sequencing (TAR-SEQ) using a 54-gene NGS myeloid panel is offered to all new patients referred for myeloid malignancies, as part of a prospective observational study. Here, we evaluated the diagnostic, prognostic, and potential therapeutic utility of clinical grade TAR-SEQ in the routine workflow of 179 patients with myeloproliferative neoplasms (MPN). Of 13 patients with triple negative (TN) MPN, who lacked driver mutations in JAK2, CALR, and MPL, TAR-SEQ confirmed clonal hematopoiesis in 8 patients. In patients with intermediate-risk myelofibrosis (MF), TAR-SEQ helped optimize clinical decisions in hematopoietic cell transplant (HCT)-eligible patients through identifying a high molecular risk (HMR) mutation profile. The presence of an HMR profile favored HCT in 9 patients with intermediate-1 risk MF. Absence of an HMR profile resulted in a delayed HCT strategy in 10 patients with intermediate-2 risk MF, 7 of which were stable at the last follow-up. Finally, TAR-SEQ identified patients with various targetable mutations in IDH1/2 (4%), spliceosome genes (28%), and EZH2 (7%). Some of these patients can be potential candidates for future targeted therapy trials. In conclusion, we have demonstrated that TAR-SEQ improves the characterization of TN MPN, can be integrated in clinical practice as an additional tool to refine decision making in HCT, and has the potential to identify candidates for future targeted therapy trials.

Newly Diagnosed Breast Cancer: Comparison of Contrast-enhanced Spectral Mammography and Breast MR Imaging in the Evaluation of Extent of Disease.

Purpose To compare the diagnostic performances of contrast material-enhanced spectral mammography and breast magnetic resonance (MR) imaging in the detection of index and secondary cancers in women with newly diagnosed breast cancer by using histologic or imaging follow-up as the standard of reference. Materials and Methods This institutional review board-approved, HIPAA-compliant, retrospective study included 52 women who underwent breast MR imaging and contrast-enhanced spectral mammography for newly diagnosed unilateral breast cancer between March 2014 and October 2015. Of those 52 patients, 46 were referred for contrast-enhanced spectral mammography and targeted ultrasonography because they had additional suspicious lesions at MR imaging. In six of the 52 patients, breast cancer had been diagnosed at an outside institution. These patients were referred for contrast-enhanced spectral mammography and targeted US as part of diagnostic imaging. Images from contrast-enhanced spectral mammography were analyzed by two fellowship-trained breast imagers with 2.5 years of experience with contrast-enhanced spectral mammography. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for both imaging modalities and compared by using the Bennett statistic. Results Fifty-two women with 120 breast lesions were included for analysis (mean age, 50 years; range, 29-73 years). Contrast-enhanced spectral mammography had similar sensitivity to MR imaging (94% [66 of 70 lesions] vs 99% [69 of 70 lesions]), a significantly higher PPV than MR imaging (93% [66 of 71 lesions] vs 60% [69 of 115 lesions]), and fewer false-positive findings than MR imaging (five vs 45) (P < .001 for all results). In addition, contrast-enhanced spectral mammography depicted 11 of the 11 secondary cancers (100%) and MR imaging depicted 10 (91%). Conclusion Contrast-enhanced spectral mammography is potentially as sensitive as MR imaging in the evaluation of extent of disease in newly diagnosed breast cancer, with a higher PPV. © RSNA, 2017.

Integration of Technical, Bioinformatic, and Variant Assessment Approaches in the Validation of a Targeted Next-Generation Sequencing Panel for Myeloid Malignancies.

CONTEXT: - Detection of variants in hematologic malignancies is increasingly important because of a growing number of variants impacting diagnosis, prognosis, and treatment response, and as potential therapeutic targets. The use of next-generation sequencing technologies to detect variants in hematologic malignancies in a clinical diagnostic laboratory setting allows for efficient identification of routinely tested markers in multiple genes simultaneously, as well as the identification of novel and rare variants in other clinically relevant genes. OBJECTIVE: - To apply a systematic approach to evaluate and validate a commercially available next-generation sequencing panel (TruSight Myeloid Sequencing Panel, Illumina, San Diego, California) targeting 54 genes. In this manuscript, we focused on the parameters that were used to evaluate assay performance characteristics. DATA SOURCES: - Analytical validation was performed using samples containing known variants that had been identified previously. Cases were selected from different disease types, with variants in a range of genes. Panel performance characteristics were assessed and genomic regions requiring additional analysis or wet-bench approaches identified. CONCLUSIONS: - We validated the performance characteristics of a myeloid next-generation sequencing panel for detection of variants. The TruSight Myeloid Sequencing Panel covers more than 95% of target regions with depth greater than 500×. However, because of unique variant types such as large insertions or deletions or genomic regions of high GC content, variants in CEBPA, FLT3, and CALR required supplementation with non-next-generation sequencing assays or with informatics approaches to address deficiencies in performance. The use of multiple bioinformatics approaches (2 variant callers and informatics scripts) allows for maximizing calling of true positives, while identifying limitations in using either method alone.

Determination of origin and intended use of plutonium metal using nuclear forensic techniques.

Nuclear forensics techniques, including micro-XRF, gamma spectrometry, trace elemental analysis and isotopic/chronometric characterization were used to interrogate two, potentially related plutonium metal foils. These samples were submitted for analysis with only limited production information, and a comprehensive suite of forensic analyses were performed. Resulting analytical data was paired with available reactor model and historical information to provide insight into the materials' properties, origins, and likely intended uses. Both were super-grade plutonium, containing less than 3% 240Pu, and age-dating suggested that most recent chemical purification occurred in 1948 and 1955 for the respective metals. Additional consideration of reactor modeling feedback and trace elemental observables indicate plausible U.S. reactor origin associated with the Hanford site production efforts. Based on this investigation, the most likely intended use for these plutonium foils was 239Pu fission foil targets for physics experiments, such as cross-section measurements, etc.

Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy.

In myelofibrosis (MF), driver mutations in JAK2, MPL, or CALR impact survival and progression to blast phase, with the greatest risk conferred by triple-negative status. Subclonal mutations, including mutations in high-molecular risk (HMR) genes, such as ASXL1, EZH2, IDH1/2, and SRSF2 have also been associated with inferior prognosis. However, data evaluating the impact of next-generation sequencing in MF patients treated with JAK1/2 inhibitors are lacking. Using a 54-gene myeloid panel, we performed targeted sequencing on 100 MF patients treated with ruxolitinib (n = 77) or momelotinib (n = 23) and correlated mutational profiles with treatment outcomes. Ninety-nine patients had at least 1 mutation identified, 46 (46%) had 2 mutations, and 34 (34%) patients had ≥3 mutations. Seventy-nine patients carried a mutation in JAK2V617F, 14 patients had mutations in CALR, 6 patients had an MPL mutation, and 2 patients were triple negative. No mutation was significantly associated with spleen or anemia response. A high Dynamic International Prognostic Scoring System score and pretreatment transfusion dependence were associated with a shorter time to treatment failure (TTF), and this association retained significance on multivariable analysis. Patients with ASXL1 (hazard ratio [HR], 1.86; P = .03) and EZH2 mutations (HR, 2.94; P = .009) and an HMR profile (HR, 2.06; P = .01) had shorter TTF. On multivariate analysis, ASXL1 or EZH2 mutations were independently associated with shorter TTF and overall survival. These findings help identify patients unlikely to have a durable response with current JAK1/2 inhibitors and provide a framework for future studies.