Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

First and second SARS-CoV-2 waves in inner London: A comparison of admission characteristics and the effects of the B.1.1.7 variant

IntroductionA second wave of SARS-CoV-2 infection spread across the UK in 2020 linked with emergence of the more transmissible B.1.1.7 variant. The emergence of new variants, particularly during relaxation of social distancing policies and implementation of mass vaccination, highlights the need for real-time integration of detailed patient clinical data alongside pathogen genomic data. We linked clinical data with viral genome sequence data to compare cases admitted during the first and second waves of SARS-CoV-2 infection. MethodsClinical, laboratory and demographic data from five electronic health record (EHR) systems was collected for all cases with a positive SARS-CoV-2 RNA test between March 13th 2020 and February 17th 2021. SARS-CoV-2 viral sequencing was performed using Oxford Nanopore Technology. Descriptive data are presented comparing cases between waves, and between cases of B.1.1.7 and non-B.1.1.7 variants. ResultsThere were 5810 SARS-CoV-2 RNA positive cases comprising inpatients (n=2341), healthcare workers (n=1549), outpatients (n=874), emergency department (ED) attenders not subsequently admitted (n=532), inter-hospital transfers (n=281) and nosocomial cases (n=233). There were two dominant waves of hospital admissions, with wave one starting from March 13th (n=838) and wave two from October 20th (n=1503), both with a temporally aligned rise in nosocomial cases (n=96 in wave one, n=137 in wave two). 1470 SARS-CoV-2 isolates were successfully sequenced, including 216/838 (26%) admitted cases from wave one, 472/1503 (31%) admitted cases in wave two and 121/233 (52%) nosocomial cases. The first B.1.1.7 variant was identified on 15th November 2020 and increased rapidly such that it comprised 400/472 (85%) of sequenced isolates from admitted cases in wave two. Females made up a larger proportion of admitted cases in wave two (47.3% vs 41.8%, p=0.011), and in those infected with the B.1.1.7 variant compared to non-B.1.1.7 variants (48.0% vs 41.8%, p=0.042). A diagnosis of frailty was less common in wave two (11.5% v 22.8%, p<0.001) and in the group infected with B.1.1.7 (14.5% v 22.4%, p=0.001). There was no difference in severity on admission between waves, as measured by hypoxia at admission (wave one: 64.3% vs wave two: 65.5%, p=0.67). However, a higher proportion of cases infected with the B.1.1.7 variant were hypoxic on admission compared to other variants (70.0% vs 62.5%, p=0.029). ConclusionsAutomated EHR data extraction linked with SARS-CoV-2 genome sequence data provides valuable insight into the evolving characteristics of cases admitted to hospital with COVID-19. The proportion of cases with hypoxia on admission was greater in those infected with the B.1.1.7 variant, which supports evidence the B.1.1.7 variant is associated with more severe disease. The number of nosocomial cases was similar in both waves despite introduction of many infection control interventions before wave two, an observation requiring further investigation.

Activation of anti-HBV immune activity by DNA vaccine via electroporation using heat shock proteins as adjuvant / 生物工程学报

Although DNA vaccination is now a promising strategy against hepatitis B virus (HBV) infection, this approach has relatively modest antiviral effect, indicating that immunosuppressive mechanisms may occur in the long-term established infection. In this study, we studied the immunogenicity and anti-HBV efficiency of a combination of HBV surface (HBsAg) and core (HBcAg) DNA vaccine, enhanced by heat shock protein (HSP) gp96 or HSP70 and mediated by in vivo electroporation. Immunization with gp96 adjuvanted HBsAg/HBcAg DNA formulation induced potent T cell and antibody immunity against HBsAg and HBcAg. Notably, treatment with gp96 or HSP70 as adjuvant resulted in reduction of Treg populations by around 20%. Moreover, compared with nonimmunized control mice, immunization with gp96 or HSP70 adjuvanted DNA vaccine dramatically decreased serum HBsAg and viral DNA levels, and HBcAg expression in liver. These results may therefore provide an effective strategy for designing gp96-based DNA vaccine for immunotherapy of chronic HBV infection.

Enhancement of cellular and humoral immune responses of HBV DNA vaccine by HSP70 and gp96 / 生物工程学报

While currently therapeutic vaccines for chronic hepatitis B virus (HBV) infection are actively being developed to complement standard antiviral treatments, their immune activity, especially T cell activity, remains to be further improved. Here, we investigated the role of heat shock proteins HSP70 and gp96 on cellular and humoral immunity, using the main structure antigens of hepatitis core (HBcAg) and surface (HBsAg) as the DNA vaccine. By ELISPOT (enzyme linked immunospot assay), IFN-gamma intracellular staining, [3H]-thymidine incorporation and ELISA (enzyme linked immunosorbent assay) analyses, we showed that immunization with HBsAg/HBcAg DNA formulation along with HSP70 or gp96 induced significant increase of T-cell (about 1-6-fold) and antibody (about 20%-60%) immunity against HBsAg and HBcAg. These results may provide bases for designing HSP70- and gp96-based vaccines aimed at eliciting T-cell responses for therapeutic applications.

Expression of Rho GTPase family member RhoA and CDC42 protein in patients with acute leukemia / 白血病·淋巴瘤

Objective To detect the proteins levels of RhoA and CDC42 in bone marrow mononucleated cells (BMMC) of patients with primary acute leukemia,and further determine the role of abnormal interactions between hematopoietic progenitor and bone marrow microenvironment on abnormal behaviors of leukemia cells. Methods BMMC samples were separated from 54 primary acute leukemia patients and 22 normal donors and the cell lysis samples were prepared. RhoA and CDC42 proteins were determined by Western blotting. Independent pair T test was conducted to evaluate whether the differences in RhoA and CDC42 expression were statistically significant between leukemia patients and normal donors. Spearman was applied in analyzing the correlation between expression of RhoA and CDC42 proteins and clinical characters of patients. Results RhoA and CDC42 proteins level of primary acute leukemia patients was significantly higher than that of normal samples. Especially, patients with M2,M3 and M5 subtypes exhibited significant higher RhoA proteins levels and M3 subtype exhibited significant higher CDC42 protein levels. Conclusion RhoA and CDC42 protein levels of primary acute leukemia patients are significantly higher than that of normal donors. This result suggests that RhoA and CDC42 associated efficient migration of leukemia cells could be implicated in abnormal interaction of leukemic cell with bone marrow microenvironment.