Extraperitoneal Open Radical Cystectomy: A New Standard in Frail Patients with Muscle-Invasive Bladder Cancer?

: Radical cystectomy (RC) represents one of the most complex and morbid surgical procedures in the field of Urology. Extraperitoneal open RC has emerged as an alternative to the traditional transperitoneal approach for the treatment of muscle-invasive bladder cancer. Frailty is one of the most important risk factors for perioperative morbidity and mortality, and this category of patients can benefit the most from the extraperitoneal approach.

Perceived warmth and competence predict callback rates in meta-analyzed North American labor market experiments.

Extensive literature probes labor market discrimination through correspondence studies in which researchers send pairs of resumes to employers, which are closely matched except for social signals such as gender or ethnicity. Upon perceiving these signals, individuals quickly activate associated stereotypes. The Stereotype Content Model (SCM; Fiske 2002) categorizes these stereotypes into two dimensions: warmth and competence.

Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll-like receptors 7 and 8.

This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll-like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double-blind, placebo-controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single-dose cohorts received one dose of enpatoran (1, 3, 9, 25, 50, 100, or 200 mg) or placebo using a sentinel dosing strategy.

Long-term structural and symptomatic effects of intra-articular sprifermin in patients with knee osteoarthritis: 5-year results from the FORWARD study.

Objective: The FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) trial assessed efficacy and safety of the potential disease-modifying osteoarthritis drug (DMOAD) sprifermin in patients with knee osteoarthritis. Here, we report 5-year efficacy and safety results.

Methods: Patients were randomised to intra-articular sprifermin 100 µg or 30 µg every 6 months (q6mo) or 12 months, or placebo, for 18 months.

Safety and clinical activity of atacicept in the long-term extension of the phase 2b ADDRESS II study in systemic lupus erythematosus.

Objectives: Atacicept reduced SLE disease activity in the phase 2b ADDRESS II study, particularly in patients with high disease activity (HDA; SLEDAI-2K ≥10) at screening. We assessed long-term safety and efficacy of atacicept in the long-term extension (LTE) of ADDRESS II.

Methods: In the 24-week, randomized, double-blind, placebo-controlled ADDRESS II study, patients received weekly atacicept (75 or 150 mg) or placebo.

Management of renal extraskeletal mesenchymal chondrosarcoma.

Background: Primary mesenchymal chondrosarcoma of the kidney is an extremely rare malignant tumor. To our best knowledge, only 9 such cases have been reported so far.

Case Presentation: In the current paper, we present the case of a 67 year-old patient with recurrent left lumbar pain, increased fatigability and intermittent macroscopic hematuria.

Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation.

Rationale: Transforming growth factor (TGF)-beta has a central role in driving many of the pathological processes that characterize pulmonary fibrosis. Inhibition of the integrin alpha(v)beta6, a key activator of TGF-beta in lung, is an attractive therapeutic strategy, as it may be possible to inhibit TGF-beta at sites of alpha(v)beta6 up-regulation without affecting other homeostatic roles of TGF-beta.

Objectives: To analyze the expression of alpha(v)beta6 in human pulmonary fibrosis, and to functionally test the efficacy of therapeutic inhibition of alpha(v)beta6-mediated TGF-beta activation in murine bleomycin-induced pulmonary fibrosis.

Sequential activation of individual caspases, and of alterations in Bcl-2 proapoptotic signals in a mouse model of Huntington's disease.

Caspases play an important role in neurodegeneration in Huntington's disease (HD). Members of the Bcl-2 family are critical modulators of terminal cell death pathways. However, alterations of Bcl-2 family members and their functional role in an in vivo model of HD have not been documented.

Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice.

Minocycline mediates neuroprotection in experimental models of neurodegeneration. It inhibits the activity of caspase-1, caspase-3, inducible form of nitric oxide synthetase (iNOS) and p38 mitogen-activated protein kinase (MAPK). Although minocycline does not directly inhibit these enzymes, the effects may result from interference with upstream mechanisms resulting in their secondary activation.

Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction.

Objective: Caspase-1 plays an important functional role mediating neuronal cell death and dysfunction after experimental traumatic brain injury (TBI) in mice. Minocycline, a derivative of the antibiotic tetracycline, inhibits caspase-1 expression. This study investigates whether minocycline can ameliorate TBI-mediated injury in mice.

Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury.

Evidence indicates that both necrotic and apoptotic cell death contribute to tissue injury and neurological dysfunction following spinal cord injury. Caspases have been implicated as important mediators of apoptosis following acute central nervous system insults. We investigated whether caspase-1 and caspase-3 are involved in spinal cord injury-mediated cell death, and whether caspase inhibition may reduce tissue damage and improve outcome following spinal cord injury.

Malonate and 3-nitropropionic acid neurotoxicity are reduced in transgenic mice expressing a caspase-1 dominant-negative mutant.

Increasing evidence implicates caspase-1-mediated cell death as a major mechanism of neuronal death in neurodegenerative diseases. In the present study we investigated the role of caspase-1 in neurotoxic experimental animal models of Huntington's disease (HD) by examining whether transgenic mice expressing a caspase-1 dominant-negative mutant are resistant to malonate and 3-nitropropionic acid (3-NP) neurotoxicity. Intrastriatal injection of malonate resulted in significantly smaller striatal lesions in mutant caspase-1 mice than those observed in littermate control mice.

Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease.

Huntington disease is an autosomal dominant neurodegenerative disease with no effective treatment. Minocycline is a tetracycline derivative with proven safety. After ischemia, minocycline inhibits caspase-1 and inducible nitric oxide synthetase upregulation, and reduces infarction.

Functional role of caspase-1 and caspase-3 in an ALS transgenic mouse model.

Mutations in the copper/zinc superoxide dismutase (SOD1) gene produce an animal model of familial amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. To test a new therapeutic strategy for ALS, we examined the effect of caspase inhibition in transgenic mice expressing mutant human SOD1 with a substitution of glycine to alanine in position 93 (mSOD1(G93A)). Intracerebroventricular administration of zVAD-fmk, a broad caspase inhibitor, delays disease onset and mortality.

Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade.

Necrotic and apoptotic cell death both play a role mediating tissue injury following brain trauma. Caspase-1 (interleukin-1beta converting enzyme) is activated and oligonucleosomal DNA fragmentation is detected in traumatized brain tissue. Reduction of tissue injury and free radical production following brain trauma was achieved in a transgenic mouse expressing a dominant negative inhibitor of caspase-1 in the brain.

Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease.

Huntington's disease is an autosomal-dominant progressive neurodegenerative disorder resulting in specific neuronal loss and dysfunction in the striatum and cortex. The disease is universally fatal, with a mean survival following onset of 15-20 years and, at present, there is no effective treatment. The mutation in patients with Huntington's disease is an expanded CAG/polyglutamine repeat in huntingtin, a protein of unknown function with a relative molecular mass of 350,000 (M(r) 350K).