Multimodal assessment improves neuroprognosis performance in clinically unresponsive critical-care patients with brain injury.

Accurately predicting functional outcomes for unresponsive patients with acute brain injury is a medical, scientific and ethical challenge. This prospective study assesses how a multimodal approach combining various numbers of behavioral, neuroimaging and electrophysiological markers affects the performance of outcome predictions. We analyzed data from 349 patients admitted to a tertiary neurointensive care unit between 2009 and 2021, categorizing prognoses as good, uncertain or poor, and compared these predictions with observed outcomes using the Glasgow Outcome Scale-Extended (GOS-E, levels ranging from 1 to 8, with higher levels indicating better outcomes). After excluding cases with life-sustaining therapy withdrawal to mitigate the self-fulfilling prophecy bias, our findings reveal that a good prognosis, compared with a poor or uncertain one, is associated with better one-year functional outcomes (common odds ratio (95% CI) for higher GOS-E: OR = 14.57 (5.70-40.32), P < 0.001; and 2.9 (1.56-5.45), P < 0.001, respectively). Moreover, increasing the number of assessment modalities decreased uncertainty (OR = 0.35 (0.21-0.59), P < 0.001) and improved prognostic accuracy (OR = 2.72 (1.18-6.47), P = 0.011). Our results underscore the value of multimodal assessment in refining neuroprognostic precision, thereby offering a robust foundation for clinical decision-making processes for acutely brain-injured patients. ClinicalTrials.gov registration: NCT04534777 .

Effect of Surface Treatment on Titanium Surface Free Energy and its Relation to Bacterial Activity: A Systematic Review.

The surface properties of titanium dental implants, such as wettability and surface free energy, influence the adhesion of microorganisms responsible for inflammation and infection of peri-implant tissues. This systematic review aimed to investigate the relationship of titanium surface treatments, surface free energy/wettability property and its relationship with bacterial activity. This systematic review followed PRISMA 2020 (Preferred Reporting Items for Systematic Review and MetaAnalysis) guidelines and was registered in the OpenScience Framework (osf.io/ejnct). PubMed, ScienceDirect, Embase, and Scopus library databases were used from custom search strategies. Inclusion criteria were research articles that studied titanium or its alloys for wetting property and its correlation with adhesion. Of the 697 articles initially identified, 27 were selected after full-text reading and application of the eligibility criteria. In general, the evaluated studies showed that regardless of the surface treatment, there was an increase in titanium hydrophilicity and concomitant reduction in bacterial adhesion. The surface treatment of titanium results in higher surface free energy and lower bacterial adhesion. Hydrophilic titanium surfaces prevent adhesion of hydrophobic bacteria in early stages.

Effects on the accelerating electron bunches due to the presence of sulfur hexafluoride or air in the linac waveguide.

Sulfur hexafluoride gas (SF6) is used as a dielectric insulator in the acceleration process of certain medical linear accelerator waveguides. Nevertheless, some innovative development and investigation cases require intervention in the linear accelerator or, specifically, on the waveguide, which could affect the sealing of the device. In this regard, vacuum sealing systems can be compromised, affecting the properties of the radiation beams produced. The presence of sulfur hexafluoride or air inside the VARIAN 6/100 waveguide was investigated under different pressure conditions and non-uniform electric fields, adapting Monte Carlo simulation techniques for modeling radiation transport coupled with electric fields. Obtained results indicated the suitability of the proposed approach, while comparisons with theoretical approaches and experimental evidence supported the model's consistency.

Study of the effect of the substitution of Fe by Ti on the microstructure and the physical properties of the perovskite system La0.67Ca0.2Ba0.13Fe1-xTixO3 with x = 0 and 0.03 at low temperatures.

La0.67Ca0.2Ba0.13Fe1-xTixO3 samples (x = 0 and 0.03) were synthesized by the auto-combustion method. Analysis of XRD diffractograms revealed that these compounds crystallize in the cubic system with the space group Pm3̄m. The dielectric properties have been studied in the 102-106 frequency range and the 120-280 K temperature range. Analysis of AC conductivity shows that the conduction mechanisms are of polaronic origin and that they are co-dominated by the NSPT and OLPT models. The monotonic increase in conductivity with increasing temperature results from the reduction of defect centers and the increase in charge carrier mobility. Such variation is consistent with impedance variation at different frequencies and temperatures indicating semiconductor behavior. Nyquist diagrams are characterized by the appearance of semi-circular arcs. These spectra are modeled in terms of equivalent electrical circuits confirming the contribution of grains (Rg//CPEg) and grain boundaries (Rgb//CPEgb). The dielectric analysis showed an evolution of the dielectric constant in accordance with Koop's theory and the phenomenological model of Maxwell-Wagner. The low conductivity and the high values of the real permittivity at low frequency make our compounds potential candidates for energy storage and applications for electronic devices and microwaves.

RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance.

The growing global epidemic of obesity and type 2 diabetes mellitus has determined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the Western world and a leading cause of liver transplantation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close association between insulin resistance (IR), dysbiosis, and steatosis. However, all the mechanisms that lead to impaired permeability, inflammation, and fibrosis have not been fully clarified. Recently, new possible treatment modalities have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (polyphenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NAFLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the therapeutic strategies currently in use.

Research on the physical properties of LiMn0.5Fe2O4 spinel ferrites by the combination of optical, magnetic, and dielectric behaviors.

Ferrite compounds have recently attracted significant interest because of their multifunctional properties. This work investigates the optical, magnetic, and dielectric properties of a LiMn0.5Fe2O4 ferrite prepared by a solid-state reaction. Raman spectroscopy analysis substantiated the presence of the 5 active modes representing the vibration of the oxygen anion at both tetrahedral and octahedral sites. The direct optical band gap was estimated to be 3.51 eV, which indicates the semiconductor behavior of the compound. A theoretical modulation of the hysteresis loop was done to confirm the dominance of the ferromagnetic contribution over the antiferromagnetic one. Furthermore, the dielectric permittivity result indicated a colossal value of the order of 103. The dielectric losses are characterized by the Giuntini law to extract the relaxation process, which is hidden by the DC-conductivity process. Our results indicate the potential of LiMn0.5Fe2O4 for applications in multifunctional devices.

What is the real morbidity after emergency colectomy for Crohn's disease? A propensity score matched study.

BACKGROUND: In the inflammatory bowel disease literature, emergency surgery for Crohn's disease (CD) is associated with worse postoperative outcomes as compared to elective surgery. Previous studies have compared heterogeneous groups only. We hypothesized that this association would be lost after matched analysis. We aimed to compare matched CD patients undergoing elective vs emergency surgery. METHODS: The National Surgical Quality Improvement database (01/2005-12/2019) was utilized to identify adult CD surgical patients. Univariate and conditional logistic regression models were used to analyze unmatched and matched cohorts. Propensity-score matching was performed to match emergency to non-emergency patients 1:1. Our primary outcome was a composite of any complication. Our secondary endpoints were hospital readmission, unplanned reoperation and 30-day morbidity and mortality. RESULTS: In the unmatched analyses (n = 12,181/95.28% elective and n = 603/4.72% emergency) of Crohn's patients undergoing colectomy, 20% of elective and 42% of emergency patients experienced a complication (p < 0.001). Over 20 outcomes measured including length of stay (LOS), readmission, infections and respiratory, cardiovascular and renal complications, were worse in the emergency cohort. In the matched analyses (n = 400 emergency/400 elective patients) only the categories of any complication (OR 1.44, 1.06-1.96 95% CI, p = 0.02), any surgical site infection (SSI, OR 1.53, 1.07-2.19 95% CI, p = 0.02), superficial SSI (OR 2.25, 1.14-4.44 95% CI, p = 0.02), organ space SSI (1.58 OR 1.04-2.4 95% CI, p = 0.03), unplanned intubation (OR 5.0, 1.45-17.27 95% CI, p = 0.01), ventilation > 48 h (OR 9.0, 1.4-38.79 95% CI, p = 0.003) and septic shock (OR 4.5, 1.86-10.9 95% CI, p < 0.001) were higher in the emergency cohort. CONCLUSIONS: Matching CD patients resulted in a loss of the observed increase in cardiovascular and renal complications, reoperation and LOS following emergency surgery; however, SSIs and respiratory complications remained increased despite matching.

Investigation of temperature and frequency dependence of the dielectric properties of multiferroic (La0.8Ca0.2)0.4Bi0.6FeO3 nanoparticles for energy storage application.

In this work we synthesized the multifunctional (La0.8Ca0.2)0.4Bi0.6FeO3 material using a sol-gel process. Structural and morphologic investigations reveal a Pnma perovskite structure at room temperature with spherical and polygonal nanoparticles. A detailed study of the temperature dependence of the dielectric and electrical properties of the studied material proves a typical FE-PE transition with a colossal value of real permittivity at 350 K that allows the use of this material in energy storage devices. Thus, the investigation of the frequency dependence of the ac conductivity proves a correlated barrier hopping (CBH) conduction mechanism to be dominant in the temperature ranges of 150-170 K; the two observed Jonscher's power law exponents, s 1 and s 2 between 180 K and 270 K correspond to the observed dispersions in the ac conductivity spectra in this temperature region, unlike in the temperature range of 250-320 K, the small polaron tunnel (NSPT) was considered the appropriate conduction model.

Minimally invasive Ivor Lewis oesophagectomy with trans-hiatal oesophageal transection and transabdominal specimen extraction for Siewert II oesophagogastric cancer.

The optimal surgical procedure for Siewert II oesophagogastric junction cancer is still debated. The minimally invasive Ivor Lewis technique can be considered the most adequate intervention from the oncological perspective but it is still contested owing to its technical difficulties. To allow an easier thoracoscopic stage during the procedure, we performed it with laparoscopic trans-hiatal oesophageal transection and transabdominal extraction. An 80-year-old man with stage 3 Siewert II oesophagogastric junction adenocarcinoma not suitable for neoadjuvant therapy underwent minimally invasive Ivor Lewis oesophagectomy with two-field lymphadenectomy, using a laparoscopic and thoracoscopic approach in prone position. The trans-hiatal oesophageal resection permitted easy extraction of a transabdominal specimen and frozen section examination. The prone position, together with the absence of the specimen in the operative field, allowed easier mediastinal node dissection and oesophagogastric anastomosis with better visualisation. The postoperative course was uneventful. Pathology showed a G3-pT3, N2 adenocarcinoma with 6/30 metastatic lymph nodes.

Intestinal-type mucinous ovarian carcinoma arising from a seromucinous precursor lesion.

OBJECTIVE: Mucinous ovarian carcinoma is a tumor with gastrointestinal differentiation, which is not associated with endometrial-type (endometriotic or seromucinous) precursors. Here, we describe a peculiar case of mucinous ovarian tumor with intestinal differentiation arising in a seromucinous lesion, which may represent a distinct entity. CASE PRESENTATION: A 58-year woman underwent surgery due to a 14.5-cm ovarian mass with lymph nodal, peritoneal, omental and colorectal involvement. Histological examination with ancillary immunohistochemical analysis has been performed. Histologically, the mass was a carcinoma with intestinal differentiation and expansile growth pattern, arising in a seromucinous cystadenoma with intestinal metaplasia. Both the carcinoma and the metaplasia showed loss of Müllerian markers (estrogen and progesterone receptors, PAX8) and positivity for intestinal-type markers (cytokeratin 20, CDX2). CONCLUSIONS: Our case may represent the ovarian counterpart of endometrial gastrointestinal-type carcinoma, which is an aggressive entity developing from gastrointestinal metaplasia of the endometrial epithelium. Acknowledging the existence of such entity might be relevant in terms of diagnosis and patient management.

Machine learning applied to ambulatory blood pressure monitoring: a new tool to diagnose autonomic failure?

BACKGROUND: Autonomic failure (AF) complicates Parkinson's disease (PD) in one-third of cases, resulting in complex blood pressure (BP) abnormalities. While autonomic testing represents the diagnostic gold standard for AF, accessibility to this examination remains limited to a few tertiary referral centers. OBJECTIVE: The present study sought to investigate the accuracy of a machine learning algorithm applied to 24-h ambulatory BP monitoring (ABPM) as a tool to facilitate the diagnosis of AF in patients with PD. METHODS: Consecutive PD patients naïve to vasoactive medications underwent 24 h-ABPM and autonomic testing. The diagnostic accuracy of a Linear Discriminant Analysis (LDA) model exploiting ABPM parameters was compared to autonomic testing (as per a modified version of the Composite Autonomic Symptom Score not including the sudomotor score) in the diagnosis of AF. RESULTS: The study population consisted of n = 80 PD patients (33% female) with a mean age of 64 ± 10 years old and disease duration of 6.2 ± 4 years. The prevalence of AF at the autonomic testing was 36%. The LDA model showed 91.3% accuracy (98.0% specificity, 79.3% sensitivity) in predicting AF, significantly higher than any of the ABPM variables considered individually (hypotensive episodes = 82%; reverse dipping = 79%; awakening hypotension = 74%). CONCLUSION: LDA model based on 24-h ABPM parameters can effectively predict AF, allowing greater accessibility to an accurate and easy to administer test for AF. Potential applications range from systematic AF screening to monitoring and treating blood pressure dysregulation caused by PD and other neurodegenerative disorders.

Linear energy transfer characterization of five gel dosimeter formulations for electron and proton therapeutic beams.

Gel dosimeters, including radiochromic types like Fricke, as well as polymer formulations, are considered to be the only reliable option for accurate 3D dosimetry. Nevertheless, their implementation in daily clinical quality assurance still remains strongly limited for a few high specialized radiotherapy centres. Although gel dosimeters present very good water-equivalence due to their inherent chemical and isotopic compositions, addressing the corresponding dosimetry outputs is highly challenging, needing careful assessment in terms of the different radiation qualities involved in the mixed field. Accurate estimations of the linear energy transfer for each gel dosimeter formulation stands as a baseline for further accurate dose deconvolution in mixed radiation fields. The present study reports on the linear energy transfer characterization of five different gel dosimeter formulations, Fricke, Itabis, Magic, Nipam, and Pagat, for electron and proton therapeutic beams as obtained by Monte Carlo approaches, along with experimental results for validation purposes. The linear energy transfer, as a function of beam quality and penetration depth, is obtained for electron and proton therapeutic beams remarking the presence of non-negligible variations, which need to be accounted for a further accurate implementation of gel dosimetry as well as for precise dose deconvolution in mixed radiation fields.

Fricke gel xylenol orange dosimeter layers for stereotactic radiosurgery: A preliminary approach.

Investigations regarding the feasibility, reliability, and accuracy of Fricke gel dosimeter layers for stereotactic radiosurgery are presented. A representative radiosurgery plan consisting of two targets has been investigated. Absorbed dose distributions measured using radiochromic films and gelatin Fricke Gel dosimetry in layers have been compared with dose distributions calculated by using a treatment planning system and Monte Carlo simulations. The different dose distributions have been compared by means of the gamma index demonstrating that gelatin Fricke gel dosimeter layers showed agreements of 100%, 100%, and 93%, with dose and distance tolerances of 2% and 2 mm, with respect to film dosimetry, treatment planning system and Monte Carlo simulations, respectively. The capability of the developed system for three-dimensional dose mapping was shown, obtaining promising results when compared with well-established dosimetry methods. The obtained results support the viability of Fricke gel dosimeter layers analyzed by optical methods for stereotactic radiosurgery.

Skip pattern approach toward the early access of innovative anticancer drugs.

BACKGROUND: With the rapid development of innovative anticancer treatments, the optimization of tools able to accelerate the access of new drugs to the market by the regulatory authority is a major issue. The aim of the project was to propose a reliable methodological pathway for the assessment of clinical value of new therapeutic innovative options, to objectively identify drugs which deserve early access (EA) priority for solid and possibly in other cancer scenarios, such as the hematological ones. MATERIALS AND METHODS: After a comprehensive review of the European Public Assessment Report of 21 drugs, to which innovation had previously been attributed by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA), an expert panel formulated an algorithm for the balanced use of three parameters: Unmet Medical Need (UMN) according to AIFA criteria, Added Benefit (AB) according to the European Society for Medical Oncology's Magnitude of Clinical Benefit Scale (ESMO-MCBS) criteria and Quality of Evidence (QE) assessed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) method. By sequentially combining the above indicators, a final priority status (i.e. EA or not) was obtained using the skip pattern approach (SPA). RESULTS: By applying the SPA to the non-curative setting in solid cancers, the EA status was obtained by 5 out of 14 investigated drugs (36%); by enhancing the role of some categories of the UMN, additional 4 drugs, for a total of 9 (64%), reached the EA status: 2 and 3 drugs were excluded for not achieving an adequate score according to AB and QE criteria, respectively. For hematology cancer, only the UMN criteria were found to be adequate. CONCLUSIONS: The use of this model may represent a reliable tool for assessment available to the various stakeholders involved in the EA process and may help regulatory agencies in a more comprehensive and objective definition of new treatments' value in these contexts. Its generalizability in other national contexts needs further evaluation.

Chemotherapy toxicity and activity in patients with pancreatic ductal adenocarcinoma and germline BRCA1-2 pathogenic variants (gBRCA1-2pv): a multicenter survey.

BACKGROUND: Germline BRCA1-2 pathogenic variants (gBRCA1-2pv)-related pancreatic ductal adenocarcinoma (PDAC) showed increased sensitivity to DNA cross-linking agents. This study aimed at exploring safety profile, dose intensity, and activity of different chemotherapy regimens in this setting. PATIENTS AND METHODS: gBRCA1-2pv PDAC patients of any age and clinical tumor stage who completed a first course of chemotherapy were eligible. A descriptive analysis of chemotherapy toxicity, dose intensity, response, and survival outcomes was performed. RESULTS: A total of 85 gBRCA1-2pv PDAC patients treated in 21 Italian centers between December 2008 and March 2021were enrolled. Seventy-four patients were assessable for toxicity and dose intensity, 83 for outcome. Dose intensity was as follows: nab-paclitaxel 72%, gemcitabine 76% (AG); cisplatin 75%, nab-paclitaxel 73%, capecitabine 73%, and gemcitabine 65% (PAXG); fluorouracil 35%, irinotecan 58%, and oxaliplatin 64% (FOLFIRINOX). When compared with the literature, grade 3-4 neutropenia, thrombocytopenia, and diarrhea were increased with PAXG, and unmodified with AG and FOLFIRINOX. RECIST responses were numerically higher with the three- (81%) or four-drug (73%) platinum-containing regimens that outperformed AG (41%) and oxaliplatin-based doublets (56%). Carbohydrate antigen 19.9 (CA19.9) reduction >89% at nadir was reported in two-third of metastatic patients treated with triplets and quadruplets, as opposed to 33% and 45% of patients receiving oxaliplatin-based doublets or AG, respectively. All patients receiving AG experienced disease progression, with a median progression-free survival (mPFS) of 6.4 months, while patients treated with platinum-containing triplets or quadruplets had an mPFS >10.8 months. Albeit still immature, data on overall survival seemed to parallel those on PFS. CONCLUSIONS: Our data, as opposed to figures expected from the literature, highlighted that platinum-based regimens provoked an increased toxicity on proliferating cells, when dose intensity was maintained, or an as-expected toxicity, when dose intensity was reduced, while no change in toxicity and dose intensity was evident with AG. Furthermore, an apparently improved outcome of platinum-based triplets or quadruplets over other regimens was observed.

Screening indexes for cardiovascular autonomic failure in Parkinson's disease.

Autonomic failure (AF) is a common source of orthostatic hypotension (OH) in Parkinson's disease (PD). The diagnosis of AF is difficult on clinical grounds alone. We used autonomic testing and 24-h BP monitoring (ABPM) in 122 PD patients to evaluate the diagnostic accuracy of AF by (1) the reduced heart rate increase to fall in blood pressure (BP) ratio (ΔHR/ΔSBP), (2) reverse dipping (RD), and (3) increased diurnal systolic BP standard deviation (SD-SBP). Among patients with OH, ΔHR/ΔSBP yielded the best accuracy (85%), with excellent sensitivity (92%) and acceptable specificity (67%). RD and, to a lesser extent, SD-SBP had high specificity (93% and 73%, respectively) but low sensitivity, resulting in overall moderate accuracy (66% and 55%, respectively). In patients with OH, the addition of ABPM indexes to ΔHR/ΔSBP did not result in a significant improvement of accuracy. In patients without OH, RD and SD-SBP may be useful showing an accuracy of 72% and 81%, respectively, with high negative predictive value when both RD and increased SD-SBP are absent. The integration of bedside (∆HR/∆SBP) and ABPM-derived indexes can assist the clinician in screening PD patients for AF and guide referral to autonomic testing.