[Differential Diagnosis of Pulmonary Hypertension Using the Example of Collagenosis-associated PAH in the Context of Chronic Lung and Left Heart Disease]. / Differenzialdiagnostik der pulmonalen Hypertonie am Beispiel der Kollagenose assoziierten PAH im Kontext chronischer Lungen- und Linksherzerkrankungen.

Pulmonary hypertension (PH) can be diagnosed in the context of connective tissue diseases (CTD) as well as in elderly patients with multiple comorbidities. A correct clinical differential diagnosis and classification is essential before adequate therapeutic decisions can be made. Differential diagnosis of PH in CTD comprises associated pulmonary arterial hypertension (APAH), group 2 or 3 PH (PH arising from left heart or chronic lung disease), chronic thromboembolic PH (PH) and group 5 (e. g. in the context of terminal renal insufficiency). This is also true of elderly patients in whom the decision has to be made if the increasing number of coincident diseases lead to PH or have to be interpreted as comorbidities. In this manuscript, the differential diagnosis of PH is elucidated, focusing on CTD, in the context of left heart disease and chronic lung disease. Furthermore, criteria are presented facilitating an objective approach in this context.

[Current Aspects of Definition and Diagnosis of Pulmonary Hypertension]. / Aktuelle Definition und Diagnostik der pulmonalen Hypertonie.

At the 6th World Symposium on Pulmonary Hypertension (WSPH), which took place from February 27 until March 1, 2018 in Nice, scientific progress over the past 5 years in the field of pulmonary hypertension (PH) was presented by 13 working groups. The results of the discussion were published as proceedings towards the end of 2018. One of the major changes suggested by the WSPH was the lowering of the diagnostic threshold for PH from ≥ 25 to > 20 mmHg mean pulmonary arterial pressure, measured by right heart catheterization at rest. In addition, the pulmonary vascular resistance was introduced into the definition of PH, which underlines the importance of cardiac output determination at the diagnostic right heart catheterization.In this article, we discuss the rationale and possible consequences of a changed PH definition in the context of the current literature. Further, we provide a current overview on non-invasive and invasive methods for diagnosis, differential diagnosis, and prognosis of PH, including exercise tests.

[Exercise Testing in Respiratory Medicine - DGP Recommendations]. / Belastungsuntersuchungen in der Pneumologie ­ Empfehlungen der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e. V.

This document replaces the DGP recommendations published in 1998 and 2013. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method and its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for blood gas analysis and right heart catheterization during exercise, walk tests, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, obesity, monitoring of rehabilitation or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

[Exercise testing in respiratory medicine]. / Belastungsuntersuchungen in der Pneumologie.

This document replaces the DGP recommendations published in 1998. Based on recent studies and a consensus conference, the indications, choice and performance of the adequate exercise testing method in its necessary technical and staffing setting are discussed. Detailed recommendations are provided: for arterial blood gas analysis and right heart catherterization during exercise, 6-minute walk test, spiroergometry, and stress echocardiography. The correct use of different exercise tests is discussed for specific situations in respiratory medicine: exercise induced asthma, monitoring of physical training or therapeutical interventions, preoperative risk stratification, and evaluation in occupational medicine.

Successful implementation of modern critical care in the low-resources country Bosnia and Herzegovina : Single-center experience.

BACKGROUND: Critical care medicine is a relatively young discipline, developed in the mid-1950s in response to the outbreak of poliomyelitis. The mass application of mechanical ventilation and its subsequent technical advancement helped manage large numbers of patients with respiratory failure. This branch of medicine evolved much faster in high-income (HIC) than low- and middle-income countries (LMIC). Seventy years later, mankind's encounter with coronavirus disease 2019 (COVID-19) represents another major challenge for critical care medicine especially in LMIC countries where over two thirds of the world population live. METHODS: Systematic analysis of written documents related to the establishment of the first multidisciplinary medical intensive care unit (MICU) in Bosnia and Herzegovina and its development to the present day. RESULTS: We describe the experience of setting up a modern critical care program under LMIC constraints as a promising way forward to meet the increased worldwide demand for critical care. Successful development is contingent on formal education and continued mentorship from HIC, establishment of a multidisciplinary team, the support from local health care authorities, development of a formal subspecialty training, academic faculty development, and research. Novel technologies including tele-education provide additional opportunities for rapid development and dissemination of critical care medicine programs in LMIC. CONCLUSION: Critical care medicine is a critical public health need in HIC and LMIC alike. The challenges associated with the coronavirus pandemic should serve as a wakeup call for rapid development of critical care programs around the world.

Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study.

We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH; n = 42) or pulmonary arterial hypertension (PAH; n = 33) in World Health Organization (WHO) functional class II/III. In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0-2.5 mg t.i.d. titrated according to systemic systolic blood pressure (SBP). Primary end-points were safety and tolerability; pharmacodynamic changes were secondary end-points. Riociguat was generally well tolerated. Asymptomatic hypotension (SBP <90 mmHg) occurred in 11 patients, but blood pressure normalised without dose alteration in nine and after dose reduction in two. Median 6-min walking distance increased in patients with CTEPH (55.0 m from baseline (390 m); p<0.0001) and PAH (57.0 m from baseline (337 m); p<0.0001); patients in functional class II or III and bosentan pre-treated patients showed similar improvements. Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm(-5) from baseline (709 dyn·s·cm(-5); p<0.0001). 42 (56%) patients were considered to have experienced drug-related adverse events (AEs; 96% mild or moderate). Dyspepsia, headache and hypotension were the most frequent AEs. Study discontinuation because of AEs was 4%. These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms and pulmonary haemodynamics in CTEPH and PAH. Randomised controlled trials are underway.

Anaesthetic specialisation leads to improved early- and medium-term survival following major vascular surgery.

OBJECTIVE: Vascular surgical specialisation is associated with improved outcomes. We aimed to assess the effect of anaesthetic specialisation on outcome following major vascular surgery. DESIGN: Retrospective cohort study. METHODS: Patients undergoing major vascular surgery (lower limb revascularisation, elective and ruptured abdominal aortic aneurysm repair, endovascular aneurysm repair and carotid endarterectomy) over a five-year period were identified from a prospective database. The primary outcomes were death within 30 days and death within two years of surgery. Potential risk factors for mortality were assessed using multivariate logistic regression modelling. RESULTS: The analysis cohort comprised 1155 patients followed up for a median of 583 days. Mortality within two years of surgery was 16%. For the overall cohort, care from vascular anaesthetists was independently associated with reduced 30-day (odds ratio 0.22; 95% CI 0.12-0.62) and medium-term mortality (0.31; 95% CI 0.18-0.55). For elective patients (n=851), vascular anaesthesia reduced two-year mortality (odds ratio 0.29; 95% CI 0.15-0.58; P=0.0004) though not 30-day mortality (odds ratio 0.55; 95% CI 0.15-1.95; P=0.35). For emergency patients, care by a vascular anaesthetist influenced neither 30-day mortality (odds ratio 0.33; 95% CI 0.08-1.41; P=0.13) nor medium-term mortality (odds ratio 0.45; 95% CI 0.17-1.21; P=0.11). CONCLUSIONS: Anaesthetic specialisation reduced early- and medium-term mortality rates following major vascular surgery. If replicated by prospective studies, these results suggest that vascular surgery services would benefit from specialised anaesthetic support.

[60-year old woman with round lesion of the right upper lobe of the lung after heart transplantation]. / 60-jährige Patientin mit Raumforderung im rechten Lungenoberlappen nach Herztransplantation.

We report on a woman presenting with fever and novel round lesion in the lung four months after heart transplantation. Microbiologic assessment of bronchial lavage and operative specimen revealed pulmonary nocardiosis. Furthermore, cerebral involvement has been observed. Antibiotic treatment according to the microbiological sensitivity test for eleven months resulted in complete remission of pulmonary and cerebral nocardiosis. Immunosuppressive treatment increases the risk for opportunistic infections early after transplantation as well as malignancies during the late course.

Randomized clinical trial of folate supplementation in patients with peripheral arterial disease.

BACKGROUND: The aim was to determine whether folate supplementation improved arterial function in patients with peripheral arterial disease (PAD). METHODS: Individuals with PAD were randomly assigned to receive 400 microg folic acid (45 patients) or 5-methyltetrahydrofolate (5-MTHF) (48) daily, or placebo (40) for 16 weeks. Primary endpoints were changes in plasma total homocysteine (tHcy), ankle : brachial pressure index (ABPI) and pulse wave velocity (PWV). Secondary outcomes were changes in plasma inflammatory markers. RESULTS: Plasma tHcy was significantly reduced in folic acid and 5-MTHF groups compared with controls: median difference: - 2.12 (95 per cent confidence interval - 3.70 to - 0.75) micromol/l (P = 0.002) and - 2.07 (-3.48 to - 0.54) micromol/l (P = 0.007) respectively. ABPI improved significantly: median difference 0.07 (0.04 to 0.11) (P < 0.001) and 0.05 (0.01 to 0.10) (P = 0.009) respectively. Brachial-knee PWV (bk-PWV) decreased significantly in individuals receiving 5-MTHF and tended to be reduced in those taking folic acid compared with controls: median difference: - 1.10 (-2.20 to - 0.20) m/s (P = 0.011) and - 0.90 (-2.10 to 0.00) m/s (P = 0.051) respectively. Plasma levels of inflammatory markers were not affected. CONCLUSION: Folate administration reduced plasma homocysteine, and slightly improved ABPI and bk-PWV.

Homocysteine and peripheral arterial disease: systematic review and meta-analysis.

OBJECTIVE: To evaluate homocysteine (Hcy) levels in patients with peripheral arterial disease (PAD) as compared to unaffected controls, and to review the clinical effects of therapy aimed at lowering homocysteine in PAD patients. METHODS: MEDLINE, EMBASE and Cochrane databases were searched from 1950 to December 2007. We selected observational studies and trials that evaluated Hcy levels in patients with PAD compared to unaffected controls. We also included trials on the effect of Hcy-lowering therapy (folate supplementation) in PAD patients. Continuous outcomes were pooled in a random effects meta-analysis of the weighted mean difference between comparator groups. RESULTS: We retrieved 33 potentially suitable articles from our search. Meta-analysis of 14 relevant studies showed that Hcy was significantly elevated (pooled mean difference +4.31micromoll; 95% C.I. 1.71, 6.31, p<0.0001 with significant heterogeneity) in patients with PAD compared to controls. As all 14 studies consistently demonstrated raised plasma Hcy levels in PAD patients, the significant heterogeneity in this meta-analysis probably arises from differences in the degree of Hcy elevation. The effect of folate supplementation on PAD was tested in eight clinical trials but clinically important end points were inconsistently reported. CONCLUSION: Patients with PAD have significantly higher Hcy levels than unaffected controls. However, we did not find any robust evidence on clinically beneficial effects of folate supplementation in PAD.

[The heart and weaning]. / Herz und Weaning.

The initiation of and weaning from mechanical ventilation with extubation cause significant changes in intrathoracic pressures and have profound consequences for the cardiovascular function. However, in spite of the known pathophysiological relationships, frequently little attention is paid to the cardiovascular situation during the weaning period. The currently available guidelines concerning weaning and extubation/reintubation are based on only limited evidence and are thus rather general. Moreover, recommendations for the cardiovascular management during weaning reflect mainly the pathophysiological rationale. In patients with known cardiac disease, studies have demonstrated the necessity for a prolonged weaning process. On the contrary, many intensive care patients have subclinical or undiagnosed cardiac disease, and cardiovascular compensation mechanisms are frequently hampered by the underlying critical illness. Therefore, in a significant proportion of patients, weaning and extubation attempts fail due to the patient's limited cardiovascular reserves. This review summarises the relevant information for a successful weaning and extubation with special respect to the cardiovascular function.

Effect of collagen turnover and matrix metalloproteinase activity on healing of venous leg ulcers.

BACKGROUND: The presence of fibrous tissue in poorly healing venous leg ulcers suggests abnormal collagen metabolism. The aim was to determine whether there were differences in collagen turnover and matrix metalloproteinase (MMP) activity between ulcers that healed, those that did not heal and normal skin. METHODS: Biopsies were taken from the ulcers of 12 patients whose venous ulcers went on to heal and 15 patients whose ulcers failed to heal despite 12 months of compression bandaging. Biopsies were taken from 15 normal controls. Collagen turnover (collagen III N-terminal propeptide (PIIINP) and degraded collagen), and total MMP, MMP-1 and MMP-3 activities were measured. RESULTS: PIIINP and degraded collagen levels were higher in ulcers that healed compared with lesions that failed to heal (P = 0.005 and P < 0.001 respectively) and normal skin (P = 0.003 and P < 0.001). MMP-1 activity was also higher in healing ulcers than resistant ulcers (P < 0.001) and normal skin (P < 0.001). Significantly more total MMP activity was present in all ulcers than in normal skin (P < 0.001), but there was no difference in total MMP (and MMP-3 activity) between ulcers that healed and those that did not. CONCLUSION: Rapidly healing venous leg ulcers had increased collagen turnover and MMP-1 activity, which appeared to differentiate them from those that failed to heal within 12 months.

A pregnant woman with acute myocardial infarction due to coronary artery dissection: pre-hospital and in-hospital management.

A young pregnant woman (32nd week of gestation) presented with acute chest pain due to right coronary artery dissection (CAD) in a pre-hospital setting. The pre-hospital diagnosis by the ambulance staff of an acute myocardial infarction in the antenatal period based on a 12-lead ECG combined with successful treatment by percutaneous coronary intervention with stenting is novel.

[Inhalative application devices for patients suffering from asthma bronchiale]. / Inhalative Applikationsformen bei Asthma bronchiale und COPD.

Asthma is a chronic inflammatory disorder of the airways. It is caused by infiltration of eosinophils, mast cells, and CD4+ -T-lymphocytes which leads to variable airway obstruction. The core element of therapy is to control inflammation, which is best possible with inhaled steroids, the so-called controller drugs. Cromones are only second line therapeutic agents because they are not powerful enough for optimal inflammation control. Reliever drugs like beta2-agonists or anticholinergic agents serve as a symptomatic medication because they only lead to bronchial dilatation. The inflammation in COPD is caused by neutrophils, macrophages and CD8+ -T-lymphocytes. This kind of inflammation causes an irreversible airway obstruction accompanied by destruction of the lung parenchyma. By the majority, only symptomatic medication is effective for COPD, like anticholinergic agents and beta2-agonists. About 10-20% of patients with COPD are showing improvement when treated with inhaled steroids. However, the best treatment result is only guaranteed by optimal application of the medication. The most important barrier is an insufficient coordination between manual use of the inhaling system and inhalation. Various attempts are made to solve this problem, thus leading to a huge variety of application systems. However this also leads to confusion of patients and doctors because it is difficult to choose the optimal system and to use it in the most efficient way. This article provides an overview of the different application systems and compiles important details to facilitate the optimal application of inhalation therapy by the patient.

[Clinical classification and initial diagnosis of pulmonary hypertension: recommendations of the Cologne Consensus Conference 2016]. / Klinische Klassifikation der pulmonalen Hypertonie und initiale Diagnostik: Empfehlungen der Kölner Konsensus Konferenz 2016.

The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the clinical classification and diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the clinical classification and initial diagnosis of PH. This article summarizes the results and recommendations of this working group.

Respiratory muscle dysfunction in congestive heart failure: clinical correlation and prognostic significance.

BACKGROUND: In congestive heart failure (CHF), the prognostic significance of impaired respiratory muscle strength has not been established. METHODS AND RESULTS: Maximal inspiratory pressure (Pi(max)) was prospectively determined in 244 consecutive patients (207 men) with CHF (ischemic, n=75; idiopathic dilated cardiomyopathy, n=169; age, 54+/-11 years; left ventricular ejection fraction [LVEF], 22+/-10%). Pi(max) was lower in the 244 patients with CHF than in 25 control subjects (7.6+/-3.3 versus 10.5+/-3.7 kPa; P=0.001). The 57 patients (23%) who died during follow-up (23+/-16 months; range, 1 to 48 months) had an even more reduced Pi(max) (6.3+/-3.2 versus 8.1+/-3.2 kPa in survivors; P=0.001). Kaplan-Meier survival curves differentiated between patients subdivided according to quartiles for Pi(max) (P=0.014). Pi(max) was a strong risk predictor in both univariate (P=0.001) and multivariate Cox proportional hazard analyses (P=0.03); multivariate analyses also included NYHA functional class, LVEF, peak oxygen consumption (peak VO(2)), and norepinephrine plasma concentration. The areas under the receiver-operating characteristic curves for prediction of 1-year survival were comparable for Pi(max) and peak VO(2) (area under the curve [AUC], 0.68 versus 0.73; P=0.28), and they improved with the triple combination of Pi(max), peak VO(2), and LVEF (AUC, 0.82; P=0.004 compared with AUC of Pi(max)). CONCLUSIONS: In patients with CHF, inspiratory muscle strength is reduced and emerges as a novel, independent predictor of prognosis. Because testing for Pi(max) is simple in clinical practice, it might serve as an additional factor to improve risk stratification and patient selection for cardiac transplantation.