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INTRODUCTION Pneumonia is the principal cause of death among children worldwide. Lung ultrasound (LUS) is a reliable tool for the diagnosis and assessment of community-acquired pneumonia in children. Furthermore, objective parameters, including the pneumonia LUS score, might be useful for pneumonia monitoring. Thus, our aim was to present a newly developed LUS score for pediatric pneumonia (PedPne) and evaluate its relationship with commonly assessed inflammatory markers. METHODS Children referred to the Pediatric Pneumology Clinic between September 2017 and February 2018 with suspected pneumonia were screened for eligibility for inclusion in the study and informed consent was obtained. In addition to clinical assessment, LUS was performed during consultation, and inflammatory biomarkers, including C-reactive protein level, erythrocyte sedimentation rate (ESR), and leukocyte count, were measured in all inpatients. An LUS score for pneumonia and pleurisy in children (pediatric pneumonia lung ultrasound score [PedPne LUS]) was subsequently developed. Chest radiography (CXR) was also performed according to local guidelines for pneumonia diagnosis. Spearman's correlation test was used to evaluate the correlation between the PedPne score and inflammatory markers. RESULTS A total of 217 patients were screened, of which 64 patients diagnosed with consolidated pneumonia were included in this study. The median PedPne LUS score of the included patients was 8.02, which was consistent with the consolidations detected on LUS and confirmed by CXR. A very strong positive correlation was found between the LUS PedPne score and C-reactive protein and ESR, and a good correlation was found with the leukocyte count. CONCLUSION The LUS pneumonia score is a reliable parameter for the evaluation of pneumonia, and shows a strong correlation with inflammatory biomarkers. The PedPne LUS score is a potential noninvasive surrogate parameter of inflammation in pediatric pneumonia.

Mihaela Dediu,1– 3 Ioana Mihaiela Ciuca,1– 3 Monica Steluta Marc,4 Estera Boeriu,1 Liviu Laurentiu Pop1 1Pediatric Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 2National Cystic Fibrosis Centre, Timisoara, Romania; 3“Pius Branzeu” County Hospital, Timisoara, Romania; 4Pulmonology Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, RomaniaCorrespondence: Ioana Mihaiela CiucaPediatric Department, University of Medicine and Pharmacy “Victor Babes”, Timisoara, RomaniaTel + 40 744 513 283Fax +40 356 494529Email ciuca.ioana@umft.roPurpose: The aim of this cross-sectional study was to identify the major factors influencing pulmonary function in CF patients from western side of Romania.Patients and Methods: The study enrolled 51 patients with CF between the ages of 6 and 27.8 years who were monitored at regular visits to the National Cystic Fibrosis Centre and Pius Branzeu County Hospital in Timisoara, Romania, over a period of 2 years. The relationships between lung function, as measured by forced expiratory volume in 1 s (FEV1), with patient age, sex, body mass index (BMI), pancreatic insufficiency (PI), microbial infection, CF-related diabetes (CFRD), CF-associated liver disease (CFLD), and physical activity < 30 min/day, were evaluated by multivariate regression analysis.Results: The results showed that FEV1 was 0.32% higher for each increase in percentile of BMI (95% confidence interval: 0.034– 0.619). In addition, mean FEV1 was 1.52% lower with every year rise of age. PI and female sex increased the risk of impaired lung function (FEV1 < 60%). The factors most closely correlated with pulmonary function in pediatric CF patients were current age (negative) and BMI (positive).Conclusion: The findings of this study, in combination with what is known from other studies in CF, suggest that a better nutritional status and infection prophylaxis should be part of a comprehensive clinical management strategy for pediatric CF in Romania.Keywords: cystic fibrosis, pediatric, respiratory disease, cystic fibrosis outcome

The deleterious effects of the coronavirus disease 2019 (COVID-19) pandemic urged the development of diagnostic tools to manage the spread of disease. Currently, the “gold standard” involves the use of quantitative real-time polymerase chain reaction (qRT-PCR) for SARS-CoV-2 detection. Even though it is sensitive, specific and applicable for large batches of samples, qRT-PCR is labour-intensive, time-consuming, requires trained personnel and is not available in remote settings. This review summarizes and compares the available strategies for COVID-19: serological testing, Point-of-Care Testing, nanotechnology-based approaches and biosensors. Last but not least, we address the advantages and limitations of these methods as well as perspectives in COVID-19 diagnostics. The effort is constantly focused on understanding the quickly changing landscape of available diagnostic testing of COVID-19 at the clinical levels and introducing reliable and rapid screening point of care testing. The last approach is key to aid the clinical decision-making process for infection control, enhancing an appropriate treatment strategy and prompt isolation of asymptomatic/mild cases. As a viable alternative, Point-of-Care Testing (POCT) is typically low-cost and user-friendly, hence harbouring tremendous potential for rapid COVID-19 diagnosis.

Background: Pneumonia is the leading cause of death among children, thus, a correct early diagnosis would be ideal. The imagistic diagnosis still uses chest X-ray (CXR), but lung ultrasound (LUS) proves to be reliable for pneumonia diagnosis. The aim of our study was to evaluate the sensitivity and specificity of LUS compared to CXR in consolidated pneumonia. Methods: Children with clinical suspicion of bacterial pneumonia were screened by LUS for pneumonia, followed by CXR. The agreement relation between LUS and CXR regarding the detection of consolidation was evaluated by Cohen’s kappa test. Results: A total of 128 patients with clinical suspicion of pneumonia were evaluated, 74 of them were confirmed by imagery and biological inflammatory markers. The highest frequency of pneumonia was in the 0–3 years age group (37.83%). Statistical estimation of the agreement between LUS and CXR in detection of the consolidation found an almost perfect agreement, with a Cohen’s kappa coefficient of K = 0.89 ± 0.04 SD, p = 0.000. Sensitivity of LUS was superior to CXR in detection of consolidations. Conclusion: Lung ultrasound is a reliable method for the detection of pneumonia consolidation in hospitalized children, with sensitivity and specificity superior to CXR. LUS should be used for rapid and safe evaluation of child pneumonia.

During the last 30 years the developments in small cell lung cancer (SCLC) have been extremely scarce. Concurrent chemo-radiation associated with prophylactic cranial irradiation in case of complete clinical remission is standard in limited disease. In extensive disease, platinum/etoposide and topotecan remain the standard systemic approaches in the first- and second-line setting, respectively. The only notable improvement was communicated in the IMpower133 trial, by the addition of atezolizumab to the platinum/etoposide chemotherapy backbone. Against this background, the current article aims to review the most important abstracts presented at ASCO 2019 along with their potential impact for current clinical practice.

CF is a polymorphic disease whose evolution is marked by pulmonary pathology. Distal obstruction, demonstrated anatomopathological, can be evidenced by spirometry, which can only be used in certain age groups. Early detection of obstruction with appropriate therapy is essential to prolong the life expectancy of these patients. A promising parameter has been described relatively recently, lung clearance index obtained by the multiple wash-out technique. Several studies have demonstrated its efficacy and correlation with pulmonary morphological changes, pointing out that LCI is a feasible and specific parameter to detect small-age lung changes in the CF patient. In conclusion, lung clearance index is a specific parameter for the detection of cystic fibrosis pneumopathy and is currently the standard way to monitor CF pneumopathy, and in future to be used in the current practice of CF centers.

Background First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

Cystic fibrosis related diabetes (CFRD) is a redoubtable complication associated to cystic fibrosis, with an increasing frequency, directly proportional to children life expectancy. Although this complication has similar features with DM type 1 and some with type 2, the evolution and even the response to insulin therapy is different. It is also possible that other factors to influence the CFRD clinical expression and subsequently the disease evolution. Since its 1t diagnosis was associated with more frequent pulmonary exacerbations and with the deterioration of the respiratory status, therefore CFRD must be early and correctly diagnosed and managed. The aim of this paper is to present an overview of the recent updates and recommendations regarding this important CF complication.

Despite the increasing numbers of young adults being diagnosed with aggressive forms ofpancreatic cancer, there is still insufficient data regarding the evolution patterns for early stagepredictors. However, a correct and timely diagnosis is of major importance in the management andthe outcome for pancreatic cancer patients.We are reporting the case of a 39 year old male whopresented to the emergency department on the Easter holiday evening with visible signs of jaundice,no abdominal pain and no history of disease. The patient was admitted due to inconclusiveparaclinical test results, the significantly elevated value of conjugated bilirubin being the onlysignaled abnormality. During the following two weeks, a number of basic and advanced imaginginvestigations were carried out due to insufficient information offered by the clinical andparaclinical investigations. During admission, EUS ( endoscopic ultrasonography) identifies animprecisely delimited hypoechoic mass, confirmed by MRCP (Magnetic Resonance Cholangio-Pancreatography) as an uncinate process nodule. The patient is informed about the pancreaticcancer diagnosis treatment options and prognosis. Surgical management of the uncinate processmass is decided and a Cephalic Pancreaticoduodenectomy (Traverso-Longmire) is performed withpara-aortic and para-caval lymphadenectomy. The patient is discharged 17 days postoperatively,without complications; due to the histopathological diagnosis of poorly differentiated pancreaticduct adenocarcinoma, the multidisciplinary oncological meeting set the indication for combinedchemotherapy and radiotherapy. Diagnosing pancreatic cancer in young adults without specificsymptoms or a prior condition is a challenging task, more so with the limited resources and meansof investigation in an emergency hospital. In conlusion, EUS had the highest sensibility whileMRCP had the highest specificity after normal endoscopy and inconclusive abdominalultrasonography and CT scan. Another predictor of probability for an uncinate process tumor isassociated with the high-low variations of direct bilirubin levels during antispasticity medication.

Background: Pneumonia is the leading cause of death among children worldwide. Lung ultrasound has been proven to be an accurate method for diagnosis and evolution monitoring in many diseases, including pneumonia. We aimed to evauate the relation between pneumonia dimensions on ultrasound and inflammation expressed by CRP. Methods: Patients addressed to the pediatric pulmolnology ward with clinical criteria for pneumonia were included in the study, after informed consent. Lung ultrasound was performed at admission, with 7-12 linear MHz probe and 3-5 MHz convex . LUS findings definiyng pneumonia were considered consolidations with aeric bronchogramme. The largest surface of the consolidation was measured at admission , after 3 and 7 days of treatment , concomitant with C reactive protein and ESR evaluation. Result: Pneumonia was diagnosed in 49 patients; with regard to the age distribution, the average age of patients was 4.49 years . The highest frequence of pneumonia was in the 0-3 years age group : 59.18% followed in descending order by the 3-6 years group with a frequency of 18.37% and 6-12 years with 14.29%; fewer teenagers had pneumonia 8,16%. The correlation between the pneumonia surface with CRP , in the day 3 was very high 0.97, maintained in the 7th day at 0.89 correlation coefficient . Conclusion: Lung ultrasound evaluation of the pneumonia surface is a good tool for evaluation of the disease`s evolution. A good correlation is between the measurement of the pneumonia evaluated by LUS and the serum level of CRP suggesting future use for LUS in pneumonia monitoring.

Background Faced with increasing illness burden and costs, healthcare systems are working towards integrated care to streamline services and improve efficiency, especially for chronic conditions. Routine care delivery data stored in various electronic healthcare databases (EHD) has the potential to support chronic care coordination if information is integrated and accessible at the point of care. Care delivery pathways (CDPs) can be constructed by linking multiple data sources and extracting time-stamped healthcare utilization events and other medical data related to individual or groups of patients over specific time periods; CDPs may facilitate communication on current practice and ways of improving it. We aim to identify and describe the methods proposed to quantify and visualize CDPs. Methods A literature search was performed in PubMed (MEDLINE), Scopus, IEEE, CINAHL and EMBASE, without date restrictions. We will describe CPDs methods from 3 perspectives relevant for EHD use in long-term care: (1) clinical (what clinical information is used and how was it considered relevant?), (2) data science (how was the method developed and implemented?), and (3) behavioral (which behaviors and interactions are promoted among users and how?). Data extraction will be performed via deductive content analysis using selected frameworks, and inductive analysis to identify additional relevant features. We will compare these characteristics to identify common, infrequent, or missing features, and extract recommendations for future initiatives. Results The literature search identified 2349 entries, currently under title and abstract selection by 4 coders. This study will produce a comparison and synthesis of clinical, data, and behavioral features of CDPs methods and derive recommendations for CDP construction. Conclusions This review works towards a common basis for visualizing and quantifying CDPs across healthcare systems, an essential prerequisite for interoperable digital health. Key messages Visual feedback on health care trajectories, especially for chronic conditions, may support informed decisions and planning future care episodes to advance towards person-centered integrated care. We describe and compare technical and clinical characteristics of visual feedback methods available for care pathways, and behaviors they may promote in care planning, to inform future initiatives.

Introduction Obstructive sleep apnea syndrome (OSAS) is defined by recurrent episodes of significant reduction or absence of the oro-nasal airflow during sleep, in the presence of thorax and abdominal movements and snoring. The pathophysiological consequences of intermittent hypoxia determined by OSAS are represented by systemic inflammation, the release of free oxygen radicals and activation of the sympathetic nervous system. Cardiac arrhythmias are a frequent comorbidity in patients with OSAS. Hypothesis We hypothesized that the continuous positive airway pressure (CPAP) therapy has an effect on inflammatory markers (erythrocyte sedimentation rate, fibrinogen, and red cell distribution width) in patients with OSAS and cardiac arrhythmias. Evaluation of the hypothesis We tested this hypothesis on 52 patients diagnosed with OSAS and cardiac arrhythmias, divided into two groups: group A (patients who received CPAP therapy and pharmacological therapy) and group B (only pharmacological therapy). The patients were evaluated at enrollment (T0), at 3 and 6 months. We did not find a statistically significant difference of erythrocyte sedimentation rate (ESR) and fibrinogen levels between the two groups. Regarding the red cell distribution width (RDW), the CPAP treatment seems to have improved the RDW values in patients who received this treatment. Also, in patients from group A, a significant decrease in the average heart rate was noticed after 3 months. Consequences Fibrinogen and ESR cannot be used for monitoring the CPAP therapy in patients with OSAS and arrhythmias. Instead, the beneficial effect of CPAP in patients with OSAS and cardiac arrhythmias can be monitored with the help of the RDW, which could also be used for evaluating the cardiovascular risk in patients with OSAS and arrhythmias.

Study aimed to assess the level of 25-OH-cholecalciferol(vitamin D) and the relation with cholesterol, proteins and glycaemia levels in patients with cystic fibrosis. 58 patients underwent for the annual evaluations and were tested for vitamin D deficiency, as the centre�s protocol requires, besides dosage of cholesterol, glycaemia and proteins levels. Serum levels of 25-hydroxycholecalciferol were compared to levels of cholesterol, proteins and glycaemia, using Pearson correlation and logistic regression. The average value of 25-OH-cholecalciferol was 22,9 ng/mL, suggesting an important deficiency and different stages of 25-OH-cholecalciferol deficiency was found in the majority of patients. Nor a positive correlation neither negative relationship was found between vitamin D and cholesterol (r=0,23), glycaemia or proteins level. Vitamin D levels are not related to cholesterol or proteins in our study. Although cystic fibrosis is characterised by liposoluble vitamins deficiency and lipids impaired digestion, other factors influence the seric levels of vitamin D and lipids.

Objectives Patritumab is a fully human anti-human epidermal growth factor receptor 3 (HER3) antibody that blocks activation by its ligand, heregulin (HRG). Preclinical studies have demonstrated the efficacy of patritumab in aberrantly high HRG-expressing non-small cell lung cancer (NSCLC). In the phase II randomized, placebo-controlled double-blind study HERALD ( n =212 patients with NSCLC), patritumab plus erlotinib did not improve progression-free survival (PFS) compared with placebo plus erlotinib. The current study examined whether soluble HRG (sHRG) level in serum correlated with the efficacy of patritumab plus erlotinib. Materials and methods Serum was obtained from participants prior to treatment ( n =202). sHRG level was measured using a validated quantitative immune assay, and correlations with survival were blindly assessed. Results sHRG level was various (−1346–11,772pg/mL). Participants were divided into the sHRG-high or -low subgroups at the concentration defining near the third quartile, 980pg/mL. Patritumab plus erlotinib significantly improved PFS relative to placebo in the sHRG-high subgroup ( n =46, hazard ratio 0.42 [0.19–0.96], p =0.0327). In contrast, the HRG-low subgroup ( n =148) had no improvement in PFS with patritumab. Conclusion sHRG seems to be a predictive biomarker for the efficacy of patritumab plus erlotinib in NSCLC patients.

Summary This article is not intended to be a comprehensive review of all highlights presented at the recent ESMO Annual Meeting, but rather a summary from a personal point of view in three very different fields of oncology. Breast cancer and lung cancer are traditionally in the focus of interest, and again, relevant new data were presented. The third part of this overview is focused on novel treatment strategies in malignant lymphoma, a field that is also quickly evolving and traditionally underrepresented at meetings dealing with solid cancers.

Background: Necitumumab is a second-generation, recombinant, human immunoglobulin G1 EGFR antibody. In this study, we aimed to compare treatment with necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone in patients with previously untreated stage IV squamous non-small-cell lung cancer. Methods: We did this open-label, randomised phase 3 study at 184 investigative sites in 26 countries. Patients aged 18 years or older with histologically or cytologically confirmed stage IV squamous non-small-cell lung cancer, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and adequate organ function and who had not received previous chemotherapy for their disease were eligible for inclusion. Enrolled patients were randomly assigned centrally 1:1 to a maximum of six 3-week cycles of gemcitabine and cisplastin chemotherapy with or without necitumumab according to a block randomisation scheme (block size of four) by a telephone-based interactive voice response system or interactive web response system. Chemotherapy was gemcitabine 1250 mg/m2 administered intravenously over 30 min on days 1 and 8 of a 3-week cycle and cisplatin 75 mg/m2 administered intravenously over 120 min on day 1 of a 3-week cycle. Necitumumab 800 mg, administered intravenously over a minimum of 50 min on days 1 and 8, was continued after the end of chemotherapy until disease progression or intolerable toxic side-effects occurred. Randomisation was stratified by ECOG performance status and geographical region. Neither physicians nor patients were masked to group assignment because of the expected occurrence of acne-like rash-a class effect of EGFR antibodies-that would have unmasked most patients and investigators to treatment. The primary endpoint was overall survival, analysed by intention to treat. We report the final clinical analysis. This study is registered with ClinicalTrials.gov, number NCT00981058. Findings: Between Jan 7, 2010, and Feb 22, 2012, we enrolled 1093 patients and randomly assigned them to receive necitumumab plus gemcitabine and cisplatin (n=545) or gemcitabine and cisplatin (n=548). Overall survival was significantly longer in the necitumumab plus gemcitabine and cisplatin group than in the gemcitabine and cisplatin alone group (median 11·5 months [95% CI 10·4-12·6]) vs 9·9 months [8·9-11·1]; stratified hazard ratio 0·84 [95% CI 0·74-0·96; p=0·01]). In the necitumumab plus gemcitabine and cisplatin group, the number of patients with at least one grade 3 or worse adverse event was higher (388 [72%] of 538 patients) than in the gemcitabine and cisplatin group (333 [62%] of 541), as was the incidence of serious adverse events (257 [48%] of 538 patients vs 203 [38%] of 541). More patients in the necitumumab plus gemcitabine and cisplatin group had grade 3-4 hypomagnesaemia (47 [9%] of 538 patients in the necitumumab plus gemcitabine and cisplatin group vs six [1%] of 541 in the gemcitabine and cisplatin group) and grade 3 rash (20 [4%] vs one [

Vitamin K antagonists represented for more than 50 years the only oral anticoagulant treatment option, though encumbered by numerous food and drug interactions, with direct impact on the safety and efficacy of this treatment. The frequent complications of anticoagulant treatment with vitamin K antagonists led to the need for the emergence of new oral anticoagulants (NOAC). The main NOACs used today are dabigatran, rivaroxaban and apixaban. NOAC have a number of advantages over antivitamin K anticoagulants: fewer drug interactions, no food interactions, rapid onset of the anticoagulant action, rapid clearance, no need for INR monitoring. NOAC therapy must be individualized according to patient age, comorbidities and medical history, renal function, concomitant medications. Given that clinical experience with NOAC is still limited in practice, physicians (including family physicians) must monitor these patients and need to pay attention and report any side effects.

Arterial hypertension is an important risk factor for cardiovascular morbidity and mortality, with increasing incidence and prevalence. Diagnosis of resistant hypertension may be established when the values of blood pressure are ≥ 140/90 mmHg, despite lifestyle changes and treatment with three antihypertensive drugs from different therapeutic classes, one being a diuretic. One common comorbidity in patients with resistant hypertension is obstructive sleep apnea. Obesity, defined as a body mass index ≥ 30 kg/m2, is a common risk factor linking the obstructive sleep apnea syndrome (OSAS) with resistant hypertension. The diagnosis of OSAS in patients with resistant hypertension is made by polysomnography. For the confirmation of diagnosis of resistant hypertension it is necessary the ambulatory blood pressure monitoring, which allows the exclusion of false cases of resistant hypertension, white coat or masked hypertension. Treatment of OSAS with CPAP (continuos positive airway pressure) offers improvement of blood pressure values and better control of resistant hypertension, reducing the cardiovascular risk.

Background: An important percentage of CF patients associates structural lung damages associated with impaired lung function. Lung ultrasound (LUS) can detect structural features like emphysema, consolidation, interstitial inflammation or bronchiectasis while the most accurate parameter of the lung function in cystic fibrosis is the lung clearance index(LCI), therefore it would be important to evaluate the relation between the two parameters. Aim: To evaluate the relation between LUS score and lung function expressed by LCI among children with CF. Methods: Forty-two children with CF (mean age 13.93± 5.1years) who underwent the annual lung function assessment of LCI, were also evaluated by LUS. Specific characteristics on ultrasound were used for LUS score: presence of B-lines for interstitial damage cylindrical bronchiectasis and air trapping, lake sign for detection of varicose bronchiectasis or cystic bronchiectasis, parenchymal structure for consolidation. Of these, 15 patients (53.3% girls) performed a reproductible LCI. The relation between LCI as a constant and the LUS score was evaluated with Pearson correlation test. Results: At LUS, air trapping was the most frequent feature detected in 79.6% of patients and the median value of LCI was 16.53+-7.6. A median LUS score of 4.67+-3, consistent for moderate morphological lung impairment was found. LCI showed a strong positive correlation with the LUS score, with coefficient of 0.82, p Conclusion: In our study an important correlation, statistically significant, between lung damage evaluated by a LUS score and the lung clearance index was demonstrated. LUS score might be used for a primary evaluation of the CF lung damages.

Many analyses of the efficacy of neoadjuvant treatment (NAT) for early breast cancer including a meta-analysis derived from 10 randomized trials came to the conclusion that patients who would achieve pathologic complete response (pCR) following NAT would experience significant improvement in disease-free and overall survival (OS). Thus, pCR was proposed as a surrogate endpoint for OS, with pCR representing a robust prognostic marker for survival at an individual level. In the current analysis, we argue that OS following NAT-induced pCR might have reflected the initial prognosis of patients mainly defined – among other factors – by the initial pathological lymph node status while being largely independent on the type of administrated treatment, thus pleading against the pCR surrogacy hypothesis. We therefore propose to redefine pCR as a surrogate endpoint of NAT trials by the involvement of additional biologic parameters.

Purpose In the phase III PARAMOUNT trial, pemetrexed continuation maintenance therapy reduced the risk of disease progression versus placebo (hazard ratio [HR], 0.62; 95% CI, 0.49 to 0.79; P < .001). Here we report final overall survival (OS) and updated safety data. Patients and Methods In all, 939 patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) received four cycles of pemetrexed-cisplatin induction therapy; then, 539 patients with no disease progression and Eastern Cooperative Oncology Group performance status 0 or 1 were randomly assigned (2:1) to maintenance pemetrexed (500 mg/m2 on day 1 of 21-day cycles; n = 359) or placebo (n = 180). Log-rank test compared OS between arms as measured from random assignment (α = .0498). Results The mean number of maintenance cycles was 7.9 (range, one to 44) for pemetrexed and 5.0 (range, one to 38) for placebo. After 397 deaths (pemetrexed, 71%; placebo, 78%) and a median follow-up of 24.3 months for alive patients (95% CI, 23.2 to 25.1 months), pemetrexed therapy resulted in a statistically significant 22% reduction in the risk of death (HR, 0.78; 95% CI, 0.64 to 0.96; P = .0195; median OS: pemetrexed, 13.9 months; placebo, 11.0 months). Survival on pemetrexed was consistently improved for all patient subgroups, including induction response: complete/partial responders (n = 234) OS HR, 0.81; 95% CI, 0.59 to 1.11 and stable disease (n = 285) OS HR, 0.76; 95% CI, 0.57 to 1.01). Postdiscontinuation therapy use was similar: pemetrexed, 64%; placebo, 72%. No new safety findings emerged. Drug-related grade 3 to 4 anemia, fatigue, and neutropenia were significantly higher in pemetrexed-treated patients. Conclusion Pemetrexed continuation maintenance therapy is well-tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy.

Peripheral arterial disease (PAD) is a consequence of the atherosclerosis of large arteries located distal to aortic arch. The most common symptom is intermittent claudication. The most commonly used screening tool of BAP in primary care is the ankle-brachial index (ABI), especially recommended for patients older than 70 years or between 50-69 years, if they are diabetics or smokers. Management of PAD include smoking cessation, exercise, treatment with statins, antiplatelet therapy with aspirin and clopidogrel, possibly cilostazol in patients without heart failure. Surgery is recommended for patients who do not respond to drug therapy.

Rheumatoid arthritis (RA) is a chronic, progressive, destructive and deforming arthropathy, characterized by symmetrical erosive synovitis and multisystemic injury. Despite the progresses of pharmacological therapy for RA, many patients continue to have active disease with the risk of developing disability. A number of non-pharmacological therapies are used in addition to the regular treatment of RA. On October 7th, 2008, American Physical Activity guidelines were released, based on the latest physical activity techniques, with impact on the health of people with arthritis, grouped under the acronym SMART. A comprehensive management program for RA includes patient education, psycho-social interventions, adequate rest, exercise, physical and occupational therapy, nutritional and dietetics counseling, interventions to reduce the risk of cardiovascular diseases, osteoporosis and immunizations to reduce the risk of complications from immunosuppressive treatment. The objectives of this program are: disease stabilization, preventing deviations, deformities and ankylosis, combating retractions and stiffness, partial or complete restoration of motor functional capacity of patients. For achieving these goals, the treatment must adhere to the following general conditions: to be initiated early, to be continuous and complex. In conclusion, education and counseling of the patient are important for the management of RA. The physicians should explain to the patient all the treatment options and develop with him a longitudinal treatment plan, which includes the association of the pharmacological therapy with the non-pharmacological one.

Antiphospholipid syndrome is an acquired autoimmune disease characterized by the appearance of thrombosis (venous, arterial and microvascular) and/or complications during pregnancy, in the presence of antiphospholipid antibodies. The clinical spectrum of the disease is now more complex and include organ-specific and systemic symptoms induced not only by thrombotic mechanisms, but also immune-mediated. Patients diagnosed with antiphospholipid syndrome should be evaluated clinically and laboratory periodically to detect lung damage, cardiac, neurological, skin, eye, hematological, gastrointestinal complications.

Background Cystic fibrosis (CF) is the most frequent monogenic autosomal recessive disease with lethal potential, manifested by a great clinical polymorphism. Cystic fibrosis associated liver disease(CFLD) is the second non-pulmonary cause of death in cystic fibrosis, witch, beside pulmonary disease, became on of the most important management issue. Lung function and CFLD is influenced by the nutritional status, being well known that a positive correlation between increase body mass index (BMI) and respiratory disease exists; therefore the effect of the nutritional grade would be important to be assessed. Objectives The aim of this study is to evaluate the effect of the nutritional status on the cystic fibrosis associated liver disease-CFLD evolution. Methods Study included fifty-nine patients with cystic fibrosis prospectively monitored for seven years. They were routinely followed-up by clinical assessment, liver biochemical tests, ultrasound examinations and in several cases elastography. CFLD was diagnosed using ECFS criteria. All patients with CFLD received ursodeoxycholic acid and enzymes supplementation according to our guideline. Body mass index was used to evaluate the nutritional status expressed by percentages and z -scores. Results 62.7% were diagnosed with CFLD and weight deficit, without significant gender gap. About 7% of patients leave the study. Underweighted children associated various vitamins deficiency and the reduced BMI was a significant risk factor for the development of CF severe liver disease (p Conclusion Most of our children with cystic fibrosis liver disease associated an important percent of weight deficit. If the malabsorbtion is the main cause of poor nutritional status or if other features like CF liver disease are more important remain to be studied in the future. The eternal question of’ the egg or hen’ as CFLD associates low BMI or if the weight deficit determine the CFLD rate is still disputable. Further measures should be taken for the improvement of nutrition of the CF children and the prolongation of a good life for these cystic fibrosis children.

Background Cystic fibrosis (CF) is an inherited genetic disorder, clinical characterised by respiratory failure due to chronic pulmonary infection and pancreatic insufficiency. Malabsorption of fat-soluble vitamin leads to low level of vitamin A, D, E and K. It is already well know how vitamin D influences the immune response. Recent studies show the role of vitamin D on lung function in patients with cystic fibrosis. Aim to evaluate the correlation between vitamin D level and pulmonary function in cystic fibrosis’s children. Methods We design an observational study based on the evaluation of 59 children with cystic fibrosis. Biochemical assessment of every patient included dosage of 25-OH cholecalciferol levels, not related to season. Deficiency was defined as vitamin D level Results From fifty-nine patients, 56.6% of patients performed spirometry, of which 56.6% had vitamin D level determined. The majority of our patients (92.3%) had low levels of vitamin D, almost one third (23.0%) having severe deficiency of vitamin D. Comparing Vitamin D level with FEV1 we obtained an insignificant statistic correlation (p>0.05) and the correlation coefficient was r=−0.016, FVC: r=0.16 and for FEF25-75: r=−0.06. Conclusions In our study group an important percentage of vitamin D deficiency was found, despite regular vitamin supplementation. No statistical correlation was found between vitamin D level and spirometry results. A part of patient’s with ventilatory dysfunction had severe deficiency in vit. D. Measure must be instituted for an increase vit. D supplementation and subsequent improvement of lung function in our patients.

Background Pulmonary inflammation is a major cause of decline in lung function in patients with cystic fibrosis and acute exacerbations may occur therefore slowing evolution of lung disease is a primary aim of CF therapy may precede the onset of chronic infection. Methods An observational, cross-sectional transversal study including fifty seven patients evaluated the influence of factors potentially influent on the pulmonary function in CF patients. The correlation of specific parameters like age, gender, nutritional status, CF related diabetes (CFRD), CF associated liver disease (CFLD), with the lung function expressed by FEV1 were studied. Multiple linear regression analysis was performed using FEV1 as a dependent variable and the following variables of interest: age, age-at-diagnosis, BMI, sex, pancreatic insufficiency, microbial infection, CFLD, CFRD as independent variables. Results The correlation of the lung function, expressed by FEV1, was positive with BMI, every increase with a unit of BMI associated an increase of the FEV1 percentage with a mean value of 5.447 (95% CI 1.892; 9.002). The mean value of FEV1% decreased with 1.474 (95% CI −2.868; −0.080) for every increase unit increase in the patients age. With a stepwise multiple regression we obtained a significant model (p Conclusions The most important negative influence on the pulmonary status in our CF patients had the age, female sex and the MRSA colonisation, while the positive effect of enhanced BMI on the lung function was registered, as expected.

Background Hyperthermia is one of the most frequent causes of a child presentation to the paediatrician. Children with know chronic pneumopathies are likely to develop acute infectious exacerbations, like others. The aim paper presents the case of 9 years old boy with cystic fibrosis with hemoptysis and hyperthermia in the New Years Eve. Methods Patient was diagnosed with cystic fibrosis in infancy with f 508 del homozygous genotype and is known with Staphylococcus aureus chronic pulmonary infection. He was on chronic ciprofloxacin treatment and started to have fever. Results The initial supposition was a new exacerbation with Staphyloccocus or a new emergent pathogen, like Pseudomonas. Therefore he was admitted in the cystic fibrosis department and started the i.v. treatment with meropenem; unfortunately he continued to have fever and investigations revealed a minor inflammatory syndrome. Sputum samples were taken and during the evolution he continues to be febrile and developed mucosal candidiasis. Afyer 4 days of meronem, we constated the presence of granular lesions around Stenon canal, the IgM for measles was detected positive and exanthema appeared after 7 days. Conclusion Not every fever or hemoptysis in a child with cystic fibrosis signifies an exacerbation. During a viral epidemic wave we have to think of child exposure risk, especially in patients with chronic pathologies.

SUMMARY Pemetrexed, a multitargeted antifolate agent, is currently used in the treatment of non-small-cell lung cancer. Strong evidence has shown a treatment-by-histology interaction, with pemetrexed acting significantly better in the nonsquamous cell subtype. Therefore, all pemetrexed indications are restricted to this histology. Associated initially with somewhat high toxicity, the use of vitamin supplementation and corticoid premedication turned pemetrexed into one of the most convenient chemotherapy agents. At present pemetrexed is recommended as one of the preferred platinum partners in first line and as a single agent in the second-line setting for nonsquamous histology. The particular efficacy/toxicity profile has confirmed pemetrexed as the only chemotherapy agent approved for both continuation and switch maintenance therapy.

MRI is currently the method of choice to evaluate brain maturation. MRI provides improved anatomical details and accurate depiction of the morphological and signal changes of normal brain development and its disorders. It also gives insight into the microstructure of brain tissue and into mechanisms of injury through diffusion-weighted imaging and diffusion-tensor imaging, and into the brain’s biochemical composition through proton MR spectroscopy. Computational automated techniques are emerging that help to generate a 3D fetal atlas by motion-corrected high resolution images, to more precisely identify volumetric brain growth, cortical folding over gestational age and white matter organization. Validations by clinical studies are still needed, especially in applying the computational methods in the different groups of pathology encountered in the pre- and neo-natal periods.

Achieving an efficient fixation for complicated fractures and scaffold application treatments is a challenging surgery problem. Although many fixation approaches have been advanced and actively pursued, the optimal solution for long bone defects has not yet been defined. This paper promotes an innovative fixation method based on application of magnetic forces.The efficiency of this approach was investigated on the basis of finite element modeling for scaffold application and analytical calculations for diaphyseal fractures. Three different configurations have been analyzed including combinations of small cylindrical permanent magnets or stainless steel rods, inserted rigidly in the bone intramedullary canals and in the scaffold. It was shown that attractive forces as high as 75N can be achieved. While these forces do not reach the strength of mechanical forces in traditional fixators, the employment of magnetic rods is expected to be beneficial by reducing considerably the interface micromotions. It can additionally support magneto-mechanical stimulations as well as enabling a magnetically assisted targeted delivery of drugs and other bio-agents. Display Omitted An innovative magnetic fixation method is proposed for orthopedics.Magnetic rods can be used for long bone and scaffold fixation.Magnetic configurations, compatible with real patient cases, were analyzed.Magnetic fixation forces can achieve values as high as 75N.Magnetic fixation can reduce the interface micromotions and provide bone stimulation.

IntroductionIn the PARAMOUNT (“A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed plus Best Supportive Care vs. Best Supportive Care Immediately Following Induction Treatment with Pemetrexed Plus Cisplatin for Advanced Non-Squamous Non–Small-Cell Lung Cancer”) trial, patients with advanced nonsquamous non–small-cell lung cancer (NS-NSCLC) benefited from pemetrexed maintenance therapy after induction therapy with pemetrexed and cisplatin by extending survival, delaying disease progression, and maintaining quality of life (QoL). However, low-grade 1 or 2 toxicities during long-term maintenance treatment may become burdensome and impact QoL.Materials and MethodsPatients in this double-blind study (n = 539), who had completed 4 induction cycles (pemetrexed with cisplatin) without progressive disease (PD) and had an ECOG performance status of 0/1, were randomized 2:1 to pemetrexed maintenance (500 mg/m2, day 1) plus best supportive care (BSC) or placebo plus BSC until PD. Adverse events (by maximum Common Terminology Criteria for Adverse Events [CTCAE] grade) and QoL (EuroQol 5-dimensional [EQ-5D] scale) were assessed.ResultsA median of 4 maintenance cycles was administered (range, pemetrexed 1-44; mean ± SD 7.9 ± 8.3; placebo 1-38; mean ± SD 5.0 ± 5.2), with 28% of pemetrexed and 12% of placebo patients receiving ≥ 10 maintenance cycles. The pemetrexed dose intensity was 94%. More patients receiving pemetrexed (12%) than placebo discontinued because of possible drug-related CTCAEs (4%; P = .005). Overall, pemetrexed was associated with significantly more (P < .05) low-grade events (grade 1/2 nausea, grade 2 anemia, edema, and neutropenia) than placebo. Overall, the incidence of low-grade fatigue, anemia, and neutropenia decreased with long-term pemetrexed exposure; however, renal events increased across treatment arms. EQ-5D analyses demonstrated no treatment-by-time interaction or overall treatment differences between the 2 arms.ConclusionPARAMOUNT demonstrated a low incidence of low-grade toxicities with long-term pemetrexed exposure without compromising QoL in patients with NS-NSCLC.

Introduction Necitumumab, a second-generation, recombinant human immunoglobulin G1 epidermal growth factor receptor antibody in the phase 3 SQUIRE trial (NCT00981058), increased survival benefit for patients randomized to receive necitumumab plus gemcitabine-cisplatin compared with those who received gemcitabine-cisplatin. Here we characterize health-related quality of life (HRQoL) and tolerability results. Methods A total of 1093 patients with stage IV squamous non–small cell lung cancer were randomized 1:1 to receive necitumumab (800 mg absolute dose intravenously [IV]) plus gemcitabine-cisplatin (gemcitabine = 1250 mg/m 2 IV on days 1 and 8; cisplatin = 75 mg/m 2 IV on day 1) or gemcitabine-cisplatin alone (every 21 days) for up to six cycles. Patients receiving necitumumab plus gemcitabine-cisplatin without disease progression continued necitumumab until progression. HRQoL was measured by Eastern Cooperative Oncology Group performance status, the Lung Cancer Symptom Scale (LCSS), and the European Quality of Life Five-Dimensions questionnaire. Efficacy and LCSS outcomes were analyzed using the baseline maximum severity score of the LCSS. Tolerability was measured in terms of exposure to the study treatment and adverse events. Hospitalization rates were collected. Results Most patients in both study arms similarly maintained Eastern Cooperative Oncology Group performance status and comparable LCSS and European Quality of Life Five-Dimensions questionnaire assessments. Patients with a higher baseline LCSS had a greater survival benefit on the necitumumab arm. Chemotherapy exposure was similar in both treatment arms; 51% of patients on the necitumumab plus gemcitabine-cisplatin arm continued on single-agent necitumumab. The most frequent grade 4 adverse events were neutropenia (6.1% versus 7.9%) and thrombocytopenia (3.2% versus 4.3%) in the necitumumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin arms, respectively. Hospitalizations were slightly higher with necitumumab plus gemcitabine-cisplatin (36.4%) than with gemcitabine-cisplatin (34.0%). Conclusions The addition of necitumumab to gemcitabine-cisplatin was well tolerated, did not negatively affect HRQoL or toxicity, and particularly benefited patients with more severe baseline symptoms or lower HRQoL.

Contains fulltext : 157590.pdf (Publisher’s version ) (Closed access) Do individuals differ in how efficiently they process non-native sounds? To what extent do these differences relate to individual variability in sound-learning aptitude? We addressed these questions by assessing the sound-learning abilities of Dutch native speakers as they were trained on non-native tone contrasts. We used fMRI repetition suppression to the non-native tones to measure participants' neuronal processing efficiency before and after training. Although all participants improved in tone identification with training, there was large individual variability in learning performance. A repetition suppression effect to tone was found in the bilateral inferior frontal gyri (IFGs) before training. No whole-brain effect was found after training; a region-of-interest analysis, however, showed that, after training, repetition suppression to tone in the left IFG correlated positively with learning. That is, individuals who were better in learning the non-native tones showed larger repetition suppression in this area. Crucially, this was true even before training. These findings add to existing evidence that the left IFG plays an important role in sound learning and indicate that individual differences in learning aptitude stem from differences in the neuronal efficiency with which non-native sounds are processed. 15 p.

Background Recombinant granulocyte colony-stimulating factors such as Neupogen are used to treat chemotherapy-induced neutropenia. The aim of the study was to show that a new granulocyte colony-stimulating factor, XM02, is as safe and effective as Neupogen in the treatment of chemotherapy-induced neutropenia in patients with small cell or non-small cell lung cancer. Patients and methods A total of 240 patients receiving platinum-based chemotherapy were randomized in cycle 1 to treatment with daily injections (subcutaneous 5 µg/kg/d) of XM02 ( n = 160) or Filgrastim Neupogen ( n = 80) for at least 5 days and a maximum of 14 days. In subsequent cycles, all patients received XM02. Results The mean duration of severe neutropenia was 0.5 and 0.3 days in cycle 1 for XM02 and Filgrastim, respectively. In the analysis of covariance for duration of severe neutropenia in cycle 1, the estimated treatment difference "XM02 minus Filgrastim" was 0.157 days, with 95% confidence level (−0.114 days, 0.428 days), which was included in the prespecified equivalence range (−1, 1). There was no statistically significant difference of the end point incidence of febrile neutropenia in cycle 1 between XM02 and Filgrastim ( p = 0.2347). The adverse event profile was similar between XM02 and Filgrastim. Conclusion XM02 demonstrated similar efficacy and safety profile as the reference medication Filgrastim in cycle 1. In conclusion, treatment with XM02 is beneficial in ameliorating severe neutropenia and febrile neutropenia in lung cancer patients receiving myelosuppressive chemotherapy. XM02 is safe and well tolerated in the doses applied in this study.

For lung cancer, the TNM staging system included atelectasis (At) as a negative prognostic factor, within the T category. However, according to our clinical experience, we observed the opposite. The aim of the study was to evaluate the influence of At on patient outcome for unresectable stage III and IV non-small cell lung cancer (NSCLC).We prospectively evaluated the patient survival data, in correlation with the presence, At(+), or absence, At(-), of At. A distinct analysis according to stage was preplanned. Univariate and multivariate analysis were performed to refine the prognostic significance of At.We evaluated 1352 consecutively treated patients, during 1997-2004. Sixty-eight patients (5%) were identified with At, of which 46/592 (8%) were in stage III, and 22/760 (3%) were in stage IV. The survival data were significantly better for patients At(+) vs. At(-); median overall survival (OS): 21 months (95% confidence interval [CI], 12.37-29.63) vs. 10 months (95% CI, 9.25-10.75) (p0.001), and median progression free survival (PFS):17 months (95% CI, 11.71-22.29) vs. 7 months (95% CI, 6.48-7.52) (p0.001). The most consistent difference, favoring patients At(+), was noted for patients in stage III, with OS: 24 months (95% CI, 18.65-29.35) vs. 14 months (95% CI, 12.43-15.57) (p0.001), and PFS: 19 months (95% CI, 12.11-25.89) vs. 8 months (95% CI, 6.89-9.02) (p0.001). In stage IV, we noted a non-significant trend toward improved survival in patients At(+); OS: 16 months (95% CI, 4.49-27.51) vs. 9 months (95% CI, 8.51-9.49) (p=0.21), and PFS: 8 months (95% CI, 5.80-10.20) vs. 6 months (95% CI, 5.36-6.64) (p=0.12). The multivariate analysis showed that At, stage and ECOG performance status were independent predictors for survival.At predicts a better survival in patients with advanced NSCLC. The prognostic value is more stringent for stage III patients. Inclusion of At as a negative prognostic factor in the TNM staging system warrants further evaluation.