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Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients’ follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (

To study the relationship between standardized 18F-FDG PET/CT radiomic features and clinicopathological variables and programmed death ligand-1 (PD-L1) expression status in non-small cell lung cancer (NSCLC) patients.58 NSCLC patients with preoperative 18F-FDG PET/CT scans and postoperative results of PD-L1 expression were retrospectively analysed. A standardized, open-source software was used to extract 86 radiomic features from PET and low-dose CT images. Univariate analysis and multivariate logistic regression were used to find independent predictors of PD-L1 expression. The Area Under the Curve (AUC) of receiver operating characteristic (ROC) curve was used to compare the ability of variables and their combination in predicting PD-L1 expression.Multivariate logistic regression resulted in the PET radiomic feature GLRLM_LGRE (Odds Rate (OR): 0.300 vs 0.114, 95% confidence interval (CI): 0.096-0.931 vs 0.021-0.616, in NSCLC and adenocarcinoma respectively) and the CT radiomic feature GLZLM_SZE (OR: 3.338 vs 7.504, 95%CI: 1.074-10.375 vs 1.382-40.755, in NSCLC and adenocarcinoma respectively), being independent predictors of PD-L1 status. In NSCLC group, after adjusting for gender and histology, the PET radiomic feature GLRLM_LGRE (OR: 0.282, 95%CI: 0.085-0.936) remained an independent predictor for PD-L1 status. In the adenocarcinoma group, when adjusting for gender the PET radiomic feature GLRLM_LGRE (OR: 0.115, 95%CI: 0.021-0.631) and the CT radiomic feature GLZLM_SZE (OR: 7.343, 95%CI: 1.285-41.965) remained associated with PD-L1 expression.NSCLC and adenocarcinoma with PD-L1 expression show higher tumour heterogeneity. Heterogeneity-related 18F-FDG PET and CT radiomic features showed good ability to non-invasively predict PD-L1 expression.ZIEL: Untersuchung der Beziehung zwischen standardisierten 18F-FDG-PET/CT-Radiomics-Merkmalen, klinisch-pathologischen Variablen und der Expression des Programmed Death Ligand 1 (PD-L1) bei Patienten mit nichtkleinzelligem Bronchialkarzinom (non-small cell lung cancer, NSCLC).58 NSCLC-Patienten mit präoperativen 18F-FDG-PET/CT-Scans und postoperativen Befunden zur PD-L1-Expression wurden retrospektiv analysiert. Eine standardisierte Open-Source-Software wurde verwendet, um 86 Radiomics-Merkmale aus PET- und Niedrigdosis-CT-Bildern zu extrahieren. Univariate Analyse und multivariate logistische Regression wurden verwendet, um unabhängige Prädiktoren für die PD-L1-Expression zu ermitteln. Die Fläche unter der Kurve (AUC) der Receiver-Operating-Characteristic (ROC) -Kurve wurde verwendet, um die Fähigkeit der Variablen und ihrer Kombination bei der Vorhersage der PD-L1-Expression zu vergleichen.Die multivariate logistische Regression ergab das PET-Radiomics-Merkmal GLRLM_LGRE (Odds Ratio (OR): 0,300 vs. 0,114, 95%-Konfidenzintervall (KI): 0,096–0,931 vs. 0,021–0,616, bei NSCLC bzw. Adenokarzinom) und das CT-Radiomics-Merkmal GLZLM_SZE (OR: 3,338 vs. 7,504, 95%-KI: 1,074–10,375 vs. 1,382–40,755, bei NSCLC bzw. Adenokarzinom), wobei es sich um unabhängige Prädiktoren für den PD-L1-Status handelt.In der NSCLC-Gruppe blieb das PET-Radiomics-Merkmal GLRLM_LGRE (OR: 0,282, 95%-KI: 0,085–0,936) nach Berücksichtigung von Geschlecht und Histologie ein unabhängiger Prädiktor für den PD-L1-Status. In der Adenokarzinom-Gruppe waren nach Berücksichtigung des Geschlechts das PET-Radiomics-Merkmal GLRLM_LGRE (OR: 0,115, 95%-KI: 0,021–0,631) und das CT-Radiomics-Merkmal GLZLM_SZE (OR: 7,343, 95%-KI: 1,285–41,965) mit der PD-L1-Expression assoziiert.NSCLC und Adenokarzinome mit PD-L1-Expression zeigen eine höhere Tumorheterogenität. Heterogenitätsbezogene 18F-FDG-PET- und CT-Radiomics-Merkmale zeigten eine gute Fähigkeit zur nichtinvasiven Vorhersage der PD-L1-Expression.

Background The contribution of droplet-contaminated surfaces for virus transmission has been discussed controversially in the context of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. More importantly, the risk of fomite-based transmission has not been systematically addressed. Therefore, the aim of this study was to evaluate whether confirmed hospitalized coronavirus disease 2019 (COVID-19) patients can contaminate stainless steel carriers by coughing or intensive moistening with saliva and to assess the risk of SARS-CoV-2 transmission upon detection of viral loads and infectious virus in cell culture. Methods We initiated a single-center observational study including 15 COVID-19 patients with a high baseline viral load (cycle threshold value ≤25). We documented clinical and laboratory parameters and used patient samples to perform virus culture, quantitative polymerase chain reaction, and virus sequencing. Results Nasopharyngeal and oropharyngeal swabs of all patients were positive for viral ribonucleic acid on the day of the study. Infectious SARS-CoV-2 could be isolated from 6 patient swabs (46.2%). After coughing, no infectious virus could be recovered, however, intensive moistening with saliva resulted in successful viral recovery from steel carriers of 5 patients (38.5%). Conclusions Transmission of infectious SARS-CoV-2 via fomites is possible upon extensive moistening, but it is unlikely to occur in real-life scenarios and from droplet-contaminated fomites.

Supplementary Figure S7. Coding variants detected in MPM cell cultures and their relation to TERT promoter status.

Supplementary Material and Methods

Supplementary Table S6

Purpose:Human malignant pleural mesothelioma (MPM) is characterized by dismal prognosis. Consequently, dissection of molecular mechanisms driving malignancy is of key importance. Here we investigate whether activating mutations in the telomerase reverse transcriptase (TERT) gene promoter are present in MPM and associated with disease progression, cell immortalization, and genomic alteration patterns.Experimental Design:TERT promoters were sequenced in 182 MPM samples and compared with clinicopathologic characteristics. Surgical specimens from 45 patients with MPM were tested for in vitro immortalization. The respective MPM cell models (N = 22) were analyzed by array comparative genomic hybridization, gene expression profiling, exome sequencing as well as TRAP, telomere length, and luciferase promoter assays.Results:TERT promoter mutations were detected in 19 of 182 (10.4%) MPM cases and significantly associated with advanced disease and nonepithelioid histology. Mutations independently predicted shorter overall survival in both histologic MPM subtypes. Moreover, 9 of 9 (100%) mutated but only 13 of 36 (36.1%) wild-type samples formed immortalized cell lines. TERT promoter mutations were associated with enforced promoter activity and TERT mRNA expression, while neither telomerase activity nor telomere lengths were significantly altered. TERT promoter–mutated MPM cases exhibited distinctly reduced chromosomal alterations and specific mutation patterns. While BAP1 mutations/deletions were exclusive with TERT promoter mutations, homozygous deletions at the RBFOX1 and the GSTT1 loci were clearly enriched in mutated cases.Conclusions:TERT promoter mutations independently predict a dismal course of disease in human MPM. The altered genomic aberration pattern indicates that TERT promoter mutations identify a novel, highly aggressive MPM subtype presumably based on a specific malignant transformation process.

Supplementary Tables S1 to S9 with the exception of Supplementary Table S6

Supplementary Table 1 from Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells

Supplementary Figure 1 from Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells

To identify epigenetically silenced cancer-related genes and to determine molecular effects of 5-aza-2′-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) in multiple myeloma (MM), we analyzed global changes in gene expression profiles of three MM cell lines by microarray analysis. We identified up-regulation of several genes whose epigenetic silencing in MM is well known. However, much more importantly, we identified a large number of epigenetically inactivated cancer-related genes that are involved in various physiologic processes and whose epigenetic regulation in MM was unknown thus far. In addition, drug treatment of MM cell lines resulted in down-regulation of several MM proliferation-associated factors (i.e., MAF, CCND1/2, MYC, FGFR3, MMSET). Ten Aza-dC and/or TSA up-regulated genes (CPEB1, CD9, GJA1, BCL7c, GADD45G, AKAP12, TFPI2, CCNA1, SPARC, and BNIP3) were selected for methylation analysis in six MM cell lines, 24 samples from patients with monoclonal gammopathy of undetermined significance (MGUS), and 111 samples from patients with MM. Methylation frequencies of these genes ranged between 0% and 17% in MGUS samples and between 5% and 50% in MM samples. Interestingly, methylation of SPARC and BNIP3 was statistically significantly associated with a poor overall survival of MM patients (P = 0.003 and P = 0.017, respectively). Moreover, SPARC methylation was associated with loss of SPARC protein expression by immunostaining in a subset of MM patients. In conclusion, we identified new targets for aberrant methylation in monoclonal gammopathies, and our results suggest that DNA methyltransferase and histone deacetylase inhibition might play an important role in the future treatment of patients with MM. [Cancer Res 2008;68(1):44–54]

Supplementary Table 3 from Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells

Supplementary Table 2 from Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells

Supplementary Table 4 from Genome-Wide Transcriptional Response to 5-Aza-2′-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells

Introdução: Os sarcomas primários do pulmão são tumores malignos raros com incidência estimada em torno de 0,5% de todas as neoplasias pulmonares. De suas tipificações descritas na literatura, duas especialmente, os leiomiossarcomas e os rabdomiossarcomas, apresentam semelhanças em seu perfil genético, morfológico e imuno-histoquímico, o que os levou a receberem uma mesma classificação: tumor rabdomioblástico inflamatório. Esse tipo de tumor costuma acometer tecidos moles em extremidades e tronco, e predomina em meio a homens jovens e de meia-idade. Em razão do pequeno número de casos de tumores rabdomioblásticos relatados na literatura, tanto seu diagnóstico quanto seu tratamento são pouco descritos. Relato de caso: Paciente, sexo feminino, 19 anos, apresentou três episódios de infecção respiratória no lobo inferior do pulmão direito em um período de 18 meses. A tomografia computadorizada do tórax evidenciou obstrução do brônquio intermediário e áreas de bronquiectasias no lobo inferior direito. Diante disso, realizou-se bilobectomia inferior-média, conduzida por cirurgia robótica. A paciente recebeu alta hospitalar três dias depois do pós-operatório. A imuno-histoquímica revelou tumor rabdomioblástico inflamatório de baixo grau. Conclusão: Este relato apresentou um caso de tumor pulmonar raro, abordado por uma técnica cirúrgica ainda não relatada para esse tipo de patologia.

Objective By loading transfer RNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARS) are essential for protein translation. Both cytosolic ARS1-deficiencies and mitochondrial ARS2 deficiencies can cause severe diseases. Amino acid supplementation has shown to positively influence the clinical course of four individuals with cytosolic ARS1 deficiencies. We hypothesize that this intervention could also benefit individuals with mitochondrial ARS2 deficiencies. Methods This study was designed as a N-of-1 trial. Daily oral L-phenylalanine supplementation was used in a 3-year-old girl with FARS2 deficiency. A period without supplementation was implemented to discriminate the effects of treatment from age-related developments and continuing physiotherapy. Treatment effects were measured through a physiotherapeutic testing battery, including movement assessment battery for children, dynamic gait index, gross motor function measure 66, and quality of life questionnaires. Results The individual showed clear improvement in all areas tested, especially in gross motor skills, movement abilities, and postural stability. In the period without supplementation, she lost newly acquired motor skills but regained these upon restarting supplementation. No adverse effects and good tolerance of treatment were observed. Interpretation and Conclusion Our positive results encourage further studies both on L-phenylalanine for other individuals with FARS2 deficiency and the exploration of this treatment rationale for other ARS2 deficiencies. Additionally, treatment costs were relatively low at 1.10 €/day.

Whipple's disease (WD) is a rare and infectious condition leading to multi-organ impairment caused by Tropheryma whipplei (TW), a ubiquitously occurring bacterium. TW can be detected in tissues by histological detection of PAS ("periodic acid-ship reaction")-positive macrophages and by polymerase-chain-reaction (PCR). Clinically, WD is often characterized by diarrhea, abdominal pain, and weight loss. These symptoms are also typical for a flare in Crohn's disease (CD) and, therefore, can lead to fatal misdiagnosis and wrong treatment by using biologics (e.g., anti-TNF-α).We here report a young male patient with pre-existing CD. The patient's symptoms were misinterpreted as a flare of CD and illustrate the multifaceted nature of WD. After intensifying immunosuppressive therapy, the patient developed therapy-refractory diarrhea with several opportunistic infections with a final, fatal outcome.Patients with inflammatory bowel disease (IBD) are not only at risk from infectious complications known with clostridium difficile or cytomegalovirus (CMV); infection with WD should also be ruled out by endoscopy and biopsy before the escalation of the immunosuppressive regime.Der Morbus Whipple (WD) ist eine seltene und infektiöse Erkrankung, die zu Multi-Organbefall führen kann, ausgelöst durch Tropheryma whipplei (TW), ein allgegenwärtig vorkommendes Bakterium. TW kann im Gewebe durch histologischen Nachweis von PAS (“Periodic Acid-Ship Reaction”)-positiven Makrophagen und durch Polymerasekettenreaktion (PCR) nachgewiesen werden. Klinisch ist WD häufig durch Durchfall, Bauchschmerzen und Gewichtsverlust gekennzeichnet. Diese Symptome sind aber auch typisch für einen Schub bei Morbus Crohn und können daher zur Fehldiagnose und falscher Behandlung unter Verwendung von Biologika (z.B. anti-TNF-α) führen.Unser Fallbericht beschreibt einen jungen männlichen Patienten mit bereits bestehendem Morbus Crohn (CD). Die Symptome des Patienten wurden als Schub des M. Crohn falsch interpretiert und veranschaulichen die vielfältige Natur der WD-Infektion. Der Patient entwickelte nach Intensivierung der immunsuppressiven Therapie einen Therapie-refraktären Durchfall sowie zahlreiche opportunistische Infektionen mit tödlichem Ausgang.Patienten mit chronisch-entzündlicher Darmerkrankung (CED) sind nicht nur durch bekannte Infektionen mit Clostridium difficile oder Cytomegalovirus (CMV) gefährdet; eine Infektion mit T. whipplei sollte auch vor Eskalation der immunsuppressiven Therapie mittels Endoskopie und Biopsie ausgeschlossen werden.

Summary For years, clinicians and researchers working on giant cell arteritis have been battling with the conundrum of a disease that displays a short-term steroid responsiveness but is burdened by a remarkable risk of flares and chronic damage in the long term. This issue should be addressed by a change in the direction of research and clinical practice. Evidence suggests that giant cell arteritis is not a monolithic disease; it varies in extent and severity. Hence, treatment should be guided by disease stratification. The current one-size-fits-all strategy leads to overreliance on glucocorticoids and progression of glucocorticoid-related and disease-related complications. A new approach requires disease stratification using clinical, laboratory, histology, and imaging parameters. A giant cell arteritis registry might offer opportunities to scrutinise disease course and prognostic variables early; however, more studies that directly incorporate disease stratification through the above parameters are required. This Series paper also suggests that future clinical trials should be targeted at patients with different disease strata of giant cell arteritis and should incorporate ultrasound, PET-CT scanning, and other imaging modalities as key outcomes.

Non-small cell lung cancer is usually diagnosed at the advanced stage of the disease. We have novel diagnostic tools. However, prevention is still the best way to deal with this disease. Patients receive different treatments with different adverse effects. Targeted treatment with tyrosine kinase inhibitors and immunotherapy have entered everyday clinical practice. The nutritional status of a patient plays a crucial role in the treatment of the patient. Cachexia is observed in most cancer patients, and it has been identified as an independent factor in the overall survival of the patient. The improvement of nutritional status and metabolism directly impacts the quality of life, daily living, and overall survival of a lung cancer patient. We conducted a search on PubMed and Scopus and identified relevant publications. In this review, we will focus on the nutritional status of NSCLC patients and how food supplements assist in the QoL based on published literature. Additional information from other cancer types will be included where necessary.

Die primaren Erkrankungen der Muskulatur (Myopathien) im Kindesalter sind uberwiegend genetisch bedingt und bedurfen meist einer raschen Abklarung, da eine prazise Diagnose Voraussetzung fur die Einschatzung der Prognose, fur die optimale individuelle Beratung und zunehmend auch fur die Initiierung einer wirksamen Therapie ist. Der vorliegende Beitrag fasst diagnostisch relevante Aspekte der Anamnese, hinweisende klinische und Laborbefunde sowie den aktuellen Stand der erweiterten Diagnostik zusammen. Ein Algorithmus zu Auswahl und Reihenfolge diagnostischer Schritte wird vorgeschlagen, um eine zeit- und ressourcensparende Vorgangsweise wahlen zu konnen.

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old’s working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.

The role of educational facilities, including schools and universities, in the SARS-CoV-2 pandemic is heavily debated. Specifically, the risk of infection in student dormitories has not been studied. This cohort study monitored students living in dormitories in Bochum, Germany, throughout the winter term of 2020/2021. Over the course of four months, participants were tested repeatedly for SARS-CoV-2 infections using RT-PCR from gargle samples and serological testing. An online questionnaire identified individual risk factors. A total of 810 (46.5% female) students participated. Of these, 590 (72.8%) students participated in the final visit. The cross-sectional antibody prevalence was n = 23 (2.8%) in November 2020 and n = 29 (4.9%) in February 2021. Of 2513 gargle samples analyzed, 19 (0.8%) tested positive for SARS-CoV-2, corresponding to 14 (2.4%) infections detected within the study period. Gargle samples available of cases with confirmed present infection were always positive. The person-time incidence rate was 112.7 (95% CI: 54.11–207.2) per 100,000 person weeks. The standardized incidence ratio was 0.9 (95% CI 0.51–1.46, p = 0.69). In conclusion, students living in student dormitories do not appear to be major drivers of SARS-CoV-2 infections. RT-PCR from gargle samples is a patient-friendly and scalable surveillance tool for detection of SARS-CoV-2 infections.

Objectives We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. Methods This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. Results Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13–14%). Conclusion The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

Objective To investigate the effectiveness and safety of the ketogenic diet (KD) in drug-resistant epilepsy in childhood in relation to the new 2017 International League Against Epilepsy (ILAE) classification of etiology. Methods A consecutive cohort of patients treated with the KD were categorized according to the ILAE classification into known (structural, genetic, metabolic, infectious, and immune-mediated) and unknown etiology. Primary outcome was the frequency of patients achieving seizure freedom with the KD at 3 months, secondary outcomes were seizure reduction >50% at 3 months, and both seizure freedom and seizure reduction >50% at 6, 12 months, and at last follow-up (LFU), and adverse effects. Outcomes were compared between etiology groups. Results Etiology was known in 70% (129/183). Outcomes did not differ at 3 months (known vs unknown: seizure freedom 28% vs 33%, seizure reduction 62 vs 67%), but seizure freedom was significantly less frequent in known etiology at 6 months (26% vs 43%) and beyond (22% vs 37%). Logistic regression identified duration of epilepsy, number of previous antiseizure medications (ASMs), and age-appropriate psychomotor development as positive determinants of outcome. Among individual etiology groups, the effectiveness of KD was relatively best for genetic (33% at LFU) and poorest for metabolic etiology (8% at LFU). The small number of patients with infectious and immune-mediated etiology requires larger numbers in each etiology group to corroborate our results. No differences in type and frequency of adverse effects (in 71%) between etiology groups were observed, requiring medical intervention in 21%. Significance The KD was most effective in genetic and unknown etiology, many unknowns probably represent yet unidentified genetic causes. We recommend consequent diagnostic and genetic work-up to identify etiologies that respond best to the KD. The KD should be offered early to infants with genetic epilepsy before deterioration of epileptic symptoms and of psychomotor development.

Lung cancer still remains undiagnosed for most patients until the disease is inoperable.We performed search on PubMed with the keywords: EBUS, radial-EBUS, bronchoscopy, lung cancer, electromagnetic navigation, ct-biopsy, transthoracic biopsy. We present diagnostic equipment and imaging techniques such as positron emission tomography, endoscopical navigation systems, endobronchial ultrasound, radial-endobronchial ultrasound, transthoracic ultrasound biopsy, and computed tomography guided biopsies.However, lack of early disease symptoms remains the most important issue and therefore we should direct our efforts to screening and early disease diagnosis. An algorithm is proposed for biopsy upon initial disease diagnosis.

Introduction: Lung lesions and undiagnosed mesothorax lymphadenopathy is an issue that several doctors face in the everyday clinical practice. PET-CT and CT of the thorax are usually the first examinations to identify characteristics of the lesions before biopsy. Patients and Methods: We performed a retrospective study with 450 patients that had EBUS-TBNA with 22G, Upgraded 22G and 19G needles with and without PET-CT in order to identify the cost effeteness of performing EBUS-TBNA before or after PET-CT. All centers used the same PET-CT equipment and EBUS-TBNA system. Three types of needle were used for the endoscopy in order to identify similarities and differences for the cost-effectiveness. The costs in every center for every examination and materials were the same. Results: There were more block slices for 19G>22Gupgraded>21G>22G and there was cost-effectiveness when in general PET-CT was performed prior to biopsy of any lesion. 19G needle was more effective for lymphomas, while 22Gupgraded and 21G needles were more cost-effective when used for smaller lesions for primary lung cancer of metastatic disease. Conclusions: We have been using PET-CT and EBUS-TBNA in the everyday clinical practice according to the current guidelines for initial disease staging and re-staging. However; we can also use both in a cost effective method based on the initial radiologic findings.

Objectives To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. Methods A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. Results The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. Conclusion The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

Background One key pathological finding in giant cell arteritis (GCA) is the presence of interferon-gamma and interleukin (IL)-17 producing T helper (Th) 1 and Th17 cells in affected arteries. There is anecdotal evidence of successful induction and maintenance of remission with the monoclonal anti-IL-17A antibody secukinumab. Inhibition of IL-17A could therefore represent a potential new therapeutic option for the treatment of GCA. Methods This is a randomized, parallel-group, double-blind, placebo-controlled, multi-center, phase II study in which patients, treating physicians, and the associated clinical staff as well as the sponsor clinical team are blinded. It is designed to evaluate efficacy and safety of secukinumab compared to placebo in combination with an open-label prednisolone taper regimen. Patients included are naïve to biological therapy and have newly diagnosed or relapsing GCA. Fifty patients are randomly assigned in a 1:1 ratio to receive either 300 mg secukinumab or placebo subcutaneously at baseline, weeks 1, 2 and 3, and every 4 weeks from week 4. Patients in both treatment arms receive a 26-week prednisolone taper regimen. The study consists of a maximum 6-week screening period, a 52-week treatment period (including the 26-week tapering), and an 8-week safety follow-up, with primary and secondary endpoint assessments at week 28. Patients who do not achieve remission by week 12 experience a flare after remission or cannot adhere to the prednisolone tapering will enter the escape arm and receive prednisolone at a dose determined by the investigator’s clinical judgment. The blinded treatment is continued. Two optional imaging sub-studies are included (ultrasound and contrast-media enhanced magnetic resonance angiography [MRA]) to assess vessel wall inflammation and occlusion before and after treatment. The primary endpoint is the proportion of patients in sustained remission until week 28 in the secukinumab group compared to the proportion of patients in the placebo group. A Bayesian approach is applied. Discussion The trial design allows the first placebo-controlled data collection on the efficacy and safety of secukinumab in patients with GCA. Trial registration ClinicalTrials.gov NCT03765788. Registration on 5 December 2018, prospective registration, EudraCT number 2018-002610-12; clinical trial protocol number CAIN457ADE11C.