Hintergrund Pulmonale Beteiligungen bei Covid-19-Erkrankungen umfassen das Spektrum von asymptomatischen Verläufen bis hin zu schwersten akuten Lungenschädigungen im Sinne eines ARDS, aber auch in ihrer Ausprägung variable Long-Covid-Syndrom-Verläufe. Neben einer Hyperinflammation treten auch fibrosierende Lungenveränderungen auf, deren Pathogenese weiterhin nicht hinreichend verstanden wird. Das Ziel unserer Pilotstudie war die Charakterisierung von Fibrose-assoziierten Pathways bei Pat. mit Covid-19-ARDS und Long-Covid mit interstitieller Lungenbeteiligung (ILD) im Vergleich zu ILD anderer Genese.

OBJECTIVES:The aim of the study was to describe the characteristics of HIV-infected late presenters, opportunistic diseases at diagnosis and missed opportunities to diagnose HIV infection earlier.METHODS:In a retrospective cohort study, we reviewed the medical records of all adults with newly diagnosed HIV infection admitted to the Department of Infectious Diseases of the Vivantes Auguste-Viktoria Hospital, Berlin, Germany.RESULTS:In the 5-year period from 2009 to 2013, 270 late presenters were identified. The most common AIDS-defining conditions were oesophageal candidiasis (n = 136; 51%), wasting syndrome (n = 106; 40%) and pneumocystis pneumonia (n = 91; 34%). Fifty-five patients (21%) had presented with at least one HIV indicator condition on prior contact with health care services without being offered testing for HIV. Female patients and heterosexual men [not men who have sex with men ('non-MSM')] had a significantly higher chance of being among patients previously presenting with indicator conditions and not being tested [odds ratio (OR) 4.7; 95% confidence interval (CI) 2.2-10.0; P < 0.001; and OR 2.4; 95% CI 1.2-5.1; P < 0.01, respectively]. The most commonly missed indicator conditions were leucocytopenia (n = 13; 24%), thrombocytopenia (n = 12; 22%), oral candidiasis (n = 9; 16%), unexplained weight loss (n = 7; 13%), herpes zoster (n = 5; 9%) and cervical dysplasia/cancer (n = 4; 20% of women). The median time between presentation with an indicator condition and the diagnosis of HIV infection was 158.5 days [interquartile range (IQR) 40-572 days]. Patients with oral candidiasis and unexplained weight loss had the shortest time between the "missed opportunity" and the diagnosis of HIV infection. Fifty-five hospital admissions with a total cost of over EUR 500 000 and - most importantly - six in-hospital deaths might have been prevented if HIV testing had been performed in patients with documented indicator conditions.CONCLUSIONS:Indicator conditions are still missed by clinicians. Women and 'non-MSM' are at highest risk of presenting with an indicator condition but not being tested for HIV infection.

C-type lectin receptors (CTLRs) are a type of Pattern Recognition Receptors (PRRs) expressed in various immune cells that have been newly found to play important role in recognition of Mycobacterium tuberculosis (Mtb). The CTRLs in the Dectin-1 & Dectin-2 clusters on human chromosome 12 are of particular interest. Recently it was found that Mincle & MCL detect mycobacterial cord factor & Dectin-2 directly recognizes the Mannose capped Lipoarabinomannan. Several PRRs have been studied for the role of their SNPs in individual susceptibility to TB. However, no genetic studies have been done in humans for SNPs in these important CTLRs that link them to TB. The aim of our study is to find the association between the relevant SNPs in various CTLRs and TB in a case-control study. We generated a cohort of 145 pulmonary TB cases registered under the Revised National TB Control Program in Hyderabad, India & 241 healthy controls. In a pilot study, Next Generation Sequencing was performed targeting the whole genes from Dectin-1 & Dectin-2 clusters and known SNPs in other CTLRs related to TB. After various statistical adjustments, we annotated about 60 SNPs (known and unknown) that could be associated with the susceptibility or resistance to TB in those cases. We plan to sequence all the samples for these SNPs. In case of positive correlation we will perform a functional analysis of the SNPs that were mostly associated with the risk of pulmonary Tb. Our results will add an important impact for elucidating the role of SNPs in CTLRs genes in patients with pulmonary tuberculosis.

Aim: The study investigates whether early dynamic PET/CT (edPET/CT) using 18F-fluorodeoxyglucose (FDG) discriminates between affected versus non-affected sites in patients with complicated, protracted fracture healing and suspected COM in the lower extremities. Patients, methods: In nine consecutive patients (1 woman, 8 men; age 54 ± 13 years), before standard late FDG-PET/CT, altogether 10 edFDG-PET/CT examinations were performed in list mode over 5 min starting with radiopharmaceutical injection. Eight consecutive time intervals (frames), four 15-s, then four 60-s, were reconstructed. For every patient, several volumes-of-interest were selected. To measure early FDG influx and accumulation, maximum and mean ed standardized uptake values (respectively, edSUVmax, edSUVmean) were calculated in each volume-of-interest during each frame. Results were compared between affected and non-affected (contralateral) bone. Results:Starting in the 31-45s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean than did the healthy contralateral region. In conventional PET/CT, affected bone areas also significantly differed from non-affected contralateral regions. Conclusion: This pilot study suggests that edFDG-PET may offer a less time consuming add on to standard FDG-PET/CT while being equally accurate. The results should be validated prospectively in larger trials.

Summary Aim: The study investigates whether early dynamic PET/CT (edPET/CT) using 18F-fluoro- deoxyglucose (FDG) discriminates between affected versus non-affected sites in patients with complicated, protracted fracture healing and suspected COM in the lower extremities. Patients, methods: In nine consecutive patients (1 woman, 8 men; age 54 ± 13 years), before standard late FDG-PET/CT, altogether 10 edFDG-PET/CT examinations were performed in list mode over 5 min starting with radiopharmaceutical injection. Eight consecutive time intervals (frames), four 15-s, then four 60-s, were reconstructed. For every patient, several volumes-of-interest were selected. To measure early FDG influx and accumulation, maximum and mean ed standardized uptake values (respectively, ed SUVmax, edSUVmean) were calculated in each volume-of-interest during each frame. Results were compared between affected and non-affected (contralateral) bone. Results: Starting in the 31-45s frame, the affected bone area showed significantly higher ed- SUVmax and edSUVmean than did the healthy contralateral region. In conventional PET/CT, affected bone areas also significantly differed from non-affected contralateral regions. Conclusion: This pilot study suggests that edFDG- PET may offer a less time consuming add on to standard FDG-PET/CT while being equally accurate. The results should be validated pros- pectively in larger trials.

You have accessJournal of Urology1 Apr 2008GENOME-WIDE COPY NUMBER PROFILING OF RENAL CELL TUMORS USING ARRAY-CGH Jimsgene Sanjmyatav, Carsten Schwaenen, Sven Wessendorf, Jorg Schubert, and Kerstin Junker Jimsgene SanjmyatavJimsgene Sanjmyatav More articles by this author , Carsten SchwaenenCarsten Schwaenen More articles by this author , Sven WessendorfSven Wessendorf More articles by this author , Jorg SchubertJorg Schubert More articles by this author , and Kerstin JunkerKerstin Junker More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)60388-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "GENOME-WIDE COPY NUMBER PROFILING OF RENAL CELL TUMORS USING ARRAY-CGH." The Journal of Urology, 179(4S), p. 135 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 135 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Jimsgene Sanjmyatav More articles by this author Carsten Schwaenen More articles by this author Sven Wessendorf More articles by this author Jorg Schubert More articles by this author Kerstin Junker More articles by this author Expand All Advertisement PDF DownloadLoading ...

Cutaneous T-cell lymphomas (CTCLs) are characterized by the recruitment of malignant T-cell clones, predominantly of the CD4+ T-helper subpopulation, into the skin. Mycosis fungoides (MF) is the most common type of CTCL and accounts for almost 50% of all primary cutaneous lymphomas. The ProteinChip technology surface-enhanced laser desorption/ionization time of flight/mass spectrometry (SELDI-TOF-MS) was used to detect biomarkers in sera from MF patients (n = 25) and healthy controls (n = 26). Therefore, diluted sera were applied to IMAC30 ProteinChip arrays, and the resulting protein profiles were bioinformatically analyzed. A protein set that distinguishes MF patients from healthy controls with a sensitivity of 82.6% and a specificity of 100% was identified. Four significant peaks were identified by two-dimensional gel electrophoresis, immunodepletion, and SELDI-TOF-MS as transthyretin (TTR) and three TTR modifications. A subsequent enzyme-linked immunosorbent assay confirmed these findings. The ability to detect and identify proteins and protein modifications using SELDI-TOF-MS might reveal a better insight on this kind of disease and may lead to a better understanding and earlier detection of MF patients.

Objectives. To develop a noninvasive method for the detection of renal transplant rejection using ProteinChip Arrays (surface-enhanced laser desorption/ionization time-of-flight mass spectrometry).Methods. A total of 23 urine samples were collected from 13 patients showing biopsy-proven renal allograft rejection and from 10 patients without histologic signs of rejection. All 23 patients had clinical symptoms and signs of acute allograft rejection and underwent renal biopsy. Samples were centrifuged, and supernatants were directly spotted onto the ProteinChip arrays with different chromatographic surfaces. The obtained spectra in a range from 2 to 200 kDa were subjected to bioinformatic analysis using the method of Fuzzy c-means, followed by the establishment of rule bases and evaluation using the relevance index according to Kiendl.Results. Several protein peaks were identified allowing differentiation between rejection and no rejection. Using two different ProteinChip surfaces, we found two biomarkers at 25.71 kDa and 28.13 kDa that gave a diagnostic sensitivity of 90% and 93% and a specificity of 80% [SAX2) and 85% (CM 10), respectively.Conclusions. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry appears to be a promising new diagnostic tool for distinguishing renal transplant patients with no rejection from those with acute rejection.

Tumor biology of renal cell carcinoma (RCC) is not very well understood, although many studies on molecular and cellular biology have been performed. It is accepted now that cancer research has to be performed also with proteomic tools, because proteins are the real actors in the genesis and progression of cancer. Therefore, we used a ProteinChip System(R) (SELDI) which is able to detect minute amounts of protein and moreover to analyze a complex protein pattern. We analyzed 37 cases of clear cell RCC as a training set including corresponding normal tissue. From all samples protein lysates were made and spotted directly on different chip surfaces (SAX2, WCX). After a washing procedure the arrays were analyzed in the ProteinChip Reader. All profiles were subjected to a bioinformatical analysis including normalization, clustering, rule extraction and rating. Defined rules (markers) were evaluated using a test set of 24 samples (13 tumor tissues and 11 normal kidney tissues). The generated rule base for the SAX2 surface showed a sensitivity of 100% and a specificity of 97.3%. For the WCX arrays the optimal rule base showed worse results. A combined rule base for SAX2 and WCX did not result in a higher sensitivity or specificity. Using the optimal rule base for the SAX2 chip in the test set, sensitivity and specificity reached 76.9% and 100%, respectively. The ProteinChip System represents a key technology for the rapid detection of cancer specific proteomic patterns. It is possible to identify clear cell renal cancer with high sensitivity and specificity from minimal amounts of cells.

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00 am - 12:00 pm1 Apr 2005603: SELDI-TOF Mass Spectrometry Reveals Distinctive Protein Expression Profiles in the Urine of Bladder Cancer Patients Kerstin Junker, Joerg Mueller, Dominik Driesch, Ferdinand von Eggeling, and Jörg Schubert Kerstin JunkerKerstin Junker More articles by this author , Joerg MuellerJoerg Mueller More articles by this author , Dominik DrieschDominik Driesch More articles by this author , Ferdinand von EggelingFerdinand von Eggeling More articles by this author , and Jörg SchubertJörg Schubert More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34843-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "603: SELDI-TOF Mass Spectrometry Reveals Distinctive Protein Expression Profiles in the Urine of Bladder Cancer Patients." The Journal of Urology, 173(4S), p. 165 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 165 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Kerstin Junker More articles by this author Joerg Mueller More articles by this author Dominik Driesch More articles by this author Ferdinand von Eggeling More articles by this author Jörg Schubert More articles by this author Expand All Advertisement PDF downloadLoading ...

Cutaneous T-cell lymphomas (CTCL) are characterized by malignant proliferation of skin homing T-cells. Although prognosis is generally good, reliable markers are needed to identify patients at risk for a more aggressive course. ProteinChip (SELDI) technology was used as a tool for the discovery of protein patterns in lymphocytes from patients with CTCL (n=25) and unaffected controls (n=25). Lymphocytes were separated in CD4+ and CD4- fractions by magnetic cell sorting (MACS). Each whole protein extract was analysed by ProteinChip technology. The resulting protein profiles were submitted for bioinformatic analysis including a clustering algorithm, a rule extraction, a rating and a rule-base construction step. For the generated combined rule base for the CD4- cell fraction, both the sensitivity and specificity for the prediction of CTCL reached 96%, while for the CD4+ fraction they were 92% and 84%, respectively, for sensitivity and specificity. The most significant peak at 3489Da could be identified as HNP3, an alpha-defensin, by immunocapturing. These results open up both the possibility for the use of this protein signature, especially HNP3, to more effectively monitor and screen CTCL, and the avenue to identify the other relevant peaks for a better understanding of the development of this tumour.

Objective: Since accurate biomarkers for the early diagnosis or individual prognosis of the bladder carcinoma are still not available, we used the ProteinChip technology, to search for discriminating protein expressions associated with this cancer and its subtypes.Methods: A training set consisting of 30 archival urine samples from bladder carcinoma patients and 30 urinary samples from healthy volounteers, was analyzed via ProteinChip technology and computer based data mining. Mass clusters of differentially expressed proteins were verified by a second set (test set) comprising 21 bladder carcinoma urine samples and 21 non-tumor urinary samples. Expression differences between carcinoma subtype sample groups of the initial training set were assessed by a trend test.Results: Bladder carcinoma was segregated from control with a sensitivity and specificity of 80% and 90 to 97% in the trainings set, as well as 52 to 57% and 57 to 62% in the test set, respectively. Segregation of pooled tumor stages pT2-pT3 from stages pT1 and pTa was possible at the 53.3 kDa cluster of the CM10-chip array data derived rule base.Conclusion: ProteinChip technology together with adapted computer based data mining tools are useful for the rapid establishment of potential protein biomarkers. (c) 2005 Elsevier B.V All rights reserved.

A surface-enhanced laser desorption/ionization time of flight (SELDI-TOF)-based ProteinChip System was used as a tool for rapid discovery and identification of protein patterns in serum that discriminate between trisomy 21 and unaffected pregnancies. We analyzed 24 serum samples from women carrying a trisomy 21 pregnancy and 32 with an unaffected pregnancy, ranging from 10.0 to 14.0 weeks of gestation. The resulting protein profiles were submitted to a clustering algorithm, a rule extraction, a rating, and a rule base construction step. For the generated combined rule base, the specificity and sensitivity for the prediction of a trisomy 21 pregnancy reach 97% and 91%, respectively.