Although high-density lipoprotein (HDL) cholesterol is inversely correlated with cardiovascular risk, an emerging paradigm is focused on increasing reverse cholesterol transport (RCT) and HDL function via apolipoprotein A1 (ApoA1). The objective of this study was to investigate the effect of ApoA1 (CSL112) infusion on HDL protein composition, cholesterol esterification rate (CER), and cholesterol efflux capacity (CEC) in patients treated after acute myocardial infarction. CSL112 reduced levels of apolipoproteins A2, B, C, and E and serum amyloids A1 and A4, whereas ApoA1, ApoM, and lecithin-cholesterol acyltransferase were significantly elevated. Increased CEC, plasma HDL cholesterol levels, CER, and CEC also were observed in CSL112-treated patients.

Background: To characterize the effects of CSL112 (human APOA1 [apolipoprotein A1]) on the APOA1 exchange rate (AER) and the relationships with specific HDL (high-density lipoprotein) subpopulations when administered in the 90-day high-risk period post–acute myocardial infarction. Methods: A subset of patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo or CSL112 post–acute myocardial infarction. AER was measured in AEGIS-I plasma samples incubated with lipid-sensitive fluorescent APOA1 reporter. HDL particle size distribution was assessed by native gel electrophoresis followed by fluorescent imaging and detection of APOA1 and SAA (serum amyloid A) by immunoblotting. Results: CSL112 infusion increased AER peaking at 2 hours and returning to baseline 24 hours post-infusion. AER correlated with cholesterol efflux capacity ( r =0.49), HDL-cholesterol ( r =0.30), APOA1 ( r =0.48), and phospholipids ( r =0.48; all P <0.001) over all time points. Mechanistically, changes in cholesterol efflux capacity and AER induced by CSL112 reflected HDL particle remodeling resulting in increased small HDL species that are highly active in mediating ABCA1 (ATP-binding cassette transporter 1)-dependent efflux, and large HDL species with high capacity for APOA1 exchange. The lipid-sensitive APOA1 reporter predominantly exchanged into SAA-poor HDL particles and weakly incorporated into SAA-enriched HDL species. Conclusions: Infusion of CSL112 enhances metrics of HDL functionality in patients with acute myocardial infarction. This study demonstrates that in post–acute myocardial infarction patients, HDL-APOA1 exchange involves specific SAA-poor HDL populations. Our data suggest that progressive enrichment of HDL with SAA may generate dysfunctional particles with impaired HDL-APOA1 exchange capacity, and that infusion of CSL112 improves the functional status of HDL with respect to HDL-APOA1 exchange. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02108262.

The aim of this case series was to evaluate implants inserted in bone after guided bone regeneration (GBR). Fourteen patients with generalized aggressive periodontitis (GAP) who had lost one or two maxillary teeth in the incisor or premolar region were enrolled in the study. Due to bone resorption, the lateral width and vertical height of the bone were insufficient for implant placement. GBR was carried out in a staged approach using titanium-reinforced e-PTFE (expanded polytetrafluoroethylene) membranes. No bone grafts or bone substitute materials were used. After 6 to 8 months, turned-surface implants (n = 47) were inserted in augmented and nonaugmented bone sites and prosthetically treated with single crowns. All patients were examined during a 3- to 6-month recall schedule over a 10- to 20-year period, and clinical and radiographic examinations were performed. GBR yielded mean vertical and lateral bone gains of 4.5 and 7.0 mm, respectively. The implant survival rate was 100%, mucositis was present in 28.8% of sites, and peri-implantitis was not found. The annual bone loss at tooth sites was significantly higher than at implant sites in augmented bone (0.5% vs 0.2%, respectively; P = .000), and the adjacent teeth had significantly higher annual bone loss (0.8%; P = .000). Thus, severely periodontally compromised patients can be managed successfully in the long-term with the described clinical protocol.

ZusammenfassungHintergrund und ZielePemphigus gehört zu den seltenen, aber potentiell lebensbedrohlichen Autoimmunerkrankungen. Typisch sind Blasen und Erosionen der Haut und der Schleimhäute. Grundsätzlich unterscheiden wir zwei Subtypen: Pemphigus vulgaris (PV) und Pemphigus foliaceus (PF). In dieser Studie wurden die klinisch‐pathologischen Daten aus einem Register für bullöse Autoimmundermatosen analysiert mit dem Ziel, das Autoantikörperprofil und das Therapieansprechen bei Patienten mit PV und PF genauer zu charakterisieren.Patienten und MethodenIn einer retrospektiven Studie wurden die Daten von 69 Patienten mit PV und PF analysiert. Zur Beurteilung des klinischen Verlaufs, der Remissionen und Rezidive sowie des Schweregrads der Krankheit bei Erstmanifestation und während des gesamten Beobachtungszeitraums diente der ABSIS (Autoimmune Bullous Skin Intensity Score) (ABSIS). Mittels ELISA wurden die Spiegel von Anti‐Desmoglein (Dsg)‐1‐ und Anti‐Dsg‐ IgG‐Autoantikörpern im Serum bestimmt.ErgebnisseDie mittlere Remissionszeit bei Patienten mit PV und PF betrug 63 Wochen. PV‐Patienten mit Schleimhautbeteiligung zeigten eine schnellere Heilung. Bei PV‐Patienten mit moderat oder stark erhöhten Anti‐Dsg1‐IgG‐Autoantikörpern im Serum zu Beginn erfolgte im Lauf des Beobachtungszeitraums ein Absinken der Anti‐Dsg3‐IgG‐Spiegel.SchlussfolgerungenUnsere Studie liefert neue Erkenntnisse zum Krankheitsverlauf bei Patienten mit PV und PF und offenbart, dass ein Phänotyp mit Schleimhautbeteiligung eine stärkere Neigung zur Remission aufweist.

BACKGROUND AND OBJECTIVES:Pemphigus diseases are potentially life-threatening and rare autoimmune bullous disorders characterized by blisters and erosions of the skin and mucous membranes. These disorders can be largely divided into two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to evaluate the autoantibody profile and response to therapy of PV and PF patients by analyzing the clinicopathological data from a registry for bullous autoimmune dermatoses.PATIENTS AND METHODS:In a retrospective study, data from 69 patients with PV and PF were included in the analysis. The Autoimmune Bullous Skin Intensity Score (ABSIS) was used to assess the clinical course, remissions, relapses and severity of the disease at first manifestation and throughout the observation period. ELISA was performed to assess levels of anti-desmoglein (Dsg)-1 and anti-Dsg3 IgG serum autoantibodies.RESULTS:The mean remission time in PV and PF patients was 63 weeks. PV patients with mucosal involvement showed a more favorable healing process. In PV patients with a moderate/high anti-Dsg1 IgG serum level at baseline, anti-Dsg3 IgG levels decreased during the observation period.CONCLUSIONS:Our study provides additional insights into the clinical course of patients with PV and PF, revealing that a mucosal phenotype is associated with a higher tendency towards remission.

Background/Aim: We evaluated the potential of the kinase inhibitors sorafenib, lenvatinib and selumetinib on increasing the uptake of technetium-99m into thyroid cancer cells. Materials and Methods: Four established cell lines and three patient's cell cultures were treated with 0.1, 1 and 5 μM of sorafenib, lenvatinib and selumetinib for 72 hours. After incubation with 1 MBq of technetium-99m, the radioactivity uptake was measured. Results: The experiments showed heterogeneous results. Maximum technetium-99m uptake increases of 312% (sorafenib), 326% (lenvatinib) and 759% (selumetinib) were obtained using the highest applied concentrations. In some tests, an uptake reduction or no effect was observed. Conclusion: Kinase inhibitors have a positive effect on technetium-99m uptake. Due to study limitations, a redifferentiating effect of the drugs could not be definitely proven. Unspecific cytotoxicity might have a confounding effect.

Background: Apolipoprotein A-I (apoA-I) exchange rate (AER) into plasma high density lipoprotein (HDL) may represent a cell-free measure of HDL function, and predict recurrent major adverse cardiovascular events post-acute myocardial infarction (AMI). Purpose: To characterise the effects of CSL112 (apoA-I (human)) on AER and the relationships with specific HDL subpopulations when administered in the 90-day high-risk period post AMI. Methods: Patients from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study received either placebo, 2g or 6g CSL112 post AMI. The rate of apoA-I exchange into HDL was measured in AEGIS-I plasma samples incubated with fluorescent apoA-I-NBD (7-nitrobenz-2-oxa-1,3-diazole) lipid-sensitive reporter for 30 min at 37°C. HDL particle size distribution was assessed by native gel electrophoresis followed by fluorescent imaging and detection of apoA-I and serum amyloid A (SAA1/SAA2) by western blotting. Results: CSL112 infusion increased AER peaking 2 h post infusion and returning to baseline by 24 h. AER was correlated with cholesterol efflux capacity, HDL-C, apoA-I and phosphatidylcholine (all p<0.001). CSL112 infusion induced transient changes in HDL particle size distribution. Small remodelled HDL (S-HDL rem ) derived from CSL112 were detected in plasma 2-4 h after infusion. Large remodeled HDL species (L-HDL rem ) accumulated 2-12 h post infusion. The apoA-1-NBD reporter was confined to distinct HDL subpopulations that contained little SAA. In plasma samples characterized by the baseline pattern of HDL particle size distribution (0 h and 24-48 h post infusion), the apoA-I-NBD reporter predominantly exchanged into the HDL3 subpopulation, but not into large HDL2. Conclusion: Infusion of CSL112 increased AER via exchange into SAA-poor HDL particles. AER may represent a clinically amenable biomarker of HDL functionality. Figure: HDL particle remodelling and AER in a representative subject infused with 6g CSL112 .

Abstract Background Cognitive impairment in chronic kidney disease, especially in end stage renal disease, is a public health problem. Nevertheless, the cause of chronic kidney disease still remains unclear. A prevalence of cognitive impairment in patients with end stage renal disease of up to 87% has been found. Methods The study at hand deals with the research on the – potential – effect of timing on cognitive performance when testing cognitive impairment in hemodialysis patients during the dialysis cycle. We tested cognitive performance with a neuropsychological test battery (RBANS, Repeatable Battery for the Assessment of Neuropsychological Status) on two occasions while patients were on dialysis as well as on a dialysis-free day. In addition, all participants were rated using the Geriatric Depression Scale (GDS) and several demographic and clinical variables were recorded in order to investigate their possible influence on cognitive performance. The patients were recruited in three dialysis centers in the central region of Hesse, Germany. Twenty-six participants completed the 3 testings during a period of 6 weeks. The testing was carried out in the dialysis centers. Results Looking at the total scale score, patients achieved the best cognitive performance in the RBANS during the first 2 h on dialysis with 81.1 points. When comparing the scores of the three measurement occasions (first 2 h, Timepoint 1 vs. last 2 h, Timepoint 2 vs. dialysis free day, Timepoint 3, however, no significant difference in the total scale score was detected. But patients showed significantly better cognitive performance in language in the first 2 h (p < 0.001) as well as in the last 2 h (p < 0.001) compared with the dialysis-free day. Conclusion Due to the high prevalence of cognitive impairment, there is an increasing need to assess cognitive function in dialysis patients. Our data show that the time point of testing (first 2 h on hemodialysis vs. last 2 h on hemodialysis vs. Hemodialysis free day) had no influence of cognitive function in hemodialysis patients in routine indications.

After in vivo fertilisation, the preimplantation embryo goes through cleavage during migration along the oviduct in mammals or the fallopian tube in a woman and ends up inside the uterus. This study investigates the effect of a protocol aimed at closely reproducing that natural oxygen concentration in the oviduct (7 % O2 from day 1 to day 3 and 2 % from day 3 to day 5), in contrast to the concentrations (5 % or 20 %) widely used in practice in ART using morphokinetic. Female mice (BI6/CBAca) were sacrificed, and zygotes were isolated 20 h after mating and randomly allocated to three parallel groups, which were grown under high atmospheric, low, or sequential oxygen concentrations. Zygotes were cultured in GTL medium (Vitrolife) and observed by the Primovision time-lapse system. Blastocyst rate at 120 h in the sequential group (91.3 %) was significantly increased over the high (76.3 %) and low (74.4 %) groups. Blastocyst size was also enlarged in the sequential group compared to the high and low groups. Moreover, cell division in the sequential group was significantly faster at almost every cleavage stage than it was in the other groups. Notably, the duration of the interims between stages also differed significantly between the groups. This study demonstrated that, in comparison to routinely used high or low oxygen conditions, oxygen concentrations mimicking changes in the oviduct and uterus significantly improve the blastocyst rate and size and accelerate cell division at several stages as well as the interims between cleavage events.

Oral lichen planus (OLP) is a common, chronic relapsing inflammatory disorder of the mucous membranes, which causes major discomfort. Current treatment includes topical/systemic glucocorticoids, immune modulators and systemic immunosuppressants, which may lead to considerable side-effects. The aim of this study was to determine the clinical and immunological efficacy of photodynamic therapy (PDT) in OLP as an alternative, easy-to-use, safe and non-invasive treatment. Twenty patients with OLP were treated with PDT in a prospective case-controlled pilot-study. PDT was performed on the most extensive oral lesion in 4 sessions (day 1, 3, 7, 14). Peripheral blood and lesional T cells were analysed before (day 1) and after PDT treatment (day 28). PDT led to a statistically significant reduction of clinical parameters (lesion size, ABSIS, Thongprasom-score) and improvement of all evaluated quality-of-life (QOL) items. The clinical improvement was accompanied by a significant decrease of the relative number of CD4+ and CD8+ T cells in mucosal OLP-lesions. Furthermore, CXCL10 plasma levels were decreased and the number of activated peripheral CD4 + CD137+ and CD8 + CD137+ T cells and IL-17-secreting T cells was diminished. PDT treatment in OLP leads to lesion reduction and improvement of QOL, and induces local and systemic anti-inflammatory effects. The study identifies PDT as a novel therapeutic option in OLP.

Purpose: To assess the differences in outcomes between interface flushing with a balanced salt solution after refractive lenticule removal in simultaneous uneventful bilateral small-incision lenticule extraction (SMILE). Setting: Six study centers in Germany. Design: Prospective case series. Methods: Patients with myopia or myopic astigmatism of similar magnitude in both eyes with a spherical equivalent less than or equal to 10.0 diopters (D), preoperative corrected distance visual acuity (CDVA) of 0.80 decimal or better, and anisometropia less than or equal to 2.0 D were enrolled and followed for 3 months. One eye of each patient was treated with interface flushing after dry extraction of the lenticule. Flushing was performed with 1.0 cc balanced salt solution using a single-use 27-gauge cannula. The uncorrected distance visual acuity (UDVA) at 1 day, 1 week, and 3 months; the CDVA at 3 months; and postoperative differences at the slitlamp examination were recorded. Statistical analyses were performed with logarithm of the minimum angle of resolution values using paired t tests. The P value for significance was less than 0.05. Results: The study analyzed 470 eyes. One day postoperatively, the mean UDVA was 0.81 in the non-flush group and 0.83 in the flush group (P = .110). At the last visit 3 months postoperatively, the mean UDVA was 1.04 and 1.05, respectively (P = .172). No significant differences in the rate of postoperative complications were found. Conclusion: Interface irrigation with 1.0 cc of balanced salt solution after the removal of the refractive lenticule has neither advantages nor disadvantages in terms of visual recovery, postoperative complications, or final visual acuity. (C) 2018 ASCRS and ESCRS

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Streptococcus pneumoniae (S. pneumoniae) is the most common bacterial cause of community-acquired pneumonia. Increasing rates of antibiotic-resistant S. pneumoniae strains impair therapy and necessitate alternative treatment options. In this study, we analysed insect-derived antimicrobial peptides (AMPs) for antibacterial effects on S. pneumoniae in a human in vitro infection model. AMP effects on bacterial growth were examined by colony forming unit (CFU)-assays, and growth curve measurements. Furthermore, cytotoxicity to primary human macrophages was detected by measuring lactate-dehydrogenase release to the supernatant. One AMP (Defensin 1) was tested in a model of primary human monocyte-derived macrophages infected with S. pneumoniae strain D39 and a multi-resistant clinical isolate. Inflammatory reactions were characterised by qPCR and multiplex-ELISA. In total, the antibacterial effects of 23 AMPs were characterized. Only Tribolium castaneum Defensin 1 showed significant antibacterial effects against S. pneumoniae strain D39 and a multi-resistant clinical isolate. During in vitro infection of primary human macrophages with S. pneumoniae D39, Defensin 1 displayed strong antibacterial effects, and consequently reduced bacteria-induced cytokine expression and release. In summary, Tribolium castaneum Defensin 1 showed profound antibacterial effectivity against Streptococcus pneumoniae D39 and a multi-resistant clinical isolate without unwanted cytotoxic or inflammatory side effects on human blood-derived macrophages.

Obgleich T‑Negativierungen infolge von Cardiac Memory bei Schrittmacherpatienten bereits vor 50 Jahren erstmals beschrieben wurden, ist über die Prävalenz und über klinische Prädiktoren dieses Phänomens wenig bekannt. Nach Ausschluss von 238 Patienten wegen Schenkelblockierungen im EKG oder wegen Schrittmacherabhängigkeit wurden insgesamt 325 Patienten eingeschlossen, die sich zur Routinekontrolle ihres Schrittmachers ambulant vorstellten. Bei allen Patienten wurde während passagerer Inhibierung ihres Schrittmachers ein 12-Kanal-Standard-EKG abgeleitet. Cardiac Memory konnte bei 115 der 325 Patienten (35 %) dokumentiert werden und zeigte eine deutliche Abhängigkeit zur ventrikulären Stimulationshäufigkeit mit einer Prävalenz von 9 % bei einer ventrikulären Stimulationshäufigkeit ≤25 % und einer Prävalenz von 86 % bei einer ventrikulären Stimulationshäufigkeit ≥75 %. Cardiac Memory wurde bei jedem dritten Patienten nach Schrittmacherimplantation beobachtet mit einem Anstieg der Prävalenz auf über 80 % bei häufiger ventrikulärer Stimulation. Cardiac Memory infolge ventrikulärer Stimulation hat keinen Krankheitswert und darf nicht mit morphologisch ähnlichen T‑Wellen-Negativierungen bei akutem Koronarsyndrom, bei schwerer linksventrikulärer Hypertrophie oder bei Myokarditis verwechselt werden.

Background: The MEK (mitogen-activated protein kinase)–inhibitor selumetinib led to increased radioiodine uptake and retention in a subgroup of patients suffering from radioiodine refractory differentiated thyroid cancer (RR-DTC). We aimed to analyse the effect of selumetinib on the expression of sodium iodide symporter (NIS; SLC5A5) and associated miRNAs in thyroid cancer cells. Methods: Cytotoxicity was assessed by viability assay in TPC1, BCPAP, C643 and 8505C thyroid cancer cell lines. NIS, hsa-let-7f-5p, hsa-miR-146b-5p, and hsa-miR-146b-3p expression was determined by quantitative RT-PCR. NIS protein was detected by Western blot. Radioiodine uptake was performed with a Gamma counter. Results: Selumetinib caused a significant reduction of cell viability in all thyroid cancer cell lines. NIS transcript was restored by selumetinib in all cell lines. Its protein level was found up-regulated in TPC1 and BCPAP cells and down-regulated in C643 and 8505C cells after treatment with selumetinib. Treatment with selumetinib caused a down-regulation of hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p in TPC1 and BCPAP cells. In 8505C cells, a stable or down-regulated hsa-miR-146b-5p was detected after 1h and 48h of treatment. C643 cells showed stable or up-regulated hsa-let-7f-5p, hsa-miR-146b-5p and hsa-miR-146b-3p. Selumetinib treatment caused an increase of radioiodine uptake, which was significant in TPC1 cells. Conclusions: The study shows for the first time that selumetinib restores NIS by the inhibition of its related targeting miRNAs. Further studies are needed to clarify the exact mechanism activated by hsa-miR-146b-5p, hsa-miR-146b-3p and hsa-let7f-5p to stabilise NIS. Restoration of NIS could represent a milestone for the treatment of advanced RR-DTC.

Pemphigus vulgaris ( PV ) is a severe autoimmune blistering disease of the skin and mucous membranes. As autoantibodies play an essential role in the disease pathogenesis, the serological detection of anti‐desmoglein 3 IgG represents a central tool in the diagnosis of the disease. In this study, we show the validation of a novel lateral flow immunoassay ( LFIA ) which rapidly detects anti‐desmoglein 3 (Dsg3) IgG in human serum. In contrast to other diagnostic procedures, the assay is compact and simple to perform and delivers a fast ”yes” or “no” answer within 10 minutes without additional hardware requirements for test evaluation. For validation, a blinded collection of 200 sera including 100 sera from 14 PV patients, 75 sera from 24 bullous pemphigoid patients and 25 sera from 6 patients with pemphigus foliaceus collected at different time points during disease was used. Presence or non‐presence of anti‐Dsg3 IgG within sera was confirmed using a commercially available Dsg3‐ ELISA . For qualitative evaluation, Dsg3‐ LFIA test results were assessed by two independent groups of human observers. Furthermore, quantitative evaluation using POCS can reader was applied. The Dsg3‐ LFIA demonstrated reliable test results with a sensitivity and specificity of 78.1% and 97.1%, respectively. Test results from POCS can and human observers showed a substantial agreement. The Dsg3‐ LFIA represents a new diagnostic tool for the immediate and reliable detection of anti‐desmoglein 3 serum IgG autoantibodies that does not require additional hardware. Further prospective trials are warranted to validate the Dsg3 LFIA in pemphigus.

OBJECTIVE:Eustachian tube dysfunction (ETD) affects approximately 1% of adults in the general population. Non treated Eustachian tube dysfunction can result in chronic middle ear diseases, which have been shown to significantly affect taste sensitivity. A promising treatment is balloon dilatation of the Eustachian tube. The primary aim of the present study was to investigate whether individuals with ETD had impairment in chemosensory functions, and the changes of the chemosensory function after balloon dilatation of the Eustachian tube.METHODS:26 patients (17 female, 9 male) (=56 ears) suffering from ETD with a mean age of 39±15years were included in the present study. 20 patients (76%) returned to be evaluated at the follow up (=40 ears) 51±22days after balloon dilatation. For pre- and post operation, gustatory function was measured with a lateralized gustatory test with the taste strips and olfactory function was tested by means of the Sniffin' Sticks test battery (threshold, discrimination and identification (ID)).RESULTS:Patients' baseline taste function (summed taste score 9.8±3.5 (mean±SD)) was significantly impaired compared to normative data (summed taste score 12.4±2.3; p=0.002). After balloon dilatation of the Eustachian tube, the taste function remained stable (summed taste score 9.4±4.3; p=0.814). Olfactory function (odor ID, summed score (TDI)) improved postoperatively (TDI 32.4±3.6) compared to pre-operative scores (TDI 33.6±4.0; p=0.012), but not to a clinically relevant extent.CONCLUSION:This study suggests, that patients suffering from ETD exhibit reduced taste scores. Balloon dilatation of the Eustachian tube does not seem to influence gustatory function, but olfactory function showed improvement.

Purpose To describe the vascularization of peripheral lung carcinoma in CEUS and to compare with B-mode ultrasound (US) and clinical data. Materials and Methods From April 2004 until September 2015, n = 89 patients with peripheral lung carcinoma were investigated by B-mode US and CEUS. The extent (EE: hypoechoic, hyperechoic), homogeneity (HE: homogeneous, inhomogeneous) and time of enhancement (TE) have been defined. Early pulmonary-arterial enhancement (PA) before contrast floating to the thoracic wall was differentiated from simultaneous or delayed bronchial-arterial enhancement (BA). CEUS parameters were compared by B-mode US and histology. Results n = 25 patients had early PA enhancement (TE: 8 +/- 3.7 s), and n = 64 (72 %) had simultaneous/delayed BA enhancement (TE: 17.6 +/- 6.2 s) (p < 0.001). PA enhancement (EE/HE) was hyperechoic (n = 11/25), homogeneous (n = 11/25) and showed an air bronchogram more often (n = 11/17, p < 0.001). BA enhancement (EE/HE) was frequently hypoechoic (n = 34/64) and inhomogeneous (n = 54/64). BA enhancement was associated with necrosis (n = 36/42, p = 0.009). PA and BA enhancement distributed to different histologies: n = 42 adenocarcinomas (18 PA, 24 BA), n = 30 squamous cell carcinomas (4 PA, 26 BA), n = 13 other types of NSCLC (3 PA, 10 BA), and n = 4 SCLC (0 PA, 4 BA) (p = 0.016). Conclusion The vascularization of peripheral lung carcinomas is heterogeneous and is influenced by histology. In this study, lung carcinomas are predominantly supplied by bronchial arteries, whereas a part of adenocarcinomas and non-adenocarcinomas show PA enhancement.

Primary resistance to induction therapy is an unsolved clinical problem in acute myeloid leukemia (AML). Here we investigated drug resistance in AML at the level of cellular metabolism in order to identify early predictors of therapeutic response. Using extracellular flux analysis, we compared metabolic drug responses in AML cell lines sensitive or resistant to cytarabine or sorafenib after 24 h of drug treatment to a small cell lung cancer (SCLC) cell line exposed to etoposide. Only drug-resistant AML cells maintained oxidative metabolism upon drug exposure while SCLC cells displayed an overall metabolic shift towards glycolysis, i. e. a Warburg effect to escape drug toxicity. Moreover, primary AML blasts displayed very low glycolytic activity, while oxygen consumption was readily detectable, indicating an essential role of oxidative pathways in the bioenergetics of AML blasts. In line with these observations, analysis of the mitochondrial membrane potential using tetramethylrhodamine ethyl ester staining and flow cytometry allowed for clear discrimination between drug sensitive and resistant AML cell line clones and primary blasts after 24 h of treatment with cytarabine or sorafenib. Our data reveal a distinct metabolic phenotype of resistant AML cells and suggest that disrupting oxidative metabolism rather than glycolysis may enhance the cytotoxic effects of chemotherapy in AML.