Recombinant polio-rhinovirus immunotherapy for recurrent paediatric high-grade glioma: a phase 1b trial.

Background: Outcomes of recurrent paediatric high-grade glioma are poor, with a median overall survival of less than 6 months. Viral immunotherapy, such as the polio-rhinovirus chimera lerapolturev, is a novel approach for treatment of recurrent paediatric high-grade glioma and has shown promise in adults with recurrent glioblastoma. The poliovirus receptor CD155 is ubiquitously expressed in malignant paediatric brain tumours and is a treatment target in paediatric high-grade glioma.

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients.

How Do Experienced Professors Teach Palliative Medicine in European Universities? A Cross-Case Analysis of Eight Undergraduate Educational Programs.

Background: In Europe in recent decades, university teaching of palliative medicine (PM) has evolved. In some countries it has been introduced as a compulsory subject in all medical schools, but in a majority of countries it remains an isolated subject at few universities.

Objective: To explore how PM has been introduced into the curricula and how it is currently being taught at different European universities.

Recurrent Glioblastoma Treated with Recombinant Poliovirus.

Background: The prognosis of patients with recurrent World Health Organization (WHO) grade IV malignant glioma is dismal, and there is currently no effective therapy. We conducted a dose-finding and toxicity study in this population of patients, evaluating convection-enhanced, intratumoral delivery of the recombinant nonpathogenic polio-rhinovirus chimera (PVSRIPO). PVSRIPO recognizes the poliovirus receptor CD155, which is widely expressed in neoplastic cells of solid tumors and in major components of the tumor microenvironment.

Towards assessing cortical bone porosity using low-frequency quantitative acoustics: A phantom-based study.

Purpose: Cortical porosity is a key characteristic governing the structural properties and mechanical behaviour of bone, and its quantification is therefore critical for understanding and monitoring the development of various bone pathologies such as osteoporosis. Axial transmission quantitative acoustics has shown to be a promising technique for assessing bone health in a fast, non-invasive, and radiation-free manner. One major hurdle in bringing this approach to clinical application is the entanglement of the effects of individual characteristics (e.

Comparative analysis of specialization in palliative medicine processes within the World Health Organization European region.

Context: Palliative medicine (PM), still in the development phase, is a new, growing specialty aimed at caring for both oncology and non-oncology patients. There is still confusion about the training offered in the various European PM certification programs.

Objectives: To provide a detailed, comparative update and analysis of the PM certification process in Europe, including the different training approaches and their main features.

The 'surprise' question in advanced cancer patients: A prospective study among general practitioners.

Background: Using the 'surprise' question 'Would you be surprised if this patient died in the next year?' may improve physicians' prognostic accuracy and identify people appropriate for palliative care.

Aim: Determine the prognostic accuracy of general practitioners asking the 'surprise' question about their patients with advanced (stage IV) cancer.

Design: Prospective cohort study.

A teenager with tetralogy of fallot becomes a soccer player.

Patient: Male, 0 FINAL DIAGNOSIS: Tetralogy of Fallot Symptoms: -

Medication: - Clinical Procedure: - Specialty: Cardiology.

Objective: Unusual or unexpected effect of treatment.

Background: Tetralogy of Fallot (ToF) is the most common form of cyanotic congenital defect.

Acute coronary syndrome myopericarditis - not always a straightforward diagnosis.

Unlabelled:

Objective:

Background: Patients with acute cardiac symptoms, elevated cardiac troponin, and culprit-free angiograms are a consistent proportion of patients admitted with presumed acute coronary syndromes (ACS). Current literature on this population of patients justifies the diagnostic importance of cardiovascular magnetic resonance (CMR) imaging.

Case Report: This report describes the case of a 58-year-old cyclist in which CMR allowed us to perform a diagnosis of myopericarditis mimicking acute STEMI against other evidence.

Complicated and delayed diagnosis of tuberculous peritonitis.

Background: Peritoneal tuberculosis is very rare in European countries. However, its incidence is increasing due to the continued immigration of people from endemic areas affected by tuberculosis.

Case Report: The authors report a case of tuberculous peritonitis in a 46-year-old male patient from North Africa.

Palliative care training and research: the development in europe and the bologna experience.

Development of palliative care (PC) culture spur the need of proper and formal training. Palliative medicine is not fully recognized as an academic medical discipline due to its humanistic influences, and studies show that physicians declare to be not prepared to provide care and pain management to dying patients. Nowadays, despite leading countries in PC being considered more innovative than other countries,such as Italy, facts show that the achievement of acknowledged discipline went through a long process.

Right Ventricular Overload Due to Severe Pulmonary Valve Regurgitation in 44-Year-Old GUCH.

Notoriously, the valvular disease of the right heart have always received less attention than the left heart valvular disease both by echocardiographers and by researchers, probably due to the long period of latent asymptomatic and for the intrinsic difficulties of examination. However, it is increasingly recognized that right-sided valve disease is not a benign lesion and has a significant and independent impact on morbidity and mortality. Pulmonary regurgitation (PR) is common after surgical or percutaneous relief of pulmonary stenosis and following repair of tetralogy of Fallot.

A prominent crista terminalis associated with atrial septal aneurysm that mimics right atrial mass leading to atrial arrhythmias: a case report.

Introduction: The crista terminalis is a variant of normal anatomical structures within the right atrium that mimics an atrial mass on a transthoracic echocardiogram. Atrial septal aneurysm is a rare but well-recognized cardiac abnormality of uncertain clinical significance. The association between crista terminalis and atrial septal aneurysm is unusual but not completely casual.

Investment of palliative medicine in bridging the gap with academia: a call to action.

Palliative care and palliative medicine define a relatively new medical discipline that has arisen in response to the need for better approaches to caring for people with advanced life-limiting illnesses. For professional, managerial and cultural reasons, it has evolved largely outside of academic structures. As the discipline has matured, its needs for education, training, intellectual discourse, evidence development and new science have become more apparent.

Heterobiaryl human immunodeficiency virus entry inhibitors.

Previously disclosed HIV (human immunodeficiency virus) attachment inhibitors, exemplified by BMS 806 (formally BMS378806, 1), are characterized by a substituted indole or azaindole ring linked to a benzoylpiperazine via a ketoamide or sulfonamide group. In the present report, we describe the discovery of a novel series of potent HIV entry inhibitors in which the indole or azaindole ring of previous inhibitors is replaced by a heterobiaryl group. Several of these analogues exhibited IC(50) values of less than 5 nM in a pseudotyped antiviral assay, and compound 13k was demonstrated to exhibit potency and selectivity similar to those of 1 against a panel of clinical viral isolates.

Design and synthesis of human immunodeficiency virus entry inhibitors: sulfonamide as an isostere for the alpha-ketoamide group.

The crystal structures of many tertiary alpha-ketoamides reveal an orthogonal arrangement of the two carbonyl groups. Based on the hypothesis that the alpha-ketoamide HIV attachment inhibitor BMS 806 (formally BMS378806, 26) might bind to its gp120 target via a similar conformation, we designed and synthesized a series of analogs in which the ketoamide group is replaced by an isosteric sulfonamide group. The most potent of these analogs, 14i, demonstrated antiviral potency comparable to 26 in the M33 pseudotyped antiviral assay.

How to identify and calculate glenoid bone deficit.

In recent years, we have seen increased interest in bone lesions of the glenoid rim as acute fractures (Bony-Bankart) and as chronic bone defect in instability. This derives from three main clinical and statistical findings: a significant incidence of bony Bankart lesion after a first dislocation, a high percentage of glenoid bone defects in chronic instability, and, finally, a close relationship between bone defect and incidence of recurrence after arthroscopic stabilization. The authors agree on determining glenoid bone defect that exceeds 15-20% as the main contraindication to arthroscopic stabilization.

Enfuvirtide: the first therapy to inhibit the entry of HIV-1 into host CD4 lymphocytes.

Highly active antiretroviral therapy (HAART) based on combinations of drugs that target key enzymes in the life-cycle of human immunodeficiency virus (HIV) has considerably reduced morbidity and mortality from HIV infection since its introduction in the mid-1990s. However, the growing problem of the emergence of HIV strains that are resistant not only to individual drugs, but to whole drug classes, means that agents with new mechanisms of action are needed. Here, we describe the discovery and development of enfuvirtide (Fuzeon), the first drug to inhibit the entry of HIV-1 into host cells.

Monoclonal antibodies that bind to the core of fusion-active glycoprotein 41.

The heptad repeat regions HR1 and HR2 of HIV-1 gp41 can associate to form heterooligomers through helical coil-coil interactions that are believed to play a key role in virus-induced membrane fusion. The HR1/HR2 complex was proposed to be the core structure of the fusion-active conformation of gp41. Here, we show that two human monoclonal antibodies, Fab-d and 50-69, specifically recognize the putative fusion-active conformation of gp41.

A phase II study of two HIV type 1 envelope vaccines, comparing their immunogenicity in populations at risk for acquiring HIV type 1 infection. AIDS Vaccine Evaluation Group.

Several immunogens induce HIV-specific neutralization and in vitro lymphoproliferation in adults at low HIV-1 risk, but responses in persons at high HIV-1 risk are not known. We performed a multicenter, double-blinded, adjuvant-controlled trial with two gp120 vaccines in 296 HIV-1-uninfected volunteers, including 176 reporting higher HIV-1 risk activities. The immunogens were remarkably well tolerated.

Effect of highly active antiretroviral therapy and thymic transplantation on immunoreconstitution in HIV infection.

The purpose of this study was to determine whether thymic transplantation in addition to highly active antiretroviral therapy (HAART) will restore T cell function in HIV infection. Eight treatment-naive HIV-infected patients with CD4+ T cell counts of 200-500/mm3 were randomized into thymic transplantation and control arms. All patients received HAART (zidovudine, lamivudine, and ritonavir) for 6 weeks prior to transplantation.

Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry.

T-20, a synthetic peptide corresponding to a region of the transmembrane subunit of the HIV-1 envelope protein, blocks cell fusion and viral entry at concentrations of less than 2 ng/ml in vitro. We administered intravenous T-20 (monotherapy) for 14 days to sixteen HIV-infected adults in four dose groups (3, 10, 30 and 100 mg twice daily). There were significant, dose-related declines in plasma HIV RNA in all subjects who received higher dose levels.