Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors

xlomafota.13 shared this article with you from Inoreader Feasibility and possible value of quantitative semi-automated diffusion weighted imaging volumetry of neuroblastic tumors Via Latest Results for Cancer Imaging Abstract Background To assess the feasibility and possible value of semi-automated diffusion weighted imaging (DWI) volumetry of whole neuroblastic tumors with apparent diffusion coefficient (ADC) map evaluation after neoadjuvant chemotherapy. Methods Pediatric patients who underwent surgical resection of neuroblastic tumors at our institution from 2013 to 2019 and who received a preoperative MRI scan with DWI after chemotherapy were included. Tumor volume was assessed with a semi-automated approach in DWI using a dedicated software prototype. Quantitative ADC values were calculated automatically of the total tumor volume after manual exclusion of necrosis. Manual segmentation in T1 weighted and T2 weighted sequences was used as reference standard for tumor volume comparison. The Student's t test was used for parametric data while the Wilcoxon rank sum test and the Kruskal-Wallis test were applied for non-parametric data. Results Twenty seven patients with 28 lesions (neuroblastoma (NB): n = 19, ganglioneuroblastoma (GNB): n = 7, ganglioneuroma (GN): n = 2) could be evaluated. Mean patient age was 4.5 ± 3.2 years. Median volume of standard volumetry (T1w or T2w) was 50.2 ml (interquartile range (IQR): 91.9 ml) vs. 45.1 ml (IQR: 98.4 ml) of DWI (p = 0.145). Mean ADC values (× 10− 6 mm2/s) of the total tumor volume (without necrosis) were 1187 ± 301 in NB vs. 1552 ± 114 in GNB/GN (p = 0.037). The 5th percentile of ADC values of NB (614 ± 275) and GNB/GN (1053 ± 362) provided the most significant difference (p = 0.007) with an area under the curve of 0.848 (p < 0.001). Conclusions Quantitative semi-automated DWI volumetry is feasible in neuroblastic tumors with integrated analysis of tissue characteristics by providing automatically calculated ADC values of the whole tumor as well as an ADC heatmap. The 5th percentile of the ADC values of the whole tumor volume proved to be the most significant parameter for differentiation of the histopathological subtypes in our patient cohort and further investigation seems to be worthwhile. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Adsorption of Methyl Blue onto Activated Carbon Derived from Red Oak ( Quercus rubra ) Acorns: a 2 6 Factorial Design and Analysis

xlomafota.13 shared this article with you from Inoreader Adsorption of Methyl Blue onto Activated Carbon Derived from Red Oak ( Quercus rubra ) Acorns: a 2 6 Factorial Design and Analysis Via Latest Results for Water, Air, & Soil Pollution Abstract In this study, red oak (Quercus rubra) acorns were used as precursor for preparing activated carbon by thermal activation. Red oak activated carbon (RAC) was evaluated for the removal of methyl blue (MB), using batch adsorption experiments. SEM images taken before and after adsorption experiments showed difference of surface morphology. A 26 full factorial design approach was used to determine the main and interaction effect of independent factors on dye removal rate. The six independent factors used for this study were sorbent dosage, initial dye concentration, pH, temperature, mixing rate (rpm), and mixing time. The response of this factorial design was percentage of dye removal (R%) from an aqueous solution. All independent factors showed significant influence. Initial dye concentration and adsorbent dose exhibited largest negative and positive influence on removal rate, respectively. The factorial experiments also demonstrated significan t synergistic/ antagonistic interaction between all these factors. Optimum conditions for adsorption were adsorbent dosage = 0.25 g/50 ml, initial dye concentration = 10.0 mg L 1, pH = 10, temperature = 45 °C, mixing rate = 175 rpm, and mixing time = 2.0 h. Under these conditions, response, dye removal rate R, was maximized, with a value of 97.18%. The findings of this study could be useful for industrial wastewater treatment systems. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effectiveness of low-level laser therapy on recovery from neurosensory disturbance after sagittal split ramus osteotomy: a systematic review and meta-analysis

xlomafota.13 shared this article with you from Inoreader Effectiveness of low-level laser therapy on recovery from neurosensory disturbance after sagittal split ramus osteotomy: a systematic review and meta-analysis Via Latest Results for Maxillofacial Plastic and Reconstructive Surgery Abstract Background Orthognathic surgery such as bilateral sagittal split ramus osteotomy (BSSRO) for the treatment of mandibular deformities is one of the most common procedures in maxillofacial operations that may lead to neurosensory disturbance. In this study, we aimed to evaluate the effectiveness of low-level laser therapy (LLLT) on augmenting recovery of neurosensory disturbance of inferior alveolar nerve (IAN) in patients who underwent BSSRO surgery. Methods A comprehensive literature search was conducted by two independent authors in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Embase, and Google Scholar electronic databases. Besides, a manual search of all textbooks and relevant articles were conducted. Searches took place in August 2020 and were limited to published and peer-reviewed articles from 2000 to 2020. All analysis was performed using the comprehensive meta-analysis (CMA) and the STATA MP (version:16) software. The weighted mean difference (WMD) using the inverse variance method and the standard mean difference (SMD) was considered for continuous variables. Results Seventy-four papers were retrieved after removing duplicate studies and finally, eight studies were assessed for qualitative synthesis and five for meta-analysis. Totally, 94 patients were included in the meta-analysis. Based on the meta-analysis, it was shown that LLLT was not effective in a short interval (0 to 48 h) after surgery, but in a period of more than 1 month after surgery, the positive results of treatment can be observed strikingly. Also, LLLT side/group showed no significant difference in some aspects of neurosensory recovery such as thermal sensation compared to the placebo side/group. Conclusions The meta-analysis of randomized controlled trials revealed that LLLT generally improves IAN sensory disturbance caused by BSSRO. Further high-quality clinical trials with longer follow-up periods and larger sample sizes are recommended. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

An update on the pathogenesis of Hashimoto’s thyroiditis

xlomafota.13 shared this article with you from Inoreader An update on the pathogenesis of Hashimoto's thyroiditis Via Latest Results for Journal of Endocrinological Investigation Abstract It is 70 years since Noel Rose embarked on his pioneering studies that lead to the discovery of autoimmune thyroiditis and the elucidation of Hashimoto's thyroiditis. This short review to honour his passing focuses on the developments in our understanding of the causes and pathogenesis of HT over the last five years. Recent genetic studies have reported heritability estimates for HT and associated diseases for the first time, and emphasised the complexity of the genetic factors involved, including monogenic forms of HT. Environmental factors continue to be elucidated, especially as a side effect of drugs which modulate the immune system therapeutically. Regarding pathogenetic mechanisms, multiple cytokine networks have been identified which involve the thyroid cells in a circuit of escalating proinflammatory effects, such as the expression of inflammasome components, and an array of different defects in T regulatory cells may underlie the loss of self-tole rance to thyroid autoantigens. Finally, a number of studies have revealed fresh insights into disease associations with HT which may have both pathological and clinical significance, the most intriguing of which is a possible direct role of the autoimmune process itself in causing some of the persistent symptoms reported by a minority of patients with levothyroxine-treated HT. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases

xlomafota.13 shared this article with you from Inoreader The Roles of Insulin-Like Growth Factor Binding Protein Family in Development and Diseases Via Latest Results for Advances in T... Abstract The insulin-like growth factor (IGF) system comprises ligands of IGF-I/II, IGF receptors (IGFR), IGF binding proteins (IGFBPs), and IGFBP hydrolases. The IGF system plays multiple roles during various disease development as IGFs are widely involved in cell proliferation and differentiation through regulating DNA transcription. Meanwhile, IGFBPs, which are mainly synthesized in the liver, can bind to IGFs and perform two different functions: either inhibition of IGFs by forming inactive compounds with IGF or enhancement of the function of IGFs by strengthening the IGF–IGFR interaction. Interestingly, IGFBPs may have wider functions through IGF-independent mechanisms. Studies have shown that IGFBPs play important roles in cardiovascular disease, tumor progression, fetal growth, and neuro-nutrition. In this review, we emphasize that different IGFBP family members have common or unique functions in numerous diseases; moreover, IGFBPs may serve as biomarkers for dis ease diagnosis and prediction. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review

xlomafota.13 shared this article with you from Inoreader Efficacy of Tofacitinib in the Treatment of Psoriatic Arthritis: A Systematic Review Via Latest Results for Advances in T... Abstract Introduction Therapeutic approaches for psoriatic arthritis (PsA) include non-pharmacologic therapies, symptomatic treatments, tumor necrosis factor inhibitors, interleukin inhibitors, cytotoxic T lymphocyte antigen 4 immunoglobulin, and Janus kinase inhibitors. This systematic review aimed to provide complete and up-to-date information on efficacy of tofacitinib in the treatment of PsA, giving special attention to non-skin manifestations (peripheral arthritis, axial disease, enthesitis, and dactylitis). Methods A search of studies published between January 2016 and June 2020 was carried out on PubMed and Google Scholar. Results The number of studies with tofacitinib in PsA is limited and most of them are post hoc analyses from OPAL Broaden and OPAL Beyond. Tofacitinib has been demonstrated to be efficacious for the treatment of all disease manifestations in PsA. Superior effectivity to placebo is achieved at the earliest time point evaluated, and maintained over time. Patients who switch from placebo to tofacitinib show the same improvements; however, the time to initial response is faster in patients who firstly receive tofacitinib, compared with those switching subsequently. Additional data suggest that tofacitinib may be also effective for the treatment of the axial domain. Conclusions Tofacitinib has been demonstrated to be efficacious for the treatment of peripheral and axial involvement, enthesitis, and dactylitis manifestation in PsA. Further prospective and long-term studies are required to corroborate and complete the present results. Similarly, real-world evidence is also necessary to complement the information obtained in clinical trials, and thereby to have a better overview of real efficacy and safety of the drug. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Time to Treatment Discontinuation in German Patients with Schizophrenia: Long-Acting Injectables versus Oral Antipsychotics

xlomafota.13 shared this article with you from Inoreader Time to Treatment Discontinuation in German Patients with Schizophrenia: Long-Acting Injectables versus Oral Antipsychotics Via Latest Results for Clinical Drug Investigation Abstract Background and Objective Long-acting injectable antipsychotics (LAIs) are associated with better treatment adherence and persistence than oral antipsychotics (OAPs) in patients with schizophrenia. However, real-world evidence assessing the impact of treatment with LAIs in Germany is limited. To fill this gap, we compared antipsychotic medication adherence and risk of treatment discontinuation (TD) among schizophrenia patients newly initiated on LAI or who switched their OAP regimen (overall cohort; OC). Methods Claims data of German schizophrenia patients who initiated LAIs or switched their OAP during 2012–2016 (index date) were retrospectively analyzed. Treatment switch was defined as add-on medication to existing prescription or terminating the existing prescription and initiating another OAP. Adherence and time to treatment discontinuation (TTD) were estimated. Determinants of treatment discontinuation were analyzed using two Cox regression models. Model 1 controlled for age, sex, and Charlson Comorbidity Index (CCI); model 2 also included insurance status, and medication, visit, and psychiatric inpatient stay costs. Sensitivity analysis on patients who terminated existing prescriptions and initiated new OAPs (complete switch cohort; CSC) was performed. Results In OC (n = 2650), LAI users had better adherence (35.4% vs. 11.6%), persistence (no 60-day gap; 40.7% vs. 19.8%), and longer TTD (median [95% confidence interval (CI)] 216 [193–249] vs. 50 [46–56] days) than OAP users. OAP usage (hazard ratio [HR] 1.89, 95% CI 1.73–2.06; p < 0.001) and greater CCI (HR 1.04, 95% CI 1.00–1.07; p = 0.023) were associated with greater risk of TD in model 1. Model 2 showed similar results. LAI users in CSC also had better adherence, persistence, and longer TTD. In CSC too, OAP usage and greater CCI were associated with greater risk of TD in model 1, but only CCI was significant in model 2. Higher pre-index psychiatric inpatient costs were associated with lower risk of TD (HR 0.99, 95% CI 0.98–1.00; p = 0.014). Limitations Inherent limitations of claims data and lack of control on OAP administration may have influenced the results. Conclusion This real-world study associates LAIs with better medication adherence and lower antipsychotic discontinuation risk than OAPs. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects

xlomafota.13 shared this article with you from Inoreader First-in-Man Safety, Tolerability, and Pharmacokinetics of a Novel and Highly Selective Inhibitor of Matrix Metalloproteinase-12, FP-025: Results from Two Randomized Studies in Healthy Subjects Via Latest Results for Clinical Drug Investigation Abstract Background and Objectives Matrix metalloproteinases (MMPs) are proteases with different biological and pathological activities, and many have been linked to several diseases. Targeting individual MMPs may offer a safer therapeutic potential for several diseases. We assessed the safety, tolerability, and pharmacokinetics of FP-025, a novel, highly selective oral matrix metalloproteinase-12 inhibitor, in healthy subjects. Methods Two randomized, double-blind, placebo-controlled studies were conducted. Study I was a first-in-man study, evaluating eight single ascending doses (SADs) (50–800 mg) in two formulations: i.e., neat FP-025 in capsule (API-in-Capsule) and in an amorphous solid dispersion (ASD-in-Capsule) formulation. In Study II, three multiple ascending doses (MADs) (100, 200, and 400 mg, twice daily) of FP-025 (ASD-in-Capsule) were administered for 8 days, including a food-effect evaluation. Results Ninety-six subjects were dosed. Both formulations were well tolerated with one adverse event (AE) reported in the 800 mg API-in-Capsule SAD group and seven AEs throughout the MAD groups. The exposure to FP-025 was low with the API-in-Capsule formulation; it increased dose-dependently with the ASD-in-Capsule formulation, with which exposure to FP-025 increased in a greater-than-dose-proportional manner at lower doses (≤ 100 mg) but less proportionally at higher doses. The elimination half-life (t1/2) was between 6 (Study I) and 8 h (Study II). Accumulation of FP-025 was approximately 1.7-fold in the MAD study. Food intake delayed the rate of absorption, but without effect in the extent of absorption or bioavailability. Conclusion FP-025 was well tolerated and showed a favorable pharmacokinetic profile following ASD-in-Capsule dosing. Efficacy studies in target patient populations, including asthma, chronic obstructive pulmonary disease (COPD), and pulmonary fibrosis, are warranted. Trial registration number: www.clinicaltrials.gov: NCT02238834 (Study I); NCT03304964 (Study II). Trial registration date: Study I was registered on 12 September 2014 while study II was registered on 9 October 2017. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR -Activating Mutations

xlomafota.13 shared this article with you from Inoreader Updated Overall Survival in a Randomized Study Comparing Dacomitinib with Gefitinib as First-Line Treatment in Patients with Advanced Non-Small-Cell Lung Cancer and EGFR -Activating Mutations Via Latest Results for Drugs Abstract Background ARCHER 1050, an ongoing, randomized, open-label, phase III trial of dacomitinib versus gefitinib in newly diagnosed patients with advanced non-small-cell lung cancer (NSCLC) and an EGFR-activating mutation, reported significant improvement in overall survival (OS) with dacomitinib. Objective This paper reports an updated OS analysis of ARCHER 1050 after an extended follow-up. Patients and methods In this multinational, multicenter trial, adults (aged ≥ 18 years or ≥ 20 years in Japan and Korea) with newly diagnosed NSCLC and EGFR mutation (exon 19 deletion or exon 21 L858R substitution), and no history of central nervous system metastases, were randomized 1:1 to receive dacomitinib 45 mg/day (n = 227) or gefitinib 250 mg/day (n = 225). Randomization was stratified by race and EGFR mutation type. An ad hoc updated analysis of OS was conducted at the protocol-defined cut-off of 48 months from first dosing of the last enrolled patient (13 May 2019). Results After a median follow-up of 47.9 months, 133 (58.6%) patients had died in the dacomitinib arm and 152 (67.6%) in the gefitinib arm. The hazard ratio (HR) for OS was 0.748 (95% CI 0.591–0.947; two-sided P = 0.0155); median OS was 34.1 months with dacomitinib versus 27.0 months with gefitinib. The HR for OS in patients with dose reduction(s) in the dacomitinib arm (n = 154) compared with all patients in the gefitinib arm was 0.554 (95% CI 0.420–0.730); median OS was 42.5 months for patients with dose reduction(s) in the dacomitinib arm. The most common adverse events were diarrhea (87.7%), paronychia (61.7%), dermatitis acneiform (49.3%), and stomatitis (43.6%) with dacomitinib, and diarrhea (55.8%) and alanine aminotransferase increased (40.2%) with gefitinib. Conclusions The OS benefit from first-line treatment with dacomitinib versus gefitinib was maintained after extended follow-up in patients with advanced NSCLC with EGFR-activating mutations. ClinicalTrials.gov NCT01774721 (registered 24 January 2013). View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A virtual reality-based data analysis for optimizing freehand external ventricular drain insertion

xlomafota.13 shared this article with you from Inoreader A virtual reality-based data analysis for optimizing freehand external ventricular drain insertion Via Latest Results for International Journal of Computer Assisted Radiology and Surgery Abstract Purpose This work exploits virtual reality technique to analyse and optimize the preoperative planning of freehand external ventricular drain (EVD) insertion. Based on the three-dimensional (3D) virtual brain models, neurosurgeons can directly observe the anatomical landmarks and complete the simulated EVD insertion. Simulation data is used to optimize preoperative planning parameters to ensure the surgical performance. Methods We used the computed tomography (CT) scans to construct the 3D virtual brain models. A group of EVD insertions were simulated by inserting virtual catheters at different entry points. The key parameters including the location of entry point, the catheter orientation, the catheter tip position on lateral ventricles, and the insertion depth were recorded. A data analysis method was then applied to optimize these parameters, resulting in the optimal parameters for the EVD insertion. Results When the lateral distance of entry point ranged from 2.5 to 3 cm, the success rate of 204 cases was 97.79%, which was higher than that of the classic method (59.52%). The optimal insertion angle towards the sagittal plane ranged from 10.46° to 12.73°. To prevent penetrating the lateral ventricles, the insertion depth was optimized to be 3.28 to 4.58 cm. Conclusions The proposed data analysis method is helpful to optimize the key parameters of the preoperative planning, and provides useful references for neurosurgeons to perform the freehand EVD insertion. The EVD insertion experiments on 3D printing model had a success rate of 93.75%, which verified the effectiveness of the data analysis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A new platform for laparoscopic training: initial evaluation of the ex-vivo live multivisceral training device

xlomafota.13 shared this article with you from Inoreader A new platform for laparoscopic training: initial evaluation of the ex-vivo live multivisceral training device Via Latest Results for Surgical Endoscopy Abstract Background Various training models have been developed for laparoscopic training. Inanimate models including cadavers, ex-vivo simulator, and virtual reality (VR), are less realistic and often fail to display specific events such as bleeding, bile leakage, etc. Animal models provide more realistic experience, but constraints like cost involved, anesthetic requirement, and ethical approval have limited its application. We have designed a new training ex-vivo simulator—Smagister to address these issues. Methods The Smagister consists of a normothermic machine perfusion platform, multivisceral organ of porcine abdominal cavity (liver, gallbladder, pancreas, stomach, intestine, kidney, uterus, bladders, etc.), high-definition display, and software system. Blood gas analysis and number of peristalsis per hour were recorded. A questionnaire was used to subjectively assess vitality of the organ cluster every hour. Three laparoscopic procedures including cholecystectomy (LC), enterotomy closure (LEC) and hepatectomy (LLR) were performed on Smagister, with demonstration of specific events for each procedure. Six experts compared the procedures with actual surgery in terms of feasibility to complete procedures and demonstration of complications. Results The fluctuation of perfusate glucose (6.1–8.2 mmol/L) and lactate (5.82–6.55 mmol/L) suggested metabolic function of the multivisceral organs. The mean number of peristalsis was 2.2/min. The simulated surgical view and anatomic structures closely resembled actual surgery during continuous perfusion (3.5 ± 1.0, 3.8 ± 0.8, respectively). The evaluation scores of haptic feedbacks were 3.8 ± 0.8, resembling live tissue handling. LC, LEC, and LLR were performed well on the Smagister, with clear display of the specific events. All six experts considered Smagister as a suitable training modality for both basic and advanced laparoscopic surgery. Conclusion The amalgamation of live animal model and ex-vivo simulation in Smagister centralizes the virtue of both modalities, expands the training field, and provides high-fidelity laparoscopic training for both novice and senior surgeons. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.