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Background and Purpose: This review aims to provide a comprehensive overview of the literature and elucidate open questions for future clinical trials concerning diagnostics and treatment modalities for cervical cancer of unknown primary (CUP).
Methods: A literature search for head and neck CUP was performed with focus on diagnostics and therapies as well as molecular markers.
Results: High level evidence on CUP is limited. However, it seems that a consensus exists regarding the optimal diagnostic procedures. The correct implementation of biomarkers for patient stratification and treatment remains unclear. An even greater dispute dominates about the ideal treatment with publications ranging from sole surgery to surgery with postoperative bilateral radiotherapy with inclusion of the mucosa and concomitant chemotherapy.
Conclusions: Cervical CUP represents a very heterogeneous malignant disease. On this account many aspects concerning treatment optimization remain unclear, despite a considerable number of publications in the past. Future research in form of prospective randomized trials is needed in order to better define patient stratification criteria and enable tailored treatment.
Global change effects on biodiversity and human wellbeing call for improved long-term environmental data as a basis for science, policy and decision making, including increased interoperability, multifunctionality, and harmonization. Based on the example of two global initiatives, the International Long-Term Ecological Research (ILTER) network and the Group on Earth Observations Biodiversity Observation Network (GEO BON), we propose merging the frameworks behind these initiatives, namely ecosystem integrity and essential biodiversity variables, to serve as an improved guideline for future site-based long-term research and monitoring in terrestrial, freshwater and coastal ecosystems. We derive a list of specific recommendations of what and how to measure at a monitoring site and call for an integration of sites into co-located site networks across individual monitoring initiatives, and centered on ecosystems. This facilitates the generation of linked comprehensive ecosystem monitoring data, supports synergies in the use of costly infrastructures, fosters cross-initiative research and provides a template for collaboration beyond the ILTER and GEO BON communities.
Background: We aimed to determine the association between seizure termination and side effects of isoflurane for the treatment of refractory status epilepticus (RSE) and super-refractory status epilepticus (SRSE) in neurointensive care units (neuro-ICUs).
Methods: This was a multicenter retrospective study of patients with RSE/SRSE treated with isoflurane for status epilepticus termination admitted to the neuro-ICUs of nine German university centers during 2011–2018.
Results: We identified 45 patients who received isoflurane for the treatment of RSE/SRSE. During isoflurane treatment, electroencephalograms showed no epileptiform discharges in 33 of 41 (80%) patients, and burst suppression pattern was achieved in 29 of 41 patients (71%). RSE/SRSE was finally terminated after treatment with isoflurane in 23 of 45 patients (51%) for the entire group and in 13 of 45 patients (29%) without additional therapy. Lengths of stay in the hospital and in the neuro-ICU were significantly extended in cases of ongoing status epilepticus under isoflurane treatment (p = 0.01 for length of stay in the hospital, p = 0.049 for length in the neuro-ICU). During isoflurane treatment, side effects were reported in 40 of 45 patients (89%) and mainly included hypotension (n = 40, 89%) and/or infection (n = 20, 44%). Whether side effects occurred did not affect the outcome at discharge. Of 22 patients with follow-up magnetic resonance imaging, 2 patients (9%) showed progressive magnetic resonance imaging alterations that were considered to be potentially associated with RSE/SRSE itself or with isoflurane therapy.
Conclusions; Isoflurane was associated with a good effect in stopping RSE/SRSE. Nevertheless, establishing remission remained difficult. Side effects were common but without effect on the outcome at discharge.
Purpose: There are little or no published data comparing the outcomes of ILUVIEN® (0.19 mg fluocinolone acetonide [FAc]) and OZURDEX® (0.7 mg dexamethasone [DEX]) implants in patients with diabetic macular edema (DME), and this case sought to compare their outcomes.
Methods: This case was extracted from a monocentric audit involving a pool of 25 patients (33 eyes) with DME and treated with a single FAc implant between October 2013 and December 2016. This case, a 61-year-old male with a pseudophakic lens, is from a patient that had received 4 intravitreal injections of a DEX implant prior to FAc implant and then was monitored for 3 years until re-treatment with a second FAc implant. Parameters measured included visual acuity (VA), central retinal thickness (CRT), and intraocular pressure (IOP).
Results: After the DEX implants, CRT transiently improved. In March 2014, the decision was taken to administer an FAc implant, and this led to a reduction in CRT below 300 µm (from a baseline of 748 µm), and this was sustained for 30 months. VA remained above 65 Early Treatment Diabetic Retinopathy Study letters to month 36, after which time a second FAc implant (in April 2017) was administered due to recurrence of edema and CRT decreased to below 300 µm and VA improved to 70 letters. Side effects included elevated IOP, which was effectively managed with IOP-lowering drops.
Conclusion: A single injection of FAc implant led to sustained improvements in CRT and VA that lasted for between 30 and 36 months, which is in contrast to the DEX implant where re-treatment was generally required within 6–7 months. After 36 months, re-treatment with the FAc implant again led to improved VA and CRT, and responses that were similar to those achieved with the first FAc implant.
Riboswitches reflect a novel concept in gene regulation that is particularly suited for technological adaptation. Therefore, we characterized thermodynamically the ligand binding properties of a synthetic, tetracycline (tc)-binding RNA aptamer, which regulates gene expression in a dose-dependent manner when inserted into the untranslated region of an mRNA. In vitro, one molecule of tc is bound by one molecule of partially pre-structured and conformationally homogeneous apo-RNA. The dissociation constant of 770 pM, as determined by fluorimetry, is the lowest reported so far for a small molecule-binding RNA aptamer. Additional calorimetric analysis of RNA point mutants and tc derivatives identifies functional groups crucial for the interaction and including their respective enthalpic and entropic contributions we can propose detailed structural and functional roles for certain groups. The conclusions are consistent with mutational analyses in vivo and support the hypothesis that tc-binding reinforces the structure of the RNA aptamer, preventing the scanning ribosome from melting it efficiently.
Purpose: To compare the effective lens position (ELP), anterior chamber depth (ACD) changes, and visual outcomes in patients with and without pseudoexfoliation syndrome (PEX) after cataract surgery.
Design: Prospective, randomized, fellow-eye controlled clinical case series.
Methods: This prospective comparative case series enrolled 56 eyes of 56 consecutive patients with (n = 28) or without PEX (n = 28) and clinically significant cataract who underwent standard phacoemulsification and were implanted with single-piece acrylic posterior chamber intraocular lenses (IOLs). The primary outcome parameters were the ACD referring to the distance between the corneal anterior surface and the lens anterior surface, which is an indicator of the postoperative axial position of the IOL (the so-called ELP) and distance corrected visual acuity (DCVA).
Results: Before surgery, the ACD was 2.54 ± 0.42 mm in the PEX group and 2.53 ± 0.38 mm in the control group (p = 0.941). Postoperatively, the ACD was 4.29 ± 0.71 mm in the PEX group and 4.33 ± 0.72 mm in the normal group, respectively (p = 0.533). There was no significant difference in ACD changes between groups (PEX group: 1.75 ± 0.74 mm, control group: 1.81 ± 0.61 mm, p = 0.806) and DCVA pre- (p = 0.469) and postoperatively (PEX group: 0.11 ± 0.13 logMAR, control group: 0.09 ± 0.17 logMAR, p = 0.245) between groups.
Conclusion: Preoperative and postoperative ACD, as an indicator of ELP, between PEX eyes and healthy eyes after cataract surgery showed no significant difference. Phacoemulsification induced similar changes in eyes with PEX compared to healthy eyes.
In our previous work we showed that NGAL, a protein involved in the regulation of proliferation and differentiation, is overexpressed in human breast cancer (BC) and predicts poor prognosis. In neoadjuvant chemotherapy (NACT) pathological complete response (pCR) is a predictor for outcome. The aim of this study was to evaluate NGAL as a predictor of response to NACT and to validate NGAL as a prognostic factor for clinical outcome in patients with primary BC. Immunohistochemistry was performed on tissue microarrays from 652 core biopsies from BC patients, who underwent NACT in the GeparTrio trial. NGAL expression and intensity was evaluated separately. NGAL was detected in 42.2% of the breast carcinomas in the cytoplasm. NGAL expression correlated with negative hormone receptor (HR) status, but not with other baseline parameters. NGAL expression did not correlate with pCR in the full population, however, NGAL expression and staining intensity were significantly associated with higher pCR rates in patients with positive HR status. In addition, strong NGAL expression correlated with higher pCR rates in node negative patients, patients with histological grade 1 or 2 tumors and a tumor size <40 mm. In univariate survival analysis, positive NGAL expression and strong staining intensity correlated with decreased disease-free survival (DFS) in the entire cohort and different subgroups, including HR positive patients. Similar correlations were found for intense staining and decreased overall survival (OS). In multivariate analysis, NGAL expression remained an independent prognostic factor for DFS. The results show that in low-risk subgroups, NGAL was found to be a predictive marker for pCR after NACT. Furthermore, NGAL could be validated as an independent prognostic factor for decreased DFS in primary human BC.
Nowadays, several options are available to treat patients with conductive or mixed hearing loss. Whenever surgical intervention is not possible or contra-indicated, and amplification by a conventional hearing device (e.g., behind-the-ear device) is not feasible, then implantable hearing devices are an indispensable next option. Implantable bone-conduction devices and middle-ear implants have advantages but also limitations concerning complexity/invasiveness of the surgery, medical complications, and effectiveness. To counsel the patient, the clinician should have a good overview of the options with regard to safety and reliability as well as unequivocal technical performance data. The present consensus document is the outcome of an extensive iterative process including ENT specialists, audiologists, health-policy scientists, and representatives/technicians of the main companies in this field. This document should provide a first framework for procedures and technical characterization to enhance effective communication between these stakeholders, improving health care.