Refine
Year of publication
Document Type
- Article (5423) (remove)
Has Fulltext
- yes (5423)
Keywords
- inflammation (80)
- COVID-19 (62)
- SARS-CoV-2 (47)
- cancer (38)
- glioblastoma (38)
- apoptosis (37)
- Inflammation (34)
- breast cancer (34)
- prostate cancer (30)
- autophagy (29)
Institute
- Medizin (5423) (remove)
Simple Summary: Penile cancer is a rare but aggressive malignancy characterized by rapid tumor growth as well as prompt metastasis in groin lymphatics. While localized diseases can be successfully cured by surgery in most cases, no truly effective treatment options have been established for metastatic diseases as of yet. In the current investigation, we assessed the value of selected members of the PI3K/mTOR/AKT pathway to serve as tumor markers or therapeutic targets for this disease. Higher expression of AKT was significantly more prevalent in high-grade tumors and independently predictive of the worse survival parameters, while increased expression of pmTOR was associated with an inferior prognosis as well. Treatment with the pan-AKT inhibitor capivasertib in PeCa cell lines induced significant reduction of cell viability and movement capacity. These findings might aid in the understanding of the molecular tumor background as well as development of novel treatment options for advanced penile cancer.
Abstract: The PI3K/mTOR/AKT pathway might represent an intriguing option for treatment of penile cancer (PeCa). We aimed to assess whether members of this pathway might serve as biomarkers and targets for systemic therapy. Tissue of primary cancer from treatment-naïve PeCa patients was used for tissue microarray analysis. Immunohistochemical staining was performed with antibodies against AKT, pAKT, mTOR, pmTOR, pS6, pPRAS, p4EBP1, S6K1 and pp70S6K. Protein expression was correlated with clinicopathological characteristics as well as overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and metastasis-free survival (MFS). AKT inhibition was tested in two primarily established, treatment-naïve PeCa cell lines by treatment with capivasertib and analysis of cell viability and chemotaxis. A total of 76 patients surgically treated for invasive PeCa were included. Higher expression of AKT was significantly more prevalent in high-grade tumors and predictive of DSS and OS in the Kaplan–Meier analysis, and an independent predictor of worse OS and DSS in the multivariate regression analysis. Treatment with pan-AKT inhibitor capivasertib in PeCa cell lines induced a significant downregulation of both total AKT and pAKT as well as decreased cell viability and chemotaxis. Selected protein candidates of the mTOR/AKT signaling pathway demonstrate association with histological and survival parameters of PeCa patients, whereas AKT appears to be the most promising one.
Introduction: The estimation of age-at-death of unidentified cadavers is a central aspect of the identification process. With increasing age, the incidence of glomerulosclerosis and the thickness of the carotid wall have been observed to also increase. This correlation has been demonstrated in various international histological studies. The aim of our study was to assess whether these correlations also apply to a Western European population.
Methodology: In this retrospective observational study, kidney and common carotid artery samples from 216 cases autopsied at the Institute of Legal Medicine at the Justus-Liebig University in Giessen, Germany, were examined. Only cases with available tissue samples from both body sides were included. Exclusion criteria were poor sample quality and an age younger than 21 years. After histological processing, the tissue samples were assessed and digitally evaluated. Regression and classification analyses were used to investigate the correlation between age-at-death and intima-media thickness and age-at-death and the incidence of renal glomerular sclerosis.
Results: Of the 216 autopsy cases, 183 were included for evaluation. Analysis of the carotid artery segments showed a strong correlation (Pearson correlation coefficient r = 0.887) between the intima-media-complex thickness and chronological age. Classification of the glomerulosclerotic incidence showed a correlation of 37.7–43.1% with the predicted age group.
Discussion: Both the intima-media thickness and the proportion of sclerotic glomeruli can be used to estimate age in Western European cadavers. On the basis of these results, both methods are suited to supplement other already established methods for age-at-death estimation in the identification of an unknown cadaver.
This case series assessed a commercial airline flight from Tel Aviv, Israel, to Frankfurt, Germany, that occurred on March 9th, 2020. Among 102 passengers on a Boeing 737-900 aircraft were 24 members of a tourist group. Starting 7 days earlier, the group had contact with a hotel manager who later received a diagnosis of coronavirus disease 2019 (COVID-19). No member of the group had received a diagnosis of COVID-19 before the flight, and no measures to prevent transmission (eg, wearing of masks) had been applied. The flight duration was 4 hours 40 minutes.
Objectives: To evaluate peri-implant tissue dimensions following nonsurgical (NS) and surgical therapy (S) employing different decontamination protocols of advanced ligature-induced peri-implantitis in dogs.
Material & Methods: Peri-implantitis defects (n = 5 dogs, n = 30 implants) were randomly and equally allocated in a split-mouth design to NS or S treatment using either an Er:YAG laser (ERL), an ultrasonic device (VUS), or plastic curettes + local application of metronidazole gel (PCM), respectively. Horizontal bone thickness (hBT) and soft tissue thickness (hMT) were measured at different reference points: (v0) at the marginal portion of the peri-implant mucosa (PM); (v1) at 50% of the distance from PM to bone crest (BC); (v2) at the BC; (v3) at the most coronal extension of the bone-to-implant contact. Vertical peri-implant tissue height was calculated from PM to BC.
Results: All of the treatment groups showed a gradual hMT increase from v0 to the v2 reference point, followed by a reduction from v2 to the v3 region. The S-VUS subgroup tended to be associated with higher hMT values at the v0 region than the NS-VUS subgroup (0.44 mm versus 0.31 mm). PM-BC distance varied from 2.22 to 2.83 mm in the NS group, and from 2.07 to 2.38 in the S group.
Conclusion: Vertical and horizontal peri-implant tissue dimensions were similar in different treatment groups.
Assessment of the acute effects of 2C-B vs. psilocybin on subjective experience, mood, and cognition
(2023)
2,5-dimethoxy-4-bromophenethylamine (2C-B) is a hallucinogenic phenethylamine derived from mescaline. Observational and preclinical data have suggested it to be capable of producing both subjective and emotional effects on par with other classical psychedelics and entactogens. Whereas it is the most prevalently used novel serotonergic hallucinogen to date, it's acute effects and distinctions from classical progenitors have yet to be characterized in a controlled study. We assessed for the first time the immediate acute subjective, cognitive, and cardiovascular effects of 2C-B (20 mg) in comparison to psilocybin (15 mg) and placebo in a within-subjects, double-blind, placebo-controlled study of 22 healthy psychedelic-experienced participants. 2C-B elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution largest under psilocybin. Participants demonstrated equivalent psychomotor slowing and spatial memory impairments under either compound compared with placebo, as indexed by the Digit Symbol Substitution Test, Tower of London, and Spatial Memory Task. Neither compound produced empathogenic effects on the Multifaceted Empathy Test. 2C-B induced transient pressor effects to a similar degree as psilocybin. The duration of self-reported effects of 2C-B was shorter than that of psilocybin, largely resolving within 6 hours. Present findings support the categorization of 2C-B as a psychedelic of moderate experiential depth at doses given. Tailored dose-effect studies are needed to discern the pharmacokinetic dependency of 2C-B's experiential overlaps.
Background: Symptoms, severity, and acuteness of peripheral artery disease (PAD) are major determinants of severe limb symptoms, subsequent risk of cardiovascular events, and mortality. Lower-extremity revascularization (LER) is a key option to relieve symptoms and to prevent limb loss in symptomatic patients with PAD. This study aimed to quantify the burden of disease among patients with PAD-LER in England.
Methods: A retrospective population-based study of linked primary and secondary care electronic health records, included 13,869 adult patients (aged ⩾ 18 years) with PAD-LER from 2003 to 2018. The incidence of first ever PAD-LER was estimated both overall and by type of procedure (endovascular/surgical). Health resource utilization associated with PAD-related complications and treatment patterns were assessed.
Results: A high annual incidence of lower-limb revascularization (41.2 per 1000 person years) and a nearly double incidence of endovascular first revascularization compared with open surgery were observed. More than 70% of patients with PAD-LER had a history of hyperlipidemia and hypertension and roughly one-third were diabetic and had a history of coronary artery disease. Cardiovascular mortality accounted for one-third (34.1 per 1000 person years) of all-cause mortality. Over 93% of patients were hospitalized for any reason and the commonest reasons for hospitalization were cardiovascular diseases and PAD with about one-third hospitalized for revascularization reoccurrence.
Conclusion: There is a significant burden of PAD-LER to the individual and society with ongoing healthcare resource utilization, treatment, and increasing mortality.
Background: Number of positive prostate biopsy cores represents a key determinant between high versus very high-risk prostate cancer (PCa). We performed a critical appraisal of the association between the number of positive prostate biopsy cores and CSM in high versus very high-risk PCa. Methods: Within Surveillance, Epidemiology, and End Results database (2010–2016), 13,836 high versus 20,359 very high-risk PCa patients were identified. Discrimination according to 11 different positive prostate biopsy core cut-offs (≥2–≥12) were tested in Kaplan–Meier, cumulative incidence, and multivariable Cox and competing risks regression models. Results: Among 11 tested positive prostate biopsy core cut-offs, more than or equal to 8 (high-risk vs. very high-risk: n = 18,986 vs. n = 15,209, median prostate-specific antigen [PSA]: 10.6 vs. 16.8 ng/ml, <.001) yielded optimal discrimination and was closely followed by the established more than or equal to 5 cut-off (high-risk vs. very high-risk: n = 13,836 vs. n = 20,359, median PSA: 16.5 vs. 11.1 ng/ml, p < .001). Stratification according to more than or equal to 8 positive prostate biopsy cores resulted in CSM rates of 4.1 versus 14.2% (delta: 10.1%, multivariable hazard ratio: 2.2, p < .001) and stratification according to more than or equal to 5 positive prostate biopsy cores with CSM rates of 3.7 versus 11.9% (delta: 8.2%, multivariable hazard ratio: 2.0, p < .001) in respectively high versus very high-risk PCa. Conclusions: The more than or equal to 8 positive prostate biopsy cores cutoff yielded optimal results. It was very closely followed by more than or equal to 5 positive prostate biopsy cores. In consequence, virtually the same endorsement may be made for either cutoff. However, more than or equal to 5 positive prostate biopsy cores cutoff, based on its existing wide implementation, might represent the optimal choice.
Objectives: To determine the diagnostic accuracy of dual-energy CT (DECT) virtual noncalcium (VNCa) reconstructions for assessing thoracic disk herniation compared to standard grayscale CT. Methods: In this retrospective study, 87 patients (1131 intervertebral disks; mean age, 66 years; 47 women) who underwent third-generation dual-source DECT and 3.0-T MRI within 3 weeks between November 2016 and April 2020 were included. Five blinded radiologists analyzed standard DECT and color-coded VNCa images after a time interval of 8 weeks for the presence and degree of thoracic disk herniation and spinal nerve root impingement. Consensus reading of independently evaluated MRI series served as the reference standard, assessed by two separate experienced readers. Additionally, image ratings were carried out by using 5-point Likert scales. Results: MRI revealed a total of 133 herniated thoracic disks. Color-coded VNCa images yielded higher overall sensitivity (624/665 [94%; 95% CI, 0.89–0.96] vs 485/665 [73%; 95% CI, 0.67–0.80]), specificity (4775/4990 [96%; 95% CI, 0.90–0.98] vs 4066/4990 [82%; 95% CI, 0.79–0.84]), and accuracy (5399/5655 [96%; 95% CI, 0.93–0.98] vs 4551/5655 [81%; 95% CI, 0.74–0.86]) for the assessment of thoracic disk herniation compared to standard CT (all p < .001). Interrater agreement was excellent for VNCa and fair for standard CT (ϰ = 0.82 vs 0.37; p < .001). In addition, VNCa imaging achieved higher scores regarding diagnostic confidence, image quality, and noise compared to standard CT (all p < .001). Conclusions: Color-coded VNCa imaging yielded substantially higher diagnostic accuracy and confidence for assessing thoracic disk herniation compared to standard CT.
The coronavirus pandemic continues to challenge global healthcare. Severely affected patients are often in need of high doses of analgesics and sedatives. The latter was studied in critically ill coronavirus disease 2019 (COVID-19) patients in this prospective monocentric analysis. COVID-19 acute respiratory distress syndrome (ARDS) patients admitted between 1 April and 1 December 2020 were enrolled in the study. A statistical analysis of impeded sedation using mixed-effect linear regression models was performed. Overall, 114 patients were enrolled, requiring unusual high levels of sedatives. During 67.9% of the observation period, a combination of sedatives was required in addition to continuous analgesia. During ARDS therapy, 85.1% (n = 97) underwent prone positioning. Veno-venous extracorporeal membrane oxygenation (vv-ECMO) was required in 20.2% (n = 23) of all patients. vv-ECMO patients showed significantly higher sedation needs (p < 0.001). Patients with hepatic (p = 0.01) or renal (p = 0.01) dysfunction showed significantly lower sedation requirements. Except for patient age (p = 0.01), we could not find any significant influence of pre-existing conditions. Age, vv-ECMO therapy and additional organ failure could be demonstrated as factors influencing sedation needs. Young patients and those receiving vv-ECMO usually require increased sedation for intensive care therapy. However, further studies are needed to elucidate the causes and mechanisms of impeded sedation.
Background: Various kinase inhibitors are known to be ATP-binding cassette (ABC) transporter substrates and resistance acquisition to kinase inhibitors has been associated to increased ABC transporter expression. Here, we investigated the role of the ABC transporters ABCB1, ABCC1, and ABCG2 during melanoma cell resistance acquisition to the V600-mutant BRAF inhibitors PLX4032 (vemurafenib) and PLX4720. PLX4032 had previously been shown to interfere with ABCB1 and ABCG2. PLX4720 had been demonstrated to interact with ABCB1 but to a lower extent than PLX4032.
Findings: PLX4032 and PLX4720 affected ABCC1- and ABCG2-mediated drug transport in a similar fashion. In a panel of 16 V600E BRAF-mutated melanoma cell lines consisting of four parental cell lines and their sub-lines with acquired resistance to PLX4032, PLX4720, vincristine (cytotoxic ABCB1 and ABCC1 substrate), or mitoxantrone (cytotoxic ABCG2 substrate), we detected enhanced ABC transporter expression in 4/4 cytotoxic ABC transporter substrate-resistant, 3/4 PLX4720-resistant, and 1/4 PLX4032-resistant melanoma cell lines.
Conclusion: PLX4032 has the potential to induce ABC transporter expression but this potential is lower than that of PLX4720 or cytotoxic ABC transporter substrates. Since ABC transporters confer multi-drug resistance, this is of relevance for the design of next-line therapies.
Objectives: The aim of this study was to investigate the relationship between anamnestic, axiographic and occlusal parameters and postural control in healthy women aged between 41 and 50 years. Materials and methods: A total of 100 female participants aged between 41 and 50 (45.12 ± 2.96) years participated in the study. In addition to completing a general anamnesis questionnaire, lower jaw movements were measured axiographically, dental occlusion parameters were determined using a model analysis and postural parameters were recorded using a pressure measurement platform. The significance level was 5%. Results: An increasing weight and a rising BMI lead to a weight shifted from the rearfoot (p ≤ 0.01/0.04) to the forefoot (p ≤ 0.01/0.02). A limited laterotrusion on the right resulted in a lower forefoot load and an increased rearfoot load (p ≤ 0.01). Laterotrusion to the left (extended above the standard) showed a lower frontal sway (p ≤ 0.02) and a reduced elliptical area, height and width (p ≤ 0.01, 0.02, 0.03). Thus, the extent of deviation correlated with reduced right forefoot loading (p ≤ 0.03) and the extent of deflection correlated with increased left foot loading (p ≤ 0.01). The higher the extent of angle class II malocclusion, the larger the ellipse area (p ≤ 0.04) and the ellipse height (p ≤ 0.02) resulted. Conclusions: There is a connection between weight, BMI and laterotrusion, as well as between angle class II malocclusion and postural control in women aged between 41 and 50 years. Interdisciplinary functional examinations of mandibular movements treating possible limitations can be conducive for an improvement of postural control. Clinical relevance: Angle class II malocclusion has a negative influence on postural control.
The aim of this study was to determine association between constitutional, medical history and axiographic parameters with postural control parameters. Overall, 106 healthy female subjects aged between 21 and 30 years were measured. Data collection was carried out by completing a questionnaire on constitutional parameters, illnesses, accidents and medical/orthodontic therapies, as well as by axio- and posturographic measurements. Data were analyzed using correlations, pair comparisons and group comparisons. The significance level was set at p ≤ 0.05. The statistical evaluation showed significant correlations between sporting exercise and body sway in the sagittal direction (p ≤ 0.03), the BMI and the load on the forefoot/rear foot (p ≤ 0.01), the mouth opening and the load on the forefoot/rearfoot (p ≤ 0.01) and the presence of a deviation with the load on the left/right foot (p ≤ 0.01). The physical condition as well as the temporo-mandibular system are associated with the postural control in young women. Therefore, a holistic diagnosis and therapy will be supported by the present outcomes.
Objectives: The possible etiologic relevance of occupational factors such as cadmium, cutting oils, diesel fuel and fumes, herbicides, polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls, soot, tar, mineral oil, and solvents to prostate cancer was studied.
Methods: A case-referent study design was used to recruit 192 subjects with histologically confirmed prostate cancer and 210 referents who had prostate cancer histologically excluded either in one of two urologic practices (Hamburg and Frankfurt) or in the urological policlinic of the Frankfurt University. Data were gathered with a self-administered questionnaire and analyzed using logistic regression to control for age, region, and cigarette smoking. A job-exposure matrix was used for assigning exposure. For the calculation of dose-years, the duration of contact with specific substances was weighted by the intensity and probability of exposure according to a job-exposure matrix.
Results: The analysis of dose-years yielded a statistically significant association between occupational exposure to diesel fuel or fumes and prostate cancer (odds ratio 3.7, 95% confidence interval 1.4-9.8, for subjects exposed to more than 25 dose-years in a comparison with subjects never exposed). For the other substances, no statistically significant differences in exposure were found between the cases and referents. When only jobs with a high exposure probability were used to classify the participants as exposed, only exposure to PAH was significantly associated with prostate cancer.
Conclusion: In keeping with results from other studies, this study provides further evidence that exposure to diesel fuel or fumes - possibly mediated through PAH - may be associated with the development of prostate cancer.
Objectiv:e To explore the association of physical activity (PA) with musculoskeletal pain (MSK pain).
Design: Cross-sectional study
Setting: 14 countries (Argentina, Australia, Austria, Brazil, Chile, France, Germany, Italy, the Netherlands, Singapore, South Africa, Spain, Switzerland and the USA).
Participants: Individuals aged 18 or older.
Primary and secondary outcome measures: PA volumes were assessed with an adapted version of the Nordic Physical Activity Questionnaire-short. Prevalence of MSK pain was captured by means of a 20-item checklist of body locations. Based on the WHO recommendation on PA, participants were classified as non-compliers (0–150 min/week), compliers (150–300 min/week), double compliers (300–450 min/week), triple compliers (450–600 min/week), quadruple compliers (600–750 min/week), quintuple compliers (750–900 min/week) and top compliers (more than 900 min/week). Multivariate logistic regression was used to obtain adjusted ORs of the association between PA and MSK pain for each body location, correcting for age, sex, employment status and depression risk.
Results: A total of 13 741 participants completed the survey. Compared with non-compliers, compliers had smaller odds of MSK pain in one location (thoracic pain, OR 0.77, 95% CI 0.64 to 0.93). Double compliance was associated with reduced pain occurrence in six locations (elbow, OR 0.70, 95% CI 0.50 to 0.98; forearm, OR 0.63, 95% CI 0.40 to 0.99; wrist, OR 0.74, 95% CI 0.57 to 0.98; hand, OR 0.57, 95% CI 0.40 to 0.79; fingers, OR 0.72, 95% CI 0.52 to 0.99; abdomen, OR 0.61, 95% CI 0.41 to 0.91). Triple to top compliance was also linked with lower odds of MSK pain (five locations in triple compliance, three in quadruple compliance, two in quintuple compliance, three in top compliance), but, at the same time, presented increased odds of MSK pain in some of the other locations.
Conclusion: A dose of 300–450 min WHO-equivalent PA/week was associated with lower odds of MSK pain in six body locations. On the other hand, excessive doses of PA were associated with higher odds of pain in certain body locations.
Background: The pro-inflammatory status of the elderly triggers most of the age-related diseases such as cancer and atherosclerosis. Atherosclerosis, the leading cause world wide of morbidity and death, is an inflammatory disease influenced by life-style and genetic host factors. Stimuli such as oxLDL or microbial ligands have been proposed to trigger inflammation leading to atherosclerosis. It has recently been shown that oxLDL activates immune cells via the Toll-like receptor (TLR) 4/6 complex. Several common single nucleotide polymorphisms (SNPs) of the TLR system have been associated with atherosclerosis. To investigate the role of TLR-6 we analyzed the association of the TLR-6 SNP Pro249Ser with atherogenesis.
Results: Genotyping of two independent groups with CAD, as well as of healthy controls revealed a significant association of the homozygous genotype with a reduced risk for atherosclerosis (odds ratio: 0.69, 95% CI 0.51-0.95, P = 0.02). In addition, we found a trend towards an association with the risk of restenosis after transluminal coronary angioplasty (odds ratio: 0.53, 95% CI 0.24-1.16, P = 0.12). In addition, first evidence is presented that the frequency of this protective genotype increases in a healthy population with age. Taken together, our results define a role for TLR-6 and its genetic variations in modulating the inflammatory response leading to atherosclerosis.
Conclusions: These results may lead to a better risk stratification, and potentially to an improved prophylactic treatment of high-risk populations. Furthermore, the protective effect of this polymorphism may lead to an increase of this genotype in the healthy elderly and may therefore be a novel genetic marker for the well-being during aging.
Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts
(2014)
Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.
Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.
Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.
Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.
Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
Background & Aims: Genetic variations near the interferon lambda 3 gene (IFNL3, IL28B) are the most powerful predictors for sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both IFNL3 polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants.
Methods: The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55%) achieved SVR. The IFNL3 polymorphisms were genotyped by polymerase chain reaction and melting curve analysis.
Results: A significant correlation was found between the IFNL3 polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, IFLN3 SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles.
Conclusions: Our data support a clear association between IFNL3 genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the IFNL3 genotype.
Purpose: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival.
Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records.
Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups.
Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.
Background: We evaluated the Kidney Donor Risk Index (KDRI) scoring system for kidney transplantation in the Eurotransplant Senior Program (ESP) that allocates kidneys from older donors to older recipients (≥65 years).
Material and methods: We retrospectively analyzed data of 37 kidney transplant recipients and 36 kidney donors who participated in kidney transplantation program according to the ESP at our center from January 2004 until December 2013.
Results: Mean recipient and donor age was 67.9±2.6 and 70.5±4.0 years respectively. The mean KDRI score was 1.7±0.27. Uncensored graft survival after 1 year and 5 years was 64.2% and 53.7% respectively. Subgroup analysis showed that in kidney transplantation with KDRI >1.83, graft survival was significantly reduced compared to lower KDRI subgroups. KDRI was significantly correlated with serum creatinine level at discharge (r=0.4).
Conclusions: ESP kidneys represent a group of high-risk grafts with high KDRI scores. Higher KDRI scores in ESP kidneys was associated with reduced postoperative short-term and long-term graft outcomes. KDRI might be useful in decision-making for selecting donors for ESP kidney transplantation.
Association of mortality and early tracheostomy in patients with COVID-19: a retrospective analysis
(2022)
COVID-19 adds to the complexity of optimal timing for tracheostomy. Over the course of this pandemic, and expanded knowledge of the disease, many centers have changed their operating procedures and performed an early tracheostomy. We studied the data on early and delayed tracheostomy regarding patient outcome such as mortality. We performed a retrospective analysis of all tracheostomies at our institution in patients diagnosed with COVID-19 from March 2020 to June 2021. Time from intubation to tracheostomy and mortality of early (≤ 10 days) vs. late (> 10 days) tracheostomy were the primary objectives of this study. We used mixed cox-regression models to calculate the effect of distinct variables on events. We studied 117 tracheostomies. Intubation to tracheostomy shortened significantly (Spearman’s correlation coefficient; rho = − 0.44, p ≤ 0.001) during the course of this pandemic. Early tracheostomy was associated with a significant increase in mortality in uni- and multivariate analysis (Hazard ratio 1.83, 95% CI 1.07–3.17, p = 0.029). The timing of tracheostomy in COVID-19 patients has a potentially critical impact on mortality. The timing of tracheostomy has changed during this pandemic tending to be performed earlier. Future prospective research is necessary to substantiate these results.