The role of the perioperative prone position in the low recurrence of pressure injuries in the pelvic region.

OBJECTIVE: A pressure injury (PI) is a localised area of damage to the skin and/or underlying soft tissue as a result of a sustained mechanical loading. There are three key aetiological mechanisms to PI formation-direct cell deformation, inflammatory oedema and ischaemic damage-which are typically activated sequentially to drive a spiral of injury. This article discusses the role of the perioperative prone position as a rational approach to reducing the recurrence of pelvic PI after reconstructive surgery. METHOD: Patients with deep PI in the pelvic region, who were operated on from 2011 to 2019, were retrospectively evaluated. The protocol of care included training in the prone position, followed by maintenance of the prone position for 4-6 weeks postoperatively. The reconstruction was performed with fasciocutaneous and myocutaneous local or regional flaps. RESULTS: The study evaluated a total of 26 patients. The rate of recurrence of PIs was 15.4% (4/26) in the mean follow-up of 54 months. Regarding postoperative complications, four cases of partial dehiscence of the suture occurred. CONCLUSION: This perioperative protocol of maintaining a prone position seems to be safe for the patient, and it can be used to prevent or reduce the recurrence of deep PIs on the pelvic region after reconstructive surgery.

Development, Characterization, and In Vivo Evaluation of a Novel Aptamer (Anti-MUC1/Y) for Breast Cancer Therapy.

MUC1, the transmembrane glycoprotein Mucin 1, is usually found to be overexpressed in a variety of epithelial cancers playing an important role in disease progression. MUC1 isoforms such as MUC1/Y, which lacks the entire variable number of tandem repeat region, are involved in oncogenic processes by enhancing tumour initiation. MUC1/Y is therefore considered a promising target for the identification and treatment of epithelial cancers; but so far, the precise role of MUC1/Y remains to be elucidated. In this work, we developed and identified a DNA aptamer that specifically recognizes the splice variant MUC1/Y for the first time. The DNA aptamer could bind to a wide variety of human cancer cells, and treatment of MUC1/Y positive cells resulted in reduced growth in vitro. Moreover, MUC1/Y aptamer inhibited the tumour growth of breast cancer cells in vivo. The present study highlights the importance of targeting MUC1/Y for cancer treatment and unravels the suitability of a DNA aptamer to act as a new therapeutic tool.

Feasibility study of the Fricke chemical dosimeter as an independent dosimetric system for the small animal radiation research platform (SARRP).

For the small animal radiation research platform (SARRP) with X-ray beams in the medium energy range (tube operating voltage at 220 kVp), reference dosimetry is based on the AAPM TG-61 recommendations following the in-phantom method. The objective of this study was to evaluate the feasibility of the Fricke solution as a dosimeter to determine the absorbed dose to water. Feasibility studies at this X-ray energy range are not widely available. We evaluated the accuracy, dose linearity and dose rate dependence in a comparison with an NE 2571 Farmer ionization chamber (IC) and measurements in water. The G(Fe3+) factor was calculated from the curve fitting of the chemical yields for two radioactive sources (192Ir and 60Co) and one X-ray system with a tube operating at 150 and 250 kVp. The same methodology was followed for the dependence of the G(Fe3+) value on the energy and the dose agreement assessment for 180 and 200 kVp in the SARRP. The Fricke system exhibits a good linear response over the range of 5-70 Gy and an accuracy better than 2% for a 2 Gy/min dose rate. The dose rate dependence is smaller than 1% for dose rates greater than 1 Gy/min. The dependence of the G(Fe3+) value on the energy is smaller than 0.41%, with dose agreements better than 2%. The feasibility of the dosimeter for measurements at high doses and high dose rates makes it a suitable tool for dosimetric verifications in several preclinical irradiation configurations.

Small-field dosimetry with a high-resolution 3D scanning water phantom system for the small animal radiation research platform SARRP: a geometrical and quantitative study.

Improvements in dosimetry in preclinical radiation research facilitate the application of results to the newest radiotherapy techniques, reducing gaps that hinder translation. Currently, guidelines for small-field kV photon dosimetry of small animal irradiators have not been published, and most of the publications are based on radiochromic film dosimetry. In this study, we evaluated the performance of four detectors, three ionization chambers (ICs): (PTW Advanced Markus, PTW Semiflex 31010, PTW PinPoint-3D 31016) and one solid-state detector (PTW 60017 unshielded Diode E) regarding their suitability for relative dosimetry of the small animal radiation research platform SARRP (220 kVp). The measurements were performed in a high-resolution 3D scanning phantom, centering the detectors in the field following the in-plane and cross-plane profiles method at two depths. Depth dose curves (PDDs) and profiles were measured in water for field sizes ranging from 40 × 40 mm2 to 5 × 5 mm2. Quantitative analysis was performed through global and local dose differences (DDs) between the PDDs and the Advanced Markus parallel plate IC data and through the gamma index (γ) criteria for profiles compared against data from EBT3 films provided by the manufacturer. Compared to the Advanced Markus IC, the PDD results suggest that PinPoint-3D is suitable for depth measurements at this beam quality, even near the surface, with agreements better than 1%. Semiflex 31010 was accurate to within 1.5% for measurements deeper than 5 mm. Diode E showed a dramatic DD and should not be recommended for the field sizes and kVp evaluated in this study. In agreement with γ analyses, PinPoint-3D and Diode E are good candidates for profile measurements of field sizes from 40 × 40 mm2 to 10 × 10 mm2. For 5 × 5 mm2 profiles, only Diode E showed good results, making it a recommended detector for profile measurements.

Anti-MUC1 Aptamer as Carrier Tool of the Potential Radiosensitizer 1,10 Phenanthroline in MCF-7 Breast Cancer Cells.

BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.

Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer.

Both aptamers and siRNA technologies have now reached maturity, and both have been validated with a product in the market. However, although pegaptanib reached the market some time ago, there has been a slow process for new aptamers to follow. Today, some 40 aptamers are in the market, but many in combination with siRNAs, in the form of specific delivery agents. This combination offers the potential to explore the high affinity and specificity of aptamers, the silencing power of siRNA, and, at times, the cytotoxicity of chemotherapy molecules in powerful combinations that promise to delivery new and potent therapies. In this review, we report new developments in the field, following up from our previous work, more specifically on the use of aptamers as delivery agents of siRNA in nanoparticle formulations, alone or in combination with chemotherapy, for the treatment of cancer.

Validating Fricke dosimetry for the measurement of absorbed dose to water for HDR 192Ir brachytherapy: a comparison between primary standards of the LCR, Brazil, and the NRC, Canada.

Two Fricke-based absorbed dose to water standards for HDR Ir-192 dosimetry, developed independently by the LCR in Brazil and the NRC in Canada have been compared. The agreement in the determination of the dose rate from a HDR Ir-192 source at 1 cm in a water phantom was found to be within the k = 1 combined measurement uncertainties of the two standards: D NRC/D LCR = 1.011, standard uncertainty = 2.2%. The dose-based standards also agreed within the uncertainties with the manufacturer's stated dose rate value, which is traceable to a national standard of air kerma. A number of possible influence quantities were investigated, including the specific method for producing the ferrous-sulphate Fricke solution, the geometry of the holder, and the Monte Carlo code used to determine correction factors. The comparison highlighted the lack of data on the determination of G(Fe3+) in this energy range and the possibilities for further development of the holders used to contain the Fricke solution. The comparison also confirmed the suitability of Fricke dosimetry for Ir-192 primary standard dose rate determinations at therapy dose levels.

Analysis of surgical results and of residual postoperative deformities in preaxial polydactyly of the hand.

PURPOSE: Polydactyly is the most common congenital anomaly of the hand. It may occur as a separate event or as part of a syndrome, with preaxial polydactyly of the hand (or thumb duplication) being the most common among Caucasians. The present study analyzed the surgical results and the residual postoperative deformities of patients with thumb duplication. METHODS: Thirty-one patients with duplicated thumbs were surgically treated from January 2002 to April 2008 and 19 of them, who had returned during the late postoperative period, were evaluated. Each case was typed according to Wassel's classification into seven types and the most common category was type IV. Removal of radial component was done in 18 patients aged on average 51 months. RESULTS: Patients and parents were satisfied with both the functional results and the appearance of the reconstructed thumb. In the subjective evaluation of residual deformities, axis deviation and residual prominence were commonly found. There were coherencies in data between both subjective and objective outcomes. The children that had difficulty in holding very small objects in the subjective functional result were the same children with residual deformities in the objective result. Patient's age at surgery and Wassel's type influenced the analysis of residual postoperative deformities. There was statistically significant difference in cases of type VII and in patients operated at more than three years of age. Correlation between type VII and patient's age at time of surgery was found. The children with type VII duplication were operated later. CONCLUSIONS: For a better result, surgical correction should be performed before three years of age, thus correcting all the changes detected, mainly in type VII, in order to reduce the incidence of residual deformity. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Radiotherapy-Induced Skin Reactions Induce Fibrosis Mediated by TGF-ß1 Cytokine.

PURPOSE: This study aimed to investigate radiation-induced lesions on the skin in an experimental animal model. Methods and Materials: Cutaneous wounds were induced in Wistar rats by 4 MeV energy electron beam irradiation, using a dose rate of 240 cGy/min, for 3 different doses (10 Gy, 40 Gy, and 60 Gy). The skin was observed 5, 10, and 25 days (D) after ionizing radiation exposition. RESULTS: Infiltrate inflammatory process was observed in D5 and D10, for the 40 Gy and 60 Gy groups, and a progressive increase of transforming growth factor ß1 is associated with this process. It could also be noted a mischaracterization of collagen fibers at the high-dose groups. CONCLUSION: It was observed that the lesions caused by ionizing radiation in rats were very similar to radiodermatitis in patients under radiotherapy treatment. ADVANCES IN KNOWLEDGE: This study is important to develop strategies to prevent radiation-induced skin reactions.

Monte Carlo Dosimetry of the 60Co BEBIG High Dose Rate for Brachytherapy.

INTRODUCTION: The use of high-dose-rate brachytherapy is currently a widespread practice worldwide. The most common isotope source is 192Ir, but 60Co is also becoming available for HDR. One of main advantages of 60Co compared to 192Ir is the economic and practical benefit because of its longer half-live, which is 5.27 years. Recently, Eckert & Ziegler BEBIG, Germany, introduced a new afterloading brachytherapy machine (MultiSource®); it has the option to use either the 60Co or 192Ir HDR source. The source for the Monte Carlo calculations is the new 60Co source (model Co0.A86), which is referred to as the new BEBIG 60Co HDR source and is a modified version of the 60Co source (model GK60M21), which is also from BEBIG. OBJECTIVE AND METHODS: The purpose of this work is to obtain the dosimetry parameters in accordance with the AAPM TG-43U1 formalism with Monte Carlo calculations regarding the BEBIG 60Co high-dose-rate brachytherapy to investigate the required treatment-planning parameters. The geometric design and material details of the source was provided by the manufacturer and was used to define the Monte Carlo geometry. To validate the source geometry, a few dosimetry parameters had to be calculated according to the AAPM TG-43U1 formalism. The dosimetry studies included the calculation of the air kerma strength Sk, collision kerma in water along the transverse axis with an unbounded phantom, dose rate constant and radial dose function. The Monte Carlo code system that was used was EGSnrc with a new cavity code, which is a part of EGS++ that allows calculating the radial dose function around the source. The spectrum to simulate 60Co was composed of two photon energies, 1.17 and 1.33 MeV. Only the gamma part of the spectrum was used; the contribution of the electrons to the dose is negligible because of the full absorption by the stainless-steel wall around the metallic 60Co. The XCOM photon cross-section library was used in subsequent simulations, and the photoelectric effect, pair production, Rayleigh scattering and bound Compton scattering were included in the simulation. Variance reduction techniques were used to speed up the calculation and to considerably reduce the computer time. The cut-off energy was 10 keV for electrons and photons. To obtain the dose rate distributions of the source in an unbounded liquid water phantom, the source was immersed at the center of a cube phantom of 100 cm3. The liquid water density was 0.998 g/cm3, and photon histories of up to 1010 were used to obtain the results with a standard deviation of less than 0.5% (k = 1). The obtained dose rate constant for the BEBIG 60Co source was 1.108±0.001 cGyh-1U-1, which is consistent with the values in the literature. The radial dose functions were compared with the values of the consensus data set in the literature, and they are consistent with the published data for this energy range.

Morphometric and Functional Analysis of Axonal Regeneration after End-to-end and End-to-side Neurorrhaphy in Rats.

BACKGROUND: End-to-side neurorrhaphy is controversial in the literature and has sparked debate over its degree of recovery. In this study, nerve regeneration was assessed in rats after end-to-side neurorrhaphy by morphometric analysis, electromyography, electron microscopy, and retrograde horseradish peroxidase (HRP) and Fluoro-Gold (FG; Fluorochrome Inc., Denver, Colo.) transport and then compared to end-to-end neurorrhaphy and sham operation. METHODS: Thirty-seven animals were operated on and divided randomly into 4 groups: group 1, sham; group 2, end-to-end neurorrhaphy; group 3, end-to-side neurorrhaphy with an epineural window; and group 4, end-to-side neurorrhaphy without an epineural window. Three months after surgery, HRP was injected into the peroneal muscles. After 48 hours, nerve segments and lumbar spine segments were collected. Electromyography data were compared between groups, and FG uptake was compared in 20 other animals. Analysis of variance with Tukey-Kramer correction was used for group comparison. RESULTS: The fiber count after end-to-end neurorrhaphy was higher than after end-to-side neurorrhaphy with an epineural window (q = 5.243 and P < 0.01) or without an epineural window (q = 4.951 and P < 0.01). HRP labeling showed a difference between group 2 and end-to-side neurorrhaphy with an epineural window (q = 5.291 and P < 0.01) and without an epineural window (q = 5.617 and P < 0.01). There was also a difference in mean area labeled with FG. Furthermore, the amplitudes of the action potentials were significantly higher in groups 1 and 2. CONCLUSIONS: There was nerve regeneration in all groups studied. However, the end-to-end neurorrhaphy group had better reinnervation than the end-to-side neurorrhaphy groups.

Apoptosis induction of cardiomyocytes and subsequent fibrosis after irradiation and neoadjuvant chemotherapy.

PURPOSE: Breast cancer treatments can induce important cardiovascular complications. The aim of this study was to evaluate cardiac alterations after irradiation and chemotherapy in an animal model. MATERIAL AND METHODS: Wistar rats were divided into three groups: Control, TC+ IR (received chemotherapy and irradiation) and IR (received only irradiation). After 5 months, echocardiography was performed, the animals were euthanized, and the left ventricle was analyzed using light microscopy techniques and Polymerase Chain Reaction (PCR). RESULTS: Echocardiography showed decreases in ejection fraction and cardiac output, in TC+ IR group. Both TC+ IR and IR showed reduced intramyocardial vessel-to-cardiomyocyte ratio, increased connective tissue, cardiomyocyte hypertrophy, increased numbers of apoptotic nuclei and increased Bax/Bcl2 expression. We also observed increased Transforming growth factor (TGF) beta 1 mRNA expression in both groups, but type 1 Procollagen expression was increased in TC+ IR group only. CONCLUSIONS: The study suggests that the induced cardiac remodelling begins with the reduction of intramyocardial vessels in the left ventricle tissue. The main consequence is the loss of cardiomyocytes through apoptosis, leading to the replacement of healthy tissue by fibrous tissue. It was observed that the damage caused by the combination of irradiation and chemotherapy induced functional alterations that did not occur when the animals were only irradiated.

MiR-34a is up-regulated in response to low dose, low energy X-ray induced DNA damage in breast cells.

BACKGROUND: MicroRNAs are non-coding RNAs involved in the regulation of gene expression including DNA damage responses. Low doses of low energy X-ray radiation, similar to those used in mammographic exams, has been described to be genotoxic. In the present work we investigated the expression of miR-34a; a well described p53-regulated miRNA implicated in cell responses to X-ray irradiation at low doses. METHODS: Non-cancerous breast cell line MCF-10A and cancerous T-47D and MCF-7 cell lines were submitted to a low-energy X-ray irradiation (ranging from 28-30 Kv) using a dose of 5 Gy. The expression level of miR-34a, let-7a and miR-21 was assessed by qRT-PCR at 4 and 24 hours post-irradiation. DNA damage was then measured by comet assay and micronuclei estimation in MCF-10A and MCF-7 cell lines, where an increase of miR-34a levels could be observed after irradiation. The rate of apoptotic cells was estimated by nuclear staining and fluorescence microscopy. These experiments were also performed at low doses (3; 12 and 48 mGy) in MCF-10A and MCF-7 cell lines. RESULTS: We have observed an increase in miR-34a expression 4 hours post-irradiation at 5 Gy in MCF-10A and MCF-7 cell lines while its level did not change in T-47D, a breast cancer cell line bearing non-functional p53. At low doses, miR-34a was up-regulated in non-tumoral MCF-10A to a higher extent as compared to MCF-7. MiR-34a levels decreased 24 hours post-irradiation. We have also observed DNA damage and apoptosis at low-energy X-ray irradiation at low doses and the high dose in MCF-10A and MCF-7 4 and 24 hours post-irradiation relative to the mock control. CONCLUSION: Low energy X-ray is able to promote DNA strand breaks and miR-34a might be involved in cell responses to low energy X-ray DNA damage. MiR-34a expression correlates with X-ray dose, time after irradiation and cell type. The present study reinforces the need of investigating consequences of low dose X-ray irradiation of breast cells.

Fire in the surgical center.

BACKGROUND AND OBJECTIVES: There are several factors in operating rooms that increase the risk of fire. Besides being an oxygen-enriched environment, it contains combustible materials and equipment with available ignition sources. Although fires in operating rooms are a relatively rare event, the consequences are potentially serious and mostly avoidable. We present a case report of a fire occurring in the surgical drape during a blepharoplasty in which oxygen was supplemented by nasal catheter. CASE REPORT: Female patient, 52-years old, without comorbidities, admitted to hospital for a bilateral blepharoplasty. After monitoring and venoclysis, the patient underwent intravenous sedation and additional oxygen given via spectacle-type catheter at a flow rate of4 L.min(-1), followed by local anesthesia in the eyelids. During surgery, the use of electric scalpel provoked combustion in the surgical drapes and burns on the patient's face. CONCLUSIONS: Anesthesiologists play an important role preventing fire in operating rooms, as they can recognize possible ignition sources and rationally administer the oxygen, especially in open systems. The first step toward prevention is to be constantly aware of potential fire.

[Analysis of Cost-effectiveness of screening for breast cancer with conventional mammography, digital and magnetic resonance imaging]. / Análise de Custo-efetividade do rastreamento do câncer de mama com mamografia convencional, digital e ressonância.

A cost-effectiveness analysis was conducted in screening for breast cancer. The use of conventional mammography, digital and magnetic resonance imaging were compared with natural disease history as a baseline. A Markov model projected breast cancer in a group of 100,000 women for a 30 year period, with screening every two years. Four distinct scenarios were modeled: (1) the natural history of breast cancer, as a baseline, (2) conventional film mammography, (3) digital mammography and (4) magnetic resonance imaging. The costs of the scenarios modeled ranged from R$ 194.216,68 for natural history, to R$ 48.614.338,31, for screening with magnetic resonance imaging. The difference in effectiveness between the interventions ranged from 300 to 78.000 years of life gained in the cohort. The ratio of incremental cost-effectiveness in terms of cost per life-year gains, conventional mammographic screening has produced an extra year for R$ 13.573,07. The ICER of magnetic resonance imaging was R$ 2.904.328,88, compared to no screening. In conclusion, it is more cost-effective to perform the screening with conventional mammography than other technological interventions.

Malfunction of the extracorporeal circulation system: case report.

BACKGROUND AND OBJECTIVES: The introduction of extracorporeal circulation in clinical practice was decisive for the development of modern cardiovascular surgery. Addition of new procedures and equipment, however, brings inherent risks and complications. The objective of this report is to describe a malfunction of the oxygenation system and emphasize the importance of the interaction among the medical team members to prevent errors and complications. CASE REPORT: During valve replacement and IVC correction surgery, we observed a darker shade of red in the blood on the exit of the oxygenator. Laboratory tests demonstrated severe acidosis and hypoxemia. The entire system was evaluated, but the cause of the malfunction was not found. Measures to reduce damage were successfully instituted. After the surgery, the whole system underwent technical evaluation. CONCLUSIONS: Interaction among the medical team members, early diagnosis, and immediate intervention were fundamental for a favorable outcome.

Thyrotoxic crisis associated with gestational trophoblastic disease.

BACKGROUND AND OBJECTIVES: Human chorionic gonadotropin (HCG) and thyrotrophic hormone (TSH) have analogies in their structures, as well as in their receptors. The high levels of HCG seen in gestational trophoblastic diseases may induce secondary hyperthyroidism. The objective of this report was to present a case in which the administration of iodinated contrast triggered a thyrotoxic crisis. CASE REPORT: Patient with complete hydatidiform mole who was admitted to the operating room with severe vaginal bleeding after a tomographic exam with iodinated contrast. During anesthetic induction, the patient presented symptoms compatible with thyrotoxic crisis. CONCLUSIONS: The incidence of severe presentations associated with gestational trophoblastic disease tends to decrease with early diagnosis. Still, the anesthesiologist should be aware of the possibility of those patients developing thyrotoxic crisis.

Effects of lanthanum on human lymphocytes viability and DNA strand break.

Lanthanum (La) is a rare-earth metal with applications in agriculture, industry, and medicine. Since lanthanides show a broad spectrum of applications there is an increased risk of contamination for humans. We examined the effects of lanthanum in Jurkat cells and human peripheral lymphocytes (HPL), and we found that it was cytotoxic and genotoxic on both cell lines. Additionally, HPL were more sensitive to La treatment than Jurkat cells and necrosis was the pathway by which La induced cytotoxicity. Vitamin E was able to diminish the DNA strand breaks induced suggesting that oxidative stress may be involved in the genotoxic process.