Acesso aos níveis de atenção à saúde em um município do Estado de São Paulo: perspectivas de gestores, profissionais e usuários

Pós-graduação em Saúde Coletiva - FMB

Evaluation of serial C-reactive protein measurements after surgical treatment of pleural empyema

OBJECTIVE: Serial C-reactive protein measurements have been used to diagnose and monitor the response to therapy in patients with pneumonia and other infectious diseases. Nonetheless, the role of C-reactive protein measurement after surgical treatment for pleural empyema is not well defined. The aim of this study is to describe the behavior of C-reactive protein levels after the surgical treatment of pleural empyema and to correlate this parameter with the patient's prognosis. METHODS: We retrospectively analyzed the records of patients with pleural empyema treated by either chest-tube drainage or surgery from January 2006 to December 2008. C-reactive protein levels were recorded preoperatively and 2 and 7 days postoperatively. The clinical outcome was binary: success or failure (mortality or the need for repeated pleural intervention). RESULTS: The study group comprised fifty-two patients. The median C-reactive protein values were as follows: 146 mg/L (pre-operative), 134 mg/L (post-operative day 2), and 116 mg/L (post-operative day 7). There was a trend toward a decrease in these values during the first week after surgery, but this difference was only statistically significant on day 7 after surgery. Over the first week after surgery, the C-reactive protein values decreased similarly in both groups (successful and failed treatment). No correlation between the preoperative C-reactive protein level and the clinical outcome was found. CONCLUSIONS: We observed that, in contrast to other medical conditions, C-reactive protein levels fall slowly during the first postoperative week in patients who have undergone surgical treatment for pleural empyema. No correlation between the perioperative C-reactive protein level and the clinical outcome was observed.

The effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder

Background. - Persistent impairment in cognitive function has been described in euthymic individuals with bipolar disorder. Collective work indicates that obesity is associated with reduced cognitive function in otherwise healthy individuals. This sub-group post-hoc analysis preliminarily explores and examines the association between overweight/obesity and cognitive function in euthymic individuals with bipolar disorder. Methods. - Euthymic adults with DSM-IV-TR-defined bipolar I or II disorder were enrolled. Subjects included in this post-hoc analysis (n = 67) were divided into two groups (normal weight, body mass index [BMI] of 18.5-24.9 kg/m(2); overweight/obese, BMI >= 25.0 kg/m(2)). Demographic and clinical information were obtained at screening. At baseline, study participants completed a comprehensive cognitive battery to assess premorbid IQ, verbal learning and memory, attention and psychomotor processing speed, executive function, general intellectual abilities, recollection and habit memory, as well as self-perceptions of cognitive failures. Results. - BMI was negatively correlated with attention and psychomotor processing speed as measured by the Digit Symbol Substitution Test (P < 0.01). Overweight and obese bipolar individuals had a significantly lower score on the Verbal Fluency Test when compared to normal weight subjects (P < 0.05). For all other measures of cognitive function, non-significant trends suggesting a negative association with BMI were observed, with the exception of measures of executive function (i.e. Trail Making Test B) and recollection memory (i.e. process-dissociation task). Conclusion. - Notwithstanding the post-hoc methodology and relatively small sample size, the results of this study suggest a possible negative effect of overweight/obesity on cognitive function in euthymic individuals with bipolar disorder. Taken together, these data provide the impetus for more rigorous evaluation of the mediational role of overweight/obesity (and other medical co-morbidity) on cognitive function in psychiatric populations. (C) 2011 Elsevier Masson SAS. All rights reserved.

Specialisation within vascular surgery

Despite its short existence, vascular surgery has already grown out of the scope of a mono-specialty. Meanwhile emerging interests of other competing specialties push into the field of vascular care. Continuous technological innovation drives the need for sub-specialisation to provide disease-centred expertise; however, treatment success equally depends on balanced patient-centred care. Vascular surgeons are amidst this controversy and are currently challenged by their own demand to offer all aspects of vascular care - as "the vascular specialist". This article discusses the natural driving forces towards sub-specialisation and appraises advantages and limitations with respect to the future of integrated vascular care.

CTLA4-Ig Restores Rejection of MHC Class-II Mismatched Allografts by Disabling IL-2-Expanded Regulatory T Cells

Allograft acceptance and tolerance can be achieved by different approaches including inhibition of effector T cell responses through CD28-dependent costimulatory blockade and induction of peripheral regulatory T cells (Tregs). The observation that Tregs rely upon CD28-dependent signals for development and peripheral expansion, raises the intriguing possibility of a counterproductive consequence of CTLA4-Ig administration on tolerance induction. We have investigated the possible negative effect of CTLA4-Ig on Treg-mediated tolerance induction using a mouse model of single MHC class II-mismatched skin grafts in which long-term acceptance was achieved by short-term administration of IL-2/anti-IL-2 complex. CTLA4-Ig treatment was found to abolish Treg-dependent acceptance in this model, restoring skin allograft rejection and Th1 alloreactivity. CTLA4-Ig inhibited IL-2-driven Treg expansion, and prevented in particular the occurrence of ICOS(+) Tregs endowed with potent suppressive capacities. Restoring CD28 signaling was sufficient to counteract the deleterious effect of CTLA4-Ig on Treg expansion and functionality, in keeping with the hypothesis that costimulatory blockade inhibits Treg expansion and function by limiting the delivery of essential CD28-dependent signals. Inhibition of regulatory T cell function should therefore be taken into account when designing tolerance protocols based on costimulatory blockade. Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons

COVARIATE-ADJUSTED NONPARAMETRIC ANALYSIS OF MAGNETIC RESONANCE IMAGES USING MARKOV CHAIN MONTE CARLO

Permutation tests are useful for drawing inferences from imaging data because of their flexibility and ability to capture features of the brain that are difficult to capture parametrically. However, most implementations of permutation tests ignore important confounding covariates. To employ covariate control in a nonparametric setting we have developed a Markov chain Monte Carlo (MCMC) algorithm for conditional permutation testing using propensity scores. We present the first use of this methodology for imaging data. Our MCMC algorithm is an extension of algorithms developed to approximate exact conditional probabilities in contingency tables, logit, and log-linear models. An application of our non-parametric method to remove potential bias due to the observed covariates is presented.

[Role of coronary artery bypass grafting in the treatment of coronary artery disease - a well-balanced information of the patients and objective decision making are welcome]

Most recently discussion about the optimal treatment for different subsets of patients suffering from coronary artery disease has re-emerged, mainly because of the uncertainty caused by doctors and patients regarding the phenomenon of unpredictable early and late stent thrombosis. Surgical revascularization using multiple arterial bypass grafts has repeatedly proven its superiority compared to percutaneous intervention techniques, especially in patients suffering from left main stem disease and coronary 3-vessels disease. Several prospective randomized multicenter studies comparing early and mid-term results following PCI and CABG have been really restrictive, with respect to patient enrollment, with less than 5% of all patients treated during the same time period been enrolled. Coronary artery bypass grafting allows the most complete revascularization in one session, because all target coronary vessels larger than 1 mm can be bypassed in their distal segments. Once the patient has been turn-off for surgery, surgeons have to consider the most complete arterial revascularization in order to decrease the long-term necessity for re-revascularization; for instance patency rate of the left internal thoracic artery grafted to the distal part left anterior descending artery may be as high as 90-95% after 10 to 15 years. Early mortality following isolated CABG operation has been as low as 0.6 to 1% in the most recent period (reports from the University Hospital Berne and the University Hospital of Zurich); beside these excellent results, the CABG option seems to be less expensive than PCI with time, since the necessity for additional PCI is rather high following initial PCI, and the price of stent devices is still very high, particularly in Switzerland. Patients, insurance and experts in health care should be better and more honestly informed concerning the risk and costs of PCI and CABG procedures as well as about the much higher rate of subsequent interventions following PCI. Team approach for all patients in whom both options could be offered seems mandatory to avoid unbalanced information of the patients. Looking at the recent developments in transcatheter valve treatments, the revival of cardiological-cardiosurgical conferences seems to a good option to optimize the cooperation between the two medical specialties: cardiology and cardiac surgery.

Major bleeding of the upper aerodigestive tract due to oral anticoagulant/antibiotic interactions

INTRODUCTION Although a well-known complication in certain medical specialties, major bleeding due to the interaction between oral anticoagulants and antibiotics has been rarely reported concerning the upper aerodigestive tract. We report three cases of life-threatening bleeding of the upper aerodigestive tract in a context of antibiotic therapy in patients treated with oral anticoagulants. CASE SERIES Three male patients under coumadin anticoagulation therapy presented major bleeding in three different contexts (epistaxis, peritonsillar abscess and postoperative course after total laryngectomy). Surgical intervention for hemostasis was required in all cases, with coagulation correction in two. Complications were severe anemia (2/3) and chronic heart failure (1/3). DISCUSSION/CONCLUSIONS Interactions between two drugs commonly used in otolaryngology can result in major bleeding. The goal of this article is to raise practitioners' awareness of a potentially fatal, although rare, complication. We also review the main preventive strategies.

Thoracic target volume delineation using various maximum-intensity projection computed tomography image sets for stereotactic body radiation therapy

The motion of lung tumors during respiration makes the accurate delivery of radiation therapy to the thorax difficult because it increases the uncertainty of target position. The adoption of four-dimensional computed tomography (4D-CT) has allowed us to determine how a tumor moves with respiration for each individual patient. Using information acquired during a 4D-CT scan, we can define the target, visualize motion, and calculate dose during the planning phase of the radiotherapy process. One image data set that can be created from the 4D-CT acquisition is the maximum-intensity projection (MIP). The MIP can be used as a starting point to define the volume that encompasses the motion envelope of the moving gross target volume (GTV). Because of the close relationship that exists between the MIP and the final target volume, we investigated four MIP data sets created with different methodologies (3 using various 4D-CT sorting implementations, and one using all available cine CT images) to compare target delineation. It has been observed that changing the 4D-CT sorting method will lead to the selection of a different collection of images; however, the clinical implications of changing the constituent images on the resultant MIP data set are not clear. There has not been a comprehensive study that compares target delineation based on different 4D-CT sorting methodologies in a patient population. We selected a collection of patients who had previously undergone thoracic 4D-CT scans at our institution, and who had lung tumors that moved at least 1 cm. We then generated the four MIP data sets and automatically contoured the target volumes. In doing so, we identified cases in which the MIP generated from a 4D-CT sorting process under-represented the motion envelope of the target volume by more than 10% than when measured on the MIP generated from all of the cine CT images. The 4D-CT methods suffered from duplicate image selection and might not choose maximum extent images. Based on our results, we suggest utilization of a MIP generated from the full cine CT data set to ensure a representative inclusive tumor extent, and to avoid geometric miss.

EVALUATION OF THE QUANTITATIVE ACCURACY OF A COMMERCIALLY-AVAILABLE POSITRON EMISSION MAMMOGRAPHY SCANNER

Objective: The PEM Flex Solo II (Naviscan, Inc., San Diego, CA) is currently the only commercially-available positron emission mammography (PEM) scanner. This scanner does not apply corrections for count rate effects, attenuation or scatter during image reconstruction, potentially affecting the quantitative accuracy of images. This work measures the overall quantitative accuracy of the PEM Flex system, and determines the contributions of error due to count rate effects, attenuation and scatter. Materials and Methods: Gelatin phantoms were designed to simulate breasts of different sizes (4 – 12 cm thick) with varying uniform background activity concentration (0.007 – 0.5 μCi/cc), cysts and lesions (2:1, 5:1, 10:1 lesion-to-background ratios). The overall error was calculated from ROI measurements in the phantoms with a clinically relevant background activity concentration (0.065 μCi/cc). The error due to count rate effects was determined by comparing the overall error at multiple background activity concentrations to the error at 0.007 μCi/cc. A point source and cold gelatin phantoms were used to assess the errors due to attenuation and scatter. The maximum pixel values in gelatin and in air were compared to determine the effect of attenuation. Scatter was evaluated by comparing the sum of all pixel values in gelatin and in air. Results: The overall error in the background was found to be negative in phantoms of all thicknesses, with the exception of the 4-cm thick phantoms (0%±7%), and it increased with thickness (-34%±6% for the 12-cm phantoms). All lesions exhibited large negative error (-22% for the 2:1 lesions in the 4-cm phantom) which increased with thickness and with lesion-to-background ratio (-85% for the 10:1 lesions in the 12-cm phantoms). The error due to count rate in phantoms with 0.065 μCi/cc background was negative (-23%±6% for 4-cm thickness) and decreased with thickness (-7%±7% for 12 cm). Attenuation was a substantial source of negative error and increased with thickness (-51%±10% to -77% ±4% in 4 to 12 cm phantoms, respectively). Scatter contributed a relatively constant amount of positive error (+23%±11%) for all thicknesses. Conclusion: Applying corrections for count rate, attenuation and scatter will be essential for the PEM Flex Solo II to be able to produce quantitatively accurate images.

AN IMPLANTABLE MOSFET DOSIMETER MODIFIED TO ACT AS A FIDUCIAL MARKER

In external beam radiation therapy, it is imperative that the prescribed dose is administered to the correct location and in the correct amount. Though several ex vivo methods of quality assurance are currently employed to achieve this goal, verifying that the correct dose is received within the patient in situ is impossible without the capability of measuring dose inside the patient. Recently, a method of measuring dose delivered within the patient has been developed, an implantable MOSFET dosimeter. This dosimeter is implanted within the patient and records the dose received. Since the dosimeter is implanted in the patient, it could serve a dual function as a fiducial marker for image guided radiation therapy (IGRT) treatment if it could be modified to be visible on x-rays. In this study, modifications to the MOSFET dosimeter were made to increase its visibility for IGRT treatment. To test whether the modifications hindered the dosimeter’s ability to accurately measure and transmit dose information, the energy dependence, angular dependence and wireless read range of the modified dosimeter were measured and compared to unmodified dosimeters. It was found that the modified dosimeter performed as well as the unmodified dosimeter while also being suitable for use as a fiducial marker for IGRT treatment.

Clinical Impact of Couch Top and Rails on IMRT and Arc Therapy

Purpose: To evaluate the clinical impact of the Varian Exact Couch on dose and volume coverage to targets and critical structures and tumor control probability (TCP) for 6-MV IMRT and Arc Therapy. Methods: Five clinical prostate patients were planned with both, 6-MV 8-field IMRT and 6-MV 2-field RapidArc using the Eclipse treatment planning system (TPS). These plans neglected treatment couch attenuation, as is standard clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the DVHs from each plan iteration. We used a tumor control probability (TCP) model to calculate losses in tumor control resulting from not accounting for the couch top and rails. We also verified dose measurements in a phantom. Results: Failure to account for the treatment couch and rails resulted in clinically unacceptable dose and volume coverage losses to the target for both IMRT and RapidArc. The couch caused average dose losses (relative to plans that ignored the couch) to the prostate of 4.2% and 2.0% for IMRT with the rails out and in, respectively, and 3.2% and 2.9% for RapidArc with the rails out and in, respectively. On average, the percentage of the target covered by the prescribed dose dropped to 35% and 84% for IMRT (rails out and in, respectively) and to 18% and 17% for RapidArc (rails out and in, respectively). The TCP was also reduced by as much as 10.5% (6.3% on average). Dose and volume coverage losses for IMRT plans were primarily due to the rails, while the imaging couch top contributed most to losses for RapidArc. Both the couch top and rails contribute to dose and coverage losses that can render plans clinically unacceptable. A follow-up study we performed found that the less attenuating unipanel mesh couch top available with the Varian Exact couch does not cause a clinically impactful loss of dose or coverage for IMRT but still causes an unacceptable loss for RapidArc. Conclusions: Both the imaging couch top and rails contribute to dose and coverage loss to a degree that, if included, would prevent the plan from meeting clinical planning criteria. Therefore, the imaging and mesh couch tops and rails should be accounted for in Arc Therapy and the imaging couch and rails only in IMRT treatment planning.

IN-VIVO CT DOSIMETRY DURING VIRTUAL COLONOSCOPY

Virtual colonoscopy (VC) is a minimally invasive means for identifying colorectal polyps and colorectal lesions by insufflating a patient’s bowel, applying contrast agent via rectal catheter, and performing multi-detector computed tomography (MDCT) scans. The technique is recommended for colonic health screening by the American Cancer Society but not funded by the Centers for Medicare and Medicaid Services (CMS) partially because of potential risks from radiation exposure. To date, no in‐vivo organ dose measurements have been performed for MDCT scans; thus, the accuracy of any current dose estimates is currently unknown. In this study, two TLDs were affixed to the inner lumen of standard rectal catheters used in VC, and in-vivo rectal dose measurements were obtained within 6 VC patients. In order to calculate rectal dose, TLD-100 powder response was characterized at diagnostic doses such that appropriate correction factors could be determined for VC. A third-order polynomial regression with a goodness of fit factor of R2=0.992 was constructed from this data. Rectal dose measurements were acquired with TLDs during simulated VC within a modified anthropomorphic phantom configured to represent three sizes of patients undergoing VC. The measured rectal doses decreased in an exponential manner with increasing phantom effective diameter, with R2=0.993 for the exponential regression model and a maximum percent coefficient of variation (%CoV) of 4.33%. In-vivo measurements yielded rectal doses ranged from that decreased exponentially with increasing patient effective diameter, in a manner that was also favorably predicted by the size specific dose estimate (SSDE) model for all VC patients that were of similar age, body composition, and TLD placement. The measured rectal dose within a younger patient was favorably predicted by the anthropomorphic phantom dose regression model due to similarities in the percentages of highly attenuating material at the respective measurement locations and in the placement of the TLDs. The in-vivo TLD response did not increase in %CoV with decreasing dose, and the largest %CoV was 10.0%.

THE MECHANISM OF TUMORIGENESIS IN THE IMMORTALIZED HUMAN PANCREATIC CELL LINES: CELL CULTURE MODELS OF HUMAN PANCREATIC CANCER

The mechanism of tumorigenesis in the immortalized human pancreatic cell lines: cell culture models of human pancreatic cancer Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in the world. The most common genetic lesions identified in PDAC include activation of K-ras (90%) and Her2 (70%), loss of p16 (95%) and p14 (40%), inactivation p53 (50-75%) and Smad4 (55%). However, the role of these signature gene alterations in PDAC is still not well understood, especially, how these genetic lesions individually or in combination contribute mechanistically to human pancreatic oncogenesis is still elusive. Moreover, a cell culture transformation model with sequential accumulation of signature genetic alterations in human pancreatic ductal cells that resembles the multiple-step human pancreatic carcinogenesis is still not established. In the present study, through the stepwise introduction of the signature genetic alterations in PDAC into the HPV16-E6E7 immortalized human pancreatic duct epithelial (HPDE) cell line and the hTERT immortalized human pancreatic ductal HPNE cell line, we developed the novel experimental cell culture transformation models with the most frequent gene alterations in PDAC and further dissected the molecular mechanism of transformation. We demonstrated that the combination of activation of K-ras and Her2, inactivation of p16/p14 and Smad4, or K-ras mutation plus p16 inactivation, was sufficient for the tumorigenic transformation of HPDE or HPNE cells respectively. We found that these transformed cells exhibited enhanced cell proliferation, anchorage-independent growth in soft agar, and grew tumors with PDAC histopathological features in orthotopic mouse model. Molecular analysis showed that the activation of K-ras and Her2 downstream effector pathways –MAPK, RalA, FAK, together with upregulation of cyclins and c-myc were involved in the malignant transformation. We discovered that MDM2, BMP7 and Bmi-1 were overexpressed in the tumorigenic HPDE cells, and that Smad4 played important roles in regulation of BMP7 and Bmi-1 gene expression and the tumorigenic transformation of HPDE cells. IPA signaling pathway analysis of microarray data revealed that abnormal signaling pathways are involved in transformation. This study is the first complete transformation model of human pancreatic ductal cells with the most common gene alterations in PDAC. Altogether, these novel transformation models more closely recapitulate the human pancreatic carcinogenesis from the cell origin, gene lesion, and activation of specific signaling pathway and histopathological features.