Paradoxical effect of anti-inflammatory drugs on IL-6 mRNA expression in patients with PTSD during treatment.

The pathophysiology of posttraumatic stress disorder (PTSD) is associated with the activation of the innate immune system, including cytokines like interleukin 6 (IL-6). However, the role of IL-6 in the etiology and treatment of PTSD still remains elusive. We conducted a prospective controlled trial to investigate the development of IL-6 during psychosomatic treatment in individuals with PTSD in comparison with individuals without PTSD. We assessed IL-6 mRNA expression before and after 2 months of psychosomatic treatment in individuals with and without PTSD. Severities of PTSD and depressive symptoms were assessed in parallel. Linear mixed regression was applied for statistical analysis, including the factors diagnosis PTSD and pre-post treatment after subgrouping for intake of anti-inflammatory drugs. The development of IL-6 mRNA expression during treatment was affected by the use of anti-inflammatory drugs. In the subgroup without intake of anti-inflammatory drugs, no significant statistical treatment effect in individuals with and without PTSD emerged. In the subgroup of individuals taking anti-inflammatory drugs, a significant interaction effect of the factors pre-post treatment and diagnosis PTSD was observed. Whereas IL-6 mRNA expression in individuals without PTSD decreased according to amelioration of symptoms, IL-6 mRNA expression in individuals with PTSD increased significantly during treatment, in opposite direction to symptom severity. Anti-inflammatory drugs might affect IL-6 mRNA expression in individuals with PTSD in a paradoxical way. This study offers a further piece of evidence that IL-6 could be involved in the pathophysiology of PTSD and PTSD-specific immunologic molecular mechanisms.

The course of tumor-related epilepsy in glioblastoma patients: A retrospective analysis.

PURPOSE: Many patients with glioblastoma suffer from tumor-related seizures. However, there is limited data on the characteristics of tumor-related epilepsy achieving seizure freedom. The aim of this study was to characterize the course of epilepsy in patients with glioblastoma and the factors that influence it. METHODS: We retrospectively analyzed the medical records of glioblastoma patients treated at the University Hospital Erlangen between 01/2006 and 01/2020. RESULTS: In the final cohort of patients with glioblastoma (n = 520), 292 patients (56.2 %) suffered from tumor-related epilepsy (persons with epilepsy, PWE). Levetiracetam was the most commonly used first-line antiseizure medication (n = 245, 83.9 % of PWE). The onset of epilepsy was preoperative in 154/292 patients (52.7 %). 136 PWE (46.6 %) experienced only one single seizure while 27/292 PWE (9.2 %) developed drug-resistant epilepsy. Status epilepticus occurred in 48/292 patients (16.4 %). Early postoperative onset (within 30 days of surgery) of epilepsy and total gross resection (compared with debulking) were independently associated with a lower risk of further seizures. We did not detect dose-dependent pro- or antiseizure effects of radiochemotherapy. CONCLUSION: Tumor-related epilepsy occurred in more than 50% of our cohort, but drug-resistant epilepsy developed in less than 10% of cases. Epilepsy usually started before tumor surgery.

Intraday repeatability of macular layers measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography.

PURPOSE: To assess the intraday repeatability of macular architecture measurements in glaucomatous and non-glaucomatous patients using spectral-domain optical coherence tomography (SD-OCT) and to evaluate the independence from intraindividual intraocular pressure (IOP) fluctuations. METHODS: In this single-center, time-point comparison study, 88 eyes with glaucoma, 53 eyes with ocular hypertension (OHT), and 253 healthy eyes underwent two standardized SD-OCT and intraocular pressure (IOP) measurements on the same day with a 5-h time gap. Bland-Altman plots, intraclass correlation coefficients (ICC), and random-effects model were used to analyze repeatability of entire retinal thickness, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, and inner nuclear layer measurements. RESULTS: Intraday measurements were highly reproducible in all 3 groups. ICC were greater than 0.90, respectively. The pairwise comparisons of morphometric parameters showed a statistically significant difference (P < 0.001, respectively) between groups (glaucoma vs. control, glaucoma vs. OHT) and a significant influence of time points. No correlation was found between IOP fluctuations and morphometric parameters (P > 0.05, respectively), except for a weak positive correlation with GCL (rho = 0.109, P = 0.031). CONCLUSIONS: The evaluation of macular morphometric parameters of SD-OCT showed a high intraday repeatability and an excellent degree of agreement in glaucoma, ocular hypertension, and healthy groups. The fixed effects of time points were statistically significant. Except for a weak positive correlation of ganglion cell layer, variability did not appear to be affected by intraday IOP changes. Additional research is required to fully understand the impact of IOP fluctuations on macular morphometric parameters, considering the small observed IOP changes.

Prognostic relevance of ARFI elastography in comparison to liver histology and the FIB-4 score.

PURPOSE: Liver histology has prognostic relevance and is used in surveillance and therapeutic strategies. This longitudinal study was designed to evaluate the prognostic relevance of ARFI elastography in comparison to liver histology and to the FIB-4 score in a 5-year observation interval. MATERIALS AND METHODS: Based on the hospital database, patients with an elastography examination of the liver between 2010-2012, a liver biopsy, and a follow-up of 5 years were included in the study. The AUROCs of the events liver-related death, HCC, and liver decompensation/variceal bleeding were calculated for ARFI elastography, liver histology, and FIB-4 and compared using the DeLong test. RESULTS: In the final analysis 113 patients were included with 30 (26.5 %) patients having high-grade fibrosis and 19 (16.8 %) having liver cirrhosis in histology. The AUROC for liver-related death in the 5-year interval (9.7 %, n=11) was 0.80 [0.68-0.92] for ARFI elastography, 0.79 [0.66-0.92] for liver histology, and 0.66 [0.53-0.79] for FIB-4 with a p-value of 0.83 comparing ARFI to histology and a p-value of 0.02 comparing ARFI to FIB-4. The AUROC for liver decompensation/variceal bleeding (13.3 %, n=15) was 0.86 [0.76-0.94] for ARFI, which is significantly higher than the AUROC of liver histology with 0.71 [0.56-0.86] (p=0.02) and FIB-4 with 0.67 [0.54-0.80] (p=0.003). There was no significant difference for the event HCC when comparing ARFI to histology (p=0.33) or FIB-4 (p=0.14). CONCLUSION: The prognostic value of ARFI elastography seems to not be inferior to liver histology regarding liver-related survival and might even outperform histology and the FIB-4 score for predicting some liver-related complications.

Depression and anxiety among nurses during the COVID-19 pandemic: Longitudinal results over 2 years from the multicentre VOICE-EgePan study.

AIMS: To examine symptoms of depression and generalised anxiety among nurses over 2 years during the pandemic and compare them to the general population. BACKGROUND: The COVID-19 pandemic has led to a significant increase in mental stress among the population worldwide. Nursing staff have been identified as being under remarkable strain. DESIGN: A multicentre prospective longitudinal study. METHODS: Symptoms of depression and generalised anxiety in 507 nurses were examined at four different time points (T1: April-July 2020, T2: November 2020-January 2021, T3: May-July 2021, T4: February-May 2022). Results were compared with values of the German general population, presence of gender-specific differences was analysed and frequencies of clinically relevant levels of depression and anxiety were determined. RESULTS: Throughout the study (T1-T4), a significant increase in depressive and anxiety symptoms was observed. At all four measurement time points, nurses showed significantly higher prevalence for depression and anxiety compared to the German general population. No significant gender differences were found. Frequencies for probable depression and generalised anxiety disorder among nurses were: 21.6% and 18.5% (T1), 31.4% and 29.2% (T2), 29.5% and 26.2% (T3), 33.7% and 26.4% (T4). CONCLUSION: During the pandemic, symptoms of depression and generalised anxiety among nurses increased significantly and remained elevated. Their symptom levels were permanently higher than in the general population. These findings strongly suggest that the circumstances of the pandemic severely affected nurses´ mental health. RELEVANCE TO CLINICAL PRACTICE: The COVID-19 pandemic caused a great mental strain on caregivers. This study was able to demonstrate the significant increase in depression and anxiety among nurses during the pandemic. It highlights the urgent need for prevention, screening and support systems in hospitals. IMPLICATIONS FOR THE PROFESSION: Supportive programmes and preventive services should be developed, not least to prevent the growing shortage of nurses in the health care systems. REPORTING METHOD: The study adhered to relevant EQUATOR guidelines. The STROBE checklist for cohort study was used as the reporting method. PATIENT CONTRIBUTION: Five hundred and seven nurses completed the questionnaire and provided data for analysis. TRIAL AND PROTOCOL REGISTRATION: The study was registered with the German Clinical Trials Register (https://drks.de/search/en) under the following ID: DRKS00021268.

A comparative study of cystoid macula edema following glaucoma drainage device surgery versus trabeculectomy.

PURPOSE: To assess and compare the risk for development of cystoid macula edema (CME) after glaucoma drainage device (GDD) implantation versus conventional trabeculectomy with mitomycin (trab) for glaucoma. METHODS: Retrospective review of consecutive patients receiving trab or GDD implantation between 2016 and 2018. Inclusion criteria were availability of pre- and postoperative spectral domain optical coherence tomography (SD-OCT) of the macula. SD-OCT images were evaluated for presence of CME qualitatively, central subfield thickness (CST) and macular volume (MV). RESULTS: 73 eyes could be included, 42 received trab and 31 GDD surgery. Eyes receiving trab on average had 0.8 ± 0.8 previous intraocular operations, while eyes with GDD implantation had 3.1 ± 1.9 (p < 0.001). Occurrence of postoperative CME was significantly more frequent after GDD implantation (6 out of 31 (19.4%)) than after trab (2 out of 42 eyes = 4.8%), (p = 0.049). Mean preoperative CST as well as MV was comparable in both groups (CST before trab: 282.7 ± 23.0 µm, CST before GDD 284.2 ± 27.3 µm, p = 0.287; MV before trab: 7.8 ± 1.1 mm3, MV before GDD: 8.0 ± 0.8mm3, p = 0.305). Mean postoperative CST and MV were significantly higher after GDD (CST 338.5 ± 129.3 µm, MV 8.8 ± 2.6 mm3) than after trabeculectomy (CST 290.6 ± 60.2 µm, p = 0.038; MV 7.8 ± 1.2mm3, p = 0.039). CONCLUSIONS: In real-life conditions, GDD surgery seems to be associated with a higher risk to develop CME when compared to conventional trabeculectomy. This information may be helpful for glaucoma surgeons to advise the patients on postoperative risks of surgery.

Time-dependent risk factors for epileptic seizures in glioblastoma patients: A retrospective analysis of 520 cases.

OBJECTIVE: Epilepsy is a common comorbidity of glioblastoma. Seizures may occur in various phases of the disease. We aimed to assess potential risk factors for seizures in accordance with the point in time at which they occurred. METHODS: We retrospectively analyzed medical files of adult patients with de novo glioblastoma treated at our institution between January 2006 and January 2020. We categorized seizures as preoperative seizures (POS), early postoperative seizures (EPS; before initiation of radio[chemo]therapy [RCT]), seizures during radiotherapy (SDR; during or <30 days after RCT), and posttherapeutic seizures (PTS; ≥30 days after completion of RCT). We addressed associations between patients' characteristics and their seizures. RESULTS: In the final cohort (N = 520), 292 patients experienced seizures. POS, EPS, SDR, and/or PTS occurred in 29.6% (154/520), 6.0% (31/520), 13.8% (70/509), and 36.1% (152/421) of patients, respectively. POS occurred more frequently in patients with higher Karnofsky Performance Scale scores (odds ratio [OR] = 3.27, p = .001) and tumor location in the temporal lobe (OR = 1.51, p = .034). None of the parameters we analyzed was related to the occurrence of EPS. SDR were independently associated with tumor location (parietal lobe, OR = 1.86, p = .027) and POS, but not EPS, and were independent of RCT. PTS were independently associated with tumor progression (OR = 2.32, p < .001) and with occurrence of SDR (OR = 3.36, p < .001), and negatively correlated with temporal lobe location (OR = .58, p < .014). In patients with tumors exclusively located in the temporal lobe, complete tumor resection was associated with a decreased risk of postoperative seizures. SIGNIFICANCE: Seizures in glioblastoma patients have various, time-dependent risk factors. Temporal lobe localization was a risk factor for preoperative seizures; surgery may have had a protective effect in these patients. RCT did not have dose-dependent pro- or anticonvulsive effects. PTS were associated with tumor progression.

Novel point-of-care biomarkers of the dry anophthalmic socket syndrome: tear film osmolarity and matrix metalloproteinase 9 immunoassay.

PURPOSE: To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS). METHODS: In this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated. RESULTS: Patients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004). CONCLUSIONS: Measuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.

Cervical intraepithelial neoplasia grade 3: development during pregnancy and postpartum.

PURPOSE: The aims of the present study were to evaluate the development of untreated cervical intraepithelial neoplasia (CIN) 3 during pregnancy and to assess persistence, progression, and regression rates postpartum to identify factors associated with regression. METHODS: In a tertiary gynecology and obstetrics department, a total of 154 pregnant women with CIN 3 were treated in the dysplasia unit. The follow-up findings were analyzed retrospectively on the basis of histological, cytological, and human papillomavirus (HPV) testing of 154 pregnant women confirmed as having CIN 3 in colposcopically guided biopsies. RESULTS: The rates of persistence, regression, and progression of CIN 3 in these women were 76.1%, 20% and 3.2%, respectively. Data for the delivery mode was available for 126 women. The rate of regression was almost twice as high with vaginal delivery as with cesarean section, at 27.4 vs. 15.2%, whereas the rate of progression was lower with vaginal delivery, at 2.7 vs. 6.5%. CONCLUSION: The rate of persistence of CIN observed in this study is comparable to that reported in other studies. The study provides strong evidence for greater regression among women who have vaginal deliveries. Careful work-up is recommended postpartum for this group of women in order to rule out persistent CIN 3 or invasive disease.

Artificial intelligence for the classification of focal liver lesions in ultrasound - a systematic review.

Focal liver lesions are detected in about 15% of abdominal ultrasound examinations. The diagnosis of frequent benign lesions can be determined reliably based on the characteristic B-mode appearance of cysts, hemangiomas, or typical focal fatty changes. In the case of focal liver lesions which remain unclear on B-mode ultrasound, contrast-enhanced ultrasound (CEUS) increases diagnostic accuracy for the distinction between benign and malignant liver lesions. Artificial intelligence describes applications that try to emulate human intelligence, at least in subfields such as the classification of images. Since ultrasound is considered to be a particularly examiner-dependent technique, the application of artificial intelligence could be an interesting approach for an objective and accurate diagnosis. In this systematic review we analyzed how artificial intelligence can be used to classify the benign or malignant nature and entity of focal liver lesions on the basis of B-mode or CEUS data. In a structured search on Scopus, Web of Science, PubMed, and IEEE, we found 52 studies that met the inclusion criteria. Studies showed good diagnostic performance for both the classification as benign or malignant and the differentiation of individual tumor entities. The results could be improved by inclusion of clinical parameters and were comparable to those of experienced investigators in terms of diagnostic accuracy. However, due to the limited spectrum of lesions included in the studies and a lack of independent validation cohorts, the transfer of the results into clinical practice is limited.