The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC

The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/panerb inhibitors. A number of techniques have been employed for genotypic assessment of tumourassociated DNA to identify EGFR mutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Treatment of atherosclerotic renovascular disease

Treatment of atherosclerotic renovascular disease is controversial and revascularization is not a beneficial approach to all patients. Conditions as progressive deterioration of renal function, refractory hypertension or accelerated cardiovascular disease, especially recurrent pulmonary edema, could profit from renal angioplasty with stent placement. Surgical revascularization is a good option for patients who will need concomitant surgical corrections of abdominal aortic lesions. Treatment of all other patients must be individualized. Medical therapy is indicated for all patients with atherosclerotic renovascular disease. Observational studies pointed out to the beneficial effect of controlling blood pressure (<130/80 mm Hg), glucose and lipids profile, lifestyle modifications, specific use of platelet antiaggregant therapy, Angiotensin Conversion Enzyme Inhibitors (ACEI) and statins. All others cardiovascular risk factors must be controlled. The evaluation and management of other systemic atherosclerotic vascular lesions is important, especially coronary, carotid and abdominal aortic. This paper presents a review of evidences to rationale the atherosclerotic renovascular disease treatment. © 2008 Bentham Science Publishers Ltd.

Indications for early hip revision surgery in the UK : A re-analysis of NJR data

This study determined the rate and indication for revision between cemented, uncemented, hybrid and resurfacing groups from NJR (6 th edition) data. Data validity was determined by interrogating for episodes of misclassification. We identified 6,034 (2.7%) misclassified episodes, containing 97 (4.3%) revisions. Kaplan-Meier revision rates at 3 years were 0.9% cemented, 1.9% for uncemented, 1.2% for hybrids and 3.0% for resurfacings (significant difference across all groups, p<0.001, with identical pattern in patients <55 years). Regression analysis indicated both prosthesis group and age significantly influenced failure (p<0.001). Revision for pain, aseptic loosening, and malalignment were highest in uncemented and resurfacing arthroplasty. Revision for dislocation was highest in uncemented hips (significant difference between groups, p<0.001). Feedback to the NJR on data misclassification has been made for future analysis. © 2012 Wichtig Editore.

Marked increase in proton pump inhibitors use in Australia

Objectives: To examine the trends in the prescribing of subsidised proton pump inhibitors (PPIs) and histamine receptor antagonists (H2RAs), in the Australian population from 1995 to 2006 to encourage discussion regarding appropriate clinical use. PPIs and H2RAs are the second highest drug cost to the publicly subsidised Pharmaceutical Benefits Scheme (PBS). Design: Government data on numbers of subsidised scripts, quantity and doses for PPIs and H2RAs were analysed by gender and age, dose and indication. Main outcome measure: Drug utilisation as DDD [defined daily dose]/1000 population/day. Results: The use of combined PPIs increased by 1318%. Utilisation increased substantially after the relaxation of the subsidised indications for PPIs in 2001. Omeprazole had the largest market share but was substituted by its S-enantiomer esomeprazole after its introduction in 2002. There was considerable use in the elderly with the peak use being in those aged 80 years and over. The utilisation of H2RAs declined 72% over 12 years. Conclusions: PPI use has increased substantially, not only due to substitution of H2RAs but to expansion in the overall market. Utilisation does not appear to be commensurate with prevalence of gastro-oesophageal reflux disease (GORD) nor with prescribing guidelines for PPIs, with significant financial costs to patients and PBS. This study encourages clinical discussion regarding quality use of these medicines. © 2010 John Wiley & Sons, Ltd.

Mascara laringea. Uma nova opcao para a manutencao da permeabilidade das vias aereas superiores

The laryngeal mask has been demonstrating to be a new option for the maintenance of the airway permeability in anesthetized patients. It permits easy and fast insert. The authors made a review about the laryngeal mask including the main indications, advantages and possible injuries associated to its use.

Bone scintigraphy in testicular tumors

Purpose: Testicular tumors do not occur frequently. Primary treatment is surgical, and radiotherapy and chemotherapy can play important roles in cases of metastatic disease. Bone scintigraphy is used largely for early detection of skeletal metastases from several tumors, and conventional radiographic studies are less sensitive than the nuclear technique for such a purpose. The aim of this study was to identify the role of bone scintigraphy in cases of testicular tumors, regardless of the grade. Materials and Methods: The authors examined 28 patients (8 to 52 years old) with proved testicular tumors using Tc-99m MDP (750 MBq; 20 mCi) injected intravenously. Whole-body images were obtained 2 hours later, at 500,000 counts per image. Radiographic studies were obtained to investigate abnormal areas noted on scintigraphy. Results: The results of bone scintigraphy were abnormal in seven cases, consisting of variable but diffuse uptake in the iliac bone on the same side as the affected testicle. MDP uptake was substantial in five of these patients (four seminomas, one nonseminoma; only two radiographic studies were abnormal), and the two other patients had moderate uptake of the radiopharmaceutical (two seminomas; radiographic studies were normal). Metastases were confirmed by biopsy in three cases. Discussion: Early metastases from seminomas can occur through the lymphatic drainage toward the iliac lymph node chain. This could explain these findings. The scintigraphic aspects of the affected iliac bones seem characteristic. Conclusions: Early detection of metastases is very important to ensure the efficacy of radiotherapy and chemotherapy. Bone scintigraphy may play an important role in such cases and seems to be more sensitive than conventional radiography. Testicular tumor metastases should be considered when iliac involvement is observed. Paget's disease should be included in a differential diagnosis.

Avaliação da prescrição médica em pediatria, baseada nos indicadores do uso de medicamentos selecionados pela oms em municipio do interior do estado de São Paulo

The World Health Organization (WHO) recommends that prescriptions of medicaments must be one parameter utilized to know how the medication is used by people. To do so, one specific methodology has been indicated, that is, the selected indicators of the use the medicaments. We applied this methodology with the aim of presenting a descriptive study of the physician prescription in Pediatric Clinic of the Health Basics Units. The results obtained are: the average number of medicaments prescribed with prescription was 2.6; the percentage of the medicaments prescribed with the generic name was 32%; the percentage of the prescriptions with antibiotics was 44.6%; the percentage of the prescriptions with injections was 10.4%; the percentage of the medicaments prescribed that are part of the municipal list was 22.8%, 27.5% for the program Dose Certs of the secretary of the State of São Paulo, and 50.4% by adding by adding the two lists. The essentiality of the medicaments prescribed may be considered very low, because only 32.6% appear in the RENAME. The percentage of the medicaments really dispensed was 39.9%. The medicaments more prescribed, according to the classification of the Anatomic-Therapeutic-Chemical (ATC), were the ones which acted in Respiratory System (26.8%), followed by anti-infectives for systemic use (16.4%) and by medicaments with acted in Alimentary tract and metabolism (15.8%). The conclusion is that the prescribers are moved by commercial influence of the drug makers, first because of the low prescription of medicaments by their generic name, second by the low number of medicaments effectively dispensed and then the low concordance between the ones prescribed and the ones included in the lists patterned by Tabatinga and by the State of São Paulo.

Effects of contrast material on computed tomographic measurements of lung volumes in patients with acute lung injury

Background. Intravenous injection of contrast material is routinely performed in order to differentiate nonaerated lung parenchyma from pleural effusion in critically ill patients undergoing thoracic computed tomography (CT). The aim of the present study was to evaluate the effects of contrast material on CT measurement of lung volumes in 14 patients with acute lung injury. Method. A spiral thoracic CT scan, consisting of contiguous axial sections of 10 mm thickness, was performed from the apex to the diaphragm at end-expiration both before and 30 s (group 1; n=7) or 15 min (group 2; n=7) after injection of 80 ml contrast material. Volumes of gas and tissue, and volumic distribution of CT attenuations were measured before and after injection using specially designed software (Lungview®; Institut National des Télécommunications, Evry, France). The maximal artifactual increase in lung tissue resulting from a hypothetical leakage within the lung of the 80 ml contrast material was calculated. Results. Injection of contrast material significantly increased the apparent volume of lung tissue by 83 ± 57 ml in group 1 and 102 ± 80 ml in group 2, whereas the corresponding maximal artifactual increases in lung tissue were 42 ± 52 ml and 31 ± 18 ml. Conclusion. Because systematic injection of contrast material increases the amount of extravascular lung water in patients with acute lung injury, it seems prudent to avoid this procedure in critically ill patients undergoing a thoracic CT scan and to reserve its use for specific indications.

Uso do óxido nítrico em pediatria

Objective: To review the literature on inhaled nitric oxide and to describe its main clinical applications in pediatrics. Sources of data: A 10 year literature review with selection of the most important publications on inhaled nitric oxide, using the Medline and Cochrane Systematic Review databases. Summary of the findings: This review was organized as follows: introduction; metabolism and biological effects; clinical applications; dosage, gas administration and weaning; precautions and side-effects. Inhaled nitric oxide use was described in persistent pulmonary hypertension and hypoxia of the newborn, acute respiratory distress syndrome, primary pulmonary hypertension, heart surgery, chronic obstructive pulmonary disease, sickle cell anemia, and bronchospastic disease. Conclusions: Inhaled nitric oxide is a therapeutic approach with wide clinical applications in pediatrics. Its use is safe when administered in pediatric intensive care units under strict monitoring. As a pulmonary vasodilator, nitric oxide has beneficial effects on gas exchange and ventilation. Controlled trials, focusing on early gas administration should be performed under many clinical conditions, especially acute respiratory distress syndrome.

Surgical and clinical management of a patient with Glanzmann thrombasthenia: A case report

A 6-year-old girl with Glanzmann thrombasthenia presented with caries and periapical lesions in the primary mandibular second molars and moderate gingivitis of the maxillary and mandibular anterior teeth. Dental extraction was recommended, and before every surgical intervention, the patient underwent platelet-concentrate transfusion to prevent hemorrhage. Epsilon aminocaproic acid was administered 6 hours before, and 48 hours after every dental procedure to prevent bleeding. In this case, treatment was effective in the prevention of hemorrhagic complications, during the required dental procedures.

Increased implantation and pregnancy rates obtained by placing the tip of the transfer catheter in the central area of the endometrial cavity

The influence of endometrial cavity length (ECL) on implantation and pregnancy rates after 400 embryo transfers was studied prospectively in a population with the indication of IVF/intracytoplasmic sperm injection (ICSI). The tip of the transfer catheter was placed above or below the half point of the ECL in a randomized manner. Two analyses were performed: (i) absolute position (AP); embryo transfers were divided into three groups according to the distance between the end of the fundal endometrial surface and the catheter tip (DTC - distance tip catheter): AP 1 (n = 212), 10-15 mm; AP 2 (n = 158), 16-20 mm; and AP 3 (n = 30), ≥21 mm. (ii) relative position (RP) - embryo transfers were divided into four groups according to their RP [RP = (DTC/ECL) × 100]: RP 1 (n = 23), ≤40%; RP 2 (n = 177), 41-50%; RP 3 (n = 117), 51-60%; and RP 4 (n = 83), ≥61%. Analysis based on relative distance revealed significantly higher implantation and pregnancy rates (P < 0.05) in more central areas of the ECL. However, analysis based on absolute position did not reveal any difference. In conclusion, the present results demonstrated that implantation and pregnancy rates are influenced by the site of embryo transfer, with better results being obtained when the catheter tip is positioned close to the middle area of the endometrial cavity. In this respect, previous analysis of the ECL is the fundamental step in establishing the ideal site for embryo transfers.