Impact of Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography on Therapeutic Decisions and Radiotherapy Planning in Head and Neck Squamous Carcinoma: A Retrospective Study of 46 Patients.

BACKGROUND Positron emission tomography/computed tomography (PET/CT) using fluorodeoxyglucose (FDG) is essential in oncology for precise tumor delineation. This study evaluated FDG PET/CT's impact on therapeutic decisions in head and neck cancer, comparing metabolic tumor volumes (MTV) measured by different methods with radiotherapy targets, crucial for treatment planning and patient outcomes. MATERIAL AND METHODS We retrospectively analyzed 46 patients with histologically confirmed head and neck cancer who underwent FDG PET/CT examination before radiotherapy. The mean age was 62 years (46-78 years). Then, we calculated MTV of the primary tumor or local recurrence using a local threshold of 41% of the standard uptake volume (SUV) corrected for lean body mass (SULmax) of the lesion and absolute threshold of SUV 2.5. Descriptive analysis of the recruited patients was assessed based on the clinical database (Medsol). RESULTS The study included 45 patients with squamous carcinoma and 1 with sarcoid cell carcinoma. PET/CT examination led to therapeutic decision changes in 11 cases. No significant difference was found in median values of Gross Tumor Volume (GTV) and MTV absolute (p=0.130). However, significant differences were observed in MTV local, MTV absolute, and GTV median values (p<0.001), with both MTVs showing significant correlation with GTV (p<0.01), especially MTV absolute (r=0.886). CONCLUSIONS FDG PET/CT examination prior to radiotherapy significantly influences therapeutic decisions in head and neck cancer patients. Based on our findings, the absolute threshold method (SUV: 2.5) appears to be an effective approach for calculating MTV for radiotherapy planning purposes.

Comparison of pre-mortem 2D-3D ultrasound examination to post-mortem micro-CT of carotid arteries - first experiences.

Background and purpose:

A prerequisite for the treatment of carotid atherosclerosis is the accurate measurement of the stenosis, that is most commonly evaluated by duplex ultrasonography. In this study, we aimed to verify the reliability of 2D and 3D ultrasonography, comparing the data to results of post-mortem micro-CT examination.

Neurological patients with any life-threatening, presumably fatal neurological disease were enrolled. Ultrasound examinations were performed with a Philips Epiq 5G machine, using a VL13-5 broadband linear volume array transducer. Plaque length, diameter and vessel area reduction (stenosis) were calculated using the 2D images. Finally, the stenosis was reassessed using automatized, 3D application as well. After the death of the patient, autopsy was performed, during which the previously examined carotid artery was removed. The samples were examined with micro-CT. Similar to the ultrasound examination, plaque length, diameter and vessel area reduction (stenosis) were determined.

Ten vessels of seven patients were eligible for complex comparison. Plaque diameter and length measured by CT did not correlate with the ultrasound data. CT-measured axial plaque and vessel areas showed no correlation with ultrasound results either. While determining the strength of correlation between stenoses measured by the different modalities, significant correlation was found between the results measured by ultrasound (2D) and CT (Pearson r: 0.902, P<0.001).

Three-dimensional ultrasound analysis is a spectacular method for examining carotid plaques, as it can assist in a more detailed evaluation of the plaque morphology and composition, thereby identifying plaques with a particularly high risk of stroke. Micro-CT is an excellent tool for the exact determination of calcified plaque areas, but ultrasound images are not suitable yet for such a precise examination due to acoustic shadowing and artifacts.

Carbonic Anhydrase Inhibitor Acetazolamide Enhances CHOP Treatment Response and Stimulates Effector T-Cell Infiltration in A20/BalbC Murine B-Cell Lymphoma.

The inhibition of cancer-related carbonic anhydrase (CA) activity is a promising way to intensify anti-tumor responses. In vitro data suggest improved efficacy of cytotoxic drugs in combination with CA-inhibitors in several cancer types. Despite accumulating data on CA-expression, experimental or clinical studies towards B-cell lymphoma therapy are missing. We therefore decided to test the effect of the CA-inhibitor acetazolamide (AA) on the conventional CHOP treatment regimen using the A20/BalbC in vivo syngeneic mouse lymphoma model. Tumor growth characteristics, 18F-MISO-PET activity, histomorphology, cell proliferation, and T-cell immune infiltrate were determined following single or multiple dose combinations. All results point to a significant increase in the anti-tumor effect of CHOP+AA combinations compared with the untreated controls or with the single CHOP or AA treatments. CD3+ and CD8+ T-cell immune infiltrate increased 3-4 times following CHOP+AA combination compared with the classical CHOP protocol. In conclusion, CA-inhibitor AA seems to act synergistically with the anti-tumor treatment CHOP in aggressive lymphoma. Further to a cytotoxic effect, AA and other more selective blockers potentially support tumor-associated immune responses through the modification of the microenvironment. Therefore, CA-inhibitors are promising candidates as adjuvants in support of specific immunotherapies in lymphoma and other malignancies.

Exophthalmos in a young woman with no graves' disease - a case report of IgG4-related orbitopathy.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-rd) is characterized by lymphoplasmacytic infiltration and tissue fibrosis. Orbital manifestations of IgG4-rd may include unilateral or bilateral proptosis, cicatricial extraocular muscle myopathy, orbital inflammation and pain which may mimic ophthalmic Graves' disease. CASE PRESENTATION: A 25-year-old woman has been referred to the endocrinology clinic, 4 months after delivery, with suspected Graves' orbitopathy. She has had bronchial asthma and recurrent skin rashes of unknown aetiology for the last 10 years and was treated for dacryoadenitis with steroid containing eye drops 5 years ago. During pregnancy she developed eyelid swelling. After delivery, eyelid redness and retrobulbar pain evolved. Proptosis was demonstrated by Hertel's exophthalmometry. Orbital magnetic resonance imaging showed enlarged lateral and superior rectus muscles in both orbits. Thyroid function tests were in the normal range and no thyroid stimulating hormone (TSH) receptor autoantibodies were present. The eye muscle involvement pattern raised suspicion, and the high IgG4 level with positive histology of the lacrimal gland confirmed the diagnosis of immunoglobulin G4-related orbitopathy. Rapid improvement was observed following oral methylprednisolone. CONCLUSIONS: IgG4-related orbitopathy may mimic Graves' orbitopathy. Euthyroid patients with no TSH receptor autoantibodies should be evaluated for immunoglobulin G4-related orbitopathy. Once IgG4-related orbitopathy is proven, other manifestations of IgG4-related disease have to be searched for; lifelong follow-up is warranted.

[Is second-line immunomodulatory treatment effective in multiple sclerosis?] / Elonyös a másodvonalbeli immunmoduláns kezelés sclerosis multiplexben?

BACKGROUND AND PURPOSE: Natalizumab is the first evidence based monoclonal antibody, which was launched for treatment in relapsing remitting multiple sclerosis in Hungary in 2010. Standardized follow-up is required to use it. METHODS: Our aim was to evaluate the efficacy and to monitor the safety of natalizumab treatment by using an electronic database established for MS registry. Clinical activity was measured by annual relapse rates, functional status of patients measured by EDSS and MFSC. Radiological activity was evaluated by standard MRI protocol. Data, results of MS patients and side effects of natalizumab treatment were recorded in iMed software. RESULTS: 31 patients started the natalizumab treatment after 6.5±5.8 years from the onset of MS. The efficacy of treatment was evaluated after a mean of 67 (min: 14 max: 128) infusions in December 2016. The drop-out rate was low, due to the presence of neutralising antibodies in one case, pregnancy in two cases and development of malignant disease in one case which was not related to the natalizumab treatment. The treatment was well tolerated with excellent compliance without serious side effects. The annual relapse rate reduced from a mean of 1.7 to 0.03 (p<0.000001) in the first 12 months of treatment compared to the pretreatment 12 month activity, and it stayed at low level during the whole follow up. EDSS was stable or improved with an exception of two cases. In 23 subjects (77%) lack of new/enlarging T2 lesions and lack of gadolineum-enhancing lesions on MRI were observed. 18 patients (60%) had no evidence of disease activity (NEDA-3). PASAT test improved in most of the cases. CONCLUSION: The natalizumab therapy was very effective in all cases including those patients who had active disease under the previous immunomodulatory treatment.

The Effect of Passive Movement for Paretic Ankle-Foot and Brain Activity in Post-Stroke Patients.

BACKGROUND: This study aims at investigating the short-term efficacy of the continuous passive motion (CPM) device developed for the therapy of ankle-foot paresis and to investigate by fMRI the blood oxygen level-dependent responses (BOLD) during ankle passive movement (PM). METHODS: Sixty-four stroke patients were investigated. Patients were assigned into 2 groups: 49 patients received both 15 min manual and 30 min device therapy (M + D), while the other group (n = 15) received only 15 min manual therapy (M). A third group of stroke patients (n = 12) was investigated by fMRI before and immediately after 30 min CPM device therapy. There was no direct relation between the fMRI group and the other 2 groups. All subjects were assessed using the Modified Ashworth Scale (MAS) and a goniometer. RESULTS: Mean MAS decreased, the ankle's mean plantar flexion and dorsiflexion passive range of motion (PROM) increased and the equinovalgus improved significantly in the M + D group. In the fMRI group, the PM of the paretic ankle increased BOLD responses; this was observed in the contralateral pre- and postcentral gyrus, superior temporal gyrus, central opercular cortex, and in the ipsilateral postcentral gyrus, frontal operculum cortex and cerebellum. CONCLUSION: Manual therapy with CPM device therapy improved the ankle PROM, equinovalgus and severity of spasticity. The ankle PM increased ipsi- and contralateral cortical activation.

[Differential diagnosis of Graves' orbitopathy. Case report]. / Az endokrin orbitopathia differenciáldiagnosztikája.

Graves' orbitopathy is the extrathyroidal manifestation of Graves' disease, which is the most common cause of exophthalmos. As eye symptoms usually coincide with the development of thyrotoxicosis, the diagnosis of the disease is rarely difficult. The aim of the authors was to summarize the differential diagnosis of Graves' orbitopathy based on literature review and presentation of their own four problematic cases on this topic. They conclude that symptoms similar to endocrine orbitopathy are present in other disorders. Endocrinologists need to be aware of these other conditions to avoid treatment failures.

[Deletion 15q26 syndrome]. / 15q26-microdeletio-szindróma.

The association of short stature, microcephaly, congenital cardiac anomaly and intellectual deficit should always raise the suspicion of chromosomal etiology. If G-banded karyotyping fails to detect large chromosomal aberrations, array comparative genomic hybridization (array CGH) should be performed to screen for submicroscopic pathological copy number changes. The authors present a six-year-old girl whose symptoms arose from a 4.1 Mb loss in the 15q26.2-26.3 telomeric region. The syndrome is characterized by a resistance to the insulin-like growth factor 1 - in our case the increased level of the insulin-like growth factor 1 together with the persistent longitudinal growth failure was an important finding and differential diagnostic feature. A brief overview of the literature is provided.

Repeated diagnostic ultrasound exposure modifies the structural properties of CA1 dendrites and alters the hippocampal transcriptome.

The development of neurons is regulated by several spatiotemporally changing factors, which are crucial to give the ability of neurons to form functional networks. While external physical stimuli may impact the early developmental stages of neurons, the medium and long-term consequences of these influences have yet to be thoroughly examined. Using an animal model, this study focuses on the morphological and transcriptome changes of the hippocampus that may occur as a consequence of fetal ultrasound examination. We selectively labeled CA1 neurons of the hippocampus with in-utero electroporation to analyze their morphological features. Furthermore, certain samples also went through RNA sequencing after repetitive ultrasound exposure. US exposure significantly changed several morphological properties of the basal dendritic tree. A notable increase was also observed in the density of spines on the basal dendrites, accompanied by various alterations in individual spine morphology. Transcriptome analysis revealed several up or downregulated genes, which may explain the molecular background of these alterations. Our results suggest that US-derived changes in the dendritic trees of CA1 pyramidal cells might be connected to modification of the transcriptome of the hippocampus and may lead to an increased dendritic input.

[Coding of laboratory parameters using the LOINC system at the Clinical Center of the University of Debrecen]. / Laboratóriumi paraméterek kódolása a LOINC-rendszer szerint a Debreceni Egyetem Klinikai Központjában.

INTRODUCTION: The research utility of the bulk of the medical data generated at the Clinical Center of the University of Debrecen, which is constituted mainly by the clinical diagnostic laboratory results and medical images, is quite constrained in its present unstandardized form. The primary aim of the Big Data Research and Development project at the University of Debrecen is to facilitate data transformation and standardization to propagate its research utility for the potential end-users. Data generated in the in vitro diagnostic laboratory setting are an ideal candidate for the aforementioned goals. Data generated in Hungarian language in this particular setting are typically acronyms that do not particularly confirm to any standard norms and the transformation of these data using the globally acknowledged Logical Observation Identifiers Names and Codes (LOINC) was the primary goal of this research project. Globally the LOINC is used by healthcare providers, government agencies, insurance companies, software and device manufacturers, researchers and reference laboratories for identifying medical laboratory observations and promote unhindered fluency between various systems. OBJECTIVE: The aim of the project was to assure compliance of the various routine diagnostic laboratory parameters (n = 448) generated at the Department of Laboratory Medicine of the University of Debrecen to the LOINC system paying particular attention to and accommodating data sensitive to timeline and methodology. METHODS: Keywords allocated to individual parameters determined by the laboratory were provided by the IT service provider of the facility. The individual codes for the various parameters were manually identified using the search engine of the LOINC database available at http://www.loinc.org, only upon attainment of proficiency in use of the database and ample familiarity with the scientific literature on the topic. RESULTS: All routine diagnostic laboratory parameters were LOINC coded with no exception. The list of LOINCs' was made available on the https://labmed.unideb.hu/hu/loinc-tablazatok web link of the University of Debrecen. CONCLUSION: The transformation of diagnostic laboratory parameters to globally recognized LOINCs' improves and further facilitates the international integration of data generated at the University of Debrecen, furthermore propels communications between laboratories and parties of interest beyond international boundaries and borders. Orv Hetil. 2023; 164(27): 1043-1051.

Relationship between gadolinium-based MRI contrast agent consumption and anthropogenic gadolinium in the influent of a wastewater treatment plant.

Gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI) are highly resistant in the environment. They pass through wastewater treatment plants (WWTPs) unhindered escaping degradation. Although GBCAs are subjects of intensive research, we recognized that a quantitative approach to the mass balance of gadolinium, based on known input and output data, is missing. The administered amount of Gd as GBCAs, the number of out- and inpatients and the concentration of rare earth elements (REEs) in wastewater were monitored for 45 days in a medium sized city (ca. 203,000 inhabitants) with two MRI centres. An advection-dispersion type model was established to describe the transport of Gd in the wastewater system. The model calculates with patient locality, excretion kinetics of Gd and the yield of wastewater. The estimated and measured daily amount of anthropogenic gadolinium released to the WWTP were compared. GBCAs (Omniscan and Dotarem) were administered to 1008 patients representing a total of 700 ± 1 g Gd. The amount of total Gd entering the WWTP was 531 ± 2 g, of which the anthropogenic contribution (i.e. GBCAs) was 261 ± 6 g (49 ± 1 % of the total Gd) during the sampling campaign. Local residents and inpatients should fully release Gd in the city, but outpatients only partially. Overall, 37 ± 1 % of the total administered Gd was recovered in the wastewater, so the remaining 63 ± 1 % of administered Gd is expected to be dispensed outside of the sewer system. Our approach enables to better understand the dispersion of GBCAs originated Gd in an urban environment.

Connectivity-based parcellation reveals interhemispheric differences in the insula.

The aim of this work was to use probabilistic diffusion tractography to examine the organization of the human insular cortex based on the similarities of its remote projections. Forty right-handed healthy subjects (33.8 ± 12.7 years old) with no history of neurological injury were included in the study. After the spatial standardization of diffusion tensor images, insular cortical masks were delineated based on the Harvard-Oxford Cortical Atlas and were used to initiate fibertracking. Cluster analysis by the k-means algorithm was employed to partition the insular voxels into two groups that featured the most distinct distribution of connections. In order to perform volumetric comparisons, the assigned label maps were transformed back to space of the subjects' native anatomical MR images. The outlines of the change in connectivity profile did not respect the known cytoarchitectural subdivisions and were shown to be independent from the gyral anatomy. Interhemispheric asymmetry in the volumes of connectivity-based subdivisions was observed putatively marking a leftward functional dominance of the anterior insula and its reciprocally interconnected targets which influences the size of insular area where similar connections are represented. The fractional anisotropy values were not significantly different between the hemipsheres or connectivity-based clusters; however, the mean diffusivity was higher in the anterior insula in both hemispheres.

Leukoaraiosis is associated with arterial wall thickness: a quantitative analysis.

Leukoaraiosis refers to an age-related, abnormal appearance of the brain white matter on neuroimaging. The association between leukoaraiosis and cerebrovascular disease suggests that ischemia may be an important contributing factor; however, the pathogenesis of the condition remains controversial. We hypothesized that physical abnormalities of blood vessels might be culpable and compared the external and internal measurements of blood vessel walls between brains that demonstrated leukoaraiosis on imaging and normal control brains. Fourteen brains of individuals who had been diagnosed as having severe leukoaraiosis and five non-leukoaraiosis control brains were studied. Arterial cross-sections were evaluated by length measurements with an image analysis device. Arterial wall thickness and the ratio of the outer and inner diameters of the vessel were measured. We measured a total of 108 vessels in the leukoaraiosis group and 95 vessels in the control group. The vessel walls of the leukoaraiosis patients were an average of 5.5 µm thicker than the walls of control vessels of the same inside diameter (P = 0.0000, 95% CI 3.01-8.08) and an average of 2.3 µm thicker than walls of control vessels of the same outside diameter (P = 0.016, 95% CI 0.48-4.17). Our data provide evidence that leukoaraiosis is associated with vessel wall thickening in an additive fashion and indicate that structural vascular abnormalities are associated with leukoaraiosis.

Ultrasound Used for Diagnostic Imaging Facilitates Dendritic Branching of Developing Neurons in the Mouse Cortex.

Neuronal differentiation and synaptogenesis are regulated by precise orchestration of intrinsic and extrinsic chemical and mechanical factors throughout all developmental steps critical for the assembly of neurons into functional circuits. While ultrasound is known to alter neuronal migration and activity acutely, its chronic effect on neuronal behavior or morphology is not well characterized. Furthermore, higher-frequency (3-5 MHz) ultrasound (HFU) is extensively used in gynecological practice for imaging, and while it has not been shown harmful for the developing brain, it might be associated with mild alterations that may have functional consequences. To shed light on the neurobiological effects of HFU on the developing brain, we examined cortical pyramidal cell morphology in a transgenic mouse model, following a single and short dose of high-frequency ultrasound. Layer V neurons in the retrosplenial cortex of mouse embryos were labeled with green and red fluorescent proteins by in utero electroporation at the time of their appearance (E14.5). At the time of their presumptive arrival to layer V (E18.5), HFU stimulation was performed with parameters matched to those used in human prenatal examinations. On the third postnatal day (P3), basic morphometric analyses were performed on labeled neurons reconstructed with Neurolucida. Low-intensity HFU-treated cells showed significantly increased dendritic branching compared to control (non-stimulated) neurons and showed elevated c-fos immunoreactivity. Labeled neurons were immunopositive for the mechanosensitive receptor TRPC4 at E18.5, suggesting the role of this receptor and the associated signaling pathways in the effects of HFU stimulation.

Central Nervous System Involvement in Primary Sjögren's Syndrome: Narrative Review of MRI Findings.

Central nervous system (CNS) involvement is one of the numerous extraglandular manifestations of primary Sjögren's syndrome (pSS). Moreover, neurological complaints precede the sicca symptoms in 25-60% of the cases. We review the magnetic resonance imaging (MRI) lesions typical for pSS, involving the conventional examination, volumetric and morphometric studies, diffusion tensor imaging (DTI) and resting-state fMRI. The most common radiological lesions in pSS are white matter hyperintensities (WMH), scattered alterations hyperlucent on T2 and FLAIR sequences, typically located periventricularly and subcortically. Cortical atrophy and ventricular dilatation can also occur in pSS. Whilst these conditions are thought to be more common in pSS than healthy controls, DTI and resting-state fMRI alterations demonstrate evident microstructural changes in pSS. As pSS is often accompanied by cognitive symptoms, these MRI alterations are expectedly related to them. This relationship is not clearly delineated in conventional MRI studies, but DTI and resting-state fMRI examinations show more convincing correlations. In conclusion, the CNS manifestations of pSS do not follow a certain pattern. As the link between the MRI lesions and clinical manifestations is not well established, more studies involving larger populations should be performed to elucidate the correlations.

Phantom Study on the Robustness of MR Radiomics Features: Comparing the Applicability of 3D Printed and Biological Phantoms.

The objectives of our study were to (a) evaluate the feasibility of using 3D printed phantoms in magnetic resonance imaging (MR) in assessing the robustness and repeatability of radiomic parameters and (b) to compare the results obtained from the 3D printed phantoms to metrics obtained in biological phantoms. To this end, three different 3D phantoms were printed: a Hilbert cube (5 × 5 × 5 cm3) and two cubic quick response (QR) code phantoms (a large phantom (large QR) (5 × 5 × 4 cm3) and a small phantom (small QR) (4 × 4 × 3 cm3)). All 3D printed and biological phantoms (kiwis, tomatoes, and onions) were scanned thrice on clinical 1.5 T and 3 T MR with 1 mm and 2 mm isotropic resolution. Subsequent analyses included analyses of several radiomics indices (RI), their repeatability and reliability were calculated using the coefficient of variation (CV), the relative percentage difference (RPD), and the interclass coefficient (ICC) parameters. Additionally, the readability of QR codes obtained from the MR images was examined with several mobile phones and algorithms. The best repeatability (CV ≤ 10%) is reported for the acquisition protocols with the highest spatial resolution. In general, the repeatability and reliability of RI were better in data obtained at 1.5 T (CV = 1.9) than at 3 T (CV = 2.11). Furthermore, we report good agreements between results obtained for the 3D phantoms and biological phantoms. Finally, analyses of the read-out rate of the QR code revealed better texture analyses for images with a spatial resolution of 1 mm than 2 mm. In conclusion, 3D printing techniques offer a unique solution to create textures for analyzing the reliability of radiomic data from MR scans.

High Neutrophil-Lymphocyte Ratio and Low Lymphocyte-Monocyte Ratio Combination after Thrombolysis Is a Potential Predictor of Poor Functional Outcome of Acute Ischemic Stroke.

(1) Background: Ischemic stroke is one of the leading causes of death and disability. An inflammatory response is observed in multiple stages of cerebral ischemia, particularly in the acute phase. Recent publications revealed that the neutrophil−lymphocyte ratio (NLR) and lymphocyte−monocyte ratio (LMR) may be used to predict long-term prognosis in acute ischemic stroke (AIS) after thrombolysis. To test whether there is a relationship between the combination of these parameters and long-term prognosis, we analyzed the NLR−LMR combination in AIS patients treated with intravenous recombinant tissue plasminogen activator (rtPA); (2) Methods: The study included 285 adults with a diagnosis of AIS and rtPA treatment within a 4.5 h time window. Blood samples were obtained at admission and 24 h after thrombolysis to calculate pre- and post-thrombolysis NLR and LMR. Clinical data, including NIHSS was registered on admission and day 1. The long-term outcome was defined 90 days post-event by the modified Rankin Scale (mRS). Therapy-associated intracranial hemorrhage (ICH) was classified according to ECASS II. Receiver operating characteristic curve (ROC) analysis was performed to determine optimal cutoffs of NLR and LMR as predictors of therapy outcomes; (3) Results: Patients were stratified by cutoffs of 5.73 for NLR and 2.08 for LMR. The multivariate logistic regression model, including all possible confounders, displayed no significant association between NLR or LMR with 3-months functional prognosis. The combination of high NLR−low LMR vs. low NRL−high LMR as obtained 24 h after thrombolysis was found to be an independent predictor of poor 3-months functional outcome (mRS ≥ 2; OR 3.407, 95% CI 1.449 to 8.011, p = 0.005). The proportion of patients between low NLR−high LMR and high NLR−low LMR groups from admission to day 1 showed no significant change in the good outcome group. On the other hand, in the poor outcome group (mRS ≥ 2), low NLR−high LMR and high NLR−low LMR groups displayed a significant shift in patient proportions from 67% and 21% at admission (p = 0.001) to 36% and 49% at 24 h after thrombolysis (p < 0.001), respectively; (4) Conclusions: Our study demonstrated for the first time that a high NLR−low LMR combination as observed at 24 h after thrombolysis can serve as an independent predictor of 3-months poor outcome in AIS patients. This simple and readily available data may help clinicians to improve the prognostic estimation of patients and may provide guidance in selecting patients for personalized and intensified care post-thrombolysis.

Low α2-Plasmin Inhibitor Antigen Levels on Admission Are Associated With More Severe Stroke and Unfavorable Outcomes in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis.

Background: Intravenous administration of recombinant tissue plasminogen activator (rt-PA) fails to succeed in a subset of acute ischemic stroke (AIS) patients, while in approximately 6-8% of cases intracerebral hemorrhage (ICH) occurs as side effect. Objective: Here, we aimed to investigate α2-plasmin inhibitor (α2-PI) levels during thrombolysis and to find out whether they predict therapy outcomes in AIS patients. Patients/Methods: In this prospective, observational study, blood samples of 421 AIS patients, all undergoing i.v. thrombolysis by rt-PA within 4.5 h of their symptom onset, were taken before and 24 h after thrombolysis. In a subset of patients (n = 131), blood was also obtained immediately post-lysis. α2-PI activity and antigen levels were measured by chromogenic assay and an in-house ELISA detecting all forms of α2-PI. α2-PI Arg6Trp polymorphism was identified in all patients. Stroke severity was determined by NIHSS on admission and day 7. Therapy-associated ICH was classified according to ECASSII. Long-term outcomes were defined at 3 months post-event by the modified Rankin Scale (mRS). Results: Median α2-PI activity and antigen levels showed a significant drop immediately post-lysis and increased to subnormal levels at 24 h post-event. Admission α2-PI levels showed a significant negative stepwise association with stroke severity. Patients with favorable long-term outcomes (mRS 0-1) had significantly higher admission α2-PI antigen levels (median:61.6 [IQR:55.9-70.5] mg/L) as compared to patients with poor outcomes (mRS 2-5: median:59.7 [IQR:54.5-69.1] and mRS 6: median:56.0 [IQR:48.5-61.0] mg/L, p < 0.001). In a Kaplan-Meier survival analysis, patients with an α2-PI antigen in the highest quartile on admission showed significantly better long-term survival as compared to those with α2-PI antigen in the lowest quartile (HR: 4.54; 95%CI:1.92-10.8, p < 0.001); however, in a multivariate analysis, a low admission α2-PI antigen did not prove to be an independent risk factor of poor long-term outcomes. In patients with therapy-related ICH (n = 34), admission α2-PI antigen levels were significantly, but only marginally, lower as compared to those without hemorrhage. Conclusions: Low α2-PI antigen levels on admission were associated with more severe strokes and poor long-term outcomes in this cohort. Our results suggest that in case of more severe strokes, α2-PI may be involved in the limited efficacy of rt-PA thrombolysis.

Non-surgical orbital decompression using diuresis in dysthyroid optic neuropathy: a case report.

Introduction: Dysthyroid optic neuropathy (DON) is a rare, severe form of thyroid eye disease, in which decreased visual acuity is accompanied by characteristic MRI findings. The treatment of DON has always been a challenge. Case presentation: In a patient in whom visual acuity deteriorated on the left eye, mannitol 20% 200 mL followed by furosemide 40 mg 6 h later, administered daily, were initiated on the day of admission. Visual function by ophthalmology methods, and orbital compartment volumes and water content by MRI were followed. Intravenous diuretics resulted in an immediate therapeutic response. Visual acuity improved from 20/50 to 20/25 after 2 days of treatment. MRI revealed decreasing water content of both the muscle and connective tissue compartments without any volume changes. Subsequently, corticosteroids and orbital irradiation were started. Orbital decompression surgery was not required. Discussion/conclusion: Edematous swelling of orbital tissues is an established contributor of local pressure increase in thyroid eye disease. Diuretics reduce orbital pressure and, if confirmed by others, may be useful additions to the standard of care in sight-threatening DON.

Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study.

Heart failure following acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell (PBMC) suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC) were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and echocardiography were used to quantitate cardiac function. Analysis of soluble factors present in APOSEC was performed by enzyme-linked immunosorbent assay (ELISA) and activation of signalling cascades in human cardiomyocytes by APOSEC in vitro was studied by immunoblot analysis. Intravenous administration of a single dose of APOSEC resulted in a reduction of scar tissue formation in both AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of ejection fraction (57.0 vs. 40.5%, p < 0.01), a better cardiac output (4.0 vs. 2.4 l/min, p < 0.001) and a reduced extent of infarction size (12.6 vs. 6.9%, p < 0.02) as determined by MRI. Exposure of primary human cardiac myocytes with APOSEC in vitro triggered the activation of pro-survival signalling-cascades (AKT, Erk1/2, CREB, c-Jun), increased anti-apoptotic gene products (Bcl-2, BAG1) and protected them from starvation-induced cell death. Intravenous infusion of culture supernatant of apoptotic PBMC attenuates myocardial remodelling in experimental AMI models. This effect is probably due to the activation of pro-survival signalling cascades in the affected cardiomyocytes.