The purpose of this study was to investigate the impact of transient elevations in postoperative intraocular pressure (IOP) on the clinical outcome of Descemet membrane endothelial keratoplasty ...(DMEK) surgery in non-glaucoma patients.
Retrospective analysis from a prospective database of eyes without preexisting glaucoma that underwent DMEK with 90% anterior chamber and 20% sulfur hexafluoride endotamponade. Group A included eyes without postoperative IOP increase (IOP <30 mm Hg and a relative increase from preoperative value <10 mm Hg). Group B included eyes with IOP elevation (postoperative IOP ≥30 mm Hg or a relative increase from preoperative value ≥10 mm Hg) handled according to a standardized protocol. The impact of elevated IOP within 3 days after DMEK surgery was evaluated regarding best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) at 1, 3, and 6 months.
One hundred seventy-six eyes from 164 patients were included. An IOP increase after DMEK occurred in 20 eyes (11.3%; 19 patients, group B), and the mean peak IOP was 48 ± 12 mm Hg (range 32-69 mm Hg). There were no significant postoperative differences in BCVA, CCT, and ECC on comparing both groups. The BCVA increased significantly (P < 0.001, respectively), whereas CCT (P < 0.001, respectively) and ECC (P < 0.001, respectively) decreased significantly from preoperative values. The rebubbling rate tended to be higher in group B without statistical significance (6.4% vs. 10%, P = 0.648).
Temporary IOP elevation after DMEK may not affect functional and morphological outcomes in non-glaucoma patients. However, careful postoperative IOP monitoring and appropriate management are crucial to avoid irreversible ocular damage.
Neural stem cells (NSCs) generate neurons throughout life in the hippocampal dentate gyrus (DG). How gene expression signatures differ among NSCs and immature neurons remains largely unknown. We ...isolated NSCs and their progeny in the adult DG using transgenic mice expressing a GFP reporter under the control of the Sox2 promoter (labeling NSCs) and transgenic mice expressing a DsRed reporter under the control of the doublecortin (DCX) promoter (labeling immature neurons). Transcriptome analyses revealed distinct gene expression profiles between NSCs and immature neurons. Among the genes that were expressed at significantly higher levels in DG NSCs than in immature neurons was the growth factor insulin-like growth factor 2 (IGF2). We show that IGF2 selectively controls proliferation of DG NSCs in vitro and in vivo through AKT-dependent signaling. Thus, by gene expression profiling of NSCs and their progeny, we have identified IGF2 as a novel regulator of adult neurogenesis.
Purpose: Ab interno glaucoma surgery, such as trabecular aspiration or ab interno trabeculotomy, has been introduced as an alternative, non-filtering procedure to lower intraocular pressure in ...glaucoma patients. The purpose of the present study was to assess the feasibility of intraoperative spectral domain optical coherence tomography (iOCT) for improving ab interno glaucoma surgery.
Materials and Methods: Intraoperative optical coherence tomography was performed to visualize the anterior chamber angle, the aspiration canula during trabecular aspiration, and the trabectome device during ab interno trabeculotomy. A commercially available 840-nm iOCT was used in a clinical setting, a 1310-nm spectral-domain OCT in an experimental setting.
Results: In the clinical setting using the 840-nm iOCT, visualization of the aspiration canula and the trabectome device was possible, however, with rather limited visibility of the chamber angle and the trabecular meshwork. In the experimental setting, the 1310-nm OCT enabled excellent visualization of the chamber angle and detailed evaluation of the instrument-trabecular meshwork relation.
Conclusions: Intraoperative use of optical coherence tomography may be helpful for ab interno glaucoma surgery. Adjustments of the commercially available iOCT, including longer wavelengths and oblique scanning options, are necessary for the clinical use.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic ...chemoperfusion.
54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1-11) treatment sessions were performed with melphalan (92%) or fotemustin (8%). Inflammatory indices were calculated as follows: neutrophils/nl to lymphocytes/nl ratio (NLR), systemic immune-inflammation index (platelets/nl × neutrophils/nl/lymphocytes/nl; SII), and platelets/nl to lymphocytes/nl ratio (PLR). The cut-off for dichotomization purposes was set at the median (inflammatory indices, hepatic tumor burden) or the upper level of normal. Kaplan Meier analysis was performed for median overall survival (OS) in months, and Cox proportional hazard model for uni(UVA) and multivariate (MVA) hazard ratio (HR, 95%CI) analyses were performed.
Median OS of the study cohort was 7.7 (6.3-10.9) months. In UVA OS was prolonged for low C reactive protein (CRP) (13.5
. 5.2; p = 0.0005), low SII (10.8
. 5.6; p = 0.0005), low NLR (11.1
. 6.3; p = 0.0045), low aspartate aminotransferase (AST) (11.5
. 5.6; p = 0.015), alanine aminotransferases (ALT) (11.5
. 5.6; p = 0.01), and tumor burden ≦ 50% (8.2
. 4.8; p = 0.007). MVA confirmed low CRP (HR: 0.29, 0.11-0.7; p = 0.005), low SII (HR: 0.19, 0.11-0.7; p = 0.008), and low ALT (HR: 0.13, 0.02-0.63; p = 0.011) as independent predictors for prolonged OS. Patients with ≦ 1, 2, 3 elevated significant MVA-factors survived a median of 14.9, 7.7, and 3.9 months, respectively (p = 0.0001).
Pretreatment inflammatory markers (CRP, SII) and AST were independent prognostic survival markers in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. A combination of factors may help to identify patients potentially benefitting from treatment.
We have assessed the role of ric-b8 in the control of heart rate after the gene was implicated in a recent genome-wide association study of resting heart rate. We developed a novel murine model in ...which it was possible to conditionally delete ric-8b in the sinoatrial (SA) node after the addition of tamoxifen. Despite this, we were unable to obtain homozygotes and thus studied heterozygotes. Haploinsufficiency of ric-8b in the sinoatrial node induced by the addition of tamoxifen in adult animals leads to mice with a reduced heart rate. However, other electrocardiographic intervals (e.g., PR and QRS) were normal, and there was no apparent arrhythmia such as heart block. The positive chronotropic response to isoprenaline was abrogated, whereas the response to carbachol was unchanged. The pacemaker current I
(funny current) has an important role in regulating heart rate, and its function is modulated by both isoprenaline and carbachol. Using a heterologous system expressing HCN4, we show that ric-8b can modulate the HCN4 current. Overexpression of ric-8b led to larger HCN4 currents, whereas silencing ric-8b led to smaller currents. Ric-8b modulates heart rate responses in vivo likely via its actions on the stimulatory G-protein.
The relationship between central pulse pressure (CPP) measured at the time of primary percutaneous coronary intervention (PPCI) and long-term prognosis after ST-segment elevation myocardial ...infarction (STEMI) has not been investigated. CPP measurements were performed in 1348 patients with STEMI (327 women; mean age 62.5 ± 12.1 years) undergoing PPCI. Aortic systolic and diastolic blood pressure was measured before intervention. The primary outcome was 8-year all-cause mortality. The median 25–75th percentile CPP value was 55.0 43.0–70.0 mmHg. CPP correlated negatively with heart rate (
P
< 0.001), body mass index (
P
= 0.007), Killip class (
P
< 0.001) and initial area at risk (
P
< 0.001) and positively with age (
P
< 0.001), female sex (
P
< 0.001), diabetes (
P
= 0.012), arterial hypertension (
P
< 0.001) and glomerular filtration rate (
P
= 0.004). There were 181 deaths over the follow-up. In patients with CPP within the 1st, 2nd and 3rd tertiles, the Kaplan–Meier estimates of mortality were 17.3%, 10.8% and 24.2%, respectively; univariable hazard ratio HR =1.52, 95% confidence interval CI 0.99 to 2.32;
P
= 0.055 for tertile 1 vs. tertile 2 and HR =2.09 1.36–3.21;
P
< 0.001 for tertile 3 vs. tertile 2. For CPP values lower than 35 mmHg and higher than 71 mmHg, the association between CPP and all-cause mortality was significant (HR =1.276 1.004–1.621 for the 35 mmHg value and HR =1.289 1.003–1.657 for the 71 mmHg value) compared with the CPP reference value (54 mmHg). After adjustment, the association between CPP and all-cause mortality was attenuated (P = 0.304). In patients with STEMI undergoing PPCI there is a U-shaped association between CPP and mortality up to 8 years after PPCI.
Emitters showing thermally activated delayed fluorescence (TADF) in electroluminescent devices rely on efficient reverse intersystem crossing (rISC) arising from small thermal activation barriers ...between the lowest excited triplet and singlet manifolds. A small donor–acceptor compound consisting of a demethylacridine donor and a methylbenzoate acceptor group is used as a model TADF emitter. The spectroscopic signatures of this system are characterized using a combination of photoluminescence and photoluminescence excitation, and the photoluminescence decay dynamics are recorded between delays of 2 ns and 20 ms. Above T = 200 K, our data provide convincing evidence for TADF at intermediate delays in the microsecond range, whereas triplet–triplet annihilation and slow triplet decay at later times can be observed over the entire temperature range from T = 80 K to room temperature. Moreover, close to room temperature, we find a second and faster up-conversion mechanism, tentatively assigned to reverse internal conversion between different triplet configurations. An interpretation of these experimental findings requires a calculation of the deformation patterns and potential minima of several electronic configurations. This task is performed with a range-separated hybrid functional, outperforming standard density functionals or global hybrids. In particular, the systematic underestimation of the energy of charge transfer (CT) states with respect to local excitations within the constituting chromophores is replaced by more reliable transition energies for both kinds of excitations. Hence, several absorption and emission features can be assigned unambiguously, and the observed activation barriers for rISC and reverse internal conversion correspond to calculated energy differences between the potential surfaces in different electronic configurations.
•HIF-1α and CAIX are molecular markers able to estimate hypoxia response in EC.•Population and histological differences affect esophageal hypoxia assessment.•For personalized treatment, tumor ...microenvironment, stage and histology need to be considered.•Standardization of measuring techniques is crucial for guiding hypoxia research and clinical application in EC.•Hypoxia imaging techniques have the potential to provide individualized information to guide treatment of EC.
In this systematic review, the existing evidence of available hypoxia-associated molecular response biomarkers in esophageal cancer (EC) patients is summarized and set into the context of the role of hypoxia in the prediction of esophageal cancer, treatment response and treatment outcome.
A systematic literature search was performed in Web of Science, MEDLINE, and PubMed databases using the keywords: hypoxia, esophagus, cancer, treatment outcome and treatment response. Eligible publications were independently evaluated by two reviewers. In total, 22 out of 419 records were included for systematic review. The described search strategy was applied weekly, with the last update being performed on April 3rd, 2017.
In esophageal cancer, several (non-)invasive biomarkers for hypoxia could be identified. Independent prognostic factors for treatment response include HIF-1α, CA IX, GLUT-1 overexpression and elevated uptake of the PET-tracer 18F-fluoroerythronitroimidazole (18F-FETNIM). Hypoxia-associated molecular responses represents a clinically relevant phenomenon in esophageal cancer and detection of elevated levels of hypoxia-associated biomarkers and tends to be associated with poor treatment outcome (i.e., overall survival, disease-free survival, complete response and local control).
Evaluation of tumor micro-environmental conditions, such as intratumoral hypoxia, is important to predict treatment outcome and efficacy. Promising non-invasive imaging-techniques have been suggested to assess tumor hypoxia and hypoxia-associated molecular responses. However, extensive validation in EC is lacking. Hypoxia-associated markers that are independent prognostic factors could potentially provide targets for novel treatment strategies to improve treatment outcome. For personalized hypoxia-guided treatment, safe and reliable makers for tumor hypoxia are needed to select suitable patients.
We applied the Social Cognitive Theory to investigate whether parent-child relationships, bullying victimization, and teacher-student relationships are directly as well as indirectly via ...self-efficacy in social conflicts associated with adolescents' willingness to intervene in a bullying incident. There were 2071 (51.3% male) adolescents between the ages of 12 and 17 from 24 schools in Germany who participated in this study. A mediation test using structural equation modeling revealed that parent-child relationships, bullying victimization, and teacher-student relationships were directly related to adolescents' self-efficacy in social conflicts. Further, teacher-student relationships and bullying victimization were directly associated with adolescents' willingness to intervene in bullying. Finally, relationships with parents, peers and teachers were indirectly related to higher levels of students' willingness to intervene in bullying situations due to self-efficacy in social conflicts. Thus, our analysis confirms the general assumptions of Social Cognitive Theory and the usefulness of applying its approach to social conflicts such as bullying situations.
XELAVIRI compared sequential (Arm A) versus initial (Arm B) irinotecan in combination with fluoropyrimidine plus bevacizumab in patients with metastatic colorectal cancer, trial identification: ...NCT01249638. In the full analysis set of the study, non-inferiority of time to failure of strategy (TFS) was not shown. The present analysis was performed to evaluate the effect of gender on treatment outcome and tolerability.
The study end-points overall response rate (ORR), progression-free survival (PFS), TFS and overall survival (OS) were evaluated in female versus male patients and in molecular subgroups (i.e. RAS mutational status). Interaction of treatment and gender was tested by likelihood ratio tests.
In total, 281 male and 140 female patients (n = 421) were evaluated. Among the male patients, the ORR was 33.6% without and 58.3% with initial irinotecan (P < 0.001). PFS (hazard ratio HR 0.54; 95% confidence interval CI 0.42–0.69; P < 0.001) and OS (HR 0.63; 95% CI 0.47–0.85; P = 0.002) were also significantly better with initial irinotecan. Among the female patients, the ORR was 42.7% in Arm A and 43.1% in Arm B, PFS was similar (HR 1.09; 95% CI 0.76–1.55; P = 0.649) without and with initial irinotecan. A strong trend for inferior outcome with regard to OS with initial irinotecan was observed (HR 1.46; 95% CI 0.95–2.24; P = 0.081) and the trend reached significance in the multivariate analysis (HR 1.78; 95% CI 1.08–2.95; P = 0.02). Formal interaction of treatment and gender was observed for ORR (P = 0.018), PFS (P = 0.002) and OS (P = 0.001). Treatment-related adverse events were not significantly different between male and female patients.
The present analysis suggests that gender interacts with efficacy of initial irinotecan when used in combination with fluoropyrimidines and bevacizumab. Although male patients derived a significant and clinically meaningful benefit from initial combination chemotherapy, this was not observed in female patients.
•We evaluate the efficacy of initial irinotecan according to gender in mCRC.•Male patients seem to benefit from initial irinotecan, whereas women do not.•Baseline characteristics and toxicities were similar in male versus female patients.
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