[Primary intraosseous cavernous hemangioma of the cranium: a case report]. / Pervichnaya vnutrikostnaya kavernoznaya gemangioma kostei cherepa: obzor literatury i opisanie klinicheskogo nablyudeniya khirurgicheskogo lecheniya.

Primary intraosseous cavernous hemangioma (PICH) is a rare benign vascular tumor. This neoplasm is common in the spine and less common in skull. Toynbee J. first described this tumor in 1845. PICH of the cranium does not always have typical X-ray features and should be always differentiated with other more common skull lesions. Surgical resection is preferable since total resection is followed by favorable prognosis. We present a 65-year-old patient with asymptomatic tumor of the right parietal bone. CT revealed osteolytic lesion that required total resection and skull repair. Histopathological analysis revealed intraosseous cavernous hemangioma.

Patient-specific quality assurance failure prediction with deep tabular models.

Purpose.Patient-specific quality assurance (PSQA) failures in radiotherapy can cause a delay in patient care and increase the workload and stress of staff. We developed a tabular transformer model based directly on the multi-leaf collimator (MLC) leaf positions (without any feature engineering) to predict IMRT PSQA failure in advance. This neural model provides an end-to-end differentiable map from MLC leaf positions to the probability of PSQA plan failure, which could be useful for regularizing gradient-based leaf sequencing optimization algorithms and generating a plan that is more likely to pass PSQA.Method.We retrospectively collected DICOM RT PLAN files of 968 patient plans treated with volumetric arc therapy. We constructed a beam-level tabular dataset with 1873 beams as samples and MLC leaf positions as features. We trained an attention-based neural network FT-Transformer to predict the ArcCheck-based PSQA gamma pass rates. In addition to the regression task, we evaluated the model in the binary classification context predicting the pass or fail of PSQA. The performance was compared to the results of the two leading tree ensemble methods (CatBoost and XGBoost) and a non-learned method based on mean-MLC-gap.Results.The FT-Transformer model achieves 1.44% Mean Absolute Error (MAE) in the regression task of the gamma pass rate prediction and performs on par with XGBoost (1.53 % MAE) and CatBoost (1.40 % MAE). In the binary classification task of PSQA failure prediction, FT-Transformer achieves 0.85 ROC AUC (compared to the mean-MLC-gap complexity metric achieving 0.72 ROC AUC). Moreover, FT-Transformer, CatBoost, and XGBoost all achieve 80% true positive rate while keeping the false positive rate under 20%.Conclusions.We demonstrated that reliable PSQA failure predictors can be successfully developed based solely on MLC leaf positions. FT-Transformer offers an unprecedented benefit of providing an end-to-end differentiable map from MLC leaf positions to the probability of PSQA failure.

Antibiotics increase aggression behavior and aggression-related pheromones and receptors in Drosophila melanogaster.

Aggression is a behavior common in most species; it is controlled by internal and external drivers, including hormones, environmental cues, and social interactions, and underlying pathways are understood in a broad range of species. To date, though, effects of gut microbiota on aggression in the context of gut-brain communication and social behavior have not been completely elucidated. We examine how manipulation of Drosophila melanogaster microbiota affects aggression as well as the pathways that underlie the behavior in this species. Male flies treated with antibiotics exhibited significantly more aggressive behaviors. Furthermore, they had higher levels of cVA and (Z)-9 Tricosene, pheromones associated with aggression in flies, as well as higher expression of the relevant pheromone receptors and transporters OR67d, OR83b, GR32a, and LUSH. These findings suggest that aggressive behavior is, at least in part, mediated by bacterial species in flies.

[Intraoperative ultrasound-assisted surgery of spinal tumors]. / Khirurgiya spinal'nykh opukholei s ispol'zovaniem intraoperatsionnogo ul'trazvukovogo issledovaniya.

OBJECTIVE: To improve technique of intraoperative ultrasound-assisted microsurgery of spinal tumors. MATERIAL AND METHODS: There were 68 patients with 70 spinal tumors who underwent intraoperative ultrasound-assisted resection between 2007 and 2018. Age of patients varied from 21 to 80 (mean 48.5±14.3). Intradural tumors were diagnosed in 54 (79.4%) patients (of them intramedullary in 16 (23.5%) and extramedullary in 38 (55.9%) cases). Fourteen patients (20.6%) had extradural tumors. Intraoperative ultrasound was used to determine localization, margins and structure of tumors, interrelations with neural structures, zones of dura opening and myelotomy. We also assessed quality of resection and spinal decompression. RESULTS: In surgery of spinal tumors, intraoperative ultrasound allows to localize the tumor with 95.3% sensitivity, determine the character of its growth, shape, size and internal structure. One can also differentiate the margins of neoplasm, control accuracy of approach, select the optimal zone for dura opening and myelotomy, objectively assess spinal cord and nerve roots decompression in real-time mode. Quality of intraoperative ultrasonography images is comparable to preoperative MRI, and even exceed resolution of MR scans in some cases. CONCLUSION: In our study, intraoperative ultrasound has proven to be a method complementing preoperative CT and MRI. This approach provides additional data in real-time mode to form a complete picture of surgical area, increase accuracy of manipulations and reduce surgical trauma.

[Lumbar microdiscectomy using intraoperative ultrasound]. / Poiasnichnaia mikrodiskéktomiia s primeneniem intraoperatsionnogo ul'trazvukovogo issledovaniia.

OBJECTIVE: To analyze advisability of intraoperative ultrasound during lumbar microdiscectomy. MATERIAL AND METHODS: We used intraoperative ultrasound to identify and localize various tissues and structures of the spinal canal, optimize surgical approach to the herniated disc and assess decompression of neural structures. The study was conducted in 48 patients with herniated discs of the lumbar spine who were operated for the period from 2014 to 2017. We used ultrasound devices BK Medical Pro Focus 2202 and BK Medical Flex Focus 400 with neurosurgical transducer Craniotomy 8862 and Burr-Hole 8863. Examinations were performed before and after flavotomy during neural decompression and after decompression. All patients underwent laboratory, clinical and instrumental survey. We analyzed changes of functional and neurological status and investigated various possibilities of intraoperative ultrasound and its impact on postoperative outcomes. RESULTS: Intraoperative ultrasound is valuable to verify various tissues and structures of the lumbar spine. On-line scanning gives a correct volumetric representation of the various anatomical structures and their spatial relationships that is essential for less traumatic and more radical surgery. CONCLUSION: Intraoperative ultrasound is easy, harmless, inexpensive and widely available method of intraoperative imaging. US data may be comparable with those of intraoperative CT and MRI. Intraoperative ultrasound during lumbar microdiscectomy results better postoperative outcomes.

KidsBrainIT: A New Multi-centre, Multi-disciplinary, Multi-national Paediatric Brain Monitoring Collaboration.

OBJECTIVES: Validated optimal cerebral perfusion pressure (CPP) treatment thresholds in children do not exist. To improve the intensive care unit (ICU) management of the paediatric traumatic brain injury (TBI) population, we are forming a new paediatric multi-centre collaboration to recruit standardised ICU data for running and reporting upon models for assessing autoregulation and optimal CCP (CPPopt). MATERIALS AND METHODS: We are adapting the adult BrainIT group's approach to develop a new Paediatric Brain Monitoring and Information Technology Group (KidsBrainIT), which will include a repository to store prospectively collected high-resolution physiological, clinical, and outcome data. In the first phase of this project there are 7 UK Paediatric Intensive Care Units, 1 Spanish, 1 Belgium, and 1 Romanian Centre interested in participating. In subsequent phases, we plan to open recruitment to other centres both within Europe, US and abroad. We are collaborating with the Leuven Group and plan to use their LAx (low-frequency autoregulation index), DATACAR (dynamic adaptive target of active cerebral autoregulation), CPPopt and visualisation methodologies. We also plan to use the continuous diffuse optical monitoring and tomography technology developed in Barcelona as an acute surrogate end-point for optimising brain perfusion. This technology allows non-invasive continuous monitoring of deep tissue perfusion and oxygenation in adults but its clinical application in infants and children with TBI has not been studied previously. RESULTS: We report on the current status of setting up this new collaboration and also on pilot analyses in two centres which are the basis of our rationale for the need for a prospective validation study of CPPopt in children. Specifically, we demonstrated that CPPopt varied with time for each patient during their paediatric intensive care unit (PICU) stay, and the median overall CPPopt levels for children aged 2-6 years, 7-11 years and 12-16 years were 68.83, 68.09, and 72.17 mmHg respectively. Among survivors and patients with favourable outcome (GOS 4 and 5), there were significantly higher proportions with CPP monitoring time within CPPopt (p = 0.04 and p = 0.01 respectively). CONCLUSIONS: There is a need and an interest in forming a multi-centre PICU collaboration for acquiring data and performing analyses for determining validated CPPopt thresholds in the paediatric TBI population. KidsBrainIT is being formed to meet that need.

Prostate-induced orgasms: A concise review illustrated with a highly relevant case study.

Current medical literature does not describe precisely the activation and mechanisms of prostate orgasms. This brief review describes what we know about the anatomy and physiology of the prostate and its involvement in reproduction and especially its stimulation for sexual recreation. It is illustrated with a highly relevant case history. Clin. Anat. 31:81-85, 2018. © 2017 Wiley Periodicals, Inc.

[Treatment of syringomyelia associated with adhesive arachnoiditis]. / Lechenie siringomielii, assotsiirovannoi s adgezivnym arakhnoiditom.

The prevalence of syringomyelia (SM) caused by adhesive arachnoiditis (AA) is 2 to 4 cases per 100000 population. Surgical treatment of this pathology usually includes implantation of shunts into the cyst cavity or opening and drainage of the cavity. In this case, SM continues to progress in 72-100% of patients. Unsatisfactory outcomes of this surgical approach necessitate searching for other treatment options. PURPOSE: To define the optimal amount of surgery for SM associated with AA and the criteria for assessment of surgery outcomes. MATERIAL AND METHODS: The authors treated 47 SM patients in the period from 2010 to 2015. Of these, 34 (72.3%) patients underwent surgery; a total of 40 operations were performed. The patients' age ranged from 18 to 64 years (mean, 43.5 years). Tethering of the spinal cord was eliminated in 25 patients; 9 patients underwent cyst shunting. RESULTS: Among operated patients, 5 patients had grade 1 arachnopathy, 13 patients had grade 2 arachnopathy, 12 patients had grade 3 arachnopathy, and 4 patients had grade 4 arachnopathy. The minimal postoperative follow-up period was 11 months. After shunting, the condition improved in 8 of 9 patients; in 7 patients, the condition returned to the baseline level within the first postoperative year; in 6 (66.7%) of these patients, the disease continued to progress. After surgical release of spinal cord tethering, satisfactory long-term results were achieved in 13 (86.6%) patients with grade 1-2 arachnopathy. In 3 (50%) patients with grade 3 arachnopathy, the condition was stabilized. Among patients with grade 4 arachnopathy, progression of the disease was stopped in 1 patient; the condition worsened in 2 (50%) patients. Among all the operated patients, complications developed in 7 patients. There were no lethal outcomes. CONCLUSIONS: In grade 1-2 arachnopathy, progression of SM after release of spinal cord tethering occurs only in 13.4% of patients. Therefore, release of spinal cord tethering is recommended for these patients. In grade 3-4 arachnopathy, the rate of relapse after this surgery is more than 80%. Therefore, given the simplicity and a lower risk of complications of cyst shunting, this procedure is advisable for these patients.

Safety, pharmacokinetics, and pharmacodynamics of RSLV-132, an RNase-Fc fusion protein in systemic lupus erythematosus: a randomized, double-blind, placebo-controlled study.

Blood-borne RNA circulating in association with autoantibodies is a potent stimulator of interferon production and immune system activation. RSLV-132 is a novel fully human biologic Fc fusion protein that is comprised of human RNase fused to the Fc domain of human IgG1. The drug is designed to remain in circulation and digest extracellular RNA with the aim of preventing activation of the immune system via Toll-like receptors and the interferon pathway. The present study describes the first clinical study of nuclease therapy in 32 subjects with systemic lupus erythematosus. The drug was well tolerated with a very favorable safety profile. The approximately 19-day serum half-life potentially supports once monthly dosing. There were no subjects in the study that developed anti-RSLV-132 antibodies. Decreases in B-cell activating factor correlated with decreases in disease activity in a subset of patients.

Frailty and osteoporosis in older women--a prospective study.

UNLABELLED: Despite sharing common risk factors and biological pathways, the relationship between frailty and osteoporosis (OP) is not clear. This prospective study has shown that frailty defined by the Vulnerable Elders Survey can predict a decrease in bone mineral density after 1 year. Thus, frail older women should be assessed for osteoporosis. INTRODUCTION: Frailty and OP share common risk factors such as age, sarcopenia, lack of physical activity, low body weight, and smoking. Despite shared risk factors and biological pathways, the relationship between frailty and OP is not clear. The purpose of our prospective study was to examine this relationship in a community sample of older women. METHODS: A sample of 235 community-dwelling women was assessed for demographic, medical, frailty and OP status at baseline, and after at least 1 year. Frailty was assessed using the Cardiovascular Health study (CHS) frailty phenotype and using the Vulnerable Elders Survey (VES-13). OP was measured using dual photon absorptiometry bone mineral density (BMD). Descriptive statistics and regression models were used. RESULTS: At baseline, 235 women with a mean age of 77.6 (SD = 5.4), body mass index (BMI) of 28.3 (SD = 5.2) kg/m(2), and BMD of 0.7 (SD = 0.2) g/cm(2)were assessed. No correlation was found between BMD and the CHS (BMD spine, r = 0.009, p = 0.889; BMD hips, r = 0.050, p = 0.473) or the VES-13 (BMD spine, r = 0.034, p = 0.605; BMD hips, r = -0.042, p = 0.537) frailty scales. One hundred fifty-two (63.9 %) women were assessed after 1 year. In a regression model, women who were frail at baseline (VES-13) were found to have a statistically significantly lower hip and spine BMD at follow-up (controlling for BMI) than women who were non-frail at baseline (p = 0.0393, hip; p = 0.0069, spine). CONCLUSIONS: Frailty status as defined by the VES-13 predicts a decrease in BMD after 1 year.

Comparative mortality risks of antipsychotic medications in community-dwelling older adults.

BACKGROUND: All antipsychotic medications carry warnings of increased mortality for older adults, but little is known about comparative mortality risks between individual agents. AIMS: To estimate the comparative mortality risks of commonly prescribed antipsychotic agents in older people living in the community. METHOD: A retrospective, claims-based cohort study was conducted of people over 65 years old living in the community who had been newly prescribed risperidone, olanzapine, quetiapine, haloperidol, aripiprazole or ziprasidone (n = 136 393). Propensity score-adjusted Cox proportional hazards models assessed the 180-day mortality risk of each antipsychotic compared with risperidone. RESULTS: Risperidone, olanzapine and haloperidol showed a dose-response relation in mortality risk. After controlling for propensity score and dose, mortality risk was found to be increased for haloperidol (hazard ratio (HR) = 1.18, 95% CI 1.06-1.33) and decreased for quetiapine (HR = 0.81, 95% CI 0.73-0.89) and olanzapine (HR = 0.82, 95% CI 0.74-0.90). CONCLUSIONS: Significant variation in mortality risk across commonly prescribed antipsychotics suggests that antipsychotic selection and dosing may affect survival of older people living in the community.

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study.

OBJECTIVE: To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes. DESIGN: Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality. SETTING: Nursing homes in the United States. PARTICIPANTS: 75,445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥ 65, were eligible for Medicaid, and lived in a nursing home in 2001-5. MAIN OUTCOME MEASURES: Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders. RESULTS: Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine. CONCLUSIONS: Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.

Increased penile expression of transforming growth factor and elevated systemic oxidative stress in rabbits with chronic partial bladder outlet obstruction.

There is a growing body of evidence to support the direct link between obstructive bladder dysfunction and erectile dysfunction (ED). However, there have been few pathophysiological studies to determine the relationship between lower urinary tract syndrome (LUTS) and ED. As the transforming growth factor-ß1 (TGF-ß1) that induces the synthesis of collagen in the penile tissues is critical for the development of ED, the first aim of this study was to investigate the expression of TGF-ß1 in the penis from male rabbits with chronic partial bladder outlet obstruction (PBOO). Besides, it has been suggested that oxidative stress plays a significant role in the pathophysiological mechanism of ED. Thus, the second aim of this study was to further investigate whether the urinary or serum oxidative stress markers are involved in chronic PBOO-induced penile dysfunction. A total of 16 male New Zealand White rabbits were separated equally into four groups: a control group and PBOO groups obstructed for 2, 4 and 8 weeks respectively. Using the RT-PCR and Western blot analysis, a progressive increase of TGF-ß1 in penis was found at 2, 4 and 8 weeks after obstruction. Moreover, the biomarkers for oxidative stress or oxidative damage were significantly detected in the penis of rabbits after PBOO, which include the enhancement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and plasma, plasma malondialdehyde (MDA) and total antioxidant capacity (TAC), as well as reduction of glutathione (GSH). On the basis of our results, the increase of TGF-ß1 and elevated systemic oxidative stress may play key roles to contribute to penile dysfunction after chronic PBOO.

Temporal trends in adherence to cardiovascular medications in elderly patients after hospitalization for heart failure.

Although the complexity of treatment regimens for patients with heart failure (HF) has increased over time because of the increased availability of efficacious medications, little is known about temporal trends in adherence to treatment regimens in these patients. We assessed trends in adherence to angiotensin-system blockers (ABs), ß-blockers (BBs), and spironolactone (SL) for HF in Medicare beneficiaries enrolled in two statewide pharmacy benefit programs from 1995 to 2004. The proportion of days covered (PDC) (%) was assessed after the first dispensing among users of an AB, BB, or SL. Proportions of full adherence (PDC >80%) did not change over time for ABs (54% in both 1996 and 2003) but increased slightly for BBs (from 47% in 1996 to 57% in 2003) and SL (from 31% in 1996 to 42% in 2003). Black race and dialysis treatment predicted poor adherence to any medications. Adherence to BBs and SL increased modestly over time, but overall nonadherence remained high.

Amnestic effect of cocaine after the termination of its stimulant action.

The effects of cocaine on memory are controversial. Furthermore, the psychostimulant action of cocaine can be a critical issue in the interpretation of its effects on learning/memory models. The effects of a single administration of cocaine on memory were investigated during the presence of its motor stimulating effect or just after its termination. The plus-maze discriminative avoidance task (PM-DAT) was used because it provides simultaneous information about memory, anxiety and motor activity. In Experiment I, mice received saline, 7.5, 10, 15 or 30 mg/kg cocaine 5 min before the training session. In Experiment II, mice were trained 30 min after the injection of saline, 7.5, 10, 15 or 30 mg/kg cocaine. In Experiment III, mice received 30 mg/kg cocaine 30 min pre-training and pre-test. In Experiment IV, mice received 30 mg/kg cocaine immediately post-training. Tests were always conducted 24 h following the training session. Given 5 min before training, cocaine promoted a motor stimulant effect at the highest dose during the training session but did not impair memory. When cocaine was injected 30 min pre-training, the drug did not modify motor activity, but produced marked amnestic effects at all doses tested. This amnesia induced by cocaine given 30 min pre-training was not related to a state-dependent learning because it was not abolished by pre-test administration of the drug. Post-training cocaine administration did not induce memory deficits either. Our results suggest that the post-stimulant phase is the critical moment for cocaine-induced memory deficit in a discriminative task in mice.

Myelosuppression and kinase selectivity of multikinase angiogenesis inhibitors.

BACKGROUND: Myelosuppression has been observed with several multikinase angiogenesis inhibitors in clinical studies, although the frequency and severity varies among the different agents. Inhibitors targeting vascular endothelial growth factor receptor (VEGFR) often inhibit other kinases, which may contribute to their adverse-event profiles. METHODS: Kinase selectivity of pazopanib, sorafenib, and sunitinib was evaluated in a panel of 242 kinases. Cellular potency was measured using autophosphorylation assays. Effect on human bone marrow progenitor growth in the presence of multiple growth factors was evaluated and correlated with the kinase selectivity. RESULTS: Sunitinib inhibited more kinases than pazopanib and sorafenib, at potencies within 10-fold of VEGFR-2. All three compounds potently inhibited VEGFR-2, platelet-derived growth factor receptor-beta and c-Kit, However, pazopanib was less active against Flt-3 in both kinase and cellular assays. The inhibitory properties of pazopanib, sorafenib, and sunitinib were dependent on the growth factor used to initiate bone marrow colony formation. Addition of stem cell factor and/or Flt-3 ligand with granulocyte-macrophage colony stimulating factor resulted in significant shifts in potency for sorafenib and sunitinib but less so for pazopanib. CONCLUSION: Activity against c-kit and Flt-3 by multikinase angiogenesis inhibitors provide a potential explanation for the differences in myelosuppression observed with these agents in patients.

Comparative gastrointestinal safety of weekly oral bisphosphonates.

SUMMARY: Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. INTRODUCTION: Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. METHODS: We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. RESULTS: A total of 10,420 new users were studied, mean age = 79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. CONCLUSIONS: We found no important difference in gastrointestinal safety between weekly oral bisphosphonates.