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Hirschsprung disease is the most common neurocristopathy in children, resulting in the congenital loss of enteric ganglia. Rare reports of skip lesions have previously been reported in the literature. We present a case of skip lesions known prior to surgery and managed by pull-through of the right colon that allowed the preservation of the colon.

Cigarette smoking is associated with increased risk for all histologic types of lung cancer, but why the strength of this association is stronger for squamous cell carcinoma than adenocarcinoma of the lung (SQC-L, ADC-L) is not fully understood. Because nicotine and tobacco-specific nitrosamines contribute to carcinogenesis by activating nicotinic acetylcholine receptors (nAChRs) on lung tumors and epithelial cells, we investigated whether differential expression of nAChR subtypes in these tumors could explain their different association with smoking. Expression of nAChR subunit genes in paired tumor and non-tumor lung specimens from 40 SQC-L and 38 ADC-L patients was analyzed by quantitative PCR. Compared to normal lung, both tumors share: i) transcriptional dysregulation of CHRNA3/CHRNA5/CHRNB4 (α3, α5, β4 subunits) at the chromosomal locus that predisposes to lung cancer; and ii) decreased expression of CHRFAM7A (dupα7 subunit); this last subunit negatively modulates α7-nAChR activity in oocytes. In contrast, CHRNA7 (α7 subunit) expression was increased in SQC-L, particularly in smokers and non-survivors, while CHRNA4 (α4 subunit) expression was decreased in ADC-L. Thus, over-representation of cancer-stimulating α7-nAChR in SQC-L, also potentiated by smoking, and underrepresentation of cancer-inhibiting α4β2-nAChR in ADC-L could explain the different tobacco influences on the tumorigenic process in each cancer type, This study was supported by grants to C. Montiel and F. Arnalich from the Ministry of Economy, Industry and Competitiveness, Government of Spain (SAF2014-56623-R) and Foundation “Mutua Madrileña Investigación Biomédica” (FMM2011), Spain. A.B. is recipient of a fellowship (Beca FPI, Universidad Autónoma Madrid). J.L.C. and C.M.S. are recipients of fellowships (Beca FPU from Ministerio de Educación, Cultura y Deporte and Beca FPI from Ministry of Economy, Industry and Competitiveness, Government of Spain, respectively)

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB. Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies. Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth. Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB. Lay summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)., This article was possible thanks to the inputs from the Instituto de Salud Carlos III, ISCIII (PI09/00751, PI10/02082, PI13/02340). The project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 668596 (ChiLTERN) and grant agreement No 826121 (iPC). JCR is supported by the Catalan Agency for Management of University and Research Grants (AGAUR, 2019 FI_B01024). LT is supported by an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813). DS is supported by the Gilead Research Scholar in Liver Disease. JML is supported by the European Union's Horizon 2020 research and innovation programme (HEPCAR, 667273-2), Institucio Catalana de Recerca i Estudis Avancats (ICREA), U.S. Department of Defense (CA150272P3), an Accelerator Award (CRUCK, AECC, AIRC) (HUNTER, C9380/A26813), National Cancer Institute, Tisch Cancer Institute (P30-CA196521), Samuel Waxman Cancer Research Foundation, Spanish National Health Institute (SAF2016-76390) and AGAUR (SGR-1358). CA and MRS were supported by Ramon y Cajal (RYC-2010-07249) and Miguel Servet (CPII14/00021) programs of the Ministry of Science and Innovation of Spain and ISCIII, respectively. CA, MRS and MS received funding from CIBERehd (CB06/04/0033) and AGAUR (2017-SGR-490). IGTP is a member of the CERCA network of institutes. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

With the development of technology, easy access to it and the pressures of today's world, conditions are created in which people may be tempted to commit digital frauds It is important that educational institutions encourage the students aware of the use of social networks in a licit manner and the importance of technology in the development of the individual competitiveness and organizational. This research addresses the implementation of teaching-learning strategies aimed at reinforcing academically honest behavior during virtual activities and empowering students with their own knowledge. Through the teaching interventions it was possible to reduce the illicit interactions of the students during the evaluations by 26% and increase the student performance to 84%.

T1 colorectal polyps with at least 1 risk factor for metastasis to lymph node should be treated surgically and are considered endoscopically unresectable. Optical analysis, based on the Narrow-Band Imaging International Colorectal Endoscopic (NICE) classification system, is used to identify neoplasias with invasion of the submucosa that require endoscopic treatment. We assessed the accuracy of the NICE classification, along with other morphologic characteristics, in identifying invasive polyps that are endoscopically unresectable (have at least 1 risk factor for metastasis to lymph node).We performed a multicenter, prospective study of data collected by 58 endoscopists, from 1634 consecutive patients (examining 2123 lesions) at 17 university and community hospitals in Spain from July 2014 through June 2016. All consecutive lesions10 mm assessed with narrow-band imaging were included. The primary end point was the accuracy of the NICE classification for identifying lesions with deep invasion, using findings from histology analysis as the reference standard. Conditional inference trees were fitted for the analysis of diagnostic accuracy.Of the 2123 lesions analyzed, 89 (4.2%) had features of deep invasion and 91 (4.3%) were endoscopically unresectable. The NICE classification system identified lesions with deep invasion with 58.4% sensitivity (95% CI, 47.5-68.8), 96.4% specificity (95% CI, 95.5-97.2), a positive-predictive value of 41.6% (95% CI, 32.9-50.8), and a negative-predictive value of 98.1% (95% CI, 97.5-98.7). A conditional inference tree that included all variables found the NICE classification to most accurately identify lesions with deep invasion (P.001). However, pedunculated morphology (P.007), ulceration (P = .026), depressed areas (P.001), or nodular mixed type (P.001) affected accuracy of identification. Results were comparable for identifying lesions that were endoscopically unresectable.In an analysis of 2123 colon lesions10 mm, we found the NICE classification and morphologic features identify those with deep lesions with96% specificity-even in non-expert hands and without magnification. ClinicalTrials.gov number NCT02328066.

Background The analysis of tumour-infiltrating immune cells within patients’ tumour samples in colorectal cancer (CRC) has become an independent predictor of patient survival. The tumour microenvironment and the immune checkpoints, such as PD-L1/PD-1, are relevant to the prognoses and also appear to be relevant for further CRC therapies. Methods We analysed the presence and features of the infiltrated monocyte/macrophage and lymphocyte populations in both tumour and peritumour samples from patients with CRC (n = 15). Results We detected a large number of CD14+ monocytes/macrophages with an alternative phenotype (CD64+CD163+) and CD4+ lymphocytes that infiltrated the tumour, but not the peritumour area. The monocytes/macrophages expressed PD-L1, whereas the lymphocytes were PD-1+; however, we did not find high PD-L1 levels in the tumour cells. Coculture of circulating naïve human monocytes/macrophages and lymphocytes with tumour cells from patients with proficient mismatch repair CRC induced both an alternative phenotype with higher expression of PD-L1 in CD14+ cells and the T-cell exhaustion phenomenon. The addition of an α-PD-1 antibody restored lymphocyte proliferation. Conclusion These results emphasise the interesting nature of immune checkpoint shifting therapies, which have potential clinical applications in the context of colorectal cancer.

This article belongs to the Special Issue 3D Cell Culture Based on Marine Resources., Plocabulin is a novel microtubule-disrupting antitumor agent of marine origin that is currently undergoing phase II clinical trials. Plocabulin has potent antiproliferative and antiangiogenic actions in carcinoma cell lines and has antitumor activity in xenografted mice. Here, we used three-dimensional (3D) tumor organoids derived from three colorectal cancer (CRC) patients to study the effect of plocabulin in a personalized assay system that ensures dose dependence and high reproducibility. The cytotoxicity of plocabulin was an order of magnitude higher than that of the active irinotecan derivative SN38 (7-ethyl-10-hydroxy-camptothecin) in tumor organoids at different passages. Moreover, plocabulin maintained its strong cytotoxic activity in wash-out experiments, in which a short pulse treatment of tumor organoids was as efficient as continuous treatment. Our data show that plocabulin has a very potent cytotoxic action in CRC patient-derived tumor organoids, supporting ongoing clinical trials with plocabulin and the use of organoid assays to provide personalized validation of antitumor drugs., This study was supported by grants SAF2016-76377-R (AEI/FEDER, UE), SAF2017-90604-REDT (Nurcamein) and ISCIII-CIBERONC CB16/12/00273 (to A.M.) from the Spanish Ministry of Science, Innovation and Universities.

Introdução: O diplégico espástico apresenta uma série de comprometimentos funcionais devido à condição física que lhe é imposta, principalmente em membros inferiores. A Terapia Assistida por Animais (TAA), na qual o principal componente da equipe é o animal, começa a se destacar, apesar de ser um recurso terapêutico ainda pouco pesquisado. Objetivo: Neste estudo, objetivou-se verificar a influência da TAA na sua funcionalidade. Método: Realizou-se um trabalho qualiquantitativo, caracterizado por um estudo de caso, com uma criança diplégica espástica. Para mensuração dos resultados, aplicaram-se ao cuidador da criança o questionário Pediatric Evaluation of Disability Inventory (PEDI) e uma entrevista semiestruturada. A evolução da criança foi registrada em diário de campo pelos pesquisadores. Resultados: Ao término do estudo, identificou-se uma melhora funcional nos quesitos de autocuidado, mobilidade e função social. Conclusão: Percebeu-se que a TAA é um recurso terapêutico lúdico e estimulante, capaz de proporcionar melhor desempenho das atividades funcionais da criança.

Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome.The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis. Total and individual symptom scores were recorded in a diary card throughout the study. QOL, quality of sleep, nasal cytology, rate of drug intake, and safety were also assessed at pre-defined time-points.In all, adult patients (31 in each group) were enrolled, of whom 22 dropped out. Both treatment regimens considerably decreased the total and individual symptoms scores from baseline and achieved similar levels up to week 14. Continuous treatment was generally better than on-demand from week 15 onwards, reaching statistical significance from weeks 17 to 21 (from week 19 to 21 for nasal pruritus). Both regimens substantially improved QOL and sleep quality. Both treatments were well tolerated, although the on-demand group reported more adverse events.The present open label study in 62 patients indicates that levocetirizine 5 mg reliably controls persistent rhinitis over a period of 6 months, and shows a trend to be more effective in controlling the symptoms of rhinitis, improving QOL and decreasing nasal inflammation, when administered as long-term continuous therapy rather than as on-demand therapy.

Experimental small bowel transplantation (SBT) in rats has been proven to be a useful tool for the study of ischemia-reperfusion and immunological aspects related to solid organ transplantation. However, the model is not completely refined, specialized literature is scarce and complex technical details are typically omitted or confusing. Most studies related to acute rejection (AR) use the orthotopic standard, with small sample sizes due to its high mortality, whereas those studying chronic rejection (CR) use the heterotopic standard, which allows longer term survival but does not exactly reflect the human clinical scenario. Various animal strains have been used, and the type of rejection and the timing of its analysis differ among authors. The double purpose of this study was to develop an improved unusual AR model of SBT using the heterotopic technique, and to elaborate a guide useful to implement experimental models for studying AR. We analyzed the model's technical details and expected difficulties in overcoming the learning curve for such a complex microsurgical model, identifying the potential problem areas and providing a step-by-step protocol and reference guide for future surgeons interested in the topic. We also discuss the historic and more recent options in the literature. Fil: Andres, Ane Miren. Hospital Universitario La Paz; España Fil: Santamaria, Monica. Hospital Universitario La Paz; España Fil: Hernandez Oliveros, Francisco. Hospital Universitario La Paz; España Fil: Guerra, Laura. Hospital Universitario La Paz; España Fil: Lopez, Sergio. Hospital Universitario La Paz; España Fil: Stringa, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina Fil: Vallejo, Maria Teresa. Hospital Universitario La Paz; España Fil: Largo, Carlota. Hospital Universitario La Paz; España Fil: Encinas, Jose Luis. Hospital Universitario La Paz; España Fil: Garcia de las Heras, Maria Soledad. Universidad Rey Juan Carlos; España Fil: Lopez Santamaria, Manuel. Hospital Universitario La Paz; España Fil: Tovar, Juan Antonio. Hospital Universitario La Paz; España

Allergen-specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The traditional subcutaneous route is burdened by the risk of severe adverse events; therefore, safer routes of administration (e.g. local routes) have been developed and are being investigated. Controlled clinical trials have failed to demonstrate the clinical efficacy and the safety of oral or bronchial administration, and these routes have been abandoned. Local nasal immunotherapy proved effective and safe in 17 of 18 controlled trials; thus it could be considered to be a viable route of immunotherapy. Nevertheless, nasal immunotherapy is effective in rhinitis only and requires a particular administration technique; therefore, its use is slowly declining. In contrast, the efficacy of sublingual administration in the treatment of asthma and rhinitis in adults and children is supported by numerous controlled trials. The safety profile, assessed in clinical trials and post-marketing surveillance studies, is satisfactory; the most frequent side effects are gastrointestinal complaints, which can be easily managed by proper adjustment of the dose. The World Health Organization now considers sublingual immunotherapy as a valid alternative to the subcutaneous route, including its use in children. The long-lasting efficacy of treatment via the sublingual route has been documented recently but a number of points still need to be investigated, including mechanisms of action, optimal dosage, cost-effectiveness and patient's adherence.

Histamine is one of the most important steps in the phlogistic allergic reaction. Its activity is due to the link to specific receptors on the cellular surface. H1-receptors of second generation are the most currently prescribed drugs in allergic diseases for their high selectivity, little or no central sedative effect, rapid onset of action and long half lives. Antihistamines can modulate part of immunological mechanisms involved in the pathogenesis of allergic inflammation reducing mediator release and expression of adhesion molecules, regulating the release of cytokines, chemokines and consequently inflammatory cells recruitment. The anti-inflammatory effects of cetirizine, desloratadine and levocetirizine are reviewed. Quality of life is considered too, as a main parameter in a global evaluation of the antihistamine's effects.

Background: Desloratadine (DL) and levocetirizine (LCZ) are the newest commercialized antihistamines. Pharmacokinetics, pharmacodynamics and clinical data are available for both drugs, but there is to date no direct comparison involving the nose and skin at the same time. We compared the effects of a single dose of the two drugs in the nose and skin over 24 h. Methods: Twenty-three patients with symptomatic allergic rhinitis were enrolled in a randomized double-blind crossover administration of DL and LCZ. The histamine-induced wheal and flare was measured at baseline and 2 and 24 h after dosing. A reflective total symptom score (rTSS) for the previous 24 h was assessed before and after each dose. An instant symptom score was also measured at various time points after each drug. Results: LCZ provided greater inhibition of the flare at 2 h (p = 0.05) and at 24 h (p = 0.007) and greater inhibition of the wheal only at 2 h (p = 0.02). The decrease in wheal and flare was significant versus baseline (p = 0.007) with both drugs. The rTSS of the previous 24 h decreased significantly with both LCZ (11.53 vs. 8.0; p < 0.05) and DL (11.3 vs. 7.9; p < 0.05). The instant TSS progressively decreased in parallel with both drugs, but a difference in favor of LCZ was seen 2 h after dosing. Conclusions: Single doses of DL and LCZ had a comparable effect on nasal symptoms, but LCZ was faster and displayed a greater effect on histamine wheal.

Purpose To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. Design Retrospective nonrandomized comparative trial. Patients and methods Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. Main outcome measures If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. Results Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. Conclusions Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.

PURPOSE: To evaluate the safety and efficacy of weekly docetaxel plus trastuzumab in women with HER-2–overexpressing metastatic breast cancer. Efficacy was correlated with serum HER-2 extracellular domain (ECD) levels. PATIENTS AND METHODS: Thirty women with metastatic breast cancer were treated with weekly docetaxel and trastuzumab as first- or second-line therapy. Both docetaxel 35 mg/m2/wk and trastuzumab 2 mg/kg/wk were delivered in 4-week cycles consisting of three weekly treatments followed by 1 week of rest. A loading dose of trastuzumab 4 mg/kg was administered 1 day before the start of the first cycle. RESULTS: The median delivered dose-intensity of docetaxel was 24 mg/m2/wk (range, 18 to 27 mg/m2/wk). The intent-to-treat overall response rate (ORR) was 63% (95% confidence interval [CI], 44% to 80%). The ORR in patients whose tumors were HER-2–positive by fluorescence in situ hybridization was 67% (16 of 24 patients; 95% CI, 45% to 84%). In patients with elevated serum HER-2 ECD at baseline, the ORR was 76% (95% CI, 53% to 92%), compared with 33% (95% CI, 7% to 70%) in patients with low HER-2 ECD levels (P = .04). Variations in HER-2 ECD concentrations during treatment correlated with response to treatment. Median time to progression was 9 months. Acute toxicity, including myelosuppression, was mild. Fatigue, fluid retention, and excessive tearing became more common with repetitive dosing. CONCLUSION: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2–overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.

Background: Adverse reactions to drugs are common in the clinical practice. Many outpatients are frequently referred to allergists in order to determine which drugs they can safely take in the future. Objective: We set up an oral single-dose tolerance test procedure to find out for each patient one or more alternative drugs that can be taken when needed. Methods: 452 outpatients (130 male, 322 female) with well-documented reactions (urticaria/angioedema, respiratory symptoms, laryngeal edema, anaphylaxis, exfoliative skin diseases) underwent the challenge. All tests were preceded by a single-blind placebo: if a reaction occurred, a second placebo was administered. Otherwise, a single dose (1/10 of the therapeutic one) of an alternative drug was given blindly and the patient was then observed for 6 h. The drugs used were different in structure from those suspected of having caused the adverse reaction. The patients were followed up at 4- to 6-month intervals, in order to detect any reaction that may have occurred with the tested drugs. Results: 98 patients (89 women) had untoward reactions after the first placebo and 34 out of them reacted to the second placebo, too. During challenges the reaction rate ranged between 4.6 and 9.0%; these reactions were easily managed and none of them was severe. We followed up 407 patients: 87.2% of them were able to use one or more of the suggested drugs without reactions, 9.3% did not take the drugs and only 3.5% reported reactions to the previously tested drugs. Conclusion: The challenge procedure proved to be a simple tool for managing patients with adverse reactions to drugs. Its safety and reliability were validated by a long-term follow-up.

A variety of surgical procedures have been developed to accelerate orthodontic treatment of adult patients seeking to enhance their smiles or masticatory function. While most of these techniques are invasive, the minimally invasive piezocision technique reduces trauma by combining microincisions and localized piezoelectric bone surgery. A method for combining piezocision with the use of computed tomography is presented here. By creating a three-dimensional model of the arch, the depth and location of the corticotomies can be precisely planned, and a surgical guide can be fabricated and used to prevent any damage to the dental roots.

BACKGROUND: This study was performed to evaluate the outcomes of patients with locally advanced breast cancer (LABC) who were treated with a multidisciplinary approach including primary systemic chemotherapy and noncross-resistant adjuvant chemotherapy. METHODS: Patients with LABC received 4 or 6 cycles of doxorubicin and docetaxel (DT) as primary systemic chemotherapy (PST) every 21 days. Patients with adequate response underwent surgery followed by adjuvant chemotherapy according to pathologic response: complete (pCR), 2 more cycles of DT; partial (pPR), 2 more cycles of DT followed by 6 cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (5-FU) (CMF); and minor (pMR), 6 cycles of CMF. Patients then received radiation and tamoxifen (hormone receptor-positive patients only). RESULTS: Eighty-eight patients were evaluable. Seventy-four patients had an adequate response to DT and were considered operable, and 72 underwent surgery. Ten patients (13.9%) achieved a pCR, 22 (30.5%) achieved a pPR, and 40 achieved a pMR (55.5%). Fourteen patients were considered nonoperable after DT and underwent salvage CMF therapy. Five of these patients underwent surgery and 1 had achieved a pCR. The estimated 5-year recurrence-free survival (RFS) rates for patients with pCR, pPR, and pMR were 80%, 77%, and 59%, respectively, and the estimated 5-year overall survival (OS) rates were 90%, 91%, and 74%, respectively. The 5-year OS rates were 82% for initially operable and 21% for initially inoperable patients (P ≤ .001) CONCLUSIONS: Multidisciplinary therapy that includes PST with DT and adjuvant therapy with CMF administered according to the clinical and pathologic response is associated with high long-term RFS and OS rates in patients with LABC. Clinical or pathologic PR or CR to DT predicts improved RFS and OS. Cancer 2010. Published 2010 by the American Cancer Society.

9 páginas Latin America consumes less than 2.7% of the morphine in the world, as reported by the governments to the International Narcotics Control Board. Methods to improve access to opioids for the treatment of pain have been developed by the Pain & Policy Studies Group (PPSG), a World Health Organization Collaborating Center at the University of Wisconsin. This article describes the preparation and implementation of an action plan in Colombia as a part of an international fellowship program on opioid policy developed by the PPSG and funded by the Open Society Institute. The action plan for Colombia included three steps: 1) a survey of regulators and health care providers to identify the current situation and their perceptions of opioid availability in the regions of the country; 2) a workshop with representatives of the Ministry of Health, the national and state competent authorities, pain and palliative care physicians, and international leaders; and 3) implementation workshops at the local level throughout the country. For the survey, response rates of 47% and 96% were registered among physicians and competent authorities, respectively. The survey identified significant regional differences in perceived opioid availability between physicians and regulators. Focus group discussions during the workshop identified several reasons leading to limited availability of opioids in the country, including deficiencies in the procurement process, insufficient human resources, excessive bureaucratic tasks, insufficient number of pharmacies authorized to dispense controlled medications in the country, lack of training in the health care professions, and overly restrictive laws and regulations governing opioid availability. The third step of the action plan has not been implemented. Additional and continuous monitoring needs to be implemented to measure the progress of this project.

The Virtual Technology Center at the University of Houston has developed a web application, called VClass, that completely automates the process of capturing and publishing in-class lectures on the web using nothing more than a standard computer. The captured lectures are distributed to students as streaming video that includes audio, notes, and any projected media. Beyond classroom capture technology, VNet also features numerous course management features such as assignment posting, discussion forums, and announcements. After just 2 years more than 200 courses are using VNet at the University of Houston to publish more than 11,000 resources. VNet receives over 1,200 unique users daily from all over the world - including Venezuela, Brazil, China, South Africa, France, Mexico and Iraq. This presentation will cover how VClass functions and how VClass has impacted teaching and learning at the University of Houston.

Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and of avoiding the side effects. More than 30 randomized controlled trials have been published so far, in addition to several post marketing surveys. Thus, the literature provides a solid documentation of the safety profile of this treatment. Concerning the randomized controlled trials, the more frequently reported side effect of SLIT is the oral itching or swelling, followed by gastrointestinal complaints. These side effects are invariantly described as mild and easily managed by temporarily adjusting the dose. Systemic relevant adverse events (asthma, urticaria, angioedema) occur sporadically, with their rate not being different from the placebo groups. Moreover, the safety profile seems not to differ in adults and children. More interestingly, the post marketing surveys consistently showed that the occurrence of all side effects is less than 20% of patients and less than 1 per 1,000 doses, thus being quite insignificant compared to subcutaneous immunotherapy. The most recent surveys showed that the rate of adverse events does not increase in children below the age of 5 years, being traditionally considered as a prudential limit for injection IT. Finally, it seems that the occurrence of some adverse events, at variance with injection route, does not depend strictly on the dose of allergen administered.

SummaryRationaleThe development of chronic obstructive pulmonary disease (COPD) in smokers and their susceptibility to infections is not fully understood. Recent evidences suggest that Clara cells play a part in host defense, immunomodulatory response and airways remodelling through the production of specific factors such as Clara cell 16 (CC-16). This protein has never been related to patients’ lung function tests, blood gases parameters and diseases severity.ObjectivesTo evaluate a possible correlation between CC-16 expression in sputum, measured by a new methodological approach, and the degree of severity in patients with moderate and severe COPD. We also analyzed possible correlations between CC-16 and cytological sputum population, arterial blood gases and lung function.Main FindingsWe analyzed 20 patients, mean age 72.95, classified on the basis of the global initiative for chronic obstructive lung disease guidelines (GOLD 2006). The samples were processed for cytological analysis and CC-16 levels were assessed by Western blot. We found lower levels of CC-16 in severe COPD compared to moderate ones (p

Sublingual immunotherapy (SLIT) is accepted in the official documents and is currently used in many European countries. In recent years, new clinical data on efficacy and safety have been published, including meta-analyses in adults and children and surveys of safety in children younger than age 5 years. Moreover, it has been shown that, similar to the injection route, SLIT can prevent the onset of new sensitizations and the onset of asthma. Additionally, the mechanisms of action are beginning to be systematically studied. Some points need further investigation, such as the effect in asthma, the mechanisms of action, and the optimal dose to be administered.

Primary systemic therapy (PST) is the standard approach to the management of patients with locally advanced breast cancer (LABC). The authors hypothesized that the intratumoral administration of a nonreplicating adenoviral vector (Ad5) that contains the human wild-type p53, AdCMV-p53, combined with chemotherapy, could increase the efficacy of PST as measured by pathologic complete response.: In a prospective, open-label, Phase II trial, 13 patients with LABC were treated with 6 3-week cycles of PST, which consisted of intratumoral injections of Ad5CMV-p53 for 2 consecutive days plus docetaxel and doxorubicin followed by surgery. p53 status was determined at baseline and was assessed immediately after the first injection (up to 48 hours). Clinical response was assessed by clinical and radiologic methods.: The trial was terminated early, because none of the patients achieved a pathologic complete response. The median age was 56 years (range, 39-71 years), and the median tumor size was 8 cm (range, 5-11 cm). Eight patients (73%) had a p53 mutation. Serial biopsies showed an increase in p53 messenger RNA (mRNA) and p21(WAF1/Cip1) mRNA. All 12 evaluable patients achieved an objective clinical response. The surgical specimens revealed scattered tumor cells with extensive tumor-infiltrate leukocytes (predominantly T-lymphocytes). At a median follow-up of 37 months (range, 30-41 months), 4 patients (30%) developed systemic recurrence, and 2 patients died. The estimate breast cancer-specific survival rate at 3 years was 84% (95% confidence interval, 65.7-100%). There was no increase in systemic toxicity.: Ad5CMV-p53 combined with PST is safe, active, and associated with local immunomodulatory effects. The promising clinical activity of this combination deserves further investigation in randomized studies.

Allergen specific immunotherapy, together with drugs and allergen avoidance, is a cornerstone in the management of respiratory allergy. The non-injection or local routes were developed with the main goal of improving the safety and minimizing the risk of those side effects, which can accompany the injection route. The pure oral route and the bronchial route showed, in the clinical trials, only a marginal efficacy with not negligible side effects. Therefore, these routes are no longer recommended for clinical use. The nasal route proved effective and safe, but its efficacy is strictly limited to the nose. Moreover, the practical problems with administration have made the use of nasal immunotherapy progressively declining. The efficacy of the sublingual route is confirmed by numerous controlled trials, and a meta analysis (in allergic rhinitis). The safety profile, as derived from clinical trials and post marketing surveillance studies, is satisfactory, with mild gastrointestinal complaints being the more frequent side effect reported. Recent studies have also demonstrated that SLIT has a long-lasting effect and a preventive effect on the onset of new skin sensitizations, and interesting data on adherence and mechanisms of action have become recently available. Based on these experimental data, SLIT is now officially accepted as a viable alternative to the subcutaneous route in adults and children. Several points still need to be elucidated, including: mechanisms of action, optimal dosages, and indications in pediatric patients.

We tested the hypothesis that contact allergy plays a role in chronic urticaria, and included the Italian series of patch tests in the diagnostic workup. Of 121 patients with chronic urticaria, 50 (41%) tested positive to contact allergens. In all patients, avoidance measures led to a complete remission within 1 month. We suggest that testing for contact sensitization can be helpful in the management of chronic urticaria.

Sublingual immunotherapy (SLIT) was proposed for clinical practice about 20 years ago with the main aim of improving the safety and avoiding the adverse effects of traditional treatment for allergic airways disease. To date, 32 randomized controlled trials and 6 postmarketing surveys have been published that provide a robust documentation of the safety profile of the treatment.Looking at the randomized trials it emerges that the more frequent adverse event of SLIT is oral itching or swelling, followed by gastrointestinal complaints. These adverse events are invariably described as mild and easily managed by adjusting the dose. Relevant systemic adverse events (asthma, urticaria, angioedema) occur sporadically and, with the exception of oral/gastrointestinal adverse events, the incidence of adverse events seems not to differ between the placebo and active groups. The safety profile of SLIT does not differ between adults and children.The postmarketing surveys consistently show that the incidence of adverse events associated with SLIT is less than 10%, corresponding to less than 1 adverse event per 1000 doses, and is thus quite superior to the safety profile of subcutaneous immunotherapy. Of note, the most recent data show that the rate of adverse events with SLIT is not increased in children below the age of 5 years.

Chronic Urticaria (CU) is a skin disorder characterizedby erithematous wheals, intense itch, with or withoutangioedema, daily for at least 6–8 weeks and can persistsfor years (1, 2). It remains a big problem in terms ofaetiology, pathogenetic mechanism and pharmacologictreatment. A critical aspect in the management of CU isits burden on patient’s well-being and quality of life.The expression quality of life, and more specificallyhealth-related quality of life (HRQoL), has been intro-duced to refer the impact of an illness and its therapyupon a patient, as perceived by the patient himself (3).With rising frequency HRQoL assessment is included inoutcome research, providing data about the consequencesof disease and treatment from the patient’s perspective.Accordingly a large number of instruments have beenvalidated, both generic and disease specific. Genericquestionnaire has been developed to assess HRQoL inall health conditions. Specific questionnaires, whilstevaluating the multiple aspects of HRQoL, comprisecontent specific to the health problem in question, makingthem more sensitive and potentially more responsive tochanges following clinical intervention.Although CU can be a problem that interferes withsubjective well-being and daily life, usually its evaluationhas focused on clinical endpoints. While numerousstudies are now available about HRQL in other derma-tological conditions, only few reports on this topic inpatients with CU have been found in the literaturesearch. Using the generic Nottingham Health Profile,O’Donnel et al. (4) showed that adult patients with CUreport QoL scores comparable with those of patientssuffering from coronary artery disease. Health statusand subjective satisfaction in CU have been recentlyassessed by mean of two generic tools, SF-36 and SAT-P(5); the presence of CU seems to have a substantialburden on both physical and emotional components ofhealth status, with a consequent negative influence onsubjective satisfaction. Poon and colleagues evaluatedthe nature of disability caused in CU patients using aspeciality-specific measure, and highlighted the degree ofBackground: Health-related quality of Life in patients with chronic urticaria isevaluated by mean of generic instruments or questionnaire designed for skindiseases. No disease-specific tool is now available for the assessment of chronicurticaria impact from patients 3viewpoint.Objective: The aim of our study is to develop and validate a new questionnairespecifically designed for the assessment of quality of life in chronic urticaria(Chronic Urticaria Quality of Life Questionnaire – CU-Q

Purpose of review For the present article we collected and reviewed the more relevant experimental results concerning the asthma-rhinitis link in allergic diseases, published since January 2002. Recent findings During the last 2 years, particular attention has been devoted to the behaviour of the immune response in the two compartments of the airways. The recent experimental data, mainly obtained with specific nasal or bronchial allergen challenges, have confirmed that the link between the nose and the bronchi is bidirectional, and that a systemic cross-talk occurs. Furthermore, the pathogenic role of paranasal sinus infections in respiratory allergy has been better elucidated. It was shown that, in sinusitis, a T helper type 2 polarization exists, which can be reverted by proper therapy. On the other hand, despite the abundant experimental evidence, our view of the united airways is still not complete, and several points need to be developed. Summary The new findings on the asthma-rhinitis link have confirmed the current pathogenic view of respiratory allergy. These findings have important implications from a therapeutic point of view, and therefore encourage and promote the search for novel integrated treatment strategies.

Background: Few articles are available about chronic urticaria (CU) impact on patients’ quality of life (QoL). The aim of our study was to evaluate QoL in CU patients both focusing on health status and subjective satisfaction. We adopted two generic tools: SF-36 (an health status questionnaire) and SAT-P (a satisfaction profile). Methods: Twenty-one untreated patients (five males, 16 females; aged 46.3 ± 12.4) affected by CU, were enrolled. SF-36 and SAT-P scores of CU patients were compared with scores of a group of 27 patients with respiratory allergy. Published reference values of 608 and 241 Italian healthy subjects were used as controls, respectively, for SF-36 and SAT-P. Results: Patients with CU compared with allergic patients referred significantly lower scores in physical functioning (P = 0.046), role physical (P = 0.01), bodily pain (P = 0.0001), general health (P = 0.0043) and role emotional (P = 0.04), and compared with reference sample reported lower scores in all SF-36 domains (P

References 1. Bilo BM, Rueff F, Mosbech H, Bonifazi F, Oude-Elberink JN. Diagnosis of hymenoptera venom allergy. Allergy 2005;60:1339–1349. 2. Cochrane CG, Weigle W, Dixon FJ. The role of polymorphonuclear leukocytes in the initiation and cessation of the Arthus vasculitis. J Exp Med 1959;100:481. 3. Ting TV, Hashkes PJ. Update on childhood vasculitides. Curr Opin Rheumatol 2004;16:560–565. 4. Sharan G, Anand RK, Sinha KP. Schonlein-Henoch syndrome after insect bite. Br Med J 1966;5488:656. 5. Burke DM, Jellinek HL. Nearly fatal case of Schonlein-Henoch syndrome following insect bite. Am J Dis Child 1954;88:772–774. 6. Bonifazi F, Jutel M, Bilo BM, Birnbaum J, Muller U. Prevention and treatment of hymenoptera venom allergy: guidelines for clinical practice. Allergy 2005;60:1459–1470.

Background Due to optimal safety of sublingual immunotherapy (SLIT), it was suggested that a slow up-dosing phase maybe not necessary, and therefore the treatment will be more patient-friendly, avoiding dosing mistakes. Patients Twenty adult patients suffering allergic rhinitis due to Parietaria, were enrolled. Half of them received the traditional schedule and the other half immediately started with 200 STU. Results No difference was observed between the traditional up-dosing treatment schedule and no-updosing treatment schedule in terms of side effects, even mild local side effects was grater with traditional regimen.

Rationale Adverse Drug Reactions (ADRs) frequently complicate medical treatments. Between 15% and 30% of hospitalized patients experience ADR, and 0.2% to 29.3% of outpatients require hospitalization for ADR. Despite the wide diffusion of the problem, there aren't studies considering its impact on patients' Health Related Quality of Life (HRQoL). Aim of this study was to evaluate the emotional, practical and social burden of ADR on patients' daily life, by means of a new questionnaire (ADR-QoL). This new questionnaire covers 23 aspects that could be affected by the presence of previous ADRs. Methods QoL was administered to 113 (32 M, 81 F; age 40 + 14.8) consecutive outpatients with previous ADRs. Measurement consisted of a five points Likert scale (1=not at all; 5=very much). 110 questionnaires were eligible for the analysis. Results The most relevant aspect, in 92% of patients, is the requirement of safe treatments for each possible disease. Family was involved in the problem in more than 90% of cases, whereas GP was informed in about 80% of cases. 87% didn't intake no drug, even if needed, without consulting an allergist. Reactions of fear and anxiety resulted to be present in all patients, most of them regarding medical emergencies and pain treatment. No impact by ADRs on social life and work emerged in our sample. Conclusions Our results show a significant impact of ADR on emotional domains. Our questionnaire could be useful in detecting emotional reactions that interfere with treatment management, in order to reach the best level of adherence for each patients.

Objective To review the available published data concerning the use of sublingual immunotherapy (SLIT) in respiratory allergy to primarily evaluate the clinical efficacy and safety of the treatment and to secondarily consider the mechanisms of action and any unresolved questions. Data Sources Articles in the medical literature (starting from 1986 up to November 2003) derived from searching the MEDLINE database with the keywords sublingual immunotherapy, respiratory allergy, asthma , and rhinitis . Sources included review articles, randomized controlled clinical trials, postmarketing surveillance studies, and relevant reports from meeting proceedings. Study Selection Articles concerning safety, efficacy, and mechanisms of SLIT published in English-language, peer-reviewed journals. Results SLIT proved effective and safe in adults and children. As with traditional subcutaneous immunotherapy, SLIT has long-lasting efficacy and a preventive effect on new sensitizations. Conclusion SLIT is a viable alternative to subcutaneous immunotherapy. Its use in pediatric patients seems to be particularly promising.