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Introduction: Serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements have proven to be useful for therapy monitoring in patients hospitalized for acute decompensated heart failure (ADHF). The POC-HF pilot study investigated whether serial NTproBNP measurements influenced treatment decisions in these patients. Methods: Patients hospitalized for ADHF were randomly assigned to an intervention group (serial NT-proBNP measurements made available to treating physicians) or a control group (care as usual). HF therapy was administered at the discretion of the treating physician. The primary endpoint was dose changes in HF therapy during hospitalization. Secondary endpoints included changes in NT-proBNP levels, recovery from HF symptoms, length of hospital stay, and quality of life. Results: 52 patients (35% female; mean age 81.8 years) were included. The availability of serial NT-proBNP values was associated with higher dosages of ACE inhibitors (relative treatment effect (RTE) day 11:0.74, p = 0.007) and loop diuretics (RTE day 11:0.77, p = 0.005), and lower dosages of beta-blockers (RTE day 11:0.43, p = 0.002). NT-proBNP levels decreased (-752 pg/ml, p = 0.162) and recovery rates from ADHF symptoms were more pronounced in the intervention group, but without statistical significance. No differences were found in terms of the length of hospital stay and quality of life. Conclusion: The results of this pilot trial indicate that serial NT-proBNP measurements are possibly associated with faster up-titration of HF medication, more pronounced NT-proBNP decrease, and faster recovery from symptoms than symptom-guided therapy in patients hospitalized for ADHF. These preliminary findings require further validation through larger studies. [ABSTRACT FROM AUTHOR]

Lymphoedema is a chronic and dynamic condition that requires the investment of time and resources to appropriately manage. It fluctuates in response to illness, activity, and age, as well as in response to environmental conditions. This qualitative study explored the impact of the climate and climatic variations on lymphoedema. Focus groups were completed with patients (n = 12) and therapists (n = 7) to explore, in depth, their experiences of managing lymphoedema throughout the year. The results suggested that heat and humidity definitely alter the severity of lymphoedema, and a range of individual strategies are required in order to control symptoms. Central to effectively managing lymphoedema is the notion that every body is different and every lymphoedema is different, and therefore understanding one's own body, what it needs, and what resources are available is essential in maintaining lymphoedema in the face of climate change. [ABSTRACT FROM AUTHOR]

Compression is the cornerstone of treatment for lymphoedema; however, in patients with Stage III lymphoedema that causes a significant alteration of limb shape and size, additional creative problem solving is required in order to find a solution that fits the person, their limb and their personal circumstances. Medical adaptive compression (MAC) systems provide solutions to complex situations. We present two cases of individuals who completed an inpatient rehabilitation stay for intensive treatment of their lymphoedema and were fitted with MAC devices to ensure long-term success. [ABSTRACT FROM AUTHOR]

Primary lymphoedema, axillary web syndrome (AWS) and yellow nail syndrome may be related. Mr B is a 66-year-old gentleman with genital lymphoedema and lymphoedema of all four extremities. In 2023, he was diagnosed with non-Hodgkin lymphoma and also underwent cardiac surgery. In November 2023, he completed an inpatient rehabilitation at the Földi clinic in Germany, where he received intensive treatment for his lymphoedema and was also diagnosed with bilateral AWS. The presence of AWS in a patient with primary lymphoedema and no history of axillary surgery is unique. Although AWS typically presents after axillary surgery, this case highlights that it can also occur in patients without lymph node surgery. While the precise cause of this presentation of AWS is not known, it may be connected to yellow nail syndrome or potentially the recent chemotherapy treatment. This article will describe the clinical case, highlighting the need for further research on AWS present in primary lymphoedema. [ABSTRACT FROM AUTHOR]

Long‐term, intense endurance exercise training can occasionally induce endothelial micro‐damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well‐trained male participants (10 runners and 10 cyclists) performed a strenuous high‐intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal‐3 and sST2 concentrations were investigated by enzyme‐linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal‐3 and sST2 concentrations and ECs were elevated after exercise (P < 0.001), without interaction between exercise modalities. Circulating Gal‐3 and sST2 concentrations both showed a positive relationship with ECs (rrm = 0.68, P = 0.001 and rrm = 0.57, P = 0.010, respectively, both n = 18). The EC association with Gal‐3 was significant only in cyclists, but equally strong for both modalities. Gal‐3 was also related to exercise‐induced CTi (rrm = 0.57, P = 0.011, n = 18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise‐released Gal‐3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise‐induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long‐term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. New Findings: What is the central question of this study?Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear.What is the main finding and its importance?We show that galectin‐3 (Gal‐3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal‐3 is an enhanced cardiac contractility. Acute exercise‐released Gal‐3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations. [ABSTRACT FROM AUTHOR]

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Doxycycline-inducible expression of SERCA2a improves calcium handling and reverts cardiac dysfunction in pressure overload-induced cardiac hypertrophy. Ant J Physiol Heart Circ Physiol 287: H2164-H2172, 2004. First published July 15, 2004; doi:10.1152/ajpheart.00428. 2004.--Delayed cardiac relaxation in failing hearts has been attributed to reduced activity and/or expression of sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase 2a (SERCA2a). Although constitutive overexpression of SERCA2a has proven effective in preventing cardiac dysfunction, it is unclear whether increasing SERCA2a expression in hearts with preexisting hypertrophy will be therapeutic. To test this hypothesis, we generated a binary transgenic (BTG) system that allows tetracycline-inducible, cardiac-specific SERCA2a expression. In this system (tet-on SERCA2a), a FLAG-tagged SERCA2a transgene is expressed in the presence of doxycycline (Dox) but not in the absence of Dox (2.3-fold more mRNA, 45% more SERCA2a protein). Calcium transients measured in isolated cardiac myocytes from nonbanded Dox-treated BTG mice showed an accelerated calcium decline and an increased systolic [Ca.sup.2+] peak. Sarcoplasmic reticulum (SR) calcium loading was increased by 45% in BTG mice. In the presence of pressure overload (aortic banding), echocardiographic analysis revealed that expression of SERCA2a-FLAG caused an improvement in fractional shortening. SERCA2a-FLAG expression alleviated the resultant cardiac dysfunction. This was illustrated by an increase in the rate of decline of the calcium transient. Cell shortening and SR calcium loading were also improved in cardiac myocytes isolated from banded BTG mice after SERCA2a overexpression. In conclusion, we generated a novel transgenic mouse that conditionally overexpresses SERCA2a. This model is suitable for both long- and short-term studies of the effects of controlled SERCA2a expression on cardiac function. In addition, inducible overexpression of SERCA2a improved cardiac function and calcium handling in mice with established contractile dysfunction. heart failure; cardiac myocytes; transgenic mice; sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase

In many types of heart failure cardiac myocyte [Ca.sup.2+] handling is abnormal because of downregulation of key [Ca.sup.2+]-handling proteins like sarco(endo)plasmic reticulum [Ca.sup.2+]-ATPase (SERCA)2a and ryanodine receptor (RyR)2. The alteration in SERC2a and RyR2 expression results in altered cytosolic [Ca.sup.2+] transients, leading to abnormal contraction. Sorcin is an EF-hand protein that confers the property of caffeine-activated intracellular [Ca.sup.2+] release in nonmuscle cells by interacting with RyR2. To determine whether sorcin could improve the contractile function of the heart, we overexpressed sorcin in the heart of either normal or diabetic mice and in adult rat cardiomyocytes with an adenoviral gene transfer approach. Sorcin overexpression was associated with an increase in cardiac contractility of the normal heart and dramatically rescued the abnormal contractile function of the diabetic heart. These effects could be attributed to an improvement of the [Ca.sup.2+] transients found in the cardiomyocyte after sorcin overexpression. Viral vector-mediated delivery of sorcin to cardiac myocytes is beneficial, resulting in improved contractile function in diabetic cardiomyopathy. calcium handling; gene therapy

Background and Objective: Whether immunological biomarkers combined with clinical characteristics measured during an exacerbation-free period are predictive of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) frequency and severity is unknown. Method: We measured immunological biomarkers and clinical characteristics in 271 stable chronic obstructive pulmonary disease (COPD) patients (67% male, mean age 63 years) from "The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland" cohort on a single occasion. One-year follow-up data were available for 178 patients. Variables independently associated with AECOPD frequency and severity were identified by multivariable regression analyses. Receiver operating characteristic analysis was used to obtain optimal cutoff levels and measure the area under the curve (AUC) in order to assess if baseline data can be used to predict future AECOPD. Results: Higher number of COPD medications (adjusted incident rate ratio [aIRR] 1.17) and platelet count (aIRR 1.03), and lower FEV1% predicted (aIRR 0.84) and IgG2 (aIRR 0.84) were independently associated with AECOPD frequency in the year before baseline. Optimal cutoff levels for experiencing frequent (>1) AECOPD were ≥3 COPD medications (AUC = 0.72), FEV1 ≤40% predicted (AUC = 0.72), and IgG2 ≤2.6 g/L (AUC = 0.64). The performance of a model using clinical and biomarker parameters to predict future, frequent AECOPD events in the same patients was fair (AUC = 0.78) but not superior to a model using only clinical parameters (AUC = 0.79). The IFN-lambda rs8099917GG-genotype was more prevalent in patients who had severe AECOPD. Conclusions: Clinical and biomarker parameters assessed at a single point in time correlated with the frequency of AECOPD events during the year before and the year after assessment. However, only clinical parameters had fair discriminatory power in identifying patients likely to experience frequent AECOPD. [ABSTRACT FROM AUTHOR]

Significant variability in adherence to COPD management recommendations has been reported. We aimed to evaluate real-life COPD pharmacotherapy prescribing patterns and adherence to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) global strategy in Switzerland. A questionnaire-based survey was conducted among Swiss general practitioners (GPs) and pulmonologists (PULs) from May 1 to November 30, 2017. Participants were invited to complete a questionnaire on their next 5–10 consecutive patients already receiving a pharmacological treatment for COPD. They were requested to assess dyspnea using the modified Medical Research Council (mMRC) dyspnea scale and to determine whether a treatment adjustment was indicated. Fifty-three PULs and 39 GPs completed questionnaires on 511 COPD patients. Dyspnea with mMRC grade ≥2 was reported in 62.5% of the patients, and 31.9% had had at least two exacerbations (or at least one with hospital admission) in the last 12 months. The vast majority (87.1%) of GOLD A patients were overtreated. In the GOLD B group, 52.2% of prescriptions were concordant with GOLD 2017 recommendations, but 37% of patients were overtreated. Among GOLD C patients, 49.2% received GOLD-adherent treatment and 47.5% were overtreated. In the GOLD D category, 78.8% of the patients received a treatment consistent with recommendations but 15.2% were undertreated. After reassessment of patient status, treatment was modified in 50.3% of the patients. This study confirms that discordance of real-world prescription patterns with international guidance is frequent. Further educational efforts are required to improve adherence to COPD management recommendations. [ABSTRACT FROM AUTHOR]

Aims: Switch from angiotensin converting enzyme inhibitor treatment to sacubitril/valsartan (sac/val) is associated with benefit in heart failure with reduced ejection fraction (HFrEF). Reports on management of this switch are largely based on randomized controlled trials, retrospective analyses, and hospital‐based care, while patients with chronic heart failure (CHF) are frequently followed‐up in primary care. The THESEUS study aimed to characterize the transition to sac/val and early maintenance period of HFrEF in primary care. Method and results: THESEUS was a prospective, observational, non‐interventional study, performed at primary care sites throughout Switzerland. Patient characteristics, sac/val transition, and maintenance were reported at study enrolment and approximately 3 and 6 months after sac/val initiation. The primary endpoint was achievement of 200 mg BID sac/val with maintenance for ≥12 weeks. Secondary outcomes included dosing regimens, healthcare utilization in the 6 months prior to sac/val initiation and during the study, patient well‐being, safety, and tolerability. Fifty‐eight patients with CHF were enrolled from 45 primary care centres. Six patients were excluded, and 19 achieved the primary endpoint (36.5%, Achievers). Non‐Achievers underwent fewer titration steps than Achievers (1.9 ± 0.9 vs. 3.1 ± 1.4). In both groups, patient well‐being improved and the percentage of New York Heart Association III patients decreased. Healthcare utilization decreased (19% vs. 30.8% in the 6 months pre‐enrolment period). The most frequent reasons for target dose non‐achievement were asymptomatic and symptomatic hypotension (15.3% and 12.1%, respectively). Conclusions: Results from THESEUS suggest that transition to sac/val is manageable in primary care, with a safety profile corresponding to reports from specialized heart failure care. [ABSTRACT FROM AUTHOR]

Introduction: Objective data on the association of maximal aerobic capacity (VO2max) with work related physical activity are sparse. Thus, it is not clear whether occupational physical activity (OPA) contributes to an increase of VO2max. This study examined the association of VO2max with work and non-work related physical activity in a Swiss working population. Methods: In this cross-sectional study, a total of 337 healthy and full-time employed adults were recruited. Demographic data, height, weight and BMI were recorded in all subjects. Participants were classified into nine occupational categories (ISCO-88) and merged into three groups with low, moderate, and high OPA. Physical activity was objectively measured by the SenseWear Mini Armband on seven consecutive days (23 hours per day). Participants were regarded as sufficiently active when accumulating ≥30 min of moderate-to-vigorous physical activity per day. VO2max was evaluated using the multistage 20-meter shuttle run test. Results: Data of 303 participants were considered for analysis (63% male, age 33 yrs, SD 12). Multiple linear regression analysis (adjusted R2 = 0.69) revealed significant positive associations of VO2max with leisure-time physical activity (LTPA) at vigorous intensity (β = 0.212) and sufficient moderate-to-vigorous physical activity (β = 0.100) on workdays. Female gender (β = -0.622), age (β = -0.264), BMI (β = -0.220), the ratio of maximum to resting heart rate (β = 0.192), occupational group (low vs. high OPA, β = -0.141), and smoking (β = -0.133) were also identified as independent predictors of VO2max. Conclusions: The present results suggest that VO2max is positively associated with LTPA, but not with OPA on workdays. This finding emphasizes the need for employees to engage in sufficient high-intensity physical activity in recreation for maintaining or improving VO2max with regard to health benefits. [ABSTRACT FROM AUTHOR]

This study aimed to determine physical performance criteria of different occupational groups by investigating physical activity and energy expenditure in healthy Swiss employees in real-life workplaces on workdays and non-working days in relation to their aerobic capacity (VO2max). In this cross-sectional study, 337 healthy and full-time employed adults were recruited. Participants were classified (nine categories) according to the International Standard Classification of Occupations 1988 and merged into three groups with low-, moderate- and high-intensity occupational activity. Daily steps, energy expenditure, metabolic equivalents and activity at different intensities were measured using the SenseWear Mini armband on seven consecutive days (23 hours/day). VO2max was determined by the 20-meter shuttle run test. Data of 303 subjects were considered for analysis (63% male, mean age: 33 yrs, SD 12), 101 from the low-, 102 from the moderate- and 100 from the high-intensity group. At work, the high-intensity group showed higher energy expenditure, metabolic equivalents, steps and activity at all intensities than the other groups (p<0.001). There were no significant differences in physical activity between the occupational groups on non-working days. VO2max did not differ across groups when stratified for gender. The upper workload limit was 21%, 29% and 44% of VO2max in the low-, moderate- and high-intensity group, respectively. Men had a lower limit than women due to their higher VO2max (26% vs. 37%), when all groups were combined. While this study did confirm that the average workload limit is one third of VO2max, it showed that the average is misrepresenting the actual physical work demands of specific occupational groups, and that it does not account for gender-related differences in relative workload. Therefore, clinical practice needs to consider these differences with regard to a safe return to work, particularly for the high-intensity group. [ABSTRACT FROM AUTHOR]

Background: In vitro diagnostic (IVD) investigations are indispensable for routine patient management. Appropriate testing allows early-stage interventions, reducing late-stage healthcare expenditure (HCE). Aim: To investigate HCE on IVDs in two developed markets and to assess the perceived value of IVDs on clinical decision-making. Physician-perceived HCE on IVD was evaluated, as well as desired features of new diagnostic markers. Methods: Past and current HCE on IVD was calculated for the US and Germany. A total of 79 US/German oncologists and cardiologists were interviewed to assess the number of cases where: physicians ask for IVDs; IVDs are used for initial diagnosis, treatment monitoring, or post-treatment; and decision-making is based on an IVD test result. A sample of 201 US and German oncologists and cardiologists was questioned regarding the proportion of HCE they believed to be attributable to IVD testing. After disclosing the actual IVD HCE, the physician’s perception of the appropriateness of the amount was captured. Finally, the association between physician-rated impact of IVD on decision-making and perceived contribution of IVD expenditure on overall HCE was assessed. Results: IVD costs account for 2.3% and 1.4% of total HCE in the US and Germany. Most physicians (81%) believed that the actual HCE on IVDs was >5%; 19% rated the spending correctly (0–4%, p<0.001). When informed of the actual amount, 64% of physicians rated this as appropriate (p<0.0001); 66% of decision-making was based on IVD. Significantly, more physicians asked for either additional clinical or combined clinical/health economic data than for the product (test/platform) alone (p<0.0001). Conclusions: Our results indicate a poor awareness of actual HCE on IVD, but a high attributable value of diagnostic procedures for patient management. New markers should deliver actionable and medically relevant information, to guide decision-making and foster improved patient outcomes. [ABSTRACT FROM AUTHOR]

The prevalence of complicated hypertension is increasing in America and Europe. This survey was undertaken to assess the status quo of primary care management of hypertension in patients with the high-risk comorbid diseases metabolic syndrome (MetS) and/or type 2 diabetes mellitus (non-insulin depending diabetes mellitus (NIDDM)). Data of anti-hypertensive treatment of 4594 Swiss patients were collected over 1 week. We identified patients with exclusively NIDDM ( N = 95), MetS ( N = 168), and both ( N = 768). Target blood pressure (TBP) attainment, frequency of prescribed substance-classes, and correlations to comorbidities/end-organ damages were assessed. In addition, we analyzed the prescription of unfavorable beta-blockers (BB) and high-dose diuretics (Ds). In NIDDM, Ds (61%), angiotensin receptor blockers (ARBs) (40%), and angiotensin converting enzyme inhibitors (ACEIs) (31%) were mostly prescribed, while in MetS, drugs prevalence was Ds (68%), ARBs (48%), and BB (41%). Polypharmacy in patients with MetS correlated with body mass index; older patients (>65 years) were more likely to receive dual-free combinations. TBP was attained in 25.2% of NIDDM and in 28.7% of MetS patients. In general, low-dose Ds use was more prevalent in NIDDM and MetS, however, overall, Ds were used excessively (NIDDM: 61%, MetS: 68%), especially in single-pill combination. Patients with MetS were more likely to receive ARBs, ACEIs, CCBs, and low-dose Ds than BBs and/or high-dose Ds. Physicians recognize DM and MetS as high-risk patients, but select inappropriate drugs. Because the majority of patients may have both, MetS and NIDDM, there is an unmet need to define TBP for this specific population considering the increased risk in comparison to patients with MetS or NIDDM alone. [ABSTRACT FROM AUTHOR]

The article presents a study on myeloid differentiation factor (MyD) 88/interleukin (IL)-1 in the development of acute myocarditis to end-stage heart failure. It states that bone marrow origin having inflammatory infiltrates, and the MyD88 and IL-1 shown on bone-marrow derived cells were critical for the development of the disease. It notes that the role of MyD88/IL-1 in postinflammatory cardiac fibrosis and heart failure applies the need of therapeutic ways against inflammatory cardiomyopathy.

Recently, novel corticotropin-releasing factor-related peptides, named urocortin 1, 2, and 3, and a distinct cardiac and peripheral vascular receptor (corticotropin-releasing factor receptor 2) were described being part of a peripheral corticotropin-releasing factor system modulating cardiovascular function in response to stress. Vasorelaxation and blood pressure lowering have been reported after acute administration of these peptides. No data are available on the acute and chronic effects of urocortin 2 on blood pressure in models of arterial hypertension. To test these effects, hypertensive salt-sensitive and normotensive salt-resistant Dahl rats were randomly assigned to twice-daily applications of urocortin 2 or vehicle for 5 weeks. Blood pressure, heart rate, and left ventricular dimension and function were recorded at baseline, after initial application, and, together with cardiac and aortic expression of urocortin 2 and its receptor, after 5 weeks of treatment. Urocortin 2 significantly reduced blood pressure in hypertensive rats without affecting heart rate. Long-term urocortin 2 treatment in hypertensive rats induced sustained blood pressure reduction and diminished the development of hypertension-induced left ventricular hypertrophy and the deterioration of left ventricular contractile function. Corticotropin-releasing factor receptor 2 expression was preserved despite chronic stimulation by urocortin 2. In conclusion, our study shows that, in an animal model of arterial hypertension, urocortin 2 has immediate and sustained blood pressure-lowering effects. Beneficial effects on blood pressure, left ventricular dimension, and function, together with preserved receptor expression, suggest that corticotropin-releasing factor receptor 2 stimulation by urocortin 2 may represent a novel approach to the treatment of arterial hypertension. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to test whether baseline echocardiography in newly detected hypertension improves left ventricular mass index and blood pressure control. This is a randomized trial with primary care patients. Methods: After routine clinical work-up 177 consecutive patients with newly detected hypertension were randomized according to result of their echocardiogram (echo group and control group). Treating physicians were encouraged to prescribe angiotensin II receptor antagonist therapy for patients with evidence of hypertensive target organ damage. Mean blood pressure (BP) and echocardiographic left ventricular mass index were measured at baseline and after 6 months of therapy in both groups. Results: More patients with hypertensive target organ damage were identified in the echo group as compared to the control group (58 of 91 [64%] v 42 of 86 [49%] patients (difference 15%, 95% CI 1%–29%). In the echo group, 41 patients (45%) received angiotensin II receptor antagonist therapy as compared to 27 patients (31%) in the control group (difference 14%, 95% CI 0–28%). After 6 months, there were no differences in mean left ventricular mass index, mean diastolic 24-h ambulatory BP monitoring, or mean systolic and diastolic office BP between the two groups. Conclusions: In patients with newly detected hypertension, baseline echocardiography detects more patients with hypertensive target organ damage, but does not lead to a reduction in left ventricular mass index or improved BP control after 6 months of therapy. [Copyright &y& Elsevier]

Summary: Objective: Lung auscultation is a central part of the physical examination at hospital admission. In this study, the physicians’ estimation of airway obstruction by auscultation was determined and compared with the degree of airway obstruction as measured by FEV1/FVC values. Methods: Two hundred and thirty-three patients consecutively admitted to the medical emergency room with chest problems were included. After taking their history, patients were auscultated by an Internal Medicine registrar. The degree of airway obstruction had to be estimated (0=no, 1=mild, 2=moderate and 3=severe obstructed) and then spirometry was performed. Airway obstruction was defined as a ratio of FEV1/FVC <70%. The degree of airway obstruction was defined on FEV1/FVC as mild (FEV1/FVC <70% and >50%), moderate (FEV1/FVC <50% >30%) and severe (FEV1/FVC <30%). Results: One hundred and thirty-five patients (57.9%) had no sign of airway obstruction (FEV1/FVC >70%). Spirometry showed a mild obstruction in 51 patients (21.9%), a moderate obstruction in 27 patients (11.6%) and a severe obstruction in 20 patients (8.6%). There was a weak but significant correlation between FEV1/FVC and the auscultation-based estimation of airway obstruction in Internal Medicine Registrars (Spearman''s =0.328; P<0.001). The sensitivity to detect airway obstruction by lung auscultation was 72.6% and the specificity only 46.3%. Thus, the negative predictive value was 68% and the positive predictive value 51%. In 27 patients (9.7%), airway obstruction was missed by lung auscultation. In these 27 cases, the severity of airway obstruction was mild in 20 patients, moderate in 5 patients and severe in 2 patients. In 82 patients (29.4%) with no sign of airway obstruction (FEV1/FVC >70%), airway obstruction was wrongly estimated as mild in 42 patients, as moderate in 34 patients and as severe in 6 patients, respectively. By performing multiple logistic regression, normal lung auscultation was a significant and independent predictor for not having an airway obstruction (OR 2.48 (1.43–4.28); ). Conclusion: Under emergency room conditions, physicians can quite accurately exclude airway obstruction by auscultation. Normal lung auscultation is an independent predictor for not having an airway obstruction. However, airway obstruction is often overestimated by auscultation; thus, spirometry should be performed. [Copyright &y& Elsevier]

Abstract: Background: Abnormalities of intracellular calcium handling are widely recognized as a common hallmark of heart failure in animal models and humans. Modifying the interaction of phospholamban (PLB) with the sarcoplasmic reticulum ATPase (SERCA) by PLB mutants improves cardiac function but may also lead to heart failure. In this study we describe the in vivo effects of a new approach to modify the PLB–SERCA interaction using a recombinant, intracellularly expressed chicken-antibody derived protein (PLADP) targeting the cytoplasmic domain of PLB in the cardiomyopathic BIO 14.6 hamster. Methods and results: In vivo gene transfer was performed in 12–14-week-old BIO 14.6 cardiomyopathic hamsters using intracoronary delivery of adenovirus containing the PLADP or the β-galactosidase (LacZ) gene (8×109 PFU per animal). A third group was injected with saline (Sham). Echocardiography was performed before and, together with hemodynamic measurements, repeated 4–5 days after gene transfer. Indo-1 calcium transients and myocyte contractility were measured in isolated cardiomyocytes from the BIO 14.6 hamster transfected with the PLADP. Gene expression (LacZ) was found in 54±15% of cells throughout the heart without any signs of myocardial inflammation. Echocardiographic and hemodynamic indices of left ventricular function were significantly increased after gene transfer with the PLADP, compared to controls. Measurements of myocyte contractility and calcium transients in isolated cardiac myocytes from BIO 14.6 hamsters revealed improved intracellular calcium handling and contractility. Conclusion: In vivo adenoviral gene transfer with the PLADP resulted in short-term intracellular expression of a PLADP, improving LV function and enhancing myocardial contractility in the failing cardiomyopathic hamster heart. The PLADP enhanced contractility and cardiac function by improving intracellular calcium handling. Expression of antibody-derived protein represents a new approach to modify protein–protein interactions at the cellular level. [Copyright &y& Elsevier]