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Objetivo: Vários estudos têm demonstrado que Radicais Livres de Oxigênio (RLO) contribuem para o dano celular decorrente da isquemia e reperfusão. Este estudo foi desenvolvido como o objetivo de avaliar os efeitos da isquemia e reperfusão renal em ratos, tratados ou não com alopurinol, sobre a lipoperoxidação (LPO) das membranas celulares renais. Método: Foram usados ratos Wistar distribuídos em 4 grupos e submetidos a períodos de isquemia e reperfusão renal ou não, dependendo do grupo. Também foram submetidos ou não a tratamento com alopurinol na dose de 50 e 150 mg/Kg por via intraperitoneal, 5 e 1 horas antes do procedimento. Na avaliação da lipoperoxidação utilizou-se os métodos do TBARS e QL. Resultados: Os resultados demonstraram aumento da LPO nos animais submetidos a isquemia e reperfusão renal. No entanto, estes efeitos deletérios foram reduzidos com o pré-tratamento com alopurinol (p

Abstract Background Coronary artery anomalies (CAAs) are currently undergoing profound changes in understanding potentially pathophysiological mechanisms of disease. Aim of this study was to investigate the prevalence of anomalous origin and course of coronary arteries in consecutive symptomatic patients, who underwent cardiac 64-slice multidetector-row computed tomography angiography (MDCTA). Methods Imaging datasets of 748 consecutive symptomatic patients referred for cardiac MDCTA were analyzed and CAAs of origin and further vessel course were grouped according to a recently suggested classification scheme by Angelini et al. Results An overall of 17/748 patients (2.3%) showed CAA of origin and further vessel course. According to aforementioned classification scheme no Subgroup 1- (absent left main trunk) and Subgroup 2- (anomalous location of coronary ostium within aortic root or near proper aortic sinus of Valsalva) CAA were found. Subgroup 3 (anomalous location of coronary ostium outside normal "coronary" aortic sinuses) consisted of one patient with high anterior origin of both coronary arteries. The remaining 16 patients showed a coronary ostium at improper sinus (Subgroup 4). Latter group was subdivided into a right coronary artery arising from left anterior sinus with separate ostium (subgroup 4a; n = 7) and common ostium with left main coronary artery (subgroup 4b; n = 1). Subgroup 4c consisted of one patient with a single coronary artery arising from the right anterior sinus (RAS) without left circumflex coronary artery (LCX). In subgroup 4d, LCX arose from RAS (n = 7). Conclusions Prevalence of CAA of origin and further vessel course in a symptomatic consecutive patient population was similar to large angiographic series, although these patients do not reflect general population. However, our study supports the use of 64-slice MDCTA for the identification and definition of CAA.

Sézary syndrome (SS) is a rare and aggressive variant of cutaneous T-cell lymphoma. It is characterized by the copresence of CD4+ neoplastic lymphocytes, named Sezary cells, mainly in the blood, lymph nodes, and skin where they induce chronic inflammation that in turn impairs the patient's QOL and fuels neoplastic cells. SS is not readily cured, but immunotherapy is becoming an effective option for this lymphoma. In this study, we investigated, in a large cohort of patients with SS, the expression and function of the immune checkpoint molecule CD39, which degrades proinflammatory extracellular adenosine triphosphate. We showed that the SNP rs10748643 A/G within the ENTPD1 gene coding for the CD39 protein controls its expression level. Patients carrying the A/G‒G/G genotype showed a significantly higher frequency of clonal CD4+CD39+ SS cells than those carrying the A/A genotype. Different from other cancers, high CD39 expression correlates with a better prognosis. Comparing primary G/G with A/A lymphoma cells, we observed that G/G SS cells have a higher ability to degrade adenosine triphosphate, increased apoptotic susceptibility, and upon activation, reduced IL-2 production. Accordingly, CD39 enzymatic inhibition enhances SS cell viability and IL-2 production on activation. These results strongly suggest a special caution for SS treatment with therapeutic inhibitors of CD39., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as pDC, neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-β and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-β were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found., (© 2019 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Purpose: Many US medical schools have adopted learning communities to provide a framework for advising and teaching functions. Faculty who participate in learning communities often have additional educator roles. Defining potential conflicts of interest (COIs) among these roles is an important consideration for schools with existing learning communities and those looking to develop them, both for transparency with students and also to comply with regulatory requirements., Methods: A survey was sent to the institutional contact for each of the 42 Learning Communities Institute (LCI) member medical schools to assess faculty opinions about what roles potentially conflict. The survey asked the role of learning community faculty in summative and formative assessment of students and whether schools had existing policies around COIs in medical education., Results: In all, 35 (85%) LCI representatives responded; 30 (86%) respondents agreed or strongly agreed that learning community faculty should be permitted to evaluate their students for formative purposes, while 19 (54%) strongly agreed or agreed that learning community faculty should be permitted to evaluate their students in a way that contributes to a grade; 31 (89%) reported awareness of the accreditation standard ensuring "that medical students can obtain academic counseling from individuals who have no role in making assessment or promotion decisions about them," but only 10 (29%) had a school policy about COIs in education. There was a wide range of responses about what roles potentially conflict with being a learning community faculty., Conclusion: The potential for COIs between learning community faculty and other educator roles concerns faculty at schools with learning communities, but most schools have not formally addressed these concerns., Competing Interests: Declaration of Conflicting Interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Eosin has been traditionally employed as a topical treatment for psoriasis, but the biological mechanism of its therapeutic action has not been fully elucidated., Objectives: To analyse eosin effects on psoriatic skin in vivo and keratinocytes and endothelial cells in vitro., Materials & Methods: Skin biopsies were taken from psoriatic plaques before and after a three-day eosin treatment and processed for histological analysis. Cultured human psoriatic keratinocytes and dermal endothelial cells were treated with eosin, and release of inflammatory chemokines was analysed by multiplexed bead-based immunoassay and ELISA., Results: In patients, the three-day eosin treatment significantly reduced the number of infiltrating T lymphocytes, neutrophilic granulocytes, and dermal dendritic cells. A reduction in VEGF-A expression was also observed. In vitro, eosin treatment significantly decreased the release of CCL2, CCL5, and VEGF-A by keratinocytes and angiopoietin-2 by endothelial cells., Conclusions: Eosin treatment impacts on psoriatic inflammatory infiltrates and dampens the release of proinflammatory chemokines and angiogenic factors.

Background.: Mask ventilation and tracheal intubation are basic techniques for airway management and mutually inclusive rescue measures to restore ventilation. The aim of this study was to compare the effectiveness of mask ventilation between two commonly used techniques of two-handed mask ventilation in obese unconscious apnoeic adults., Methods.: Eighty-one obese adults received mask ventilation after induction using C-E clamp and modified V-E clamp techniques in a randomized crossover manner. Mechanical ventilation was provided using a pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H 2 O. The primary outcome was expired tidal volume., Results.: The BMI for the subjects was 37 ( sd 4.9) kg m -2 . The failure rates for mask ventilation (tidal volume≤anatomical dead space) were 44% for the C-E technique and 0% for the V-E technique ( P <0.001). Tidal volume was significantly lower for the C-E than the V-E technique [371 ( sd 345) vs 720 (244) ml, P <0.001]. The peak airway pressures were 21 ( sd 1.5) cm H 2 O for the C-E technique and 21 (1.3) cm H 2 O for the V-E technique., Conclusions.: Mask ventilation using the modified V-E technique is more effective than with the C-E technique in unconscious obese apnoeic adults. Subjects who fail ventilation with the C-E technique can be ventilated effectively with the V-E technique., Clinical Trial Registration.: NCT02580526., (© The Author 2017. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Rapid infusers are vital tools during massive hemorrhage and resuscitation. Sporadic reports of overheating and shutdown of the Belmont® Rapid Infuser, a commonly used system, have been attributed to 1-sided clot blockage of the fluid path. We investigated multiple causes of failure of this device., Methods: Packed red blood cells and thawed fresh frozen plasma with normal saline solution were used as base fluids for serial 10-minute trials using standard disposable sets in 2 Belmont devices. Possible contributors to device failure, including calcium-containing solutions and external leakage currents, were evaluated. Thermographic images of the heater and disposable cartridges were recorded. The effects of complete unilateral clotting were modeled by sealing half of the disposable cartridge with epoxy., Results: Clotting on the surface of the heat exchanger coil increased with calcium concentration and was only observed at calcium concentrations >12.0 mmol/L (P < 0.0001) in a 1:1 plasma:red blood cell mixture, resulting in high-pressure downstream occlusion alarms and interruption of flow., Conclusions: Clot-based occlusion can be induced in the Belmont Rapid Infuser under unrealistic conditions. In the absence of complete unilateral flow blockage, we did not observe any significant overheating of the infuser under extreme operating conditions.

Background: The wastage of red blood cell (RBC) units within the operative setting results in significant direct costs to health care organizations. Previous education-based efforts to reduce wastage were unsuccessful at our institution. We hypothesized that a quality and process improvement approach would result in sustained reductions in intraoperative RBC wastage in a large academic medical center., Study Design and Methods: Utilizing a failure mode and effects analysis supplemented with time and temperature data, key drivers of perioperative RBC wastage were identified and targeted for process improvement., Results: Multiple contributing factors, including improper storage and transport and lack of accurate, locally relevant RBC wastage event data were identified as significant contributors to ongoing intraoperative RBC unit wastage. Testing and implementation of improvements to the process of transport and storage of RBC units occurred in liver transplant and adult cardiac surgical areas due to their history of disproportionately high RBC wastage rates. Process interventions targeting local drivers of RBC wastage resulted in a significant reduction in RBC wastage (p < 0.0001; adjusted odds ratio, 0.24; 95% confidence interval, 0.15-0.39), despite an increase in operative case volume over the period of the study. Studied process interventions were then introduced incrementally in the remainder of the perioperative areas., Conclusions: These results show that a multidisciplinary team focused on the process of blood product ordering, transport, and storage was able to significantly reduce operative RBC wastage and its associated costs using quality and process improvement methods., (© 2015 AABB.)

Purposes: The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms., Methods: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals., Results: High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54)., Conclusions: Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

Concerns about pesticide exposure through food consumption have increased during the past several years. Pyrethroids are applied as insecticides throughout the world. Human metabolism of pyrethroids results in urinary metabolites that are suitable for biological monitoring. The objective of our study was to investigate the relation between food consumption and urinary levels of 3-phenoxybenzoic acid (3-PBA), a general metabolite of pyrethroids, in a non-occupational exposed adult population from the IDI-IRCCS, Rome, Italy. Information on socio-demographic characteristics, smoking, diet and self-reported household pesticide exposure was collected. Urinary 3-PBA level of each subject was measured and adjusted by urinary creatinine. We found that people consuming both raw and cooked vegetables five times weekly or more had higher mean levels of 3-PBA in urine (1.03 μg/g creatinine versus 0.52 μg/g creatinine; p=0.009 and 0.99 μg/g creatinine versus 0.58 μg/g creatinine; p=0.01, respectively) than subjects consuming less than five times weekly. In a multivariate model, after adjusting for age, sex, BMI, smoking and household insecticide exposure, high intake of raw vegetables (OR: 5.31; 95%CI: 1.32-21.3) and high intake of cooked vegetables, in particular cruciferous (OR: 4.67; 95%CI: 1.07-20.5) and leafy vegetables (OR: 6.88; 95%CI: 1.50-31.7), were associated with high urine 3-PBA levels (≥0.70 μg/g creatinine). The results of this study suggest that part of the variation in pyrethrois intake is explained by vegetable intake., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Sézary syndrome is a rare and very aggressive leukemic variant of cutaneous T-cell lymphoma characterized by extensive skin involvement and a malignant circulating CD4(+) T-cell clone which homes to the skin, over-expresses CD60, and lacks CD7, CD26 and CD49d. So far prognostic markers in this disease are limited to treatment with systemic steroids, age, serum lactate dehydrogenase, and a white blood cell count of 20×10(9)/L or higher: no other biological marker with prognostic value, especially related to malignant cells, has been described., Design and Methods: We used flow activated cell sorting analysis to compare the distribution of the T-cell receptor-Vβ repertoire and several surface molecules (CD7, CD26, CD49d and CD60) within the circulating CD4(+) T-cell population in 62 patients with Sézary syndrome, 180 with mycosis fungoides, 6 with B-cell lymphomas, and 19 with chronic eczema. We calculated the 5-year overall survival of patients with Sézary syndrome after first hospital admission using Kaplan-Meier product-limit estimates and hazard ratios from the Cox proportional hazards model., Results: We found that both higher number of CD60(+) and lower number of CD49d(+) cells within circulating CD4(+) T cells at disease presentation were significantly associated with a lower probability of survival. An exceedingly high risk of death was observed for patients with a combination of a high proportion of CD4(+)CD60(+) cells (≥ 0.5×10(9)/L) and low proportion of CD4(+)CD49d(+) cells (<0.5×10(9)/L) (hazard ratio = 12.303, 95% confidence interval 1.5-95.9; P<0.02). In addition, a skewed usage of T-cell receptor-Vβ subfamilies was observed in the circulating T-cell clone for 61.9% of all patients with Sézary syndrome, T-cell receptor-Vβ 2 and 5.1 subfamilies being the most frequently represented (42.8%), followed by T-cell receptor-Vβ 12 and 13.1., Conclusions: In this study we showed that up-regulation of CD60 and down-regulation of CD49d on circulating CD4(+) T cells are two useful markers for predicting a very poor outcome in patients with Sézary syndrome.

The beneficial health effects of emotional writing disclosure (ED) on several chronic diseases have been reported. The aim of this pilot study was to investigate the effects of two ED techniques on psoriatic patients treated with ultraviolet B (UVB) therapy. Forty patients were randomly assigned to two different ED treatments (according to Pennebaker [PW], writing about stressful events, to King [KW], writing about major life goals), or to a control group (CG). Disease severity and quality of life (QoL) were assessed at baseline, halfway through and at the end of UVB treatment, and 4 months after ED. Outcome measures were the PASI and SAPASI scores, the Skindex-29, and the GHQ-12, to assess disease severity, health-related QoL and psychological wellbeing, respectively. Increases in SAPASI scores were recorded between end of therapy and the final assessment in KW (p: 0.07) and CG individuals (p: <0.05), whereas no differences were found in PW patients. Significant differences in Skindex-29 values between PW and the other groups were reported.Patients allocated to the PW group had a longer period of remission after phototherapy. This provides preliminary evidence that such a simple and inexpensive tool may play a role in enhancing treatment efficacy and QoL.

Simple and reliable tools for identifying patients at high risk for melanoma with preventive measures have important public health implications. An individual risk score for cutaneous melanoma was constructed and externally validated. With the summary coefficients of the risk factors for cutaneous melanoma, derived from a meta-analysis, a melanoma risk score was tested in an Italian population and externally validated in a Brazilian population. Common nevi, skin and hair color, freckles, and sunburns in childhood were the variables included in the final predictive model. The discriminatory ability of the models was assessed by the receiver operating characteristic (ROC) curve. The performance of the model was also evaluated by conducting an external validation. The area under the curve (AUC) of the candidate model was 0.79 (95% confidence interval: 0.75-0.82). The same model, when applied in the Brazilian population, presented an AUC of 0.79 (95% confidence interval: 0.70-0.86). At the cut-off level of 3 and more, 89 and 80% of the melanoma cases were correctly classified as 'at risk for melanoma' in the Italian and in the Brazilian populations, respectively. The risk model is a simple tool that identifies patients for preventive measures and may be used with reasonable confidence in different populations. The risk model may help family doctors in referring patients to dermatological clinics and thus improve early diagnosis.

Background: Many studies have investigated the Mediterranean diet as a risk factor for cancer, none of which has included cutaneous melanoma. The latter is usually fatal, rendering knowledge about prevention extremely important. We assessed the role of some food components of the Mediterranean diet and cutaneous melanoma., Methods: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy including 304 incident cases of cutaneous melanoma and 305 controls, frequency matched to cases. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected. Logistic regression was the method used to estimated odds ratio and 95% CIs., Results: After careful control for several sun exposure and pigmentary characteristics, we found a protective effect for weekly consumption of fish (OR, 0.65, 95%CI = 0.43-0.97), shellfish (OR, 0.53, 95%CI = 0.31-0.89), fish rich in n-3 fatty acids (OR, 0.52, 95%CI = 0.34-0.78), daily tea drinking (OR, 0.42, 95%CI, 0.18-0.95; P(trend) = 0.025) and high consumption of vegetables (OR, 0.50, 95%CI = 0.31-0.80, P(trend) = 0.005) in particular carrots, cruciferous and leafy vegetables and fruits (OR, 0.54, 95%CI =0.33-0.86, P(trend) = 0.013), in particular citrus fruits. No association was found for alcohol consumption and any other food items., Conclusion: Overall, our findings suggest that some dietary factors present in the Mediterranean diet might protect from cutaneous melanoma.

Occupational pesticide exposure has been linked to cutaneous melanoma in epidemiological studies. We studied the association between cutaneous melanoma and the residential use of pesticides. This is a case-control study of cutaneous melanoma (287 incident cases; 299 controls). Data on pesticide use was obtained with a standardised interview. An increased risk of melanoma was found for high use (4 times annually) of indoor pesticides (odds ratio (OR)=2.18; 95% confidence intervals (CI) 1.07-4.43) compared to low use (1 times annually), after adjustment for sex, age, education, sun exposure and pigmentary characteristics. Subjects exposed for 10 years or more had two and a half times the risk (OR=2.46; 95% CI 1.23-4.94) of those exposed for less than 10 years. A dose response was observed for the intensity of pesticides use (p(trend)=0.027). The results indicate that residential pesticide exposure may be an independent risk factor for cutaneous melanoma.

Study Objectives: To determine by thrombelastography assessed coagulation, the effects of progressive hemodilution with three intravascular volume expanders., Design: Prospective, controlled, whole blood, volumetric ex vivo hemodilution study., Setting: University of Pennsylvania Medical Center Operating Rooms., Patients: 60 ASA physical status I and II patients; phlebotomy prior to administration of IV fluids or medications., Interventions: Analysis of whole blood clotting determined by six thrombelastographic channels for control and five volumetric hemodilutions (11%, 25%, 33%, 50%, and 75%) with 0.9% saline, 5% albumin, and 6% hydroxyethyl starch (n = 20 for each diluent group)., Measurements and Main Results: Thrombelastographic parameters R (minutes), angle alpha (degree), MA (mm), and lysis (%) were measured and compared to the sample control for each dilution of the same specimen. There was no significant difference between control groups in any thrombelastographic variable (R, angle alpha, MA, or lysis). No changes were seen in any variable from any diluent at 11% hemodilution. Seventy-five percent hemodilution caused significantly hypocoagulable changes from control for all thrombelastographic parameters for all three diluents. Thrombelastographic indices differed significantly from controls at intermediate hemodilutions. Both colloids caused decreases in measured angle alpha and MA at lower hemodilution than did 0.9% saline. Albumin 5% caused significant hypocoagulable changes from control values at lower hemodilution than did either 0.9% saline or 6% hydroxyethyl starch for all thrombelastographic parameters. Saline 0.9% increased angle alpha significantly at 50% hemodilution. Abnormal lysis did not occur at any dilution. Differing ex vivo effects of three different intravascular fluids thrombelastography assessed coagulation are found., Conclusion: No differences were found after 11% hemodilution with any volume expanders. Hemodilution with up to 50% saline maintained thrombelastographic indices. Albumin produced early and profound hypocoagulable effects. Significant hypocoagulability occurred for all three diluents at 75% hemodilution. The study supports the use of albumin in patients at risk for thrombosis, and saline in patients with a need for normal hemostasis.

The authors report some recently observed cases of lymphogranuloma venereum and focus their attention on the complex approach to clinical and laboratory diagnosis. Furthermore they underline the importance and the spread of this disease in new geographical area, such as Europe.

Lidocaine in the epidural space, through inhibitory effects upon coagulation, may contribute to inefficacy of epidural autologous blood patch (EBP). This study was undertaken to evaluate the effect of achievable epidural concentrations of lidocaine on blood coagulation as a step in testing this hypothesis. Ex vivo blood coagulation using whole blood (n = 20) was studied with computerized thrombelastography (TEG). Each blood specimen was exposed to serial dilutions of lidocaine hydrochloride or saline to form end-concentrations of 0.0 mM, 2.3 mM, 4.6 mM, 9.2 mM, 18.5 mM, and 36.9 mM lidocaine. Statistical analysis using analysis of variance for repeated measures revealed that the three highest lidocaine concentrations tested caused hypocoagulable and/or fibrinolytic changes as compared with controls. Achievable epidural admixtures of lidocaine and whole blood will impair coagulation. Therefore, residual lidocaine in the epidural space may contribute to failures of immediate or early EBP.