Diagnostic guidelines for the histological particle algorithm in the periprosthetic neo-synovial tissue

Background The identification of implant wear particles and non-implant related particles and the characterization of the inflammatory responses in the periprosthetic neo-synovial membrane, bone, and the synovial-like interface membrane (SLIM) play an important role for the evaluation of clinical outcome, correlation with radiological and implant retrieval studies, and understanding of the biological pathways contributing to implant failures in joint arthroplasty. The purpose of this study is to present a comprehensive histological particle algorithm (HPA) as a practical guide to particle identification at routine light microscopy examination. Methods The cases used for particle analysis were selected retrospectively from the archives of two institutions and were representative of the implant wear and non-implant related particle spectrum. All particle categories were described according to their size, shape, colour and properties observed at light microscopy, under polarized light, and after histochemical stains when necessary. A unified range of particle size, defined as a measure of length only, is proposed for the wear particles with five classes for polyethylene (PE) particles and four classes for conventional and corrosion metallic particles and ceramic particles. Results All implant wear and non-implant related particles were described and illustrated in detail by category. A particle scoring system for the periprosthetic tissue/SLIM is proposed as follows: 1) Wear particle identification at light microscopy with a two-step analysis at low (× 25, × 40, and × 100) and high magnification (× 200 and × 400); 2) Identification of the predominant wear particle type with size determination; 3) The presence of non-implant related endogenous and/or foreign particles. A guide for a comprehensive pathology report is also provided with sections for macroscopic and microscopic description, and diagnosis. Conclusions The HPA should be considered a standard for the histological analysis of periprosthetic neo-synovial membrane, bone, and SLIM. It provides a basic, standardized tool for the identification of implant wear and non-implant related particles at routine light microscopy examination and aims at reducing intra-observer and inter-observer variability to provide a common platform for multicentric implant retrieval/radiological/histological studies and valuable data for the risk assessment of implant performance for regional and national implant registries and government agencies

Delirium in acute promyelocytic leukemia patients: two case reports.

BACKGROUND: Delirium is a frequently misdiagnosed and inadequately treated neuropsychiatric complication most commonly observed in terminally ill cancer patients. To our knowledge this is the first report describing delirium in two patients aged less than 60 years and enrolled in an intensive chemotherapeutic protocol for acute promyelocytic leukemia. CASE PRESENTATION: Two female Caucasian acute promyelocytic leukemia patients aged 46 and 56 years developed delirium during their induction treatment with all-trans retinoic acid and idarubicin. In both cases symptoms were initially attributed to all-trans retinoic acid that was therefore immediately suspended. In these two patients several situations may have contribute to the delirium: in patient 1 a previous psychiatric disorder, concomitant treatments with steroids and benzodiazepines, a severe infection and central nervous system bleeding while in patient 2 steroid treatment and isolation. In patient 1 delirium was treated with short-term low-doses of haloperidol while in patient 2 non-pharmacologic interventions had a beneficial role. When the diagnosis of delirium was clear, induction treatment was resumed and both patients completed their therapeutic program without any relapse of the psychiatric symptoms. Both patients are alive and in complete remission as far as their leukemia is concerned. CONCLUSIONS: We suggest that patients with acute promyelocytic leukemia eligible to intensive chemotherapy should be carefully evaluated by a multisciplinary team including psychiatrists in order to early recognize symptoms of delirium and avoid inadequate treatments. In case of delirium, both pharmacologic and non-pharmacologic interventions may be considered

Cold, clumpy accretion onto an active supermassive black hole

Supermassive black holes in galaxy centres can grow by the accretion of gas, liberating energy that might regulate star formation on galaxy-wide scales. The nature of the gaseous fuel reservoirs that power black hole growth is nevertheless largely unconstrained by observations, and is instead routinely simplified as a smooth, spherical inflow of very hot gas. Recent theory and simulations instead predict that accretion can be dominated by a stochastic, clumpy distribution of very cold molecular clouds - a departure from the "hot mode" accretion model - although unambiguous observational support for this prediction remains elusive. Here we report observations that reveal a cold, clumpy accretion flow towards a supermassive black hole fuel reservoir in the nucleus of the Abell 2597 Brightest Cluster Galaxy (BCG), a nearby (redshift z=0.0821) giant elliptical galaxy surrounded by a dense halo of hot plasma. Under the right conditions, thermal instabilities can precipitate from this hot gas, producing a rain of cold clouds that fall toward the galaxy's centre, sustaining star formation amid a kiloparsec-scale molecular nebula that inhabits its core. The observations show that these cold clouds also fuel black hole accretion, revealing "shadows" cast by the molecular clouds as they move inward at about 300 kilometres per second towards the active supermassive black hole in the galaxy centre, which serves as a bright backlight. Corroborating evidence from prior observations of warmer atomic gas at extremely high spatial resolution, along with simple arguments based on geometry and probability, indicate that these clouds are within the innermost hundred parsecs of the black hole, and falling closer towards it