University Of Rochester Medical Center Research Articles

Policy Throughout The Pandemic

Policy Throughout The Pandemic

Next generation sequencing of sarcomas: Response to crizotinib in two cases with MET amplification.

11538 Background: Sarcoma subtypes are often defined by recurrent molecular alterations. The purpose of this study is to review the utility of next generation sequencing (NGS) in sarcoma patients and report clinical outcomes to matched therapies. Methods: The records of all patients seen at the University of Rochester Medical Center (URMC) with sarcoma and NGS profiling between 8/2013 and 3/2020 were reviewed. Responses to agents targeting reported alterations were analyzed. In patients with fluorescent-in-situ hybridization (FISH) testing, fusion events by NGS were compared with FISH results. All highlighted pathogenic alterations on the NGS profile report as well as variants of uncertain significance (VUS) were recorded. Results: Seventy-five patients met inclusion criteria. Of these, 25 received a treatment based on identified alterations; 1 had a complete response (CR), 4 had partial responses (PR), and 4 experienced disease stabilization (SD). We identified two patients with MET amplified sarcoma that responded to treatment with crizotinib. One other patient with a diagnosis of leiomyosarcoma was found to have an unusually high total mutational burden (TMB) and experienced complete pathologic response to dual checkpoint blockade. In 4 cases, testing resulted in a change in subtype diagnosis. Several rare and novel fusions were identified; a sarcoma with TPM4-NTRK3 fusion responded to larotrectinib, while a sarcoma with PML-JAK1 fusion did not respond to ruxolitinib, and a sarcoma with IL7R-BCL2 fusion progressed on venetoclax. Table summarizes matched therapies in responders. Conclusions: NGS profiling led to a targeted therapy with a clinical benefit rate of 12% in this cohort. NGS profiling led to a change in diagnosis in 5% of this cohort. Multi-institutional collaborations to track outcomes of matched therapy would help determine the utility of therapies in rare cancers and unusual alterations.[Table: see text]

Clinical Faceoff: How Will Recent Price Transparency Policies Impact Orthopaedic Surgery and its Patients?

Clinical Faceoff: How Will Recent Price Transparency Policies Impact Orthopaedic Surgery and its Patients?

Toxicological assessment of e‐cigarette or vaping product use associated lung injury (EVALI) cartridges and constituents

Rationale Definitive causative agents of the outbreak associated with the use of e-cigarette, or vaping product use associated lung injury (EVALI) are unknown. Patients diagnosed with EVALI have used vape products containing tetrahydrocannabinol (THC) and vitamin E acetate (VEA). Hypothesis We hypothesized that inhalation of these EVALI vape cartridges and their constituents induce pulmonary toxicity, mediated by oxidative damage and inflammatory responses, leading to acute lung injury, and alters SARS-CoV-2 related proteins. Methods Vaping products were recovered from hospitalized patients at the University of Rochester Medical Center. Cartridge constituents were characterized by gas chromatography and mass spectrometry. Comparative toxicity of exposure to common vape cartridge components such as medium-chain triglyceride (MCT) oil, VEA, and patient-derived cartridge aerosols was assessed by in vitro and in vivo models. Lung epithelial cells (BEAS-2B) and monocytes (Mono-Mac-6). Cells were exposed to MCT, VEA, and cartridge aerosols and the elicited inflammatory response, barrier function, and lipid-laden index were determined. C57BL/6 mice were exposed to MCT, VEA, and vape cartridge aerosols for three days (1 hr/day). The immune response was determined by differential cell counts, cytokine milieu, and lipidomics analysis in bronchoalveolar lavage fluid (BALF). Lung surfactant protein (SP-A), SARS-CoV-2 proteins (ACE2 and TMPRSS2) were quantified in the lung homogenates. Results Constituents identified patient-derived vaping products included reactive hydrocarbons and various forms of cannabinoids. VEA and cartridge aerosols induced significantly increased IL-6 and IL-8 responses in lung epithelial cells and monocytes. MCT, VEA, and cartridge aerosols induced barrier dysfunction. Increased lipid-laden indices were observed in MM6 cells. In mice, acute exposure to cartridge aerosols caused a significant infiltration of leukocytes in BALF and increased IL-6, eotaxin, and G-CSF in the BALF. Lipidomics analysis showed significantly increased eicosanoid inflammatory mediators and leukotrienes. Reduced levels of SP-A levels were seen in lung homogenates. Exposure to cartridge aerosols showed the most significant effects and toxicity compared to MCT and VEA. SARS-CoV-2 related proteins were not affected. Conclusion Acute exposure to vape cartridges induces cytotoxicity, barrier dysfunction, and elicit an inflammatory response in lung cells and mice, which are potential predictive toxicological markers of EVALI. Toxicity of vape cartridges was independent of SARS-CoV-2 proteins. This study provides important identification of potential chemical constituents, toxicological responses, and potential biomarkers of EVALI.

Role of Family Environment on Recognition of Diverse Gender Identities and Presentation to Care

* Abbreviations: GAMC — : gender-affirming medical care TGGD — : transgender and gender-diverse LGBTQ+ — : lesbian, gay, bisexual, transgender, queer, etc In 2018, the American Academy of Pediatrics recommended that all transgender and gender-diverse (TGGD) youth “have access to comprehensive, gender-affirming, and developmentally appropriate health care.”1 In its position statement, The American Academy of Pediatrics acknowledges mounting evidence that gender-affirming medical care (GAMC) for TGGD youth improves health and developmental outcomes2,3 and describes the critical role that pediatricians play in diagnosing, supporting, and facilitating access to care for TGGD youth. Furthermore, the timing of presentation to care for peri-pubertal youth is critical because delays in care impact whether and to what extent a youth can benefit from treatment with pubertal suppression. Access to puberty suppression may have an impact not only on mental health outcomes, but also on the need for or type of future surgical interventions.4,5 It is vital that providers who care for youth understand the factors that impact youth’s timing of presentation to gender-affirming care so that we may facilitate timely access to GAMC for all youth, particularly those with intersectional identities that have an additional impact on access to health care. In this issue of Pediatrics … Address correspondence to Jamie E. Mehringer, MD, Pediatrics and Adolescent Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Box 690, Rochester, NY 14642. E-mail: jamie_mehringer{at}urmc.rochester.edu

Treatment of Peanut Allergy.

1. Amy Burris, MD*,† 2. Theresa Bingemann, MD*,† 1. *Department of Medicine: Allergy, Immunology, and Rheumatology and 2. †Division of Pediatric Allergy and Immunology, University of Rochester Medical Center, Rochester, NY Peanut allergy (PA) affects 0.5% to 2% of children and is often a persistent condition that poses the risk of life-threatening reactions on exposure to peanut. It is the most common food allergy to cause anaphylaxis and death. Because allergy testing does not predict the severity of reactions, it is imperative that peanut-allergic children have access to epinephrine autoinjectors at all times. Although cutaneous reactions, including generalized urticaria, angioedema, and atopic dermatitis, are the most common, anaphylaxis accounts for more than one-third of reactions. Recently, research has focused on prevention strategies for PA. In high-risk infants, early introduction of peanut at younger than 11 months of age plays a crucial role in preventing PA. Conversely, avoidance of peanut is associated with increased risk of PA. Guidelines recommend early introduction of peanut to infants with no eczema or mild to moderate eczema. Infants with severe eczema should be promptly referred to an allergist for evaluation of peanut sensitization before introduction. Disruption of the skin barrier, as with eczema, plays a role in the development of food allergy. Transcutaneous exposure of food allergens may promote allergic sensitization, whereas allergen exposure through the gut may promote tolerance. Studies show that increased environmental peanut exposure leads to increased risk of PA, especially in children with eczema. Aggressive emollient therapy early in life may decrease the risk of developing eczema. Studies examining the role of early emollient therapy and development of food allergy are ongoing. The cross-reactivity between peanut allergens and environmental allergens means that apparent sensitization to peanut does not necessarily …

Abstract P310: Impact of COVID-19 Pandemic on Stroke Care at the University of Rochester Medical Center

Introduction: The impact of the COVID-19 pandemic response on medical care for stroke is unknown. Methods: We used local “Get With The Guidelines” stroke data for patients with ischemic stroke (IS), transient ischemic attack (TIA), and intracerebral hemorrhage/subarachnoid hemorrhage (ICH/SAH) from March 20–April 14, 2020 (study period) and January 1–March 19, 2020 (control period #1) and March 20–April 14, 2019 (control period #2). We examined daily admission rates, transfers, tPA administration, thrombectomy, and time from last well to hospital arrival. Results: There were 349 patients (n=40 study period, n=225 control period #1, n=84 control period #2); 263 with IS, 37 with TIA, and 49 with ICH/SAH. Overall, 46% were female, 82% white, with median age 70 years (IQR 58-82 years). Daily admission rates were 1.4 IS/day for the study period compared to 2.1 IS/day (Incident rate ratio [IRR] 1.49 95% CI 1.05-2.13, p=0.027) and 2.2 IS/day (IRR 1.57 1.04-2.37, p=0.033) for control periods #1 and #2 ( Table ), respectively. There was only one admission for TIA in the study period compared to approximately one every 4 days in control period #1 (IRR 7.2 95% CI 1.0-53.7, p=0.053) and one every 2 days in control period #2 (IRR 14.0 95% CI 1.8-106.5, p=0.011). ICH/SAH admissions were fewer in the study period. Transfers were less common with approximately one transfer every four days in the study period compared to one each day of the control periods. Rates of tPA, thrombectomy, and time from last well to first hospital contact did not differ across the epochs. Conclusions: Our data suggest the COVID-19 pandemic response has led to reduced admission volumes for all stroke types in the University of Rochester Medical Center catchment area, partly due to decreases in hospital transfers. These data raise the question whether fewer patients sought care for stroke symptoms at the height of the COVID-19 pandemic.

Optimising rapid on‐site evaluation‐assisted endobronchial ultrasound‐guided transbronchial needle aspiration of mediastinal lymph nodes: The real‐time cytopathology intervention process

Lymph node sampling by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the state of art procedure for staging the mediastinum and hilar regions in lung cancer patients. Our experience of implementing the real-time cytopathology intervention (RTCI) process for intraoperative EBUS-TBNAs is presented. This study is aimed to describe in detail the RTCI process for EBUS-TBNAs, and assess its utility and diagnostic yield before and after its implementation in parallel to conventional rapid on-site evaluation (c-ROSE). A retrospective review of all EBUS-TBNAs between July 2016 and July 2017 at the University of Rochester Medical Center was performed. Final diagnoses, patient clinical data, and number of non-diagnostic samples (NDS) were reviewed. The numbers of NDS obtained from EBUS-TBNAs with no cytology assistance (NCA), with RTCI and with c-ROSE were analysed. Non-diagnostic lymph node samples were found in 20 out of 116 (17%), three out of 114 (2.6%) and 33 out of 286 (11.5%) cases with NCA, RTCI and c-ROSE, respectively. Application of statistical analysis revealed significant difference in the NDS between the groups of cases in the operating room with NCA and RTCI (P=.005). The different settings and variables between the cases performed using RTCI in the operating room and those assisted with c-ROSE in the bronchoscopy suite preclude legitimate comparison. Our results indicate that the use of RTCI could yield a significantly low proportion of NDS when assisting EBUS-TBNA of mediastinal and hilar lymph node for lung cancer patients enhancing the diagnostic efficiency of the procedure.

Proactive C-L Psychiatry: Re-envisioning Psychiatric Care in Medical Settings

Proactive C-L Psychiatry: Re-envisioning Psychiatric Care in Medical Settings

127. walking to the Virtual Era. Analysis of the Telehealth Experience in the Infectious Diseases Clinic During the COVID Pandemic

BackgroundThe COVID pandemic has changed and will continue changing the way we practice medicine. We sought to investigate the impact of telehealth (TH) in the delivery of healthcare in the general infectious diseases (GID), and HIV clinic during the COVID pandemic.The University of Rochester Medical Center is a major tertiary care and referral center for ID in upstate New York. From March through May of 2020, the clinics were closed, and nearly all visits were conducted by TH.MethodsWe surveyed (either by telephone or online) a total of 260 patients who participated in TH visits, with a mean age of 56 years in the HIV group and 59 years in the GID group. With a predominance of 62.8 of males v/s 37.2 of females.We collected information regarding the reason for the TH visits, access to technology, patient satisfaction, and preferences over in-person visits. We obtained the volume and no-show rate from prior years through EPIC. We evaluated compliance between in-person and TH visits using statistical analysis.ResultsWe found 93.4% of GID and 84.3% of HIV patients surveyed, either strongly agreed or somewhat agreed that their TH visit was as satisfactory as a clinic visit. 67.5% of GID and 63% of HIV patients agreed that the option of TH would increase their compliance rate in the future. The no-show rate during the TH period in the HIV group decreased from 23% to 5% compared to the previous year, while the no-show rate in GID decreased from 9% to 4%. These results were statistically significant with a P-value < 0.005 in both groups. ConclusionGID patients were more likely to have TH for hospital follow-up, follow-up of acute problems, and outpatient antibiotic therapy, compared to HIV patients, who more often had TH for chronic problems. GID patients were more likely to have the capability for televideo visits when compared to the HIV group, although this was not statistically significant. TH was statistically significant in improving patient compliance with appointments in both the HIV and ID clinics. Patients were overall highly satisfied with their TH experience and many patients also reported that continued availability of telemedicine would improve their compliance with appointments. Disclosures All Authors: No reported disclosures

Depression Screening and Rates of Mood Disorder Diagnosis and Suicide in Younger and Older Adults

Rates of suicide are elevated among older adults in the U.S. and around the world, with the highest rates in older men (CDC, 2019; WHO, 2014). More than half of older adults who die by suicide were in contact with a primary care physician within the month prior to death, and almost one-third within the prior week (Luoma et al., 2002; Stene-Larsen & Reneflot, 2019), demonstrating the importance of better identification and treatment of mental health issues among older adults across healthcare systems. Depression, a well-established risk factor for suicide, goes under-diagnosed and under-treated, especially among older adults (Bryant, 2010). The University of Rochester Medical Center has led integration of patient-reported outcomes assessment via large-scale implementation of PROMIS measures across multiple departments. We compared results of PROMIS depression screening from 1/1/2015 to 8/31/2019 with mood disorder diagnoses within the year prior and year following screening. Twenty-six percent (39491/154669) of adults under age 65 and 23% (11694/51702) of those age 65 and older screened positive for mild, moderate, or severe depression. Whereas 29.0% of younger adults who screened positive received mood disorder diagnoses, 22.1% of older adults received a diagnosis (χ2(1)=214.69, p<.001). Suicide outcomes using National Death Index data will also be reported. Results confirm depression is underdiagnosed (and, by extension, likely undertreated) at all ages, but show a distinct disparity for older adults, which may put them at greater risk for negative outcomes such as suicide.

A Preliminary Assessment of HeterozygousCFHR3-CFHR1Deletion As a Permissive Mutation in Carfilzomib-Induced Atypical Hemolytic Uremic Syndrome

Carfilzomib is a critical chemotherapy medication used to treat patients with relapsed or refractory multiple myeloma. Unfortunately, drug-induced atypical hemolytic uremic syndrome (aHUS) has been established as a devastating and unpredictable side-effect of carfilzomib. Loss-of-function mutations in alternative complement pathway regulatory genes, such as complement factor H (CFH) and its related proteins (CFHRs), are the most frequently identified genetic abnormalities seen with aHUS. In our recently published work, two of three patients treated at the University of Rochester Medical Center for carfilzomib-induced aHUS were found to harbor the heterozygousCFHR3-CFHR1deletion, a genetic variant that is generally considered benign, implicating it in development of disease. We sought to further characterize the relationship between the heterozygousCFHR3-CFHR1deletion and development of carfilzomib-induced aHUS by conducting a case-control study. We screened banked frozen peripheral blood mononuclear cell (PBMC) samples from subjects treated with carfilzomib-based regimens at Washington University. Criteria for aHUS case selection were defined as all of the following: elevated LDH, decreased haptoglobin or elevated total bilirubin, evidence of schistocytes on peripheral blood smear, de novo anemia and thrombocytopenia, acute kidney injury, no evidence of infectious diarrhea (if tested), and active carfilzomib treatment at the time of disease. To ensure that controls had adequate exposure to carfilzomib, controls were selected from subjects who received ≥20 treatment cycles. Additional control selection criteria included: age &amp;gt;40 years, no evidence of hemolysis (LDH &amp;lt;250 U/L, total bilirubin &amp;lt;1.2 mg/dL), no de novo anemia or thrombocytopenia (hemoglobin &amp;gt;9 g/dL and platelets &amp;gt;100 x 109/L), and no chronic or acute kidney disease (creatinine &amp;lt;1.5 mg/dL). Ultimately, three cases of aHUS and four controls were identified. Corresponding PBMC samples were submitted to the Molecular Otolaryngology and Renal Research Laboratories for multiplex ligation-dependent probe amplificationCFH-CFHR5genomic region testing. We found that two of three case samples (4 of 6 total [67%], including the previously published cases), and two of four control samples (50%) harbored the heterozygousCFHR3-CFHR1mutation. No otherCFH-CFHR5genomic region mutations were detected. The frequency of heterozygousCFHR3-CFHR1deletion was not found to be significantly different between case and control groups. Given the large amount of carfilzomib exposure among the control group, this result suggests that the heterozygousCFHR3-CFHR1deletion is likely not a predisposing mutation in the development carfilzomib-induced aHUS. However, an adequately powered case-control study would be required to statistically rule-out the association. Disclosures Wildes: Seattle Genetics:Consultancy;Janssen:Research Funding;Carevive Systems:Consultancy.Lipe:Janssen:Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline:Membership on an entity's Board of Directors or advisory committees;Celgene:Membership on an entity's Board of Directors or advisory committees;Amgen:Membership on an entity's Board of Directors or advisory committees.

Urinary tract cytology: a cytologic-histopathologic correlation with The Paris System, an institutional study

Urothelial carcinoma (UC) requires lifelong monitoring, commonly through urinary cytology and cystoscopy. Urine cytology has a relatively high sensitivity for detecting high-grade urothelial carcinoma (HGUC); however, its sensitivity for low-grade urothelial neoplasm (LGUN) is significantly lower with wide interobserver variability. The Paris System (TPS) was proposed to create standardized diagnostic categories with defined cytomorphologic criteria. We attempt to evaluate diagnostic efficacy of identifying UC using TPS through cytologic-histologic correlation. A retrospective search identified 170 cases of urine cytology cases with concurrent biopsies collected during a 2-year time period at University of Rochester Medical Center. Patient age, sex, smoking history, prior malignancy diagnoses, cystoscopy findings, specimen collection method, UroVysion results, and 1-year follow-up of surgical pathology cases were included. Cytologic-histologic correlation was identified in 59% of cases, with 18% true positives and 41% true negatives. Discordant results were identified in 41% of cases; of these, 4% were false positives, 11% false negatives, 12% potential sampling bias, and 14% were low-grade urothelial carcinoma (LGUC). The analysis of this 2-year study finds a positive predictive value of urine cytology for HGUC to be 81%, a negative predictive value of 79%, a sensitivity of 61%, a specificity of 91%, and an accuracy of 79%. Our results support TPS's ability to improve the reliability and accuracy of interpretations in urine cytology for HGUC. Nevertheless, additional studies are essential to improve the diagnostic accuracy of LGUN, and urine adequacy, in order to improve patient care and early detection, while identifying potential sampling bias.

Chronic therapeutic anticoagulation is associated with decreased thrombotic complications in SARS‐CoV‐2 infection

BackgroundThrombotic disease complicates severe SARS‐CoV‐2 infection and is associated with increased morbidity and mortality. Various anticoagulation strategies have been evaluated in hospitalized patients to prevent complications. The impact of chronic anticoagulation before SARS‐CoV‐2 infection on the risk for subsequent thrombosis has not been systematically studied. MethodsThis was a retrospective single‐center study. All patients with positive SARS‐CoV‐2 PCR testing from March 13, 2020, through May 6, 2020, at the University of Rochester Medical Center were identified. We included all patients receiving therapeutic anticoagulation for at least 1 month before COVID diagnosis. We documented the rate of thrombotic complications, type of anticoagulation, bleeding complications, and mortality. ResultsA total of 107 SARS‐CoV2‐infected patients were chronically anticoagulated before SARS‐CoV‐2 testing with a median age of 78. Of those, 42 required hospital admission, with 17 requiring intensive care. No patients, inpatient or outpatient, were diagnosed with a new symptomatic thrombotic complication. Three patients had minor bleeding in the hospital. Thirteen (12%) patients died (69% male). ConclusionOur uncontrolled findings suggest that chronic anticoagulation at the time of infection may protect against thrombotic complications and decrease disease severity.

Achieving Life Milestones in Duchenne/Becker Muscular Dystrophy: A Retrospective Analysis.

To understand the milestones achieved in the transition from childhood to adulthood for patients with Duchenne and Becker muscular dystrophies (DMD/BMD). We performed a retrospective chart review on patients aged 15 years or older with a clinical diagnosis of DMD/BMD who received care from January 1, 2008, to January 1, 2018 at the University of Kansas Medical Center and the University of Rochester Medical Center. Participants were identified using local Muscular Dystrophy Asssociation-funded clinic lists, neuromuscular research databases, and electronic medical record review. Data were abstracted using a uniform template on education, employment, community resources, relationships, and end-of-life discussions and is presented as mean, median, or frequency with associated 95% confidence interval (CI). A total of 109 patients were identified: patients ranged in age from 15 to 56 years with a median of 24, and covered a 5-state region and Ontario, Canada. Seventy-eight percent of patients had DMD and were, on average, 8.5 years younger than patients with BMD. Over half (56.9%, 95% CI 47.6-66.2) were high school graduates or beyond. Sixteen percent did not have their highest level of education documented. Only 20.0% had an occupation (95% CI 12.7-27.7), most frequently in education and administrative support (34%). The majority were still living with parents (80.7%, 95% CI 73.3-88.1). A minority reported having end-of-life discussions (17.4%, 95% CI 10.3-24.6). Psychosocial elements reflecting the transition to adulthood are inconsistently reported in clinical documentation. A prospective study will further elucidate this transition.

M. Gabriela Sava Finalist of the 2020 MCDM Junior Researcher Best Paper Award

In April 2020, M. Gabriela Sava received the great news that her paper “An analysis of the sensitivity and stability of patients’ preferences can lead to more appropriate medical decisions,” published in Annals of Operations Research was selected as a finalist for the 2020 MCDM Junior Researcher Best Paper Award. The paper was in collaboration with Dr. Luis G. Vargas and Dr. Jerrold H. May from University of Pittsburgh and Dr. James G. Dolan from University of Rochester Medical Center. The award honors junior academic researchers and practitioners who work in the area of multi-criteria decision-making for their excellence, creativity and innovation. Gabriela was nominated for this prestigious award by the Associate Editor of the IJAHP, Dr. Birsen Karpak from Youngstown State University.

The Lighter Side of Telemedicine

From the Division of Infectious Diseases, University of Rochester Medical Center, Rochester, NY. Correspondence to: Ted Louie, MD, Division of Infectious Diseases, University of Rochester Medical Center, Box 689 Elmwood Ave, Rochester, NY. E-mail: [email protected]. The authors have no funding or conflicts of interest to disclose.

Shoulder Joint

Figure 1 illustrates the glenohumeral joint of a normal shoulder joint, where the humeral head of the humerus articulates with the glenoid part of the scapula. In a normal shoulder joint, the articular surfaces should be parallel as noted in Figure 1. Nana Ohene Baah is an Assistant Professor, Interventional Radiology, University of Rochester Medical Center, Rochester, NY. Ashwani Kumar Sharma is an Associate Professor, Interventional Radiology, University of Rochester Medical Center, Rochester, NY.

Predictors of Atrial Fibrillation During Long-Term Implantable Cardiac Monitoring Following Cryptogenic Stroke.

BackgroundFollowing cryptogenic stroke, guidelines recommend cardiac monitoring for occult atrial fibrillation (AF). We aimed to evaluate predictors of AF during long‐term implantable cardiac monitoring.Methods and ResultsWe studied 293 consecutive patients who underwent implantable cardiac monitor implant (Medtronic LINQ) following hospitalization for cryptogenic stroke at the University of Rochester Medical Center from January 2013 to September 2018. Multivariable Cox proportional hazards regression modeling was used to identify predictors of AF during long‐term monitoring. At 36 months of follow‐up, the cumulative rate of implantable cardiac monitor–detected AF events was 32% in the total study population. Multivariable analysis identified age ≥70 years as the most powerful predictor of the development of AF events during follow‐up (hazard ratio, 2.28 [95% CI, 1.39–3.76]; P=0.001). Replacing age with the CHA2DS2‐VASc (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, age, sex category) score resulted in a weaker association, for which each 1‐point increment in the CHA2DS2‐VASC score was associated with an 18% increased risk of developing AF (95% CI, 1.00–1.38; P=0.047). Consistent results were shown using Kaplan–Meier analysis by age and by the CHA2DS2VASc score.ConclusionsCryptogenic stroke patients continue to develop AF episodes during 36 months of implantable cardiac monitoring following the index event. Age is the most powerful predictor of occult AF in this population.

Histopathological distinction of non-invasive and invasive bladder cancers using machine learning approaches

BackgroundOne of the most challenging tasks for bladder cancer diagnosis is to histologically differentiate two early stages, non-invasive Ta and superficially invasive T1, the latter of which is associated with a significantly higher risk of disease progression. Indeed, in a considerable number of cases, Ta and T1 tumors look very similar under microscope, making the distinction very difficult even for experienced pathologists. Thus, there is an urgent need for a favoring system based on machine learning (ML) to distinguish between the two stages of bladder cancer.MethodsA total of 1177 images of bladder tumor tissues stained by hematoxylin and eosin were collected by pathologists at University of Rochester Medical Center, which included 460 non-invasive (stage Ta) and 717 invasive (stage T1) tumors. Automatic pipelines were developed to extract features for three invasive patterns characteristic to the T1 stage bladder cancer (i.e., desmoplastic reaction, retraction artifact, and abundant pinker cytoplasm), using imaging processing software ImageJ and CellProfiler. Features extracted from the images were analyzed by a suite of machine learning approaches.ResultsWe extracted nearly 700 features from the Ta and T1 tumor images. Unsupervised clustering analysis failed to distinguish hematoxylin and eosin images of Ta vs. T1 tumors. With a reduced set of features, we successfully distinguished 1177 Ta or T1 images with an accuracy of 91–96% by six supervised learning methods. By contrast, convolutional neural network (CNN) models that automatically extract features from images produced an accuracy of 84%, indicating that feature extraction driven by domain knowledge outperforms CNN-based automatic feature extraction. Further analysis revealed that desmoplastic reaction was more important than the other two patterns, and the number and size of nuclei of tumor cells were the most predictive features.ConclusionsWe provide a ML-empowered, feature-centered, and interpretable diagnostic system to facilitate the accurate staging of Ta and T1 diseases, which has a potential to apply to other types of cancer.