Mihai Gheorghiade, MD-Life and Concepts

How do you capture an idea, shape it, and then bring it into the world? Of his many talents, this ability was a fundamental characteristic of Mihai Gheorghiade. A quick glance through PubMed confirms his prodigious output, likely to overwhelm any novice or even expert scholar. His contribution to heart failure, especially acute heart failure (AHF), is profound, He authored several major concepts in acute heart failure, disseminated further by his students. Most concepts remained indelibly linked to his name: Digoxin trials research(1–3), AHFS (acute heart failure syndromes) definition(4), hemodynamic congestion(5), hospitalized heart failure (HHF) (6), the vulnerable phase(7,8), neutral hemodynamic agents(9), registries(10–12) and pre-trial registries(13), the “6-axis model”(14) and then the “8-axis model”(15). His work shaped the field of AHF

Improving Postdischarge Outcomes in Acute Heart Failure

The global burden that acute heart failure (AHF) carries has remained unchanged over the past several decades (1). European registries (2–5) showed that 1-year outcome rates remain unacceptably high (Table 1) and confirm that hospitalization for AHF represents a change in the natural history of the disease process(6). As patients hospitalized for HF have a bad prognosis, it is crucial to utilize hospitalization as an opportunity to: 1) assess the individual components of the cardiac substrate; 2) identify and treat comorbidities; 3) identify early, safe endpoints of therapy to facilitate timely hospital discharge and outpatient follow-up; and 4) implement and begin optimization guideline-directed medical therapies (GDMTs). As outcomes are influenced by many factors, many of which are incompletely understood, a systematic approach is proposed that should start with admission and continues through post-discharge (7)

Acute Dyspnea and Decompensated Heart Failure

The majority of patients hospitalized with acute heart failure (AHF) initially present to the emergency department (ED). Correct diagnosis followed by prompt treatment ensures optimal outcomes. Paradoxically, identification of high risk is not the unmet need, given nearly all ED AHF patients are hospitalized; rather, it is identification of low-risk. Currently, no risk-stratification instrument can be universally recommended to safely discharge ED patients. With the exception of diagnosis, management recommendations are largely expert opinion, informed by existing evidence and tradition. In the absence of robust evidence, we propose a framework for management to guide the busy clinician

CyberKnife(® )radiosurgery in the treatment of complex skull base tumors: analysis of treatment planning parameters

BACKGROUND: Tumors of the skull base pose unique challenges to radiosurgical treatment because of their irregular shapes, proximity to critical structures and variable tumor volumes. In this study, we investigate whether acceptable treatment plans with excellent conformity and homogeneity can be generated for complex skull base tumors using the Cyberknife(® )radiosurgical system. METHODS: At Georgetown University Hospital from March 2002 through May 2005, the CyberKnife(® )was used to treat 80 patients with 82 base of skull lesions. Tumors were classified as simple or complex based on their proximity to adjacent critical structures. All planning and treatments were performed by the same radiosurgery team with the goal of minimizing dosage to adjacent critical structures and maximizing target coverage. Treatments were fractionated to allow for safer delivery of radiation to both large tumors and tumors in close proximity to critical structures. RESULTS: The CyberKnife(® )treatment planning system was capable of generating highly conformal and homogeneous plans for complex skull base tumors. The treatment planning parameters did not significantly vary between spherical and non-spherical target volumes. The treatment parameters obtained from the plans of the complex base of skull group, including new conformity index, homogeneity index and percentage tumor coverage, were not significantly different from those of the simple group. CONCLUSION: Our data indicate that CyberKnife(® )treatment plans with excellent homogeneity, conformity and percent target coverage can be obtained for complex skull base tumors. Longer follow-up will be required to determine the safety and efficacy of fractionated treatment of these lesions with this radiosurgical system

MicroRNA-214 targets PTK6 to inhibit tumorigenic potential and increase drug sensitivity of prostate cancer cells.

Prostate cancer is the most commonly diagnosed cancer in men with African American men disproportionally suffering from the burden of this disease. Biomarkers that could discriminate indolent from aggressive and drug resistance disease are lacking. MicroRNAs are small non-coding RNAs that affect numerous physiological and pathological processes, including cancer development and have been suggested as biomarkers and therapeutic targets. In the present study, we investigated the role of miR-214 on prostate cancer cell survival/migration/invasion, cell cycle regulation, and apoptosis. miR-214 was differentially expressed between Caucasian and African American prostate cancer cells. Importantly, miR-214 overexpression in prostate cancer cells induced apoptosis, inhibiting cell proliferation and colony forming ability. miR-214 expression in prostate cancer cells also inhibited cell migration and 3D spheroid invasion. Mechanistically, miR-214 inhibited prostate cancer cell proliferation by targeting protein tyrosine kinase 6 (PTK6). Restoration of PTK6 expression attenuated the inhibitory effect of miR-214 on cell proliferation. Moreover, simultaneous inhibition of PTK6 by ibrutinib and miR-214 significantly reduced cell proliferation/survival. Our data indicates that miR-214 could act as a tumor suppressor in prostate cancer and could potentially be utilized as a biomarker and therapeutic target

The Value of the History and Physical for Patients with Newly Diagnosed Brain Metastases Considering Radiosurgery

Background: For patients with brain metastases, systemic disease burden has historically been accepted as a major determinant of overall survival (OS). However, less research has focused on specific history and physical findings made by clinicians and how such findings pertain to patient outcomes at a given time point. The aim of this study is to determine how the initial clinical assessment of patients with brain metastases, as part of the history and physical at the time of consultation, correlates with patient prognosis.Methods: We evaluated a prospective, multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or CyberKnife) from 2001-2014. Relevant history of present illness (HPI) and past medical history (PMH) variables included comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, and seizure history. Physical exam findings included a sensory exam, motor exam, and cognitive function. Univariate and multivariate Cox regression analyses were used to identify predictors of OS.Results: 294 patients were included in the final analysis with a median OS of 10.8 months (95% C.I., 7.8-13.7 months). On univariate analysis, significant HPI predictors of OS included age, primary diagnosis, performance status, extracranial metastases, systemic disease status, and history of surgery. Significant predictors of OS from the PMH included cardiac, vascular, and infectious comorbidities. On a physical exam, findings consistent with cognitive deficits were predictive of worse OS. However, motor deficits or changes in vision were not predictive of worse OS. In the multivariate Cox regression analysis, predictors of worse OS were primary diagnosis (p=0.002), ECOG performance status (OR 1.73, p<0.001), and presence of extracranial metastases (OR 1.22, p=0.009).Conclusion: Neurologic deficits and systemic comorbidities noted at presentation are not associated with worse overall prognosis for patients with brain metastases undergoing radiosurgery. When encountering new patients with brain metastases, the most informative patient-related characteristics that determine prognosis remain performance status, primary diagnosis, and extent of extracranial disease

Treatment of malignant tumors of the skull base with multi-session radiosurgery

<p>Abstract</p> <p>Objective</p> <p>Malignant tumors that involve the skull base pose significant challenges to the clinician because of the proximity of critical neurovascular structures and limited effectiveness of surgical resection without major morbidity. The purpose of this study was to evaluate the efficacy and safety of multi-session radiosurgery in patients with malignancies of the skull base.</p> <p>Methods</p> <p>Clinical and radiographic data for 37 patients treated with image-guided, multi-session radiosurgery between January 2002 and December 2007 were reviewed retrospectively. Lesions were classified according to involvement with the bones of the base of the skull and proximity to the cranial nerves.</p> <p>Results</p> <p>Our cohort consisted of 37 patients. Six patients with follow-up periods less than four weeks were eliminated from statistical consideration, thus leaving the data from 31 patients to be analyzed. The median follow-up was 37 weeks. Ten patients (32%) were alive at the end of the follow-up period. At last follow-up, or the time of death from systemic disease, tumor regression or stable local disease was observed in 23 lesions, representing an overall tumor control rate of 74%. For the remainder of lesions, the median time to progression was 24 weeks. The median progression-free survival was 230 weeks. The median overall survival was 39 weeks. In the absence of tumor progression, there were no cranial nerve, brainstem or vascular complications referable specifically to CyberKnife^®radiosurgery.</p> <p>Conclusion</p> <p>Our experience suggests that multi-session radiosurgery for the treatment of malignant skull base tumors is comparable to other radiosurgical techniques in progression-free survival, local tumor control, and adverse effects.</p