Treatment Of High-risk Patients Research Articles

MINI OPCAB Mammary to LAD and Optimal Medical Treatment in High Risk Patients with Multivessel Coronary Disease Long Term Results

MINI OPCAB Mammary to LAD and Optimal Medical Treatment in High Risk Patients with Multivessel Coronary Disease Long Term Results

Five-year treat-to-target outcomes after methotrexate induction therapy with or without other csDMARDs and temporary glucocorticoids for rheumatoid arthritis in the CareRA trial

ObjectivesTo compare outcomes of different treatment schedules from the care in early rheumatoid arthritis (CareRA) trial over 5 years.MethodsPatients with RA completing the 2-year CareRA randomised controlled trial were eligible...

Laboratory parameters related to severe disease and death in SARS-CoV-2 pneumonia: Retrospective analysis.

The clinical evolution of coronavirus disease 2019 (COVID‐19) is highly variable and hospitalized patients can rapidly develop conditions requiring oxygen support, intensive care unit (ICU) or high dependency unit (HDU) care. Early identification of high‐risk patients is mandatory. We retrospectively collected the medical history, symptoms, radiological, and laboratory findings of COVID‐19 patients hospitalized between February and April 2020. Laboratory data were collected at the first, last, and middle times of hospitalization. We used arterial oxygen partial pressure and fractional inspired oxygen ratio (P/F) to evaluate respiratory status. Outcomes considered were death and ICU/HDU admission. We used the χ 2 or Fisher's exact test to examine differences between categorical variables. Continuous variables were analyzed using the Wilcoxon matched pairs signed‐ranks test and Mann–Whitney test sample test. Of 71 patients admitted, 92% had interstitial pneumonia, and 17% an unfavorable outcome. Negative predictors were age, cerebrovascular disease, obesity, and chronic obstructive pulmonary disease. Baseline P/F was strongly associated with all outcomes. Markers linked to immunological dysregulation like elevated neutrophil‐to‐lymphocyte ratio exhibited prognostic significance over time. A validated prognostic score comprehensive of all these conditions for early staging and management of COVID‐19 patients is urgently needed. Further studies are desirable to evaluate whether laboratory tests can target early treatment in high‐risk patients.

Results of Register in Patients with Acute Coronary Syndrome and Atrial Fibrillation Receiving Rivaroxaban.

Aim To evaluate outcomes in patients with acute coronary syndrome and atrial fibrillation who receive rivaroxaban and the patients' compliance with the antithrombotic therapy.Material and methods The study was performed from October 2017 through December 2019 and included 129 patients. Events between the discharge from the hospital and 12 months of follow-up were recorded. The primary endpoint was development of major, minor or requiring medical attention bleeding according to the TIMI scale. The secondary endpoint was a combination of recurrent myocardial infarction, nonfatal acute ischemic cerebrovascular disease, nonfatal systemic embolism, stent thrombosis, and cardiovascular mortality.Results 32 (24.8%) patients early terminated the antiplatelet treatment and 22 (17.1%) patients terminated the rivaroxaban treatment. 26 (20.2 %) patients had hemorrhagic complications. The highest incidence of hemorrhage was observed within the first 2 months after the discharge. None of the bleedings was fatal. Composite endpoint events were observed in 24 (18.6 %) patients, including 14 (10.9 %) who died from cardiovascular causes.Conclusion The compliance with the antiplatelet therapy was insufficient. The incidence of hemorrhagic complications was relatively high; minor and requiring medical attention hemorrhages mostly contributed to the structure of these complications. The observed incidence of recurrent ischemic events associated with a high mortality presents a more serious problem compared to hemorrhagic complications of the combination antiplatelet therapy and warrants a more aggressive tactics of the antiplatelet treatment in high-risk patients.

Urothelial Carcinoma in The Era of Immune Checkpoint Inhibitors

Bladder cancer is the seventh most frequent cancer worldwide. The majority of patients present with nonmuscle invasive disease, while 20% of the patients are diagnosed with muscle-invasive bladder cancer. The treatment of nonmuscle invasive disease is endoscopic resection followed by intravesical adjuvant treatment for high risk patients. The standard treatment of localized muscle-invasive disease is neoadjuvant chemotherapy followed by radical cystectomy. Platinum-based chemotherapy is the first-line treatment in locally advanced or metastatic urothelial carcinoma. Immune checkpoint inhibitors have been approved for the treatment of metastatic urothelial carcinoma as second-line treatment or first-line in platinum-ineligible patients. Recently, pembrolizumab have been approved in bacillus Calmette-Guérin (BCG)-refractory nonmuscle invasive bladder cancer. This review summarizes the current evidence concerning immunotherapy in the treatment of urothelial carcinoma.

Lung Cancer Strategist Program: A novel care delivery model to improve timeliness of diagnosis and treatment in high-risk patients

IntroductionThe diagnosis and treatment of lung cancer is challenged by complex diagnostic pathways and fragmented care that can lead to care disparities for vulnerable patients. MethodsA multi-institutional, multidisciplinary conference was convened to address the complexity of lung cancer care particularly in patients at high-risk for treatment delay. The resulting care delivery model, called the Lung Cancer Strategist Program (LCSP), was led by a thoracic-trained advanced practice provider (APP) with emphasis on expedited surgery and early oncologic consultation in the assessment of a newly diagnosed suspicious lung nodule. We performed a retrospective review to evaluate care efficiency and oncologic outcomes in the first 100 LCSP patients compared to 100 concurrent patients managed via routine surgical referral. ResultsIn the 78 LCSP and 41 routine referral patients managed via nodule surveillance, LCSP patients had a shorter time from suspicious finding to work-up (3 vs. 26 days, p < 0.001) and to surveillance decision (12.5 vs. 39 days, p < 0.001). In the 22 LCSP and 59 routine referral patients treated for intrathoracic malignancy, LCSP patients had fewer hospital visits (4 vs 6, p < 0.001), clinicians seen (1.5 vs. 2, p = 0.08), and diagnostic studies (4 vs 5, p = 0.01) with a shorter time to diagnosis (30.5 vs. 48 days, p = 0.02) and treatment (40.5 vs. 68.5 days, p = 0.02). ConclusionsPatient triage through a thoracic-trained APP in consultation with surgical, medical, and radiation oncology facilitates rapid assessment of benign versus malignant lesions with reduced time to diagnosis and treatment, even among patients at high-risk for treatment delay.

A ROR1 Bispecific T Cell Engager for the Treatment of Chronic Lymphocytic Leukaemia Demonstrates Enhanced Function Following Ibrutinib Treatment

ROR1 is expressed on a range of solid and haematological malignancies, including chronic lymphocytic leukaemia, mantle cell lymphoma and a subset of acute lymphoblastic lymphoma, making it an attractive therapeutic target. In keeping with this, ROR1 CAR T cells and a ROR1 antibody, are being investigated as novel treatments [NCT02222688, NCT02776917 & NCT02706392]. BiTEs are small, 55kDa antibody based therapeutics composed of two single chain variable fragments (scFv) linked in tandem by a flexible linker. One scFv binds to tumour antigens and the other to the CD3 complex, bringing target cells and T cells in close proximity, facilitating formation of cytotoxic synapses and resulting in target cell death. We have generated a fully humanised ROR1 BiTE which unlike conventional antibodies recruits and utilises the inherent cytotoxic potential of polyclonal resident T cells and does not require ex vivo cell manipulation. We therefore investigated the potential of a ROR1 BiTE for the treatment of CLL.We first assessed the efficacy of our ROR1 BiTE against SKW6.4, Jeko1 and Kasumi-2 haematological cell lines which are ROR1 positive, confirming significant cytotoxicity even at low concentrations of 1ng/ml (Figure 1A). To demonstrate in vivo potential, mice were injected with SKW6.4 cells and disease established before treatment with T cells and 5 days of ROR1 BiTE or control PBS therapy. BiTE treated animals had improved survival compared to the control cohort (50 days vs 18 days), despite only a single infusion of T cells (Figure 1B).We next assessed the potential of the BiTE to target primary CLL cells: allogeneic healthy donor T cells were co-cultured with CLL cells (3:1 effector:target ratio) in the presence of ROR1 BiTE with resultant decrease in CLL viability at 24 hours (Mean CLL survival 32%, Figure 1C). In contrast, we saw minimal cytotoxicity in co-cultures of autologous patient T cells and CLL cells with ROR1 BiTE under identical conditions (Mean CLL survival 92%, Figure 1D). We hypothesised this was secondary to the previously described multifactorial T cell dysfunction in CLL.Ibrutinib, the first in class Bruton's tyrosine kinase inhibitor, demonstrates impressive efficacy in front line and relapsed/refractory CLL patients including those with high risk 17p deletion. In addition, it modulates the tumour micro-environment, skews T cells to a Th1 phenotype, reduces PD-1 expression and reverses pseudo-exhaustion. In view of this, we isolated T cells from patients receiving Ibrutinib and cultured them with autologous CLL cells and demonstrated significantly enhanced cytotoxicity compared to patients not exposed to Ibrutinib (Mean CLL survival 43% vs 85%, p=0.012) (Figure 1E). This cohort included patients who had failed multiple prior lines of therapy and/or 17p deleted cases. Ibrutinib treatment was also associated with markedly enhanced secretion of a range of pro-inflammatory mediators including IFNγ and TNFα (Figure 1F). To ensure this effect was not due to Ibrutinib increasing sensitivity of CLL cells to a ROR1 BiTE, we analysed matched samples from 2 patients pre and post treatment. Post Ibrutinib T cells demonstrated enhanced killing, irrespective of the CLL cells exposure to Ibrutinib, confirming enhanced T cell function as the driving force of improved BiTE mediated cytotoxicity (Figure 1G).Taken together, we demonstrate the potential of a ROR1 BiTE to target haematological malignancies and highlight for CLL, the clinical context in which BiTEs are used is critical for effective responses. Baseline T cell dysfunction in untreated or relapsed CLL patients will likely limit efficacy, whilst Ibrutinib treatment allows for improved T cell effector function. In keeping with this CD19 CAR T cells demonstrate superior expansion, function and persistence when generated from CLL patients on Ibrutinib, confirming a global positive immunomodulatory role. Other small molecule inhibitors may improve T cell function by reducing tumour bulk but Ibrutinib inhibits other tyrosine kinases including ITK, which may play a role in T cell modulation. Despite Ibrutinib monotherapy being effective, patients often have a low level disease burden and minimal residual disease is rarely achieved. BiTE treatment for high risk patients in this situation represents a rational option to deepen responses. Overall, our data supports the assessment of our ROR1 BiTE in the post Ibrutinib setting for CLL. [Display omitted] DisclosuresGohil:UCL Business: Patents & Royalties. Nathwani:UCL Business: Patents & Royalties. Della Peruta:UCL Business: Patents & Royalties.

Chemical Inhibition of the Macrophage Inhibitor Factor (MIF) Induces Cell Cycle Arrest and Apoptosis in Lymphoid and Myeloid Leukemia

More selective and less toxic chemotherapeutic agents are needed as frontline treatments in high-risk patients and as salvage agents in relapse disease. In a search for natural products with anti-cancer activity, we previously reported that the isothiocyanate sulforaphane has anti-leukemic properties in pediatric T- and B-cell acute lymphoblastic leukemia by inducing G2/M cell cycle arrest and apoptosis (PLOS ONE, 2012). We hypothesized that sulforaphane forms adducts in leukemia cells resulting in the inactivation of proteins required for survival. Here we report that the macrophage inhibitor factor (MIF) is targeted by sulforaphane in lymphoid leukemia cells. Taking advantage of the electrophilic carbon of isothiocyanate (N=C=S) group in sulforaphane that spontaneously forms thionacyl adducts with sulfhydryl groups of cellular proteins, we performed a cell displacement assay by competition of a biotinylated derivative isothiocyanate with an excess (100 μM) of sulforaphane. Immunoblots showed loss of the biotin label in the macrophage inhibitor factor (MIF) by pre-incubation with sulforaphane in Nalm-6 (B-ALL) and KOPTK1 (T-ALL) cell lines. Although MIF has been targeted in colon cancer, gallbladder cancer, thyroid and squamous carcinomas, the anti-leukemic properties of MIF inhibition in blood cancers have not been explored yet. Prior to testing the effect of MIF inhibition with small molecules, we confirmed that MIF and its receptor CD74 are expressed in a panel of lymphoid (Nalm-6, REH, RS4, Jurkat, DND41, KOPTK-1) and myeloid (K562, HL60, U937, Kasumi, HEL) cell lines. The selective MIF inhibitor 4-iodo-6-phenylpyrimidine (4-IPP) induced cell death in a dose-dependent manner in myeloid and lymphoid cell lines but not significantly in LCL lymphoblastoid cells used as non-leukemic control; acute lymphoblastic leukemia cell lines were more sensitive to 4-IPP inhibition than myeloid leukemia cell lines. Annexin V staining showed increased apoptosis upon treatment with 4-IPP and analysis of DNA content by propidium iodide staining revealed a dose dependent arrest in S-phase. In contrast to sulforaphane and consistent with a cell cycle deregulation, immunoblot analysis showed increased cyclin E1 and a reduction of Cyclin B1. Finally, the capacity of 4-IPP to control leukemia burden in vivo will be evaluated in a cell-based xenograft model. Altogether, MIF emerges as a novel therapeutic target in leukemia that can be targeted with small molecule inhibitors. DisclosuresNo relevant conflicts of interest to declare.

DYRK3 contributes to differentiation and hypoxic control in neuroblastoma

Neuroblastoma (NB), a pediatric cancer of the peripheral sympathetic nervous system, represents the most frequent solid malignancy in infants. Treatment of high-risk patients is still challenging and, depending on the genetic make-up and involved risk factors, the 5-year survival rate can drop to only 30%. Here, we found that the expression of the Dual Specificity Tyrosine Phosphorylation Regulated Kinase 3 (DYRK3) is increased in NB and is associated with decreased survival in NB patients. We further identified DYRK3 as a cytoplasmic kinase in NB cells and found that its levels are increased by hypoxic conditions. Further mechanistic studies revealed that DYRK3 acts as a negative regulator of HIF-driven transcriptional responses, suggesting that it functions in a negative feedback loop controlling the hypoxic response. Moreover, DYRK3 negatively impacted on NB cell differentiation, proposing an oncogenic role of this kinase in the etiology of NB. In summary, we describe novel functions of the DYRK3 kinase in NB, which will help to further improve the understanding of this disease eventually leading to the design of improved therapeutic concepts.

PDB5 Determination of Payer Budget Impact from Using an Innovative in Vitro Diagnostic in the Management of Diabetic Kidney Disease

To evaluate the budget impact from implementing a proactive testing regime for chronic kidney disease in patients with type-2 diabetes (T2D). PromarkerD is an innovative biomarker-based blood test that predicts risk of diabetic kidney disease (DKD) and renal decline in T2D patients. This research aims to assess whether PromarkerD could reduce costs to US payers (currently $50 billion to the US healthcare system). This four-year model evaluated potential net savings to US payers from covering the PromarkerD test versus standard-of-care (SOC) in T2D patients with no/mild DKD (KDIGO categories G1-3b). Parameters were derived from prior literature and clinical studies, and included costs and frequency of testing, costs associated with changes to patient treatment strategies, and savings from slowing DKD progression and ESRD interventions (dialysis and kidney transplants). Model assumptions included testing rates (annual for low-risk, biannual for high-risk), 80% adherence to preventative medications, and a 20% decline in progression through DKD stages. Covering PromarkerD testing per million T2D patients could produce savings for US payers of $2.3 billion over four years, against costs of $1.5 billion (net savings: $846m). Savings arise from slower DKD stage progression ($1.4b), delayed dialysis and transplants ($667m), and fewer unplanned dialysis ($272m), while costs include testing ($665m), and preventative treatments in high-risk patients ($793m). Sensitivity analysis showed that if the decline in progression was set to 15%, net savings were still $353m. Changing SOC by implementing an alternative PromarkerD testing regime in T2D patients could reduce unnecessary adoption of new therapeutic interventions in low risk patients, and enable early intervention for high risk patients, thereby slowing progression and lessening the need for expensive dialysis and transplants. This study demonstrates substantial near-term savings to US payers in the treatment of DKD through early, accurate and cost-effective prognosis with the PromarkerD test.

147-LB: Targeted Intervention for At-Risk Patients with Diabetes to Reduce Readmissions

With benefits to patient outcomes, provider burden, and health system costs, the goal of reducing hospital readmissions for patients with diabetes mellitus (DM) is multifaceted. Current studies have neither elucidated a clear approach to accurately identify at-risk patients nor implemented reliable interventions to significantly reduce readmissions. We trialed a Quality Improvement project utilizing a diabetes Nurse Practitioner (NP)/Certified Diabetes Care and Education Specialist (CDCES) to see at-risk patients during initial hospitalization and in close clinic follow-up after discharge with an endpoint of reducing future readmissions. Over 21 months, 79 hospitalized patients with DM were identified as high-risk for readmission. Identifying factors included previous admission, DKA/HHS, new DM diagnosis, new to insulin, high-dose steroid use, or provider discretion. The NP/CDCES provided DM management, education, and coordinated discharge. Patients were called shortly after discharge and had a 2-4 week clinic follow-up with the NP/CDCES. The primary endpoint was number of readmissions 180 days post-discharge after NP/CDCES intervention versus number of previous readmissions pre-intervention. Change in hemoglobin A1C, time to post-hospital phone call, and time to outpatient follow-up were also evaluated. Pre- and post-intervention readmission rates remained unchanged; average pre-intervention readmissions per patient was 1.7 versus 1.88 post-intervention readmissions (p=0.74). However, a secondary endpoint of reduction in A1C was statistically significant, with a mean decrease in A1C of 0.97% per patient (p=0.0025). Time to post-hospital phone call and early follow-up did not affect readmission rates. While targeted inpatient-to-outpatient intervention for high-risk patients with DM did not reduce readmission rates, our data suggests coordinated inpatient intervention with close hospital follow-up may improve A1C in high-risk patients with diabetes. Disclosure A. Harris: None. K. Grdinovac: None.

Prospects of Neutralizing Nanobodies Against SARS-CoV-2.

Since December 2019, the SARS-CoV-2 has erupted on a large scale worldwide and spread rapidly. Passive immunization of antibody-related molecules provides opportunities for prevention and treatment of high-risk patients and children. Nanobodies (Nbs) have many strong physical and chemical properties. They can be atomized, administered by inhalation, and can be directly applied to the infected site, with fast onset, high local drug concentration/high bioavailability, and high patient compliance (no needles). It has very attractive potential in the treatment of respiratory viruses. Rapid and low-cost development of Nbs targeting SARS-CoV-2 can quickly be achieved. Nbs against SARS-CoV-2 mutant strains also can be utilized quickly to prevent the virus from escaping. It provides important technical supports for the treatment of the SARS-CoV-2 and has the potential to become an essential medicine in the toolbox against the SARS-CoV-2.

Analysis of enamel/restoration interface submitted cariogenic challenge and fluoride release.

The treatment of high-risk patients still is a challenge. The understanding and development non-invasive, non-destructive, and non-ionizing techniques, can help to guide the treatment and the diagnosis of primary and recurrent caries. The present study evaluated the behavior of enamel/restoration interface after a cariogenic challenge by Fourier domain optical coherence tomography (FD-OCT), scanning electron microscopy (SEM) examination, and the fluoride release of the different restorative materials. Cavities (1.5 × 0.5 mm) were performed in enamel surface and divided into groups (n=8): glass ionomer cement (GIC), resin-modified glass ionomer cement (RMGIC), and resin composite (RC). The samples were submitted to pH-cycling, and the solutions analyzed for cumulative fluoride by ion-analyzer. The morphology was analyzed by SEM through replicas. The optical attenuation coefficient (OAC) was calculated through exponential decay from the images generated by FD-OCT. Data were analyzed considering α=0.05. OAC values increased for all groups after pH-cycling indicating demineralization (p < .05). Considering the remineralizing solution, RMGIC presented higher fluoride release rate, followed by GIC, while RC did not release any fluoride. Yet for the demineralizing solution, RMGIC and GIC released similar fluoride rates, overcoming RC (p < .05). Micrographs revealed no changes on the restorations margins, although enamel detachment was observed for RC and GIC after pH-cycling.

Early Detection of Cerebral Herniation by Continuous Electroencephalography and Quantitative Analysis.

Continuous electroencephalography (cEEG) and quantitative analysis of EEG (qEEG) are used in various circumstances such as detecting seizures, identifying acute or delayed cerebral ischemia, monitoring sedative therapy, or assessing prognosis. The authors report 2 cases: (1) Case #1 was a patient with unilateral cerebral edema and uncal herniation with asymmetric cEEG and qEEG changes detected an hour before clinical examination changes were noted and (2) Case #2 was a patient with diffuse cerebral edema and trans-tentorial herniation with symmetric cEEG and qEEG changes detected an hour before clinical examination changes were noted. These cases demonstrate the ability of cEEG and qEEG in early detection of different types of cerebral herniation. qEEG can be utilized by intensive care unit (ICU) staff not trained in EEG interpretation as a surveillance method to detect cerebral herniation, which may provide an opportunity for early intervention in high-risk patients.

A questionnaire survey on evaluation for penetration and compliance of the Japanese Guideline on Febrile Neutropenia among hematology-oncology physicians and surgeons

PurposeThe Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy.MethodsA questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics.ResultA total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency < 10% regimen. The medians of complete and complete plus partial compliance rates were 46.4% (range 7.0–92.8) and 77.8% (range 35.4–98.7). The complete compliance rates were less than 30% in seven recommendations, including the MASCC score assessment.ConclusionGL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

Current Therapy of the Patients with MDS: Walking towards Personalized Therapy.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia and peripheral cytopenias. Nowadays, MDS therapy is selected based on risk. The goals of therapy are different in low-risk and high-risk patients. In low-risk MDS, the goal is to decrease transfusion needs and to increase the quality of life. Currently, available drugs for newly diagnosed low-risk MDS include growth factor support, lenalidomide and immunosuppressive therapy. Additionally, luspatercept has recently been added to treat patients with MDS with ring sideroblasts, who are not candidates or have lost the response to erythropoiesis-stimulating agents. Treatment of high-risk patients is aimed to improve survival. To date, the only currently approved treatments are hypomethylating agents and allogeneic stem cell transplantation. However, the future for MDS patients is promising. In recent years, we are witnessing the emergence of multiple treatment combinations based on hypomethylating agents (pevonedistat, magrolimab, eprenetapopt, venetoclax) that have proven to be effective in MDS, even those with high-risk factors. Furthermore, the approval in the US of an oral hypomethylating agent opens the door to exclusively oral combinations for these patients and their consequent impact on the quality of life of these patients. Relapsed and refractory patients remain an unmet clinical need. We need more drugs and clinical trials for this profile of patients who have a dismal prognosis.

How to manage synchronous endometrial and ovarian cancer patients?

BackgroundsWe aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC).MethodsThe medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses.ResultsThe demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis.ConclusionsAlthough DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.

Ablation of a life-threatening arrhythmia in a patient with Brugada syndrome.

Brugada syndrome is an autosomal dominant arrhythmogenic disease associated with an increased risk of ventricular fibrillation and sudden cardiac death. The mainstay of treatment in high-risk patients is an implantable cardioverter-defibrillator (ICD), however radiofrequency ablation has been proposed over the past decade as an additional therapy in patients with recurrent ICD firing. We report a case of Brugada syndrome with an electrical storm which was successfully managed by radiofrequency ablation.

Predicting Long-Term Mortality in TAVI Patients Using Machine Learning Techniques.

Background: Whereas transcatheter aortic valve implantation (TAVI) has become the gold standard for aortic valve stenosis treatment in high-risk patients, it has recently been extended to include intermediate risk patients. However, the mortality rate at 5 years is still elevated. The aim of the present study was to develop a novel machine learning (ML) approach able to identify the best predictors of 5-year mortality after TAVI among several clinical and echocardiographic variables, which may improve the long-term prognosis. Methods: We retrospectively enrolled 471 patients undergoing TAVI. More than 80 pre-TAVI variables were collected and analyzed through different feature selection processes, which allowed for the identification of several variables with the highest predictive value of mortality. Different ML models were compared. Results: Multilayer perceptron resulted in the best performance in predicting mortality at 5 years after TAVI, with an area under the curve, positive predictive value, and sensitivity of 0.79, 0.73, and 0.71, respectively. Conclusions: We presented an ML approach for the assessment of risk factors for long-term mortality after TAVI to improve clinical prognosis. Fourteen potential predictors were identified with the organic mitral regurgitation (myxomatous or calcific degeneration of the leaflets and/or annulus) which showed the highest impact on 5 years mortality.

The current diagnosis and treatment of high-risk patients with chronic primary and secondary mitral valve regurgitation.

Mitral valve regurgitation (MR) is due primarily to either primary degeneration of the mitral valve with Barlow's or fibroelastic disease or is secondary to ischemic or nonischemic cardiomyopathies. Echocardiography is essential to assess MR etiology and severity, the remodeling of cardiac chambers and to characterize longitudinal chamber changes to determine optimal therapies. Surgery is recommended for severe primary MR if persistent symptoms are present or if left ventricledysfunction is present with an EF <60% or a left ventricleend-systolic diameter ≥40mm. For secondary MR, therapy of heart failure with vasodilators and diuretics improves forward cardiac output. Coronary artery bypass grafts (CABG) or percutaneous coronary intervention (PCI) should be considered for severe MR due to ischemia. This review summarizes the pathophysiology, the characteristics, the management and the different interventions for high risk patients with chronic primary and secondary MR.