Early rise in brain damage markers and high ICOS expression in CD4+ and CD8+ T cells during checkpoint inhibitor-induced encephalomyelitis

We report a case of rapid eradication of melanoma brain metastases and simultaneous near-fatal encephalomyelitis following double immune checkpoint blockade. Brain damage marker S-100B and C reactive protein increased before symptoms or signs of encephalomyelitis and peaked when the patient fell into a coma. At that point, additional brain damage markers and peripheral T cell phenotype was analyzed. The analyses were repeated four times during the patient’s recovery. Axonal damage marker neurofilament light polypeptide (NFL) and astrocytic damage marker glial fibrillar acidic protein (GFAP) were very high in blood and cerebrospinal fluid and gradually normalized after immunosuppression and intensive care. The costimulatory receptor inducible T cell costimulatory receptor (ICOS) was expressed on a high proportion of CD4+ and CD8+T cells as encephalomyelitis symptoms peaked and then gradually decreased in parallel with clinical improvement. Both single and double immune checkpoint inhibitor-treated melanoma patients with other serious immune-related adverse events (irAE) (n=9) also expressed ICOS on a significantly higher proportion of CD4+ and CD8+T cells compared with controls without irAE (n=12). In conclusion, our results suggest a potential role for ICOS on CD4+ and CD8+T cells in mediating encephalomyelitis and other serious irAE. In addition, brain damage markers in blood could facilitate early diagnosis of encephalitis

Hydrogen chloride-induced surface disordering on ice

Characterizing the interaction of hydrogen chloride (HCl) with polar stratospheric cloud ice particles is essential for understanding the processes responsible for ozone depletion. We studied the interaction of gas-phase HCl with ice between 243 and 186 K by using (i) ellipsometry to monitor the ice surface and (ii) coated-wall flow tube experiments, both with chemical ionization mass spectrometry detection of the gas phase. We show that trace amounts of HCl induce formation of a disordered region, or quasi-liquid layer, at the ice surface at stratospheric temperatures. We also show that surface disordering enhances the chlorine activation reaction of HCl with chlorine nitrate (ClONO(2)) and also enhances acetic acid (CH(3)COOH) adsorption. These results impact our understanding of the chemistry and physics of ice particles in the atmosphere

Posttraumatic Stress Symptoms and Emerging Adult Sexual Minority Men: Implications for Assessment and Treatment of Childhood Sexual Abuse

Emerging adulthood (EA) is a developmental period marked by unique challenges that affect health including burgeoning occupational, relational, and financial stability; and increased risk taking in terms of sexual behavior(s) and substance use. Data were collected from 296 HIV-uninfected sexual minority men with childhood sexual abuse (CSA) histories. We analyzed baseline assessment data from a multisite randomized controlled trial that tested the efficaciousness of an experimental psychosocial treatment and examined vulnerabilities known to be linked with CSA. Our analyses compared EA sexual minority men, aged 18-29, with older sexual minority men (OSMM) on posttraumatic stress disorder (PTSD) and other mental health and substance use outcomes. We found higher odds of PTSD, odds ratio (OR) = 0.57, 95% CI [0.33, 0.96]; panic disorder or panic disorder with agoraphobia, OR = 0.36, 95% CI [0.16, 0.85]; and cocaine use, OR = 0.50, 95% CI [0.25, 0.97], among OSMM and higher odds of alcohol intoxication, OR = 5.60, 95% CI [3.20, 9.82]; cannabis use, OR = 3.09, 95% CI [1.83, 5.21]; and non-HIV sexually transmitted infections, OR = 3.03, 95% CI [1.29, 7.13], among the EA men. These results present a complex picture of health risks among sexual minority men in general and EA sexual minority men in particular. HIV seroconversion linked health risk behaviors, among sexual minority men, may be better addressed via increased attention to treating trauma and comorbid mental health and substance use problems using evidence-based psychosocial assessments and integrated treatment platforms that are tailored to this population