The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48

Mast cells are well known for their harmful role in IgE-mediated hypersensitivity reactions, but their physiological role remains a mystery. Several recent studies have reported that mast cells play a critical role in innate immunity in mice by releasing tumor necrosis factor alpha (TNF-alpha) to recruit neutrophils to sites of enterobacterial infection. In some cases, the mast cell TNF-alpha response was triggered when these cells directly bound FimH on the surface of Escherichia coli. We have identified CD48, a glycosylphosphatidylinositol-anchored molecule, to be the complementary FimH-binding moiety in rodent mast cell membrane fractions. We showed that (i) pretreatment of mast cell membranes with antibodies to CD48 or phospholipase C inhibited binding of FimH+ E. coli, (ii) FimH+ E. coli but not a FimH- derivative bound isolated CD48 in a mannose-inhibitable manner, (iii) binding of FimH+ bacteria to Chinese hamster ovary (CHO) cells was markedly increased when these cells were transfected with CD48 cDNA, and (iv) antibodies to CD48 specifically blocked the mast cell TNF-alpha response to FimH+ E. coli. Thus, CD48 is a functionally relevant microbial receptor on mast cells that plays a role in triggering inflammation.     

Simple Mobile Application for Calculating “Ergotrauma” Made Using an Excel Sheet

How to cite this article: Anand A, Saigal S, Panda R, Kodamanchili S, Shrivastava P, Das A, et al. Simple Mobile Application for Calculating “Ergotrauma” Made Using an Excel Sheet. Indian J Crit Care Med 2021;25(9):1081.     

Reanalyzing the Mortality Analysis of COVID-19 Deaths in a Tertiary Care Center in India

How to cite this article: Anand A, Panghal R, Kaler P, Saigal S, Panda R, Kodamanchili S, et al. Reanalyzing the Mortality Analysis of COVID-19 Deaths in a Tertiary Care Center in India. Indian J Crit Care Med 2021; 25(10):1211.

Sir,Recently, one of the most awaited publications by the premier government medical institute of our country, titled “Clinicoepidemiological Features and Mortality Analysis of Deceased Patients with COVID-19 in a Tertiary Care Center”, was a very delightful read.¹ All the intensivists of India look up to this institute for regular guidelines of management of COVID-19. It is a very informative and learning piece analyzing mortality among the patients admitted to one of the (intensive care units) ICU of this center.When compared with other similar studies across the globe, this paper does not provide supplementary data that could have answered questions like how many of the admitted patients were intubated in total and what was the mortality rate among the subgroup who were intubated.^2,3 Rather a retrospective approach of data representation has been employed, which tells that among the total 247 deceased patients, 24.2% were intubated and 30.3% of total deceased were intubated within 24 hours. Even this representation does not throw light on how many patients of total 654 patients were intubated during their ICU stay. The policy guiding intubation of patients should also be specified as if it was decided by the intensivist on duty or by any fixed institutional criteria.The incidence of pulmonary embolism (PE) among the deceased in the original paper is 2.8%, which is quite less than reported by Mahmoud et al. in a meta-analysis who reported the overall PE rate in ICU to be 19%, and on autopsy, 22% of deceased patients were found to have PE in COVID-19.⁴ The question that remains unanswered is how were those patients, who died in this published paper, diagnosed with PE. The diagnosis of PE was a clinical diagnosis or radiological diagnosis or by autopsy should have been specified. If the incidence of PE is so less than what was the antithrombotic practice of the institute as this piece of information can help to save many lives.     

Antiretroviral therapy in prevention of HIV and TB: update on current research efforts

There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies.     

Development of a quantitative cell-based ELISA, for a humanized anti-IL-2/IL-15 receptor beta antibody (HuMikbeta(1)), and correlation with functional activity using an antigen-transfected murine cell line

The HuMikbeta(1), a humanized IgG1 monoclonal antibody directed toward the IL-2/IL-15 receptor beta-chain (CD122), inhibits the actions of the inflammatory cytokine IL-15, and may be useful for immunotherapy of an array of autoimmune disorders as well as diseases associated with the retrovirus human T-cell lymphotrophic virus 1 (HTLV-1). In order to facilitate the production of material for clinical investigation, we developed a cell-based ELISA (CbELISA) for measuring the binding activity, as a potential biological activity marker, of the HuMikbeta(1) monoclonal antibody to a transfected 32D mouse cell line (32Dbeta) expressing IL-2Rbeta antigen on the cell surface. There is specific binding of HuMikbeta(1) to the transfected cell line, titrating out in the concentration range of 1-1,000 ng/ml. Under identical conditions, there was no binding of HuMikbeta(1) to the parent cell line 32D. Satisfactory binding curves with HuMikbeta(1) were obtained with 32Dbeta cells grown between 3 and 19 passages in culture and at seed densities of 2 x 10(5)-4 x 10(6) cells/well. The binding was specific for Mikbeta antibodies recognizing the IL-2/IL-15 receptor beta subunit as demonstrated by binding of HuMikbeta(1), Mikbeta(2) and Mikbeta(3) antibodies, and lack of binding of irrelevant humanized and chimeric antibodies and isotype-matched human IgG1 to the 32Dbeta cell. Also, the human IgG1 and irrelevant humanized and chimeric antibodies did not interfere with the HuMikbeta(1) binding. The assay could detect changes in binding activity of HuMikbeta(1) antibody under stressful conditions (heat and low pH) and the results paralleled the effect of stress on the physicochemical characteristics. More importantly, the binding activity shows an apparent correlation to inhibition of IL-15-induced proliferation of 32Dbeta cells with HuMikbeta(1). In conclusion, the cell-based ELISA method represents a simple, reproducible accurate quantitative assay for monitoring HuMikbeta(1) activity and could be used as a potency marker assay for monitoring the lot-lot consistency and functional stability of HuMikbeta(1) product.     

Repeatability of left ventricular dyssynchrony and function parameters in serial gated myocardial perfusion SPECT studies

Background  

The purpose of this study was to establish the repeatability of left-ventricular (LV) dyssynchrony and function parameters measured from serial gated myocardial perfusion SPECT (GMPS) studies.