Campbellshea9109

Graft-versus-host disease (GVHD) causes failed reconstitution of donor plasmacytoid dendritic cells (pDCs) that are critical for immune protection and tolerance. We used both murine and human systems to uncover the mechanisms whereby GVHD induces donor pDC defects. GVHD depleted Flt3-expressing donor multipotent progenitors (MPPs) that sustained pDCs, leading to impaired generation of pDCs. see more MPP loss was associated with decreased amounts of MPP-producing hematopoietic stem cells (HSCs) and oxidative stress-induced death of proliferating MPPs. Additionally, alloreactive T cells produced GM-CSF to inhibit MPP expression of Tcf4, the transcription factor essential for pDC development, subverting MPP production of pDCs. GM-CSF did not affect the maturation of pDC precursors. Notably, enhanced recovery of donor pDCs upon adoptive transfer early after allogeneic HSC transplantation repressed GVHD and restored the de novo generation of donor pDCs in recipient mice. pDCs suppressed the proliferation and expansion of activated autologous T cells via a type I IFN signaling-dependent mechanism. They also produced PD-L1 and LILRB4 to inhibit T cell production of IFN-γ. We thus demonstrate that GVHD impairs the reconstitution of tolerogenic donor pDCs by depleting DC progenitors rather than by preventing pDC maturation. MPPs are an important target to effectively bolster pDC reconstitution for controlling GVHD.We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human COVID-19 clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies to help guide decisions. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in 2 animal disease models. The standard human malaria HCQ prophylaxis (6.5 mg/kg given weekly) and treatment (6.5 mg/kg given daily) did not significantly benefit clinical outcome, nor did it reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. Similarly, when used for prophylaxis or treatment, neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Results from these 2 preclinical animal models may prove helpful in guiding clinical use of HCQ for prophylaxis/treatment of COVID-19.

In China, the optimal management of individuals living with chronic HBV infection remains an unmet need. The EVOLVE was a 5-year prospective, longitudinal, observational study that compared the clinical outcomes in treatment-naïve CHB patients receiving entecavir (ETV) or lamivudine (LAM)-based therapies.

Males or females aged ≥18 years, diagnosed with CHB regardless of cirrhosis or HBeAg status were enrolled from Tier 2 city hospitals (between 2012-2014). The choice of initial therapy and subsequent treatment modifications was at the discretion of treating physicians. Key outcomes included treatment modifications, virologic response (HBV DNA <300copies/mL), and HBV disease progression.

Of the 3408 patients enrolled, 1807 and 628 received ETV and LAM-based therapy, respectively. The mean age was 39.5 years, 74% were male, and 22.9% had cirrhosis. The rate of treatment modification was higher in the LAM-based vs ETV group (25.9% vs 13.7%); viral breakthrough was the most common reason in LAM-based group vs financial reasons in ETV group. At week 240, the virologic response rate was 73% in both treatment groups. Compared with LAM-based therapy, ETV was associated with a significantly lower incidence of viral breakthrough (12.6% vs 2.1%) and genotypic resistance (10.1% vs 1.2%; p<0.0001 for both); significantly lower risk of HBV disease progression (14.0% vs 10.7%; p=0.0113); and lower rates of progression to decompensated cirrhosis (9.6% vs 6.4%) and hepatocellular carcinoma (1.9% vs 0.8%).

This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough, and resistance with ETV vs LAM-based therapy.

This real-world, longitudinal study demonstrated a significantly lower risk of HBV-related disease progression, viral breakthrough, and resistance with ETV vs LAM-based therapy.

Information on the usefulness of screen-and-test strategies of pregnant women for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is lacking.

We retrospectively reviewed the Ljubljana Maternity Hospital database and searched for pregnant women, who were admitted to the hospital between March 15 and May 16, 2020, for a planned procedure or hospitalization. Their medical records were examined and SARS-CoV-2 test results were retrieved.

During the two-month period analyzed, there were a total of 265 scheduled admissions of pregnant women to our hospital. Two hundred two (76.2%) were tested for SARS-CoV-2 1 day prior to admission. All tested negative for SARS-CoV-2 RNA, regardless of having coronavirus disease 2019 (COVID-19)-compatible signs or symptoms (n=28) or not (n=174).

In a population with a low SARS-CoV-2 burden, usefulness of universal testing of pregnant women before admission to the hospital is limited. We recommend that obstetric units in regions with low SARS-CoV-2 burden enforce rational use of personal protective equipment and diligent screening protocols using targeted questionnaires, whereas SARS-CoV-2 laboratory testing should be performed only in screen-positives those with high clinical suspicion of COVID-19 and/or suspected epidemiological history.

In a population with a low SARS-CoV-2 burden, usefulness of universal testing of pregnant women before admission to the hospital is limited. We recommend that obstetric units in regions with low SARS-CoV-2 burden enforce rational use of personal protective equipment and diligent screening protocols using targeted questionnaires, whereas SARS-CoV-2 laboratory testing should be performed only in screen-positives those with high clinical suspicion of COVID-19 and/or suspected epidemiological history.