Infections in decompensated cirrhosis: Pathophysiology, management, and research agenda.

Bacterial infections in patients with cirrhosis lead to a 4-fold increase in mortality. Immune dysfunction in cirrhosis further increases the risk of bacterial infections, in addition to alterations in the gut microbiome, which increase the risk of pathogenic bacteria. High rates of empiric antibiotic use contribute to increased incidence of multidrug-resistant organisms and further increases in mortality. Despite continous advances in the field, major unknowns regarding interactions between the immune system and the gut microbiome and strategies to reduce infection risk and improve mortality deserve further investigation. Here, we highlight the unknowns in these major research areas and make a proposal for a research agenda to move toward improving disease progression and outcomes in patients with cirrhosis and infections.

Corrigendum: Direct oral anticoagulants for the treatment of cerebral venous thrombosis - a protocol of an international phase IV study.

[This corrects the article DOI: 10.3389/fneur.2023.1251581.].

Quantitative and functional changes in platelets and fibrinogen following cardiopulmonary by-pass in children.

Introduction: Cardiopulmonary bypass (CPB) causes coagulopathy, increasing the risk of postoperative bleeding and mortality. The underlying causes of post-CPB coagulopathy and the factors associated with its occurrence are not yet fully understood. This study assesses platelet and fibrinogen concentration and function following CPB in children with congenital heart diseases (CHD). Methods: We analyzed prospective data from 104 patients aged 0-16 years who underwent CPB surgery for CHD. Blood samples were collected before surgery and within 30 min of CPB completion. In addition to usual coagulation tests, functional analyses were performed using point of care systems with thromboelastometry and impedance aggregometry. Results: Platelet count, fibrinogen concentration, and platelet and fibrinogen activities significantly decreased after CPB. The duration of CPB was directly associated with a reduction in platelet count and fibrinogen level (r = -0.38, p < 0.001; r = -0.21, p = 0.03, respectively), but not with their measured activity. Postoperative percentages of baseline values for platelet count (58.36% [43.34-74.44] vs. 37.44% [29.81-54.17], p < 0.001) and fibrinogen concentration (73.68% [66.67-82.35] vs. 65.22% [57.89-70.83], p < 0.001) were significantly higher in patients who did not experience hypothermia during surgery. Age was inversely associated with the decrease in platelet count (r = 0.63, p < 0.001), TRAPTEM AUC (r = 0.43, p < 0.001), fibrinogen concentration (r = 0.44, p < 0.001) and FIBTEM MCF (r = 0.57, p < 0.001). Conclusion: Post-CPB coagulopathy is multifactorial and not solely attributed to hemodilution. It also involves functional changes in coagulation cascade components, which can be demonstrated by thromboelastometry and impedance aggregometry. Young children, patients requiring prolonged CPB surgery, or those experiencing hypothermia are particularly affected.

Worldwide Prevalence and Description of Cyclic Vomiting Syndrome According to the Results of the Rome Foundation Global Epidemiology Study.

BACKGROUND AIMS: Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction (DGBI) of unknown origin. This study aimed to evaluate the global prevalence of this disorder and its associated factors. METHODS: Data were collected from nationwide Internet surveys in 26 countries, with subjects evenly distributed by age, sex and country. The survey included the Rome IV questionnaire as well as an extensive supplemental questionnaire to evaluate additional factors. RESULTS: 54,127 participants completed the questionnaire (51% male, mean age 44.3 years). The pooled prevalence of CVS was 0.3% (95% CI 0.3-0.4%; n=187), highest in Brazil (1%, 95% CI 0.6-1.5), and lowest in Japan and Germany (with no subject who fulfilled the criteria for CVS). The mean age of participants with CVS was 36.7 years (standard deviation 13.5) and it was more common in females (56.7% vs 43.5%). Factors independently associated with this syndrome were female sex (OR 1.52, 95% CI 1.13-2.03), young age (OR 2.57, 95% CI 1.34-4.94, for people between the ages of 18 and 39 years, compared to those older than 65 years), depression (OR 3.14, 95% CI 2.05-4.82, p<0.001) and anxiety (OR 1.79, 95% CI 1.15-2.78, p<0.001). Individuals with CVS had impaired quality of life (QoL) (PROMIS-10 score: physical QoL mean, 12.9 vs 15.5, p<0.001; mental QoL mean 12.3 vs 14.4, p<0.001) compared to others. CONCLUSIONS: CVS is a relatively common disorder that has a negative impact on quality of life. It is important to raise awareness on this syndrome to avoid underdiagnosis and improve clinical practice.

Lateral and Medial Elbow Tendinopathy and Previous Injuries to Adjacent Joints: A Multicenter Observational Study.

BACKGROUND: Lateral and medial elbow tendinopathies are common soft tissue disorders affecting 1-3% of the general population, causing significant pain and functional impairment in the elbow and upper limb. While often associated with overuse and repetitive strain, their exact etiology, including potential associations with prior injuries in adjacent joints, remains unclear. This preliminary study aims to explore the distribution of lateral and medial elbow tendinopathies and investigate the occurrence of previous lesions in adjacent joints among diagnosed individuals, providing foundational insights for future research. METHODS: A multicenter cross-sectional observational study was conducted involving 90 subjects diagnosed with lateral and/or medial elbow tendinopathy. The data collection occurred during the initial consultations, including demographic information, clinical assessments, and history of prior injuries in adjacent joints. RESULTS: Among the sample, 44.4% reported prior injuries to adjacent joints in the affected upper limb, with 45.6% of these injuries identified as musculotendinous in nature. The analysis also showed that the type of elbow tendinopathy was significantly associated with sex (p = 0.01) and occupational origin (p = 0.022). CONCLUSIONS: While a notable percentage of the subjects reported prior musculoskeletal injuries in the same limb, the study's geographic limitations and reliance on self-reported data introduce potential recall bias. These preliminary findings suggest a possible relationship between prior adjacent joint injuries and elbow tendinopathy. Further research with larger sample sizes and more rigorous study design is needed to confirm these observations and explore the underlying mechanisms.

Real-world outcomes on quality-of-life improvement in patients with nasal polyposis treated with mepolizumab. RINOSUR study.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by nasal obstruction, reduced sense of smell, rhinorrhea, and facial pain for more than 12 weeks, significantly affecting quality of life (QoL), especially in patients with NSAID-exacerbated respiratory disease (NERD). Initial treatment includes intranasal corticosteroids and nasal irrigations, followed by systemic corticosteroids (SC) in severe cases, as well as endoscopic sinus surgery (ESS) and biological agents. Mepolizumab, a monoclonal antibody against IL-5, has been shown to reduce eosinophilic inflammation in CRSwNP. This study evaluates the improvement in quality of life of patients with CRSwNP treated with mepolizumab before December 2023, recorded by the RINOSUR group. A retrospective observational multicenter cohort study is presented in adult patients with severe asthma and concomitant CRSwNP, treated with mepolizumab 100 mg. Variables such as sex, asthma, allergies, NERD, corticosteroid dependence, and serum eosinophil count were recorded. All patients underwent nasal endoscopy and completed the SNOT22 questionnaire. Therapeutic response was evaluated at 12 months. Out of 143 patients recruited, only 28.6% had the necessary data. 61% were women with a mean age of 55 years. All were corticosteroid-dependent and had required at least one ESS. A 22% reduction in SC cycles was observed, and no patient required revision surgery in the 12 months following treatment. The SNOT22 score was reduced by 53 points, and serum eosinophilia also showed a significant decrease. Mepolizumab is effective in treating severe uncontrolled CRSwNP, improving QoL and reducing dependence on systemic corticosteroids. Its activity is monitored by peripheral blood eosinophilia. Consistency in data collection is crucial to evaluate efficacy and manage the disease.

Association between the lactate-albumin ratio and microcirculation changes in Pediatric Septic patients.

A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98-23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08-1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01-1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21-10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65-0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis.

Practical Guidelines by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) on Nutritional Management of Patients with Chronic Obstructive Pulmonary Disease: A Review.

Malnutrition is common in chronic obstructive pulmonary disease (COPD) patients and is associated with worse lung function and greater severity. This review by the Andalusian Group for Nutrition Reflection and Investigation (GARIN) addresses the nutritional management of adult COPD patients, focusing on Morphofunctional Nutritional Assessment and intervention in clinical practice. A systematic literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, followed by critical appraisal based on Scottish Intercollegiate Guidelines Network (SIGN) guidelines. Recommendations were graded according to the European Society for Clinical Nutrition and Metabolism (ESPEN) system. The results were discussed among GARIN members, with consensus determined using a Likert scale. A total of 24 recommendations were made: 2(A), 6(B), 2(O), and 14(GPP). Consensus exceeded 90% for 17 recommendations and was 75-90% for 7. The care of COPD patients is approached from a nutritional perspective, emphasizing nutritional screening, morphofunctional assessment, and food intake in early disease stages. Nutritional interventions include dietary advice, recommendations on food group intake, and the impact of specialized nutritional treatment, particularly oral nutritional supplements. Other critical aspects, such as physical activity and quality of life, are also analyzed. These recommendations provide practical guidance for managing COPD patients nutritionally in clinical practice.

Effects of Some Olive Fruits-Derived Products on Oxidative Stress and Cardiovascular Biomarkers on Experimental Diabetes Mellitus.

The aim of this study is to assess the possible effect of olive seed oil (OSO) and destoned and dehydrated olive oil (DDOO), in comparison with extra-virgin olive oil (EVOO), on some cardiovascular biomarkers in an experimental model of diabetes mellitus. Diabetic animals showed evident alterations in biomarkers involved in the evolution of diabetic vasculopathy, marked by increases in biomarkers that favor vascular damage, which was between 1.5 and five times as many as those in non-diabetic animals, and a smaller number of biomarkers that protect against such damage (25-75% less than in healthy controls) was observed. The three oils administered decreased the concentration of biomarkers of vascular damage (35-45% in the serum lipid profile, 15-40% in early biomarkers of vascular inflammation and 20-60% in platelet aggregation and in thromboxane/prostacyclin imbalance). The greatest effect was by the antioxidant, both in the inhibition of lipid peroxidation and in the increase of glutathione. DDOO showed a significantly greater effect on oxidative stress and on thromboxane/prostacyclin imbalance than those shown by OSO and EVOO. This greater effect may possibly be explained by its higher triterpenoid content (913 mg/kg, compared to 113 mg/kg in OSO and 75 mg/kg in EVOO). We conclude, in the light of the results of this study, that these oils meet two basic conditions: they could improve the yield of the olive industry, and they equal, and may even increase, the beneficial effects of EVOO on cardiovascular disease.

Nociception Coma Scale-Revised with Personalized Painful Stimulus Versus Standard Stimulation in Persons with Disorders of Consciousness: An International Multicenter Study.

Background/Objectives: Persons with disorders of consciousness (DoCs) may perceive pain without being able to communicate their discomfort. The Nociception Coma Scale (NCS) and its revised form (NCS-R) have been proposed to assess nociception in persons with DoCs. The main aim of this international multicenter study was to confirm (or not) our preliminary results and compare the NCS-R scores of standard stimulus (NCS-R-SS) to scores of personalized painful stimuli (NCS-R-PS). A secondary aim of the study was to verify possible correlations between the NCS-R-PS and Coma Recovery Scale-Revised (CRS-R) and to estimate convergent validity. Methods: Sixty-one patients with prolonged DoCs (pDoCs) were enrolled from seven European post-acute rehabilitation centers. Responsiveness and pain perception were assessed by CRS-R and NCS-R with standard stimulus (NCS-R-SS) and personalized stimulation (NCS-R-PS). ClinicalTrials.gov Identifier: NCT06012357. Results: our results support our prior findings on the superiority and the validity of the personalized painful stimulus approach in assessment of pain in persons with DoCs in comparison with the standardized pain assessment methodology. Conclusions: A more in-depth and tailored assessment of pain perception in persons with a DoC may lead to better acknowledgment of its presence and by extension an objective foundation for more aggressive and appropriate pain management.

Prevalence of Unwanted Loneliness and Associated Factors in People over 65 Years of Age in a Health Area of the Region of Murcia, Spain: HELPeN Project.

Background/Objectives: Population aging poses many challenges to public health, highlighting loneliness and social isolation as severe problems that affect the physical and mental health of older adults. During the COVID-19 pandemic, these became aggravated. The objective of the present study was to assess the prevalence of loneliness and its relationship with social isolation, depression, cognitive deterioration, sleep quality, and the level of physical mobility and functioning of older adults in Health Area 3 of the Region of Murcia. Methods: A descriptive, observational, and cross-sectional study was performed. The inclusion criteria were age ≥ 65, living in Health Area 3 of the Region of Murcia, and not being institutionalized. The following variables were evaluated: sociodemographic variables, loneliness (UCLA scale), social isolation (DUFSS), depression (GDS), cognitive deterioration (Pfeiffer), sleep quality (PSQI), and mobility (Barthel index). A univariate and multivariate regression model was created to examine how the dependent variable was related to the independent variables. Results: A total of 102 older adults participated in the study. Of these, 31.4% perceived unwanted loneliness and 14.7% low social support. The multivariate regression analysis showed that social isolation, geriatric depression, and cognitive deterioration were significant predictors of loneliness. Conclusions: The findings highlight the importance of developing multifaceted interventions that address not only social isolation but also other interrelated factors such as depression, cognitive deterioration, and sleep quality. The strategies should be centered on community programs and support networks. It is fundamental to perform longitudinal studies to better understand the causal relationships between these variables.

Chronic Pain Management Approaches among Spanish Physiotherapists: Influences, Practices, Barriers, and Challenges.

This study evaluated Spanish physiotherapists' orientations toward biopsychosocial and biomedical approaches in chronic pain management through a cross-sectional survey of 447 registered professionals. Validated questionnaires assessed knowledge, attitudes, and beliefs. Multivariate analysis of covariance (MANCOVA) identified influential factors and ordinal regression determined the frequency of biopsychosocial application. Content analysis of open-ended responses explored barriers to biopsychosocial implementation. Over 50% of physiotherapists favored the biopsychosocial model, influenced by interdisciplinary work settings, advanced pain knowledge, and specific training. Comprehensive pain knowledge significantly impacted both biomedical and biopsychosocial orientations inversely. The biomedical approach was more prevalent among those with lower education levels and less pain knowledge, particularly at the beginning or over 20 years into their careers. Despite the theoretical preference for biopsychosocial among Spanish physiotherapists, practical application was infrequent, with only 9.8% always using it and 40.7% frequently. Self-reported confidence and skills were crucial determinants of biopsychosocial implementation frequency. Significant barriers included inadequate psychological skills (63.6%), coordination challenges (47.6%), time constraints (43.6%), patient misconceptions (34.2%), and systemic issues. These findings align with international research, highlighting the need to bridge the gap between theoretical knowledge and clinical practice. Addressing these challenges through targeted training and systemic reforms is crucial for improving chronic pain management globally.

Enhanced Electrochemical Detection of Nonelectroactive Compounds Based on Surface Supramolecular Interactions on Chevron-like Graphene Nanoribbons Modified through Click Chemistry.

In this study, we have developed a nanostructured electrochemical sensor based on modified graphene nanoribbons tailored for the analysis of nonelectroactive compounds via a surface competitive assay. Stigmasterol, a nonelectroactive phytosterol, was selected as a representative case. Chevron-like graphene nanoribbons, chemically synthesized, were immobilized onto glassy carbon electrodes and covalently functionalized to allow the on-surface formation of a supramolecular complex. To this end, the nanoribbons were first modified through a diazotization process by electrochemical reduction of a 4-azidoaniline diazonium salt, leaving the electrode surface with azide groups exposed to solution. Next, the incorporation of a ferrocene group, as a redox probe, was carried out by a click chemistry reaction between ethynylferrocene and these azide groups. Finally, the recognition event leads to the formation of a supramolecular complex between ferrocene and a macrocyclic receptor on the electrode surface. To this end, the receptors cucurbit[7]uril, cucurbit[8]uril, and ß-cyclodextrin were evaluated, with the better results obtained with ß-cyclodextrin. Atomic force microscopy and scanning electron microscopy measurements were performed for the morphological characterization of the resulting electrochemical platform surface. The ability of ß-cyclodextrin to form an inclusion complex with ferrocene or with stigmasterol allows to perform a competitive assay, which translates into the decrease and recovery of the ferrocene electrochemical signal. For stigmasterol determination, a linear concentration range between 200 and 750 µM and a detection limit of 60 µM were obtained, with relative errors and relative standard deviations less than 7.1 and 9.8%, respectively.

Effect of electric current in viability, biofilm formation and antibiotic resistance of Pseudomonas aeruginosa: A systematic review.

BACKGROUND: The bactericidal effect of electric current has been studied in various microorganisms such as Pseudomonas aeruginosa. The objective of this review is to identify the experimental parameters with the greatest antibacterial effect in the shortest time. METHODS: Literature search was conducted in the databases PubMed, Science Direct, and Google Scholar. Only original articles published between 2014-2023 were included, where the effect of electric current on viability, biofilm formation, and/or antibiotic resistance in P. aeruginosa was analyzed. Quality control criteria considered included specifying control and experimental groups, replicates performed, experimental parameters, and study limitations. RESULTS: Ten studies were included, which involved the strains Xen5, Xen41, PAO1 persistent cells, and PA14. An average reduction of 3.5 log in biofilm formation was observed in the included studies. The electric current parameters that achieved the greatest effect were 500 µA DC with platinum electrodes for 4 days [5.2-5.5 log], 200 µA intermittent with titanium electrodes for 4 days [4.99 log], and 150 ± 60 µA with silver electrodes for 24 hours [4 log]. Complete eradication of PAO1 persistent cells was achieved in 1 hour with a treatment of 70 µA/cm2 DC followed by 1.5 µg/mL tobramycin for 1 hour each. CONCLUSIONS: The bactericidal effect of electric current is proportional to the exposure time and current intensity. The electrode material influences the effectiveness of the treatment, possibly because of redox reactions, while differences are observed in the effect on the cell membrane and gene expression when using metallic or carbon electrodes, suggesting differences in the mechanism of action.

Sex Differences in Chronic Postsurgical Pain after Open Thoracotomy.

STUDY OBJECTIVE: To determine the incidence of chronic postsurgical pain (CPSP) in women after open thoracotomy. Secondary objectives were to compare relevant patient and procedural variables between women and men. DESIGN: Observational cohort study. SETTING: Ten university-affiliated hospitals. SUBJECTS: Ninety-six women and 137 men. INTERVENTIONS: Scheduled open thoracotomy. MEASUREMENTS: Pain histories, psychological measures, and perceived health status and catastrophizing scores were obtained. The diagnosis of chronic postsurgical pain was by physical examination at 4 months. Standard preoperative, intraoperative, and postoperative data were also recorded. MAIN RESULTS: The chronic postsurgical pain incidence was significantly higher in women (53.1%) than in men (38.0%) (p = 0.023). At baseline, women had significantly worse scores on psychological measures (perception of mental state [p = 0.01], depression [p = 0.006], and catastrophizing [p < 0.001]). Women also reported more preoperative pain in the operative area (p = 0.011) and other areas (p = 0.030). CONCLUSION: These findings show that the incidence of physician-diagnosed chronic postsurgical pain is higher in women than in men after surgeries involving thoracotomy. Sex and gender should be included in future clinical research on pain in surgical settings.

Exploring the optical behavior and relative translucency parameter of CAD-CAM resin-based composites, polymer-infiltrated ceramic network, and feldspar porcelain.

OBJECTIVES: To evaluate and compare the optical properties and relative translucency parameter of CAD-CAM restorative materials. METHODS: Four CAD-CAM materials were evaluated: Lava Ultimate (LU), Grandio Blocs (GB), VITA Enamic (VE), and VITA Mark II (VM). Disk-shaped samples in shade A2-HT were prepared (n = 10) and polished to 1.00 ± 0.01 mm of thickness. Scattering (S), absorption (K), albedo (a) coefficient, transmittance (T%), light reflectivity (RI), infinite optical thickness (X∞), and radiative transfer coefficients (µa, and µ'S) were calculated using Kubelka-Munk method and Thennadil's semi-empirical approach. Root Mean Square Error (RMSE) and Goodness of Fit (GFC) were used as performance optical behavior. Translucency differences were evaluated using the relative translucency parameter (RTP00) and 50:50 % translucency perceptibility and acceptability thresholds (TPT00 and TAT00). RESULTS: The spectral distribution of S, K, T%, RI, and X∞ was wavelength-dependent. GFC and RMSE values indicated good spectral behavior matches and good comparative spectral values for RI in LU-GB, LU-VE, and GB-VE, and for K in VE-VM. VM displayed the highest scattering values across the wavelengths, while VE and VM showed lower absorption at shorter wavelengths. LU and GB had the highest transmittance. The X∞ values indicated that all 1.0 mm thick materials could be influenced by the background. No good spectral match and no good comparative spectral values were found between CAD-CAM materials and anterior bovine maxillary specimens. VM had the lowest RTP00 values with perceptible and unacceptable differences compared to CAD-CAM materials evaluated. SIGNIFICANCE: Understanding the optical behavior of different CAD-CAM materials was essential for guiding clinicians in material selection and optimizing their clinical performance. The findings confirm that the different compositions and microstructure impact the optical properties and translucency of CAD-CAM restorative materials.

Chemometric study on the effect of cooking on bioactive compounds in tomato pomace enriched sauces.

Tomato pomace (TP) is an underutilized source of bioactive compounds with potential application in the food sector. A factorial experiment was designed to compare three culinary techniques, Thermomix®, Roner®, and traditional pan-frying, for the preparation of tomato sauces, enriched or not with TP, applying two temperatures and two cooking times. A multivariate analysis was performed on all the results obtained for the metabolites. The addition of TP significantly increased the content of bioactive compounds, especially phenolic compounds. OPLS-DA models were generated using cooking technique, temperature, and time as discriminant factors. The cooking technique had a greater effect on the phenolic content than cooking temperature or time. Thermomix® released bioactive compounds from the tomato into the sauce to a similar extent as pan-frying. Roner® proved to be effective in preserving the volatile fraction of the sauce. The Thermomix® significantly increased the amount of bioactive compounds, while the Roner® increased the volatile compounds.

Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41/GEICO 69-O/ANITA Phase III Trial.

PURPOSE: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer. METHODS: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1. RESULTS: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA-mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs. CONCLUSION: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Influence of microstructure on optical properties of CAD-CAM lithium disilicate glass-ceramics.

OBJECTIVES: To evaluate the influence of microstructure and chemical composition on the optical properties of CAD-CAM lithium disilicate glass-ceramics. METHODS: Samples (n = 5; 1.0 mm thickness) of shades A1, A2, and A3 were fabricated from CAD-CAM ceramic blocks (Ivoclar Vivadent): IPS e.max® CAD LT (emLT) and HT (emHT). Samples were polished to 1.0 ± 0.01 mm in thickness. The optical properties (R- reflectance; T- transmittance; µs'- reduced scattering and µa- absorption coefficients) from the post-crystallized samples were determined using the inverse adding-doubling (IAD) method based on integrating-sphere measurements. Additionally, scanning electron microscopy (SEM) and X-ray diffraction (XRD) techniques were used to evaluate the microstructural properties. Energy-dispersive X-ray (EDX) was employed to analyze the chemical composition. The chemical and structural characterization were performed before and after crystallization of the ceramic samples. RESULTS: emLT showed higher values of µs'and lower values of µa and T than emHT for each shade in all wavelengths (p < 0.003). Considering T for emHT, there were no statistical differences for shades A1 and A2 at 488 nm and 514.5 nm (p > 0.003) and shades A1 and A3 at 457.9 nm (p > 0.003). emLT showed particle length ranging from 0.74 to 2.78 µm (mean = 1.57 µm and RF-relative frequency = 28 %) and particle width ranging from 0.21 to 0.74 µm (mean = 0.30 µm and RF = 31 %). emHT showed particle length ranging from 0.83 to 3.08 µm (mean = 1.86 µm and RF = 21 %) and particle width ranging from 0.24 to 1.12 µm (mean = 0.56 µm and RF = 28 %). In comparison with emHT, emLT showed greater vol% for C, K, and Zr and lower vol% for O and Al. SIGNIFICANCE: The optical properties of CAD-CAM lithium disilicate glass-ceramics are influenced by the chemical composition and, consequently, by the material microstructure.