Breg Cells in Celiac Disease Isolated or Associated to Hashimoto's Thyroiditis

Hashimoto's thyroiditis (HT) may occur associated with celiac disease (CD). Regulatory B cells (Breg) subsets have been shown to play a significant role in autoimmune processes. Therefore, we have characterized their distribution in the peripheral blood obtained from 10 patients with isolated HT, 10 patients with HT + CD, 9 patients with isolated CD, and 9 healthy donors (HD). Th17 cells were significantly increased in patients with HT and in patients bearing both HT and CD, while patients with isolated CD exhibited a lower percentage of Th17, as compared with healthy donors. CD24hiCD38hi Breg cells were significantly higher in patients with HT + CD and in patients with isolated CD as compared to both HD patients and patients with isolated HT (p = 0.0010). On the contrary, Breg memory phenotypes (CD24hiCD38- and CD24hiCD27+) significantly decreased in patients with HT + CD as compared with the isolated disorders. Following CpG oligodeoxynucleotide stimulation, IL-10+ CD24hiCD38hi Breg cells were similar in all groups of patients, despite these cells would have been higher in CD patients. In conclusion, celiac disease, isolated and even more when associated with HT, determines a peculiar behavior of Breg cells which are increased in number but possibly functionally defective. Furthermore, the association CD + HT was characterized by a reduction of Breg memory subsets as compared with the isolated disorders. The behavior of Th17 subset in patients with celiac disease associated with HT might have been sensitive to the effect of long-lasting GFD, and it is essentially determined by the presence of thyroid autoimmunity

Critical COVID-19 Patients Through First, Second And Third Wave: Retrospective Observational Study Comparing Outcomes In ICU.

Introduction- The time-course of the COVID-19 pandemic was characterized by subsequent waves identified by peaks of Intensive Care Unit (ICU) admission rates. During these periods, progressive knowledge of the disease led to the development of specific therapeutic strategies. This retrospective study investigates whether this led to improvement in outcomes of COVID-19 patients admitted to ICU. Methods- Outcomes were evaluated in consecutive adult COVID19 patients admitted to our ICU, divided into three waves based on the admission period: the first wave from February 25th, 2020, to July 6th, 2020; the second wave from September 20th, 2020, to February 13th, 2021; the third wave from February 14th, 2021 to April 30th, 2021. Differences were assessed comparing outcomes and by using different multivariable Cox models adjusted for variables related to outcome. Further sensitivity analysis was performed in patients undergoing invasive mechanical ventilation. Results- Overall, 428 patients were included in the analysis: 102, 169 and 157 patients in the first, second and third wave. The ICU and in-hospital crude mortalities were lower by 7% and 10% in the third wave compared to the other 2 waves (p>0.05). A higher number of ICU and hospital free days at day 90 was found in the third wave when compared to the other 2 waves (p=0.001). Overall, 62.6% underwent invasive ventilation, with decreasing requirement during the waves (p=0.002). The adjusted Cox model showed no difference in the Hazard Ratio for mortality among the waves. In the propensity-matched analysis the hospital mortality rate was reduced by 11% in the third wave (p=0.044). Conclusions - With application of best practice as known by the time of the first three waves of the pandemic, our study failed to identify a significant improvement in mortality rate when comparing the different waves of the COVID-19 pandemic, notwithstanding, the sub-analyses showed a trend in mortality reduction in the third wave. Rather, our study identified a possible positive effect of dexamethasone on mortality rate reduction and the increased risk of death related to bacterial infections in the three waves

Draft Genome Sequence of the Probiotic Yeast Kluyveromyces marxianus fragilis B0399

Here, we report the draft genome sequence of Kluyveromyces marxianus fragilis B0399, the first yeast approved as a probiotic for human consumption not belonging to the genus Saccharomyces The genome is composed of 8 chromosomes, with a total size of 11.44\ua0Mb, including mitochondrial DNA

Cytomegalovirus blood reactivation in COVID-19 critically ill patients: risk factors and impact on mortality.

Purpose: Cytomegalovirus (CMV) reactivation in immunocompetent critically ill patients is common and relates to a worsening outcome. In this large observational study, we evaluated the incidence and the risk factors associated with CMV reactivation and its effects on mortality in a large cohort of COVID-19 patients admitted to the intensive care unit (ICU). Methods: Consecutive patients with confirmed SARS-CoV-2 infection and acute respiratory distress syndrome admitted to three ICUs from February 2020 to July 2021 were included. The patients were screened at ICU admission and once or twice per week for quantitative CMV-DNAemia in the blood. The risk factors associated with CMV blood reactivation and its association with mortality were estimated by adjusted Cox proportional hazards regression models. Results: CMV blood reactivation was observed in 88 patients (20,4%) of the 431 patients studied. SAPS II score (HR 1,031, 95% CI 1,010-1,053, p=0,006), platelet count (HR 0,0996, 95% CI 0,993-0,999, p=0,004), invasive mechanical ventilation (HR 2,611, 95% CI 1,223-5,571, p=0,013) and secondary bacterial infection (HR 5,041; 95% CI 2,852-8,911, p<0,0001) during ICU stay were related to CMV reactivation. Hospital mortality was higher in patients with (67,0%) than in patients without (24,5%) CMV reactivation but the adjusted analysis did not confirm this association (HR 1,141, 95% CI 0,757-1,721, p=0,528). Conclusion: The severity of illness and the occurrence of secondary bacterial infections were associated with an increased risk of CMV blood reactivation, which, however, does not seem to influence the outcome of COVID-19 ICU patients independently

Deletions in VANGL1 are a risk factor for antibody-mediated kidney disease

We identify an intronic deletion in VANGL1 that predisposes to renal injury in high risk populations through a kidney-intrinsic process. Half of all SLE patients develop nephritis, yet the predisposing mechanisms to kidney damage remain poorly understood. There is limited evidence of genetic contribution to specific organ involvement in SLE.(1,2) We identify a large deletion in intron 7 of Van Gogh Like 1 (VANGL1), which associates with nephritis in SLE patients. The same deletion occurs at increased frequency in an indigenous population (Tiwi Islanders) with 10-fold higher rates of kidney disease compared with non-indigenous populations. Vangl1 hemizygosity in mice results in spontaneous IgA and IgG deposition within the glomerular mesangium in the absence of autoimmune nephritis. Serum transfer into B cell-deficient Vangl1(+/-) mice results in mesangial IgG deposition indicating that Ig deposits occur in a kidney-intrinsic fashion in the absence of Vangl1. These results suggest that Vangl1 acts in the kidney to prevent Ig deposits and its deficiency may trigger nephritis in individuals with SLE