Effectiveness Of Tocilizumab In Aortitis And Aneurysms Associated With Giant Cell Arteritis.

OBJECTIVE: Aortitis in Giant Cell Arteritis (GCA-aortitis) is a frequent complication that may lead to aneurysms. Tocilizumab (TCZ) was approved in GCA, but the efficacy in GCA-aortitis and aneurysms has not been analyzed to date. Our aim was to assess the effectiveness and safety of TCZ in a wide series of GCA-aortitis and aneurysms. METHODS: Multicentre observational study with GCA-aortitis treated with TCZ. GCA was diagnosed by: a) ACR criteria, b) temporal artery biopsy, and/or c) imaging techniques. Aortitis was diagnosed mainly by PET/CT. Main outcomes were EULAR and imaging remission. Others were clinical remission, analytical normalization, corticosteroid-sparing effect, and the prevention and improvement of aneurysms. RESULTS: 196 patients with GCA-aortitis treated with TCZ. After 6 months, 72.2% reached EULAR remission but only 12% an imaging remission; increasing up-to 81.4% and 31.8%, respectively, at 24 months. A rapid clinical remission, ESR and CRP normalization was observed in 47.4%, 84.3% and 55.6%, at 1 month, increasing to 89.6%, 85.3% and 80.3% at 24 months, respectively. Aneurysms were present in 10 (5%) patients. Five of them required early surgery, while 3 others enlarged. No patient on TCZ therapy developed aneurysms during follow-up. CONCLUSION: In patients with GCA-aortitis treated with TCZ, a rapid and maintained clinical and analytical improvement was observed. However, there was an uncoupling between clinical and EULAR remission with imaging remission.

Antimicrobial Potential of Chitosan Films Incorporated with Alcoholic Extract from Mimosa tenuiflora Leaves.

Antimicrobial films were prepared with chitosan containing the methanolic extract of M. tenuiflora leaves (FECT20%, FECT30%, and FECT40%), and their antimicrobial activities were evaluated by agar diffusion. The films were characterized by IR spectroscopy, scanning electron microscopy (SEM) and TG/DTG curves. TG/DTG curves showed thermal stability of chitosan-extract films up to 166 ºC. Micrographs of chitosan-extract films revealed an increase in porosity with the addition of extract. The FECT40% film showed inhibition zone diameters (IZ) against Micrococcus luteus, Staphylococcus aureus, Bacillus subtilis, and B. cereus, ranging from 1.0 ± 0.02 to 0.72 ± 0.09 cm. Only FECT30% and FECT40% inhibited the P. aeruginosa with IZs of 0.68 ± 0.02 and 0.77 ± 0.06 cm, respectively. In turn, the extract showed inhibition against B. subtilis and B. cereus, with IZs values of 0.92 ± 0.2 cm and 0.72 ± 0.05 cm, respectively. Additionally, the crude extract presented antioxidant potential with inhibition percentages of 32.74% ± 0.90 for ABTS and 27.04% ± 1.36 for DPPH. The antimicrobial and antioxidant activities of the crude extract, as well as the antimicrobial property of chitosan-extract films, suggests the potential of these biopolymers for the development of wound healing bandages and new food packaging alternatives.

A Coordinated School Health Program Effect on Cardiorespiratory Fitness of South Texas Preschool Children: A Cluster Randomized Trial.

BACKGROUND: The purpose of this study was to assess the effects of the Bienestar/NEEMA Coordinated School Health Program (BN CSHP) on cardiorespiratory fitness (CRF) of preschool children. METHODS: A cluster randomized trial was conducted of preschools in South Texas. Of 48 eligible schools, 28 were randomly assigned (14 intervention, 14 control). Family demographics and household health characteristics were collected from parents and CRF from children. Generalized linear mixed model (GLMM) was used to analyze the data. RESULTS: Family demographics, household health characteristics, and children's weight, obesity prevalence, and sedentary activity of the control group were similar to the intervention group at baseline. After adjusting for covariates, the number of laps ran by children in the control group increased by 23% (CI: -5% to 60%) per each data collection period compared with 53% (CI: 7% to 119%) in the intervention group. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: State mandates, parent engagement, and funding are key for designing effective health and Physical Education (PE) programs. CONCLUSION: Children in the BN CSHP, compared to those in the control group, had a significantly higher increase in their CRF. This finding is important because of the health benefits of CRF in children. CLINICALTRIALS: gov Identifier: NCT05501392.

Behavioral Modification of Leucauge mariana Induced by an Ichneumonid Spider-Parasitoid, Hymenoepimecis castilloi, in the Colombian Andes.

Hymenoepimecis is a genus of Darwin wasps in the Polysphincta group of genera (Hymenoptera: Ichneumonidae: Pimplinae) known as ectoparasitoids of a broad spectrum of spiders. The parasitoid induces production of a web known as cocoon web, which provides shelter and support for the wasp pupa. In this study, we describe for the first time the interaction between Hymenoepimecis castilloi Pádua & Sääksjärvi (Hymenoptera: Ichneumonidae) and its host spider Leucauge mariana (Taczanowski) (Araneae: Tetragnathidae) in the Colombian Andes, provide new records of wasp genus distribution, and described the behavioral modifications induced in the spider. Web modifications occurred in the webs of both solitary and aggregated individuals. Adhesive spirals were lacking, and webs were connected to vegetation by multiple threads in all cocoon webs, which was not seen attached to webs of non-parasitized spiders. All parasitoid cocoons were observed hanging on a vertical line in the hub of the cocoon web. As previously described for other species, we believe that this modified web design results in increased web strength and favors parasitoid development during the pupal stage.

A phase II study of neoadjuvant liposomal irinotecan with 5-FU and oxaliplatin (NALIRIFOX) in pancreatic adenocarcinoma.

For patients with localized pancreatic cancer with minimal vascular involvement, optimal survivability requires a multidisciplinary approach of surgical resection and systemic chemotherapy. FOLFIRINOX is a combination chemotherapy regimen that offers promising results in the perioperative and metastatic settings; however, it can cause significant adverse effects. Such toxicity can negatively impact some patients, resulting in chemotherapy discontinuation or surgical unsuitability. In an effort to reduce toxicities and optimize outcomes, this investigation explores the safety and feasibility of substituting liposomal irinotecan (nal-IRI) for nonliposomal irinotecan to improve tumor drug delivery and potentially reduce toxicity. This regimen, NALIRIFOX, has the potential to be both safer and more effective when administered in the preoperative setting.

For patients with pancreatic cancer with little to no cancer near the blood vessels, the best life expectancy usually requires surgery and chemotherapy. FOLFIRINOX is a chemotherapy medicine that offers promising results for both patients getting surgery and for patients with widespread disease. However, it can cause harmful side effects. The side effects can be so bad that the chemotherapy has to be stopped or that surgery is no longer possible. In order to reduce the harmful side effects and improve outcomes, this investigation looks into the safety and practicality of using a different version of one of the medicines. The different version hopes to improve drug delivery and reduce harmful side effects. This regimen, NALIRIFOX, can be safer and more effective in patients awaiting surgery. Clinical Trial Registration: UF-STO-PANC-004 (NCT03483038) (ClinicalTrials.gov).

Glycosylation differences of an anti-VEGF monoclonal antibody (PRO-169) and its extensive comparison with Bevacizumab.

PRO-169 is an anti-VEGF monoclonal antibody developed by Laboratorios Sophia that shares its sequence with Bevacizumab (BVZ); though, PRO-169 is intended for intravitreal administration. In this study, analytical characterization showed that PRO-169 had glycosylation differences in comparison to BVZ reference product (RP); since it had more content of G1F, G2F, sialic acid and high mannose. Further investigation was performed to evaluate if differences between both products would affect the efficacy and safety profile of PRO-169. PRO-169 had no alteration in its in vitro biological activity; moreover, no cytotoxicity or immunogenicity concerns should be expected as demonstrated by different orthogonal methods at analytical, in vitro and in vivo assays. These results support moving to the clinical testing of PRO-169 since no major complications will be expected with its clinical use for the treatment of ophthalmic diseases.

Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis.

Background: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood. Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis. Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups. Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.

Measurements, Predictions, and Control in Microgrids and Power Electronic Systems.

The systems used to distribute electricity are currently undergoing a series of changes that are aiding in the development of smart grids.

Associations of Total Body Fat Mass and Skeletal Muscle Index with All-Cause and Cancer-Specific Mortality in Cancer Survivors.

Purpose: The importance of body composition on cancer outcomes is of great clinical interest. Measures of body composition that differentiate fat mass from skeletal muscle mass can help redefine our understanding of body composition for cancer survival. We investigated whether the risk of all-cause and cancer-specific mortality differ by levels of total fat mass and sarcopenia status in cancer survivors. Our secondary aim was a subgroup analysis assessing the role of race within these associations. Methods: Participants included 1682 adult cancer survivors who had undergone a dual-energy X-ray absorptiometry (DXA) examination to measure body composition, from the 1999-2006 and 2011-2018 National Health and Nutrition Examination Survey (NHANES). Total fat mass was categorized into tertiles (we assessed high vs. low tertiles), and sarcopenia was considered as having an appendicular skeletal muscle mass index less than 7.26 kg/m2 for males and less than 5.45 kg/m2 for females. Multivariable Cox proportional hazard models estimated the adjusted hazard ratio (aHR) and 95% confidence interval (CI). Results: The mean age of study participants was 61.9 years, and they were followed up for an average of 9.67 years. The prevalence of sarcopenia was 25.0% (N = 304), and 33.4% (N = 561) had a high total fat mass. Participants with a higher fat mass (aHR = 1.30, 95% CI = 1.06-1.61) and with sarcopenia (aHR = 1.51, 95% CI = 1.22-1.88) had a 30% and 51% increased risk of all-cause mortality compared to participants with a low fat mass and with no sarcopenia, respectively. Further, sarcopenia (aHR = 1.74, 95% CI = 1.23-2.29) was associated with a higher risk of cancer-specific mortality in cancer survivors. The association between sarcopenia and all-cause mortality was twice as strong in Black people (aHR = 2.99, 95% CI = 1.39-6.06) compared to White people (aHR = 1.53, 95% CI = 1.19-1.95). Conclusions: Our findings show the opposing relations of fat mass and appendicular skeletal muscle mass index with mortality in a national sample of cancer survivors, and that the relationships may differ by race. These results emphasize the importance of maintaining a healthy body composition among cancer survivors.

Advanced Hepatocellular Carcinoma in Adults Without Cirrhosis: A Single-Institution Retrospective Review.

Background: Although up to one in five cases of hepatocellular carcinoma (HCC) occurs in patients without cirrhosis, there is scarce literature characterizing non-cirrhotic HCC (NCHCC). Existing NCHCC research is primarily limited to surgical case series and there is a lack of data on unresectable NCHCC. Aim: The purpose of this retrospective review was to compare the characteristics of unresectable NCHCC and cirrhotic hepatocellular carcinoma (CHCC). Methods: A retrospective chart review of adult patients with unresectable HCC treated from 2007 to 2017 was performed at the University of Florida Shands Hospital. The data set was stratified into two cohorts: NCHCC and CHCC. Continuous variables were compared using Wilcoxon-Mann-Whitney tests and Kruskal-Wallis rank-sum tests. Categorical variables were compared using Pearson's Chi-squared tests and Fisher's exact tests. Overall survival was explored utilizing the Kaplan-Meier and log-rank method. Results: There were 1494 adult patients included in the final analysis, including 264 patients (17.7%) with NCHCC and 1230 patients (82.3%) with CHCC. Median age was 61.0 years old and median follow-up time was 30.2 months. NCHCC patients were older than CHCC patients (66.3 years vs 61.9 years; p < 0.0001). NHCC tumors were larger than CHCC tumors (7.92 ± 4.85 vs 4.38 ± 3.12 cm; p < 0.0001) and more likely to be associated with distant metastases (23.35% vs 15.91%; p = 0.0055). There was no difference in overall survival, with a median of 23.5 months in NCHCC and 22.4 months in CHCC (p = 0.9196). Conclusion: Our findings suggest that unresectable NCHCC and CHCC have unique characteristics but similar overall survival. To the best of our knowledge, this is the largest comparison of CHCC and NCHCC.

Optimal Reactive Power Compensation in Distribution Networks with Radial and Meshed Structures Using D-STATCOMs: A Mixed-Integer Convex Approach.

This paper deals with the problem regarding the optimal siting and sizing of distribution static compensators (D-STATCOMs) in electrical distribution networks to minimize the expected total annual operating costs. These costs are associated with the investments made in D-STATCOMs and expected energy losses costs. To represent the electrical behavior of the distribution networks, a power flow formulation is used which includes voltages, currents, and power as variables via incidence matrix representation. This formulation generates a mixed-integer nonlinear programming (MINLP) model that accurately represents the studied problem. However, in light of the complexities involved in solving this MINLP model efficiently, this research proposes a mixed-integer convex reformulation. Numerical results regarding the final annual operating costs of the network demonstrate that the proposed mixed-integer convex model is efficient for selecting and locating D-STATCOMs in distribution networks, with the main advantage that it is applicable to radial and meshed distribution grid configurations. A comparative analysis with respect to metaheuristic optimizers and convex approximations confirms the robustness of the proposed formulation. All numerical validations were conducted in the MATLAB programming environment with our own scripts (in the case of metaheuristics) and the CVX convex disciplined tool via the Gurobi solver. In addition, the exact MINLP model is solved using the GAMS software.

Atezolizumab plus tivozanib for immunologically cold tumor types: the IMMCO-1 trial.

Immune checkpoint inhibitor therapy represents a significant advance in cancer care. The interaction between PD-1 and PD-L1 induces immune tolerance and the inhibition of this interaction is an effective treatment strategy for numerous malignancies. Despite its demonstrated potential, immunotherapy is not clinically effective in immunogenically 'cold' tumors such as pancreatic cancer, prostate cancer and neuroendocrine tumors. Through the inhibition of VEGF, it may be possible to potentiate the effect of immune checkpoint blockade in tumors that have traditionally shown a lack of clinical response to immunotherapy. This signal-seeking, single-arm, prospective clinical trial aims to determine the objective response of tivozanib and atezolizumab in advanced immunogenically cold solid tumors. Clinical Trial Registration: NCT05000294 (ClinicalTrials.gov).

Effectiveness of radiotherapy for local control in T3N0 rectal cancer managed with total mesorectal excision: a meta-analysis.

INTRODUCTION: The total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy's benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated. A systematic review and meta-analysis were undertaken to determine whether radiotherapy altered the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME. MATERIALS AND METHODS: Studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening, and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty; and all were performed independently by at least two investigators. Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted. RESULTS: Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4-78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy. A non-significant LR reduction with radiotherapy alongside TME was estimated, mean relative risk (RR) 0.63 (95% Confidence Interval 0.31-1.29; I2 = 41.8%). CONCLUSIONS: A non-significant LR benefit with radiotherapy's addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted.

Tocilizumab in visual involvement of giant cell arteritis: a multicenter study of 471 patients.

Background: Visual involvement is the most feared complication of giant cell arteritis (GCA). Information on the efficacy of tocilizumab (TCZ) for this complication is scarce and controversial. Objective: We assessed a wide series of GCA treated with TCZ, to evaluate its role in the prevention of new visual complications and its efficacy when this manifestation was already present before the initiation of TCZ. Design: This is an observational multicenter study of patients with GCA treated with TCZ. Methods: Patients were divided into two subgroups according to the presence or absence of visual involvement before TCZ onset. Visual manifestations were classified into the following categories: transient visual loss (TVL), permanent visual loss (PVL), diplopia, and blurred vision. Results: Four hundred seventy-one GCA patients (mean age, 74 ± 9 years) were treated with TCZ. Visual manifestations were observed in 122 cases (26%), of which 81 were present at TCZ onset: PVL (n = 60; unilateral/bilateral: 48/12), TVL (n = 17; unilateral/bilateral: 11/6), diplopia (n = 2), and blurred vision (n = 2). None of the patients without previous visual involvement or with TVL had new episodes after initiation of TCZ, while only 11 out of 60 (18%) patients with PVL experienced some improvement. The two patients with diplopia and one of the two patients with blurred vision improved. Conclusion: TCZ may have a protective effect against the development of visual complications or new episodes of TVL in GCA. However, once PVL was established, only a few patients improved.

Association of social determinants of health with late diagnosis and survival of patients with pancreatic cancer.

Background: Pancreatic cancer disparities have been described. However, it is unknown if they contribute to a late diagnosis and survival of patients with metastatic disease. Identifying their role is important as it will open the door for interventions. We hypothesize that social determinants of health (SDH) such as income, education, race, and insurance status impact (I) stage of diagnosis of PC (Stage IV vs. other stages), and (II) overall survival (OS) in Stage IV patients. Methods: Using the National Cancer Database, we evaluated a primary outcome of diagnosis of Stage IV PC and a secondary outcome of OS. Primary predictors included race, income, education, and insurance. Covariates included age, sex and Charlson-Deyo comorbidity score. Univariate, multivariable logistic regression models evaluated risk of a late diagnosis. Univariate, multivariable Cox proportional hazards model examined OS. 95% confidence intervals were used. Results: 230,877 patients were included, median age of 68 years (SD 12.1). In univariate analysis, a better education, higher income, and insurance decreased the odds of Stage IV PC, while Black race increased it. In multivariable analysis, education [>93% high-school completion (HSC) vs. <82.4%, OR 0.96 (0.93-0.99)] and insurance [private vs. no, OR 0.72 (0.67-0.74)] significantly decreased the risk of a late diagnosis, whereas Black race increased the odds [vs. White, OR 1.09 (1.07-1.12)]. In univariate Cox analysis, having a higher income, insurance and better education improved OS, while Black race worsened it. In multivariable Cox, higher income [>$63,333 (vs. <$40,277), HR 0.87 (0.85-0.89)] and insurance [private vs. no, HR 0.77 (0.74-0.79)] improved OS. Conclusions: SDH impacted the continuum of care for patients with advanced pancreatic cancer, including stage at diagnosis and overall survival.

Clinical Updates for Colon Cancer Care in 2022.

Colon cancer needs better screening and treatment options. Its incidence in the young population is rising. Recent changes in guidelines recommend beginning screening for colon cancer at the age of 45. Circulating tumor DNA presents an opportunity to select patients for administration of adjuvant chemotherapy. Immunotherapy is an option for patients with a deficiency in mismatch repair proteins. However, its efficacy outside of this group of patients remains a challenge. Targeted therapies such as BRAF inhibitors are an option for patients with poor prognosis, for whom cytotoxic chemotherapy is not as effective. This review presents the recently published evidence regarding screening and treating patients with colon cancer.

Derivative-Free Power Flow Solution for Bipolar DC Networks with Multiple Constant Power Terminals.

This paper analyzes the power flow solution in bipolar direct current networks with radial structures considering multiple monopolar and bipolar constant power loads. The electrical configuration of the bipolar DC grid considers that the reference pole is non-grounded along the feeder, which produces important neutral currents and voltage imbalances along the DC grid. The power flow problem is formulated through the triangular-based representation of the grid topology, which generates a recursive formulation that allows determining the voltage values in the demand nodes through an iterative procedure. The linear convergence of the triangular-based power flow method is tested through multiple load variations with respect to the nominal grid operative condition. Numerical results in the 21- and the 85-bus grids reveal the relevant variations in the voltage profiles and total grid power losses when the neutral cable is solidly grounded or not.