Surgical Outcomes in a Lung Cancer-Screening Program Using Low Dose Computed Tomography / Resultados quirúrgicos de un programa de cribado de cáncer de pulmón utilizando tomografía computarizada de baja dosis

OBJECTIVE: Lung cancer (LC) is the leading cause of death from cancer worldwide. More than 27,000 LCs are diagnosed annually in Spain, and most are unresectable. Early detection and treatment reduce LC mortality. This study describes surgical outcomes in a longstanding LC screening cohort in Spain. METHODS: We conducted a retrospective study of surgical outcomes in a LC screening (LCS) program using low dose computed tomography (LDCT) since the year 2000. A descriptive analysis of clinical and radiological parameters, presence or absence of a preoperative diagnosis, pathological staging, morbidity, mortality, and survival was performed. RESULTS: Ninety-seven (2.5%) LC were diagnosed in 3825 screened. Twenty individuals with LC had no surgery due to advanced stage or small cell histology. Eighty-seven surgical procedures were carried out for suspected or biopsy proven LC, detected by LDCT. Most operated patients were male (57[85%]) aged 64 ± 9.1 years. Nine patients underwent a second operation for a metachronous primary lung cancer. Mean tumor size was 15.2 ± 7.6 mm. Eight nodules were benign (9.2%). Lobectomy was performed in 56 cases (83.6%). Adenocarcinoma (n = 39; 58.2%) was the most frequent histological type followed by squamous cell carcinoma (n = 17; 25.4%). Fifty-nine (88%) tumors were in Stage I. Thirteen patients (15.4%) had 16 complications. The estimated survival rates at 5 and 10 years for stage I were 93% (95% CI: 79%-98%) and 83% (95% CI: 65%-92%), respectively. CONCLUSION: Lung cancer screening was associated with excellent surgical outcomes with 5 and 10-year survival rates exceeding 90 and 80%, respectively

OBJETIVO: El cáncer de pulmón (CP) es la principal causa de muerte por cáncer en todo el mundo. En España se diagnostican anualmente más de 27.000 CP y la mayoría son irresecables. La detección y el tratamiento tempranos reducen la mortalidad por CP. Este estudio describe los resultados quirúrgicos en una cohorte de cribado de CP de larga duración en España. MÉTODOS: Llevamos a cabo un estudio retrospectivo de los resultados quirúrgicos de un programa de cribado de CP (CCP) usando tomografía computarizada de baja dosis (LDCT, por sus siglas en inglés) en marcha desde el año 2000. Se realizó un análisis descriptivo de los parámetros clínicos y radiológicos, presencia o ausencia de un diagnóstico preoperatorio, estadificación patológica, morbilidad, mortalidad y supervivencia. RESULTADOS: Se diagnosticaron 97 (2,5%) CP entre 3.825 sujetos cribados. Veinte personas con CP no se sometieron a cirugía debido a un estado avanzado de la enfermedad o a una histología de células pequeñas. Se llevaron a cabo 87 procedimientos quirúrgicos por sospecha de CP o CP demostrado mediante biopsia, detectados en la LDCT. La mayoría de los pacientes operados fueron varones (57 [85%]) de 64 años ± 9,1 años. Nueve pacientes se sometieron a una segunda operación por un cáncer de pulmón primario metacrónico. El tamaño medio del tumor fue de 15,2 ± 7,6 mm. Ocho nódulos fueron benignos (9,2%). Se realizó lobectomía en 56 casos (83,6%). El adenocarcinoma (n = 39; 58,2%) fue el tipo histológico más frecuente seguido por el carcinoma de células escamosas (n = 17; 25,4%); 59 (88%) tumores se encontraban en estadio I. Trece pacientes (15,4%) tuvieron 16 complicaciones. Las tasas de supervivencia estimadas a los 5 y 10 años para el estadio I fueron del 93% (IC 95%: 79 al 98%) y del 83% (IC 95%: 65 al 92%), respectivamente. CONCLUSIÓN: El CCP se asoció con excelentes resultados quirúrgicos y con tasas de supervivencia a los 5 y 10 años superiores al 90 y al 80%, respectivamente

Surgical Outcomes in a Lung Cancer-Screening Program Using Low Dose Computed Tomography.

OBJECTIVE: Lung cancer (LC) is the leading cause of death from cancer worldwide. More than 27,000 LCs are diagnosed annually in Spain, and most are unresectable. Early detection and treatment reduce LC mortality. This study describes surgical outcomes in a longstanding LC screening cohort in Spain. METHODS: We conducted a retrospective study of surgical outcomes in a LC screening (LCS) program using low dose computed tomography (LDCT) since the year 2000. A descriptive analysis of clinical and radiological parameters, presence or absence of a preoperative diagnosis, pathological staging, morbidity, mortality, and survival was performed. RESULTS: Ninety-seven (2.5%) LC were diagnosed in 3825 screened. Twenty individuals with LC had no surgery due to advanced stage or small cell histology. Eighty-seven surgical procedures were carried out for suspected or biopsy proven LC, detected by LDCT. Most operated patients were male (57[85%]) aged 64±9.1 years. Nine patients underwent a second operation for a metachronous primary lung cancer. Mean tumor size was 15.2±7.6mm. Eight nodules were benign (9.2%). Lobectomy was performed in 56 cases (83.6%). Adenocarcinoma (n=39; 58.2%) was the most frequent histological type followed by squamous cell carcinoma (n=17; 25.4%). Fifty-nine (88%) tumors were in Stage I. Thirteen patients (15.4%) had 16 complications. The estimated survival rates at 5 and 10 years for stage I were 93% (95% CI: 79%-98%) and 83% (95% CI: 65%-92%), respectively. CONCLUSION: Lung cancer screening was associated with excellent surgical outcomes with 5 and 10-year survival rates exceeding 90 and 80%, respectively.

Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors.

BACKGROUND: The etiology and the molecular basis of lung adenocarcinomas (LuADs) in nonsmokers are currently unknown. Furthermore, the scarcity of available primary cultures continues to hamper our biological understanding of non-smoking-related lung adenocarcinomas (NSK-LuADs). PATIENTS AND METHODS: We established patient-derived cancer cell (PDC) cultures from metastatic NSK-LuADs, including two pairs of matched EGFR-mutant PDCs before and after resistance to tyrosine kinase inhibitors (TKIs), and then performed whole-exome and RNA sequencing to delineate their genomic architecture. For validation, we analyzed independent cohorts of primary LuADs. RESULTS: In addition to known non-smoker-associated alterations (e.g. RET, ALK, EGFR, and ERBB2), we discovered novel fusions and recurrently mutated genes, including ATF7IP, a regulator of gene expression, that was inactivated in 5% of primary LuAD cases. We also found germline mutations at dominant familiar-cancer genes, highlighting the importance of genetic predisposition in the origin of a subset of NSK-LuADs. Furthermore, there was an over-representation of inactivating alterations at RB1, mostly through complex intragenic rearrangements, in treatment-naive EGFR-mutant LuADs. Three EGFR-mutant and one EGFR-wild-type tumors acquired resistance to EGFR-TKIs and chemotherapy, respectively, and histology on re-biopsies revealed the development of small-cell lung cancer/squamous cell carcinoma (SCLC/LuSCC) transformation. These features were consistent with RB1 inactivation and acquired EGFR-T790M mutation or FGFR3-TACC3 fusion in EGFR-mutant tumors. CONCLUSIONS: We found recurrent alterations in LuADs that deserve further exploration. Our work also demonstrates that a subset of NSK-LuADs arises within cancer-predisposition syndromes. The preferential occurrence of RB1 inactivation, via complex rearrangements, found in EGFR-mutant tumors appears to favor SCLC/LuSCC transformation under growth-inhibition pressures. Thus RB1 inactivation may predict the risk of LuAD transformation to a more aggressive type of lung cancer, and may need to be considered as a part of the clinical management of NSK-LuADs patients.

Allergy in adolescent population (14-18 years) living in Campania region (Southern Italy). A multicenter study.

Summary: Adolescents (Ad) constitute a difficult to manage population among individuals suffering from asthma. The aim of our study was to assess the prevalence, clinical characteristics and age of onset of allergic sensitization and clinical symptoms in a sample of atopic Ad living in the Campania region (Southern Italy). Sixteen Allergy units or Centers belonging to the Italian Association of Hospital and Territorial Allergologists (AAIITO, Campania region) participated in this cross-sectional study. A case report form (CRF) was specifically designed for this study and commercial allergen extracts used for screening SPTs were provided by ALK-Abelló Group (Milan, Italy). A total of 443 patients were examined (females, f 220, 49.6 %; males, m 223, 50.3%). Dust mites represent the most common sensitizing agents in allergic Ad living in Campania region (Dermatoph. pteronyssinus 67.4% and Dermatoph. farinae 66.5%), followed by Parietaria (58.9%), grasses (45.8%), Artemisia vulgaris (16.7%), Olea Europaea (32.2%), dog dander (17.1%), cat dander (20.0%), Alternaria alternata (8.1%), Cupressus sempervirens (4.9%), Betula pendula (4.7%), other allergens (19.4%). An interesting comparison has been made between clinical data of our Ad with data of elderly patients (E). The role of allergic sensitization is significantly higher in Ad compared to E. Dermatophagoides pteronyssinus is the first sensitizing allergen in Ad and the last in E. Parietaria constitutes the first sensitizing pollen both in Ad and E, the percentage of sensitization is higher in Ad. Another important difference is the higher prevalence of As, as only symptom, in E compared to Ad (19.7% versus 7.6%). In conclusion, our findings confirm the high prevalence and clinical significance of airway allergic sensitization in the adolescents living in Campania region.

Allergic sensitization to common pets (cats/dogs) according to different possible modalities of exposure: an Italian Multicenter Study.

BACKGROUND: The query "are there animals at home?" is usually administered for collecting information on anamnesis. This modality to consider exposure to pet allergens constitutes a potential bias in epidemiological studies and in clinical practice. The aim of our study was to evaluate/quantify different modalities of exposure to cat/dog in inducing allergic sensitization. METHODS: Thirty Italian Allergy units participated in this study. Each centre was required to collect the data of at least 20 consecutive outpatients sensitized to cat/dog allergens. A standardized form reported all demographic data and a particular attention was paid in relieving possible modalities of exposure to cat/dog. RESULTS: A total 723 patients sensitized to cat/dog were recorded, 359 (49.65%) reported direct pet contact, 213 patients (29.46%) were pet owners, and 146 subjects (20.19%) were exposed to pets in other settings. Other patients were sensitized by previous pet ownership (150-20.75%) or indirect contact (103-14.25%), in 111 subjects (15.35%) any contact was reported. CONCLUSIONS: Only 213 patients (29.46%) would be classified as "exposed to animals" and 510 (70.54%) as "not exposed" according to usual query. Our classification has shown that many "not-exposed" subjects (399-55.19%) were "really exposed". The magnitude of exposure to pet allergens at home is not related exclusively to pet ownership. These considerations should be taken into account during the planning of epidemiological studies and in clinical practice for the management of pet allergic individuals.

Injerto costal para reconstrucción nasal: experiencia de 6 años en el Hospital San Juan de Dios / Costal graft for nasal reconstruction: 6 years experience in San Juan de Dios Hospital

Introducción: El injerto de preferencia para cirugía nasal es el cartílago septal. El Injerto de cartílago costal otorga gran material para trabajo ya que posee características similares al cartílago septal. Este injerto se utiliza generalmente para cirugías de dorso nasal, nariz en silla de montar, laterorrinias, disfunciones de la válvula nasal interna y/o externa, poca proyección nasal y rinoplastías de revisión. Objetivo: Conocer las características, resultados y complicaciones de las rinoplastías con injerto de cartílago costal realizadas en el Hospital San Juan de Dios (HSJD) entre los años 2010 y 2016. Material y método: Estudio retrospectivo con revisión de fichas clínicas de pacientes sometidos a cirugías de reconstrucción nasal con injerto de cartílago costal en el HSJD entre enero 2010 y agosto 2016. Resultado: Entre los años 2010 y 2016 se realizaron 20 rinoplastías con uso de cartílago costal: 14 eran hombres (70%) y 6 eran mujeres (30%). En 14 pacientes se usó el cartílago costal en la primera cirugía. No se presentaron complicaciones a corto, mediano y largo plazo. Conclusión: El injerto de cartílago costal es una herramienta útil a la hora de enfrentarse a cirugías complicadas. La técnica quirúrgica no es dificultosa y tiene una baja tasa de complicaciones.

Introduction: The ideal graft for nasal surgery is septal cartilage. The costal cartilage has similar characferistics to the septal cartilage. This particular graft is generally used for nasal dorsum, saddle nose, nasal deviations, dysfunctions of the internal or external nasal valve, poor nasal projection and revision rhinoplasty. Aim: Determine the characteristics, outcomes and complications of rhinoplasty with costal cartilage graft made in the San Juan de Dios Hospital (HSJD) between 2010 and 2016. Material and method: Retrospective study with reviewing medical records of all patients underwent nasal surgery reconstruction with costal cartilage graft in the HSJD between January 2010 and August 2016. Results: Between 2010 and 2016 a total of 20 rhinoplasties were performed with use of costal cartilage. Of these 14 were men (70%) and 6 were women (30%). In 14 patients we used the costal cartilage in the first surgery. No complications in short, medium and long term were presented. Conclusion: The rib cartilage graft is a useful tool when dealing with complicated surgeries. The surgical technique is not difficult and has a low complication rate.

Molecular characterization and population structure study of cambuci: strategy for conservation and genetic improvement.

Cambuci (Campomanesia phaea) belongs to the Myrtaceae family and is native to the Atlantic Forest of Brazil. It has ecological and social appeal but is exposed to problems associated with environmental degradation and expansion of agricultural activities in the region. Comprehensive studies on this species are rare, making its conservation and genetic improvement difficult. Thus, it is important to develop research activities to understand the current situation of the species as well as to make recommendations for its conservation and use. This study was performed to characterize the cambuci accessions found in the germplasm bank of Coordenadoria de Assistência Técnica Integral using inter-simple sequence repeat markers, with the goal of understanding the plant's population structure. The results showed the existence of some level of genetic diversity among the cambuci accessions that could be exploited for the genetic improvement of the species. Principal coordinate analysis and discriminant analysis clustered the 80 accessions into three groups, whereas Bayesian model-based clustering analysis clustered them into two groups. The formation of two cluster groups and the high membership coefficients within the groups pointed out the importance of further collection to cover more areas and more genetic variability within the species. The study also showed the lack of conservation activities; therefore, more attention from the appropriate organizations is needed to plan and implement natural and ex situ conservation activities.

Effects of omalizumab in severe asthmatics across ages: A real life Italian experience.

BACKGROUND: This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18-39, 40-64 and ≥ 65 years. RESULTS: Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased significantly after Omalizumab but the percentage of exacerbation-free patients was higher in younger people (76.9%) compared to middle aged patients (49.2%) and the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826], p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to elderly asthmatics. Also, a significantly reduced ACT improvement (ß = -1.070; p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab improves all asthma outcomes independently of age, although the magnitude of the effects observed in the elderly seems to be lower than in the other age groups.

Total and mutated EGFR quantification in cell-free DNA from non-small cell lung cancer patients detects tumor heterogeneity and presents prognostic value.

Mutation analysis of epidermal growth factor receptor (EGFR) gene is essential for treatment selection in non-small cell lung cancer (NSCLC). Analysis is usually performed in tumor samples. We evaluated the clinical utility of EGFR analysis in plasma cell-free DNA (cfDNA) from patients under treatment with EGFR inhibitors. We selected 36 patients with NSCLC and EGFR-activating mutations. Blood samples were collected at baseline and during treatment with EGFR inhibitors. Wild-type EGFR, L858R, delE746-A750, and T790M mutations were quantified in cfDNA by droplet digital PCR. Stage IV patients had higher total circulating EGFR copy levels than stage I (3523 vs. 1003 copies/mL; p < 0.01). There was high agreement for activating mutations between baseline cfDNA and tumor samples, especially for L858R mutation (kappa index = 0.679; p = 0.001). In 34 % of advanced NSCLC patients, we detected mutations in cfDNA not previously detected in tumor samples and double mutations in 17 %. Patients with baseline total EGFR copy levels above the median presented decreased overall survival (OS) (341 vs. 870 days, p < 0.05) and progression-free survival (PFS) (238 vs. 783 days; p < 0.05) compared with those with total EGFR copy levels below the median. Patients with baseline concentrations of activating mutations above the median (94 copies/mL) had lower OS (317 vs. 805 days; p < 0.05) and PFS (195 vs. 724 days; p < 0.05). During follow-up, T790M resistance mutation was detected in 53 % of patients. Total and mutated EGFR analysis in cfDNA seems a relevant tool to characterize the molecular profile and prognosis of NSCLC patients harboring EGFR mutations.

Presencia de síndrome de burnout en una muestra de residentes y otorrinolaringólogos de Chile / Burnout syndrome in a sample of residents and otolaryngologists from Chile

Introducción: El síndrome de Burnout o desgaste profesional relacionado con el trabajo se genera frente a un estrés laboral crónico en individuos que trabajan con personas. Se caracteriza por un agotamiento emocional, despersonalización y baja realización personal. Objetivo: Evaluar el síndrome de Burnout en los médicos residentes y otorrinolaringólogos (ORL) del país y establecer una relación entre las características sociodemográficas. Material y método: Se realizó un estudio de corte transversal. Se envió el inventario Burnout de Maslach (MBI) mediante correo electrónico a todos los residentes y ORL miembros de la Sociedad Chilena de Otorrinolaringología, Medicina y Cirugía de Cabeza y Cuello (SOCHIORL). Se utilizó test exacto de Fisher para evaluar asociación entre variables cualitativas. Resultados: De un total de 432 miembros de la SOCHIORL se recibieron 133 encuestas, de las cuales se analizaron 117 contestadas correctamente. El 100% del total de los encuestados presentó Burnout ya sea de alto grado o intermedio. Los que presentaron mayor porcentaje de alto grado de Burnout son aquellos entre 25 y 35 años, con 53% (p =0,03). El mayor grado de Burnout se observó en los residentes (57%) (p =0,03). Conclusión: El síndrome de Burnout tiene una alta prevalencia entre los ORL del país, especialmente en residentes y jóvenes ORL y quienes llevan pocos años en el desarrollo de la especialidad. Es necesario buscar herramientas para enfrentar y combatir esta realidad.

Introduction: Burnout syndrome is generated against a chronic work stress on individuals working with people. It is characterized by emotional exhaustion, depersonalization and reduced personal accomplishment. Aim: To assess Burnout in residents and otolaryngologists (ORL) in the country and establish a relationship between sociodemographic characteristics. Material and method: A cross sectional study was conducted. Maslach Burnout Inventory (MBI) was sent via email to all residents and ORL members of the Chilean Society of Otolaryngology, Medicine and Head and Neck Surgery (SOCHIORL). Fisher exact test was used to assess the association between qualitative variables. Results: Of a total of 432 members of SOCHIORL, 133 surveys were received, of which 117 were analysed. 100% of respondents had Burnout, either high or intermediate degree. Those with higher percentage of high Burnout are those between 25 and 35 years (53%) (p =0.03). The greatest degree of Burnout was observed in residents (57%) (p =0.03). Conclusion: Burnout syndrome is highly prevalent among ORL in Chile, especially in residents and young ORL with few years in the medical practice of the specialty. It is necessary to search for tools to confront and combat this reality.

Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal-adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 ± 0.07 vs 0.04 ± 0.03 µg ml(-1) , P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 ± 0.59 vs 1.09 ± 0.39 µg ml(-1) , P = 0.232). CONCLUSION: C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC.

Early Growth Response 3 regulates genes of inflammation and directly activates IL6 and IL8 expression in prostate cancer.

BACKGROUND: Transcription factor EGR3 (Early Growth Response 3) is a little-studied member of the EGR family that is highly expressed in human prostate tumours compared with normal tissue. Its function in prostate cancer, however, is unknown. METHODS: Stable shRNA silencing was achieved in naturally overexpressing prostate cancer cells, followed by Affymetrix expression analysis. Fold changes of ⩾2 and ⩽-2 were considered valid and t-tests P-values of ⩽0.01 were considered statistically significant. Potential EGR3 target genes were validated by real-time qPCR, chromatin immunoprecipitation, and gain-of-function experiments. Promoter analysis confirmed the presence of consensus binding sites in the promoters of target genes. RESULTS: Early Growth Response 3 regulates the expression of ∼330 genes, 35% of which are involved in immune responses and inflammatory processes, and 15% crosstalk with the NF-κB signalling pathway. In particular, EGR3 induces the expression of over 50 secreted cytokines, growth factors, and matrix remodelling factors. Two interleukins of great relevance to prostate cancer, IL6 and IL8, were further validated as EGR3 target genes: both promoters contain EGR consensus binding sites and are pulled down in intact cells by EGR3 chromatin immunoprecipitation. Silencing of EGR3 decreased IL6 and IL8 expression, whereas overexpression of EGR3 in nontransformed cells induced IL6 and IL8 expression. CONCLUSIONS: Chronic inflammation plays a critical role in prostate cancer and elevated production of pro-inflammatory cytokines IL8 and IL6, in particular, contributes to disease progression and to the onset of castration resistance. It is shown for the first time that EGR3 is involved in the upregulation of both IL6 and IL8. Together with our previous observation that EGR3 is highly expressed in prostate tumours compared with normal tissue and strongly correlates with IL6 and IL8 expression in clinical samples, the present study suggests that EGR3 promotes excessive production of IL6 and IL8 observed during the progression of prostate cancer.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.

Análisis de los pacientes con diabetes controlados a nivel primaria en el Servicio de Salud Concepción / Analysis of diabetic patients controlled at primary level in Concepcion Health Service

To evaluate diabetic patients in control in Concepcion Health Service, evaluating coverage, metabolic control and complications. Material: A retrospective analysis of the statistical record of 2011 (REM) using the CIE-10 classification was done. Estimation is performed with the National Health Survey of 2010. Results: 26,638 patients are controlled, achieving a 67.9 percent coverage (point estimate based on the National Health Survey of 2010), being lower in the group between 15 and 44 years old (34 percent). 38.4 percent had good metabolic control (HbA1C less than 7) and 20.8 percent poor control (HbA1C greater than 9). According to age, the group over 65 had better control and the group between 15 and 44 years worse control. The complication described was diabetic foot (51.9 percent), retinopathy (5 percent) and nephropathy (4.6 percent). Discussion: The prevalence of diabetes is increasing every year in Chile. There is acceptable coverage and early diagnosis, but still are poorly controlled cases and require a multifactorial management that begins with a self-care of their diabetes...

TGFBI expression is an independent predictor of survival in adjuvant-treated lung squamous cell carcinoma patients.

BACKGROUND: Transforming growth factor ß-induced protein (TGFBI) is a secreted protein that mediates cell anchoring to the extracellular matrix. This protein is downregulated in lung cancer, and when overexpressed, contributes to apoptotic cell death. Using a small series of stage IV non-small cell lung cancer (NSCLC) patients, we previously suggested the usefulness of TGFBI as a prognostic and predictive factor in chemotherapy-treated late-stage NSCLC. In order to validate and extend these results, we broaden the analysis and studied TGFBI expression in a large series of samples obtained from stage I-IV NSCLC patients. METHODS: TGFBI expression was assessed by immunohistochemistry in 364 completely resected primary NSCLC samples: 242 adenocarcinomas (ADCs) and 122 squamous cell carcinomas (SCCs). Kaplan-Meier curves, log-rank tests and the Cox proportional hazards model were used to analyse the association between TGFBI expression and survival. RESULTS: High TGFBI levels were associated with longer overall survival (OS, P<0.001) and progression-free survival (PFS, P<0.001) in SCC patients who received adjuvant platinium-based chemotherapy. Moreover, multivariate analysis demonstrated that high TGFBI expression is an independent predictor of better survival in patients (OS: P=0.030 and PFS: P=0.026). CONCLUSIONS: TGFBI may be useful for the identification of a subset of NSCLC who may benefit from adjuvant therapy.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy

Objectives: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. Methods: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998- 2000 and 2010-2012. Results: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P<.0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P<.0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). Conclusions: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions (AU)

Antecedentes: Se trata de una encuesta multicéntrica realizada en Italia para evaluar el impacto de la sensibilización a polen de ciprés en sujetos atópicos y establecer si la concentración de este polen en el aire ha cambiado a lo largo del tiempo. Métodos: El estudio fue realizado por alergólogos que recopilaron 100-200 sujetos consecutivos con pruebas cutáneas positivas (Prick) realizadas en 2012. Se recogieron los síntomas estacionales, junto con la concentración de polen de ciprés (obtenida por la asociación italiana de aerobiología) en 1998-2000 y 2010-2012. Resultados: En cuanto a los resultados obtenidos fueron examinados 2258 pacientes atópicos (56% mujeres; edad 2-84), sensibilizados frente al menos uno de los aeroalérgenos testados (Dermatophagoides, gramíneas, parietaria, olivo, cipres, abedul, Alternaria tenuis y epitelio de gato). El 62.9%, 16.1% y 32.7% de los pacientes que vivían en el centro, norte y sur de Italia, respectivamente, mostraron sensibilización a polen de ciprés (p<0.0001). Observamos un pico de concentración de polen de ciprés de febrero a marzo en los años 1998-2000 y 2010-2012, en todas las áreas. Los pacientes monosensibilizados a ciprés mostraron de forma prevalente rinitis (90.7-97.6%) y conjuntivitis (38.1-100%). La prevalencia de rinitis, conjuntivitis y asma se incrementa progresivamente (p<0.0001) del sur hacia el norte de Italia en los sujetos polisensibilizados. La misma tendencia se observó en los síntomas invernales típicos de la alergia al ciprés. Conclusiones: En conclusión, actualmente el polen de ciprés es el aeroalérgeno sensibilizante más frecuente (según resultados de prueba cutánea) en varias áreas de Italia central. Las variaciones del periodo de polinización pueden favorecer el incremento observado en la sensibilización a este polen. Los síntomas predominantes son rinitis y conjuntivitis. El impacto clínico de esta alergia es pobre en áreas del sur de Italia, siendo alto en las áreas del norte (AU)

[Mucopenetrating nanoparticles: vehicles for the oral administration of paclitaxel]. / Nanoparticules mucopénétrantes: véhicules pour l'administration orale du paclitaxel.

Paclitaxel is an anticancer drug used as solution for perfusion for the treatment of certain types of cancers. In the last years, a number of strategies have been proposed for the development of an oral formulation of this drug. However, this task is quite complicated due to the poor aqueous solubility of paclitaxel as well as the fact that this compound is substrate of the intestinal P-glycoprotein and the cytochrome P450 enzymatic complex. In this work, we have developed pegylated nanoparticles with mucopenetrating properties in order to conduct paclitaxel onto the surface of the enterocyte. These nanoparticles displayed a size of about 180 nm and a drug loading close to 15% by weight. The pharmacokinetic study in mice has shown that these nanoparticles were capable to offer therapeutic plasma levels of paclitaxel up to 72 hours. In addition, the oral relative bioavailability of paclitaxel when loaded in nanoparticles pegylated with poly(ethylene glycol) 2000 (PEG) was found to be 85%. In a subcutaneous model of tumour in mice, these pegylated nanoparticles administered orally every 3 days have demonstrated a similar efficacy than Taxol® administered intravenously every day during 9 days. All of these results suggested that these pegylated nanoparticles were capable to cross the mucus layer of the gut and, then, reach the surface of the enterocytes. The PEG molecules would facilitate the adhesion of nanoparticles to this epithelial surface, minimise the pre-systemic metabolism of paclitaxel and, thus, promote its absorption.

Is there any relationship between allergic sensitization to milk and animal allergens in atopic adults?

No data on the relationship between allergic sensitization to animal dander and milk allergens are available in literature in adults. Considering the high rate of allergic sensitization to mammals in atopic adults living in Naples area, we aimed to evaluate if sensitization to milk allergens could be a risk factor for these subjects. From 755 consecutive outpatients examined between May 1 2009 and December 31 2010, we selected those with an immediate skin reaction to animal dander and milk. A clinical history including evaluation of pet exposure, the results of skin-prick tests (SPTs) and specific IgE antibodies for milk allergens were recorded. Among three hundred sixty SPT-positive patients, 140 were sensitized to animal dander (38.9%) and 9 to milk allergens (6.4%). Among one hundred forty patients sensitized to animals only one was sensitized also to milk allergens; among 9 milk-sensitized individuals 5 were allergic also to animal allergens (only one to cow dander) while 4 were not sensitized to mammals. Our results suggest that relationship between allergic sensitization to milk and animal allergens is negligible in adult atopic individuals living in urban area of Naples and that high rate of sensitization to animals is likely to be due to other mechanisms such as direct/indirect exposure, and allergen cross-reactions.

Miocardiopatía dilatada en paciente con lupus eritematoso sistémico: reporte de un caso / Dilated cardiomyopathy in patient with systemic lupus erythematosus: case report

INTRODUCCIÓN: El Lupus Eritematoso Sistémico (LES) es una enfermedad autoinmune de etiología desconocida, cuyo cuadro clínico incluye diversas manifestaciones cardiovasculares, lasque se pueden presentar entre el 50 y 60 por ciento de los pacientes. La miocarditis es infrecuente (10 por ciento), pudiendo evolucionar tanto a miocardiopatía dilatada como a la mejoría. PRESENTACIÓN DEL CASO: Mujer de 40 años con antecedentes de LES diagnosticado el año 2008 y hospitalización anterior por cuadro de síndrome nefrótico, consulta en la urgencia del Hospital Guillermo Grant Benavente el por cuadro clínico de dos semanas de evolución caracterizado por disnea de mínimo esfuerzo, oliguria y edema continuo de extremidades inferiores. Destacan dentro de sus exámenes de ingreso: creatinina de 1,8 mg/dl, PCR <5 mg/l e índice proteinuria/creatininuria aislada >5; radiografía de tórax muestra cardiomegalia. Se hospitaliza en servicio de medicina interna para manejo. Evoluciona con mayor disnea ydolor torácico, por lo que se realiza ecocardiograma que revela miocardiopatía dilatada y disfunción sistólica severa. Se añade al tratamiento esteroidal previo, furosemida, carvedilol, enalapril y bolos de metilprednisolona y ciclofosfamida. Paciente evoluciona satisfactoriamente, con disminución de la disnea y leve edema de las extremidades inferiores, aunque permanece con valores de creatinina alterados. Luego de un mes es dada de alta. DISCUSIÓN: Señalamos que la miocardiopatía dilatada es una complicación infrecuente del LES, y si bien es cierto es la principal explicación para el cuadro clínico de insuficiencia cardiaca en esta paciente, no explica por si sola la sintomatología, considerando el antecedente de compromiso renal.

INTRODUCTION: Systemic Lupus Erythematosus is an autoimmune disease of unknown etiology, whose clinical picture includes various cardiovascular manifestations, which occur in between the 50 and 60 percent of the patients. Myocarditis is a rare complication (10 percent) and may evolve to dilated cardiomyopathy, or to the improvement. CASE REPORT: Forty year old woman with a history of Systemic Lupus Erythematosus diagnosed in 2008 and previous hospitalization for nephrotic syndrome, consultates in the urgency of Guillermo Grant Benavente Hospital because of a two weeks clinical picture characterized by small effort dyspnea, oliguria and continuous edema of lower extremities.Stands in their entrance examinations: creatinine 1.8 mg / dl, CRP <5 mg/l, proteinuria /creatinine index >5; X-ray shows cardiomegaly. It is decided to hospitalized the patient. Evolves with increasing respiratory distress and chest pain, so it is decided to do echocardiogram, wich revealed dilated cardiomyopathy and severe systolic dysfunction. It´s added to her prevoiuos steroid treatment, furosemide, carvedilol, enalapril, methylprednisolone and cyclophosphamide. The patient has a satisfactory evolution, with decreased dyspnea and mild edema of the lower extremities, although it remains with altered values of creatinine. The patient is sent home and referred to early control. DISCUSSION: We propose that dilated cardiomyopathy is a rare complication of Systemic Lupus Erythematosus, and though we can say that it is the main explanation for the clinical picture of this patient, it does not explain by itself the symptomatology, considering the history of renal involvement.