Analysis of 415 adverse events in dental practice in Spain from 2000 to 2010

Introduction: The effort to increase patient safety has become one of the main focal points of all health care professions, despite the fact that, in the field of dentistry, initiatives have come late and been less ambitious. The main objective of patient safety is to avoid preventable adverse events to the greatest extent possible and to limit the negative consequences of those which are unpreventable. Therefore, it is essential to ascertain what adverse events occur in each dental care activity in order to study them in-depth and propose measures for prevention. Objectives: To ascertain the characteristics of the adverse events which originate from dental care, to classify them in accordance with type and origin, to determine their causes and consequences, and to detect the factors which facilitated their occurrence. Material and Methods: This study includes the general data from the series of adverse dental vents of the Spanish Observatory for Dental Patient Safety (OESPO) after the study and analysis of 4,149 legal claims (both in and out of court) based on dental malpractice from the years of 2000 to 2010 in Spain. Results: Implant treatments, endodontics and oral surgery display the highest frequencies of adverse events in this series (25.5%, 20.7% and 20.4% respectively). Likewise, according to the results, up to 44.3% of the adverse events which took place were due to predictable and preventable errors and complications. Conclusions: A very significant percentage were due to foreseeable and preventable errors and complications that should not have occurred. Key words:Patient safety, adverse event, medical care risk, dentistry.     

Scratching the surface of the statistical analysis for thoracic surgeons

Introduction Data analysis has evolved significantly over the last three decades. Completing complex statistical calculations manually is no longer necessary. S...     

Failed remyelination of the nonhuman primate optic nerve leads to axon degeneration,retinal damages,and visual dysfunction

White matter disorders of the central nervous system (CNS), such as multiple sclerosis (MS), lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems, including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue to prevent neuronal degeneration and promote recovery. Most of these strategies have been developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined nonhuman primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculomotor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This nonhuman primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair promyelinating/neuroprotective therapies to the clinic for myelin disorders, such as MS.

White matter disorders are a large group of neurological diseases of various origins. Those affecting the central nervous system (CNS), such as multiple sclerosis (MS), lead to failure of nerve conduction, axon degeneration, and result in long-lasting neurological disabilities and tissue atrophy (1). The loss of myelin and healthy axons are believed to be responsible for irreversible damages, which affect a variety of sensory and motor systems, including vision. In MS, 70% of patients are affected with optic neuritis. It can manifest in an acute episode with decreased vision that can recover over several weeks in the majority of patients, while permanent visual symptoms persist in 40 to 60% of patients (2, 3). Chronic optic neuritis can lead to significant optic nerve atrophy and retinal alterations, affecting mainly the retinal inner layers, including the retinal nerve fiber and ganglion cell layers (4). Several visual assays, including visual fields (VF) (5), pupillary responses to luminance and color (pupillary light reflex, PLR) (6), electroretinograms (ERG) (7), optical coherence tomography (OCT) (4, 8), and visual evoked potential (VEP) (9–11) are routinely performed to assess noninvasively the anatomical and electrophysiological perturbations of visual functions in MS. While functional recovery was reported in some patients (9), the lack of anatomical–electrophysiological correlation has prevented to attribute directly these improvements to remyelination or other regenerative processes.Animal models of demyelination induced by toxins, such as lyso-phosphatidylcholine (LPC), are suitable for studying the mechanisms of demyelination/remyelination and developing approaches aimed at promoting CNS remyelination, as they show little inflammation and, therefore, provide means to assay directly the effect of a therapy on remyelination. However, most of these models are developed in short-lived rodents and spontaneously repair, thus lacking the long-lasting progressive degenerative disease context of MS. Besides, these models do not reflect the size or complex organization of the human primate CNS (12). They do not inform on the biology of primate cells, which differs from rodents (13, 14), nor on the security, toxicity, and long-term efficacy of cell- or compound-based promyelinating/neuroprotective therapies. Thus, experiments in long-lived nonhuman primates appear an essential step toward clinical trials.While promoting remyelination may prevent axon degeneration, only a few promyelination strategies have been translated to the clinic (15,16). One of the roadblocks is the absence of studies addressing the clinical benefit of promyelination approaches that could be applied to the clinic (17). A positive correlation between changes in VEP parameters and the degree of demyelination/remyelination was established in rodents (18–21), cats (22), and dogs (23), and exploited successfully to follow promyelination therapies in rodents (24, 25). OCT has been used to identify loss of optic nerve and retinal damages in animal models of myelin disorders as well (23, 26). While used seldomly in nonhuman primates (27), none of these clinical assays were exploited to monitor the impact of optic nerve demyelination in nonhuman primates.We previously demonstrated that LPC injection in the macaque optic nerve induced demyelination with fair axon preservation but little remyelination up to 2 mo post demyelination (28). Taking advantage of the fact that nonhuman primates are long-lived and are able to perform several tasks awake, as do humans, we questioned whether this model could be used to follow the consequence of long-term demyelination on axon preservation, and whether multimodal noninvasive assays, such as VF, VEP, OCT, and PLR could be instrumental to follow/predict the functional and anatomical outcome of optic nerve demyelination. Using multidisciplinary approaches, we provide compelling evidence that LPC-induced demyelination of the macaque optic nerve leads to modified VF, VEP, PLR, and altered inner retinal layers, but preserved photoreceptors based on OCT and ERG. These clinical and functional anomalies were correlated at the histological level with failed remyelination and progressive optic nerve axon loss, followed by neuronal and fiber loss of the inner retinal layers. The postmortem validation of OCT, VEP, and PLR as pertinent markers of optic nerve demyelination/degeneration could further help the translation of therapeutic strategies toward the clinic for myelin diseases associated with long-term demyelination of the optic nerve.     

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.     

Ca’ Granda,an avant-garde hospital between the Renaissance and Modern age: a unique scenario in European history

The Ospedale Maggiore, known as Ca’ Granda, was founded in 1456 by will of Francesco Sforza, Duke of Milan, and was considered for almost five centuries a model for Milanese, Italian and even European healthcare. Attracting patients from all over Europe, the Ca’ Granda distinguished itself for the introduction of new treatments and innovative health reforms. In the burial ground of the hospital still lie the bodies of the deceased patients, who came from the poorest strata of the population. The study of their remains aims to give back a general identity and a story to each of these persons as well as reconstruct a fraction of the sixteenth century population of Milano as concerns lifestyle and disease and examine practises and therapy of this exceptional hospital. It is estimated that about two million commingled bones and articulated skeletons rest in the crypt, together with other types of findings (e.g., ceramic, coins, clothing). These remains are the object of a large project involving various disciplines ranging from humanities to hard sciences. The aim of this paper is to bring this historical gem to the attention of scholars and provide a glimpse of what its contents have already revealed.     

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m² with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m² (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.     

TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Different Stages of the Disease

Background: T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19. Methods: We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry. Results: Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3⁺CD4⁺CD45RO⁻CD62L⁻ and CD3⁺CD8⁺CD45RO⁻CD62L⁻ T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3⁺CD4⁺CD45RO⁻CD62L⁺ and CD3⁺CD8⁺CD45RO⁻CD62L⁺ T cell frequencies and increased CD3⁺CD8⁺CD45RO⁻CD62L⁻ cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets. Conclusions: The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19.     

The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery

Although there is no spontaneous regeneration of mammalian spinal axons after injury, they can be enticed to grow if cAMP is elevated in the neuronal cell bodies before the spinal axons are cut. Prophylactic injection of cAMP, however, is useless as therapy for spinal injuries. We now show that the phosphodiesterase 4 (PDE4) inhibitor rolipram (which readily crosses the blood-brain barrier) overcomes inhibitors of regeneration in myelin in culture and promotes regeneration in vivo. Two weeks after a hemisection lesion at C3/4, with embryonic spinal tissue implanted immediately at the lesion site, a 10-day delivery of rolipram results in considerable axon regrowth into the transplant and a significant improvement in motor function. Surprisingly, in rolipram-treated animals, there was also an attenuation of reactive gliosis. Hence, because rolipram promotes axon regeneration, attenuates the formation of the glial scar, and significantly enhances functional recovery, and because it is effective when delivered s.c., as well as post-injury, it is a strong candidate as a useful therapy subsequent to spinal cord injury.