An improved survival of smokers who quit smoking at diagnosis of lung cancer has been established in particular for early stages of lung cancer but data from routine clinical practice are scarce. Moreover, apart from studies focusing on lung cancer with an oncogenic driver mutation, the prognosis of never-smokers and long-term non-smokers (“non-smokers”) has not been studied. We retrospectively analysed overall survival (OS) in all patients diagnosed with SCLC (171) and NSCLC (713) at our institutions from 2006 to 2014. In a case-control analysis matched for histology, gender, stage, and performance state, we compared non-smokers with quitters at diagnosis of lung cancer and continuing smokers. These analyses were performed for the whole population and for SCLC, squamous-cell carcinoma (SCC), and adenocarcinoma (ADC). In the case-control population, non-smokers were 3–5 years older at diagnosis of lung cancer than quitters or smokers. Median OS was 13.9 months, which compares favourably with survival in other recent cohorts and clinical studies with similar populations. In localized lung cancer stages I-III, OS of nonsmokers (22.2 mo) and continuing smokers (23.0 mo) was similar, but better in quitters (43.0 mo). In stage IV, there was no difference in the whole population, but analysis of histology subgroups revealed a trend towards poorer survival of nonsmokers in SCLC and SCC. In ADC, the survival curves showed no difference between quitters and non-smokers until 28 months but then diverged in favour of non-smokers, pointing to two subpopulations which may be driver-mutation positive patients (better survival) and driver-mutation negative patients. Favourable OS can be reached in a specialized lung cancer centre in routine clinical practice. The better survival of a subgroup of patients with metastasized ADC may be due to patients with driver mutation. Except for metastasized ADC, nonsmokers with lung cancer do not have a better prognosis than smokers but develop lung cancer at a later age. The poor survival of non-smokers points to unknown risk factors. In localized disease stages, quitting smoking at diagnosis is associated with markedly improved survival.

We present a patient with lymphangioleiomyomatosis (LAM) on long-term sirolimus (now 79 months) who has had a second successful pregnancy. The second pregnancy on uninterrupted low-dose sirolimus (plasma levels 3-5 mg/L) was uncomplicated both with respect to mother and child suggesting that low-dose sirolimus might be safe in selected pregnant patients with stable LAM. The long-term time course in this patient is in agreement with recent reports of a long-term beneficial effect of sirolimus in LAM. In this patient, the pregnancies did not seem to impair the long-term improvement of lung-function on sirolimus.

ABSTRACT Background Standard therapy for refractory or resistant relapsed small-cell lung cancer (SCLC) has not yet been established. We conducted an open-label, multicenter, non-randomized phase II study to confirm the efficacy and safety of amrubicin, a topoisomerase inhibitor, in the treatment of refractory or resistant SCLC. Material and methods Patients with SCLC that is refractory or relapsed within 90 days of completing previous treatment received amrubicin at a dose of 40 mg/m2 for 3 consecutive days, every 21 days.The study treatment was repeated until disease progression or intolerable toxicity. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Planned sample size was 80 patients to achieve power of at least 80% with one-sided alpha of 0.05, and expected and threshold value for primary endpoint as 20% and 10%. All patients were followed-up until one year after the last patient enrollment. Results Between November 2009 and February 2011, 82 patients were enrolled from 25 institutions. The median number of treatment cycles was four (range, one to 22 cycles).The ORR was 32.9% (p  Conclusions Amrubicin demonstrated the favorable tumor response and survival with acceptable toxicity. Single-agent amrubicin could be considered as a standard regimen in the treatment of refractory or resistant relapsed SCLC. Disclosure All authors have declared no conflicts of interest.

ABSTRACT Introduction Treatment of patients with small cell lung cancer (SCLC) is challenging due to the generally poor prognosis of the disease and the lack of new treatment options. There are few data on how delivered treatment has changed during the past decade in routine clinical practice and how this has effected overall survival. Methods We retrospectively analyzed all patients diagnosed with SCLC at our institution (lung cancer center certified by the German Cancer Society (DKG)) since 2002. Analysis included lines of treatment delivered, progression free survival (PFS) at each therapy line, use of radiotherapy, overall survival (OS), and use of PET-CT. Results Preliminary analysis included 102 patients, of which 41 % had limited disease (LD) and 59 % had extensive disease (ED). For all patients, platinum doublet with etoposide has remained standard first line therapy. For patients with LD, the use of simultaneous thoracic radiochemotherapy replaced sequential chemotherapy followed by thoracic radiotherapy. In order to achieve a smaller radiation field, simultaneous radiochemotherapy was usually preceded by 2 cycles of chemotherapy. For patients with extensive disease, the use of cisplatinum instead of carboplatin increased in good performance status patients due to improved antiemesis (apprepitant). As second line therapy, oral topotecan has largely replaced EpiCO (epirubicin, cyclophosphamide, vincristin). One patient with early recurrence of brain metastasis after radiotherapy and topotecan was treated successfully with oral temozolomide. Since August 2007, all ED patients responding to first line therapy received prophylactic cranial radiation. OS tended to increase throughout the study period (LD: from 14 to 17 months, ED: from 6.7 to 10.1 months). Conclusions New treatment options were successfully implemented in routine clinical practice and resulted in improved survival. However, survival remains unsatisfactory emphasizing the need for early detection and development of additional treatment strategies. Disclosure All authors have declared no conflicts of interest.

We report a successful pregnancy in a patient with longstanding LAM on treatment with sirolimus. During temporary discontinuation fo sirolimus in early pregnancy, lung function declined but recovered after resumption of sirolimus. Pregnancy was complicated by a persistent pneumothorax which was treated surgically postnatally. The child has had a normal development despite exposure to low dose sirolimus intermittently during early embryonal and mid-fetal life.

Die aktuelle Leitlinie der ESC stellt ein hilfreiches und im klinischen Alltag praktikables Instrument in der Risikostratifizierung von Patienten im Kontext eines geplanten operativen Eingriffes als auch im perioperativen Management dar. Besonders wertvoll erscheinen die klare Strukturierung der Risikostratifizierung von Patienten und geplantem operativem Eingriff in den 3 Risikokategorien niedrig, mittel und hoch und die sich daraus ableitenden Konsequenzen im medikamentösen als auch diagnostischen und interventionellen prä-, peri- und postoperativen Management. Der grundlegende Algorithmus und Entscheidungsbaum wird auch in den parallel zu diesem Kommentar publizierten Pocket-Leitlinien der Deutschen Gesellschaft für Kardiologie eine zentrale Stellung einnehmen.

Commonly, pulmonary hypertension is clinically suspected because of unexplained exertional dyspnoea or as a chance finding in clinical examination revealing signs of right heart failure. The systematic diagnostic approach and exact classification is based on the Venice classification. Basic investigations include ECG, chest radiograph, lung function studies and echocardiography. Echocardiography is the most important investigation for the diagnosis of pulmonary hypertension. It also serves as non invasive control during treatment and as the main screening test for pulmonary hypertension. Echocardiographic criteria of pulmonary hypertension are a dilated and hypertrophied right ventricle, paradoxic septum movement, a dilated right atrium, and a distended inferior Vena cava. Using Doppler echocardiography, the right ventricular and thus pulmonary arterial systolic pressure can be determined from the tricuspid regurgitant jet velocity. CT of the chest serves to exclude pulmonary embolism and interstitial lung disorders. Cardiac MRI is increasingly being used for analysis of right ventricular morphology, function and haemdynamics. The 6 minute walk test and cardiopulmonary exercise test are used to assess severity and response to treatment and give prognostic information. For the definite diagnosis of pulmonary hypertension, right heart catheterisation is required for the determination of the pulmonary vascular resistance and pharmacological testing of "reversibility".

Neben den klassischen kardiovaskulären Risikofaktoren werden prothrombogene Veränderungen des Gerinnungssystems als wichtige Marker für ein erhöhtes Atheroskleroserisiko angesehen. Erworbene Störungen der Hämostase sind häufig bei älteren Patienten anzutreffen und stehen im Zusammenhang mit der erhöhten Prävalenz chronischer Erkrankungen in diesem Kollektiv. Pathophysiologisch ist eine Verknüpfung von Krankheiten, die mit einer Hyperinsulinämie einhergehen, wie dem Diabetes mellitus, dem metabolischen Syndrom und der arteriellen Hypertonie, und einem veränderten Gleichgewicht der hämostaseologischen Faktoren gut belegt. Die Hyperinsulinämie ist als Indikator peripherer Insulinresistenz ein unabhängiger Risikofaktor der koronaren Herzkrankheit. Plasminogenaktivatorinhibitor wird als pathophysiologisches Bindeglied dieser Assoziation betrachtet. Chronische Entzündungsprozesse, die im Alter häufig sind, können über eine Hyperfibrinogenämie weiter zur Störung des hämostaseologischen Gleichgewichts beitragen. Schließlich ist denkbar, dass diese prothrombogenen Veränderungen die Progression der Atherosklerose im Alter beschleunigen und das Auftreten akuter Koronarsyndrome begünstigen. Diese Zusammenhänge unterstreichen, dass die optimierte Behandlung von chronischen Begleiterkrankungen ein wichtiger Aspekt der Primär- und Sekundärprävention atherosklerotischer Manifestationen im Alter ist. Darüber hinaus bietet die prothrombogene Aktivierung des Gerinnungssystems einen vielversprechenden Ansatzpunkt für spezifische Therapienkonzepte.

HISTORY AND CLINICAL FINDINGS A 55-year-old female patient reported left-sided chest pain at rest as well as during exercise, which recurred during the last three years before admission. Cardiovascular risk factors included hypercholesterolemia and smoking. The physical examination of the patient was unremarkable. INVESTIGATIONS The ECG at rest showed T-wave inversions in leads I, aVL, V3-V6 and ergometric exercise testing resulted in angina pectoris and descending ST-segments in leads V3-V6. Stress thallium 201 scintigraphy demonstrated a reversible perfusion deficit of the the anterior wall at peak exercise. The left ventricular angiogram and echocardiogram revealed normal end-diastolic dimensions and regular systolic contractions without signs of left ventricular hypertrophy. Selective coronary arteriography excluded hemodynamically relevant stenosis of the coronary arteries. A coronary artery fistula originating from a large, ectatic first diagonal branch with drainage into the left ventricle was observed. TREATMENT AND COURSE Because the patient rejected interventional therapy she was treated conservatively and follow-up investigations 3 and 4 years after arteriography revealed unchanged clinical symptomatology. CONCLUSION In this case a "coronary steal" phenomenon caused by the coronary fistula induced myocardial ischemia. Therefore if present congenital coronary anomalies have to be considered in patients with chest pain and normal coronary angiogram.

Long-term intermittent heparin-induced extracorporeal low-density lipoprotein (LDL)-cholesterol precipitation was performed in three men - aged 32, 52 and 56 years - with severe familial hypercholesterolaemia and angiographically demonstrated coronary heart disease. This significantly lowered by 65-70% their LDL-cholesterol concentration and by 48-54% their fibrinogen concentration. Fibrinogen elimination reduced plasma viscosity by 13-14% and clearly raised the transcutaneously measured partial pressure of oxygen by 33-50%. Clinically the improved microcirculation achieved a decrease in angina symptoms: the walking distance of the 52-year-old man increased from about 100 m to 4000 m, the daily need of glyceryl trinitrate falling from an average of 12 to 4 aerosol doses.

Five thousand consecutive percutaneous transluminal coronary angioplasties (PTCA) were electively performed between January 1988 and June 1993. They were analysed for the incidence of acute coronary occlusion, its acute treatment and subsequent course. In 133 patients (2.7%) the occlusion persisted. Recanalization by repeat PTCA was attempted in all of them, but succeeded in only 68 (51%). In 65 patients recanalization was impossible. In 25 of the latter--patients with a small infarct vessel and infarction having already occurred in the vessel's supply area while the haemodynamics remained stable--conservative treatment was practised. Acute surgical revascularization was undertaken in 30 patients (23%) with a large area and/or haemodynamic instability. In all, 14 patients died (overall death rate 0.28%, death rate of patients with occlusion 11%), ten of them before operative intervention was possible.--Not all coronary artery occlusions can be treated nonsurgically. Consequently, availability of surgical intervention at the place of elective PTCA is mandatory.

Treatment of chronic severe bronchial asthma with corticosteroids is inadequate in a minority of patients and is often accompanied by considerable side effects. Additional specific immunosuppression appears to be therapeutically promising.Three patients (2 women, aged 44 and 29, a man aged 57 years), all with chronic severe asthma requiring corticosteroids, were given cyclosporin (mean dose 1.8 mg/kg; serum level 72 +/- 35 ng/ml) additional to conventional bronchospasmolytic drugs for 9 to 20 months.The frequency and intensity of asthmatic attacks markedly decreased in all three patients. The mean peak-flow measurements in the mornings before broncholysis had increased by 23% over the precyclosporin level of the calculated normal value. Peak flow variability improved by 13%. The mean one-second forced expiratory volume (FEV1) rose from 37 to 66% of the normal value (P < or = 0.05) and correlated with the serum cyclosporin level (correlation coefficient 0.58-0.97). The frequency of acute severe asthmatic attacks (FEV1 < or = 40%) requiring additional hospitalization with intravenous administration of glucocorticoids fell by 30%. The systemic corticosteroid maintenance dosage could be significantly reduced or the drug discontinued in two patients.These observations indicate that cyclosporin can be useful in the treatment of selected cases of chronic severe steroid-refractory asthma. Prospective studies are needed to judge its long-term efficacy.

More than 25 years ago it was demonstrated that an improvement in various parameters of blood flow in patients who have an hyperviscosity syndrome improves coronary blood flow. Hyperfibrinogenemia with resulting increase in plasma viscosity and erythrocyte aggregation has been demonstrated in patients with coronary heart disease. Poiseuille's law, which describes the interaction between vascular resistance, vessel geometry and blood viscosity, indicates--when applied to coronary artery disease--that an increase in the viscosity of blood, especially of plasma, can in the poststenotic microcirculation be a flow-limiting factor and a critical determinant of oxygen supply to myocardium that is at risk of ischaemia. An increased concentration of fibrinogen, which is the substance that causes the increase in plasma viscosity, has been shown to correlate prospectively with the risk of serious cardiovascular events. Patients with multiple-vessel coronary heart disease and treatment-refractory angina pectoris have clearly increased fibrinogen values. Chronic intermittent urokinase administrations--given with the aim of achieving fibrinogenolysis of the elevated fibrinogen concentration at a dose of 500 000 IU urokinase three times weekly -improves the rheological parameters and achieves an impressive decrease in symptoms. It is thus important in clinical practice to take into account that patients with atherosclerosis and a fibrinogen concentration of more than 300 mg may develop perfusion disorders and worsening of their symptoms.

The effect of fenofibrate (a clofibrate derivative) on fibrinogen concentration, blood viscosity and myocardial microcirculation was examined in 35 patients with coronary heart disease (n = 27) or hypertension (n = 8). After eight weeks' administration of 250 mg fenofibrate daily cholesterol and triglycerides levels decreased significantly, as did the fibrinogen concentration, from a mean of 300.7 +/- 75.1 mg/dl to 252.3 +/- 61.2 mg/dl (P less than 0.01). Plasma viscosity and erythrocyte aggregation were also significantly lowered (from 1.43 +/- 0.09 to 1.37 +/- 0.07 mPas and 15.0 +/- 3.1 to 13.5 +/- 2.2, respectively; P less than 0.01). In eight of twelve subjects selected from the whole group thallium myocardial scintigraphy demonstrated, after eight weeks of treatment with fenofibrate, a global (in two) or regional (in six) increase in blood flow. Reduction of fibrinogen concentration may in coronary heart disease achieve an improvement in myocardial microcirculation with decreased myocardial ischaemia.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study