Classification of HHV-6A and HHV-6B as distinct viruses

Shortly after the discovery of human herpesvirus 6 (HHV-6), two distinct variants, HHV-6A and HHV-6B, were identified. In 2012, the International Committee on Taxonomy of Viruses (ICTV) classified HHV-6A and HHV-6B as separate viruses. This review outlines several of the documented epidemiological, biological, and immunological distinctions between HHV-6A and HHV-6B, which support the ICTV classification. The utilization of virus-specific clinical and laboratory assays for distinguishing HHV-6A and HHV-6B is now required for further classification. For clarity in biological and clinical distinctions between HHV-6A and HHV-6B, scientists and physicians are herein urged, where possible, to differentiate carefully between HHV-6A and HHV-6B in all future publications.     

French Spine Surgery Society guidelines for management of spinal surgeries during COVID-19 pandemic

Since the outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in China, various measures have been adopted in order to attenuate the impact of the virus on the population. With regard to spine surgery, French physicians are devoted to take place in the national plan against COVID-19, the French Spine Surgery Society therefore decided to elaborate specific guidelines for management of spinal disorders during COVID-19 pandemic in order to prioritize management of patients. A three levels stratification was elaborated with Level I: Urgent surgical indications, Level II: Surgical indications associated to a potential loss of chance for the patient and Level III: Non-urgent surgical indications. We also report French experience in a COVID-19 cluster region illustrated by two clinical cases. We hope that the guidelines formulated by the French Spine Surgery Society and the experience of spine surgeons from a cluster region will be helpful in order optimizing the management of patients with urgent spinal conditions during the pandemic.     

Variability in estimation of coronary dimensions from 6F and 8F catheters

To investigate the suitability of diagnostic 6F catheters for coronary angiographic measures in the clinical setting, we determined the relative accuracy and reproducibility of the measures obtained with these catheters as scaling devices in 59 stenoses. Comparison was made with duplicate injections, obtained before angioplasty, using an 8F guiding catheter as scaling device. Intra- and interobserver variability was evaluated in 15 stenoses. The coefficient of variation averaged 18.3% for the minimal lumen diameter, 10.4% for the percent stenosis, and only 7.4% for the reference diameter. Reproducibility of angiographic measures done with the 6F catheter was similar to that obtained with the 8F catheter, although accuracy was lower with the 6F for the measurement of reference diameter. Thus, quantitative coronary angiography (QCA) measures derived from routine diagnostic angiograms may be suitable for determination of reference diameter, allowing enough precision for determination of the size of a coronary device for intervention, but these measures may lack accuracy for precise determination of minimum diameter and percent stenosis, making their use questionable in studies looking at individual changes in coronary stenosis dimensions. © 1996 Wiley-Liss, Inc.     

Diabetes and COVID-19 in Congolese patients

BackgroundThe global pandemic Coronavirus Disease 2019 (COVID-19) due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is reported to be potentially severe in patients with morbid conditions. One common reported comorbidities is diabetes. We aimed in this study to precise the clinical characteristics and outcomes in a series of congolese diabetic patients affected by COVID-19 infection.Patients and methodsWe retrospectely studied from 256 COVID-19 patients, a cohort of 30 persons with previously known diabetes. The glycaemia controls have been obtained by plasma glucose assay. All patients have been tested positive to SARS-CoV-2 by RT-PCR method.ResultsThe COVID-19 diabetic patients represented 11,7% of all COVID-19 patients with confidence interval of 95% [7,77–15,65]. Older individuals and male sex were predominent. Dyspnea and sauration of oxygen < 90 were significatives and added risk factors were noted in 63.3% of patients, particulary hyperglycaemia with hypertension or obesity. The mortality rate at the percentage of 36.7% was more prevalent in patients with added comorbidities (30%) versus without comorbidities (6.7%).ConclusionCongolese COVID-19 diabetic patients of male sex and older age exhibiting arterial hypertension and obesity are the most exposed to severe COVID-19 and increasead mortality rate.     

CD169+ macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling

CD169⁺ macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169⁺ macrophages require RANKL for formation of their niche and their differentiation. Here, we demonstrate that they are also dependent on direct lymphotoxin beta (LTβ) receptor (R) signaling. In the absence or the reduced expression of either RANK or LTβR, their differentiation is perturbed, generating myeloid cells expressing SIGN-R1 in LNs. Conditions of combined haploinsufficiencies of RANK and LTβR revealed that both receptors contribute equally to LN CD169⁺ macrophage differentiation. In the spleen, the Cd169-directed ablation of either receptor results in a selective loss of marginal metallophilic macrophages (MMMs). Using a RANKL reporter mouse, we identify splenic marginal zone stromal cells as a source of RANKL and demonstrate that it participates in MMM differentiation. The loss of MMMs had no effect on the splenic B cell compartments but compromised viral capture and the expansion of virus-specific CD8⁺ T cells. Taken together, the data provide evidence that CD169⁺ macrophage differentiation in LN and spleen requires dual signals from LTβR and RANK with implications for the immune response.

CD169⁺ macrophages are strategically localized at the lymphatic sinuses of lymph nodes (LNs) and the marginal zone of the spleen, where they capture lymph- and blood-borne antigens, respectively (1). These macrophages reside close to B cells and mesenchymal stromal cells. B cells are a constitutive source of lymphotoxin (LT) α and LTβ that bind to the LTβ receptor (R) as LTα₁β₂ heterotrimer (2). Lack of B cells and unconditional or B cell–specific ablation of LTα or LTβ lead to loss of CD169⁺ macrophages in LNs and the spleen (3–6). Conversely, B cell–specific overexpression of LTαβ results in an increase of their numbers (7). Furthermore, administration of the decoy fusion protein LTβR-Fc or LTβR inactivation negatively affects their presence in both organs (3, 8, 9). However, although the myeloid cell lineage has been shown to express LTβR (10–12), it remains unclear whether the dependency on LTβR signaling is direct or implies an intermediate cell partner such as the adjacent stromal cells (9, 13, 14).We have recently shown that receptor activator of NF-κB ligand (RANKL) from marginal zone reticular cells (MRCs) regulates the differentiation of CD169⁺ macrophages in the LN (15). Like LTα and LTβ, RANKL is a member of the TNF superfamily and binds to the signaling receptor RANK (16). Stromal RANKL activates the lymphatic endothelial cells to form a cellular niche for macrophages and directly stimulates their differentiation into the CD169⁺ macrophages of the subcapsular sinus (subcapsular sinus macrophages, SSMs). However, a role of stromal RANKL for the splenic CD169⁺ macrophages has not been addressed. LTαβ and RANKL share many similarities in their biological functions. They are both indispensable for the organogenesis of secondary lymphoid organs (17, 18), are involved in the organogenesis of the thymus (19), and contribute to the formation of the intestinal microfold cells (20). However, RANKL stands out for its role in osteoclastogenesis (16), while LTαβ regulates the production of homeostatic chemokines and the differentiation of follicular dendritic cells (2).In the context of partially overlapping functions, we scrutinized the implication of the RANK–RANKL and LTβR–LTαβ axes in the differentiation of LN and splenic CD169⁺ macrophages. Using Cd169-directed conditional deficiency of RANK or LTβR, we report that direct RANK and LTβR signals are required for their differentiation in the LN and the spleen. In the absence of the receptors, LN CD169⁺ macrophages were replaced by myeloid cells phenotypically similar to the SIGN-R1⁺ medullary sinus macrophages. Deficiency of one copy of either Rank or Ltbr alleles sufficed for a prominent decrease in macrophage numbers, but the heterozygous deletion of both genes had a compound effect. Altered macrophage differentiation had a negative impact on lymph-borne antigen transport to B cells. In the spleen, Cd169-directed RANK or LTβR deficiency elicited a selective loss of the CD169⁺ MMMs. By the use of a RANKL reporter mouse together with RT-qPCR of sorted splenic stromal subsets, we identified CCL19⁺ splenic MRCs as a source of RANKL and demonstrated in Ccl19-cre RANKL-deficient mice that stromal RANKL participates in MMM differentiation. Their specific loss had no effect on the marginal zone B cell compartment but compromised viral capture and the formation of the virus-specific CD8⁺ T cell response. Taken together, the data provide evidence that CD169⁺ macrophage differentiation is dependent on the dual signals emanating from LTβR and RANK, with implications for the immune response to lymph- and blood-borne pathogens.     

Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Endometrial cancer (EC) incidence rates vary ~10-fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low-risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow-up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m²), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m²) and HT use (to all non-HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks.