The long term vaccine‐induced anti‐SARS‐CoV‐2 immune response is impaired in quantity and quality under TNFα blockade

alexandrossfakianakis shared this article with you from Inoreader The long term vaccine‐induced anti‐SARS‐CoV‐2 immune response is impaired in quantity and quality under TNFα blockade via Journal of Medical Virology Abstract Background The humoral immune response to SARS-CoV-2 vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with TNFα inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity and the ability to neutralise a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Methods Serum levels of anti-SARS-CoV-2 IgG, IgG avidity and neutralising antibodies (NA) were determined in anti-TNFα patients (n=10) and controls (n=24 healthy individuals; n=12 patients under other disease-modifying anti-rheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralisation assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolour flow cytometry. Results IgG avidity and anti-pre-VOC NA titres decreased f aster in anti-TNFα recipients than in controls 6 months after the second vaccination (healthy individuals: avidity: p≤0.0001; NA: p=0.0347; oDMARDs: avidity: p=0.0012; NA: p=0.0293). Total plasma cell counts were increased in anti-TNFα patients (Healthy individuals: p=0.0344; oDMARDs: p=0.0254), whereas absolute numbers of SARS-CoV-2-specific cells were comparable 7 days after vaccination. These patients had lower BA.2 NA titres compared to both other groups, even after the third vaccination. Conclusions We show a reduced SARS-CoV-2 neutralising capacity in patients under TNFα blockade. In this cohort, the plasma cell response appears to be less specific and show stronger bystander activation. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced. This article is protected by copyright. All rights reserved. View on Web

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Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study

alexandrossfakianakis shared this article with you from Inoreader Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: a cross‐sectional study via Journal of Medical Virology Abstract Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, ECC and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n=2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Co mpared to single HR-HPV infection, multiple HR-HPV infections do not increase the risk of HSIL+, while single HR-HPV coinfected with LR-HPV seems to reduce the risk of HSIL+ (OR=0.515, CI: 0.370-0.719, P＜0.001). Multiple HR-HPV infections cannot be risk-stratified for triage of HR-HPV-positive women. This article is protected by copyright. All rights reserved. View on Web

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Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial

alexandrossfakianakis shared this article with you from Inoreader Initiating Intramuscular Depot Medroxyprogesterone Acetate (DMPA-IM) Increases Frequencies of Th17-like Human Immunodeficiency Virus (HIV) Target Cells in the Genital Tract of Women in South Africa: A Randomized Trial via Clinical Infectious Diseases Advance Access Abstract BackgroundCervicovaginal CD4+ T cells are preferential targets for human immunodeficiency virus (HIV) infection and have consequently been used as a proxy measure for HIV susceptibility. The ECHO randomized trial offered a unique opportunity to consider the association between contraceptives and Th17-like cells within a trial designed to evaluate HIV risk. In a mucosal substudy of the ECHO trial, we compared the impact of initiating intramuscular depot medroxyprogesterone acetate (DMPA-IM), copper-IUD, and the levonorgestrel (LNG) implant on cervical T cells. Methods Cervical cytobrushes from 58 women enrolled in the ECHO trial were collected at baseline and 1 month after contraceptive initiation. We phenotyped cervical T cells using multiparameter flow cytometry, characterized the vaginal microbiome using 16s sequencing, and determined proteomic signatures associated with Th17-like cells using mass spectrometry. Results Unlike the LNG implant or copper-IUD, DMPA-IM was as sociated with higher frequencies of cervical Th17-like cells within 1 month of initiation (P = .012), including a highly susceptible, activated population co-expressing CD38, CCR5, and α4β7 (P = .003). After 1 month, women using DMPA-IM also had more Th17-like cells than women using the Cu-IUD (P = .0002) or LNG implant (P = .04). Importantly, in women using DMPA-IM, proteomic signatures signifying enhanced mucosal barrier function were associated with the increased abundance of Th17-like cells. We also found that a non–Lactobacillus-dominant microbiome at baseline was associated with more Th17-like cells post–DMPA-IM (P = .03), although this did not influence barrier function. Conclusions Our data suggest that D MPA-IM–driven accumulation of HIV-susceptible Th17-like cells might be counteracted by their role in maintaining mucosal barrier integrity. View on Web

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Challenges in the interpretation of a germline TERT variant in a patient with juvenile myelomonocytic leukemia

alexandrossfakianakis shared this article with you from Inoreader Challenges in the interpretation of a germline TERT variant in a patient with juvenile myelomonocytic leukemia via Pediatric Blood & Cancer Abstract Dyskeratosis congenita (DC) is a bone marrow failure syndrome with extrahematopoietic abnormalities. DC is a paradigmatic telomere biology disorder (TBD) caused by germline mutations in genes responsible for telomere maintenance including TERT. Cryptic TBD is a bone marrow failure syndrome due to premature telomere shortening but without additional symptoms, frequently clinically indistinguishable from severe aplastic anemia (SAA) or hypoplastic myelodysplastic syndrome. We present the complex diagnostic pathway in a boy with a rare germline p.Thr726Met TERT variant with previous reports of SAA association and compromised enzymatic function who presented with juvenile myelomonocytic leukemia, which is a rare myelodysplastic/myeloproliferative neoplasm of childhood. View on Web

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Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth

alexandrossfakianakis shared this article with you from Inoreader Review of guidance for the selection of regenerative endodontics, apexogenesis, apexification, pulpotomy, and other endodontic treatments for immature permanent teeth via International Endodontic Journal Abstract This review guidance is a work in progress because the limitations of regenerative endodontics are still being discovered. The endodontic treatments for immature permanent teeth with a necrotic pulp can vary considerably among endodontic practitioners. Whereas, Regenerative endodontic treatments are growing in popularity and are creating ever more complex treatment protocols, involving revascularization and/or autologous platelet-rich plasma and scaffolds to elicit host stem cell de novo tissue formation to res-establish the vitality of immature teeth for the purpose of continuing root maturation. Despite much evolving controversy about their potential benefits, risks, prognosis, and contraindications. This review is aimed to discuss how to ensure that regenerative endodontic treatments are successful, by strictly adhering to case selection criteria, and following precise steps to accomplish and monitor the success of the treatment. A review of the endodontic literature was performed, together with practical observations of the problems and outcomes of performing regenerative endodontic treatments. Traditionally, apexification has long been the treatment of choice provided to immature teeth with a necrotic pulp. Regenerative endodontics may be provided as an alternative to apexification, if the tooth and patient meets all the case selection criteria, and if there are no contraindications. Regenerative endodontics has the unique potential advantage of being able to continue the root development in immature permanent teeth, thereby potentially saving the teeth for the lifetime of the patient. Whereas, conventional endodontic root canal treatment, Cvek partial pulpotomy, apexogenesis, and apexification, should always be provided when these treatments are more likely to benefit the patient because they can be more successful than regenerative endodontics. View on Web

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Clinical and Molecular Analysis of Recurrent Gram-Negative Bloodstream Infections

alexandrossfakianakis shared this article with you from Inoreader Clinical and Molecular Analysis of Recurrent Gram-Negative Bloodstream Infections via Clinical Infectious Diseases Advance Access Abstract Background The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. Methods We used a prospectively ascertained cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (both pulsed field gel electrophoresis [PFGE] and whole genome sequencing [WGS]) was used to define whether these episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors associated with recurrence. Results Of the 1423 patients with GNB-BSI that met criteria for inclusion in this study, 60 (4%) had recurrent GNB-BSI. Non-white race (OR: 2.35; CI95% 1.38-4.01; p = 0.002), admission to a surgical service (OR: 2.18; CI95% 1.26-3.75; p = 0.005) and presence of an indwelling cardiac device (OR: 2.73; CI95% 1.21-5.58, p =  0.009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30/48) and 38% were due to reinfection (18/48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47/48) of cases. Median time to relapse and reinfection was similar (113 days [IQR: 35-222 days] vs. 174 days [IQR: 69-599 days], p = 0.13). Presence of a cardiac device was associated with relapse (Relapse: 7/27 [26%]; Non-relapse: 65/988 [7%]; p = 0.002). Conclusions In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Presence of a cardiac device was a risk factor for relapse. View on Web

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SARS-CoV-2 hyperimmune intravenous human immunoglobulins neutralizes Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5 for treatment of COVID-19

alexandrossfakianakis shared this article with you from Inoreader SARS-CoV-2 hyperimmune intravenous human immunoglobulins neutralizes Omicron subvariants BA.1, BA.2, BA.2.12.1, BA.3 and BA.4/BA.5 for treatment of COVID-19 via Clinical Infectious Diseases Advance Access ABSTRACT Our study demonstrates that neither 2020-convalescent plasma (CP) nor 2019/2020-immunoglobulin (IVIG) neutralize Omicron subvariants BA.1 to BA.5. In contrast, hyperimmune 2020-hCoV-2IG lots neutralized Omicron VOCs, similar to 2022-CP from BA.1 breakthrough infections. Therefore, high-titer hCoV-2IG and CP could be evaluated for treatment of high-risk individuals infected with circulating Omicron subvariants. View on Web

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