Κυριακή 5 Φεβρουαρίου 2023

HBsAg (‐)/HBsAb (‐)/HBeAg (‐)/HBeAb (+)/HBcAb (+) predicts a high risk of hepatitis B reactivation in patients with B‐cell lymphoma receiving rituximab based immunochemotherapy

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Abstract

Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase HR, 10.123; 95% CI, 3.389 to 30.239; P < 0.001; validation phase HR, 18.619; 95% CI, 1.684 to 205.906; P = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; P < 0.001). The mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.

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Intravaginal delivery for CRISPR‐Cas9 technology: for example, the treatment of HPV infection

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ABSTRACT

The increasing incidence of sexually transmitted diseases (STDs) in women, including human papillomavirus (HPV) infection, has led to the need to develop user friendly potential prevention methods. At present, although there are several therapeutic parts, none of them has a preventive effect, but they are only limited to providing patients with symptom relief. Researchers have now recognized the need to find effective local preventive agents. One of the potential undiscovered local fungicides is the vaginal delivery of CRISPR/Cas9. CRISPR/Cas9 delivery involves silencing gene expression in a sequence-specific manner in the pathogenic agent, thus showing microbicidal activity. However, vaginal mucosal barrier and physiological changes (such as pH value and variable epithelial thickness in the menstrual cycle) are the main obstacles to effective delivery and cell uptake of CRISPR/Cas9. In order to enhance the vaginal delivery of CRISPR/Cas9, so far, nano-carrier systems such as lipi d delivery systems, macromolecular systems, polymer nanoparticles, aptamers and cell-penetrating peptides have been extensively studied. In this paper, various nano-carriers and their prospects in the preclinical stage are described, as well as the future significance of CRISPR/Cas9 vaginal delivery based on nano-carriers.

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A high prevalence of neutrophil‐specific antibodies in ELANE‐mutated severe congenital neutropenia

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Abstract

An assay for neutrophil-specific antibodies is frequently used in the workup of chronic severe neutropenia and is suggestive of autoimmune, or sporadically alloimmune neutropenia, rather than severe congenital neutropenia (SCN). We analyzed a neutropenia consortium database for the outcomes of antibody testing initiated before receiving genetic diagnosis in Polish SCN cohort. Test results, performed in a single reference laboratory, were available for 14 patients with ELANE-mutated SCN or cyclic neutropenia, and were frequently positive (36%). We note that the trigger for genetic studies in severe neutropenia should not be affected by antibody-positivity and should be clinically driven.

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Real‐world effectiveness of preemptive therapy (PET) for cytomegalovirus (CMV) disease prevention in CMV high‐risk donor seropositive/recipient seronegative (D+R‐) liver transplant recipients (LTxR)

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Real-world effectiveness of preemptive therapy (PET) for cytomegalovirus (CMV) disease prevention in CMV high-risk donor seropositive/recipient seronegative (D+R-) liver transplant recipients (LTxR)


Abstract

Background

Despite superiority of preemptive therapy (PET) compared to universal prophylaxis for prevention of cytomegalovirus (CMV) disease in the CAPSIL randomized trial among CMV D+R- liver transplant recipients (LTxRs), real-world effectiveness may be lower because of logistical concerns about feasibility of PET.

Methods

We retrospectively assessed PET as standard clinical care at a single transplant center among 50 consecutive adult CMV D+R- LTxRs undergoing a first liver transplant between 4/4/2019 and 5/18/2021 and compared outcomes and adherence to those randomized to PET in the CAPSIL study (N = 100). The primary outcome was CMV disease and secondary outcomes were biopsy-confirmed acute allograft rejection, retransplant, invasive fungal infections, and death, all assessed by 1-year post-transplant. Exploratory outcomes included virologic parameters and measures of adherence to protocol-specified CMV qPCR monitoring.

Results

Baseline characteristics were similar between groups. The cumulative incidence of CMV disease at 1-year post-transplant was 4/50 (8%) versus 9/100 (9%) in the real-world and CAPSIL cohorts, respectively, p = 1.0. The rate of breakthrough CMV disease during the 100-day PET period was low (2/50 [4%]) and similar to the PET cohort from the CAPSIL study (3/100 [3%]).  All secondary and exploratory outcomes were not significantly different between the real-world and CAPSIL PET cohorts.

Conclusions

In this first reported study of real-world PET, the feasibility and effectiveness for CMV disease prevention and for other clinical outcomes in CMV D+R- LTxRs were similar to those reported with PET in a clinical trial. Additional studies to confirm feasibility and generalizability in other settings are warranted.

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Differences in morphology of temporomandibular joint ankylosis of traumatic and infective origin

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The aim of this study was to determine whether there are any differences in morphology between temporomandibular joint ankylosis (TMJA) of traumatic and infective origin. Cone beam computed tomography (CBCT) scans of 25 patients (28 joints) with TMJA of traumatic origin (trauma group) and 15 patients (15 joints) with TMJA of infectious origin (infection group) were included. The following morphological parameters were evaluated on multiple sections of the CBCT scans: lateral juxta-articular bone growth, residual condyle, residual glenoid fossa, ramus thickening, ankylotic mass fusion line, sclerosis of the ankylosed condyle and spongiosa of the glenoid fossa, and mastoid and glenoid fossa air cell obliteration. (Source: International Journal of Oral and Maxillofacial Surgery)
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A new glutamine synthetase index to evaluate hepatic lobular restoration in advanced fibrosis during anti‐HBV therapy

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Abstract

Hepatic lobular architecture distortion is a deleterious turning point and a crucial histological feature of advanced liver fibrosis in chronic liver diseases. Regression of fibrosis has been documented in chronic hepatitis B (CHB) patients. However, whether lobular architecture could be restored following fibrosis regression after antiviral therapy is still unclear. Glutamine synthetase (GS) is generally expressed by perivenular hepatocytes around hepatic veins (HV). In this study, we defined abnormal lobular architecture (GSPT) as GS expressing in the vicinity of portal tracts (PT), which denotes parenchymal extinction and lobular collapse. We defined normal lobular architecture (GSHV) as GS positivity area not approximating PTs. Therefore, we propose a new GS-index, defined as the percentage of GSHV/(GSHV+GSPT), to evaluate the extent of architectural disruption and restoration. We evaluated 43 CHB patients with advanced fi brosis (Ishak stage ≥ 4). Post-treatment liver biopsy was performed after 78 weeks of anti-HBV therapy. The median GS-index improved from 7% (IQR: 0%-23%) at baseline to 36% (IQR: 20%-57%) at week 78 (P < 0.001). Totals of 22 patients (51%) had significant GS-index improvement from 0% (IQR: 0%-13%) to 55% (IQR: 44%-81%), while the other half had almost no change between 17% (IQR: 0%-33%) to 20% (IQR: 12%-31%). When GS-index78w ≥ 50% was used to define hepatic lobular restoration, 37% of patients (16/43) achieved lobular restoration, with much improvement in ALT and AST levels (median value of ∆/Baseline in ALT: restored vs. non-restored was 79.1% vs. 48.8%, P = 0.018; median value of ∆/Baseline in AST: restored vs. non-restored was 69.1% vs. 32.5%, P = 0.005). More importantly, lobular restoration correlated with fibrosis regression (median value of ∆/Baseline in Ishak stage: restored vs. non-restored was 25.0% vs. 0%, P = 0.008). Therefore, in the era of antiviral therapy for CHB, restoration of hepatic lobular architecture is achievable in patients with advanced fibrosis. GS-index provides additional insight into fibrosis regression that goes beyond collagen degradation.

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Guidance on the use of convalescent plasma to treat immunocompromised patients with COVID-19

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Abstract
COVID-19 convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immune compromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has yet to be determined, and related best practices guidelines are lacking. A group of individuals with expertise spanning infectious diseases, virology and transfusion medicine was assembled to render an expert opinion statement pertaining to the use of CCP for IC patients. For optimal effect, CCP should be recently and locally collected to match circulating variant. CCP should be considered for the treatment of IC patients with acute and protracted COVID-19; dosage depends on clinical setting (acute vs protracted COVID-19). CCP containing high-titer SARS-CoV-2 antibodies, retains activity against circul ating SARS-CoV-2 variants, which have otherwise rendered monoclonal antibodies ineffective.
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