Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Age and genetic selection affect auto-immune profiles of chickens

Specificity, antibody isotype distribution and levels, of natural autoantibodies (NAAb) may be potential informative parameters for immune mediated natural disease resistance, immune modulation, and maintenance of physiological homeostasis. In a previous study we detected IgM and IgG antibodies to liver antigens in plasma from 1 year old chickens. Auto-immune profiles directed towards liver antigens differed between chicken lines divergently selected for specific antibody responses to sheep red blood cells. In the present study we measured the presence and typed levels and antibody isotypes (IgG and IgM) of NAAb binding the ‘auto-antigen’ complex chicken liver cell lysate (CLL) in plasma samples obtained from chickens at 5 weeks and at 1-year of age, respectively, by quantitative western blotting.Extensive staining patterns of plasma antibodies binding CLL were found for both isotypes and at both ages in all birds. At both ages, IgM and IgG bound similar numbers of CLL antigens, which remained almost constant for IgM, whereas the number of IgG stained bands in time was enhanced. Significant differences of binding patterns of NAAb (stained antigen fragments of CLL and staining intensity) were detected between the three different chicken lines at both ages and between both ages, and lines could be clustered on the basis of their auto-antibody profile. The present results indicate that analysis of the plasma NAAb repertoire of poultry like in mammals could provide a way of distinguishing differences of immune competence (as reflected by the selection criterion of antibody responses) between individuals and lines, and could provide tools to select individual birds for health and other traits. The age-dependency of the auto-immune profile suggest that such profiles may also reflect immune maturation, which should be taken into account when relating an auto-immune profile with other traits.     

Effects of synthetic and biological disease modifying antirheumatic drugs on lipid and lipoprotein parameters in patients with rheumatoid arthritis

BackgroundDyslipidemia in rheumatoid arthritis (RA) patients is frequently observed, and treatment with anti-rheumatic drugs has an impact on lipid profiles. Pathophysiologically, inflammation leads to decreased blood lipids and lipoproteins; RA treatment reduces inflammation and therefore may increase lipids and lipoproteins. Whether the lipid changes with RA treatment confer an increased risk of cardiovascular disease or just reflect their potentially atheroprotective anti-inflammatory effect is currently unclear due to limited and conflicting data.ObjectiveThe aim of this review is to summarize the current knowledge on the effects of synthetic and biological disease modifying antirheumatic drugs for the treatment of RA on lipid and lipoprotein parameters.ResultsRecent studies on methotrexate emphasize its anti-atherogenic effect. Golimumab combined with methotrexate revealed a trend towards an anti-atherogenic potential. The known pro-atherogenic lipid-spectrum alterations caused by tofacitinib can be effectively treated with atorvastatin. Tocilizumab signals a favorable impact on the extent of lipid modifications when combined with methotrexate. Abatacept indicated a trend towards an anti-atherogenic lipid profile demonstrated by favorable effects on HDL-C and on the TC/HDL-C ratio. Rituximab has beneficial effects on HDL-C and ApoA1, as well as on the ApoB/ApoA1 ratio.Clinical implicationsAnti-rheumatic drugs have various effects on lipid parameters, which in part appear pro-atherogenic. However, because many of these lipid changes may well reflect their potentially atheroprotective anti-inflammatory action the cardiovascular impact of these changes remains unclear. Whatsoever, cardiovascular safety trials for antirheumatic drugs would be valuable.     

Perception of Men's Beauty and Attractiveness by Women with Low Sexual Desire

IntroductionDespite the high prevalence of hypoactive sexual desire disorder (HSDD), especially among women, this sexual disorder remains poorly understood. Among the multiple factors possibly involved in HSDD, particularities in the cognitive evaluations of social stimuli need to be better characterized. Especially, beauty and attractiveness judgments, two dimensions of interpersonal perception that are related but differ on their underlying motivational aspects, may vary according to the level of sexual desire.AimThe main goal of this study was to investigate whether women with and without HSDD differ in their evaluations of beauty and attractiveness of men's faces and voices.MethodsYoung women from the general population (controls, n = 16) and with HSDD (patients, n = 16) took part in the study. They were presented with a series of neutral/nonerotic voices and faces of young men from the GEneva Faces And Voices database.Main Outcome MeasuresRatings of beauty (i.e., assessments of aesthetic pleasure) and of attractiveness (i.e., assessments of the personal propensity to feel attracted to someone) and the frequency to which the participants pressed a key to see or listen to each stimulus again were the main outcome measures.ResultsRatings of attractiveness were lower than ratings of beauty in both groups of women. The dissociation between beauty and attractiveness was larger in women with HSDD than in control participants. Patients gave lower attractiveness ratings than the controls and replayed the stimuli significantly less often.ConclusionThese results suggest that women with HSDD are characterized by specific alterations of the motivational component of men's perception, very early in the process of interpersonal relationships. Our findings have significant implications, both in better understanding the specific cognitive processes underlying hypoactive sexual desire and more largely the evaluative processes involved in human mate choice. Ferdenzi C, Delplanque S, Vorontsova-Wenger O, Pool E, Bianchi-Demicheli F, and Sander D. Perception of men's beauty and attractiveness by women with low sexual desire. J Sex Med 2015;12:946–955.     

Mikania micrantha extract enhances cutaneous wound healing activity through the activation of FAK/Akt/mTOR cell signaling pathway

Mikania micrantha (MM) has been traditionally used for various health benefits, including mental health, anti-inflammatory, wound dressing, and healing of sores. However, the molecular mechanisms and dose required for the wound healing activity of MM have yet to be reported. Therefore, a study was conducted to evaluate the wound healing potential of a cold methanolic extract of MM through in vitro and in vivo studies. Human dermal fibroblast adult (HDFa) cells were treated with 0 (control), 75 ng/ml, 125 ng/ml, 250 ng/ml, and 500 ng/ml of MMmethanolic extract (MME) for 24 h. MME at 75 ng/ml has significantly (p˂0.05) promoted HDFa cell proliferation and migration. Further, MME has also been shown to enhance the invasiveness of human umbilical vascular endothelial cells (HUVECs), indicating the neovasculature for wound healing. The tube formation assay demonstrated a significant (p<0.05) increase in the angiogenic effect of the MME starting at a concentration of 75 ng/ml as compared to the control. Treatment of excision wounds in Wistar rats with 5% and 10% MME ointment significantly enhanced wound contraction compared to control animals. Incision wounds in rats treated with 5% and 10% MME showed a significant (p<0.01) increase in tensile strength compared to control. HDFa cells, and granulation tissue collected on day 14 post-wounding, revealed the modulation of the FAK/Akt/mTOR cell signaling pathway during the enhancement of wound healing. The results of gel zymography showed increased activity of MMP-2 and MMP-9 in the HDFa cells after treatment with the extract.  It is concluded that MMEcan potentially accelerate cutaneous wound healing.     

Potentilla anserine L. polysaccharide protects against cadmium-induced neurotoxicity

Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl₂-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl₂ treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl₂, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl₂-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca²⁺-CaMKII-dependent Akt/mTOR pathway.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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