Showing papers by "Rambam Health Care Campus published in 2021"

Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma

Abstract: Background Lenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib ...

Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma.

Abstract: Background The role of adjuvant treatment in high-risk muscle-invasive urothelial carcinoma after radical surgery is not clear. Methods In a phase 3, multicenter, double-blind, randomized, controlled trial, we assigned patients with muscle-invasive urothelial carcinoma who had undergone radical surgery to receive, in a 1:1 ratio, either nivolumab (240 mg intravenously) or placebo every 2 weeks for up to 1 year. Neoadjuvant cisplatin-based chemotherapy before trial entry was allowed. The primary end points were disease-free survival among all the patients (intention-to-treat population) and among patients with a tumor programmed death ligand 1 (PD-L1) expression level of 1% or more. Survival free from recurrence outside the urothelial tract was a secondary end point. Results A total of 353 patients were assigned to receive nivolumab and 356 to receive placebo. The median disease-free survival in the intention-to-treat population was 20.8 months (95% confidence interval [CI], 16.5 to 27.6) with nivolumab and 10.8 months (95% CI, 8.3 to 13.9) with placebo. The percentage of patients who were alive and disease-free at 6 months was 74.9% with nivolumab and 60.3% with placebo (hazard ratio for disease recurrence or death, 0.70; 98.22% CI, 0.55 to 0.90; P Conclusions In this trial involving patients with high-risk muscle-invasive urothelial carcinoma who had undergone radical surgery, disease-free survival was longer with adjuvant nivolumab than with placebo in the intention-to-treat population and among patients with a PD-L1 expression level of 1% or more. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 274 ClinicalTrials.gov number, NCT02632409.).

Lumasiran, an RNAi Therapeutic for Primary Hyperoxaluria Type 1

Abstract: Background Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and syste...

Emerging SARS-CoV-2 variants of concern and potential intervention approaches.

Abstract: The major variant of concerns (VOCs) have shared mutations in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike proteins, mostly on the S1 unit and resulted in higher transmissibility rate and affect viral virulence and clinical outcome. The spike protein mutations and other non-structural protein mutations in the VOCs may lead to escape approved vaccinations in certain extend. We will discuss these VOC mutations and discuss the need for combination therapeutic strategies targeting viral cycle and immune host responses.

Return to training in the COVID-19 era: The physiological effects of face masks during exercise

Abstract: COVID-19 outbreak has a profound impact on almost every aspect of life. Universal masking is recommended as a means of source control. Routinely exercising in a safe environment is an important strategy for healthy living during this crisis. As sports clubs and public spaces may serve a source of viral transmission, masking may become an integral part of physical activity. This study aimed to assess the physiological effects of wearing surgical masks and N95 respirators during short term strenuous workout. This was a multiple cross-over trial of healthy volunteers. Using a standard cycle ergometry ramp protocol, each subject performed a maximal exercise test without a mask, with a surgical mask, and with an N95 respirator. Physiological parameters and time to exhaustion were compared. Each subject served his own control. Sixteen male volunteers (mean age and BMI of 34 ±4 years and 28.72 ±3.78 kg/m2, respectively) completed the protocol. Heart rate, respiratory rate, blood pressure, oxygen saturation, and time to exhaustion did not differ significantly. Exercising with N95 mask was associated with a significant increase in end-tidal carbon-dioxide (EtCO2 ) levels. The differences were more prominent as the load increased, reaching 8mmHg at exhaustion (none vs. N95, p=0.001). In conclusion, in healthy subjects, short term moderate-strenuous aerobic physical activity with a mask is feasible, safe, and associated with only minor changes in physiological parameters, particularly a mild increase in EtCO2 . Subjects suffering from lung diseases should have a cautious evaluation before attempting physical activity with any mask.

COVID-19 dynamics after a national immunization program in Israel.

Abstract: Studies on the real-life effect of the BNT162b2 vaccine for Coronavirus Disease 2019 (COVID-19) prevention are urgently needed. In this study, we conducted a retrospective analysis of data from the Israeli Ministry of Health collected between 28 August 2020 and 24 February 2021. We studied the temporal dynamics of the number of new COVID-19 cases and hospitalizations after the vaccination campaign, which was initiated on 20 December 2020. To distinguish the possible effects of the vaccination on cases and hospitalizations from other factors, including a third lockdown implemented on 8 January 2021, we performed several comparisons: (1) individuals aged 60 years and older prioritized to receive the vaccine first versus younger age groups; (2) the January lockdown versus the September lockdown; and (3) early-vaccinated versus late-vaccinated cities. A larger and earlier decrease in COVID-19 cases and hospitalization was observed in individuals older than 60 years, followed by younger age groups, by the order of vaccination prioritization. This pattern was not observed in the previous lockdown and was more pronounced in early-vaccinated cities. Our analysis demonstrates the real-life effect of a national vaccination campaign on the pandemic dynamics.

Disease activity and humoral response in patients with inflammatory rheumatic diseases after two doses of the Pfizer mRNA vaccine against SARS-CoV-2.

Abstract: Background The registration trials of messenger RNA (mRNA) vaccines against SARS-CoV-2 did not address patients with inflammatory rheumatic diseases (IRD). Objective To assess the humoral response after two doses of mRNA vaccine against SARS-CoV-2, in patients with IRD treated with immunomodulating drugs and the impact on IRD activity. Methods Consecutive patients treated at the rheumatology institute, who received their first SARS-CoV-2 (Pfizer) vaccine, were recruited to the study, at their routine visit. They were reassessed 4–6 weeks after receiving the second dose of vaccine, and blood samples were obtained for serology. IRD activity assessment and the vaccine side effects were documented during both visits. IgG antibodies (Abs) against SARS-CoV-2 were detected using the SARS-CoV-2 IgG II Quant (Abbott) assay. Results Two hundred and sixty-four patients with stable disease, (mean(SD) age 57.6 (13.18) years, disease duration 11.06 (7.42) years), were recruited. The immunomodulatory therapy was not modified before or after the vaccination. After the second vaccination, 227 patients (86%) mounted IgG Ab against SARS-CoV-2 (mean (SD) 5830.8 (8937) AU/mL) and 37 patients (14%) did not, 22/37 were treated with B cell-depleting agents. The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients. Conclusions The vast majority of patients with IRD developed a significant humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2 virus. Only minor side effects were reported and no apparent impact on IRD activity was noted.

Serologic Status and Toxic Effects of the SARS-CoV-2 BNT162b2 Vaccine in Patients Undergoing Treatment for Cancer.

Abstract: Importance The efficacy and safety profile of SARS-CoV-2 vaccines have been acquired from phase 3 studies; however, patients with cancer were not represented in these trials. Owing to the recommendation to prioritize high-risk populations for vaccination, further data are warranted. Objective To evaluate the use and safety of the BNT162b2 vaccine in patients undergoing treatment for cancer. Design, Setting, and Participants In January 2021, mass SARS-CoV-2 vaccination of high-risk populations, including patients with cancer, was initiated in Israel. This cohort study prospectively enrolled and followed up patients with cancer and healthy participants between January 15 and March 14, 2021. The study was conducted at the Division of Oncology of Rambam Health Care Campus, the major tertiary (referral) medical center of northern Israel. Participants included 232 patients with cancer who were receiving active treatment after the first and second doses of the BNT162b2 vaccine and 261 healthy, age-matched health care workers who served as controls. Exposures Serum samples were collected after each vaccine dose and in cases of seronegativity. Questionnaires regarding sociodemographic characteristics and adverse reactions were administered at serum collection. A regulatory agencies–approved assay was used to assess IgG at all time points. Patients’ electronic medical records were reviewed for documentation of COVID-19 infection and results of blood cell counts, liver enzyme levels, and imaging studies. Main Outcomes and Measures Seroconversion rate after the first and second doses of the BNT162b2 vaccine and documented COVID-19 infection. Results Of the 232 patients undergoing treatment for cancer, 132 were men (57%); mean (SD) age was 66 (12.09) years. After the first dose of BNT162b2 vaccine, 29% (n = 25) patients were seropositive compared with 84% (n = 220) of the controls (P Conclusions and Relevance In this cohort study, the SARS-CoV-2 BNT162b2 vaccine appeared to be safe and achieve satisfactory serologic status in patients with cancer. There was a pronounced lag in antibody production compared with the rate in noncancer controls; however, seroconversion occurred in most patients after the second dose. Future real-world data are warranted to determine the long-term efficacy of the vaccine with regard to type of anticancer treatment.

Identification of resistance pathways and therapeutic targets in relapsed multiple myeloma patients through single-cell sequencing.

Abstract: Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR–Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors. Integration of longitudinal single-cell analysis of relapsed and refractory multiple myeloma patients in a prospective clinical trial uncovers new pathways of drug resistance and identifies potential actionable targets.

Characteristics of Early-Onset vs Late-Onset Colorectal Cancer A Review

Abstract: Importance The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. Observations Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. Conclusions and Relevance The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Safety and efficacy of BNT162b mRNA Covid19 Vaccine in patients with chronic lymphocytic leukemia.

Abstract: Patients with chronic lymphocytic leukemia (CLL) have a suboptimal humoral response to vaccination. Recently, a BNT162b2 mRNA COVID-19 vaccine was introduced with a high efficacy of 95% in immunocompetent individuals. We investigated the safety and efficacy of BNT162b2 mRNA Covid-19 vaccine in patients with CLL from nine medical centers in Israel, In total 400 patients were included, of which 373 were found to be eligible for the analysis of antibody response. The vaccine appeared to be safe and only grade 1-2 adverse events were seen in 50% of the patients. Following the second dose, antibody response was detected in 43% of the cohort. In treatment- naive patients 61% responded to the vaccine, while only 18%, 37% and 5% of patients with CLL ongoing, previously treated with BTKi, or recent anti CD20 antibody developed responses respectively. 62% and 14% of patients treated with BCL2 monotherapy or combined with anti CD20 developed immune response respectively. Neutralizing antibodies demonstrated high concordance with positive serologic response to spike (S) protein. Based on our results a simple scoring model including recent treatment with anti-CD20, age younger than 70 years, treatment naive status, and normal IGG, IGA, IGM and hemoglobin levels. The sum of all the above parameters can serve as a possible estimate to predict whether a given CLL patient will develop sufficient antibodies. In conclusion, the vaccine was found to be safe in patients with CLL, but its efficacy is limited particularly in treated patients.

Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.

Abstract: Isolated methylmalonic acidaemia (MMA) and propionic acidaemia (PA) are rare inherited metabolic diseases. Six years ago, a detailed evaluation of the available evidence on diagnosis and management of these disorders has been published for the first time. The article received considerable attention, illustrating the importance of an expert panel to evaluate and compile recommendations to guide rare disease patient care. Since that time, a growing body of evidence on transplant outcomes in MMA and PA patients and use of precursor free amino acid mixtures allows for updates of the guidelines. In this article we aim to incorporate this newly published knowledge and provide a revised version of the guidelines. The analysis was performed by a panel of multidisciplinary health care experts, who followed an updated guideline development methodology (GRADE). Hence, the full body of evidence up until autumn 2019 was re-evaluated, analysed, and graded. As a result, 21 updated recommendations were compiled in a more concise paper with a focus on the existing evidence to enable well informed decisions in the context of MMA and PA patient care. This article is protected by copyright. All rights reserved.

Hospital load and increased COVID-19 related mortality in Israel.

Abstract: The spread of Coronavirus disease 19 (COVID-19) has led to many healthcare systems being overwhelmed by the rapid emergence of new cases. Here, we study the ramifications of hospital load due to COVID-19 morbidity on in-hospital mortality of patients with COVID-19 by analyzing records of all 22,636 COVID-19 patients hospitalized in Israel from mid-July 2020 to mid-January 2021. We show that even under moderately heavy patient load (>500 countrywide hospitalized severely-ill patients; the Israeli Ministry of Health defined 800 severely-ill patients as the maximum capacity allowing adequate treatment), in-hospital mortality rate of patients with COVID-19 significantly increased compared to periods of lower patient load (250-500 severely-ill patients): 14-day mortality rates were 22.1% (Standard Error 3.1%) higher (mid-September to mid-October) and 27.2% (Standard Error 3.3%) higher (mid-December to mid-January). We further show this higher mortality rate cannot be attributed to changes in the patient population during periods of heavier load.

Humoral serologic response to the BNT162b2 vaccine is abrogated in lymphoma patients within the first 12 months following treatment with anti-CD2O antibodies.

Abstract: Patients with lymphoma, especially those treated with anti-CD20 monoclonal antibodies (MoAb), suffer high COVID-19-associated morbidity and mortality. The goal of this study was to assess the ability of lymphoma patients to generate a sufficient humoral response after two injections of BNT162b2 Pfizer vaccine and to identify factors impacting the response. Antibody titers were measured with the SARS-CoV-2 IgG II Quant (Abbott©) assay in blood samples drawn from lymphoma patients 4±2 weeks after the 2nd vaccine dose. The cutoff for a positive response was set at 50AU/ml. Positive serological responses were observed in 51% of the 162 patients enrolled in this cross-sectional study. In a multivariate analysis, an interval of.

Cancer-Associated Fibroblasts Promote Aggressive Gastric Cancer Phenotypes via Heat Shock Factor 1-Mediated Secretion of Extracellular Vesicles.

Abstract: Gastric cancer is the 3rd most lethal cancer worldwide, and evaluation of the genomic status of gastric cancer cells has not translated into effective prognostic or therapeutic strategies We therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), in particular, cancer-associated fibroblasts (CAF) However, very little is known about the role of CAFs in gastric cancer To address this, we mapped the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from gastric cancer patients A stromal gene signature was associated with poor disease outcome, and the transcription factor heat shock factor 1 (HSF1) regulated the signature HSF1 upregulated inhibin subunit beta A (INHBA) and thrombospondin 2 (THBS2), which were secreted in CAF-derived extracellular vesicles (EV) to the TME to promote cancer Together, our work provides the first transcriptional map of human gastric cancer stroma and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment

SARS-CoV-2 Vaccine and Thrombosis: An Expert Consensus on Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Abstract: Historically, the vaccination strategies developed in the second half of the 20th century have facilitated the eradication of infectious diseases. From the onset of COVID-19 pandemic to the end of April 2021, more than 150 million cases and 3 million deaths were documented worldwide with disruption of the economic and social activity, and with devastating material, physical, and psychological consequences. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community. This report is intended to provide practical answers following an overview of our knowledge on these thrombotic events that are extremely rare but have serious consequences. Vaccine hesitancy threatens to reverse the progress made in controlling vaccine-preventable diseases. These adverse events must be put into perspective with an objective analysis of the facts and the issues of the vaccination strategy during this SARS-CoV-2 pandemic. Health care professionals remain the most pertinent advisors and influencers regarding vaccination decisions; they have to be supported to provide reliable and credible information on vaccines. We need to inform, reassure, and support our patients when the prescription is made. Facing these challenges and observations, a panel of experts express their insights and propose a tracking algorithm for vaccinated patients based on a 10-point guideline for decision-making on what to do and not to do.

SPEN haploinsufficiency causes a neurodevelopmental disorder overlapping proximal 1p36 deletion syndrome with an episignature of X chromosomes in females

Abstract: Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): Position paper on diagnosis, prognosis, and treatment by the MNGIE International Network.

Abstract: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.

Signals of hope: gauging the impact of a rapid national vaccination campaign.

Abstract: A rapid coronavirus disease 2019 (COVID-19) vaccination rollout has led Israel to become the country with the highest rate of vaccinated individuals per capita worldwide. Here, we summarize the first signs for the real-world effectiveness and impact of the vaccination campaign. Preliminary data from Israel demonstrate real-life effectiveness of their COVID-19 vaccination campaign and provide insights that could inform rollout in other countries.

Six-Month Efficacy and Toxicity Profile of BNT162b2 Vaccine in Cancer Patients with Solid Tumors.

Abstract: We had previously reported short-term efficacy, immunogenicity, and safety of the BNT162b2 vaccine among cancer patients with solid tumors. We aimed to evaluate these outcomes at six months postvaccination. The study cohort comprised patients who were on treatment during vaccination and throughout six months postvaccination. Serologic tests were performed after second vaccination and six months afterward. An age-matched cohort of health care workers served as controls. Documentation of COVID-19 infection, blood tests, and imaging studies during the study period was reviewed. Participants included 154 patients and 135 controls. Six months postvaccination, 122 (79%) patients were seropositive compared with 114 (84%) controls (P = 0.32). Serology titer dramatically decreased in a similar manner in both cohorts. No COVID-19 cases were documented in controls, and one case occurred in patient cohort. All previously reported adverse effects resolved. Taken together, the pattern of immunogenicity, efficacy, and safety of BNT162b2 in patients with cancer with solid tumors at six months postvaccination resembles that of the general population. SIGNIFICANCE: Evidence regarding efficacy and safety of COVID-19 vaccines in patients with cancer indicate a favorable short-term profile. Immunomodulation due to anticancer treatments may affect immunity and immunogenicity of patients with cancer to the BNT162b2 vaccine over time. Our study sheds light on these long-term outcomes and portrays a trend that resembles the general population.This article is highlighted in the In This Issue feature, p. 2355.

Evaluation of Artificial Intelligence–Powered Identification of Large-Vessel Occlusions in a Comprehensive Stroke Center

Abstract: BACKGROUND AND PURPOSE: Artificial intelligence algorithms have the potential to become an important diagnostic tool to optimize stroke workflow. Viz LVO is a medical product leveraging a convolutional neural network designed to detect large-vessel occlusions on CTA scans and notify the treatment team within minutes via a dedicated mobile application. We aimed to evaluate the detection accuracy of the Viz LVO in real clinical practice at a comprehensive stroke center. MATERIALS AND METHODS: Viz LVO was installed for this study in a comprehensive stroke center. All consecutive head and neck CTAs performed from January 2018 to March 2019 were scanned by the algorithm for detection of large-vessel occlusions. The system results were compared with the formal reports of senior neuroradiologists used as ground truth for the presence of a large-vessel occlusion. RESULTS: A total of 1167 CTAs were included in the study. Of these, 404 were stroke protocols. Seventy-five (6.4%) patients had a large-vessel occlusion as ground truth; 61 were detected by the system. Sensitivity was 0.81, negative predictive value was 0.99, and accuracy was 0.94. In the stroke protocol subgroup, 72 (17.8%) of 404 patients had a large-vessel occlusion, with 59 identified by the system, showing a sensitivity of 0.82, negative predictive value of 0.96, and accuracy of 0.89. CONCLUSIONS: Our experience evaluating Viz LVO shows that the system has the potential for early identification of patients with stroke with large-vessel occlusions, hopefully improving future management and stroke care.

Survival Benefit for Individuals With Constitutional Mismatch Repair Deficiency Undergoing Surveillance.

Abstract: PURPOSEConstitutional mismatch repair deficiency syndrome (CMMRD) is a lethal cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors. We designed...