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Background Surgical replacement of the aortic root is the only intervention that can prevent aortic dissection and cardiovascular death in Marfan syndrome (MFS). However, in some individuals, MFS also causes sleep apnea. If sleep apnea predicts cardiovascular death, a new target for predictive, preventive, and personalized medicine (PPPM) may emerge for those individuals with MFS who have sleep apnea. Methods This is an investigator-initiated study with long-term follow-up data of 105 individuals with MFS. All individuals were screened for sleep apnea regardless of symptoms. Cardiovascular death served as a primary endpoint, and aortic events as a secondary outcome. Results Sleep apnea with an apnea–hypopnea index (AHI) > 5/h was observed in 21.0% (22/105) with mild sleep apnea in 13% (14/105) and moderate to severe sleep apnea in 7.6% (8/105). After a median follow-up of 7.76 years (interquartile range: 6.84, 8.41), 10% (10/105) had died, with cardiovascular cause of death in 80% (8/10). After adjusting for age and body mass index (BMI), the AHI score emerged as an independent risk factor for cardiovascular death (hazard ratio 1.712, 95% confidence interval [1.061–2.761], p = 0.0276). The secondary outcome of aortic events occurred in 33% (35/105). There was no effect of the AHI score on aortic events after adjusting for age and BMI (hazard ratio 0.965, 95% confidence interval [0.617–1.509]), possibly due to a high number of patients with prior aortic surgery. Interpretation Sleep apnea is emerging as an independent predictor of cardiovascular death in MFS. It seems mandatory to screen all individuals with MFS for sleep apnea and to include these individuals, with both MFS and sleep apnea, in further studies to evaluate the impact of preventive measures with regard to cardiovascular death.

Background Several strategies have been investigated to improve the 4% survival advantage of adjuvant chemotherapy in early-stage non-small-cell lung cancer (NSCLC). In this investigator-initiated study we aimed to evaluate the predictive utility of the messenger RNA (mRNA) expression levels of excision repair cross complementation group 1 (ERCC1) and thymidylate synthase (TS) as assessed in resected tumor. Patients and methods Seven hundred and seventy-three completely resected stage II-III NSCLC patients were enrolled and randomly assigned in each of the four genomic subgroups to investigator’s choice of platinum-based chemotherapy (C, n = 389) or tailored chemotherapy (T, n = 384). All anticancer drugs were administered according to standard doses and schedules. Stratification factors included stage and smoking status. The primary endpoint of the study was overall survival (OS). Results Six hundred and ninety patients were included in the primary analysis. At a median follow-up of 45.9 months, 85 (24.6%) and 70 (20.3%) patients died in arms C and T, respectively. Five-year survival for patients in arms C and T was of 65.4% (95% CI (confidence interval): 58.5% to 71.4%) and 72.9% (95% CI: 66.5% to 78.3%), respectively. The estimated hazard ratio (HR) was 0.77 (95% CI: 0.56-1.06, P value: 0.109) for arm T versus arm C. HR for recurrence-free survival was 0.89 (95% CI: 0.69-1.14, P value: 0.341) for arm T versus arm C. Grade 3-5 toxicities were more frequently reported in arm C than in arm T. Conclusion In completely resected stage II-III NSCLC tailoring adjuvant chemotherapy conferred a non-statistically significant trend for OS favoring the T arm. In terms of safety, the T arm was associated with better efficacy/toxicity ratio related to the different therapeutic choices in the experimental arm.

Background Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI. Methods Retrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint. Results Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis. Conclusions D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations.

Background: Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. Methods: Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. Results: Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. Conclusion: R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first–line treatment.

Background The percentage of pts switching from 1st gen TKI in 1st line to 3rd gen TKI in 2nd line seems to be low with 30% and it is questionable whether these data represent real world treatments. Therefore, we investigated the treatment pattern and especially the attrition rate between 1st and 2nd line therapy in EGFR mt+ pts from the NOWEL network. Methods A retrospective study of 1539 pts with non-squamous NSCLC IV was accomplished. 965/1536 (63%) pts were tested for EGFR mt+ between 2009-2018. 148/965 (15%) pts with an EGFR mt+ were identified. To calculate PFS and OS we used Kaplan Meier methods and the log rang test for p-values. Results Baseline characteristics of 148 EGFR mt+ pts: median age 65 yrs; 64% female (n = 95/148); 64% never/light smoker (n = 94/148). 135/148 pts (91%) carried an EGFR mt+ either del19 (n = 81) or L858R (n = 55). 144/148 pts were treated with TKI on 1st or 2nd line (after chemotherapy) and 4 pts received no therapy at all. 14/144 pts are still on 1st line, 9 pts were lost to follow-up and 3 pts died while on 1st line therapy. We identified 118/144 candidates for 2nd line therapy (because of progression on 1st line TKI) and only 84/118 (70%) pts received a 2nd line therapy. 30% (36/118) of pts did not receive a 2nd line therapy because of bad PS (n = 26), pts refusal (n = 2), fast progression (n = 6) and death (n = 2). After accessibility of 3rd gen TKI 72 pts were candidates for 2nd line treatment and 51/71 pts (71%) received a 2nd line therapy. MOS of pts receiving 2nd line therapy after access to 3rd gen TKI was 35 mo for pts with 2nd line therapy vs. 10 mo without 2nd line (p Conclusions In real world, a significant number of pts treated with 1st or 2nd gen TKI do not reach 2nd line therapy even with broad accessibility of 3rd gen TKI. Reasons for not receiving 2nd line therapy are in most cases deterioration of PS, death and no testing for T790M in a minority of cases. These data are important for the interpretation of the OS data of the FLAURA study as they reflect real world treatment algorithms in dedicated German lung cancer centers. Legal entity responsible for the study Carl v. Ossietzky University of Oldenburg, Prof. Dr. Griesinger. Funding Has not received any funding. Disclosure J. Roeper: Honoraria (self): Boehringer Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Falk: Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self): Roche; Honoraria (self): AstraZeneca. M. Tiemann: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche ; Honoraria (self): AstraZeneca. F. Griesinger: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Boehriger Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): MSD; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Celegene; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Siemens; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Bayer. All other authors have declared no conflicts of interest.

In spite of intensive research and a huge amount of chemotherapy trials, the prognosis of metastastic non-small cell lung cancer (NSCLC) is still poor. Erlotinib and Gefitinb are tyrosine kinase inhibitors (TKIs) which act against the EGF receptor (EGF-R). Activation of mutations in the tyrosine kinase domain leads to an increase in effectiveness. What is the clinical impact of EGF-R mutation screening? What value do TKIs in 1st, 2nd and 3rd line have in therapy for metastatic NSCLC? Which treatment options exist after failure of TKI in the 1st line? These and other clinically relevant questions in the context of TKIs are discussed in the present comprehensive review.

e21220Background: Recently FLAURA study demonstrated significant PFS and numeric OS benefit for Osimertinib 1st line vs. 1st gen. TKI’s. The number of pts switching from 1st gen. to 3rd gen. TKI (3...

Objective The efficacy and acceptance of self-regulated continuous positive airway pressure (auto-CPAP) ventilation was compared with conventional CPAP administration in the treatment of patients with obstructive sleep apnoea. Patients and methods Using a cross-over design, under polysomnographic monitoring in a sleep laboratory, 25 patients with obstructive sleep apnoea underwent conventional CPAP or auto-CPAP treatment. Using a questionnaire, patients gave their assessment of its acceptability and efficacy after each treatment session. Results The mean pressure during treatment was the same in the two groups (7.2 +/- 1.9 versus 7.1 +/- 1.9 mbar; no significant difference). Maximal pressure during auto-CPAP averaged 3.7 +/- 2.1 mbar higher than during conventional CPAP ventilation. The mean apnoea-hypopnoea index (AHI) during auto-CPAP, 4.4 +/- 4.3 mbar, during auto-CPAP was significantly higher than during conventional CPAP treatment (2.8 +/- 2.8 mbar; P = 0.044). In eight patients on auto-CPAP an AHI of 5 or less could not be reached, while an AHI of 5 or less was obtained in all but three patients under conventional CPAP. In a subgroup of 17 patients, in whom a reduction of AHI to at most 5 was achieved with both conventional and auto-CPAP, analysis of sleep pattern and of arousals was similar with the two forms of ventilation. Several patients reported that with auto-CPAP falling in sleep was more difficult and they slept less well. None of the patients preferred auto-CPAP. Conclusion By means of the auto-CPAP neither a pressure reduction nor an improvement in compliance could be achieved. Therapeutic effectiveness was significantly less as with conventional CPAP therapy.

HISTORY AND FINDINGS A 39-year-old man was hospitalized because of continually rising urinary creatinine and blood urea nitrogen concentration. He was known to have familial adenomatous polyposis (FAP), first diagnosed 18 years previously and re-Physical examination was unremarkable except for pain on percussion over both kidney regions. There was a well-healed laparotomy scar. INVESTIGATIONS Ultrasound revealed chronic bilateral obstructive renal disease, grade II-III, and computed tomography showed a conglomerate retroperitoneal tumour with obstruction of both ureters at the level of the lower pelvis. This tumour had first been noted first 3 years after the colectomy when the patient complained of abdominal pain. It had been identified histologically as a nonresectable retroperitoneal desmoid tumour. TREATMENT AND COURSE An external fistula was made, relieving the renal retention. To suppress growth of the desmoid tumour Sulindac, a nonsteroid anti-inflammatory drug, was administered. Genetic molecular analysis revealed a germ line defect in codon 1690 of the APC gene. It is intended to examine other members of the family for the presence of this defect. CONCLUSION Desmoid tumours are more common in persons with FAP and are among the most frequent extracolic causes of their death. Treatment options are critically analysed.

The treatment of patients with non-small cell lung carcinoma (NSCLC) is guided by results from clinical studies. Data about molecular changes in the tumour are not used (up to now) to decide for an individualised, tumour-tailored therapy. High-throughput technologies and modern analytical methods (e. g., microarrays) lead to exponentially increasing knowledge about genetic changes in the cells and the interaction of proteins. This results in the discovery of molecular factors with high predictive (prediction of tumour response) and prognostic (prediction of survival) value in NSCLC. Among these are ERCC1, RRM1 and some receptor tyrosine kinases. Preliminary data of prospective studies have shown promising results for the selection of specific drugs, when these tumour markers were analysed. Therefore, this review focuses on the actual value of molecular markers for decision-making in the adjuvant and palliative setting and their probable future introduction into clinical practice.

History and admission findings Two men were hospitalized (three years apart) after aspirating petroleum on their fist attempt at "fire-eating". Pt.1 (aged 25 years) complained of chest pain, dyspnea and dizziness. The other (Pt. 2; aged 29 years) had a hemoptysis. Pt. 1 had a normal body temperature, but the breath sounds were decreased over the left base. The breath sounds in Pt. 2 were normal, but he had a fever of 38.8 degrees C. Routine physical examination was unremarkable. Investigations Laboratory tests in both patients revealed increased inflammatory parameters. Chest radiographs showed that Pt. 1 had a left basal alveolar infiltrate, while Pt. 2 had an infiltrate in the right middle and upper lobe, which on computed tomography after a few days showed signs of cavitation in the left infrahilar region and the middle lobe, respectively. Pneumococci were found in the sputum of Pt. 2. Treatment and course Both patients were given antibiotics, Pt. 1 also had salbutamol inhalation treatment. The patients were discharged symptom-free after 8 and 10 days, respectively. A follow-up chest radiograph four weeks later in Pt. 1 merely showed streaky-fibrotic residues. Conclusion These two case reports and detailed literature search indicate that immediate administration of antibiotics is important, while routine steroid treatment is not necessary.

Serum leptin and ghrelin levels were investigated in patients with obstructive sleep apnoea (OSA) syndrome before and during continuous positive airways pressure (CPAP) treatment and compared with body mass index (BMI)-matched controls without OSA. Male patients (n=30) with OSA (apnoea/hypopnoea index=58+/-16, BMI=32.6+/-5.3 kg x m(-2)) underwent CPAP treatment. Fasting leptin and ghrelin were measured at baseline and 2 days, and in the case of leptin 2 months after initiation of treatment. Baseline plasma ghrelin levels were significantly higher in OSA patients than in controls. After 2 days of CPAP treatment, plasma ghrelin decreased in almost all OSA patients (n=9) to levels that were only slightly higher than those of controls (n=9). Leptin levels did not change significantly from baseline after 2 days of CPAP treatment, but were higher than in the control group. After 8 weeks, leptin levels decreased significantly, although the BMI of the patients showed no change. The decrease in leptin levels was more pronounced in patients with a BMI30 kg x m(-2). These data indicate that the elevated leptin and ghrelin levels are not determined by obesity alone, since they rapidly decreased during continuous positive airways pressure therapy.

Autoadjusting CPAP devices (APAP) are designed to continuously adjust the positive pressure to the required levels, and thus increase treatment quality and patient compliance. The results of APAP treatment strongly depend on the control mechanism of the respective APAP device. In agreement with other working groups, we have recently shown that the forced oscillation technique (FOT) is capable of detecting incipient upper airway obstruction prior to physiological reactions such as the onset of increasing esophageal pressure swings or microarousals. Therefore we studied efficacy and acceptance of a novel APAP device controlled exclusively by FOT. 100 consecutive patients with OSAS confirmed by polysomnography (mean AHI 47.9 +/- 22.6) and daytime sleepiness (Epworth sleepiness scale, ESS 12.6 +/- 3.9) were randomized to either APAP treatment (n = 50) or conventional CPAP treatment (n = 50). Polysomnographies were performed at the second treatment night and subjective sleepiness (modified ESS) was established in the morning. The respiratory disturbance was largely normalized in both treatment groups in the second treatment night (AHI 4.7 +/- 5.3 vs. 3.7 +/- 3.4; n.s.). Both groups showed largely improved sleep profiles and had markedly reduced ESS-scores (6.6 +/- 3.6 vs. 7.0 +/- 3.4; n.s.). The mean treatment pressure during APAP was significantly lower than during CPAP treatment (6.0 +/- 2.0 vs. 9.0 +/- 1.8 mbar; p < 0.001). There were no significant differences between APAP and CPAP treatment in any parameter of efficacy or acceptance. APAP treatment with this device controlled exclusively by FOT is well accepted by the patients and permits an adequate treatment of OSAS without the need for invidiual CPAP titration.

STUDY OBJECTIVES To investigate the frequency of microarousals (MA) associated with pressure changes during auto-CPAP therapy (APAP) for obstructive sleep apnea (OSA). DESIGN Patients with OSA were studied by polysomnography during APAP therapy (Somnosmart). The MA were classified on the basis of concomitant changes in APAP pressure. SETTING Sleep laboratory of a university hospital PARTICIPANTS 30 patients with moderate to severe OSA. MEASUREMENTS AND RESULTS The mean AHI during APAP was 4.7+/-4.7, the mean arousal index was 14.5+/-6.6 per hour. During epochs with a pressure variation greater than 0.5 mbar, significantly more MA occurred (0.30+/-0.17 MA per epoch) than in epochs with constant treatment pressure (0.10+/-0.054 MA per epoch; p

Ein Patient wurde wegen rezidivierender Aspirationen und Emesis eingewiesen. Angaben zur Grunderkrankung konnte er nicht machen. Richtungsweisend war aber bereits bei der Untersuchung die ausgepragte Kleinhirnsymptomatik, die Sprachstorung und die Angabe rezidivierender Aspirationen. Ein 7-jahriger Krankheitsverlauf des M. Fahr war computertomographisch dokumentiert. Die initiale Symptomatik damals bestand in zunehmender Antriebsminderung, zu der erst spater neurologische Storungen, v. a. in Form von Koordinationsstorungen hinzutraten. Die Diagnose wurde durch die typischen ausgepragten Verkalkungen im Bereich der Stammganglien und des Kleinhirns gesichert. Bedeutungsvoll ist, die zunehmende Antriebsminderung der Patienten gegenuber einer Demenz abzugrenzen.

e20560 Background: Available clinical research data shows that early mutation testing for patients with NSCLC stage IV could lead to an effective choice of therapy for patients with proven mutations. Targeted therapies achieve a higher ORR, PFS, OS and a better quality of life than chemotherapy in mt+ patients. With the advent of 2nd and 3rd generation TKI´s effective in 1st generation TKI resistant tumors, we wanted to study the impact of these drugs on the outcome of patients in a real life setting in 3 lung cancer centers. Methods: 1383 patients from the three cancer centers diagnosed with NSCLC stage IV (UICC 7) were examined. Methods for the detection of mutations included Sanger Sequencing, hybridization based COBAS testing as well as hybrid cage next generation sequencing. Results: 880/1383 (64%) consecutive patients with non-squamous cell NSCLC from the cancer centers were studied for the presence of tumor mutations, especially for EGFR and ALK mutations. The EGFR mutation rate was 16.6% (141/880), and the ALK-translocation rate 3.8% (24/635). Median OS in EGFR mt+ patients was 31 (n = 78) vs. 32 (n = 38) vs. 16 (n = 14) months respectively (center 1 vs. center 2 vs. center 3). Median OS in ALK mt+ patients was 25 (n = 17) months in center 1 and 11 (n = 5) months in center 2 (p < 0.05). Use of 3rd generation TKI Osimertinib (n = 17) lead to a significantly higher OS (n = 17, median OS 67 mo) than the use of only 1st and 2nd generation TKI (n = 113, median OS 24 mo, p < 0.000). Similarly, use of 2nd and 3rd generation ALKi impacted significantly on median OS: Crizotinib alone n = 7, 17 months, Crizotinib followed by Ceritinib and/or Brigatinib (n = 9) median OS not reached, p < 0.001. Conclusions: Smalldifferences in OS were observed, depending on the treatment centers, but the use of multiple EGFR and ALK-I impacted highly significantly on the outcome of patients with EGFR and ALK-alterations in a real life setting.

The sensitivity of a simplified variant of forced oscillation technique (FOT) was studied for assessment of dynamic upper airway obstruction during nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnoea (OSA). The airway impedance P[FOT] was measured by FOT and the oesophageal pressure (P(oes)) was recorded during stable stage II sleep in 11 patients with OSA. The CPAP level was initially set high enough to completely abolish upper airway obstruction. To induce gradually increasing upper airway re-obstruction, the CPAP pressure was then lowered stepwise. Thirty six such manoeuvres were analysed, blind, to define the first inspiration at which upper airway re-obstruction was detectable by analysis of P[FOT](t(FOT)) and by P(oes)(t(oes)), respectively. On seven occasions t(FOT) and t(oes) occurred together, in the remaining 29 cases t(FOT) preceded t(oes) with a mean latency of 6.0+/-7.7 (0-32) breath cycles. In no case did t(oes) preceed t(FOT). FOT is a highly sensitive tool for the assessment of incipient upper airway obstruction during nCPAP therapy.

Background: Manual titration of continuous positive airway pressure (CPAP) under polysomnographic control is the method most commonly employed to establish the minimal effective pressure (Peff) for the treatment of the obstructive sleep apnoea syndrome (OSA). To date, however, the reproducibility of Peff titrated in this way has not been investigated in any detail. Objectives: The present study aims to establish the reproducibility of Peff determined by manual titrations of CPAP under polysomnographic control in the sleep lab. Methods: In a group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3 (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6), with newly diagnosed OSA, manual titration of CPAP was performed on two consecutive nights using the following standard titration protocol: starting at 4 mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until no signs of airway obstruction could be seen, and arousals were no longer elicited. When no airway obstruction was detected over a period of 30 min, the pressure was lowered once during the night in steps of 1 mbar at intervals of at least 10 min, until obstructive events reappeared, whereupon the pressure was again increased as described above, until, once more, no signs of airway obstruction and no arousals occurred. The second titration was carried out in a blind manner, that is the lab technician did not know the results of the first pressure titration. Results: The mean (SD) Peff for all titrations was 8.1 mbar (2.9). A high level of correlation was found between the Peff titrated on the first night and that titrated on the second night (Spearman correlation coefficient = 0.89). In a few individual cases, however, differences of up to 3 mbar were found between Peff on the first night and Peff on the second night. On average, the Peff measured on the second night was 0.5 mbar (SD = 1.3, range: –2.0 to 3.0 mbar) higher than that of the first night. Conclusions: With standardization of the manual titration of CPAP, Peff is readily reproducible. In individual cases, however, a difference of as much as 3.0 mbar between the two titrations is possible.

Background: Portable recording devices for the diagnosis of obstructive sleep apnoea (OSA) should be carefully evaluated before being used on a routine basis in out-patients. Objective: This study was designed to evaluate the diagnostic accuracy of the new portable recording device, Somnocheck® (SC). Methods: Nocturnal polysomnographies (PSG) and SC recordings were performed simultaneously in the sleep laboratory in 51 patients with suspected OSA, and were analysed manually by a blinded investigator. Results: The apnoea/hypopnoea index (AHI) obtained by manual SC analysis correlated closely with that obtained by PSG (r = 0.98), but the correlation with AHI obtained by automatic SC analysis was markedly lower (r = 0.83). When an AHI ≧10 was defined as indicative of OSA, the sensitivity of manual SC analysis was 0.97 and its specificity 1.00. The sensitivity of automatic analysis was 0.83 and its specificity 0.95. Conclusions: In this experimental setting, the SC showed a very high diagnostic accuracy for the diagnosis of OSA and was able to define its severity precisely. The diagnostic accuracy of manual analysis was found to be superior to that of automatic analysis. Considering the results of this technical evaluation, the SC may also be expected to work reliably when it is used in an ambulatory setting.

In the case of a 21-year-old patient gastroscopy and coloscopy were performed because of recurrent abdominal pain with diarrhea and vomiting. Colonoscopy showed moderate signs of inflammation of the rectum and aphthoid ulcerations in the terminal ileum. Since the macroscopic and clinical presentation was compatible with Crohn's disease, therapy with sulfasalacine was started. Because histology showed only lymphoid hyperplasia and the patient was asymptomatic at that time, the medication was ceased. Recurrence of abdominal pain and weight loss, proteinuria and a recurrent palpable purpura of the shanks in synopsis with the result of the previous colonoscopy led to a suspected diagnosis of Schoenlein-Henoch purpura with cutaneous, renal and abdominal manifestation which was confirmed by dermal and renal biopsies.

Mit dem Somnosmart® steht ein neuartiges, ausschlieslich oszilloresistometrisch gesteuertes auto-CPAP-Gerat zur Therapie des OSAS zur Verfugung. Diese Studie sollte die therapeutische Effektivitat dieses neuen Systems untersuchen. 13 Patienten mit einem OSAS (mittlerer AHI 41,6/h) wurden im Anschlus an eine polysomnographische CPAP-Titration in einem randomisierten “cross-over”-Design sowohl mit einer konventionellen druckkonstanten CPAP-Therapie als auch mit dem Somnosmart® behandelt. Analysiert wurden die polysomnographisch erhobenen Parameter und die Beurteilung der beiden Therapieformen durch die Patienten mittels standardisierter Fragebogen. Der mittlere AHI wahrend der auto-CPAP-Therapie war mit dem AHI unter druckkonstanter CPAP-Therapie vergleichbar (3,31±3,33 vs. 3,95±2,84; n.s.). Weder eine Analyse der Schlafarchitektur noch der Arousal-Index (6,4±1,9 vs. 7,5±4,6; n.s.) zeigten signifikante Unterschiede. Auch die subjektive Einschlafneigung der Patienten war vergleichbar. Der mittlere Behandlungsdruck war jedoch unter der Somnosmart®-Therapie signifikant niedriger als unter der konventionellen Therapie (7,52±2,32 vs. 8,84±1,46; p=0,028). Insbesondere der in Seitenlage applizierte Mitteldruck war bemerkenswert niedriger als der Mitteldruck in Ruckenlage (6,60±2,85 vs. 8,03±2,21; p=0,019). Zusammenfassend zeigte sich das auto-CPAP-Gerat ebenso effektiv wie die konventionelle CPAP-Therapie, der mittlere Behandlungsdruck, besonders in Seitenlage, war jedoch signifikant niedriger.

Although it has been reported that cystic fibrosis and coeliac disease can coexist, a clear relationship between the two diseases has never been firmly established. Our case concerns a 56-year-old man with cystic fibrosis (delta F508/N1303J). Over the last two years he had been complaining about diarrhoea and meteorism. The serum level of tissue transglutaminase was elevated. Duodenoscopy showed a typical pattern for coeliac disease. This was confirmed by the biopsy. After three months on a gluten-free diet the symptoms had disappeared. In the literature there are some hypotheses to explain the coexistence of cystic fibrosis and coeliac disease. Due to pancreatic insufficiency in patients with cystic fibrosis the mucosa of the bowel may have more contact with the complete gluten protein. In addition, malnutrition might contribute to some additional mucosal damage. Both mechanisms might induce an inappropriate immune response to dietary gluten. In the literature all cystic fibrosis patients with coeliac disease were diagnosed with both diseases in childhood with a maximum latency between both diseases of 26 months. It seems unlikely that manifest coeliac disease remained undiagnosed in our patient since childhood. The long time gap between the diagnosis of cystic fibrosis and the first symptoms of the celiac disease in our patient could support the above-mentioned pathophysiological hypotheses.

HISTORY AND ADMISSION FINDINGS A 67-year-old woman complained of marked daytime sleepiness, as well as loud snoring and apnoeas during sleep. She was known to have had 3 thyroidectomies for goitre 41, 23 and 12 years ago, with known tracheal stenosis and recurrent nerve palsy for 11 years. Physical examination revealed marked stridor, hoarse voice and slightly enlarged and palpable recurrent right thyroid. INVESTIGATIONS Polysomnography demonstrated a clearly elevated obstructive sleep apnoea activity (apnoea index: 34/h, apnoea-hypopnea index: 40/h, desaturation index: 31/h, minimal saturation: 63%). Selective tracheal imaging showed subglottic tracheal stenosis with an inspiratory luminal diameter of 4 mm and an expiratory luminal diameter of 8 mm. Lung function analysis revealed marked flattening of the flow-volume curve as sign of a functionally effective tracheal stenosis. These findings indicated a secondary obstructive sleep apnoea (OSA) due to tracheal stenosis and bilateral recurrent nerve palsy. The patient declined further studies, such as bronchoscopy. TREATMENT AND COURSE As the patient did not want any surgical treatment, nasal continuous positive airway pressure therapy (CPAP) was instituted as a trial. No apnoea occurred at a pressure of 12 mm H2O and this was well tolerated. She has now continued CPAP at home for 12 months and her vigilance was markedly improved. CONCLUSIONS Tracheal stenosis or recurrent nerve palsy is a rare cause of OSA which can be effectively treated by nasal CPAP.

e23181Background: Advances in the area of molecular cancer genomics has led to the identification of an increasing number of tumor-driven genetic alterations, with many being already candidates for...

Prognostic and predictive factors of routine clinical practice among patients with small cell lung carcinoma (SCLC) were evaluated.Data from 106 patients with SCLC treated by first-line adriamycin, cyclophosphamide and etoposide (ACE) chemotherapy were analyzed. Multivariate analysis was performed.The median overall survival (mOS) of patients was 9.36 months with mOS of 31%, 8% and 3% after 1, 2 and 5 years, respectively. Using multivariate analysis ECOG performance status (p =0.008) and white blood count (WBC) (p=0.022) were independent prognostic factors for mOS. With both, three groups of outcome (good, intermediate, poor) resulting in mOS of 15.8 months, 6.87 months and 3.35 months (p0.0001) could be established, respectively. The absence of brain metastases (p=0.002), dose reduction (p=0.002) and LDH value (p=0.017) were independent predictive markers. Additionally, female gender was predictive (p=0.025) for complete response (CR).Patients with a poor prediction profil might not benefit from ACE chemotherapy. As a consequence, prognostic/predictive factors should be included as stratification criteria in prospective clinical studies.

e17740 Background: Unfortunately, lung cancer often is diagnosed at a late stage. Delays in diagnosis and initiation of treatment might contribute to the poor prognosis of most patients. The aim of this study was to assess delays in predefined time intervals (TI) between first symptoms and start of treatment and to analyze potential causes for those delays. Furthermore these TIs were correlated with clinical and pathological criteria. Methods: Unselected patients with lung cancer at our institution were interviewed using a standardized and previously validated 35 item questionnaire. Clinicopathological data were taken from the clinical records. Delay and gender was the primary endpoint of this study. Results: First results of this ongoing prospective study: n = 50 patients were studied (34% female, 20% SCLC, 4% never smokers, 62% ex-smokers). Co-morbidities and lung cancer symptoms were present in 96% and 98%, respectively. The median time intervals were: TI1 (from first symptom to general practitioner (G...

We report on a 28-year-old man with known cystic fibrosis who presented with pain and cutaneous nodules in the elbow joints. His symptoms had appeared episodically in the previous months, they were always self-limiting, and independent of pulmonary exacerbations. A radiograph of the joints was unremarkable. These findings fit well with a special form of CF-related arthritis. As in the case of classical CF arthritis, the treatment to be considered is, in particular, symptomatic administration of non-steroidal anti-inflammatory drugs and possibly glucocorticoids. Also under discussion as a further possibility is the use of antibiotics. Our patient has always refused medication. The condition again proved to be self-limiting. In contrast to the classical form of CF arthritis, the special form is not associated with either joint swelling or local warmth. In the presence of arthritic symptoms in CF patients, consideration must always be given to a hypertrophic pulmonary osteoarthropathy. The latter, however, shows typical radiological changes and is exacerbated by lung infections. The presence of arthritic pathologies in a patient with CF further underscores the fact that CF is a multiorgan morbid condition.