Contrast-enhanced spectral mammography vs. mammography and MRI - clinical performance in a multi-reader evaluation.

OBJECTIVES: To compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) to digital mammography (MG) and magnetic resonance imaging (MRI) in a prospective two-centre, multi-reader study. METHODS: One hundred seventy-eight women (mean age 53 years) with invasive breast cancer and/or DCIS were included after ethics board approval. MG, CESM and CESM + MG were evaluated by three blinded radiologists based on amended ACR BI-RADS criteria. MRI was assessed by another group of three readers. Receiver-operating characteristic (ROC) curves were compared. Size measurements for the 70 lesions detected by all readers in each modality were correlated with pathology. RESULTS: Reading results for 604 lesions were available (273 malignant, 4 high-risk, 327 benign). The area under the ROC curve was significantly larger for CESM alone (0.84) and CESM + MG (0.83) compared to MG (0.76) (largest advantage in dense breasts) while it was not significantly different from MRI (0.85). Pearson correlation coefficients for size comparison were 0.61 for MG, 0.69 for CESM, 0.70 for CESM + MG and 0.79 for MRI. CONCLUSIONS: This study showed that CESM, alone and in combination with MG, is as accurate as MRI but is superior to MG for lesion detection. Patients with dense breasts benefitted most from CESM with the smallest additional dose compared to MG. KEY POINTS: • CESM has comparable diagnostic performance (ROC-AUC) to MRI for breast cancer diagnostics. • CESM in combination with MG does not improve diagnostic performance. • CESM has lower sensitivity but higher specificity than MRI. • Sensitivity differences are more pronounced in dense and not significant in non-dense breasts. • CESM and MRI are significantly superior to MG, particularly in dense breasts.

Evolution of pathogenicity and sexual reproduction in eight Candida genomes.

Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.

Life Over Limb: Why Not Both? Revisiting Tourniquet Practices Based on Lessons Learned From the War in Ukraine.

The use of tourniquets for life-threatening limb hemorrhage is standard of care in military and civilian medicine. The United States (U.S.) Department of Defense (DoD) Committee on Tactical Combat Casualty Care (CoTCCC) guidelines, as part of the Joint Trauma System, support the application of tourniquets within a structured system reliant on highly trained medics and expeditious evacuation. Current practices by entities such as the DoD and North Atlantic Treaty Organization (NATO) are supported by evidence collected in counter-insurgency operations and other conflicts in which transport times to care rarely went beyond one hour, and casualty rates and tactical situations rarely exceeded capabilities. Tourniquets cause complications when misused or utilized for prolonged durations, and in near-peer or peer-peer conflicts, contested airspace and the impact of high-attrition warfare may increase time to definitive care and limit training resources. We present a series of cases from the war in Ukraine that suggest tourniquet practices are contributing to complications such as limb amputation, overall morbidity and mortality, and increased burden on the medical system. We discuss factors that contribute to this phenomenon and propose interventions for use in current and future similar contexts, with the ultimate goal of reducing morbidity and mortality.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Correlation of contrast agent kinetics between iodinated contrast-enhanced spectral tomosynthesis and gadolinium-enhanced MRI of breast lesions.

OBJECTIVES: Assessment of contrast agent kinetics in contrast-enhanced MRI (CE-MRI) with gadolinium-containing contrast agents offers the opportunity to predict breast lesion malignancy. The goal of our study was to determine if similar patterns exist for spectral contrast-enhanced digital breast tomosynthesis (CE-DBT) using an iodinated contrast agent. METHODS: The protocol of our prospective study was approved by the relevant institutional review board and the German Federal Office for Radiation Protection. All patients provided written informed consent. We included 21 women with a mean age of 62.4 years. All underwent ultrasound-guided biopsy of a suspect breast lesion, spectral CE-DBT and CE-MRI. For every breast lesion, contrast agent kinetics was assessed by signal intensity-time curves for spectral CE-DBT and CE-MRI. Statistical comparison used Cohen's kappa and Spearman's rho test. RESULTS: Spearman's rho of 0.49 showed significant (P = 0.036) correlation regarding the contrast agent kinetics in signal intensity-time curves for spectral CE-DBT and CE-MRI. Cohen's kappa indicated moderate agreement (kappa = 0.438). CONCLUSION: There is a statistically significant correlation between contrast agent kinetics in the signal intensity-time curves for spectral CE-DBT and CE-MRI. Observing intralesional contrast agent kinetics in spectral CE-DBT may aid evaluation of malignant breast lesions. KEY POINTS: • Contrast agent kinetics can be assessed using spectral digital breast tomosynthesis (DBT). • Contrast agent kinetics patterns in spectral DBT are similar to those in contrast-enhanced MRI. • Multiple contrast enhancement for spectral DBT gives additional diagnostic information.

Public Health Challenges and Barriers to Health Care Access for Asylum Seekers at the U.S.-Mexico Border in Matamoros, Mexico.

The Migrant Protection Protocols (MPP) and border closure to asylum seekers during the COVID-19 pandemic created a humanitarian crisis at the U.S.-Mexico border. This paper outlines the public health challenges and health care access barriers for asylum seekers living in a tent encampment in Matamoros, Mexico resulting from these policies. Thirty participants, including asylum seekers (n=20) and health care professionals (n=10) in the Matamoros asylum camp, were interviewed. Public health challenges included environmental exposures and inadequate infrastructure; poor sanitation and disease control; and limited safety, nutrition, education, and employment. Health care access barriers included lack of continuity of care and emergency services, resource insufficiencies, and interpersonal barriers. Policy responses to address these challenges include outlawing MPP and other immigration policies that infringe on human rights, collaborating with international partners, and implementing more creative and community-based approaches to asylum processing.

Detection of Hemodynamic Status Using an Analytic Based on an Electrocardiogram Lead Waveform.

OBJECTIVES: Delayed identification of hemodynamic deterioration remains a persistent issue for in-hospital patient care. Clinicians continue to rely on vital signs associated with tachycardia and hypotension to identify hemodynamically unstable patients. A novel, noninvasive technology, the Analytic for Hemodynamic Instability (AHI), uses only the continuous electrocardiogram (ECG) signal from a typical hospital multiparameter telemetry monitor to monitor hemodynamics. The intent of this study was to determine if AHI is able to predict hemodynamic instability without the need for continuous direct measurement of blood pressure. DESIGN: Retrospective cohort study. SETTING: Single quaternary care academic health system in Michigan. PATIENTS: Hospitalized adult patients between November 2019 and February 2020 undergoing continuous ECG and intra-arterial blood pressure monitoring in an intensive care setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One million two hundred fifty-two thousand seven hundred forty-two 5-minute windows of the analytic output were analyzed from 597 consecutive adult patients. AHI outputs were compared with vital sign indications of hemodynamic instability (heart rate > 100 beats/min, systolic blood pressure < 90 mm Hg, and shock index of > 1) in the same window. The observed sensitivity and specificity of AHI were 96.9% and 79.0%, respectively, with an area under the curve (AUC) of 0.90 for heart rate and systolic blood pressure. For the shock index analysis, AHI's sensitivity was 72.0% and specificity was 80.3% with an AUC of 0.81. CONCLUSIONS: The AHI-derived hemodynamic status appropriately detected the various gold standard indications of hemodynamic instability (hypotension, tachycardia and hypotension, and shock index > 1). AHI may provide continuous dynamic hemodynamic monitoring capabilities in patients who traditionally have intermittent static vital sign measurements.

Identifying Strategies to Boost COVID-19 Vaccine Acceptance in the United States.

This study presents the results of an evaluation of the root causes of COVID-19 vaccine hesitancy to inform strategies to boost vaccine acceptance among vaccine-hesitant populations in the United States. The authors conducted a literature review of the causes of vaccine hesitancy and vaccine acceptance; focus groups with patients, pre-hospital first responders, and hospital-based health care providers; a social media platform sentiment analysis to review attitudes regarding the COVID-19 vaccine; and a roundtable discussion with experts on vaccine hesitancy. Drawing on this mixed-methods analysis, the authors recommend strategies to help boost COVID-19 vaccine acceptance in the United States, grouping them according to three overall goals: boosting confidence in the safety and effectiveness of the COVID-19 vaccines, combating complacency about the pandemic, and increasing the convenience of getting vaccinated. The authors emphasize that combating misinformation about the COVID-19 vaccine is key to achieving these goals. These recommendations can inform the development of a toolkit of strategies to reach herd immunity and end the pandemic.

ECPR2: Expert Consensus on PeRcutaneous Cannulation for Extracorporeal CardioPulmonary Resuscitation.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a promising resuscitation strategy for select patients suffering from refractory out-of-hospital cardiac arrest (OHCA), though limited data exist regarding the best practices for ECPR initiation after OHCA. METHODS: We utilized a modified Delphi process consisting of two survey rounds and a virtual consensus meeting to systematically identify detailed best practices for ECPR initiation following adult non-traumatic OHCA. A modified Delphi process builds content validity and is an accepted method to develop consensus by eliciting expert opinions through multiple rounds of questionnaires. Consensus was achieved when items reached a high level of agreement, defined as greater than 80% responses for a particular item rated a 4 or 5 on a 5-point Likert scale. RESULTS: Snowball sampling generated a panel of 14 content experts, composed of physicians from four continents and five primary specialties. Seven existing institutional protocols for ECPR cannulation following OHCA were identified and merged into a single comprehensive list of 207 items. The panel reached consensus on 101 items meeting final criteria for inclusion: Prior to Patient Arrival (13 items), Inclusion Criteria (8), Exclusion Criteria (7), Patient Arrival (8), ECPR Cannulation (21), Go On Pump (18), and Post-Cannulation (26). CONCLUSION: We present a list of items for ECPR initiation following adult nontraumatic OHCA, generated using a modified Delphi process from an international panel of content experts. These findings may benefit centers currently performing ECPR in quality assurance and serve as a template for new ECPR programs.

Development of low-dose photon-counting contrast-enhanced tomosynthesis with spectral imaging.

PURPOSE: To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. MATERIALS AND METHODS: All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. RESULTS: Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. CONCLUSION: The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity.

Challenges and Effects of the COVID-19 Pandemic on Asylum Seeker Health at the U.S.-Mexico Border.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic presents health care challenges to asylum seekers living in congregate encampments, including those along the U.S.-Mexico border. It is necessary to understand the impact of the pandemic among this population to address health care needs, reduce transmission, and diminish COVID-19-related morbidity. Methods: Thirty interviews were conducted with asylum seekers and health care professionals in a temporary camp in Matamoros, Mexico to determine challenges, perceptions, and effects of the COVID-19 pandemic. Interviews were coded in NVivo12 by using a team-based approach. Results: The pandemic caused significant mental health burdens but no perceived adverse physical effects, with the U.S. border closure and health care access barriers as more pressing concerns. Participants reported access to information about COVID-19 but had varied levels of knowledge and adherence to disease reduction strategies due to camp conditions. Most participants believed that they had special protection from COVID-19, including strong immune systems or from God. The nongovernmental organizations providing health care and sanitation faced multiple challenges to implement new policies to manage COVID-19. The institution of required temperature checks and quarantine of COVID-19 positive patients led to distrust, decreased seeking of health care services among asylum seekers, and possible underreporting of COVID-19 cases. Conclusion: Our findings among asylum seekers in a Matamoros camp highlight the challenges to implementing disease reduction policies in low-resource congregate camps. Policies to address disease outbreaks focusing on the social determinants of health, health care access barriers, and community engagement may be more acceptable to asylum seekers, suggesting the need for effective strategies to provide prevention information that complements such measures.

Single Nucleotide Polymorphisms Caused by Assembly Errors.

We compare the results of three different assembler programs, Celera, Phrap and Mira2, for the same set of about a hundred thousand Sanger reads derived from an unknown bacterial genome. In difference to previous assembly comparisons we do not focus on speed of computation and numbers of assembled contigs but on how the different sequence assemblies agree by content. Threefold consistently assembled genome regions are identified in order to estimate a lower bound of erroneously identified single nucleotide polymorphisms (SNP) caused by nothing but the process of mathematical sequence assembly. We identified 509 sequence triplets common to all three de-novo assemblies spanning only 34% (3.3 Mb) of the bacterial genome with 175 of these regions (~1.5 Mb) including erroneous SNPs and insertion/deletions. Within these triplets this on average leads to one error per 7,155 base pairs. Replacing the assembler Mira2 by the most recent version Mira3, the letter number even drops to 5,923. Our results therefore suggest that a considerably high number of erroneous SNPs may be present in current sequence data and mathematicians should urgently take up research on numerical stability of sequence assembly algorithms. Furthermore, even the latest versions of currently used assemblers produce erroneous SNPs that depend on the order reads are used as input. Such errors will severely hamper molecular diagnostics as well as relating genome variation and disease. This issue needs to be addressed urgently as the field is moving fast into clinical applications.