Patient-reported daily functioning after SARS-CoV-2 vaccinations in autoimmune neuromuscular diseases

Background and purpose: There are concerns for safety regarding SARS-CoV-2 vaccines for patients with autoimmune neuromuscular disease. We compared daily functioning using disease-specific patient-reported outcome measures (PROMs) before and after SARS-CoV-2 vaccinations. Methods: In this substudy of a prospective observational cohort study (Target-to-B!), patients with myasthenia gravis (MG), chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), and idiopathic inflammatory myopathy (IIM) vaccinated against SARS-CoV-2 were included. Surveys of daily functioning (Myasthenia Gravis Activities of Daily Living, Inflammatory Rasch-Built Overall Disability Scale, Multifocal Motor Neuropathy Rasch-Built Overall Disability Scale, and Health Assessment Questionnaire-Disability Index) were sent before first vaccination and every 60 days thereafter for up to 12 months. Regression models were constructed to assess differences in PROM scores related to vaccination, compared to scores unrelated to vaccination. We also assessed the proportion of patients with deterioration of at least the minimal clinically important difference (MCID) between before first vaccination and 60 days thereafter. Results: We included 325 patients (median age = 59 years, interquartile range = 47-67, 156 [48%] female sex), of whom 137 (42%) had MG, 79 (24%) had CIDP, 43 (13%) had MMN, and 66 (20%) had IIM. PROM scores related to vaccination did not differ from scores unrelated to vaccination. In paired PROMs, MCID for deterioration was observed in three of 49 (6%) MG patients, of whom none reported a treatment change. In CIDP, MCID for deterioration was observed in eight of 29 patients (28%), of whom two of eight (25%) reported a treatment change. Conclusions: SARS-CoV-2 vaccination had no effect on daily functioning in patients with autoimmune neuromuscular diseases, confirming its safety in these patients

Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

BACKGROUND: Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. CASE PRESENTATION: A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. CONCLUSION: We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block

The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer:Development and External Validation of a Preoperative Prediction Model

Occult metastases are detected in 10–15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013–December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013–December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00–1.03), BMI (OR 0.96, 95% CI 0.93–0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01–2.74), tumor diameter (OR 1.60, 95% CI 1.04–2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20–4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16–7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.</p

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.</p

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.</p

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Male gays in the female gaze: women who watch m/m pornography

This paper draws on a piece of wide-scale mixed-methods research that examines the motivations behind women who watch gay male pornography. To date there has been very little interdisciplinary research investigating this phenomenon, despite a recent survey by PornHub (one of the largest online porn sites in the world) showing that gay male porn is the second most popular choice for women porn users out of 25+ possible genre choices. While both academic literature and popular culture have looked at the interest that (heterosexual) men have in lesbian pornography, considerably less attention has been paid to the consumption of gay male pornography by women. Research looking at women's consumption of pornography from within the Social Sciences is very focused around heterosexual (and, to a lesser extent, lesbian) pornography. Research looking more generally at gay pornography/erotica (and the subversion of the ‘male gaze’/concept of ‘male as erotic object’) often makes mention of female interest in this area, but only briefly, and often relies on anecdotal or observational evidence. Research looking at women's involvement in slashfic (primarily from within media studies), while very thorough and rich, tends to view slash writing as a somewhat isolated phenomenon (indeed, in her influential article on women's involvement in slash, Bacon-Smith talks about how ‘only a small number’ of female slash writers and readers have any interest in gay literature or pornography more generally, and this phenomenon is not often discussed in more recent analyses of slash); so while there has been a great deal of very interesting research done in this field, little attempt has been made to couch it more generally within women's consumption and use of pornography and erotica or to explore what women enjoy about watching gay male pornography. Through a series of focus groups, interviews, and an online questionnaire (n = 275), this exploratory piece of work looks at what women enjoy about gay male pornography, and how it sits within their consumption of erotica/pornography more generally. The article investigates what this has to say about the existence and nature of a ‘female gaze’

AP-1 Is a Component of the Transcriptional Network Regulated by GSK-3 in Quiescent Cells

The protein kinase GSK-3 is constitutively active in quiescent cells in the absence of growth factor signaling. Previously, we identified a set of genes that required GSK-3 to maintain their repression during quiescence. Computational analysis of the upstream sequences of these genes predicted transcription factor binding sites for CREB, NFκB and AP-1. In our previous work, contributions of CREB and NFκB were examined. In the current study, the AP-1 component of the signaling network in quiescent cells was explored.Using chromatin immunoprecipitation analysis, two AP-1 family members, c-Jun and JunD, bound to predicted upstream regulatory sequences in 8 of the 12 GSK-3-regulated genes. c-Jun was phosphorylated on threonine 239 by GSK-3 in quiescent cells, consistent with previous studies demonstrating inhibition of c-Jun by GSK-3. Inhibition of GSK-3 attenuated this phosphorylation, resulting in the stabilization of c-Jun. The association of c-Jun with its target sequences was increased by growth factor stimulation as well as by direct GSK-3 inhibition. The physiological role for c-Jun was also confirmed by siRNA inhibition of gene induction.These results indicate that inhibition of c-Jun by GSK-3 contributes to the repression of growth factor-inducible genes in quiescent cells. Together, AP-1, CREB and NFκB form an integrated transcriptional network that is largely responsible for maintaining repression of target genes downstream of GSK-3 signaling