Analysis of the implementation of a circuit for intra-operative superposition and comparison of the surgical outcomes using ICBCT in maxillofacial surgery.

PURPOSE: This paper describes a novel circuit for intraoperative analysis with ICBCT in maxillofacial surgery. The aim is to establish guidelines, define indications, and conduct an analysis of the implementation of the circuit for intraoperative comparison of surgical outcomes in relation to 3D virtual planning in maxillofacial surgery. METHODS: The study included 150 maxillofacial surgical procedures. Intraoperative actions involved fluoroscopy localization, intraoperative CBCT acquisition, segmentation, and superimposition, among other steps. Surgical times due to intraoperative superposition were measured, including time required for ICBCT positioning and acquisition, image segmentation, and comparison of 3D surfaces from the surgical planning. RESULTS: Successful intraoperative comparison was achieved in all 150 cases, enabling surgeons to detect and address modifications before concluding the surgery. Out of the total, 26 patients (17.33%) required intraoperative revisions, with 11 cases (7.33%) needing major surgical revisions. On average, the additional surgical time with this circuit implementation was 10.66 ± 3.03 min (n = 22). CONCLUSION: The results of our research demonstrate the potential for performing intraoperative surgical revision, allowing for immediate evaluation, enhancing surgical outcomes, and reducing the need for re-interventions.

Apo2L/TRAIL and immune regulation.

Apo2L/TRAIL is a member of the TNF family, with its receptors DR4 and DR5 containing a death domain. Multiple tumors are sensitive to Apo2L/TRAIL-induced apoptosis, while normal cells are not, so it constitutes a promising new antitumoral therapy. In this review we deal rather with the physiological role of Apo2L/TRAIL, which, in one hand, is clearly related with immune antitumoral surveillance. However, a role of Apo2L/TRAIL as a fine-tuning regulator of the immune system, especially in the regulation of CD8+ T cell activation and memory, has been also demonstrated. In fact, Apo2L/TRAIL can be considered as an additional mechanism needed to prevent the development of autoimmune disease. Indeed, recent developments indicate that Apo2L/TRAIL can be also useful as a treatment against certain chronic autoimmune diseases.

Down-regulation of normal human T cell blast activation: roles of APO2L/TRAIL, FasL, and c- FLIP, Bim, or Bcl-x isoform expression.

A systematic study was undertaken to characterize the role of APO 2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (APO2L/TRAIL) and Fas ligand (FasL) together with the expression of several anti- or proapoptotic proteins in the down-regulation of normal human T cell responses. We have observed for the first time that the higher sensitivity of normal human T cell blasts to apoptosis and activation-induced cell death (AICD) as compared with naive T cells correlates with the increased expression of Bcl-x short (Bcl-xS) and Bim. T cell blasts die in the absence of interleukin 2 (IL-2) with no additional effect of death receptor ligation. In the presence of IL-2, recombinant APO2L/TRAIL or cytotoxic anti-Fas monoclonal antibodies induce rather inhibition of IL-2-dependent growth and not cell death on normal human T cell blasts. This observation is of physiological relevance, as supernatants from T cell blasts, pulse-stimulated with phytohemagglutinin (PHA) or through CD3 or CD59 ligation and containing bioactive APO2L/TRAIL and/or FasL expressed on microvesicles or direct CD3 or CD59 ligation, had the same effect. Cell death was only observed in the presence of cycloheximide or after a pulse through CD3 or CD59, correlating with a net reduction in cellular Fas-associated death domain-like IL-1beta-converting enzyme-inhibitory protein long (c-FLIPL) and c-FLIPS expression. We also show that death receptor and free radical generation contribute, at least partially, to AICD induced by PHA and also to the inhibition of IL-2-dependent cell growth by CD3 or CD59 ligation. Finally, we have also shown that T cell blasts surviving PHA-induced AICD are memory CD44high cells with increased c-FLIPS and Bcl-xL expression.

Impacto de las políticas de salud en la incidencia de reperfusión de infarto agudo de miocardio durante el inicio de la pandemia por COVID-19 en Uruguay / Impact of public health policies on the incidence of acute myocardial reperfusion during the initial stages of the COVID-19 pandemic in Uruguay / Impacto das políticas de saúde na incidência de infarto do miocárdio durante a pandemia de COVID-19 no Uruguai

Introducción: las medidas sanitarias de emergencia impuestas para contener el SARS-CoV-2 pueden tener efectos colaterales en la atención de enfermedades cardiovasculares. Los datos mundiales de los países sobre la incidencia de infarto agudo de miocardio con elevación del segmento ST (IAMCEST) durante la pandemia son fundamentales para la política sanitaria futura. Objetivos: nuestro objetivo fue determinar si las medidas sanitarias de emergencia impuestas en Uruguay tuvieron un impacto directo en la calidad de la atención en la reperfusión del IAMCEST. Métodos: realizamos un estudio retrospectivo poblacional de todo el país para determinar la incidencia de reperfusión de IAMCEST (fibrinolíticos e intervención coronaria percutánea, FBL e ICP respectivamente) durante el período sanitario de emergencia. La tasa de incidencia de la reperfusión, el tiempo hasta la reperfusión y la mortalidad asociada se recopilaron de la base de datos del Fondo Nacional de Recursos (organización gubernamental única a cargo de la financiación de la reperfusión del IAMCEST en Uruguay). Estos mismos datos se recuperaron para 2019, 2018 y 2017. Resultados: se trataron durante el periodo de estudio del 2020 (136 pacientes) en comparación con 2019 (180 pacientes), 2018 (182 pacientes) y 2017 (174 pacientes). Se realizó FBL como tratamiento único en 5,1%, 7,2%, 7,7% y 12,1%, respectivamente. La razón de tasa de incidencia de IAMCEST durante el período estudiado en 2020 fue de 0,7 (IC95%: 0,59-0,91). La mediana del tiempo hasta la reperfusión fue similar en comparación con 2019, 2018 y 2017 (p = 0,4). No hubieron diferencias en la mortalidad a 15 dias entre los años evaluados.

Introduction: the emergency health measures imposed to contain SARS-CoV-2 can have collateral effects in the care of cardiovascular diseases. Global country data on the incidence of ST acute myocardial infarction during the pandemic are critical for future health policy. Objectives: our objective was to determine if the emergency health measures imposed in Uruguay had a direct impact on the quality of ST elevation acute myocardial infarction care. Methods: we carried out a population-based retrospective study of the entire country to determine the incidence of reperfusion of ST elevation acute myocardial infarction (fibrinolytic and percutaneous) during the emergency health period. The incidence rate of reperfusion, time to reperfusion, and associated mortality were collected from the Fondo Nacional de Recursos (the only government organization in charge of the reperfusion of ST elevation myocardial infarction in Uruguay). These same data were recovered for 2019, 2018 and 2017. Results: fewer patients were treated in 2020 (136 patients) compared to 2019 (180 patients), 2018 (182 patients), and 2017 (174 patients). Fibrinolytics was performed as the only treatment in 5.1%, 7.2%, 7.7% and 12.1% respectively. The proportion in incidence rate of ST elevation myocardial infarction during the study period in 2020 was lower (0.74, 95% CI: 0.59-0.91). The median time to reperfusion was similar compared to 2019, 2018, and 2017 (p = 0.4). Mortality at 15 days was similar in 2017 (8%), 2018 (6%), 2019 (11%) and 2020 (8%). Conclusion: emergency health measures were associated with a decrease in the incidence of reperfusion of ST elevation myocardial infarction without affecting the time to reperfusion and mortality.

Introdução: as medidas emergenciais de saúde impostas para conter o SARS-CoV-2 podem ter efeitos colaterais no cuidado das doenças cardiovasculares. Os dados globais do país sobre a incidência de infarto agudo do miocárdio durante a pandemia são essenciais para a futura política de saúde. Objetivos: nosso objetivo foi determinar se as medidas de saúde de emergência impostas no Uruguai tiveram um impacto direto na qualidade do atendimento infarto agudo do miocárdio. Métodos: foi realizado um estudo retrospectivo de base populacional em todo o país para determinar a incidência de reperfusão do infarto agudo do miocárdio (fibrinolítico e percutâneo) durante o período de emergência de saúde. A taxa de incidência de reperfusão, tempo de reperfusão e mortalidade associada foram coletados do Fondo Nacional de Recursos (a única organização governamental responsável pela reperfusão de infarto agudo do miocárdio no Uruguai). Esses mesmos dados foram recuperados para 2019, 2018 e 2017. Resultados: menos pacientes foram tratados em 2020 (136 pacientes) em comparação com 2019 (180 pacientes), 2018 (182 pacientes) e 2017 (174 pacientes). Fibrinolisis foi realizado como o único tratamento em 5,1%, 7,2%, 7,7% e 12,1%, respectivamente. A proporção na taxa de incidência de infarto agudo do miocárdio durante o período estudado em 2020 foi menor (0,74, IC 95%: 0,59-0,91). O tempo médio para reperfusão foi semelhante em comparação com 2019, 2018 e 2017 (p = 0,4). A mortalidade em 15 dias foi semelhante em 2017 (8%), 2018 (6%), 2019 (11%) e 2020 (8%). Conclusão: as medidas emergenciais de saúde foram associadas à diminuição da incidência de reperfusão do infarto agudo do miocárdio, sem afetar o tempo de reperfusão e a mortalidade.

Saturated free fatty acid release and intracellular ceramide generation during apoptosis induction are closely related processes.

Apoptosis induced by cells from the immune system is frequently associated with an increase in the ceramide content of target cells, due to the activation of sphingomyelinases (SMase). Some studies have also reported the release of saturated and monounsaturated free fatty acids (FFA) from apoptotic cells. However, the possible relationship between these lipid biochemistry events has not been characterized. We have analysed for the first time the release of FFA triggered by tumor necrosis factor-alpha (TNF-alpha), Fas/CD95 or the perforin/granzyme system of cytotoxic T lymphocytes (CTL) and their relationship to intracellular ceramide generation. TNF-alpha- and Fas-induced apoptosis are associated with both intracellular ceramide generation from sphingomyelin (SM) and release of palmitic-derived FFA, with similar kinetics. Intracellular SMase activation and FFA release from target cells during Fas-induced apoptosis are much more rapid and efficient if Fas-based cytotoxicity is exerted by alloantigenic CTL. In the case of perforin/granzyme-based cytotoxicity exerted by CTL, intracellular ceramide generation and FFA release from target cells seem to depend on the type of lysis induction used. Importantly, the correlation between intracellular SMase activation and the release of palmitic acid-derived FFA from target cells has been observed in all types of cytotoxicity assayed. In addition, exogenous natural ceramide induces the rapid release of the same FFA, well before any apoptotic sign is detected, and FFA release during Fas-induced apoptosis is inhibited in SM-depleted cells by chronic fumonisin-B(1) treatment. These results demonstrate a novel connection between the release of palmitic acid-derived FFA and intracellular ceramide accumulation during apoptosis induction.

Cloning, characterization and comparative analysis of pig plasma apolipoprotein A-IV.

Pig apolipoprotein (apo) A-IV cDNA was cloned, characterized and compared to the human ortholog. Mature porcine apo A-IV consists of 362 amino acids and displays a 75.6% sequence identity with human protein. Pig apo A-IV is the smallest reported mammalian apo A-IV because it lacks the repeated motifs of glutamine and glutamic acid at the carboxyl terminus. A phylogenic tree of apo A-IV mammalian proteins reveals that porcine apo A-IV is more closely related to humans and primates than to rodents. This protein is highly hydrophobic and is mainly associated with lipoproteins.

Arsenic species determination in human scalp hair by pressurized hot water extraction and high performance liquid chromatography-inductively coupled plasma-mass spectrometry.

Analytical methods for the determination of total arsenic and arsenic species (mainly As(III) and As(V)) in human scalp hair have been developed. Inductively coupled plasma-mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled to ICP-MS have been used for total arsenic and arsenic species determination, respectively. The proposed methods include a "green", fast, high efficient and automated species leaching procedure by pressurized hot water extraction (PHWE). The operating parameters for PHWE including modifier concentration, extraction temperature, static time, extraction steps, pressure, mean particle size, diatomaceous earth (DE) mass/sample mass ratio and flush volume were studied using design of experiments (Plackett-Burman design PBD). Optimum condition implies a modifier concentration (acetic acid) of 150 mM and powdered hair samples fully mixed with diatomaceous earth (DE) as a dispersing agent at a DE mass/sample mass ratio of 5. The extraction has been carried out at 100°C and at an extraction pressure of 1500 psi for 5 min in four extraction step. Under optimised conditions, limits of quantification of 7.0, 6.3 and 50.3 ng g(-1) for total As, As(III) and As(V), respectively were achieved. Repeatability of the overall procedure (4.4, 7.2 and 2.1% for total As, As(III) and As(V), respectively) was achieved. The analysis of GBW-07601 (human hair) certified reference material was used for validation. The optimised method has been finally applied to several human scalp hair samples.

Rheumatoid synovial fluid T cells are sensitive to APO2L/TRAIL.

The infiltration and accumulation of T cells in the rheumatoid arthritis (RA) synovial fluid (SF) are hallmarks of disease. We aimed to assess the functional relevance of FasL and of APO2L/TRAIL in the persistence of T cells in the rheumatoid SF. We have analyzed the expression of the activation markers HLA-DR and CD69 and also of the death receptor Fas/CD95 and death ligands FasL or APO2L/TRAIL in CD3+ lymphocytes from SF of 62 RA patients, together with their sensitivity to anti-Fas mAb or to rAPO2L/TRAIL, using as controls T lymphocytes present in SF of 20 patients with traumatic arthritis. T lymphocytes infiltrated in SF of RA patients have a chronically activated phenotype, but they are resistant to Fas-induced toxicity. However, they are more susceptible to rAPO2L/TRAIL than T cells in the SF of traumatic arthritis patients. In addition, we found very low amounts of bioactive FasL and APO2L/TRAIL associated with exosomes in SF from RA patients as compared with SF from traumatic arthritis patients. The observation on the sensitivity of RA SF T cells to rAPO2L could have therapeutic implications because bioactive APO2L/TRAIL could be beneficial as a RA treatment.

Pig major acute-phase protein and apolipoprotein A-I responses correlate with the clinical course of experimentally induced African Swine Fever and Aujeszky's disease.

In the present work, we studied the acute phase protein response after experimental virus infection in pigs. The animals were experimentally infected with African Swine Fever (ASF) or Aujeszky's disease (AD) viruses. The clinical course of ASF infection correlated with increasingly high levels of pig Major Acute-phase Protein (pig-MAP) (mean value of 6 mg/mL on day 6 post infection (p.i.), from 6 to 9 times higher than day 0) and sharp apolipoprotein A-I (apo A-I) decrease (mean value of 0.5 mg/mL, from 4 to 10 times lower than day 0 on day 4 p.i.). AD-clinical signs appeared at day 3 p.i., both in vaccinated (moderate clinical signs) and non-vaccinated pigs (severe outcome within 48 h p.i.). Pig-MAP and apo A-I profiles also followed clinical signs (changing from 0.70 mg/mL to around 3 mg/mL and from around 3 mg/mL to 0.96 mg/mL, respectively in non-vaccinated animals), with minor changes in concentration in the vaccinated group. Haptoglobin levels significantly increased in ASF and AD infected animals (mean maximum values of 2.77 and 3.96 mg/mL, respectively). Minor differences for the C-Reactive Protein in the case of ASF were observed, whereas its concentration increased more than 7 times in AD-infection. The albumin level was not modified in either case. The correlation of clinical signs to our data suggests the potential use of pig-MAP and apo A-I in monitoring infections in swine.

Immune-regulation of the apolipoprotein A-I/C-III/A-IV gene cluster in experimental inflammation.

Apolipoprotein A-IV is a member of the apo A-I/C-III/A-IV gene cluster. In order to investigate its hypothetical coordinated regulation, an acute phase was induced in pigs by turpentine oil injection. The hepatic expression of the gene cluster as well as the plasma levels of apolipoproteins were monitored at different time periods. Furthermore, the involvement of the inflammatory mediators' interleukins 1 and 6 and tumor necrosis factor in the regulation of this gene cluster was tested in cultured pig hepatocytes, incubated with those mediators and apo A-I/C-III/A-IV gene cluster expression at the mRNA level was measured. In response to turpentine oil-induced inflammation, a decreased hepatic apo A-IV mRNA expression was observed (independent of apo A-I and apo C-III mRNA) not correlating with the plasma protein levels. The distribution of plasma apo A-IV experienced a shift from HDL to larger particles. In contrast, the changes in apo A-I and apo C-III mRNA were reflected in their corresponding plasma levels. Addition of cytokines to cultured pig hepatocytes also decreased apo A-IV and apo A-I mRNA levels. All these results show that the down-regulation of apolipoprotein A-I and A-IV messages in the liver may be mediated by interleukin 6 and TNF-alpha. The well-known HDL decrease found in many different acute-phase responses also appears in the pig due to the decreased expression of apolipoprotein A-I and the enlargement of the apolipoprotein A-IV-containing HDL.

[Crohn's disease associated with focal pulmonare lesion]. / Enfermedad de Crohn asociada a la lesion pulmonar focal.

40 year-old male recently diagnosed with Crohn's disease. A routine chest X ray showed a round, well defined opacity in right lung field. A chest CT scan confirmed the finding and also described bronchiectasis. Patient had no respiratory symptoms. He was prescribed with oral sulfasalazine and corticosteroids with rapid improvement of intestinal symptoms as well as resolution of the pulmonary opacity. We describe the clinical presentation of a male newly diagnosed with Crohn's disease who was found to have an asymptomatic pulmonary lesion on imaging studies. Pulmonary complications have been previously described in inflamatory bowel disease being more common in ulcerative colitis than in Crohn's disease; these can involve the lung parenchyma, the tracheobronchial tree, and the pleura. The true prevalence and etiology of these lesions is currently unknown and are not necessarily associated with bowel disease activity. Abnormal pulmonary functions test have been reported during inflammatory bowel disease exacerbations, and although pulmonary findings can present with a variety of symptoms, subclinical presentations have also been described. Pulmonary manifestations are usually steoid-responsive, as was the case in our patients.

The human melanoma cell line MelJuSo secretes bioactive FasL and APO2L/TRAIL on the surface of microvesicles. Possible contribution to tumor counterattack.

Tumor cells have developed multiple mechanisms to evade control by the immune system. Tumoral cells expressing Fas ligand (FasL) have been proposed to "counterattack" against activated antitumoral effector immune cells, although some authors have indicated that FasL is not expressed on the surface of the same tumors, such in the case of melanoma cells. However, other factors could be implicated, such as the balance of soluble versus membrane-bound forms or the secretion of death ligands on the surface of microvesicles, as described previously by our group in human T cells. In the present study, we analyzed the expression and secretion of FasL and APO2 ligand (APO2L)/TRAIL in the human melanoma cell line MelJuSo. We have observed the expression of preformed FasL and APO2L/TRAIL in these cells, their secretion associated with microvesicles upon melanoma activation with PHA or with alpha-melanocyte stimulating hormone (alpha-MSH), and the toxicity of these microvesicles against normal human T cell blasts. We have also observed that the mechanism of secretion of FasL and APO2L/TRAIL from melanoma cells is depending both on microtubules and actin filaments. From these data, it can be concluded that the MelJuSo melanoma cell line has the possibility to "counterattack" against activated immune effector cells. However, the in vivo outcome seems more complex since it has been also described that FasL expressed in tumors has a proinflammatory effect.

Lack of Fas/CD95 surface expression in highly proliferative leukemic cell lines correlates with loss of CtBP/BARS and redirection of the protein toward giant lysosomal structures.

Fas/CD95 is a type-I membrane glycoprotein, which inducesapoptotic cell death when ligated by its physiological ligand. We generated previously hyperproliferative sublines derived from the human T-cell leukemia Jurkat, Jurkat-ws and Jurkat-hp, which lost Fas/CD95 surface expression. We have now observed that the total amount of Fas protein is similar in the sublines and in the parental cells, indicating that in the sublines Fas remains in an intracellular compartment. We have found that the protein is directed toward lysosomes in the sublines, where it is degraded. This defect in the secretory pathway correlates with loss of polyunsaturated fatty acids from cellular lipids, and with the lack of expression of endophilin-I and CtBP/BARS, enzymes that regulate vesicle fission by catalyzing the acylation of arachidonate into lysophosphatidic acid. In addition, great multillamer bodies, which contained acid phosphatase activity, absent in the parental Jurkat cells, were observed by transmission electron microscopy in the sublines.

Rheumatoid sinovial fluid T cells are sensitive to Apo2L/Trail Regulation

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Ventilación mecánica en la UCI del departamento de medicina del Hospital Cayetano Heredia / Mechanical ventilation in the ICU of the departament of medicine of the Hospital Cayetano Heredia

Este informe destaca las complicaciones observadas durante el tratamiento con soporte respiratorio en 64 pacientes en la Unidad de Cuidados Intensivos del Departamento de Medicina del Hospital Cayetano Heredia entre los años 1983 y 1985. Las complicaciones más frecuentes estuvieron relacionadas al cuidado de la vía aérea: Intubación en el bronquio derecho en 12 casos, ruptura del manguito en 11, autoextubación en 8, y salida accidental de la cánula de traqueostomía en 7. Entre las de tipo técnico destacaron: desconexión del enchufe en 9, alarma interrumpida en 7, falla del ventilador en 4 y ruptura del cable eléctrico en 2. Otras complicaciones fueron: Atelectasias en 24, desconexión del ventilador al paciente 8, fuga de presión 7 y neumotóraxa tensión en 4 casos. En 4 condiciones la muerte del paciente fue atribuída a una complicación: Neumotórax a tensión en 4, inadecuado manejo de secreciones en 1 y desconexión inadvertida del ventilador en 1 caso. Se logró destete exitoso en 21 (32 por ciento)pacientes que posteriormente fueron dados de alta sin secuelas. Las complicaciones observadas son fiel reflejo de las condiciones particulares del trabajo médico como son: Apertura reciente de la Unidad, personal de enfermería inexperto en su fase inicial, inexistencia del terapista respiratorio, pieza fundamental del equipo que labora con el enfermo crítico respiratorio, infraestructura deficiente, pobres recurso técnicos, escaso presupuesto y precario servicio de mantenimiento