Transcutaneous electromyography as a tool to assess recovery of hemidiaphragmatic paresis: A case report.

In this case report, we describe two repeated transcutaneous electromyography of the diaphragm (dEMG) measurements in an infant with suspected paresis of the right hemidiaphragm after cardiac surgery. The first measurement, performed at the time of diagnosis, showed a lower electrical activity of the right side of the diaphragm in comparison with the left side. The second measurement, performed after a period of expectative management, showed that electrical activity of the affected side had increased and was similar to the activity of the left diaphragm. This finding was accompanied by an improvement in the clinical condition. In conclusion, repeated measurement of diaphragmatic activity using transcutaneous dEMG enables the observation and quantification of spontaneous recovery over time. This information may assist the clinician in identifying patients not responding to expectative management and in determining the optimal timing of diaphragmatic surgery.

Volatile organic breath components and exercise induced bronchoconstriction in asthmatic children.

INTRODUCTION: Asthma is one of the most common chronic diseases in childhood and is generally characterized by exercise induced bronchoconstriction (EIB). Assessing EIB is time consuming and expensive as it requires a fully equipped pulmonary function laboratory. Analysis of volatile organic compounds (VOCs) in breath is a novel technique for examining biomarkers which may associate with asthma features. The aim of this pilot study was to identify potential markers in the relationship between EIB and VOCs. METHODS: Children between four and 14 years old were asked to provide a breath sample prior to undergoing an exercise challenge test to assess for EIB. RESULTS: Breath samples were collected and analyzed in 46 asthmatic children, 21 with EIB and 25 without EIB (NO-EIB). Molecular features (MFs) were not significantly different between EIB and NO-EIB controls. 29 of the 46 children were corticosteroid naïve, 10 with EIB and 13 without. In the corticosteroid naïve group EIB was associated with increased MF23 and MF14 in the lower breath sample (p-value < 0.05). CONCLUSION: This pilot study shows that EIB was related to an increased MF14 and MF23 in corticosteroid naïve children. The tentative identities of these compounds are octanal and dodecane/tetradecane respectively. These candidate biomarkers have a potential to enable non-invasive diagnosis of EIB in steroid-naïve children. Trial registration This study is registered in the Netherlands trial register (trial no. NL6087) at 14 February 2017.

Prospective Evaluation of a Circulating Tumor Cell Sensitivity Profile to Predict Response to Cisplatin Chemotherapy in Metastatic Breast Cancer Patients.

BACKGROUND: Cisplatin (cDDP) has regained interest for metastatic breast cancer (MBC) patients, given the platinum sensitivity in subtypes and better manageable toxicity. Here, the primary aim was to determine whether molecular characteristics of circulating tumor cells (CTCs) could identify patients responding to cDDP and to describe the outcomes to cDDP monotherapy in a large group of MBC patients pretreated with anthracycline- and taxane-based treatments. METHODS: Based on cell line data, a CTC-cDDP-sensitivity profile was generated. Applying an A'Herns single-stage phase II design, further investigation was considered worthwhile if 5/10 patients with a favorable profile responded to cDDP. Patients received 70mg/m2 cDDP every three weeks, CTCs were enumerated and the CTC-cDDP-sensitivity profile was determined. In total, 65 heavily pretreated MBC patients (77% received ≥2 lines of previous chemotherapy for MBC) were eligible for the per-protocol analysis. Primary endpoint was response rate, secondary endpoints included best observed response, progression-free survival (PFS) and overall survival (OS). RESULTS: The best observed response during cDDP therapy was a partial response in 7% and stable disease in 56% of the patients. None of the patients with a favorable CTC-cDDP-sensitivity profile had a response. The median baseline CTC count was 8 (range 0-3254). Patients with <5 CTCs had a better PFS and OS than patients with ≥5 CTCs (median PFS 4.5 months (95%CI 2.38-6.62) vs. 2.1 months [(95%CI 1.34-2.80)(p=0.009)] and median OS 13.1 months (95%CI 9.89-16.33) vs. 5.6 months [(95%CI 3.60-7.64)(p=0.003)]. No other factors than CTC count were associated with outcome to cDDP therapy, including triple-negative breast cancer versus ER-positive tumors. CONCLUSIONS: The CTC-cDDP-sensitivity profile was unable to select patients responding to cDDP monotherapy. In an unselected group of heavily pretreated MBC patients, cDDP yields outcomes comparable to other chemotherapeutic regimens for heavily pretreated MBC patients. CTC count was the only factor associated with outcome in these patients. CLINICAL TRIAL REGISTRATION: (https://www.trialregister.nl/trial/3885, identifier NTR4046).

WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

Using a quality of life (QoL)-monitor: preliminary results of a randomized trial in Dutch patients with early breast cancer.

PURPOSE: The diagnosis and treatment of cancer negatively affect patients' physical, functional and psychological wellbeing. Patients' needs for care cannot be addressed unless they are recognized by healthcare providers (HCPs). The use of quality of life (QoL) assessments with feedback to HCPs might facilitate the identification and discussion of QoL-topics. METHODS: 113 patients with stage I-IIIB breast cancer treated with chemotherapy were included in this randomized controlled trial. Patients were randomly allocated to receive either usual care, or usual care with an intervention consisting of a QoL-monitor assessing QoL, distress and care needs before every chemotherapy cycle visit. Patients completed questionnaires regarding QoL, illness perceptions, self-efficacy, and satisfaction with communication. From the 2nd visit onwards, patients in the intervention arm and their HCPs received a copy of the QoL overview and results were shown in patients' medical files. Audio-recordings and patients' self-reports were used to investigate effects on communication, patient management and patient-wellbeing. A composite score for communication was calculated by summing the number of QoL-topics discussed during each consultation. RESULTS: Use of the QoL-monitor resulted in a higher communication score (0.7 topics increase per visit, p = 0.04), especially regarding the disease-specific and psychosocial issues (p < 0.01). There were no differences in patient management, QoL, illness perceptions or distress. Patients in the experimental arm (n = 60) had higher scores on satisfaction with communication (p < 0.05). CONCLUSIONS: Use of a QoL-monitor during chemotherapy in patients with early breast cancer might result in a more frequent discussion of QoL-topics, associated with high levels of patients' satisfaction.

Processing transcutaneous electromyography measurements of respiratory muscles, a review of analysis techniques.

Transcutaneous electromyography (tc-EMG) has been used to measure the electrical activity of respiratory muscles during inspiration in various studies. Processing the raw tc-EMG signal of these inspiratory muscles has shown to be difficult as baseline noise, cardiac interference, cross-talk and motion artefacts can influence the signal quality. In this review we will discuss the most important sources of signal noise in tc-EMG of respiratory muscles and the various techniques described to suppress or reduce this signal noise. Furthermore, we will elaborate on the options available to develop or improve an algorithm that can be used to guide the approach for analysis of tc-EMG signals of inspiratory muscles in future research.

Airflow from nasal pulse oximetry in the screening of obstructive sleep apnea.

Obstructive Sleep Apnea (OSA) is recognized as an increasing health risk, leading to daytime sleepiness and various medical conditions, such as hypertension and heart failure. Polysomnography (PSG), the gold standard to diagnose OSA, is a resource-intensive and expensive investigation confined to the hospital.Portable home monitoring, i.e. pulse oximetry, may become an acceptable OSA screening method. The novel nasal pulse oximeter sensor (Xhale Alar) adds the possibility of combining pulse oximetry (SpO2) with airflow analysis by an integrated thermistor, which might increase the diagnostic accuracy.In the Alar pilot study, 39 adults were measured during an overnight PSG recording together with the Alar sensor. This study aims to investigate the additional value of an airflow signal compared to SpO2 analysis in OSA screening. Both time and spectral features were extracted from SpO2 and airflow signals recorded with the Alar sensor. Leave one out cross-validation was used to develop Random Forest models in screening for apnea-hypopnea index (AHI) thresholds 5 and 10. Using both AHI ≥ 5 and AHI ≥ 10 as the diagnostic cutoff, the airflow signal shows respectively an AUC of 89% and 80% compared to 78% and 77% with SpO2 analysis, showing a higher performance using an airflow signal in screening adults for OSA.

Prevalence of healthcare-associated infections in Dutch nursing homes: follow-up 2010-2017.

Following the first point-prevalence study in Dutch nursing homes conducted each November from 2007 to 2009, we conducted a follow-up point-prevalence study of healthcare-associated infections (HCAIs) each November from 2010 to 2017. Similar methods and criteria were used. Resident characteristics were recorded, data collection was performed by the attending elderly care physicians via an online survey, as well as via a specifically designed App from 2012. As of the same year, information on incontinence was added. Between 2010 until 2017 on average 1786 residents per year were included, ranging from 1571 to 2185. HCAI prevalence with respect to age (mean: 83 years) and sex (31% men and 69% women) were similar over all the years. The overall mean prevalence rate in the first four years was 6.7% versus 2.2% in the last six years. Urinary tract infection was the most prevalent HCAI (1.5%). Most HCAIs occurred among residents of rehabilitation units. The prevalence of HCAI varied by nursing home (0.0-37.0%). The average use of antibiotics was stable over the years (6.0%) irrespective of HCAI rate. Use of incontinence materials was on average 73.5% with 64.3% of residents being reported as incontinent. Those implementing improvement of infection control and surveillance within a new setting do need to continue for multiple years before seeing the success of their endeavour.

Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis.

OBJECTIVES: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions. MATERIALS AND METHODS: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed. RESULTS: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86. CONCLUSION: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing.

The Mozart study: a relation between dynamic hyperinflation and physical activity in patients with chronic obstructive pulmonary disease?

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) experience dyspnoea during exercise, resulting in a reduction of physical activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea in COPD. OBJECTIVE: The objective of the current study was to investigate the relationship between DH, in terms of the amount of DH and the development and recovery rate of DH in patients with COPD, and PA. METHODS: Thirty-five patients with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD III, median age 65). PA was assessed using an accelerometer. Subjects underwent metronome-paced tachypnoea (MPT) to induce DH. To quantify the amount of DH during MPT, a decrease in inspiratory capacity (IC) or a change in IC as percentage of total lung capacity was used. RESULTS: No significant correlations were found between the parameters describing DH and PA. Secondary correlation analyses showed a negative correlation between static hyperinflation (SH) and PA (r = -0·39; P = 0·02). The pattern of breathing during MPT and the test itself showed high interpatient variability. CONCLUSIONS: The absence of a significant correlation between DH and PA is contrary to previous studies. SH did show a correlation with PA. The variety in results and the technical difficulties in execution of the measurements ask for a new, more reliable, method to detect DH and investigate its relation with PA in patients with COPD.

Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study.

BACKGROUND: The phase 3 CAIRO3 study showed that capecitabine plus bevacizumab (CAP-B) maintenance treatment after six cycles capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients is effective, without compromising quality of life. In this post hoc analysis with updated follow-up and data regarding sidedness, we defined subgroups according to RAS/BRAF mutation status and mismatch repair (MMR) status, and investigated their influence on treatment efficacy. PATIENTS AND METHODS: A total of 558 patients with previously untreated mCRC and stable disease or better after six cycles CAPOX-B induction treatment were randomised to either CAP-B maintenance treatment (n = 279) or observation (n = 279). Upon first progression, patients were to receive CAPOX-B reintroduction until second progression (PFS2, primary end point). We centrally assessed RAS/BRAF mutation status and MMR status, or used local results if central assessment was not possible. Intention-to-treat stratified Cox models adjusted for baseline covariables were used to examine whether treatment efficacy was modified by RAS/BRAF mutation status. RESULTS: RAS, BRAF mutations, and MMR deficiency were detected in 240/420 (58%), 36/381 (9%), and 4/279 (1%) patients, respectively. At a median follow-up of 87 months (IQR 69-97), all mutational subgroups showed significant improvement from maintenance treatment for the primary end point PFS2 [RAS/BRAF wild-type: hazard ratio (HR) 0.57 (95% CI 0.39-0.84); RAS-mutant: HR 0.74 (0.55-0.98); V600EBRAF-mutant: HR 0.28 (0.12-0.64)] and secondary end points, except for the RAS-mutant subgroup regarding overall survival. Adjustment for sidedness instead of primary tumour location yielded comparable results. Although right-sided tumours were associated with inferior prognosis, both patients with right- and left-sided tumours showed significant benefit from maintenance treatment. CONCLUSIONS: CAP-B maintenance treatment after six cycles CAPOX-B is effective in first-line treatment of mCRC across all mutational subgroups. The benefit of maintenance treatment was most pronounced in patients with RAS/BRAF wild-type and V600EBRAF-mutant tumours. CLINICALTRIALS.GOV NUMBER: NCT00442637.

Exhaled breath profiles in the monitoring of loss of control and clinical recovery in asthma.

BACKGROUND: Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control. OBJECTIVES: To determine whether exhaled volatile organic compounds (VOCs) as measured by gas-chromatography/mass-spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma. METHODS: Twenty-three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within-subject breath profile differences at the different time-points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined. RESULTS: Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01). CONCLUSIONS & CLINICAL RELEVANCE: Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.

Electrical activity of the diaphragm during nCPAP and high flow nasal cannula.

OBJECTIVE: To determine if the electrical activity of the diaphragm, as measure of neural respiratory drive and breathing effort, changes over time in preterm infants transitioned from nasal continuous positive airway pressure (nCPAP) to high flow nasal cannula (HFNC). DESIGN: Prospective observational study. SETTING: Neonatal intensive care unit. PATIENTS: Stable preterm infants transitioned from nCPAP to HFNC using a 1:1 pressure to flow ratio. INTERVENTIONS: The electrical activity of the diaphragm was measured by transcutaneous electromyography (dEMG) from 30 min before until 3 hours after the transition. MAIN OUTCOME MEASURES: At eight time points after the transition to HFNC, diaphragmatic activity was compared with the baseline on nCPAP. Percentage change in amplitudedEMG, peakdEMG and tonicdEMG were calculated. Furthermore, changes in respiratory rate, heart rate and fraction of inspired oxygen (FiO2) were analysed. RESULTS: Thirty-two preterm infants (mean gestational age: 28.1±2.2 weeks, mean birth weight: 1118±368 g) were included. Compared with nCPAP, the electrical activity of the diaphragm did not change during the first 3 hours on HFNC (median (IQR) change in amplitudedEMG at t=180 min: 2.81% (-21.51-14.10)). The respiratory rate, heart rate and FiO2 remained stable during the 3-hour measurement. CONCLUSIONS: Neural respiratory drive and breathing effort assessed by electrical activity of the diaphragm is similar in the first 3 hours after transitioning stable preterm infants from nCPAP to HFNC with a 1:1 pressure-to-flow ratio.

Lethal acute liver failure in a patient treated with sunitinib.

Sunitinib is a tyrosine kinase inhibitor that is used as an anticancer drug in renal cell carcinoma (RCC), pancreatic neuroendocrine tumours (PNETs) and gastrointestinal stromal tumour. Elevated liver enzymes are frequently observed during treatment but acute liver failure is uncommon. We describe a case of fulminant acute liver failure and acute kidney injury during treatment with sunitinib for metastatic RCC.

Integration of electronic nose technology with spirometry: validation of a new approach for exhaled breath analysis.

New 'omics'-technologies have the potential to better define airway disease in terms of pathophysiological and clinical phenotyping. The integration of electronic nose (eNose) technology with existing diagnostic tests, such as routine spirometry, can bring this technology to 'point-of-care'. We aimed to determine and optimize the technical performance and diagnostic accuracy of exhaled breath analysis linked to routine spirometry. Exhaled breath was collected in triplicate in healthy subjects by an eNose (SpiroNose) based on five identical metal oxide semiconductor sensor arrays (three arrays monitoring exhaled breath and two reference arrays monitoring ambient air) at the rear end of a pneumotachograph. First, the influence of flow, volume, humidity, temperature, environment, etc, was assessed. Secondly, a two-centre case-control study was performed using diagnostic and monitoring visits in day-to-day clinical care in patients with a (differential) diagnosis of asthma, chronic obstructive pulmonary disease (COPD) or lung cancer. Breathprint analysis involved signal processing, environment correction based on alveolar gradients and statistics based on principal component (PC) analysis, followed by discriminant analysis (Matlab2014/SPSS20). Expiratory flow showed a significant linear correlation with raw sensor deflections (R(2) = 0.84) in 60 healthy subjects (age 43 ± 11 years). No correlation was found between sensor readings and exhaled volume, humidity and temperature. Exhaled data after environment correction were highly reproducible for each sensor array (Cohen's Kappa 0.81-0.94). Thirty-seven asthmatics (41 ± 14.2 years), 31 COPD patients (66 ± 8.4 years), 31 lung cancer patients (63 ± 10.8 years) and 45 healthy controls (41 ± 12.5 years) entered the cross-sectional study. SpiroNose could adequately distinguish between controls, asthma, COPD and lung cancer patients with cross-validation values ranging between 78-88%. We have developed a standardized way to integrate eNose technology with spirometry. Signal processing techniques and environmental background correction ensured that the multiple sensor arrays within the SpiroNose provided repeatable and interchangeable results. SpiroNose discriminated controls and patients with asthma, COPD and lung cancer with promising accuracy, paving the route towards point-of-care exhaled breath diagnostics.

Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

RATIONALE: Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. METHODS: 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 µg or 400 µg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. RESULTS: Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 µg salbutamol compared to 200 µg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). CONCLUSION: In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 µg compared to 200 µg salbutamol with a BAI does improve reversibility.

Reversibility after inhaling salbutamol in different body postures in asthmatic children: a pilot study.

RATIONALE: Pulmonary medication is mostly delivered in the form of medical aerosols to minimize systemic side effects. A major drawback of inhaled medication is that the majority of inhaled particles impacts in the oropharynx at the sharp bend of the airway. Stretching the airway by a forward leaning body posture with the neck extended ("sniffing position") may improve pulmonary deposition and clinical effects. METHODS: 41 asthmatic children who were planned for standard reversibility testing at the pulmonary function lab, alternately inhaled 200 µgr salbutamol with an Autohaler(®) in the standard or in the forward leaning body posture. Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF), Mean Expiratory Flow at 25% of vital capacity (MEF25) and Mean Expiratory Flow at 75% of vital capacity (MEF75) were analysed. RESULTS: The children in the forward leaning body posture group showed a significantly higher mean FEV1 reversibility than the control group after inhalation of 200 µgr salbutamol (10.2% versus 4.1%, p = 0.019). Additionally, mean MEF75 was significantly more reversible in the forward leaning body posture group versus the standard body posture group (32.2% resp. 8.9%, p = 0.013). CONCLUSION: This pilot study showed a higher reversibility of FEV1 and MEF75 after inhaling salbutamol in a forward leaning body posture compared to the standard body posture in asthmatic children. This suggests that pulmonary effects of salbutamol can be improved by inhaling in a forward leaning body posture with the neck extended. This effect is possibly due to a higher pulmonary deposition of salbutamol and should be confirmed in a randomized controlled trial.

Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction.

OBJECTIVE: Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against EIB in asthmatic children. METHODS: 31 Mild asthmatic children not currently treated with inhaled corticosteroids, 5-16 years, with EIB (fall in FEV0.5/1 ≥ 13%) were included in a prospective intervention study. They performed two ECT's within 2 weeks. Four hours before the second test children inhaled 200 µg beclomethasone-dipropionate (BDP) with a breath-actuated inhaler (BAI). RESULTS: The median fall in FEV0.5/1 after 200 µg BDP was significantly reduced from 30.9% at baseline to 16.0% (P < 0.001). Twenty children (64.5%) showed a good response to 200 µg BDP (≥ 50% decrease in fall of FEV0.5/1), while 8 children showed a moderate response (25-50%), and three children showed no response at all (< 25%). CONCLUSION: A low single dose ICS offers acute protection against EIB in the majority of asthmatic children not currently treated with inhaled corticosteroids.

Gene expression profiles in circulating tumor cells to predict prognosis in metastatic breast cancer patients.

BACKGROUND: A circulating tumor cell (CTC) count is an established prognostic factor in metastatic breast cancer (MBC). Besides enumeration, CTC characterization promises to improve outcome prediction and treatment guidance. Having shown the feasibility of quantifying clinically relevant mRNA transcripts in CTCs, we determined the prognostic value of CTC gene expression in MBC. PATIENTS AND METHODS: CTCs were isolated and enumerated from blood of 197 MBC patients who were about to start first-line systemic therapy. Of these, 180 were assessable for quantification of mRNA expression by RT-qPCR in relation to time-to-treatment failure (TTF). A prognostic CTC gene profile was generated by leave-one-out cross validation in a 103 patient discovery set and validated in 77 patients. Additionally, all 180 patients were randomly divided into two equal sets to discover and validate a second prognostic profile. RESULTS: CTC count predicted for TTF at baseline {≥5 versus <5 CTCs/7.5 ml blood, hazard ratio (HR) 2.92 [95% confidence interval (CI) 1.71-4.95] P < 0.0001}. A 16-gene CTC profile was generated in the first discovery set, which identified patients with death or TTF <9 months versus those with a better outcome. In multivariate analysis, the 16-gene profile was the only factor associated with TTF [HR 3.15 (95% CI 1.35-7.33) P 0.008]. Validation of this profile in the independent patient set pointed into the same direction, but was not statistically significant. A newly generated 8-gene profile showed similarly favorable test characteristics as the 16-gene profile, but did not significantly pass validation either. CONCLUSION: A 16-gene CTC profile was identified, which provided prognostic value on top of CTC count in MBC patients. However, validation of this profile in an independent cohort, nor of a second profile, reached statistical significance, underscoring the need to further fine-tune the still promising approach of CTC characterization.

Unilateral atelectasis in a preterm infant monitored with electrical impedance tomography: a case report.

UNLABELLED: Electrical impedance tomography (EIT) is a non-invasive, radiation-free tool to monitor regional changes in ventilation. This report describes, for the first time, that unilateral atelectasis in an extremely low birth weight infant results in a loss of regional ventilation measured by EIT in the affected lung. CONCLUSION: EIT is currently the most promising technique to monitor regional lung aeration continuously at the bedside in this vulnerable population.