Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

Identifying core MRI sequences for reliable automatic brain metastasis segmentation.

BACKGROUND: Many automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation. METHODS: We analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 339 patients with BMs from seven centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE + T2-FLAIR, T1-CE + T1 + T2-FLAIR, T1-CE + T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 100 patients from five centers. RESULTS: The model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.73). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89. CONCLUSIONS: A T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

[Non-surgical peri-implantitis treatment with or without systemic antibiotics]. / Initiële behandeling van peri-implantitis met of zonder systemische antibiotica.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

Development and external validation of an MRI-based neural network for brain metastasis segmentation in the AURORA multicenter study.

BACKGROUND: Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability. METHODS: We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers. RESULTS: Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07). CONCLUSION: Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Methylene blue active substances in plaque of Bacillus subtilis subsp. subtilis and enrichment by supplemental calcium in culture media.

A series of experiments was conducted to identify the molecular species responsible for surface active emulsification (surfactant) bioactivity in Bacillus subtilis subsp. subtilis strain ATCC PTA-125135, and to describe culture conditions to support the enriched production of said bioactivity in cultured plaque of the strain. The assay for methylene blue active substances (MBAS) was found to be suitable for describing surfactant activity, where a solvent-extracted molecular fraction from the biofilm was found to retain surfactant activity and positively quantified as MBAS. Furthermore, an HPLC-refined protein fraction was found to quantify as MBAS with approximately 1·36-fold or greater surfactant activity per mol than sodium dodecyl sulphate, and a proteomic analysis of solvent extracted residues confirmed that biofilm surface layer protein BslA was a primary constituent of extracted residues. Surfactant bioactivity, quantified as MBAS, was enriched in cultured plaque by the supplementation of culture media with calcium chloride or calcium nitrate.

[Empirical investigation to assess the quality of psychiatric treatment]. / Empirische Untersuchung zur Behandlungsqualität in der Psychiatrie.

BACKGROUND: Quality of treatment is of increasing importance in psychiatry. Since the 1950s psychiatry has developed plenty of psychological and occupational approaches in addition to an arsenal of biological procedures. These treatment options have contributed to markedly lower the residence times in psychiatric medical centers to about 3 or 4 weeks. METHOD: The quality of treatment of a psychiatric clinic was evaluated on the basis of a limited number of parameters and in a short time. The data of 657 patients were evaluated. RESULTS: The patients profited significantly from the treatment, particularly when specific therapies were available as in depression or schizophrenia. About » of the patients received no psychoactive drugs. Most of the patients could be discharged from hospital within 3 weeks. The legal basis of hospitalization did not play a decisive role in the success of treatment. Most of the patients were after-treated by general practitioners. CONCLUSION: The result underlines the effectiveness of psychiatric treatment, but also the importance of cooperation between inpatient and outpatient treatment.

Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community.

The use of multiple omics techniques (i.e., genomics, transcriptomics, proteomics, and metabolomics) is becoming increasingly popular in all facets of life science. Omics techniques provide a more holistic molecular perspective of studied biological systems compared to traditional approaches. However, due to their inherent data differences, integrating multiple omics platforms remains an ongoing challenge for many researchers. As metabolites represent the downstream products of multiple interactions between genes, transcripts, and proteins, metabolomics, the tools and approaches routinely used in this field could assist with the integration of these complex multi-omics data sets. The question is, how? Here we provide some answers (in terms of methods, software tools and databases) along with a variety of recommendations and a list of continuing challenges as identified during a peer session on multi-omics integration that was held at the recent 'Australian and New Zealand Metabolomics Conference' (ANZMET 2018) in Auckland, New Zealand (Sept. 2018). We envisage that this document will serve as a guide to metabolomics researchers and other members of the community wishing to perform multi-omics studies. We also believe that these ideas may allow the full promise of integrated multi-omics research and, ultimately, of systems biology to be realized.

3-NOP vs. Halogenated Compound: Methane Production, Ruminal Fermentation and Microbial Community Response in Forage Fed Cattle.

The aim of this study was to investigate the effects of 3-nitrooxypropanol (3-NOP) and chloroform on methane (CH4) and H2 production, ruminal metabolites and microbial community structure in cattle fed a tropical forage diet. Eight rumen-fistulated steers were fed a roughage hay diet (Rhodes grass; Chloris gayana) for 31 days (control period). Four animals received the antimethanogenic compound chloroform (1.6 g chloroform-cyclodextrin/100 kg live weight (LW)) while the other four received 3-NOP (2.5 g 3-NOP/animal/day) for 21 days. Methane decrease compared with control period was similar for both treatments (30-38%) with no differences for expelled H2 between controls and treatments. Daily weight gain (DWG) was significantly increased when animals were treated with 3-NOP compared with chloroform and control. Regarding the ruminal fermentation parameters increases in ammonia, acetate and branched chain fatty acids were observed with both compounds compared with the controls. Also, methylamines, alcohols and dimethyl sulfone (DMSO2) concentrations were significantly increased with the treatments compared with control, being greater with 3-NOP. The rumen microbial analyses revealed a similar profile for both treatments, with a shift in operational taxonomic units (OTUs) assigned to the Prevotellaceae and Campylobacteraceae family. Moreover, major archaeal OTUs associated with Methanobrevibacter and Methanosphaera were significantly affected to varying extents based on the inhibitory treatments compared to the control. The abundance of the Methanobrevibacter spp. was decreased by 3-NOP and chloroform, while the Methanomassiliicoccaceae family was inhibited only by 3-NOP. The results suggest that despite the specific mode of action of 3-NOP on methanogens, inhibition of methanogenesis by both compounds resulted in similar responses in metabolism and microbial community structure in the rumen. We hypothesized that these changes were driven by the redirection of metabolic hydrogen ([H]) by both treatments. Therefore results from previous publications using chloroform as an inhibitor of methanogenesis may be useful in predicting ruminal microbiota and fermentation responses to 3-NOP.

Input-output curves of low and high spontaneous rate auditory nerve fibers are exponential near threshold.

Input-output (IO) properties of cochlear transduction are frequently determined by analyzing the average discharge rates of auditory nerve fibers (ANFs) in response to relatively long tonal stimulation. The ANFs in cats have spontaneous discharge rates (SRs) that are bimodally distributed, peaking at low (<0.5 spikes/s) and high (∼60 spikes/s) rates, and rate-level characteristics differ depending upon SR. In an effort to assess the instantaneous IO properties of ANFs having different SRs, static IO-curves were constructed from period histograms based on phase-locking of spikes to the stimulus waveform. These curves provide information unavailable in conventional average rate-level curves. We find that all IO curves follow an exponential trajectory. It is argued that the exponential behavior represents the transduction in the IHC and that the difference among ANFs having different SRs is predominantly a difference in gain attributed most likely to synaptic drive. © 2018 The authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

[Impact of medical TV series on surgical hospital patient's perception of reality]. / Einfluss von Arzt- und Krankenhausserien auf das Wirklichkeitsempfinden chirurgischer Krankenhauspatienten.

BACKGROUND: Medical TV series are very popular. Media research emphasizes that watching TV has an influence on patient's expectations and estimations concerning upcoming surgery. We analyzed these associations in our own patients. We suspected that reality as presented in the media and the actual reality of hospitals are not always conceived as two different worlds. METHODS: Over a 15-month period a standardized questionnaire was used to interview 162 in-house patients who had been admitted for an elective standard operation. They were interviewed 1-2 days prior to surgery and shortly before discharge from hospital. The questions aimed at their social situation and their TV viewing habits with special consideration of medical TV series. RESULTS: The knowledge of medical TV series is highly associated with a realistic assessment of these programs (p < 0.05). Furthermore, the knowledge of these programs is correlated with patient's unrealistic estimations of upcoming surgery. CONCLUSION: Medical TV series have a significant influence on surgical in-house patients. Patients with knowledge of many medical TV series believe that the medical setting in these shows is realistic. This can result in false estimations concerning real surgery.

Silver Fluoride as a Treatment for Dental Caries.

Medical management of caries is a distinct treatment philosophy that employs topical minimally invasive therapies that treat the disease and is not merely prevention. This strategy is justified as an alternative or supplement to traditional care by significant disease recurrence rates following comprehensive operative treatment under general anesthesia. Silver diamine fluoride (SDF) is one agent to enable effective noninvasive treatment. The announcement of breakthrough therapy designation by the Food and Drug Administration (FDA) suggests that SDF may become the first FDA-approved drug for treating caries. Since our systematic review performed in April 2015, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety in young children, start patients with high disease severity on an intensive regimen of multiple applications over the first few weeks, and continue with semiannual maintenance doses as previously suggested. Breakthroughs in elucidating the impact of SDF on the dental plaque microbiome inform potential opportunities for understanding caries arrest. SDF can be added to the set of evidence-based noninvasive methods to treat caries lesions in primary teeth, such as the Hall crown technique and sealing lesions with accessible margins.

Impact of Medical TV Shows on Preprocedural Fear of Surgical In-House Patients.

Background and Hypotheses: The growing number of medical television series and the increasing amount of time people spend watching TV will have an influence on what they expect from their treatment in a hospital. We suspect that reality as presented in the media and the actual reality of hospitals are not always conceived of as two different worlds. Many medical TV shows present dramatic, life-threatening operations much more often than they occur in reality. Patients who frequently watch such shows might be induced to believe that even routine operations are often dangerous, which could result in higher levels of fear before such an operation. We suspect then that there is a significant relation between preoperative levels of fear and TV viewing habits. METHODS: A standardized questionnaire was used to interview 162 in-house patients who had come to the hospital for an elective standard operation in a German hospital. They were interviewed 1-2 days prior to operation and shortly before discharge from hospital. The questions aimed at their social situation, their TV viewing habits with special consideration of medical TV shows, and the patients' preprocedural fear. RESULTS: The links between levels of education, age, and gender on the one hand, and viewing habits on the other, which have been shown in cultivation research, are supported by our findings. Approximately 50% reported a relevant anxiety level above 4 (on a scale of 0-10). There is a significant association between levels of fear and TV viewing habits. Thirteen subjects (8%) indicated that they suffered the highest imaginable degree of fear, all of them frequent watchers of medical TV shows. Frequent viewers of medical TV shows were definitely more scared than all other patients (p = 0.039). The preoperative level of fear was highest in the age group of under 40 years and significantly lower (p = 0.0042) in the age group of over 70 years. CONCLUSION: The assumed effects of cultivation with in-house patients caused by watching TV series could be shown to be statistically significant. Watching medical TV shows increases the patients' preoperative fear.

[A woman with a non-healing wound on the nose]. / Een vrouw met een niet-genezend wondje op de neus.

A 57-year-old woman presented with a progressive ulceration of her left nasal ala. We made the diagnosis of trigeminal trophic syndrome. This rare disorder may develop after injury of the trigeminal nerve, which causes local paraesthesia. Subsequent manipulation - whether intentional or unintentional - results in ulceration.

A survey of US and Canadian hospitals' paediatric massive transfusion protocol policies.

BACKGROUND: Trauma is the leading cause of death in children >1 year of age, with haemorrhage as the most common cause of medically preventable deaths. While massive transfusion protocols (MTPs) have been investigated and used in adults to reduce death from haemorrhage, there are a paucity of published data on MTP practices and outcomes in children. This study aimed to survey current MTP policies and the frequency of activation at paediatric care centres. STUDY DESIGN AND METHODS: We conducted a survey of MTPs at hospitals in the United States and Canada, including children's general hospitals, children's specialty hospitals and children's units in general hospitals. We collected information on how the MTP is activated, what therapeutics are given, frequency of its use, and how it is audited for compliance. RESULTS: Forty-six survey responses were analysed. Physician discretion was the most common activation criteria (89%). A majority of sites (78%) targeted a 'high' (≥1 : 2) ratio of plasma to red blood cells (RBC). Fifteen percent of sites use antifibrinolytics in their MTPs. Eighty nine percent of sites have type-O RBC units and 48% of sites had thawed plasma units stored in an immediately available location. CONCLUSION: There is a wide variation in MTPs among paediatric hospitals with regard to both activation criteria and products administered. This underscores the need for future prospective studies to determine the most effective resuscitation methods for paediatric populations to improve outcomes and therapeutic safety for massive bleeding.

Severe Quetiapine Withdrawal Syndrome with Nausea and Vomiting in a 65-year-old Patient with Psychotic Depression.

A 65-year old patient suffering from severe psychotic depression obtained quetiapine for roughly one year. Several attempts to discontinue quetiapine by tapering the dose provoked severe withdrawal symptoms with nausea and vomitus. Pretreatment with domperidone largely prevented withdrawal so that he finally could successfully discontinue quetiapine administration.