CO-OCCURRENCE OF HYDATID CYST LIVER WITH ACUTE MYELOID LEUKAEMIA: A RARE CASE REPORT.

The term "hydatid disease" refers to echinococcosis. Echinococcosis is a zoonotic disease caused by the larval stage of the Echinococcus parasite. The disease is widespread in regions where the parasite is endemic, particularly in developing nations like India. However, there are only a couple of documented case studies of echinococcosis associated with hematological malignancy in the literature. We present an extremely uncommon case of a 36-year-old male who had liver hydatidosis and was diagnosed with acute myeloid leukemia (AML)-M1. The patient received treatment for acute myeloid leukemia (daunomycin, cytarabine, and 5-azacytidine), followed by management of hydatid disease after complete remission of acute leukemia. The patient underwent periodic evaluations for one year and exhibited satisfactory improvement.

Nemo-like kinase blocks myeloid differentiation by targeting tumor suppressor C/EBPα in AML.

CCAAT/enhancer-binding protein α (C/EBPα), a key myeloid transcription factor, drives myeloid differentiation from blast cells by regulating the expression of granulocyte colony stimulating factor receptor and C/EBPε as required for promoting granulocyte differentiation. Here, we show that serine/threonine-protein kinase NLK, also known as Nemo-like kinase, physically associates with C/EBPα and phosphorylates it at multiple sites, including Ser21, Thr226, Thr230 and S234, leading to its ubiquitin-mediated degradation. Individual phospho-point mutants of C/EBPα could be phosphorylated by NLK, but a mutant with all phosphorylatable residues replaced by alanine resisted phosphorylation and degradation by NLK, as did the single point mutants. Furthermore, although ectopic expression of NLK enhanced phosphorylation of C/EBPα levels, it markedly inhibited total C/EBPα protein levels. Conversely, NLK depletion inhibited endogenous C/EBPα phosphorylation but enhanced its total protein levels in several acute myeloid leukemia (AML) cell lines and in peripheral blood mononuclear cells isolated from number of AML patient samples. Importantly, NLK depletion in peripheral blood mononuclear cells from primary AML patients not only restored C/EBPα protein levels, but also induced myeloid differentiation, suggesting that NLK could be therapeutically targeted to restore C/EBPα to resolve differentiation arrest in AML.

Serum visfatin level in ß-thalassemia and its correlation with disease severity.

Thalassemia is a group of genetic hematological conditions characterized by the defective synthesis of one or more hemoglobin chains. This genetic anomaly alters globin chain balance, causing hemolysis, ineffective erythropoiesis, and chronic inflammatory diseases. The proinflammatory adipocytokine visfatin is predominantly produced in visceral adipose tissue. Its evaluation in individuals with thalassemia may provide valuable insights into the assessment of disease severity. The aim of this study was to investigate the potential role of visfatin in the development of ß-thalassemia and its association with the severity of the illness. The study included 40 patients with ß-thalassemia and ten healthy individuals matched by age and sex. Serum visfatin level was measured using ELISA. We found that individuals with ß-thalassemia major had significantly higher levels of serum visfatin than those with ß-thalassemia minor and the control group (P < 0.001). A receiver operating characteristic curve revealed that serum visfatin levels were different in the three groups. Our results suggest that the serum level of visfatin is significantly correlated with the severity of ß-thalassemia.

A neutrophil elastase-generated mature form of IL-33 is a potent regulator of endothelial cell activation and proliferative retinopathy.

Human interleukin-33 (IL-33) is a 270 amino acid protein that belongs to the IL-1 cytokine family and plays an important role in various inflammatory disorders. Neutrophil proteases (Cathepsin G and Elastase) and mast cell proteases (tryptase and chymase) regulate the activity of IL-33 by processing full-length IL-33 into its mature form. There is little evidence on the role of these mature forms of IL-33 in retinal endothelial cell signaling and pathological retinal angiogenesis. Here, we cloned, expressed, and purified the various mature forms of human IL-33 and then evaluated the effects of IL-3395-270, IL-3399-270, IL-33109-270, and IL-33112-270 on angiogenesis in human retinal microvascular endothelial cells (HRMVECs). We observed that IL-3395-270, IL-3399-270, IL-33109-270, and IL-33112-270 significantly induced HRMVEC migration, tube formation and sprouting angiogenesis. However, only IL-3399-270 could induce HRMVEC proliferation. We used a murine model of oxygen-induced retinopathy (OIR) to assess the role of these mature forms of IL-33 in pathological retinal neovascularization. Our 3'-mRNA sequencing and signaling studies indicated that IL-3399-270 and IL-33109-270 were more potent at inducing endothelial cell activation and angiogenesis than the other mature forms. We found that genetic deletion of IL-33 significantly reduced OIR-induced retinal neovascularization in the mouse retina and that intraperitoneal administration of mature forms of IL-33, mainly IL-3399-270 and IL-33109-270, significantly restored ischemia-induced angiogenic sprouting and tuft formation in the hypoxic retinas of IL-33-/- mice. Thus, our study results suggest that blockade or inhibition of IL-33 cleavage by neutrophil proteases could help mitigate pathological angiogenesis in proliferative retinopathies.

Targeting CERS6-AS1/FGFR1 axis as synthetic vulnerability to constrain stromal cells supported proliferation in Mantle cell lymphoma.

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL.

Recombinant YopE and LcrV vaccine candidates protect mice against plague and yersiniosis.

No licensed vaccine exists for the lethal plague and yersiniosis. Therefore, a combination of recombinant YopE and LcrV antigens of Yersinia pestis was evaluated for its vaccine potential in a mouse model. YopE and LcrV in formulation with alum imparted a robust humoral immune response, with isotyping profiles leaning towards the IgG1 and IgG2b subclasses. It was also observed that a significantly enhanced expression of IFN-γ, TNF-α, IL-6, IL-2, and IL-1ß from the splenic cells of vaccinated mice, as well as YopE and LcrV-explicit IFN-γ eliciting T-cells. The cocktail of YopE + LcrV formulation conferred complete protection against 100 LD50Y. pestis infection, while individually, LcrV and YopE provided 80 % and 60 % protection, respectively. Similarly, the YopE + LcrV vaccinated animal group had significantly lower colony forming unit (CFU) counts in the spleen and blood compared to the groups administered with YopE or LcrV alone when challenged with Yersinia pseudotuberculosis and Yersinia enterocolitica. Histopathologic evidence reinforces these results, indicating the YopE + LcrV formulation provided superior protection against acute lung injury as early as day 3 post-challenge. In conclusion, the alum-adjuvanted YopE + LcrV is a promising vaccine formulation, eliciting a robust antibody response including a milieu of pro-inflammatory cytokines and T-cell effector functions that contribute to the protective immunity against Yersinia infections. YopE and LcrV, conserved across all three human-pathogenic Yersinia species, provide cross-protection. Therefore, our current vaccine (YopE + LcrV) targets all three pathogens: Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica. However, the efficacy should be tested in other higher mammalian models.

Ring finger protein 138 inhibits transcription factor C/EBPα protein turnover leading to differentiation arrest in acute myeloid leukemia.

E3 ubiquitin ligase, ring finger protein 138 (RNF138) is involved in several biological processes; however, its role in myeloid differentiation or tumorigenesis remains unclear. RNAseq data from TNMplot showed that RNF138 mRNA levels are highly elevated in acute myeloid leukemia (AML) bone marrow samples as compared with bone marrow of normal volunteers. Here, we show that RNF138 serves as an E3 ligase for the tumor suppressor CCAAT/enhancer binding protein (C/EBPα) and promotes its degradation leading to myeloid differentiation arrest in AML. Wild-type RNF138 physically interacts with C/EBPα and promotes its ubiquitin-dependent proteasome degradation while a mutant RNF-138 deficient in ligase activity though interacts with C/EBPα, fails to down-regulate it. We show that RNF138 depletion enhances endogenous C/EBPα levels in peripheral blood mononuclear cells (PBMCs) isolated from healthy volunteers. Our data further shows that RNF138-mediated degradation of C/EBPα negatively affects its transactivation potential on its target genes. Furthermore, RNF138 overexpression inhibits all-trans-retinoic acid-induced differentiation of HL-60 cells whereas RNF138 RNAi enhances. In line with RNF138 inhibiting C/EBPα protein turnover, we also observed that RNF138 overexpression inhibited ß-estradiol (E2)-induced C/EBPα driven granulocytic differentiation in C/EBPα inducible K562-p42C/EBPα-estrogen receptor cells. Furthermore, we also recapitulated these findings in PBMCs isolated from AML patients where depletion of RNF138 increased the expression of myeloid differentiation marker CD11b. These results suggest that RNF138 inhibits myeloid differentiation by targeting C/EBPα for proteasomal degradation and may provide a plausible mechanism for loss of C/EBPα expression often observed in myeloid leukemia. Also, targeting RNF138 may resolve differentiation arrest by restoring C/EBPα expression in AML.

Bone marrow metastasis in nonhematological malignancies: A study from tertiary care center.

Introduction: Metastatic cancer presents a treatment challenge to clinicians, particularly for patients with bone marrow infiltration. For tumor staging, therapy selection, and prognosis risk stratification, the status of the bone marrow should be known for the presence or absence of metastasis. The study aimed to evaluate the hematological findings and comprehensive analysis of bone marrow in cases of nonhematological malignancies with bone marrow metastasis. Materials and Methods: This retrospective study comprised a record retrieval of the departmental archives for the past 6 years. A total of 331 patients with nonhematological malignancies were found, of whom 31.42% (104/331) showed bone marrow metastasis. An integrated clinical approach with bone marrow examination findings and immunohistochemistry whenever necessary was used to achieve a definitive diagnosis of bone marrow metastasis. Results: Among the study population, 31.42% (104/331) of patients had nonhematological malignancies that metastasized to the bone marrow. Most of the patients with bone marrow metastasis had anemia, which was found in 77.88% (81/104) of the cases. Leukoerythroblastic reaction was noted in 31.73% (33/104) of the cases, and thrombocytopenia was found in 25% (26/104) of the cases. The most common malignancy with bone marrow metastasis in adults was prostatic adenocarcinoma (28.1%) (9/32) and in pediatric cases, neuroblastoma (53.9%) (52/98). Conclusions: It is essential to diagnose nonhematological malignancies that have metastasized to the bone marrow since this necessitates tumor staging, therapy selection, and prognosis risk stratification. To conclude, not a single hematological parameter is predictive of bone marrow metastasis; however, unexplained anemia, a leukoerythroblastic blood picture, and thrombocytopenia in peripheral blood should raise suspicion for bone marrow metastasis in cases of nonhematological malignancies.

Résumé Introduction: Le cancer métastatique présente un défi de traitement pour les cliniciens, en particulier pour les patients présentant une infiltration de moelle osseuse. Pour la stadification tumorale, la sélection du traitement et la stratification du risque de pronostic, l'état de la moelle osseuse doit être connu pour la présence ou l'absence de métastases. L'étude visait à évaluer les résultats hématologiques et l'analyse complète de la moelle osseuse dans les cas de tumeurs malignes non hématologiques avec métastases de la moelle osseuse. Matériel et méthodes: Cette étude rétrospective comprenait une récupération des archives ministérielles des 6 dernières années. Un total de patients atteints de tumeurs malignes non hématologiques ont été trouvés, dont 31,42% (104/331) présentaient des osmétastases médullaires. Une approche clinique intégrée avec les résultats de l'examen de la moelle osseuse et l'immunohistochimie chaque fois que nécessairea été utilisé pour établir un diagnostic définitif de métastases médullaires. Résultats: Dans la population étudiée, 31,42 % (104/331) des patients présentaient des tumeurs malignes non hématologiques qui se métastasaient à la moelle osseuse. La plupart des patients atteints de métastases de la moelle osseuse présentaient une anémie, qui a été trouvée dans 77,88% (81/104) des cas. Une réaction leucoérythroblastique a été observée dans 31,73 % (33/104) des cas, et une thrombocytopénie a été observée dans 25 % (26/104) des cas. La tumeur maligne la plus fréquente associée aux métastases de la moelle osseuse chez l'adulte était l'adénocarcinome de la prostate (28,1 %) (9/32) et, chez les enfants, le neuroblastome (53,9 %) (52/98). Conclusions: Il est essentiel de diagnostiquer les tumeurs malignes non hématologiques qui ontmétastasé à la moelle osseuse car cela nécessite une stadification tumorale, une sélection thérapeutique et une stratification du risque de pronostic. Pour conclure, pas un seul paramètre hématologique n'est prédictif des métastases de la moelle osseuse; Cependant, une anémie inexpliquée, une image sanguine leucoérythroblastique et une thrombocytopénie dans le sang périphérique devraient faire suspecter des métastases de la moelle osseuse en cas de tumeurs malignes non hématologiques. Mots-clés: Aspiration de moelle osseuse, biopsie de la moelle osseuse, métastases de la moelle osseuse, résultats hématologiques, immunohistochimie, tumeurs malignes non hématologiques, frottis sanguin périphérique.

Antibiotic resistance: a global crisis, problems and solutions.

Healthy state is priority in today's world which can be achieved using effective medicines. But due to overuse and misuse of antibiotics, a menace of resistance has increased in pathogenic microbes. World Health Organization (WHO) has announced ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) as the top priority pathogens as these have developed resistance against certain antibiotics. To combat such a global issue, it is utmost important to identify novel therapeutic strategies/agents as an alternate to such antibiotics. To name certain antibiotic adjuvants including: inhibitors of beta-lactamase, efflux pumps and permeabilizers for outer membrane can potentially solve the antibiotic resistance problems. In this regard, inhibitors of lytic domain of lytic transglycosylases provide a novel way to not only act as an alternate to antibiotics but also capable of restoring the efficiency of previously resistant antibiotics. Further, use of bacteriophages is another promising strategy to deal with antibiotic resistant pathogens. Taking in consideration the alternatives of antibiotics, a green synthesis nanoparticle-based therapy exemplifies a good option to combat microbial resistance. As horizontal gene transfer (HGT) in bacteria facilitates the evolution of new resistance strains, therefore identifying the mechanism of resistance and development of inhibitors against it can be a novel approach to combat such problems. In our perspective, host-directed therapy (HDT) represents another promising strategy in combating antimicrobial resistance (AMR). This approach involves targeting specific factors within host cells that pathogens rely on for their survival, either through replication or persistence. As many new drugs are under clinical trials it is advisable that more clinical data and antimicrobial stewardship programs should be conducted to fully assess the clinical efficacy and safety of new therapeutic agents.

Cost-effectiveness analysis of emicizumab prophylaxis in patients with haemophilia A in India.

INTRODUCTION: Emicizumab is the initial subcutaneously administered bispecific antibody approved as a prophylactic treatment for patients with haemophilia A (PwHA). AIM: This study assessed the economic evaluation of emicizumab treatment for non-inhibitor severe haemophilia A (HA) patients in India. METHODS: A Markov model evaluated the cost-effectiveness of emicizumab prophylaxis compared to on-demand therapy (ODT), low-dose prophylaxis (LDP; 1565 IU/kg/year), intermediate-dose prophylaxis (IDP; 3915 IU/kg/year) and high-dose prophylaxis (HDP; 7125 IU/kg/year) for HA patients without factor VIII inhibitors. Inputs from HAVEN-1 and HAVEN-3 trials included transition probabilities of different bleeding types. Costs and benefits were discounted at a 3.5% annual rate. RESULTS: In the base-case analysis, emicizumab was cost-effective compared to HDP, with an incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years (QALY) of Indian rupees (INR) 27,869. Compared to IDP, ODT and LDP, emicizumab prophylaxis could be considered a cost-effective option if the paying threshold is >1 per capita gross domestic product (GDP) with ICER/QALY values of INR 264,592, INR 255,876 and INR 305,398, respectively. One-way sensitivity analysis (OWSA) highlighted emicizumab cost as the parameter with the greatest impact on ICERs. Probabilistic sensitivity analysis (PSA) indicated that emicizumab had a 94.7% and 49.4% probability of being cost-effective at willingness-to-pay (WTP) thresholds of three and two-times per capita GDP. CONCLUSION: Emicizumab prophylaxis is cost-effective compared to HDP and provides value for money compared to ODT, IDP, and LDP for severe non-inhibitor PwHA in India. Its long-term humanistic, clinical and economic benefits outweigh alternative options, making it a valuable choice in resource-constrained settings.

Cost-effectiveness analysis of low-dose prophylaxis versus on-demand treatment for moderate-to-severe hemophilia A in India.

AIM: Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency of clotting factor VIII in the blood. In resource-limited settings like India, affordability is a significant challenge in managing patients with severe HA. This study aims to assess the cost-effectiveness of intermediate-dose prophylaxis versus on-demand factor therapy in adult and pediatric populations with moderate-to-severe congenital HA without inhibitors in India. METHOD: We conducted a prospective cost-effectiveness analysis from a societal perspective, categorizing patients into a base state and a joint disease state (patients with Hemophilia suffering extensive bleeds leading to chronic joint disease). Using targeted literature search and primary market research, we developed a Markov model measuring the total cost of Hemophilia treatment and health outcomes, including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER). The model extended over a lifetime horizon of 70 years with a one-year cycle length. Sensitivity analyses assessed study robustness. RESULTS: Low-dose prophylactic therapy was cost-effective for adults (>18 years) and pediatric populations (<18 years), yielding better health outcomes (adults: 0.15 LYs and 2.43 QALYs gained; pediatric: 0.40 LYs and 3.12 QALYs gained). Intermediate-dose prophylaxis showed positive net monetary benefits in terms of Quality-Adjusted Life Years (QALYs) for both adult and pediatric populations, with dominant ICER and ICUR values in both cases. CONCLUSION: Using intermediate-dose prophylactic factor VIII therapy is a cost-effective approach that improves clinical outcomes compared to on-demand therapy in the Indian adult and pediatric HA populations without inhibitors.

Pyopneumothorax Secondary to Pulmonary Tuberculosis Superadded by Congenital Factor XIII Deficiency: A Case Report.

Pyopneumothorax is a rare complication of pulmonary tuberculosis, contributing significantly to morbidity and mortality. Additionally, factor XIII deficiency, a rare bleeding disorder, may pose a diagnostic challenge due to normal results in routine coagulation tests. We present the case of an 18-year-old boy who presented with a history of left-sided pyopneumothorax secondary to drug-sensitive Mycobacterium tuberculosis, complicated by congenital factor XIII deficiency. After three months of intercostal drainage placement, the patient developed severe anemia and bleeding tendencies, necessitating a referral to clinical hematology. Genetic testing revealed factor XIII deficiency. This case highlights the complicated interplay between tuberculosis-related complications and a coexisting genetic disorder, highlighting the importance of comprehensive clinical assessment and multidisciplinary management.

Clinicopathological Parameters of Haemophilia Patients at a Tertiary Care Centre in Northern India.

INTRODUCTION: Haemophilia affects a large number of people all over the world, yet very little is known about the clinical manifestations and diagnostic protocols of the condition in areas with limited access to resources in developing countries. Understanding the clinical spectrum and diagnostic approach will help with the design of measures to address the situation in these places. The primary objective of this study was to examine the clinicopathological parameters of haemophiliac patients. MATERIALS AND METHODS: From the departmental archive, a thorough history of each patient was retrieved, including values of bleeding time, prothrombin time, activated partial prothrombin time, and percentage of specific factor activity. RESULTS: Out of a total of 385 cases over the period of six years, 86.75% were classified as haemophilia A and 13.25% of cases were diagnosed as haemophilia B. In terms of the severity of the disease, 44.93% were classified as severe, 42.08% as moderate, and 12.99% as mild. Joint bleeding was the first and most typical clinical manifestation of the disease, accounting for 34.80% of cases, followed by ecchymosis (23.12%), post-traumatic bleeding (12.73%), epistaxis (12.20%), and gum bleeding (8.05%). 1.56% of patients had a positive screening test for the hepatitis C virus, followed by 1.30% for HIV and 0.78% for hepatitis B surface antigen. CONCLUSION: In the presence of joint bleeding, ecchymosis, and post-traumatic bleeding in an otherwise healthy individual, a clinician should be alerted to the possibility that the patient has haemophilia and should request a work-up for the bleeding disorder.

Protective antigen of Bacillus anthracis in combination with TLR4 or TLR5 agonist confers superior protection against lethal challenge in mouse model.

The immunogenicity and protective ability of recombinant PA (rPA) with two innate immune system modulators, i.e., monophosphoryl lipid A (MPLA), a TLR4 agonist, and recombinant flagellin C (FliC), a TLR5 agonist, were studied in the mouse model. BALB/c mice were inoculated with three doses of rPA + alum (Alum group), rPA + FliC + alum (FliC group), rPA + MPLA + alum (MPLA group), or only alum adjuvant (Alum alone group). Significant increases in anti-PA IgG titers were observed in the Alum, FliC and MPLA groups when compared to control Alum alone group. Similarly, a significant enhancement of proinflammatory (TNF-α, IL-1ß), Th1 (IFN-γ, IL-12(p70), IL-2) and Th2 (IL-10, IL-4) cytokines were also noticed in Alum, FliC and MPLA groups compared to Alum alone group. The rPA-specific IgG and cytokine responses in MPLA and FliC groups were significantly higher than the Alum group, suggesting enhancement of immune response by these TLR agonists. MPLA was also found to skew the IgG1:IgG2a ratio towards IgG2a. At a challenge dose of 25 LD50, complete protection was observed in mice of MPLA group whereas lesser protection was observed in FliC (87%) and Alum (50%) groups. Therefore, we suggest the use of MPLA in further development of rPA based anthrax vaccines.

Study of Hemato-morphological Features in Neuroblastoma Infiltrating Marrow.

Objective Neuroblastoma typically affects children within the first 5 years of life and accounts for 10% of all pediatric malignancies. Neuroblastoma at onset may manifest as a localized or metastatic illness. The aim of this study was to identify hematomorphological features in neuroblastoma infiltrating marrow as well as to ascertain the prevalence of bone marrow infiltration in neuroblastoma. Materials and Methods This retrospective study included newly diagnosed 79 cases of neuroblastoma, which were referred for bone marrow examination for the staging of the disease. Medical records were retrieved to acquire hematomorphological findings of peripheral blood and bone marrow smears. Statistical Package for Social Sciences, IBM Inc., USA, version 21.0 was used to analyze the data. Results The interquartile age range of neuroblastoma cases was 24.0 to 72.0 months (median = 48 months) with a male to female ratio of 2.7:1. Also, 55.6% (44/79) of cases in the study population showed evidence of marrow infiltration. The bone marrow infiltration was significantly linked to thrombocytopenia ( p = 0.043) and nucleated red blood cells ( p = 0.003) in peripheral blood. The bone marrow smears of cases with infiltration showed a significant shift to the left in the myeloid series ( p = 0.001) and an increased number of erythroid cells ( p = 0.001). Conclusion For neuroblastoma patients, a diligent, exhaustive search for infiltrating cells in bone marrow is advised if thrombocytopenia or nucleated red blood cells are identified on a peripheral blood smear and bone marrow smears showed myeloid left shift with an increased number of erythroid cells.

Early and Effective Diagnosis of Sepsis Using Flow Cytometry.

Objective Sepsis is a major global health issue due to its high death and morbidity rates. To avoid the negative effects of sepsis and decrease mortality, it is vital to diagnose and treat it as soon as possible. Blood cultures can take up to 2 days to give result, and they are not always reliable. According to recent studies, neutrophil CD64 expression might be a sensitive and specific option for assessing sepsis. This study aimed to evaluate the diagnostic performance of a flow cytometry analysis for the expression of neutrophil CD64 in sepsis and its comparison with other standard tests in a tertiary care center. Materials and Methods Prospective analysis on 40 blood samples from suspected sepsis patients admitted to intensive care units with criteria for the systemic inflammatory response syndrome on presentation was performed for expression of neutrophil CD64, C-reactive protein, procalcitonin, and complete blood count. Ten healthy volunteers were also enrolled in this prospective study. The laboratory results were compared in different groups. Results The neutrophil CD64 had the highest diagnostic value to differentiate between patients of sepsis and nonsepsis groups with a sensitivity of 100% (95% confidence interval [CI]: 77.19-100%) and 100% (95% CI: 55.32-86.83%); specificity of 90.00% (95% CI: 59.58-99.49%) and 87.24% (95% CI: 66.69-99.61%); and likelihood ratio of 10.00 and 7.84, respectively. Conclusion The neutrophil CD64 expression provides a more sensitive, specific, and novel marker for the early detection of sepsis in critically ill patients.

Broad-Spectrum Antivirals against Multiple Human and Animal Coronaviruses Infection.

Among the seven coronaviruses that infect humans, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 usually cause mild and common cold symptoms; however, infection with three coronaviruses, namely severe acute respiratory syndrome coronavirus [SARS-CoV], Middle East respiratory syndrome coronavirus [MERS-CoV], and the newly identified severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], often results in respiratory distress, cytokine storm and multiorgan failure [...].

Safety, Tolerability, and Immunogenicity of COVID-19 Bivalent Vaccination.

The COVID-19 pandemic has triggered unparalleled global disruption [...].