TY  - JOUR
AB  - Several antiviral treatment regimens for chronic hepatitis B (CHB) virus infection have been shown to be effective in suppressing viral load and reducing the risk of hepatocellular injury and its complications. It has been hypothesized that high levels of circulating HBV surface antigen(s) may lead to immune tolerance against HBV and contribute to chronic carriership. Conversely, low-level HBsAg may create a window for the reconstitution of an HBV-specific immune response through vaccination and control of infection. Previous studies in non-responders to yeast-derived HBV vaccines, using a third-generation pre-S/S vaccine, have led to up to 95% anti-HBs seroconversion. This report evaluates the long-term outcome after experimental vaccination with a pre-S/S HBV vaccine intended as a therapeutic intervention in chronic HBV carriers. Four low-level HBsAg carriers (<500 IU/mL) were vaccinated three to seven times with 20 μg PreHevbrioR. Three out of four carriers eliminated HBsAg completely and seroconverted to anti-HBs. One patient seroconverted to anti-HBs but remained with a borderline HBsAg titer (10 IU/mL). Serum anti-HBs levels following repeated vaccination varied between 27 and >1000 IU/L, respectively. Long-term observation (>6 years) showed that after discontinuing NUC treatment for at least two years, HBsAg and HBV DNA remained negative with anti-HBs positive titers ranging between 80 and >1000 IU/L. Based on our preliminary observations, there is a rationale to further evaluate the role of this vaccine as a therapeutic agent.
AU  - Roggendorf, H.*
AU  - Shouval, D.S.*
AU  - Roggendorf, M.
AU  - Gerken, G.*
C1  - 70552
C2  - 55671
TI  - Longterm outcome of therapeutic vaccination with a third generation Pre-S/S HBV vaccine (PreHevbrioR) of chronically HBV infected patients.
JO  - J. Pers. Med.
VL  - 14
IS  - 4
PY  - 2024
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - Despite the extensive literature on missing data theory and cautionary articles emphasizing the importance of realistic analysis for healthcare data, a critical gap persists in incorporating domain knowledge into the missing data methods. In this paper, we argue that the remedy is to identify the key scenarios that lead to data missingness and investigate their theoretical implications. Based on this proposal, we first introduce an analysis framework where we investigate how different observation agents, such as physicians, influence the data availability and then scrutinize each scenario with respect to the steps in the missing data analysis. We apply this framework to the case study of observational data in healthcare facilities. We identify ten fundamental missingness scenarios and show how they influence the identification step for missing data graphical models, inverse probability weighting estimation, and exponential tilting sensitivity analysis. To emphasize how domain-informed analysis can improve method reliability, we conduct simulation studies under the influence of various missingness scenarios. We compare the results of three common methods in medical data analysis: complete-case analysis, Missforest imputation, and inverse probability weighting estimation. The experiments are conducted for two objectives: variable mean estimation and classification accuracy. We advocate for our analysis approach as a reference for the observational health data analysis. Beyond that, we also posit that the proposed analysis framework is applicable to other medical domains.
AU  - Zamanian, A.*
AU  - von Kleist, H.
AU  - Ciora, O.A.*
AU  - Piperno, M.*
AU  - Lancho, G.*
AU  - Ahmidi, N.*
C1  - 70765
C2  - 55885
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Analysis of missingness scenarios for observational health data.
JO  - J. Pers. Med.
VL  - 14
IS  - 5
PB  - Mdpi
PY  - 2024
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - BACKGROUND: Nerve entrapment has been hypothesized to contribute to the multicausal etiology of axonopathy in sensorimotor diabetic neuropathy. Targeted surgical decompression reduces external strain on the affected nerve and, therefore, may alleviate symptoms, including pain and sensory dysfunction. However, its therapeutic value in this cohort remains unclear. AIM: Quantifying the treatment effect of targeted lower extremity nerve decompression in patients with preexisting painful sensorimotor diabetic neuropathy and nerve entrapment on pain intensity, sensory function, motor function, and neural signal conduction. STUDY DESIGN: This prospective, controlled trial studies 40 patients suffering from bilateral therapy-refractory, painful (n = 20, visual analogue scale, VAS ≥ 5) or painless (n = 20, VAS = 0) sensorimotor diabetic neuropathy with clinical and/or radiologic signs of focal lower extremity nerve compression who underwent unilateral surgical nerve decompression of the common peroneal and the tibial nerve. Tissue biopsies will be analyzed to explore perineural tissue remodeling in correlation with intraoperatively measured nerve compression pressure. Effect size on symptoms including pain intensity, light touch threshold, static and moving two-point discrimination, target muscle force, and nerve conduction velocity will be quantified 3, 6, and 12 months postoperatively, and compared (1) to the preoperative values and (2) to the contralateral lower extremity that continues non-operative management. CLINICAL SIGNIFICANCE: Targeted surgical release may alleviate mechanical strain on entrapped lower extremity nerves and thereby potentially improve pain and sensory dysfunction in a subset of patients suffering from diabetic neuropathy. This trial aims to shed light on these patients that potentially benefit from screening for lower extremity nerve entrapment, as typical symptoms of entrapment might be erroneously attributed to neuropathy only, thereby preventing adequate treatment.
AU  - Daeschler, S.C.*
AU  - Pennekamp, A.*
AU  - Tsilingiris, D.*
AU  - Bursacovschi, C.*
AU  - Aman, M.*
AU  - Eisa, A.*
AU  - Boecker, A.*
AU  - Klimitz, F.*
AU  - Stolle, A.*
AU  - Kopf, S.*
AU  - Schwarz, D.*
AU  - Bendszus, M.*
AU  - Kneser, U.*
AU  - Kender, Z.*
AU  - Szendrödi, J.
AU  - Harhaus, L.*
C1  - 67527
C2  - 54090
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Effect of surgical release of entrapped peripheral nerves in sensorimotor diabetic neuropathy on pain and sensory dysfunction-study protocol of a prospective, controlled clinical trial.
JO  - J. Pers. Med.
VL  - 13
IS  - 2
PB  - Mdpi
PY  - 2023
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - To investigate the association between Aorta (Ao), pulmonary artery (PA) diameters and the PA/Ao ratio with right (RV) and left ventricle (LV) volumetric properties in subjects free of cardiovascular diseases. In the KORA-MRI study, 339 subjects (mean age 56.3 ± 9.1 years; 43.7% female) underwent whole-body 3T-MRI. Ao and PA were measured on DIXON sequences. Cvi42 quantified cardiac functional parameters from a SSFP sequence. The relationship between ascending (AAo), and descending aorta (DAo), as well as PA diameters, and RV and LV function were assessed using linear regression models adjusted for age, sex, and cardiovascular risk factors. AAo and DAo diameter were associated with LV end-diastolic volume (β = 4.52, p = 0.015; ß = 7.1, p ≤ 0.001), LV end-systolic volume (β = 2.37, p = 0.031; ß = 3.66, p = 0.002), while DAo associated with RV end-diastolic volume (β = 6.45, p = 0.006) and RV end-systolic volume (β = 3.9, p = 0.011). PA diameter was associated with LV end-diastolic volume (β = 4.81, p = 0.003). Interestingly, the PA/Ao ratio was only associated with RV end-diastolic and end-systolic volume (β = 4.48, p = 0.029; ß = 2.82, p = 0.037). Furthermore, we found different relationships between men and women. Ao and PA diameter were associated with LV and RV volumetric parameters in subjects free of cardiovascular diseases suggesting that ventricular volumetric performance directly relates to vascular diameter properties.
AU  - von Krüchten, R.*
AU  - Lorbeer, R.*
AU  - Peters, A.
AU  - Bamberg, F.*
AU  - Schlett, C.L.*
AU  - Mujaj, B.*
C1  - 65527
C2  - 52718
TI  - Association between large arteries diameter and heart function in subjects free of cardiovascular diseases.
JO  - J. Pers. Med.
VL  - 12
IS  - 6
PY  - 2022
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - Familial pancreatic cancer (FPC) is an established but rare inherited tumor syndrome that accounts for approximately 5% of pancreatic ductal adenocarcinoma (PDAC) cases. No major causative gene defect has yet been identified, but germline mutations in predisposition genes BRCA1/2, CDKN2A and PALB2 could be detected in 10-15% of analyzed families. Thus, the genetic basis of disease susceptibility in the majority of FPC families remains unknown. In an attempt to identify new candidate genes, we performed whole-genome sequencing on affected patients from 15 FPC families, without detecting BRCA1/2, CDKN2A or PALB2 mutations, using an Illumina based platform. Annotations from CADD, PolyPhen-2, SIFT, Mutation Taster and PROVEAN were used to assess the potential impact of a variant on the function of a gene. Variants that did not segregate with pancreatic disease in respective families were excluded. Potential predisposing candidate genes ATM, SUFU, DAB1, POLQ, FGFBP3, MAP3K3 and ACAD9 were identified in 7 of 15 families. All identified gene mutations segregated with pancreatic disease, but sometimes with incomplete penetrance. An analysis of up to 46 additional FPC families revealed that the identified gene mutations appeared to be unique in most cases, despite a potentially deleterious ACAD9 Ala326Thr germline variant, which occurred in 4 (8.7%) of 46 FPC families. Notably, affected PDAC patients within a family carried identical germline mutations in up to three different genes, e.g., DAB1, POLQ and FGFBP3. These results support the hypothesis that FPC is a highly heterogeneous polygenetic disease caused by low-frequency or rare variants.
AU  - Slater, E.P.*
AU  - Wilke, L.M.*
AU  - Böhm, L.B.*
AU  - Strauch, K.
AU  - Lutz, M.
AU  - Gercke, N.*
AU  - Mätthai, E.*
AU  - Hemminki, K.*
AU  - Försti, A.*
AU  - Schlesner, M.*
AU  - Paramasivam, N.*
AU  - Bartsch, D.K.*
C1  - 62608
C2  - 50912
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Combinations of low-frequency genetic variants might predispose to familial pancreatic cancer.
JO  - J. Pers. Med.
VL  - 11
IS  - 7
PB  - Mdpi
PY  - 2021
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - Aldo-keto reductase family 1 (AKR1) enzymes play a crucial role in diabetic complications. Since type 2 diabetes (T2D) is associated with cancer progression, we investigated the impact of diabetes onAKR1gene expression in the context of prostate cancer (PCa) development. In this study, we analyzed benign (BEN) prostate and PCa tissue of patients with and without T2D. Furthermore, to replicate hyperglycemia in vitro, we treated the prostate adenocarcinoma cell line PC3 with increasing glucose concentrations. Gene expression was quantified using real-time qPCR. In the prostate tissue of patients with T2D,AKR1C1andAKR1C2transcripts were higher compared to samples of patients without diabetes. In PC3 cells, high glucose treatment induced the gene expression levels ofAKR1C1,C2,andC3. Furthermore, both in human tissue and in PC3 cells, the transcript levels ofAKR1C1, C2,andC3showed positive associations with oncogenes, which are involved in proliferation processes and HIF1 alpha and NF kappa B pathways. These results indicate that in the prostate glands of patients with T2D, hyperglycemia could play a pivotal role by inducing the expression ofAKR1C1, C2,andC3. The higher transcript level ofAKR1Cwas furthermore associated with upregulated HIF1 alpha and NF kappa B pathways, which are major drivers of PCa carcinogenesis.
AU  - Frankó, A.
AU  - Berti, L.
AU  - Hennenlotter, J.*
AU  - Rausch, S.*
AU  - Scharpf, M.O.*
AU  - Hrabě de Angelis, M.
AU  - Stenzl, A.*
AU  - Birkenfeld, A.L.
AU  - Peter, A.
AU  - Lutz, S.Z.*
AU  - Häring, H.-U.
AU  - Heni, M.
C1  - 60070
C2  - 48989
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Transcript levels of aldo-keto reductase family 1 subfamily C (AKR1C) are increased in prostate tissue of patients with type 2 diabetes.
JO  - J. Pers. Med.
VL  - 10
IS  - 3
PB  - Mdpi
PY  - 2020
SN  - 2075-4426
ER  - 

TY  - JOUR
AB  - This systematic review analyses the contribution of metabolomics to the identification of diagnostic and prognostic biomarkers for uterine diseases. These diseases are diagnosed invasively, which entails delayed treatment and a worse clinical outcome. New options for diagnosis and prognosis are needed. PubMed, OVID, and Scopus were searched for research papers on metabolomics in physiological fluids and tissues from patients with uterine diseases. The search identified 484 records. Based on inclusion and exclusion criteria, 44 studies were included into the review. Relevant data were extracted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist and quality was assessed using the QUADOMICS tool. The selected metabolomics studies analysed plasma, serum, urine, peritoneal, endometrial, and cervico-vaginal fluid, ectopic/eutopic endometrium, and cervical tissue. In endometriosis, diagnostic models discriminated patients from healthy and infertile controls. In cervical cancer, diagnostic algorithms discriminated patients from controls, patients with good/bad prognosis, and with/without response to chemotherapy. In endometrial cancer, several models stratified patients from controls and recurrent from non-recurrent patients. Metabolomics is valuable for constructing diagnostic models. However, the majority of studies were in the discovery phase and require additional research to select reliable biomarkers for validation and translation into clinical practice. This review identifies bottlenecks that currently prevent the translation of these findings into clinical practice.
AU  - Tokarz, J.
AU  - Adamski, J.
AU  - Rižner, T.L.*
C1  - 60903
C2  - 49662
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Metabolomics for diagnosis and prognosis of uterine diseases? A systematic review.
JO  - J. Pers. Med.
VL  - 10
IS  - 4
PB  - Mdpi
PY  - 2020
SN  - 2075-4426
ER  -