The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous ...functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
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•RNAi and CRISPR/Cas9 screens were used to find flavivirus dependencies•The screens recovered host factors involved in endocytosis and heparin sulfation•The EMC is required by DENV and ZIKV in the early stages of replication•These studies give a systems-wide view of human-flavivirus interactions
Savidis et al. identify DENV and ZIKV dependencies using orthologous RNAi and CRISPR/Cas9 approaches. Multiple host factors involved in endocytosis and transmembrane protein processing, including the endoplasmic reticulum membrane complex (EMC), are important for flaviviral replication. Together, their studies generate a systems-wide view of human-flavivirus interactions.
Background In pulmonary lobectomy, video-assisted thoracoscopic surgery (VATS) offers advantages compared with open thoracotomy. However, various issues have limited its adoption, especially in ...community settings. Single surgeon studies suggest that completely portal robotic lobectomy (CPRL) may address such limitations. This multicenter study evaluates early CPRL experience in 6 community cardiothoracic surgeons' practices. Methods Perioperative data from each surgeon's initial 20, consecutive and unselected cases of CPRL were retrospectively gathered (total n = 120) and compared with the 2009 and 2010 Society of Thoracic Surgeons database for VATS (n = 4,612) and open (n = 5,913) lobectomy. The χ2 and t test procedures were used and significance was defined at the 95% confidence level ( p < 0.05). Results One hundred sixteen lobectomies (96.7%) were completed robotically with a conversion rate of 3.3%. Preoperative patient characteristics were comparable across the CPRL, VATS, and open groups. The CPRL was equivalent to VATS on all intraoperative and postoperative outcomes, and resulted in significantly lower postoperative blood transfusion rates (0.9% vs 7.8%; p = 0.002), air leaks greater than 5 days (5.2% vs 10.8%; p = 0.05), chest tube duration (3.2 days vs 4.8 days; p < 0.001), and length of stay (4.7 days vs 7.3 days; p < 0.001) when compared with open. For these outcomes, results trended favorably for CPRL over VATS. Conclusions This early CPRL experience reveals a minimally invasive lobectomy technique that is safe and reproducible in varied practice settings. Outcomes were equivalent between CPRL and VATS, trending in favor of robotics. The CPRL was superior in several measures compared with open. The absence of patient selection and low conversion rates suggest a broad applicability of this technique.
Purpose To compare the accuracy of magnetic resonance (MR) imaging with that of computed tomography (CT) for the diagnosis of acute appendicitis in emergency department (ED) patients. Materials and ...Methods This was an institutional review board-approved, prospective, observational study of ED patients at an academic medical center (February 2012 to August 2014). Eligible patients were nonpregnant and 12- year-old or older patients in whom a CT study had been ordered for evaluation for appendicitis. After informed consent was obtained, CT and MR imaging (with non-contrast material-enhanced, diffusion-weighted, and intravenous contrast-enhanced sequences) were performed in tandem, and the images were subsequently retrospectively interpreted in random order by three abdominal radiologists who were blinded to the patients' clinical outcomes. Likelihood of appendicitis was rated on a five-point scale for both CT and MR imaging. A composite reference standard of surgical and histopathologic results and clinical follow-up was used, arbitrated by an expert panel of three investigators. Test characteristics were calculated and reported as point estimates with 95% confidence intervals (CIs). Results Analysis included images of 198 patients (114 women 58%; mean age, 31.6 years ± 14.2 range, 12-81 years; prevalence of appendicitis, 32.3%). The sensitivity and specificity were 96.9% (95% CI: 88.2%, 99.5%) and 81.3% (95% CI: 73.5%, 87.3%) for MR imaging and 98.4% (95% CI: 90.5%, 99.9%) and 89.6% (95% CI: 82.8%, 94.0%) for CT, respectively, when a cutoff point of 3 or higher was used. The positive and negative likelihood ratios were 5.2 (95% CI: 3.7, 7.7) and 0.04 (95% CI: 0, 0.11) for MR imaging and 9.4 (95% CI: 5.9, 16.4) and 0.02 (95% CI: 0.00, 0.06) for CT, respectively. Receiver operating characteristic curve analysis demonstrated that the optimal cutoff point to maximize accuracy was 4 or higher, at which point there was no difference between MR imaging and CT. Conclusion The diagnostic accuracy of MR imaging was similar to that of CT for the diagnosis of acute appendicitis.
Appendicitis is frequently diagnosed in the emergency department, most commonly using CT. The purpose of this study was to compare the diagnostic accuracy of contrast-enhanced MRI with that of ...contrast-enhanced CT for the diagnosis of appendicitis in adolescents when interpreted by abdominal radiologists and pediatric radiologists.
Our study included a prospectively enrolled cohort of 48 patients (12-20 years old) with nontraumatic abdominal pain who underwent CT and MRI. Fellowship-trained abdominal and pediatric radiologists reviewed all CT and MRI studies in randomized order, blinded to patient outcome. Likelihood for appendicitis was rated on a 5-point scale (1, definitely not appendicitis; 5, definitely appendicitis) for CT, the unenhanced portion of the MRI, and the entire contrast-enhanced MRI study. ROC curves were generated and AUC compared for each scan type for all six readers and then stratified by radiologist type. Image test characteristics, interrater reliability, and reading times were compared.
Sensitivity and specificity were 85.9% (95% CI, 76.2-92.7%) and 93.8% (95% CI, 89.7-96.7%) for unenhanced MRI, 93.6% (95% CI, 85.6-97.9%) and 94.3% (95% CI, 90.2-97%) for contrast-enhanced MRI, and 93.6% (95% CI, 85.6-97.9%) and 94.3% (95% CI, 90.2-97%) for CT. No difference was found in the diagnostic accuracy or interpretation time when comparing abdominal radiologists to pediatric radiologists (CT, 3.0 min vs 2.8 min; contrast-enhanced MRI, 2.4 min vs 1.8 min; unenhanced MRI, 1.5 min vs 2.3 min). Substantial agreement between abdominal and pediatric radiologists was seen for all methods (κ = 0.72-0.83).
The diagnostic accuracy of MRI to diagnose appendicitis was very similar to CT. No statistically significant difference in accuracy was observed between imaging modality or radiologist subspecialty.
Data supporting dementia as a risk factor for coronavirus disease 2019 (COVID-19) mortality relied on ICD-10 codes, yet nearly 40% of individuals with probable dementia lack a formal diagnosis. ...Dementia coding is not well established for people with HIV (PWH), and its reliance may affect risk assessment.
This retrospective cohort analysis of PWH with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR positivity includes comparisons to people without HIV (PWoH), matched by age, sex, race, and zipcode. Primary exposures were dementia diagnosis, by International Classification of Diseases (ICD)-10 codes, and cognitive concerns, defined as possible cognitive impairment up to 12 months before COVID-19 diagnosis after clinical review of notes from the electronic health record. Logistic regression models assessed the effect of dementia and cognitive concerns on odds of death odds ratio (OR); 95% CI (95% confidence interval); models adjusted for VACS Index 2.0.
Sixty-four PWH were identified out of 14 129 patients with SARS-CoV-2 infection and matched to 463 PWoH. Compared with PWoH, PWH had a higher prevalence of dementia (15.6% vs. 6%, P = 0.01) and cognitive concerns (21.9% vs. 15.8%, P = 0.04). Death was more frequent in PWH ( P < 0.01). Adjusted for VACS Index 2.0, dementia 2.4 (1.0-5.8), P = 0.05 and cognitive concerns 2.4 (1.1-5.3), P = 0.03 were associated with increased odds of death. In PWH, the association between cognitive concern and death trended towards statistical significance 3.92 (0.81-20.19), P = 0.09; there was no association with dementia.
Cognitive status assessments are important for care in COVID-19, especially among PWH. Larger studies should validate findings and determine long-term COVID-19 consequences in PWH with preexisting cognitive deficits.
Psychotic-spectrum disorders emerge during adolescence and early adulthood, which corresponds with the peak period for substance use initiation. Clinical and epidemiological data provide support that ...substance use is associated with psychotic symptom onset and severity. Experience-sampling methodology (ESM) data may provide additional insight into dynamic associations between substance use and psychotic symptoms. This is one of the first efforts to characterize substance use frequency and dynamic associations with psychotic symptoms and negative affect from ESM data in both clinical high risk (CHR) and early psychosis (EP) individuals.
Using ESM, 33 individuals, including 17 with CHR and 16 EP (age range: 15-24), provided information on substance use, negative affect, and psychotic symptoms 6 times a day across a 21-day data collection window. Psychotic symptoms and negative affect included multi-item variables rated on a seven-point Likert Scale. Participants reported recent substance use for 4 drug classes (nicotine, cannabis, depressants, stimulants) via a yes/no item. Descriptive information included data on substance use frequency, and momentary negative affect and psychotic symptoms. Exploratory analyses included multi-level and person-level dynamic structural equation models, which assessed contemporaneous and lagged associations between substance use and symptoms.
Twenty-seven individuals (82%) reported recurrent substance use including stimulants (
= 12, 46%), nicotine (
= 9, 27%), cannabis (
= 6, 18%), and depressants (
= 4, 12%). Individuals with any recurrent substance use indicated usage at 47.7% of answered prompts; stimulants at 23.6%; nicotine at 74.2%; cannabis at 39.1%; and depressants at 20.1%. A multi-level dynamic structural equation model reflected that substance use (any class) was associated with lagged negative affect (β = -0.02, CI: -0.06, < -0.00) but no significant contemporaneous or lagged associations between substance use and psychotic symptoms. Person-level models suggest potentially meaningful inter-individual variability.
CHR and EP individuals use a range of substances that may both reflect and influence other experiences in daily life experiences. Data reflected moderate to high rates of recurrent substance use with more consistent use within nicotine and cannabis classes. ESM data have the potential to increase our understanding of the dynamic relationships between substance use and symptoms and to inform treatment for individuals in early course psychosis.
Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of ...metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC–HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.
Objectives
To compare the diagnostic accuracy of generalist radiologists working in a community setting against abdominal radiologists working in an academic setting for the interpretation of MR when ...diagnosing acute appendicitis among emergency department patients.
Methods
This observational study examined MR image interpretation (non-contrast MR with diffusion-weighted imaging and intravenous contrast-enhanced MR) from a prospectively enrolled cohort at an academic hospital over 18 months. Eligible patients had an abdominopelvic CT ordered to evaluate for appendicitis and were > 11 years old. The reference standard was a combination of surgery and pathology results, phone follow-up, and chart review. Six radiologists blinded to clinical information, three each from community and academic practices, independently interpreted MR and CT images in random order. We calculated test characteristics for both individual and group (consensus) diagnostic accuracy then performed Chi-square tests to identify any differences between the subgroups.
Results
Analysis included 198 patients (114 women) with a mean age of 31.6 years and an appendicitis prevalence of 32.3%. For generalist radiologists, the sensitivity and specificity (95% confidence interval) were 93.8% (84.6–98.0%) and 88.8% (82.2–93.2%) for MR and 96.9% (88.7–99.8%) and 91.8% (85.8–95.5%) for CT. For fellowship-trained radiologists, the sensitivity and specificity were 96.9% (88.2–99.5%) and 89.6% (82.8–94%) for MR and 98.4% (90.5–99.9%) and 93.3% (87.3–96.7%) for CT. No statistically significant differences were detected between radiologist groups (
p
= 1.0,
p
= 0.53, respectively) or when comparing MR to CT (
p
= 0.21,
p
= 0.17, respectively).
Conclusions
MR is a reliable, radiation-free imaging alternative to CT for the evaluation of appendicitis in community-based generalist radiology practices.
Key Points
•
There was no significant difference in MR image interpretation accuracy between generalist and abdominal fellowship-trained radiologists when evaluating sensitivity (p = 1.0) and specificity (p = 0.53).
•
There was no significant difference in accuracy comparing MR to CT imaging for diagnosing appendicitis for either sensitivity (p = 0.21) or specificity (p = 0.17).
•
With experience, generalist radiologists enhanced their MR interpretation accuracy as demonstrated by improved interpretation sensitivity (OR 2.89 CI 1.44-5.77, p = 0.003) and decreased mean interpretation time (5 to 3.89 min).
Background
Computed tomography (CT) is commonly used in the Emergency Department (ED) to evaluate patients with abdominal pain, but exposes them to ionizing radiation, a possible carcinogen. MRI does ...not utilize ionizing radiation and may be an alternative.
Purpose
To compare the sensitivity of MRI and CT for acute abdominopelvic ED diagnoses.
Study Type
Prospective, observational cohort.
Population
ED patients ≥12 years old and undergoing CT for possible appendicitis.
Field Strength/Sequence
1.5 T MRI, including T1‐weighted, T2‐weighted, and diffusion‐weighted imaging sequences.
Assessment
Three radiologists independently interpreted each MRI and CT image set separately and blindly, using a standard case report form. Assessments included likelihood of appendicitis, presence of an alternative diagnosis, and likelihood that the alternative diagnosis was causing the patient's symptoms. An expert panel utilized chart review and follow‐up phone interviews to determine all final diagnoses. Times to complete image acquisition and image interpretation were also calculated.
Statistical Tests
Sensitivity was calculated for each radiologist and by consensus (≥2 radiologists in agreement) and are reported as point estimates with 95% confidence intervals. Two‐sided hypothesis tests comparing the sensitivities of the three image types were conducted using Pearson's chi‐squared test with the traditional significance level of P = 0.05.
Results
There were 15 different acute diagnoses identified on the CT/MR images of 113 patients. Using individual radiologist interpretations, the sensitivities of noncontrast‐enhanced MRI (NCE‐MR), contrast‐enhanced MR (CE‐MR), and CT for any acute diagnosis were 77.0% (72.6–81.4%), 84.2% (80.4–88.0%), and 88.7% (85.5–92.1%). Sensitivity of consensus reads was 82.0% (74.9–88.9%), 87.1% (81.0–93.2%), 92.2% (87.3–97.1%), respectively. There was no difference in sensitivities between CE‐MR and CT by individual (P = 0.096) or consensus interpretations (P = 0.281), although NCE‐MR was inferior to CT in both modes of analysis (P < 0.001, P = 0.031, respectively).
Data Conclusion
The sensitivity of CE‐MR was similar to CT when diagnosing acute, nontraumatic abdominopelvic pathology in our cohort.
Level of Evidence: 2
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2019;50:1651–1658.
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