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OBJECTIVE The treatment of symptomatic, progressive or recurrent acquired intracerebral cysts is challenging, especially when they are localized in eloquent structures. In addition to resection, endoscopic fenestration, or stereotactic puncture, the implantation of a cystoventricular shunt by stereotactic guidance (SCVS) has been reported as a minimally invasive procedure; however, only scarce data are available regarding its feasibility and efficacy. Here, the authors evaluated the feasibility and efficacy of frame-based SCVS in patients with acquired intracranial cysts. METHODS In this single-center retrospective analysis, the authors included all patients with acquired intracerebral cysts treated by SCVS following a standardized prospective protocol between 2012 and 2020. They analyzed clinical symptoms, complications, and radiological outcome with regard to cyst volume reduction by 3D volumetry. RESULTS Thirty-four patients (17 females and 17 males; median age 44 years, range 5–77 years) were identified. The median initial cyst volume was 11.5 cm3 (range 1.6–71.6 cm3), and the mean follow-up was 20 months (range 1–82 months). At the last follow-up, 27 of 34 patients (79%) showed a cyst volume reduction of more than 50%. Initial symptoms improved or resolved in 74% (n = 25) and remained stable in 24% (n = 8). No permanent clinical deterioration after treatment was observed. The total complication rate was 5.9%, comprising transient neurological deterioration (n = 1) and ventriculitis (n = 1). There were no deaths. The overall recurrence rate was 11.8%. CONCLUSIONS In this study, SCVS proved to be a safe, minimally invasive, and effective treatment with reliable long-term volume reduction, resulting in clinical improvement and a minor complication rate.

BACKGROUND: The majority of opioid overdose admissions in pediatric patients are associated with prescription opioids. Post-operative prescriptions are an addressable source of opioids in the household. This study aims to assess for sustained reduction in opioid prescribing after implementation of provider-based education at nine centers. METHODS: Opioid prescribing information was collected for pediatric patients undergoing umbilical hernia repair at nine centers between December 2018 and January 2019, one year after the start of an education intervention. This was compared to prescribing patterns in the immediate pre- and post-intervention periods at each of the nine centers. RESULTS: In the current study period, 29/127 (22.8%) patients received opioid prescriptions (median 8 doses) following surgery. There were no medication refills, emergency department returns or readmissions related to the procedure. There was sustained reduction in opioid prescribing compared to pre-intervention (22.8% vs 75.8% of patients, p

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

Background There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. Objectives In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. Methods We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. Results Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. Conclusion Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

In 2011 the European Society for the Study of Tourette Syndrome (ESSTS) published its first European clinical guidelines for the treatment of Tourette Syndrome (TS) with part IV on deep brain stimulation (DBS). Here, we present a revised version of these guidelines with updated recommendations based on the current literature covering the last decade as well as a survey among ESSTS experts. Currently, data from the International Tourette DBS Registry and Database, two meta-analyses, and eight randomized controlled trials (RCTs) are available. Interpretation of outcomes is limited by small sample sizes and short follow-up periods. Compared to open uncontrolled case studies, RCTs report less favorable outcomes with conflicting results. This could be related to several different aspects including methodological issues, but also substantial placebo effects. These guidelines, therefore, not only present currently available data from open and controlled studies, but also include expert knowledge. Although the overall database has increased in size since 2011, definite conclusions regarding the efficacy and tolerability of DBS in TS are still open to debate. Therefore, we continue to consider DBS for TS as an experimental treatment that should be used only in carefully selected, severely affected and otherwise treatment-resistant patients.

Erythema multiforme is an immune-mediated mucocutaneous disorder. Mucosal involvement usually affects the oral region, the genitals or the eyes. We report a case of esophagitis caused by erythema multiforme in a patient diagnosed with lung cancer. Esophageal manifestation in erythema multiforme is rarely seen. Besides esophagitis it can lead to esophageal strictures. Erythema multiforme is mostly triggered by infection or drugs but the association with malignancy has been described.

According to economic theory, repeated interactions can play a crucial role in shaping trust. We randomly allocated people to treatments that promote interactions with bankers. Next, these ...

Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild-type NPM1 without FLT3-ITD as the treatment of this subset of patients with intermediate-risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed miR-15a-5p and miR-21-5p as miRNAs with a major role in chemoresistance in AML. We showed that miR-15a-5p and miR-21-5p overexpression decreased apoptosis induced by cytarabine and/or daunorubicin. PDCD4, ARL2 and BTG2 genes were found to be targeted by miR-15a-5p, as well as PDCD4 and BTG2 by miR-21-5p. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that miR-15a-5p and miR-21-5p are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro-apoptotic genes PDCD4, ARL2 and BTG2. ispartof: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE vol:25 issue:1 pages:575-585 ispartof: location:England status: published

Background The purpose of this study was to evaluate the use of a stress ball as a distraction technique on stress levels of patients undergoing a dental procedure. Material and methods A randomized, split-mouth design was conducted using 20 adult subjects requiring scaling and root planing (Sc/RP) in all four quadrants. Each side of the mouth (maxillary/mandibular) received Sc/RP with local anesthetic with or without the use of a stress-ball distraction over two separate sessions. Subjects completed two pre-procedural questionnaires (Spielberger State-Trait Anxiety Inventory, STAI; Modified Dental Anxiety Scale, MDAS) before and after each treatment session. A Galvanic Skin Response (GSR) sensor (Neulog) was used throughout each session to measure skin conductance or sweat. Results No significant difference in GSR scores was found during treatment with or without the use of the stress ball. Also, no significant differences in the change in STAI or MDAS scores were found with or without the use of a stress ball. Conclusions The results of this study found that the use of a stress ball as a distraction technique did not result in any significant reduction in stress levels in subjects undergoing scaling and root planing with local anesthesia. Key words:Anxiety, distraction, stress ball.

X-ray computed tomography (XCT) is the only non-destructive technique able to perform a complete quality control of additive manufactured products in a single inspection. Yet, high-quality scans are associated with large acquisition times and limited to high-end AM parts. In this paper we investigate a deep learning U-net segmentation algorithm to improve the segmentation of low-quality XCT scans. A high-quality XCT scan is acquired and aligned with low-quality XCT scans to create the ground truth data. The accuracy of the segmentation is quantified with the Jaccard index and physical properties of the parts.

The purpose of this study was to investigate the manufacturer's claims regarding a novel needleless intraligamentary local anesthesia injection device (Numbee, BioDent) to provide effective single tooth anesthesia. Investigators compared the Numbee with a traditional inferior alveolar nerve block (IANB) during a restorative procedure on mandibular teeth. A randomized, split-mouth design was conducted with 15 adult subjects receiving an IANB on one side and a Numbee injection on the same tooth type on the contralateral side. Subjects recorded injection pain using the Visual Analog Scale (VAS) and their preferred injection technique. Anesthesia was considered profound with 2 consecutive electric pulp tester readings of 80. If subjects became symptomatic during the restorative procedure, rescue anesthesia was administered. The difference in VAS scores for injection pain between the Numbee and the IANB was not significant (p = .078). For the IANB, the incidence of profound anesthesia was 46%, and required rescue anesthesia was 20%. For the Numbee, the incidence of profound anesthesia was 0%, and required rescue anesthesia was 60%. Subject preference was evenly split (50/50%) between the 2 techniques. The IANB outperformed the Numbee device for achieving profound anesthesia and requiring less rescue anesthesia.

OBJECTIVE This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). METHODS Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. RESULTS Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p

Background: Directional deep brain stimulation (DBS) enlarges the therapeutic window by increasing side-effect thresholds and improving clinical benefits. To determine the optimal stimulation settings and interpret clinical observations, knowledge of the lead orientation in relation to the patient’s anatomy is required. Objective: To determine if directional leads remain in a fixed orientation after implantation or whether orientation changes over time. Method: Clinical records of 187 patients with directional DBS electrodes were screened for CT scans in addition to the routine postoperative CT. The orientation angle of each electrode at a specific point in time was reconstructed from CT artifacts using the DiODe algorithm implemented in Lead-DBS. The orientation angles over time were compared with the originally measured orientations from the routine postoperative CT. Results: Multiple CT scans were identified in 18 patients and the constancy of the orientation angle was determined for 29 leads at 48 points in time. The median time difference between the observations and the routine postoperative CT scan was 82 (range 1–811) days. The mean difference of the orientation angles compared to the initial measurement was –1.1 ± 3.9° (range –7.6 to 8.7°). Linear regression showed no relevant drift of the absolute value of the orientation angle over time (0.8°/year, adjusted R2: 0.040, p = 0.093). Conclusion: The orientation of directional leads was stable and showed no clinically relevant changes either in the first weeks after implantation or over longer periods of time.

Recent translational data suggest that deep brain stimulation (DBS) of the cortico-striato-thalamo-cortical (CSTC) loops improves sensorimotor gating in psychiatric disorders that show deficient prepulse inhibition (PPI), a robust operational measure of sensorimotor gating. To our knowledge we are the first to investigate this effect in patients with Tourette syndrome (TS). We measured PPI of the acoustic startle reflex in patients with TS (N = 10) or Obsessive-Compulsive Disorder (OCD) (N = 8) treated with DBS of the centromedian and ventro-oral internal thalamic nucleus and the anterior limb of internal capsule-nucleus accumbens area respectively, and aged- and gender-matched healthy controls (HC). PPI of the DBS groups was measured in randomized order in the ON and OFF stimulation condition. Statistical analysis revealed no significant difference in PPI (%) of patients with TS between ON (M = 20.5, SD = 14.9) and OFF (M = 25.2, SD = 29.7) condition. There were significantly reduced PPI levels in patients with TS in the ON condition compared to HC (M = 49.2, SD = 10.7), but no significant difference in PPI between TS in the OFF condition and HC. Furthermore, we found no significant stimulation or group effect for OCD and HC (OCD ON: M = 57.0, SD = 8.3; OCD OFF: 67.8, SD = 19.6; HC: M = 63.0, SD = 24.3). Our study has a number of limitations. Sample sizes are small due to the restricted patient collective. The study was not controlled for use of psychoactive medication or nicotine. Furthermore, we were not able to assess presurgical PPI measurements. In conclusion, we were able to show that PPI is impaired in patients with TS. This finding is in line with recent translational work. With respect to the OCD cohort we were not able to replicate our previously published data. A disability in sensorimotor gating plays a pivotal role in many psychiatric disorders therefore more research should be conducted to disentangle the potential and limitations of modulating sensorimotor gating via brain stimulation techniques.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate ‘reverse’ tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

Objective To compare directional monopolar, bipolar, and directional bipolar thalamic deep brain stimulation (DBS) in tremor patients. Methods Fourteen tremor patients (7 Essential Tremor and 7 Parkinson's Disease) implanted with directional DBS electrodes in the ventral intermediate nucleus (VIM) were enrolled. Side-effect thresholds of monopolar directional stimulation (DIRECT) were compared to circular DBS as well as, in a randomized design, to those of two different bipolar stimulation settings (BIPOLAR = circular anode; BI-DIRECT = directional anode). Tremor suppression (Tremor Rating Scale, TRS) right below the side-effect threshold was also assessed. Results Directional DBS in the individually best direction showed higher side-effect thresholds than circular DBS (p = 0.0063). The thresholds were raised further using either one of the bipolar stimulation paradigms (BIPOLAR p = 0.0029, BI-DIRECT p = 0.0022). The side-effect thresholds did not differ between both bipolar settings, but side-effects were less frequent with BI-DIRECT. No difference in TRS scores with stimulation just below the side-effect threshold was found between all stimulation conditions. Conclusions Side-effect thresholds of monopolar directional and bipolar stimulation with both circular and directional anodes were higher compared to traditional monopolar circular stimulation in the VIM. Bipolar DBS with directional anodes evoked side-effect less frequently than bipolar and monopolar directional stimulation. All stimulation settings had comparable effects on tremor suppression just below their side-effect thresholds. Thus, directional and different bipolar settings should be explored in patients with bothersome side-effects of thalamic stimulation when monopolar stimulation settings are not satisfying. Further studies are needed to explore the efficiency of the different bipolar stimulation paradigms.

A lateral flow reactor (LFR) is a low pressure drop fixed bed reactor especially suitable for end-of-pipe treatment, for example, the Shell DeNO(x) system for selective catalytic reduction of NOx. Inherently, an LFR is prone to flow maldistribution, which in turn may negatively affect conversion. A detailed study of the hydrodynamics and overall reactor performance of an LFR is presented. The characterization of the flow patterns is carried out in detail with a 2D computational fluid dynamics (CFD) model. In addition, a "double 1D" hydrodynamic model is developed and validated against the CFD results. This computationally much more efficient model is extended with catalytic reaction kinetics, accounting for intraparticle mass transfer limitations. LFR efficiency can be defined as the ratio of the amount of catalyst needed in a fixed bed with uniform distribution over the amount of catalyst needed in the LFR to reach the same overall conversion. Despite the inherently limited flow uniformity, this efficiency of the LFR remains higher than 95% as long as the flow uniformity is above 50%, that is, for nearly all practical cases.

Introduction Deep learning-based algorithms have demonstrated enormous performance in segmentation of medical images. We collected a dataset of multiparametric MRI and contour data acquired for use in radiosurgery, to evaluate the performance of deep convolutional neural networks (DCNN) in automatic segmentation of brain metastases (BM). Methods A conventional U-Net (cU-Net), a modified U-Net (moU-Net) and a U-Net trained only on BM smaller than 0.4 ml (sU-Net) were implemented. Performance was assessed on a separate test set employing sensitivity, specificity, average false positive rate (AFPR), the dice similarity coefficient (DSC), Bland-Altman analysis and the concordance correlation coefficient (CCC). Results A dataset of 509 patients (1223 BM) was split into a training set (469 pts) and a test set (40 pts). A combination of all trained networks was the most sensitive (0.82) while maintaining a specificity 0.83. The same model achieved a sensitivity of 0.97 and a specificity of 0.94 when considering only lesions larger than 0.06 ml (75% of all lesions). Type of primary cancer had no significant influence on the mean DSC per lesion (p = 0.60). Agreement between manually and automatically assessed tumor volumes as quantified by a CCC of 0.87 (95% CI, 0.77–0.93), was excellent. Conclusion Using a dataset which properly captured the variation in imaging appearance observed in clinical practice, we were able to conclude that DCNNs reach clinically relevant performance for most lesions. Clinical applicability is currently limited by the size of the target lesion. Further studies should address if small targets are accurately represented in the test data.

Aim and objective The purpose of this study was to examine the effects of toothbrushing on the change in color of extrinsic characterization of ceramic-polymer materials. Materials and methods Two ceramic-polymer materials (CeraSmart, GC; Enamic, VITA) and one lithium-disilicate material (IPS e.max CAD; Ivoclar Vivadent) were tested. Specimens of each material were prepared, characterized, and glazed per manufacturer's instructions. The treated surface of the blocks were then brushed in a toothpaste slurry with artificial saliva using a toothbrush machine with a soft toothbrush. Commission Internationale de L'Eclairage (CIE) L*a*b* values were recorded with a spectrophotometer at baseline and at 3, 6, 9, and 12 simulated years of brushing (7,300 strokes/year). A mean change in color (ΔE*) and standard deviation was determined for each group and brushing interval. Data were analyzed with a two-way repeated measures ANOVA examining the effects of toothbrushing the ceramic materials on ΔE* over time (α = 0.05). Results The difference in the ΔE* between CeraSmart and Enamic was significant at 3 years, while the differences between them were not significant at 6, 9, and 12 years of simulated brushing. The ΔE* of IPS e.max CAD was significantly lower than CeraSmart and Enamic at all time points (all p Conclusion The extrinsic stains on the ceramic-polymer materials may be more susceptible to change from simulated toothbrushing compared to the lithium-disilicate material. Clinical significance Toothbrushing may change the color of extrinsic characterization of ceramic-polymer materials. However, the change may remain clinically imperceptible to the naked eye (ΔE* > 1.0) for nearly 6 equivalent years of brushing.

The pterygopalatine fossa (PPF) is a complex and paired anatomical structure located at the skull base. A clinically and surgically relevant structure located in the pterygopalatine fossa is the sphenopalatine ganglion. Electrical stimulation of the sphenopalatine ganglion is one possible method of treating cluster headache. The pterygomaxillary fissure (PMF) defines the pterygopalatine fossa laterally and determines the surgical approach. As part of preoperative surgical planning, each patient undergoes a preoperative head computed tomography or a cone beam computed tomography. In our study cone beam computed tomography images of 90 male and 110 female PMF were analyzed. Generally, males have a wider fissure than females. Moreover, a significant inter-subject difference could be shown between males and females. The analysis of the right and left PMF according to gender and age does not show any significant intra-subject differences. Following an established protocol for high-resolution CT images the measurements were classified into four fissure types and also analyzed according to gender and age. Fissure type I is significantly more often present in males, whereas the smaller fissure types (II, III, and IV) are significantly more often found in females. Older patients presented statistically significant more often with type I, whereas the younger patients showed more often the narrower types II and IV. Due to the fact that narrow fissures smaller than 2 mm could limit the insertion of neurostimulator implants in the PPF, special attention should be paid to females and younger patients during preoperative planning.

Background: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson’s disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. Objective: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. Methods: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Results: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. Conclusion: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future.

Contains fulltext : 241592.pdf (Publisher’s version ) (Open Access) Objectives: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers. Materials and Methods: Fifteen patients (six male) with otherwise treatment-refractory OCD receiving ALIC/NAc DBS performed a flanker task with EEG recordings at three sessions: presurgery, and at follow-up with DBS on and off. We examined MFT, ERN, and task performance. Furthermore, we investigated interrelations with clinical efficacy and the explored the influence of the location of individual stimulation volumes on EEG modulations. Results: MFT and ERN were significantly attenuated by DBS with differences most pronounced between presurgery and DBS-on states. Also, we observed reaction time slowing for erroneous responses during DBS-off. Larger presurgery ERN amplitudes were associated with decreased clinical efficacy. Exploratory anatomical analyses suggested that stimulation volumes encompassing the NAc were associated with MFT modulation, whereas ALIC stimulation was associated with modulation of the ERN and clinical efficacy. Conclusion: ALIC/NAc DBS diminished MFT and ERN, demonstrating modulation of the medial frontal performance monitoring system in OCD. Furthermore, our findings encourage further studies to explore the ERN as a potential predictor for clinical efficacy. 8 p.

Background: Heart failure (HF) remains a main cause of mortality worldwide. Risk stratification of patients with systolic chronic HF is critical to identify those who may benefit from advanced HF therapies. The aim of this study is to identify plasmatic proteins that could predict early death of HF patients. Methods: The subproteome targeted by the aptamer-based assay (SOMAscan) of 1310 proteins was profiled in blood samples from 168 HF patients with reduced ejection fraction hospitalized in CHRU de Lille. Patient's outcome was assessed 3 years after inclusion. Findings: Among the 1310 proteins, 203 were significantly modulated between dead and alive patients (Wilcoxon tests, FDR 5%). The INCA molecular network was built using these 203 proteins and contained 2881 molecules (1639 proteins, 1072 microRNAs, 170 metabolites). To assess mechanistic context of HF, molecules were assigned to 34 clusters annotated to biological pathways from Gene Ontology. Analysis of the INCA network model allowed to highlight extracellular matrix organization as mechanism involved in HF. In parallel, an adaptive LASSO was performed on these 203 proteins and six proteins were selected as candidates to predict early death of HF patients: complement C3, cathepsin S and FAM107B were decreased and MAPKAPK5, MMP1 and MMP7 increased in dead patients compared with patients alive. By conventional assays, complement C3, MMP1 and MMP7 were validated but not cathepsin S due to the low sensitivity and specificity of the assay used. Interpretation: A proteomic signature of 6 plasma proteins allows identifying HF patients with a risk of early death. Funding Statement: This work was supported by grants from French Clinical Research Infrastructure Network INI-CRT (Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists), the E.U. FP7 HOMAGE (305507), “Agence Nationale de Recherche” 15-CEA-U16/”Direction Generale de l'Offre de Soins” (5- 013) and CHRU de Lille (Bonus H2018).We acknowledged Somalogic Inc as the provider of the proteomics analysis and EdgeLeap B.V. for the system biology analysis. Declaration of Interests: MC, VV, MB, OB, AH, PDG, PA, CB, GM, FP have no conflict of interest to disclose for the study performed. Ethics Approval Statement: The INCA study was approved by the ethics committee of the “Centre Hospitalier de Lille” (CP98/94, 5 November 1998) , and written informed consent was obtained for each patient.

Geospatial research and education have become increasingly dependent on cyberGIS to tackle computation and data challenges. However, the use of advanced cyberinfrastructure resources for geospatial research and education is extremely challenging due to both high learning curve for users and high software development and integration costs for developers, due to limited availability of middleware tools available to make such resources easily accessible. This tutorial describes CyberGIS-Compute as a middleware framework that addresses these challenges and provides access to high-performance resources through simple easy to use interfaces. The CyberGIS-Compute framework provides an easy to use application interface and a Python SDK to provide access to CyberGIS capabilities, allowing geospatial applications to easily scale and employ advanced cyberinfrastructure resources. In this tutorial, we will first start with the basics of CyberGIS-Jupyter and CyberGIS-Compute, then introduce the Python SDK for CyberGIS-Compute with a simple Hello World example. Then, we will take multiple real-world geospatial applications use-cases like spatial accessibility and wildfire evacuation simulation using agent based modeling. We will also provide pointers on how to contribute applications to the CyberGIS-Compute framework.

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

Background: Extended research has pointed to the efficacy of deep brain stimulation (DBS) in treatment of patients with treatment-refractory Tourette syndrome (TS). The four most commonly used DBS targets for TS include the centromedian nucleus–nucleus ventrooralis internus (CM-Voi) and the centromedian nucleus–parafascicular (CM-Pf) complexes of the thalamus, and the posteroventrolateral (pvIGPi) and the anteromedial portion of the globus pallidus internus (amGPi). Differences and commonalities between those targets need to be compared systematically.Objective: Therefore, we evaluated whether DBS is effective in reducing TS symptoms and target-specific differences.Methods: A PubMed literature search was conducted according to the PRISMA guidelines. Eligible literature was used to conduct a systematic review and meta-analysis.Results: In total, 65 studies with 376 patients were included. Overall, Yale Global Tic Severity Scale (YGTSS) scores were reduced by more than 50 in 69% of the patients. DBS also resulted in significant reductions of secondary outcome measures, including the total YGTSS, modified Rush Video-Based Tic Rating Scale (mRVRS), Yale-Brown Obsessive Compulsive Scale (YBOCS), and Becks Depression Inventory (BDI). All targets resulted in significant reductions of YGTSS scores and, with the exception of the CM-Pf, also in reduced YBOCS scores. Interestingly, DBS of pallidal targets showed increased YGTSS and YBOCS reductions compared to thalamic targets. Also, the meta-analysis including six randomized controlled and double-blinded trials demonstrated clinical efficacy of DBS for TS, that remained significant for GPi but not thalamic stimulation in two separate meta-analyses.Conclusion: We conclude that DBS is a clinically effective treatment option for patients with treatment-refractory TS, with all targets showing comparable improvement rates. Future research might focus on personalized and symptom-specific target selection.

Sepsis is a potentially lethal syndrome resulting from a maladaptive response to infection. Upon infection, glucocorticoids are produced as a part of the compensatory response to tolerate sepsis. This tolerance is, however, mitigated in sepsis due to a quickly induced glucocorticoid resistance at the level of the glucocorticoid receptor. Here, we show that defects in the glucocorticoid receptor signaling pathway aggravate sepsis pathophysiology by lowering lactate clearance and sensitizing mice to lactate-induced toxicity. The latter is exerted via an uncontrolled production of vascular endothelial growth factor, resulting in vascular leakage and collapse with severe hypotension, organ damage, and death, all being typical features of a lethal form of sepsis. In conclusion, sepsis leads to glucocorticoid receptor failure and hyperlactatemia, which collectively leads to a lethal vascular collapse.

BackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005).ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.

Aims/hypothesis We examined whether the non-HLA susceptibility locus ERBB3/IKZF4 influences progression of type 1 diabetes stage specifically according to sex. Methods SNPs of ERBB3 (rs2292239 T/G) and IKZF4 (rs1701704 G/T) were screened by allelic discrimination quantitative PCR assay in first-degree relatives of type 1 diabetes patients who had developed at least one circulating autoantibody. The effect of ERBB3/IKZF4 genotypes and sex, on the progression of single autoantibody positivity to multiple autoantibody positivity and from multiple autoantibody positivity to diabetes, was studied by Kaplan–Meier analysis and multivariate Cox regression. Results In the cohort of autoantibody-positive first-degree relatives, the risk allele frequencies for ERBB3 rs2292239 (T) and IKZF4 rs1701704 (G) were increased. There was a significant male excess at the stage of multiple autoantibody positivity (p = 0.021). In Kaplan–Meier survival analysis, progression from single to multiple antibody positivity was delayed in female participants with genotype ERBB3 GG (p = 0.018, vs ERBB3 TG+TT) or IKZF4 TT (p = 0.023, vs IKZF4 GT+GG), but not in male participants. In multivariate Cox regression models, the interaction effects between female sex and ERBB3 GG (p = 0.012; HR = 0.305 [95% CI 0.120, 0.773]) or between female sex and IKZF4 TT (p = 0.011; HR = 0.329 [95% CI 0.140, 0.777]) emerged as potential determinants of delayed progression to multiple autoantibodies. The progression from multiple autoantibody positivity to type 1 diabetes appeared not to be influenced by ERBB3/IKZF4. Conclusions/interpretation In siblings and offspring of type 1 diabetes patients, polymorphism in region ERBB3/IKZF4 may affect disease progression at the level of epitope spreading in female individuals. Our findings suggest that interaction between sex and ERBB3/IKZF4 may contribute to the post-pubertal male excess in type 1 diabetes. Graphical abstract

Purpose To assess the use of deep learning (DL) for computer-assisted glaucoma identification, and the impact of training using images selected by an active learning strategy, which minimizes labelling cost. Additionally, this study focuses on the explainability of the glaucoma classifier. Methods This original investigation pooled 8433 retrospectively collected and anonymized colour optic disc-centred fundus images, in order to develop a deep learning-based classifier for glaucoma diagnosis. The labels of the various deep learning models were compared with the clinical assessment by glaucoma experts. Data were analysed between March and October 2018. Sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and amount of data used for discriminating between glaucomatous and non-glaucomatous fundus images, on both image and patient level. Results Trained using 2072 colour fundus images, representing 42% of the original training data, the trained DL model achieved an AUC of 0.995, sensitivity and specificity of, respectively, 98.0% (CI 95.5%-99.4%) and 91% (CI 84.0%-96.0%), for glaucoma versus non-glaucoma patient referral. Conclusions These results demonstrate the benefits of deep learning for automated glaucoma detection based on optic disc-centred fundus images. The combined use of transfer and active learning in the medical community can optimize performance of DL models, while minimizing the labelling cost of domain-specific mavens. Glaucoma experts are able to make use of heat maps generated by the deep learning classifier to assess its decision, which seems to be related to inferior and superior neuroretinal rim (within ONH), and RNFL in superotemporal and inferotemporal zones (outside ONH). The first author is jointly supported by the Research Group Ophthalmology, KU Leuven and VITO NV. No outside entities have been involved in the study design, in the collection, analysis and interpretation of data, in the writing of the manuscript, nor in the decision to submit the manuscript for publication. Thus, the authors declare that there are no conflicts of interest in this work.

Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period.Pediatric-onset IBD (17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification.1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

We integrate sparse radar data into a monocular depth estimation model and introduce a novel preprocessing method for reducing the sparseness and limited field of view provided by radar. We explore the intrinsic error of different radar modalities and show our proposed method results in more data points with reduced error. We further propose a novel method for estimating dense depth maps from monocular 2D images and sparse radar measurements using deep learning based on the deep ordinal regression network by Fu et al. Radar data are integrated by first converting the sparse 2D points to a height-extended 3D measurement and then including it into the network using a late fusion approach. Experiments are conducted on the nuScenes dataset. Our experiments demonstrate state-of-the-art performance in both day and night scenes., Accepted to ICIP2021

BackgroundSubthalamic nucleus deep brain stimulation is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control.ObjectivesTo investigate in patients with Parkinson’s disease and nucleus subthalamicus deep brain stimulation (STN-DBS) whether short pulse width stimulation with 30µs maintains equal motor control as conventional 60µs stimulation over a period of 4 weeks.MethodsIn this monocentric, double-blinded, randomized crossover trial, 30 patients with Parkinson’s disease and STN-DBS were enrolled and assigned to 4 weeks of stimulation with 30µs and 4 weeks of stimulation with 60µs in randomized order (German Clinical Trials Register No. DRKS00017528). The primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life.ResultsA total of 24 patients were included in the final analysis. There was no difference in motor symptom control between the two treatment conditions. Concerning secondary outcomes there was no difference in energy consumption, non-motor symptoms, side-effects, or quality of life. On the individual level, patients preferring 30µs tended to be more dyskinetic in the 60µs setting, whereas patients preferring 60µs experienced more off-time in the 30µs setting.ConclusionsShort pulse width settings (30µs) provide equal motor symptom control as conventional (60µs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

Altres ajuts: Projekt DEAL; German Research Foundation (Grant KFO 219). To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable "QoL responders"/"non-responders". At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as "QoL non-responders". Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as 'difficulties experiencing pleasure' and 'problems sustaining concentration'. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.

Sleep stage scoring can lead to important inter-expert variability. Although likely, whether this issue is amplified in older populations, which show alterations of sleep electrophysiology, has not been thoroughly assessed. Algorithms for automatic sleep stage scoring may appear ideal to eliminate inter-expert variability. Yet, variability between human experts and algorithm sleep stage scoring in healthy older individuals has not been investigated. Here, we aimed to compare stage scoring of older individuals and hypothesized that variability, whether between experts or considering the algorithm, would be higher than usually reported in the literature. Twenty cognitively normal and healthy late midlife individuals' (61 ± 5 years; 10 women) night-time sleep recordings were scored by two experts from different research centres and one algorithm. We computed agreements for the entire night (percentage and Cohen's κ) and each sleep stage. Whole-night pairwise agreements were relatively low and ranged from 67% to 78% (κ, 0.54-0.67). Sensitivity across pairs of scorers proved lowest for stages N1 (8.2%-63.4%) and N3 (44.8%-99.3%). Significant differences between experts and/or algorithm were found for total sleep time, sleep efficiency, time spent in N1/N2/N3 and wake after sleep onset (p ≤ 0.005), but not for sleep onset latency, rapid eye movement (REM) and slow-wave sleep (SWS) duration (N2 + N3). Our results confirm high inter-expert variability in healthy aging. Consensus appears good for REM and SWS, considered as a whole. It seems more difficult for N3, potentially because human raters adapt their interpretation according to overall changes in sleep characteristics. Although the algorithm does not substantially reduce variability, it would favour time-efficient standardization.

Anthracyclines remain a cornerstone of induction chemotherapy for acute myeloid leukemia (AML). Refractory or relapsed disease due to chemotherapy resistance is a major obstacle in AML management. MicroRNAs (miRNAs) have been observed to be involved in chemoresistance. We previously observed that miR-15a-5p was overexpressed in a subgroup of chemoresistant cytogenetically normal AML patients compared with chemosensitive patients treated with daunorubicin and cytarabine. MiR-15a-5p overexpression in AML cells reduced apoptosis induced by both drugs in vitro. This study aimed to elucidate the mechanisms by which miR-15a-5p contributes to daunorubicin resistance. We showed that daunorubicin induced autophagy in myeloid cell lines. The inhibition of autophagy reduced cell sensitivity to daunorubicin. The overexpression of miR-15a-5p decreased daunorubicin-induced autophagy. Conversely, the downregulation of miR-15a-5p increased daunorubicin-induced autophagy. We found that miR-15a-5p targeted four genes involved in autophagy, namely ATG9a, ATG14, GABARAPL1 and SMPD1. Daunorubicin increased the expression of these four genes, and miR-15a-5p counteracted this regulation. Inhibition experiments with the four target genes showed the functional effect of miR-15a-5p on autophagy. In summary, our results indicated that miR-15a-5p induces chemoresistance in AML cells through the abrogation of daunorubicin-induced autophagy, suggesting that miR-15a-5p could be a promising therapeutic target for chemoresistant AML patients.

"Fondation Recherche Alzheimer (SAO-FRA 2019/0025)"was missing from the acknowledgements. This has been corrected online.

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Purpose: The purpose of this study was to determine if utilization of biologic mesh underlay during thoracoscopic congenital diaphragmatic hernia (CDH) primary repair (PR) results in reduc...

OBJECTIVE To investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients. METHODS Stimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long-term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) improvement (63 patients). RESULTS Significant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long-term UPDRS-III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%). INTERPRETATION This study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short- and long-term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527-538.

Objective The objective of this study was to effectuate a consensus of emergency physicians on minimum requirements for facility, diagnostic, and medical specialist availability as a first step toward minimum operational standards for 24/7 available emergency departments (EDs) in the Netherlands.Patients and methods A two-part e-Delphi through online survey was performed between January 2015 and May 2016, using a panel of 20 experts in emergency medicine. The aim of part I was to reach an agreement on a list of possible ED elements and their definitions. The second part addressed the actual study objective to reach consensus on operational standards. Successive rounds were submitted to the members of the panel online using SurveyMonkey. Results of each survey round were discussed and interpreted in agreement with all authors in preparation for the next round. Reaching consensus, defined as 70% or more agreement or disagreement among the panel, on the level of all items was the endpoint of this study.Results Both parts I and II required five rounds. The dropout rate of the expert panel remained zero. The availability of 52 facilities and diagnostic functionalities and the manner in which 17 medical specialties should be available to every 24/7 ED were agreed upon by the expert panel.Conclusion An expert panel agreed upon minimum operational standards for EDs in the Netherlands. These results are helpful as a first step toward a more widely supported standard for future 24/7 available EDs in the Netherlands and in addition to this other urgent care facilities.

Oxidative coupling of methane (OCM) is considered one of the most promising routes to directly convert methane into more valuable hydrocarbons. The uncertain economics related to the tradeoff between conversion and C2 selectivities is the primary reason why OCM is currently not industrially applied. In the last decades, numerous studies have focused on developing a viable catalyst that has the potential to improve the low C2 yields. But is the primary issue of OCM truly a catalyst problem? Because of the high exothermicity of the OCM process, thermal effects and path dependence are dominating in all OCM reactors of practical importance. Furthermore, irreducible diffusion limitations exist on the pellet scale. Understanding how to exploit these mass and heat transfer effects by reactor engineering is a prerequisite for the breakthrough of OCM. In this work an overview is given of criteria used to assess mass and heat transfer resistances, parametric sensitivity and runaway in catalytic packed bed reactors. The importance of mass transport limitations, runaway and/or ignition for OCM, either on the pellet scale or on the reactor scale, is shown in several examples. Both simple and advanced reactor concepts are discussed with a focus on their heat and mass transfer characteristics. Clear progress has been made in the past lustrum on all these fronts and it seems that research is on the verge of a real breakthrough to make OCM happen on an industrial scale.

To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. Continuous scores comprising 1–5 histogram or GLCM features had a significant (p = 0.0001–0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222–3.590), while DFS (45% vs. 17%, p

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.