TY - JOUR AB - Objectives: To investigate the role of blood eosinophils in predicting PH in end-stage lung disease. Methods: We conducted a retrospective study of adults with CF, COPD, and ILD who underwent RHC during lung transplant evaluations (2010-2022). Patients were classified by the 2022 ECS/ERS PH guidelines with pulmonary function and laboratory tests, including hemograms. The eosinophil threshold was set at 0.30 G/L. Results: We analyzed 663 patients (n = 89 CF, n = 294 COPD, and n = 280 ILD). Severe PH was more common in ILD (16%) than in CF (4%) and COPD (7%) (p = 0.0002), with higher eosinophil levels in ILD (p = 0.0002). No significant correlation was found between eosinophil levels and hemodynamic parameters (PAPm, PVR, and CI) across CF, COPD, and ILD (PAPm: p = 0.3974, p = 0.4400 and p = 0.2757, respectively; PVR: p = 0.6966, p = 0.1489 and p = 0.1630, respectively; CI: p = 0.9474, p = 0.5705 and p = 0.5945, respectively), nor was a correlation observed in patients not receiving OCS. Linear regression analysis confirmed the lack of association (PAPm: p = 0.3355, p = 0.8552 and p = 0.4146, respectively; PVR: p = 0.6924, p = 0.8935 and p = 0.5459, respectively; CI: p = 0.4260, p = 0.9289 and p = 0.5364, respectively), controlling for 6-MWD, Nt-proBNP, and ICS/OCS dosages. ROC analysis indicated eosinophils were ineffective in distinguishing PH severity levels across these diseases (AUC 0.54, 0.51, and 0.53, respectively). The analysis of eosinophil levels measured 18 ± 6 months prior to baseline found no predictive correlation with the presence of PH either. Eosinophil levels did not differ significantly among PH groups, but eosinophilic COPD was linked to more unclassified PH, higher CO, and greater lung volumes than non-eosinophilic COPD. Conclusions: In our cohort of end-stage CF, COPD, and ILD patients, blood eosinophilia did not predict the presence of PH but was associated with hemodynamic parameters and lung volumes in COPD. AU - Barnikel, M.* AU - Kneidinger, N.* AU - Gerckens, M. AU - Mümmler, C. AU - Lenoir, A.* AU - Mertsch, P.* AU - Veit, T.* AU - Leuschner, G.* AU - Waelde, A.* AU - Neurohr, C.* AU - Behr, J.* AU - Milger, K.* C1 - 73513 C2 - 57079 CY - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland TI - Current blood eosinophilia does not predict the presence of pulmonary hypertension in patients with end-stage lung disease. JO - J. Clin. Med. VL - 14 IS - 4 PB - Mdpi PY - 2025 SN - 2077-0383 ER - TY - JOUR AB - Background: Urinary incontinence (UI) and depression are prevalent conditions affecting millions globally and are significantly associated with various demographic, health, and socio-economic factors. This study examines the associations between UI and depression over a 14-year period using nationwide data. Methods: We analyzed cross-sectional data from the Turkish Health Studies Surveys conducted in seven different years between 2008 and 2022, including 125,276 participants aged 15 and older and excluding those with incomplete key health data. Variables included chronic conditions, BMI, depression severity (assessed by PHQ-8), socio-economic status, and lifestyle factors. Univariable and multivariable logistic regression models were used to investigate associations between UI and various risk factors over time. Results: The prevalence of UI and depression fluctuated over the 14 years, with a significant increase observed in 2014. Multivariate analysis confirmed a strong and consistent association between UI and depression across genders and age groups, even after adjusting for confounders. Higher depression severity increased the odds of experiencing UI. Age, multiple comorbidities, higher BMI, and lower socio-economic status were associated with an increased likelihood of UI. Obesity was a significant risk factor for UI in females but not in males. Urban living and higher education levels were inversely associated with UI. The simultaneous rise in UI and depression in 2014 may be linked to socio-economic changes during that period. Conclusions: The findings suggest a robust link between UI and depression, influenced by a complex interplay of health, demographic, and socio-economic factors, needing prospective studies to further investigate the causal pathway of these associations. AU - Dasdelen, M.F. AU - Dasdelen, Z.B.* AU - Almas, F.* AU - Cokkececi, B.* AU - Laguna, P.* AU - Rosette, J.d.l.* AU - Koçak, M.* C1 - 75230 C2 - 57858 CY - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland TI - Exploring the association between urinary incontinence and depression based on a series of large-scale national health studies in Türkiye. JO - J. Clin. Med. VL - 14 IS - 15 PB - Mdpi PY - 2025 SN - 2077-0383 ER - TY - JOUR AB - Background/Objectives: Our aim was to assess the feasibility of hyperspectral imaging (HSI) to detect changes in tissue oxygenation (StO2) of the back, as non-invasive spinal cord collateral network (CN) monitoring during staged endovascular repair (ER) of thoracoabdominal aortic aneurysm (TAAA). Methods: Between September 2019 and June 2021, 20 patients were treated for TAAA and underwent HSI. They were randomized 1:1 to minimally invasive staged segmental artery coil embolization (MIS2ACE) (n = 10) and staged stentgraft implantation (n = 10) as priming methods. HSI of paravertebral regions was taken during each procedure and up to 10 days after. The primary endpoint was the identification of StO2 changes after ER of TAAA. Results: TAAA Crawford Type II (n = 17) and Type III (n = 3) were treated. After stentgrafting, StO2 increased immediately (p < 0.001), followed by a decrease after 5 days (p < 0.001) and 10 days (p = 0.028). StO2 was significantly higher in the thoracic compared to the lumbar region. There was no significant difference between MIS2ACE and the first stentgrafting for StO2 (p = 0.491). Following MIS2ACE, definitive ER caused a significant decrease in StO2 after 5 days (p = 0.021), which recovered to baseline after 10 days (p = 0.130). After stentgraft priming, definitive ER caused a significant decrease in StO2 after 24 h (p = 0.008), which did not return to baseline after 5 (p < 0.001) and 10 days (p = 0.019). Conclusions: HSI detected significant changes in StO2 in the thoracic and lumbar paravertebral regions during ER of TAAA. These preliminary data suggest the efficacy of MIS2ACE in priming the CN before ER of TAAA. AU - Winther, B. AU - Branzan, D. AU - Etz, C.D.* AU - Geisler, A.A.* AU - Steiner, S. AU - Winther, H.* AU - Meixner, R. AU - Jiménez-Muñoz, M. AU - Kohler, H.* AU - Scheinert, D.* AU - Schmidt, A.* C1 - 74547 C2 - 57502 CY - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland TI - Evaluation of spinal cor blood supply with hyperspectral imaging of the paraspinous musculature during staged endovascular repair of thoracoabdominal aortic aneurysm: A sub-study of the prospective multicenter PAPA-ARTiS trial. JO - J. Clin. Med. VL - 14 IS - 9 PB - Mdpi PY - 2025 SN - 2077-0383 ER - TY - JOUR AB - Background: In Peripheral Artery Disease (PAD), there is an association between risk factors, the location of atherosclerotic lesions, and outcomes. Methods: This is a retrospective single-center analysis of adult PAD patients admitted between 2018 and 2021 with a follow-up until the end of 2023. Lesions were allocated to "suprainguinal", "infrainguinal-to-popliteal", "infrapopliteal", "two of three levels" and "all three levels" categories based on angiogram findings. The primary endpoint at the patient level was amputation-free survival and was major adverse limb events (MALEs) at the limb level. Results: A total of 2067 patients with 2633 affected limbs were analyzed, and 28.8% were female. At first admission, the median age was 68, and the most frequent PAD Fontaine stage was IIb (44.9%). Lesions were suprainguinal in 11.6%, infrainguinal-to-popliteal in 18.3%, infrapopliteal in 11.4%, two levels in 36.0%, and all three levels in 8.3%. Over 1020 days as the median follow-up, amputation-free survival was 67.6%, highest (92.5%) for suprainguinal lesions, and lowest (59.3%) for infrapopliteal lesions. At the patient level, the risk of major amputation or death was highest in infrapopliteal lesions and was equally likely in cases of two or three affected locations and was reduced in infrainguinal-to-popliteal lesions (Hazard Ratio, HR 0.62, 95% CI 0.44-0.87, p = 0.007) and suprainguinal lesions (HR 0.42, 95% CI 0.21-0.79, p = 0.008). At the limb level, compared to lesions in all three locations, the risk of MALEs was reduced in infrainguinal-to-popliteal lesions (HR 0.51, 95% CI 0.27-0.98, p = 0.044) and was equally likely in all other cases. Conclusions: Amputation-free survival was lowest in cases of infrapopliteal lesions or multi-level disease. At the limb level, isolated infrainguinal-to-popliteal lesions were associated with the lowest risk of MALEs. AU - Zimmermann, A.* AU - Holstein, D.J.F.* AU - Stürzebecher, P.* AU - Medicke, P.* AU - Niezold, A.* AU - Brunotte, M.* AU - Zeynalova, S.* AU - Wiegering, A.* AU - Seehofer, D.* AU - Schmidt, A.* AU - Steiner, S. AU - Scheinert, D.* AU - Branzan, D.* AU - Uttinger, K.L.* C1 - 75798 C2 - 58153 CY - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland TI - Outcomes at patient and limb levels in peripheral artery disease by the location of atherosclerotic lower limb lesions: An observational study from a high-volume German center. JO - J. Clin. Med. VL - 14 IS - 19 PB - Mdpi PY - 2025 SN - 2077-0383 ER - TY - JOUR AB - Background: Antiphospholipid antibody (aPL) testing is critical for the classification of antiphospholipid syndrome. The 2023 ACR/EULAR classification criteria recommend the use of enzyme-linked immunosorbent assays (ELISAs) and specific thresholds for aPL positivity. Since non-ELISA methods are increasingly used, we compared and evaluated ELISA and non-ELISA aPL assays in a real-world maximum care hospital setting. Methods: Between January 2021 and June 2024, anticardiolipin (aCL; IgG and IgM) and anti-beta2 glycoprotein I (aß2GPI; IgG and IgM) antibodies were measured using ELISA (n = 5115) and a chemiluminescence-based automated immunoassay (CLIA) (n = 3820). Results of parallel testing were compared, and associations with clinical and laboratory characteristics were evaluated. Results: A total of 946 samples were tested using ELISA and CLIA in parallel. A total of 136 (14%) specimens were positive for at least one aPL, and 55 (6%) specimens were from patients diagnosed with APS. Among the latter, 47 (85%) and 41 (75%) patients were positive when ELISA- or CLIA-based aPL assays were used, respectively. After applying the >40 units threshold of the new classification criteria, the number of aPL-positive specimens was significantly lower. In the entire cohort, the agreement between ELISA and CLIA aPL assays was acceptable only for aß2GPI IgG; the results from the two methods did not agree for aCL IgG/IgM and aß2GPI IgM. In APS patients, the agreement between ELISA and CLIA aPL assays was acceptable for aß2GPI IgG and IgM but poor for aCL IgG and IgM. Antibody levels in APS patients were significantly higher using CLIA compared to ELISA. Conclusions: The method-dependent discrepancies between ELISA- and CLIA-based aPL assays regarding the quantitative and qualitative results are substantial. Both methods are suitable for APS classification, but the choice of aPL assay may influence the classification, and therefore, aPL results should be interpreted carefully in the clinical context. AU - Kocijancic, M.* AU - Goj, T.* AU - Peter, A. AU - Klein, R.* AU - Hörber, S. C1 - 71452 C2 - 56191 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Antiphospholipid antibody testing in a maximum care hospital: Method-dependent differences. JO - J. Clin. Med. VL - 13 IS - 15 PB - Mdpi PY - 2024 SN - 2077-0383 ER - TY - JOUR AB - Background: Disease-modifying antirheumatic drugs (bDMARDs) have shown efficacy in treating Rheumatoid Arthritis (RA). Predicting treatment outcomes for RA is crucial as approximately 30% of patients do not respond to bDMARDs and only half achieve a sustained response. This study aims to leverage machine learning to predict both initial response at 6 months and sustained response at 12 months using baseline clinical data. Methods: Baseline clinical data were collected from 154 RA patients treated at the University Hospital in Erlangen, Germany. Five machine learning models were compared: Extreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), K-nearest neighbors (KNN), Support Vector Machines (SVM), and Random Forest. Nested cross-validation was employed to ensure robustness and avoid overfitting, integrating hyperparameter tuning within its process. Results: XGBoost achieved the highest accuracy for predicting initial response (AUC-ROC of 0.91), while AdaBoost was the most effective for sustained response (AUC-ROC of 0.84). Key predictors included the Disease Activity Score-28 using erythrocyte sedimentation rate (DAS28-ESR), with higher scores at baseline associated with lower response chances at 6 and 12 months. Shapley additive explanations (SHAP) identified the most important baseline features and visualized their directional effects on treatment response and sustained response. Conclusions: These findings can enhance RA treatment plans and support clinical decision-making, ultimately improving patient outcomes by predicting response before starting medication. AU - Salehi, F.* AU - Lopera Gonzalez, L.I.* AU - Bayat, S.* AU - Kleyer, A.* AU - Zanca, D.* AU - Brost, A.* AU - Schett, G.* AU - Eskofier, B.M. C1 - 71130 C2 - 56022 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Machine learning prediction of treatment response to biological disease-modifying antirheumatic drugs in rheumatoid arthritis. JO - J. Clin. Med. VL - 13 IS - 13 PB - Mdpi PY - 2024 SN - 2077-0383 ER - TY - JOUR AB - Background: Drusen and drusenoid deposits are a hallmark of age-related macular degeneration (AMD). Nowadays, a multimodal retinal imaging approach enables the detection of these deposits. However, quantitative data on subretinal drusenoid deposits (SDDs) are still missing. Here, we compare the capability of en-face drusen and SDD area detection in eyes with non-exudative AMD using conventional imaging modalities versus Retro mode imaging. We also quantitatively assess the topographic distribution of drusen and SDDs. Methods: In total, 120 eyes of 90 subjects (mean age ± standard deviation = 74.6 ± 8.6 years) were included. Coherent en-face drusen and SDD areas were measured via near-infrared reflectance, green (G-) and blue (B-) fundus autofluorescence (AF), and Retro mode imaging. Drusen phenotypes were classified by correlating en-face drusen areas using structural high-resolution spectral domain optical coherence tomography. The topographic distribution of drusen was analyzed according to a modified ETDRS (Early Treatment of Diabetic Retinopathy Study) grid. Intraclass correlation coefficient (ICC) analysis was applied to determine the inter-reader agreement in the SDD en-face area assessment. Results: The largest coherent en-face drusen area was found using Retro mode imaging with a mean area of 105.2 ± 45.9 mm2 (deviated left mode (DL)) and 105.4 ± 45.5 mm2 (deviated right mode (DR)). The smallest en-face drusen areas were determined by GAF (50.9 ± 42.6 mm2) and BAF imaging (49.1 ± 42.9 mm2) (p < 0.001). The inter-reader agreement for SDD en-face areas ranged from 0.93 (DR) to 0.70 (BAF). The topographic analysis revealed the highest number of SDDs in the superior peripheral retina, whereas sub-retinal pigment epithelium drusen were mostly found in the perifoveal retina. Retro mode imaging further enabled the detection of the earliest SDD stages. Conclusions: Retro mode imaging allows for a detailed detection of drusen phenotypes. While hundreds/thousands of SDDs can be present in one eye, the impact of SDD number or volume on AMD progression still needs to be evaluated. However, this new imaging modality can add important knowledge on drusen development and the pathophysiology of AMD. AU - Saßmannshausen, M.* AU - Sautbaeva, L.* AU - von der Emde, L.A.* AU - Vaisband, M.* AU - Sloan, K.R.* AU - Hasenauer, J. AU - Holz, F.G.* AU - Ach, T.* C1 - 71306 C2 - 56040 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Retro mode imaging for detection and quantification of Sub-RPE drusen and subretinal drusenoid deposits in age-related macular degeneration. JO - J. Clin. Med. VL - 13 IS - 14 PB - Mdpi PY - 2024 SN - 2077-0383 ER - TY - JOUR AB - In recent years, remarkable strides have been made in the management of gastrointestinal disorders, transforming the landscape of patient care and outcomes. This article explores the latest breakthroughs in the field, encompassing innovative diagnostic techniques, personalized treatment approaches, and novel therapeutic interventions. Additionally, this article emphasizes the use of precision medicine tailored to individual genetic and microbiome profiles, and the application of artificial intelligence in disease prediction and monitoring. This review highlights the dynamic progress in managing conditions such as inflammatory bowel disease, gastroesophageal reflux disease, irritable bowel syndrome, and gastrointestinal cancers. By delving into these advancements, we offer a glimpse into the promising future of gastroenterology, where multidisciplinary collaborations and cutting-edge technologies converge to provide more effective, patient-centric solutions for individuals grappling with gastrointestinal disorders. AU - Suri, C. AU - Pande, B.* AU - Sahu, T.* AU - Sahithi, L.S.* AU - Verma, H.K. C1 - 71129 C2 - 55969 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Revolutionizing gastrointestinal disorder management: Cutting-edge advances and future prospects. JO - J. Clin. Med. VL - 13 IS - 13 PB - Mdpi PY - 2024 SN - 2077-0383 ER - TY - JOUR AB - BACKGROUND: Transcatheter edge-to-edge repair (TEER) of the mitral valve (MV) can be performed using the PASCAL or MitraClip devices. Few studies offer a head-to-head outcome comparison of these two devices. MATERIAL AND METHODS: PubMed, EMBASE, Cochrane Library, Clinicaltrials.gov and WHO's International Clinical Trials Registry Platform, from 1 January 2000 until 1 March 2023, were searched. Study protocol details were registered in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023405400). Randomized Controlled Trials and observational studies reporting head-to-head clinical comparison of PASCAL and MitraClip devices were eligible for selection. Patients with severe functional or degenerative mitral regurgitation (MR) who had undergone TEER of the MV with either PASCAL or MitraClip devices were included in the meta-analysis. Data from six studies (five observational and one randomized clinical trial) were extracted and analyzed. The main outcomes were a reduction in MR to 2+ or less, improvement of New York Heart Association (NYHA) and 30-day all-cause mortality. Peri-procedural mortality, success rate and adverse events were also compared. RESULTS: Data from 785 and 796 patients that underwent TEER using PASCAL and MitraClip, respectively, were analyzed. Thirty-day all-cause mortality (Risk ratio [RR] = 1.51, 95% CI 0.79-2.89), MR reduction to maximum 2+ (RR = 1.00, 95% CI 0.98-1.02) and NYHA improvement (RR = 0.98, 95% CI 0.84-1.15) were similar in both device groups. Both devices had high and similar success rates (96.9% and 96.7% for the PASCAL and MitraClip group, respectively, p value = 0.91). MR reduction to 1+ or less at discharge was similar in both device groups (RR = 1.06, 95% CI 0.95-1.19). Composite peri-procedural and in-hospital mortality was 0.64% and 1.66% in the PASCAL and MitraClip groups, respectively (p value = 0.094). Rates of peri-procedural cerebrovascular accidents were 0.26% in PASCAL and 1.01% in MitraClip (p value = 0.108). CONCLUSIONS: Both PASCAL and MitraClip devices have high success and low complication rates for TEER of the MV. PASCAL was not inferior to MitraClip in reducing the MR level at discharge. AU - Hosseini, K.* AU - Soleimani, H.* AU - Nasrollahizadeh, A.* AU - Jenab, Y.* AU - Karlas, A. AU - Avgerinos, D.V.* AU - Briasoulis, A.* AU - Kuno, T.* AU - Doulamis, I.* AU - Kampaktsis, P.N.* C1 - 67876 C2 - 54354 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Edge-to-edge transcatheter mitral valve repair using PASCAL vs. MitraClip: A systematic review and meta-analysis. JO - J. Clin. Med. VL - 12 IS - 10 PB - Mdpi PY - 2023 SN - 2077-0383 ER - TY - JOUR AB - Artificial intelligence (AI) has gained prominence in medical imaging, particularly in obstetrics and gynecology (OB/GYN), where ultrasound (US) is the preferred method. It is considered cost effective and easily accessible but is time consuming and hindered by the need for specialized training. To overcome these limitations, AI models have been proposed for automated plane acquisition, anatomical measurements, and pathology detection. This study aims to overview recent literature on AI applications in OB/GYN US imaging, highlighting their benefits and limitations. For the methodology, a systematic literature search was performed in the PubMed and Cochrane Library databases. Matching abstracts were screened based on the PICOS (Participants, Intervention or Exposure, Comparison, Outcome, Study type) scheme. Articles with full text copies were distributed to the sections of OB/GYN and their research topics. As a result, this review includes 189 articles published from 1994 to 2023. Among these, 148 focus on obstetrics and 41 on gynecology. AI-assisted US applications span fetal biometry, echocardiography, or neurosonography, as well as the identification of adnexal and breast masses, and assessment of the endometrium and pelvic floor. To conclude, the applications for AI-assisted US in OB/GYN are abundant, especially in the subspecialty of obstetrics. However, while most studies focus on common application fields such as fetal biometry, this review outlines emerging and still experimental fields to promote further research. AU - Jost, E.* AU - Kosian, P.* AU - Jimenez Cruz, J.* AU - Albarqouni, S. AU - Gembruch, U.* AU - Strizek, B.* AU - Recker, F.* C1 - 68745 C2 - 54955 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Evolving the era of 5D ultrasound? A systematic literature review on the applications for artificial intelligence ultrasound imaging in obstetrics and gynecology. JO - J. Clin. Med. VL - 12 IS - 21 PB - Mdpi PY - 2023 SN - 2077-0383 ER - TY - JOUR AB - We aimed to review the feasibility and safe use of the percutaneous axillary artery (AxA, 100 patients) approach for endovascular repair (ER) of thoraco-abdominal aortic aneurysms (TAAA, 90 patients) using fenestrated, branched, and chimney stent grafts and other complex endovascular procedures (10 patients) necessitating AxA access. Percutaneous puncture of the AxA in its third segment was performed using sheaths sized between 6 to 14F. For closing puncture sites greater than 8F, two Perclose ProGlide percutaneous vascular closure devices (PVCDs) (Abbott Vascular, Santa Clara, CA, USA) were deployed in the pre-close technique. The median maximum diameter of the AxA in the third segment was 7.27 mm (range 4.50-10.80). Device success, defined as successful hemostasis by PVCD, was reported in 92 patients (92.0%). As recently reported results in the first 40 patients suggested that adverse events, including vessel stenosis or occlusion, occurred only in cases with a diameter of the AxA < 5 mm, in all subsequent 60 cases AxA access was restricted to a vessel diameter ≥ 5 mm. In this late group, no hemodynamic impairment of the AxA occurred except in six early cases below this diameter threshold, all of which could be repaired by endovascular measures. Overall mortality at 30 days was 8%. In conclusion, percutaneous approach of the AxA in its third segment is feasible and represents a safe alternative access to open access for complex endovascular aorto-iliac procedures. Complications are rare, especially if the maximum diameter of the access vessel (AxA) is ≥5 mm. AU - Wittig, T. AU - Sabanov, A.* AU - Schmidt, A.* AU - Scheinert, D.* AU - Steiner, S. AU - Branzan, D. C1 - 67737 C2 - 54045 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Feasibility and safety of percutaneous axillary artery access in a prospective series of 100 complex aortic and aortoiliac interventions. JO - J. Clin. Med. VL - 12 IS - 5 PB - Mdpi PY - 2023 SN - 2077-0383 ER - TY - JOUR AB - Within this single-center cohort study, we investigated the impact of optimal medical therapy on all-cause mortality, major amputation-free survival and clinically driven target lesion revascularization (CD TLR) in 552 patients with peripheral arterial disease (PAD) undergoing endovascular infrapopliteal revascularization. From the overall cohort, 145 patients were treated for intermittent claudication (IC) and 407 were treated for critical limb ischemia (CLI). Optimal medical therapy (OMT) was defined as the presence of at least one antiplatelet agent, statin and ACE inhibitor or AT-2 antagonist based on guideline recommendations. About half (55.5%) of all patients were prescribed OMT at discharge, with a higher proportion in claudicants (62.1%) versus CLI patients (53.2%). Over three years of follow-up, survival was significantly better in patients with IC (80.6 ± 3.8% vs. 59.9 ± 2.9%; p < 0.001). There was a signal towards better survival in those patients receiving OMT (log-rank p = 0.09). Similarly, amputation-free survival (AFS) was significantly better in patients with IC (p = 0.004) and also in patients receiving OMT (78.8 ± 3.6%) compared to that in those without OMT (71.5 ± 4.2%; p = 0.046). Freedom from CD TLR within three years was significantly better in the IC group (p = 0.002), but there were no statistically significant differences for CD TLR dependent on the presence of OMT (p = 0.79). In conclusion, there is still an important underuse of OMT in patients undergoing infrapopliteal interventions, which is even more pronounced in CLI despite a signal for its benefit regarding all-cause mortality and major amputation-free survival. AU - Wittig, T. AU - Pflug, T.* AU - Schmidt, A.* AU - Scheinert, D.* AU - Steiner, S. C1 - 68004 C2 - 54482 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Impact of optimal medical therapy on reintervention and survival rates after endovascular infrapopliteal revascularization. JO - J. Clin. Med. VL - 12 IS - 15 PB - Mdpi PY - 2023 SN - 2077-0383 ER - TY - JOUR AB - Background: Chronic pancreatitis (CP) often leads to recurrent pain as well as exocrine and/or endocrine pancreatic insufficiency. This study aimed to investigate the effect of pancreatic head resections on glucose metabolism in patients with CP. Methods: Patients who underwent pylorus‐preserving pancreaticoduodenectomy (PPPD), Whipple procedure (cPD), or duodenum-preserving pancreatic head resection (DPPHR) for CP between January 2011 and December 2020 were retrospectively analyzed with regard to markers of pancreatic endocrine function including steady‐state beta cell function (%B), insulin resistance (IR), and insulin sensitivity (%S) according to the updated Homeostasis Model Assessment (HOMA2). Results: Out of 141 pancreatic resections for CP, 43 cases including 31 PPPD, 2 cPD and 10 DPPHR, met the inclusion criteria. Preoperatively, six patients (14%) were normoglycemic (NG), 10 patients (23.2%) had impaired glucose tolerance (IGT) and 27 patients (62.8%) had diabetes mellitus (DM). In each subgroup, no significant changes were observed for HOMA2‐%B (NG: p = 0.57; IGT: p = 0.38; DM: p = 0.1), HOMA2‐IR (NG: p = 0.41; IGT: p = 0.61; DM: p = 0.18) or HOMA2‐%S (NG: p = 0.44; IGT: p = 0.52; DM: p = 0.51) 3 and 12 months after surgery, respectively. Conclusion: Pancreatic head resections for CP, including DPPHR and pancreatoduodenectomies, do not significantly affect glucose metabolism within a follow‐up period of 12 months. AU - Hempel, S.* AU - Oehme, F.* AU - Ehehalt, F. AU - Solimena, M. AU - Kolbinger, F.R.* AU - Bogner, A.* AU - Welsch, T.* AU - Weitz, J.* AU - Distler, M. C1 - 64163 C2 - 52096 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - The impact of pancreatic head resection on blood glucose homeostasis in patients with chronic pancreatitis. JO - J. Clin. Med. VL - 11 IS - 3 PB - Mdpi PY - 2022 SN - 2077-0383 ER - TY - JOUR AB - Although epidemiological studies suggest a lower prostate cancer incidence rate in patients with type 2 diabetes, cancer survival is markedly reduced. Underlying mechanisms that connect the two diseases are still unclear. Potential links between type 2 diabetes and prostate cancer are hallmarks of the metabolic syndrome, such as hyperglycemia and dyslipidemia. Therefore, we explored the systemic metabolism of 103 prostate cancer patients with newly diagnosed and yet untreated prostate cancer compared to 107 healthy controls, who were carefully matched for age and BMI. Here, we report that patients with prostate cancer display higher fasting blood glucose levels and insulin resistance, without changes in insulin secretion. With respect to lipid metabolism, serum triglyceride levels were lower in patients with prostate cancer. In addition, we report increased adrenal steroid biosynthesis in these patients. Our results indicate that higher fasting glucose levels in patients with prostate cancer may be explained at least in part by insulin resistance, due to the enhanced synthesis of adrenal steroids. AU - Lutz, S.Z. AU - Hennenlotter, J.* AU - Frankó, A. AU - Dannecker, C. AU - Fritsche, L. AU - Kantartzis, K. AU - Wagner, R.* AU - Peter, A. AU - Stefan, N. AU - Fritsche, A. AU - Todenhöfer, T.* AU - Stenzl, A.* AU - Häring, H.-U. AU - Heni, M. C1 - 66828 C2 - 53303 TI - Diabetes and the prostate: Elevated fasting glucose, insulin resistance and higher levels of adrenal steroids in prostate cancer. JO - J. Clin. Med. VL - 11 IS - 22 PY - 2022 SN - 2077-0383 ER - TY - JOUR AB - The aim of this systematic review was to summarise the comparative evidence on the risk of contrast-associated acute kidney injury (CA-AKI) with CO2 or iodinated contrast medium (ICM) for peripheral vascular interventions. We searched Ovid MEDLINE, Cochrane Library, Embase, Epistemonikos, PubMed-similar-articles, clinical trial registries, journal websites, and reference lists up to February 2022. We included studies comparing the risk of CA-AKI in patients who received CO2 or ICM for peripheral angiography with or without endovascular intervention. Two reviewers screened the references and assessed the risk of bias of the included studies. We extracted data on study population, interventions and outcomes. For the risk of CA-AKI as our primary outcome of interest, we calculated risk ratios (RRs) with a 95% confidence interval (CI) and performed random-effects meta-analyses. We identified three RCTs and five cohort studies that fully met our eligibility criteria. Based on a random-effects meta-analysis, the risk of CA-AKI was lower with CO2 compared to ICM (8.6% vs. 15.2%; RR, 0.59; 95% CI 0.33–1.04). Only limited results from a few studies were available on procedure and fluoroscopy time, radiation dose and CO2-related adverse events. The evidence suggests that the use of CO2 for peripheral vascular interventions reduces the risk of CA-AKI compared to ICM. However, due to the relevant residual risk of CA-AKI with the use of CO2, other AKI risk factors must be considered in patients undergoing peripheral vascular interventions. AU - Wagner, G.* AU - Glechner, A.* AU - Persad, E.* AU - Klerings, I.* AU - Gartlehner, G.* AU - Moertl, D.* AU - Steiner, S. C1 - 66947 C2 - 53382 TI - Risk of contrast-associated acute kidney injury in patients undergoing peripheral angiography with carbon dioxide compared to iodine-containing contrast agents: A systematic review and meta-analysis. JO - J. Clin. Med. VL - 11 IS - 23 PY - 2022 SN - 2077-0383 ER - TY - JOUR AB - Background: The study aimed to investigate the role of subclinical inflammation on the association between diurnal cortisol patterns and glycaemia in an aged population. (2) Methods: Salivary cortisol, interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) were analysed in a sample of 394 men and 364 women (mean age = 5 ± 6.3, 65-90 years). The ratio of morning after awakening and late-night cortisol was calculated as an indication of diurnal cortisol slope (DCS). Multivariable regression models were run to examine whether IL-6 mediates the relationship between the DCS and glycaemia. The Sobel test and bootstrapping methods were used to quantify the mediation analyses. (3) Results: In comparison to normoglycaemic counterparts (n = 676, 89.2%), an increase in IL-6 concentrations, in individuals with hyperglycaemia (HbA1c ≥ 6.5%) (n = 82, 10.8%) (p = 0.04), was significantly associated with a flatter DCS. The link between flatter DCS and elevated HbA1c level was significant mediated by a heightened IL-6 level. Our results do not suggest reverse-directionality, whereby cortisol did not mediate the association of IL-6 with HbA1c. (4) Conclusions: In our sample, the relation between flatter DCS and hyperglycaemia was partly explained by IL-6 levels. The paradigm of subclinical inflammation-mediated cortisol response on glucose metabolism could have widespread implications for improving our understanding of the pathophysiology of type 2 diabetes mellitus. AU - Johar, H. AU - Spieler, D. AU - Bidlingmaier, M.* AU - Herder, C.* AU - Rathmann, W.* AU - Koenig, W.* AU - Peters, A. AU - Kruse, J.* AU - Ladwig, K.-H. C1 - 62437 C2 - 50738 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Chronic inflammation mediates the association between cortisol and hyperglycemia: Findings from the cross-sectional population-based KORA Age Study. JO - J. Clin. Med. VL - 10 IS - 13 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - Background: COVID-19-associated restrictions impact societies. We investigated the impact in a large cohort of inflammatory bowel disease (IBD) patients. Methods: Pediatric (pIBD) and adult patients and pIBD parents completed validated questionnaires for self-perceived stress (Perceived Stress Questionnaire, PSQ) and quality of life from July to October 2020 (1st survey) and March to April 2021 (2nd survey). Analyses were stratified by age groups (6–20, >20–40, >40–60, >60 years). Perceived risk of infection and harm from COVID-19 were rated on a 1–7 scale. An index for severe outcome (SIRSCO) was calculated. Multivariable logistic regression analysis was performed. Results: Of 820 invited patients, 504 (62%, 6–85 years) patients and 86 pIBD parents completed the 1st, thereof 403 (80.4%) the 2nd survey. COVID-19 restrictions resulted in cancelled doctoral appointments (26.7%), decreased physical activity, increased food intake, unintended weight gain and sleep disturbance. PSQ increased with disease activity. Elderly males rated lower compared to females or younger adults. PSQ in pIBD mothers were comparable to moderate/severe IBD adults. Infection risk and harm were perceived high in 36% and 75.4%. Multivariable logistic models revealed associations of higher perceived risk with >3 household members, job conditions and female gender, and of perceived harm with higher SIRSCO, unintended weight change, but not with gender or age. Cancelled clinic-visits were associated with both. SARS-CoV-2 antibodies prior 2nd infection wave were positive in 2/472 (0.4%). Conclusions: IBD patients report a high degree of stress and self-perceived risk of complications from COVID-19 with major differences related to gender and age. Low seroprevalence may indicate altered immune response. AU - Koletzko, L.* AU - Klucker, E.* AU - Le Thi, T.G.* AU - Breiteneicher, S.* AU - Rubio-Acero, R.* AU - Neuhaus, L.* AU - Stark, R.G. AU - Standl, M. AU - Wieser, A.* AU - Török, H.* AU - Koletzko, S.* AU - Schwerd, T.* C1 - 63090 C2 - 51126 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Following pediatric and adult ibd patients through the COVID-19 pandemic: Changes in psychosocial burden and perception of infection risk and harm over time. JO - J. Clin. Med. VL - 10 IS - 18 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - The hepatokine fetuin A (Fet A) has been associated with diverse pathological states such as insulin resistance, type 2 diabetes, macrovascular disease, and systemic ectopic and vascular calcification. Fet A may also play a role in tumor growth and metastasis. The biological activity of Fet A may be affected by various modifications, including phosphorylation, O- and N-glycosylation and fatty acid binding. We developed an antibody-based assay for the detection of Fet A phosphorylated at serine 312. Fatty acid pattern was determined by gas chromatography. Using the antibody, we found that the phosphorylation was stable in human plasma or serum at room temperature for 8 h. We observed that Fet A is present in several glycosylation forms in human plasma, but the extent of Ser312 phosphorylation was not associated with glycosylation. The phosphorylation pattern did not change during an oral glucose tolerance test (0-120 min). We further found that human Fet A binds preferentially saturated fatty acids (>90%) at the expense of mono- and poly-unsaturated fatty acids. Our results indicate that different molecular species of Fet A are present in human plasma and that these different modifications may determine the different biological effects of Fet A. AU - Kovářová, M. AU - Kalbacher, H.* AU - Peter, A. AU - Häring, H.-U. AU - Didangelos, T.* AU - Stefan, N. AU - Birkenfeld, A.L. AU - Schleicher, E. AU - Kantartzis, K. C1 - 61208 C2 - 50097 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Detection and characterization of phosphorylation, glycosylation, and fatty acid bound to fetuin A in human blood. JO - J. Clin. Med. VL - 10 IS - 3 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - Hand injuries often result in significant functional impairments and are rarely completely restored. The spontaneous regeneration of injured appendages, which occurs in salamanders and newts, for example, has been reported in human fingertips after distal amputation, but this type of regeneration is rare in mammals and is incompletely understood. Here, we study fingertip regeneration by amputating murine digit tips, either distally to initiate regeneration, or proximally, causing fibrosis. Using an unbiased microarray analysis, we found that digit tip regeneration is significantly associated with hair follicle differentiation, Wnt, and sonic hedgehog (SHH) signaling pathways. Viral over-expression and genetic knockouts showed the functional significance of these pathways during regeneration. Using transgenic reporter mice, we demonstrated that, while both canonical Wnt and HH signaling were limited to epidermal tissues, downstream hedgehog signaling (through Gli) occurred in mesenchymal tissues. These findings reveal a mechanism for epidermal/mesenchyme interactions, governed by canonical hedgehog signaling, during digit regeneration. Further research into these pathways could lead to improved therapeutic outcomes after hand injuries in humans. AU - Maan, Z.N.* AU - Rinkevich, Y. AU - Barrera, J.* AU - Chen, K.* AU - Henn, D.* AU - Foster, D.* AU - Bonham, C.A.* AU - Padmanabhan, J.* AU - Sivaraj, D.* AU - Duscher, D.* AU - Hu, M.* AU - Yan, K.* AU - Januszyk, M.* AU - Longaker, M.T.* AU - Weissman, I.L.* AU - Gurtner, G.C.* C1 - 63103 C2 - 51294 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Epidermal-derived hedgehog signaling drives mesenchymal proliferation during digit tip regeneration. JO - J. Clin. Med. VL - 10 IS - 18 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - Aim: To compare in terms of glycemic variability two premixed insulins, Premixed Human Insulin 30/70 (PHI) and Biphasic Aspart 30 (BiAsp30), using Continuous Glucose Monitoring (CGM) and to estimate the correlation of Glycated Albumin (GA) and Fructosamine (FA) with CGM data. Patients-Data: A total of 36 well-controlled patients with type 2 Diabetes Mellitus (T2DM) underwent 7-day CGM with PHI and subsequently with BiAsp30. GA and FA were measured at the first and last day of each week of CGM. Results: BiAsp30 was associated with lower Average Blood Glucose (ABG) during the 23:00-03:00 period (PHI: 135.08 +/- 28.94 mg/dL, BiAsp30: 117.75 +/- 21.24 mg/dL, p < 0.001) and the 00:00-06:00 period (PHI: 120.42 +/- 23.13 mg/dL, BiAsp30: 111.17 +/- 14.74 mg/dL, p = 0.008), as well as with more time below range (<70 mg/dL) (TBR) during the 23:00-03:00 period in the week (PHI: 3.65 +/- 5.93%, BiAsp30: 11.12 +/- 16.07%, p = 0.005). PHI was associated with lower ABG before breakfast (PHI: 111.75 +/- 23.9 mg/dL, BiAsp30: 128.25 +/- 35.9 mg/dL, p = 0.013). There were no differences between the two groups in ABG, Time In Range and Time Below Range during the entire 24-h period for 7 days, p = 0.502, p = 0.534, and p = 0.258 respectively, and in TBR for the 00:00-06:00 period p = 0.253. Total daily insulin requirements were higher for BiAsp30 (PHI: 47.92 +/- 12.18 IU, BiAsp30: 49.58 +/- 14.12 IU, p = 0.001). GA and FA correlated significantly with ABG (GA: r = 0.512, p = 0.011, FA: r = 0.555, p = 0.005). Conclusions: In well-controlled patients with T2DM, BiAsp30 is an equally effective alternative to PHI. AU - Margaritidis, C.* AU - Karlafti, E.* AU - Kotzakioulafi, E.* AU - Kantartzis, K. AU - Tziomalos, K.* AU - Kaiafa, G.* AU - Savopoulos, C.* AU - Didangelos, T.* C1 - 62129 C2 - 50659 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Comparison of premixed human insulin 30/70 to biphasic aspart 30 in well-controlled patients with type 2 diabetes using continuous glucose monitoring. JO - J. Clin. Med. VL - 10 IS - 9 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - Observational studies suggest that early onset of menopause is associated with increased risk of hypertension. Whether this association is causal or due to residual confounding and/or reverse causation remains undetermined. We aimed to evaluate the observational and causal association between age at natural menopause (ANM) and blood pressure traits in Caucasian women. A cross-sectional and one-sample Mendelian randomization (MR) study was conducted in 4451 postmenopausal women from the CoLaus and Rotterdam studies. Regression models were built with observational data to study the associations of ANM with systolic and diastolic blood pressure (SBP/DBP) and hypertension. One-sample MR analysis was performed by calculating a genetic risk score of 54 ANM-related variants, previously identified in a genome-wide association study (GWAS) on ANM. In the two-sample MR analysis we used the estimates from the ANM-GWAS and association estimates from 168,575 women of the UK Biobank to evaluate ANM-related variants and their causal association with SBP and DBP. Pooled analysis from both cohorts showed that a one-year delay in menopause onset was associated with 2% (95% CI 0; 4) increased odds of having hypertension, and that early menopause was associated with lower DBP (β = −1.31, 95% CI −2.43; −0.18). While one-sample MR did not show a causal association between ANM and blood pressure traits, the two-sample MR showed a positive causal association of ANM with SBP; the last was driven by genes related to DNA damage repair. The present study does not support the hypothesis that early onset of menopause is associated with higher blood pressure. Our results suggest different ANM-related genetic pathways could differently impact blood pressure. AU - Roa-Díaz, Z.M.* AU - Asllanaj, E.* AU - Amin, H.A.* AU - Rojas, L.Z.* AU - Nano, J. AU - Ikram, M.A.* AU - Drenos, F.* AU - Franco, O.H.* AU - Pazoki, R.* AU - Marques-Vidal, P.* AU - Voortman, T.* AU - Muka, T.* C1 - 63129 C2 - 51338 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Age at natural menopause and blood pressure traits: Mendelian randomization study. JO - J. Clin. Med. VL - 10 IS - 19 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - Background: Application of different value sets to health-related quality of life (HRQoL) measured with the EQ-5D-3L may lead to different results due to differences in methods, perspectives, and countries used. Focusing on concordance, this study aimed at understanding the implications of applying EQ-5D-3L value sets from Sweden, Germany, Denmark, and the UK to evaluate HRQoL of patients undergoing total hip replacement (THR) in Sweden before and after surgery. Methods: We performed a longitudinal study of patients in the Swedish Hip Arthroplasty Register from preoperative stage to 1-year follow-up (n = 73,523) using data collected from 2008 to 2016. Eight EQ-5D-3L value sets from the four countries were compared based on a valuation method (visual analogue scale (VAS) or time trade-off (TTO)), perspective (experience-based or hypothetical), and country. Concordance among the value sets with patient-reported EQ VAS score was also assessed. Longitudinal changes in EQ-5D-3L index over the 1-year follow-up were compared across value sets by method, perspective, and country. Results: Value sets based on the same method and perspective showed higher concordance in EQ-5D-3L index at both measurement time points than other comparisons. In the comparisons by perspective, VAS value sets showed higher concordance than TTO value sets. The Swedish VAS and the Danish TTO value sets showed the highest levels of concordance with patient-reported EQ VAS scores. Generally, value sets based on the same method and perspective had the smallest mean differences between changes in EQ-5D-3L indices from preoperative to 1-year postoperative follow-up. Conclusion: Among THR patients value sets based on the same method and perspective, a direct transfer of results across countries could be meaningful. In cases of differences in methods and perspectives among value sets, transfer of value sets across settings would have to consider conversion through crosswalk. AU - Teni, F.S.* AU - Rolfson, O.* AU - Berg, J.* AU - Leidl, R. AU - Burström, K.* C1 - 63095 C2 - 51289 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Concordance among Swedish, German, Danish, and UK EQ-5D-3L value sets: Analyses of patient-reported outcomes in the swedish hip arthroplasty register. JO - J. Clin. Med. VL - 10 IS - 18 PB - Mdpi PY - 2021 SN - 2077-0383 ER - TY - JOUR AB - The triple-negative breast tumor boundary is made of aligned, linear collagen. The pro-oncogenic impact of linear collagen is well established; however, its mechanism of formation is unknown. An in vitro analogue of the tumor border is created by a co-culture of MDA-MB-231 cells, adipose derived stem cells, and dermal fibroblasts. Decellularization of this co-culture after seven days reveals an extracellular matrix that is linear in fashion, high in pro-oncogenic collagen type VI, and able to promote invasion of reseeded cells. Further investigation revealed linear collagen VI is produced by fibroblasts in response to a paracrine co-culture of adipose derived stem cells and MDA-MB-231, which together secrete high levels of the chemokine CCL5. The addition of monoclonal antibody against CCL5 to the co-culture results in an unorganized matrix with dramatically decreased collagen VI. Importantly, reseeded cells do not exhibit pro-oncogenic behavior. These data illustrate a cellular mechanism, which creates linear extracellular matrix (ECM) in vitro, and highlight a potential role of CCL5 for building striated tumor collagen in vivo. AU - Brett, E.* AU - Sauter, M.* AU - Timmins, E.* AU - Azimzadeh, O. AU - Rosemann, M. AU - Merl-Pham, J. AU - Hauck, S.M. AU - Nelson, P.J.* AU - Becker, K.F.* AU - Schunn, I.* AU - Lowery, A.* AU - Kerin, M.J.* AU - Atkinson, M.J. AU - Krueger, A.* AU - Machens, H.* AU - Duscher, D.* C1 - 59226 C2 - 48678 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Oncogenic linear collagen VI of invasive breast cancer is induced by CCL5. JO - J. Clin. Med. VL - 9 IS - 4 PB - Mdpi PY - 2020 SN - 2077-0383 ER - TY - JOUR AB - The recommendation for pulmonary rehabilitation (PR) in idiopathic pulmonary fibrosis (IPF) is weak with low-quality evidence. Therefore, the aim of this study is to investigate short-term PR effects and their maintenance after a 3-month follow-up. Fifty-four IPF patients were randomized into a group receiving a 3-week comprehensive, inpatient PR (n = 34, FVC: 74 +/- 19% pred.) or usual care (UC) (n = 17, FVC: 72 +/- 20%pred.). Outcomes were measured at baseline (T1), after intervention (T2), and 3 months after T2 (T3). A 6-min walk distance (6MWD) was used as the primary outcome and chronic respiratory disease questionnaire (CRQ) scores as the secondary outcome. Change in 6MWD from T1 to T2 (Delta = 61 m, 95% CI (18.5-102.4), p = 0.006) but not from T1 to T3 (Delta = 26 m, 95% CI (8.0-61.5), p = 0.16) differed significantly between groups. Higher baseline FVC and higher anxiety symptoms were significant predictors of better short-term 6MWD improvements. For the change in CRQ total score, a significant between-group difference from T1 to T2 (Delta = 3.0 pts, 95% CI (0.7-5.3), p = 0.01) and from T1 to T3 (Delta = 3.5 pts, 95% CI (1.5-5.4), p = 0.001) was found in favour of the PR group. To conclude, in addition to the short-term benefits, inpatient PR is effective at inducing medium-term quality of life improvements in IPF. PR in the early stages of the disease seems to provoke the best benefits. AU - Jarosch, I.* AU - Schneeberger, T.* AU - Gloeckl, R.* AU - Kreuter, M.* AU - Frankenberger, M. AU - Neurohr, C.* AU - Prasse, A.* AU - Freise, J.* AU - Behr, J.* AU - Hitzl, W.* AU - Koczulla, A.R.* AU - Kenn, K.* C1 - 59492 C2 - 48844 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Short-term effects of comprehensive pulmonary rehabilitation and its maintenance in patients with idiopathic pulmonary fibrosis: A randomized controlled trial. JO - J. Clin. Med. VL - 9 IS - 5 PB - Mdpi PY - 2020 SN - 2077-0383 ER - TY - JOUR AB - Bronchopulmonary dysplasia (BPD) is a multifactorial disease mainly provoked by pre- and postnatal infections, mechanical ventilation, and oxygen toxicity. In severely affected premature infants requiring mechanical ventilation, association of bacterial colonization of the lung and BPD was recently disclosed. To analyze the impact of bacterial colonization of the upper airway and gastrointestinal tract on moderate/severe BPD, we retrospectively analyzed nasopharyngeal and anal swabs taken weekly during the first 6 weeks of life at a single center inn= 102 preterm infants <1000 g. Colonization mostly occurred between weeks 2 and 6 and displayed a high diversity requiring categorization. Analyses of deviance considering all relevant confounders revealed statistical significance solely for upper airway colonization with bacteria with pathogenic potential and moderate/severe BPD (p= 0.0043) while no link could be established to the Gram response or the gastrointestinal tract. Our data highlight that specific colonization of the upper airway poses a risk to the immature lung. These data are not surprising taking into account the tremendous impact of microbial axes on health and disease across ages. We suggest that studies on upper airway colonization using predefined categories represent a feasible approach to investigate the impact on the pulmonary outcome in ventilated and non-ventilated preterm infants. AU - Lauer, T.* AU - Behnke, J.* AU - Oehmke, F.* AU - Baecker, J.* AU - Gentil, K.* AU - Chakraborty, T.* AU - Schloter, M. AU - Gertheiss, J.* AU - Ehrhardt, H.* C1 - 59902 C2 - 49107 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Bacterial colonization within the first 6 weeks of life and pulmonary outcome in preterm infants <1000 g. JO - J. Clin. Med. VL - 9 IS - 7 PB - Mdpi PY - 2020 SN - 2077-0383 ER - TY - JOUR AB - Objective: To evaluate the incidence of cancer within the first 15 years of life in children who underwent cardiac catheterization under the age of one year. Methods: In this retrospective, single center study, 2770 infants (7.8% with trisomy 21) were studied. All infants underwent cardiac catheterization under one year of age between January 1980 and December 1998. Newly diagnosed cancer in the first 15 years of life was assessed through record linkage to the German Childhood Cancer Registry (GCCR). Cancer risk in study patients was compared to the GCCR population of children less than 15 years. Patients with trisomy 21 were compared to the Danish Cytogenic Register for trisomy 21. Effective radiation doses were calculated for each tumor patient and 60 randomly selected patients who did not develop cancer. Results: In total, 24,472.5 person-years were analyzed. Sixteen children developed cancer, while 3.64 were expected (standardized incidence ratio (SIR) = 4.4, 95% confidence interval (CI): 2.5-7.2, p < 0.001). There was no preferred cancer type. The observed incidence of leukemia and solid tumors in trisomy 21 was only slightly higher (1 in 476 py) than expected (1 in 609 py, p = 0.64). There was no direct relationship between the radiation dose and the incidence of cancer. Conclusion: Cardiac catherization in the first year of life was associated with a significantly increased cancer risk in a population with congenital heart disease. AU - Stern, H.* AU - Seidenbusch, M. AU - Hapfelmeier, A.* AU - Meierhofer, C.* AU - Naumann, S.* AU - Schmid, I.* AU - Spix, C.* AU - Ewert, P.* C1 - 58701 C2 - 48289 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - Increased cancer incidence following up to 15 years after cardiac catheterization in infants under one year between 1980 and 1998-a single center observational study. JO - J. Clin. Med. VL - 9 IS - 2 PB - Mdpi PY - 2020 SN - 2077-0383 ER - TY - JOUR AB - Individuals at risk (IAR) of familial pancreatic cancer (FPC) are good candidates for screening. Unfortunately, neither reliable imaging modalities nor biomarkers are available to detect high-grade precursor lesions or early cancer. Circulating levels of candidate biomarkers LCN2, TIMP1, Glypican-1, RNU2-1f, and miRNA-196b were analyzed in 218 individuals with sporadic pancreatic ductal adenocarcinoma (PDAC, n = 50), FPC (n = 20), chronic pancreatitis (n = 10), IAR with relevant precursor lesions (n = 11) or non-relevant lesions (n = 5), 20 controls, and IAR with (n = 51) or without (n = 51) lesions on pancreatic imaging. In addition, corresponding duodenal juice samples were analyzed for Glypican-1 (n = 144) enrichment and KRAS mutations (n = 123). The panel miR-196b/LCN2/TIMP1 could distinguish high-grade lesions and stage I PDAC from controls with absolute specificity and sensitivity. In contrast, Glypican-1 enrichment in serum exosomes and duodenal juice was not diagnostic. KRAS mutations in duodenal juice were detected in 9 of 12 patients with PDAC and only 4 of 9 IAR with relevant precursor lesions. IAR with lesions on imaging had elevated miR-196b/LCN2/TIMP1 levels (p = 0.0007) and KRAS mutations in duodenal juice (p = 0.0004) significantly more often than IAR without imaging lesions. The combination miR-196b/LCN2/TIMP1 might be a promising biomarker set for the detection of high-grade PDAC precursor lesions in IAR of FPC families. AU - Bartsch, D.K.* AU - Gercke, N.* AU - Strauch, K. AU - Wieboldt, R.* AU - Matthäi, E.* AU - Wagner, V.* AU - Rospleszcz, S AU - Schäfer, A.S.* AU - Franke, F.S.* AU - Mintziras, I.* AU - Bauer, C.* AU - Grote, T.* AU - Figiel, J.* AU - Di Fazio, P.* AU - Burchert, A.* AU - Reinartz, S.* AU - Pogge von Strandmann, E.* AU - Klöppel, G.* AU - Slater, E.P.* C1 - 54606 C2 - 45691 CY - St Alban-anlage 66, Ch-4052 Basel, Switzerland TI - The Combination of MiRNA-196b, LCN2, and TIMP1 is a potential set of circulating biomarkers for screening individuals at risk for familial pancreatic cancer. JO - J. Clin. Med. VL - 7 IS - 10 PB - Mdpi PY - 2018 SN - 2077-0383 ER - TY - JOUR AB - Flatworms of the species Schmidtea mediterranea are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution. AU - Li, M.* AU - Sirko, S. C1 - 53282 C2 - 44497 CY - 1200 New York Ave, Nw, Washington, Dc 20005 Usa TI - Traumatic brain injury: At the crossroads of neuropathology and common metabolic endocrinopathies. JO - J. Clin. Med. VL - 7 IS - 3 PB - Amer Assoc Advancement Science PY - 2018 SN - 2077-0383 ER -