Propofol: a safe anaesthetic drug in experimental cardiac surgery in rabbits

Experimental surgery needs a pharmacological approach that can interfere with cardiac function

0203 The lung burden of Asbestos Fibres (AF) and Asbestos Bodies (AB) and the risk of mesothelioma (MM) for exposures ceased 30 years ago

Objectives To estimate the risk of MM according to AF and AB in the lungs. Method Freeze dried lung samples from 309 MM and 41 controls have been analysed for AF (Scanning Electronic Microscopy) and AB (Optical Microscopy) from subjects investigated and classified for probability and circumstances of asbestos exposure. Odds Ratios (OR) were obtained using logistic regression. Results 254 (82%) MMs have been classified as occupationally and 25 (8%) as non-occupationally exposed: Geometric Mean (GM) for AF burden was 1 950 000 and 608 000 ff/g dlt, respectively; and 39 300 and 3300 for AB. 75% and 58% of the AF respectively were amphibole. Controls reported a GM of 269 000 AF and 28 of AB g/dlt. For any increase of 100.000 ff/g dlt, we computed an OR of 1.7 (1.3–2.3) for amphibole, 1.1 (1.0–1.3) for chrysotile, among occupational MMs; an OR of 1.3 (1.0–1.7) and 1.1 (1.0–1.1) among non-occupational MMs. The 1997 Helsinki criteria for attribution to occupational exposure would have excluded more than 30% of MMs under study: here occupational exposures ceased on average 26 years before the disease, and therefore clearance and time since last exposure must be taken into account because are relevant determinants of the retained amount of fibres. Conclusions The risk of MM increases with the amount of retained amphibole, and to a lesser extent, of chrysotile fibres. Because occupational and non-occupation asbestos exposures have been to mixture of fibres, the lungs of MM patients are still loaded with amphibole AF

analysis of pro arrhythmic effects induced by different routes of administration of bone marrow stem cells

There has been repeated concern that intramyocardial (i.m.) delivery of cells could cause ventricular arrhythmias. The aim of the study was to evaluate the pro-arrhythmic effects of bone marrow stem cell (BMSC) injection and compare different routes of administration. An ischemia reperfusion injury was induced in New Zealand rabbits by temporal ligation of anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection. We compared different routes of BMSC injections, intramyocardial (i.m.) versus intravenous (i.v.) administration of cells. A control group was treated with i.m. injections of saline. The hourly number of supra- and ventricular premature contractions (VPCs), QT interval time and QTc time were recorded and calculated. At Day 7 after cell injections, VPCs were more frequent in the groups treated with i.m. BMSCs and i.m. saline compared with i.v. BMSCs (132 ±19; 54±14 and 34±9, respectively; P<0.01 within groups), whereas at Day 21 the number of VPCs was higher in the 2 groups treated with either i.m. or i.v. BMSCs compared with saline (96±23; 52±19 and 25±20, respectively; P<0.001 within groups). QTc time interval was prolonged during ischemia, and recovered in control and in the group treated with i.v. cells, whereas it remained longer in rabbits treated with i.m. BMSCs. These findings show that i.m. BMSC injections induced a high number of pre-arrhythmic events suggesting changes in cardiac electrophysiological properties. The i.v. administration of cells resulted in lower VPC beats and in a temporary QT prolongation. These results suggest that the combination of BMS cells and i.m. injections induced an electrical remodeling that contributed to the development of arrhythmias

Comparison of HER-2 and hormone receptor expression in primary breast cancers and asynchronous paired metastases: impact on patient management

The assessment of hormone receptors (HRs) and human epidermal growth factor receptor (HER)-2 is necessary to select patients who are candidates for hormonal and anti-HER-2 therapy. The evaluation of these parameters is generally carried out in primary tumors and it is not clear if reassessment in metastatic lesions might have an impact on patient management. The primary aim of this analysis was to compare HER-2 and HR status in primary tumors versus metastatic sites in breast cancer patients. PATIENTS AND METHODS: Seventy-five patients with available samples from primary tumors and paired metastases were included. HER-2 status was evaluated by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH); HR status was assessed by IHC. RESULTS: Nineteen percent of primary tumors were HER-2 positive; 77% were HR positive. Sites of biopsied or resected metastases were: locoregional soft tissues (n = 30), liver (n = 20), central nervous system (n = 5), bone (n = 5), pleura (n = 4), distant soft tissues (n = 3), abdomen (stomach, colon, peritoneum) (n = 3), bronchus (n = 3), and bone marrow (n = 2). For paired metastases, the HER-2 status was unchanged in 84% of cases; two patients changed from positive to negative, while 10 patients converted from negative to positive (agreement, 84%; kappa = 0.5681). A change in HR status was observed in 16 cases (21%): nine cases from positive to negative and seven cases from negative to positive (agreement, 78.7%; kappa = 0.4158). CONCLUSIONS: Further studies are necessary to better define the level of discordance in HER-2 or HR status between primary tumors and paired metastases. However, a biopsy of metastatic disease can be recommended, if feasible with minimal invasiveness, because treatment options might change for a significant proportion of patient

Treatment of Achilles Tendinopathy in Recreational Runners with Peritendinous Hyaluronic Acid Injections: A Viscoelastometric, Functional, and Biochemical Pilot Study

Background: Achilles tendinopathy (AT) affects ca. 10 million recreational runners in Europe; the practice of hyaluronic acid (HA) infiltration is being increasingly adopted. The aim of this pilot study was to monitor the effects of a three-local time-spaced injections regimen of HA in the treatment of AT in middle-aged runners combining for the first time viscoelastometric, biochemical, and functional methodologies with routine clinical examinations. Methods: Eight male runners (Age 49.3 ± 3.9), diagnosed for unilateral AT, were given three ultrasound (US) guided peritendinous HA injections at the baseline (T0) and every fifteenth day with a follow-up on the forty-fifth day (T1, T2, and T3). At all-time points patients were assessed for viscoelastic tone and stiffness, maximal voluntary isometric contraction (MVIC), and pain level (Likert scale 0-5). The peritendinous effusions of the injured tendon were collected at T0 and T2 to quantify the volume variations and the IL-1β and MMP-3 levels. Results: At T0 MVIC and pain score were significantly lower and higher, respectively, in injured tendons. The volume, IL-1β and MMP-3 levels decreased in the course of treatment and the clinical endpoints ameliorated over time. Tone, stiffness, and functional performance also varied significantly at T2 and T3, as compared to T0. Conclusions: The sequential peritendinous injections of HA were effective in the amelioration of the clinical symptoms, as well as of the functional and viscoelastic state associated with AT. The determination of the viscoelastometric state may help to precisely evaluate the healing process in AT patients

ICG fluorescence imaging in colorectal surgery: a snapshot from the ICRAL study group

Background: Fluorescence-guided visualization is a recently proposed technology in colorectal surgery. Possible uses include evaluating perfusion, navigating lymph nodes and searching for hepatic metastases and peritoneal spread. Despite the absence of high-level evidence, this technique has gained considerable popularity among colorectal surgeons due to its significant reliability, safety, ease of use and relatively low cost. However, the actual use of this technique in daily clinical practice has not been reported to date. Methods: This survey was conducted on April 2020 among 44 centers dealing with colorectal diseases and participating in the Italian ColoRectal Anastomotic Leakage (iCral) study group. Surgeons were approximately equally divided based on geographical criteria from multiple Italian regions, with a large proportion based in public (89.1%) and nonacademic (75.7%) centers. They were invited to answer an online survey to snapshot their current behaviors regarding the use of fluorescence-guided visualization in colorectal surgery. Questions regarding technological availability, indications and techniques, personal approaches and feelings were collected in a 23-item questionnaire. Results: Questionnaire replies were received from 37 institutions and partially answered by 8, as this latter group of centers do not implement fluorescence technology (21.6%). Out of the remaining 29 centers (78,4%), fluorescence is utilized in all laparoscopic colorectal resections by 72.4% of surgeons and only for selected cases by the remaining 27.6%, while 62.1% of respondents do not use fluorescence in open surgery (unless the perfusion is macroscopically uncertain with the naked eye, in which case 41.4% of them do). The survey also suggests that there is no agreement on dilution, dosing and timing, as many different practices are adopted based on personal judgment. Only approximately half of the surgeons reported a reduced leak rate with fluorescence perfusion assessment, but 65.5% of them strongly believe that this technique will become a minimum requirement for colorectal surgery in the future. Conclusion: The survey confirms that fluorescence is becoming a widely used technique in colorectal surgery. However, both the indications and methods still vary considerably; furthermore, the surgeons' perceptions of the results are insufficient to consider this technology essential. This survey emphasizes the need for further research to reach recommendations based on solid scientific evidence. Keywords: Colon cancer; Fluorescence guided surgery; ICG; Laparoscopy; Rectal cancer

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Pesticides in the environment: analysis, occurrence, impact and recommendations for their attenuation

[eng] The assessment of pesticide occurrence in different environmental compartments has become a matter of outstanding importance since its effects on exposed organisms may be considered a warning on the potential risk these substances may pose to human health. In this context, and in the framework of this doctoral thesis, the presence and fate of 52 pesticides and transformation products were evaluated in surface water, groundwater, and sediments from four river basins, and the associated environmental risk was assessed. In addition, the performance of a fungi-based bioremediation technique for the removal of pesticides was evaluated. The methods developed are based on the use of advanced extraction techniques such as on-line solid-phase extraction, pressurized liquid extraction, and QuEChERS extraction, and analyte determination with liquid chromatography coupled to tandem mass spectrometry. The use of an isotope-dilution approach ensured the reliability of the results and the satisfactory performance of the methodologies in terms of accuracy, precision, linearity, sensitivity and matrix effect. The most relevant pesticides detected in agricultural areas (Ebro River Delta, Ter River) were the herbicides widely used in rice cultivation bentazone, MCPA and propanil, while in urban and industrial areas like the lower Llobregat River basin, the most relevant pesticides were bromoxynil, diuron, linuron and terbutryn, used for both agricultural and non-agricultural purposes. In the sediments of the Llobregat River and the fish samples collected from the Adige River, most of the pesticides found are currently banned, which suggest their persistence in the environment. The assessment of the environmental risk highlighted the role of pesticides as relevant stressors in the aquatic environment. The degradation of selected pesticides by the fungus T. versicolor point at this organism as an efficient, green and economic alternative for pesticide removal during water treatment. Further pesticide pollution attenuation was attempted by contributing to the design of participatory multi-actor events to increase the awareness of farmers and stakeholders on the issue of environmental pollution by pesticides, involving them in the decision-making processes for the implementation of mitigation measures and best management practices aimed at reducing pesticide release into the environment.[spa] La evaluación de la presencia de plaguicidas en los diferentes compartimentos ambientales es de gran importancia ya que sus efectos en los organismos expuestos pueden considerarse una advertencia del riesgo potencial que estas sustancias pueden suponer para la salud humana. En este contexto, en el marco de esta tesis doctoral se ha estudiado la presencia y destino de 52 pesticidas y productos de transformación en aguas superficiales, subterráneas, sedimentos y biota de cuatro cuencas hidrográficas, y se ha evaluado el riesgo ambiental asociado. Además, se ha valorado la eficacia de una técnica de biorremediación basada en hongos para eliminar plaguicidas seleccionados. Los métodos desarrollados se basan en el uso de técnicas avanzadas de extracción como son la extracción en fase sólida (SPE) on line automatizada, la extracción mediante líquidos presurizados (PLE) seguida de purificación del extracto mediante SPE, y la extracción con QuEChERS para la preconcentración de los plaguicidas en agua, sedimento, y biota, respectivamente, y la determinación de los compuestos mediante cromatografía de líquidos acoplada a espectrometría de masas en tándem. El uso de dilución isotópica para la cuantificación garantiza la fiabilidad de los resultados y el rendimiento satisfactorio de los métodos desarrollados en términos de exactitud, precisión, linealidad y efecto de la matriz. La sensibilidad de los métodos desarrollados posibilita la evaluación de los plaguicidas seleccionados a los niveles de los estándares de calidad ambiental marcados por la Comisión Europea en el ámbito de la política de aguas. Los plaguicidas más relevantes detectados en las áreas agrícolas investigadas fueron los herbicidas bentazona, MCPA y propanil, ampliamente utilizados en el cultivo del arroz en el delta del río Ebro. El río Ter, también afectado por actividades agrícolas intensivas, resultó contaminado en menor medida por bentazona y MCPA. En áreas urbanas e industriales como la cuenca baja del río Llobregat, los compuestos más ubicuos y abundantes fueron bromoxinilo, diurón, linurón y terbutrina, utilizados tanto con fines agrícolas como no agrícolas. En esta zona, muchos de los plaguicidas encontrados superaban el límite de 100 ng/L establecido por la Unión Europea para plaguicidas individuales en aguas destinadas al consumo humano. En los sedimentos del río Llobregat y las muestras de peces recogidas en el río Adige, los plaguicidas presentan propiedades físico-químicas que los hacen más propensos a acumularse en sedimentos o bioacumularse en la biota. La mayoría de los pesticidas detectados en estas matrices están actualmente prohibidos, lo cual sugiere su persistencia en el medio ambiente. Diclorvos e irgarol superaron las concentraciones máximas admisibles establecidas por la Comunidad Europea como normas de calidad ambiental para compuestos prioritarios en aguas superficiales, mientras que los límites máximos aceptables de detección (LODs) establecidos en la Lista de Observación europea fueron superados por acetamiprid, imidacloprid, tiacloprid y metiocarb. La evaluación del riesgo ambiental ha destacado el papel de los plaguicidas como estresores relevantes en el medio acuático. Además, la co-ocurrencia de plaguicidas resulta en un aumento del riesgo en los diversos compartimentos ambientales estudiados, lo que hace necesaria la adopción de medidas para atenuar la contaminación ambiental por plaguicidas. Con este propósito, se exploró la capacidad del hongo T. versicolor para degradar malatión, acetamiprid e imidacloprid. Los resultados apuntan a este organismo como una alternativa eficaz, ecológica y económica para la eliminación de pesticidas del agua. Por otro lado, se diseñaron eventos participativos con el fin de aumentar la conciencia de los agricultores y otras partes interesadas sobre el problema de la contaminación ambiental por plaguicidas, involucrándolos en los procesos de toma de decisiones para motivar la implementación de medidas de mitigación destinadas a reducir la liberación de plaguicidas al medio ambiente