Evaluation of self-measured blood pressure monitoring in a southern rural West Virginia health system.

INTRODUCTION: At the time of the 2021 Behavioral Risk Factor Surveillance System survey, an estimated 32.3% of adults in the US and nearly half (43.4%, 776 000) of adults in West Virginia (WV) had hypertension. Further, the Interactive Atlas of Heart Disease and Stroke estimates an increase in the percentage of adults with hypertension in the US from 32.3% to 47.0%, with hypertension rates in WV rising as high as 58.7%, indicating a significant public health concern in the community. Hypertension increases the risk of several negative health outcomes, including heart disease and stroke, and leads to increased economic and chronic disease burden. Although certain unmodifiable factors (sex, age, race, ethnicity, and family history) increase the risk of developing hypertension, a healthy lifestyle - including a nutritious diet, maintaining a healthy weight, avoiding nicotine products, and participating in regular moderate physical activity - can decrease the risk of developing hypertension. Self-measured blood pressure (SMBP) monitoring, or home BP monitoring, when integrated with a provider's clinical management approach, is linked to improvements in BP management and control. This study represents a mid-point assessment of a remote SMBP monitoring program implemented by Cabin Creek Health Systems (CCHS), a federally qualified health center, and its impact on BP control. METHODS: CCHS implemented SMBP programming in March 2020 as one element of a developing comprehensive program aimed at reducing uncontrolled hypertension, and therefore chronic disease burden, in its service area and patient population. The project, funded by the Health Resources and Services Administration, continued to February 2023. This report represents a mid-point analysis and was based on the retrospective analysis of de-identified data collected for 234 patients to June 2022, who were assessed for changes in BP between the date of enrollment and the most recently available BP measurement. Patients were enrolled in the SMBP program if they exhibited current or previous indicators of uncontrolled hypertension (systolic ≥140 mmHg and/or diastolic ≥90 mmHg), at the discretion of their provider, and were equipped with an iBloodPressure cellular connected home BP monitoring system, manufactured by Smart Meter. Their BP readings were documented in the integration software TimeDoc Health and electronic health record athenahealth. RESULTS: At the time of enrollment, 201 (86.0%) patients had uncontrolled hypertension, with 116 (49.6%) patients having both uncontrolled systolic (≥140 mmHg) and diastolic (≥90 mmHg) values. At follow-up, the number of patients with uncontrolled hypertension decreased from 201 to 98 (41.9%), with only 36 (15.4%) patients having both uncontrolled systolic and diastolic values. Additionally, 26 (11.1%) patients were in hypertensive crisis at the time of enrollment, and no patients remained in crisis at the time of follow-up. The number of patients with BP values in the controlled range (systolic <140 mmHg and diastolic <90 mmHg) increased from 33 (14.1%) at enrollment to 136 (58.1%) at follow-up. Overall, there was a 44.0% increase in the number of patients with BP values in the controlled range at follow-up, and a concomitant 44.1% decrease in the number of patients in the uncontrolled range. These observations were consistent across multiple demographic indicators, including clinic location, three-digit zip code, and patient sex. CONCLUSION: Systematic implementation of remote BP monitoring, when integrated into clinician workflows, was associated with a substantial reduction in the number of patients with uncontrolled hypertension in this rural federally qualified health center. Further, CCHS was successful in implementing a remote SMBP monitoring program in a community challenged with transportation insecurity, and poor cellular and broadband access, of which lessons learned are applicable to other health systems interested in pursuing comparable efforts.

Antibody responses of variable lymphocyte receptors in the lamprey.

Lamprey and hagfish, the living representatives of jawless vertebrates, use genomic leucine-rich-repeat cassettes for the combinatorial assembly of diverse antigen receptor genes encoding variable lymphocyte receptors of two types: VLRA and VLRB. We describe here the VLRB-bearing lineage of lymphocytes in sea lamprey. These cells responded to repetitive carbohydrate or protein determinants on bacteria or mammalian cells with lymphoblastoid transformation, proliferation and differentiation into plasmacytes that secreted multimeric antigen-specific VLRB antibodies. Lacking a thymus and the ability to respond to soluble protein antigens, lampreys seem to have evolved a B cell-like system for adaptive humoral responses.

Pathologic findings and causes of death in southern right whales Eubalaena australis, Brazil.

Southern right whales Eubalaena australis (SRWs) migrate to southern Brazil for breeding and calving from June through November. Overall, there is scarce knowledge on health status and pathologic conditions in SRWs. We report the pathologic and molecular investigation results of 8 SRWs that were necropsied between 2010 and 2017 within a breeding and calving ground in Santa Catarina state, Brazil. The animals were of various ages (7 newborns/calves, 1 adult) and sex (3 females, 5 males). Five whales stranded dead; 3 stranded alive and died shortly after (n = 2) or were euthanized (n = 1). The causes of stranding and/or death were neonatal respiratory distress syndrome with meconium aspiration (n = 3) with concomitant congenital hepatopathy in one of them; trauma of unknown origin (n = 3), infectious renal and lung disease with presumed sepsis (n = 1), and euthanasia (n = 1). Three animals were PCR-positive for cetacean morbillivirus; one of them also had morbilliviral antigen in kidney via immunohistochemical analysis. These results, integrating novel findings and a published report, contribute to the pathology knowledge of this species.

Flap cover in a patient with severe haemophilia type A.

Haemophilia A is a rare haematological disorder due to deficiency of Factor VIII, causing an abnormal coagulation response to injury. In severe haemophilia A, Factor VIII level is < 1%, often manifesting with spontaneous bleeding into joints. Judicious use of recombinant Factor VIII therapy to maintain adequate levels in the intraoperative, immediate and late post-operative periods, together with adjuvant pro-coagulants, can ensure a safe outcome following surgery. We describe the successful management of one such patient suffering from Marjolin's ulcer of the right gluteal region, who needed wide local excision followed by flap cover. A protocol for management of such patients is also suggested. This is the first such case report from the Indian subcontinent, with only a few such published reports from the West.

Pathophysiology of the hepoxilins.

There is increasing evidence from various scientific groups that hepoxilins represent novel inflammatory mediators. In vitro studies have shown that the hepoxilins cause mobilization of intracellular calcium in human neutrophils, cause plasma leakage, and potently stimulate chemotaxis of human neutrophils. In vivo, the hepoxilin pathway is activated in conditions of inflammation, e.g. after pathogen infection, in inflamed conditions (psoriasis, arthritis), and hepoxilins promote inflammatory hyperalgesia and allodynia. Although much work has demonstrated an effect of hepoxilins on neutrophils, the hepoxilin pathway has been demonstrated in a variety of tissues, including the lung, brain, pituitary, pancreatic islets, skin, etc. A genetic defect linked to a deficiency in hepoxilin formation has been described and believed to be responsible for the scaly skin observed in ichthyosis. Despite their biological and chemical instability, the involvement of the hepoxilin pathway in pathology has been demonstrated in vitro and in vivo through either isolation of the hepoxilins themselves (or their metabolites) or implied through the use of stable hepoxilin analogs. These analogs have additionally shown efficacy in animal models of lung fibrosis, cancer, thrombosis and diabetes. Research on these compounds has merely scratched the surface, but results published to date have suggested that the hepoxilin pathway is a distinct and novel pathway leading to inflammation and hepoxilin antagonists may provide the means of controlling early aspects of the acute inflammatory phase. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

Correction: Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

[This corrects the article DOI: 10.7759/cureus.58941.].

Expert Opinions on the Management of Hemophilia A in India: The Role of Emicizumab.

Hemophilia A (HA) is a genetic disorder of hemostasis associated with a deficiency or reduced activity of clotting factor VIII (FVIII). This disorder remains unacceptably underdiagnosed in India. Early diagnosis and appropriate management of HA can substantially prevent morbidity and mortality. Currently, HA is managed with regular replacement therapy using standard or extended half-life FVIII concentrates or non-factor drug products. The challenges associated with FVIII concentrates include plateauing of drug effect, issues with its administration and adherence to treatment, breakthrough bleeds, and the development of inhibiting antibodies against administered clotting factors. Emicizumab is a bispecific antibody, launched in India in April 2019, for managing patients with HA. To investigate the role of emicizumab in Indian patients with HA, opinions were sought from 13 eminent hematologists and experts from India on the effectiveness of emicizumab in preventing all bleeds, spontaneous bleeds, perioperative bleeds, and intracranial hemorrhage; resolving target joints; and reducing the rate of hospitalizations and fatality associated with HA in children and adults, with or without inhibitors. The benefits of emicizumab over traditional FVIII concentrates include the subcutaneous route of delivery, less frequent dosing, and a lack of inhibitor development, in addition to providing sustained hemostasis without in-depth monitoring. It is a safe and effective management option for all HA patients, especially for patients with certain archetypes, such as those with inhibitors, those with high annualized bleed rates, those living far away from hemophilia care centers, pediatric patients and infants with intravenous access challenges, and those with a history of life-threatening bleeding events.

Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

Lung resistance-related protein (LRP) expression in malignant ascitic cells as a prognostic marker for advanced ovarian serous carcinoma.

PURPOSE: Ovarian serous carcinoma is an aggressive cancer that often presents with metastatic disease. Although primary tumor and established metastatic foci in the omentum are generally compared to identify proteins involved in drug resistance, we investigated a potential bridge, the malignant cells from ascites, as facilitator of drug resistance and recurrence. METHODS: We evaluated the expression of drug resistance markers P-glycoprotein (P-gp), canalicular multispecific organic anion transporter (MRP2), and lung resistance-related protein (LRP) in malignant cells from ascites and matched omental metastasis from 25 patients with advanced-stage ovarian serous carcinoma who were chemotherapeutic naïve and undergoing initial cytoreductive surgery. Cell viability in vitro, patient response to chemotherapy, and patient survival were correlated with these biomarkers. RESULTS: Of the 25 patients evaluated for a correlation of LRP to 1-year recurrence, we correctly predicted the 1-year recurrence of 24 patients based solely on the presence of LRP in ascitic tumor cells (p=0.01). P-gp and MRP2 were not expressed in malignant cells of ascites or omental metastases. Malignant cells from ascites had higher expression of LRP and were found to be more resistant to carboplatin treatment than cells from omental metastasis (p=0.00375) by in vitro assay. LRP expression in the malignant cells of ascites correlated with carboplatin resistance (p=0.001) by in vitro assay and recurrence at 1 year (p=0.0125). CONCLUSIONS: LRP expression in malignant cells of ascites is a promising marker to predict response to first-line chemotherapy in patients with advanced ovarian serous carcinoma.

Alterations in eicosanoid levels during U937 bcl-xL tumour growth suppression and recovery in NU/NU mice in vivo-Involvement of phospholipase A2.

We report the effects of two anti-cancer drugs, PBT-4, an experimental antagonist to the pro-inflammatory hepoxilins, and Gleevec (STI-571), an anti-leukaemic drug, on eicosanoid tumour levels in immunodeficient mice (NU/NU) xenografted with the leukaemic cell line, U937 bcl-xL. After the tumours had grown to 80-100mm(3) volume, an 8-day treatment with the drugs was initiated and the animals were monitored for 28 days. On various days, tumours were removed for measurement of 24 omega-6 eicosanoids. The data show remarkable direct correlation between inhibition of tumour AA release and 12-LOX products (including 12-HETE and hepoxilins) during PBT or STI treatment with tumour growth suppression. These findings suggest that inhibition of AA release may represent a novel underlying mechanism of action of PBT-4 (and STI) in vivo in suppressing tumour growth. As the PBT wears off, AA and 12-LOX products rise rapidly (Day 18) leading to the observed tumour growth spurt.

Hepoxilins in cancer and inflammation--use of hepoxilin antagonists.

Cancer is often accompanied with inflammatory, thrombotic, and diabetic complications. Alternatively, chronic inflammation is believed to be a causative factor in several cancers. This review article brings together reported biological actions in these areas of the unstable naturally derived hepoxilins (HX), metabolites of arachidonic acid formed through the 12-LO pathway, and those of their synthetically derived stable HX antagonists (PBT; proprietary bioactive therapeutics). Although the HX pathway has been known for some three decades since its discovery by the author with much data originating from the author's laboratory, studies by others over the past few years have confirmed early findings of the actions of HX as potent pro-inflammatory chemoattractant mediators and further showed HX to be involved in bacterial infection (Salmonella-induced intestinal inflammation and in bone inflammation caused by infection with the Lyme bacterium). The HX pathway appears to be an important early signal leading to inflammation. This provides important therapeutic potential for the PBTs as the only available selective antagonists of this pathway. The PBTs have shown benefit and efficacy in animal models of cancer and inflammation, which together with their known actions as anti-thrombotic (thromboxane (TPα) receptor antagonists) and hypoglycemic agents in vivo appears to make the PBTs suitable as therapeutics to control these disorders. The PBT structure is both stable in vivo and is essentially devoid of side effects in the animal models tested. The PBT structure serves as an important platform for selective HX and TX antagonists.

Inhibition of the catalytic function of activation-induced cytidine deaminase promotes apoptosis of germinal center B cells in BXD2 mice.

OBJECTIVE: To determine whether functional suppression of the catalytic domain of activation-induced cytidine deaminase (AID) can suppress the hyperreactive germinal center (GC) responses in BXD2 mice. METHODS: We generated transgenic BXD2 mice expressing a dominant-negative (DN) form of Aicda at the somatic hypermutation site (BXD2-Aicda-DN-transgenic mice). Real-time quantitative reverse transcriptase-polymerase chain reaction was used to determine the expression of Aicda and DNA damage/repair genes. Enzyme-linked immunosorbent assay was used to measure serum levels of autoantibodies and immune complexes (ICs). Development of GCs and antibody-containing ICs as well as numbers of proliferative and apoptotic cells were determined using flow cytometry and/or immunohistochemical analyses. Development of arthritis and kidney disease was evaluated histologically in 6-8-month-old mice. RESULTS: Suppression of the somatic hypermutation function of AID resulted in a significant decrease in autoantibody production without affecting the expression of DNA damage-related genes in GC B cells of BXD2-Aicda-DN-transgenic mice. There was decreased proliferation, increased apoptosis, increased expression of caspase 9 messenger RNA in GC B cells, and lower numbers of GCs in the spleens of BXD2-Aicda-DN-transgenic mice. Decreased GC response was associated with lower levels of IgG-containing ICs. Anti-IgM- and anti-CD40 plus anti-Ig-induced B cell proliferative responses were decreased in BXD2-Aicda-DN-transgenic mice. CONCLUSION: Inhibition of the AID somatic hypermutation function in BXD2 mice suppressed development of spontaneous GCs, generation of autoantibody-producing B cells, and autoimmunity in BXD2 mice. Suppression of AID catalytic function to limit selection-based survival of GC B cells could become a novel therapy for the treatment of autoimmune disease.

The value of using emotions in solution focused brief therapy.

A commonly stated critique of Solution Focused Brief Therapy (SFBT) is a lack of attention to the client's emotional experience and the use of emotion as a mechanism for producing meaningful change. We review and define the current research regarding emotion, feeling, and affect and its value and relevance to the clinical application of SFBT. We also provide a brief history of the SFBT model and its documented emphasis on cognitive and behavioral change versus emotional change. In embodying the spirit of this approach for examining what works and doing more of it, we propose a next step of SFBT to more overtly attend to the emotional language of clients and to purposefully create emotional experiences with our clients. We demonstrate this by providing clinical examples for how SFBT practitioners can incorporate and build upon clients' emotional language to create emotionally-changing experiences to more broadly and effectively co-create long-lasting change.

Early therapy evaluation of combined cetuximab and irinotecan in orthotopic pancreatic tumor xenografts by dynamic contrast-enhanced magnetic resonance imaging.

Early pancreatic cancer response following cetuximab and/or irinotecan therapies was measured by serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before and during therapy. Groups 1 to 4 (n  =  6/group) of SCID mice bearing orthotopic pancreatic adenocarcinoma xenografts expressing luciferase were treated with phosphate-buffered saline, cetuximab, irinotecan, or cetuximab combined with irinotecan, respectively, twice weekly for 3 weeks. DCE-MRI was performed on days 0, 1, 2, and 3 after therapy initiation, whereas anatomic magnetic resonance imaging was performed on days 0, 1, 2, 3, 6, and 13. Bioluminescence imaging was performed on days 0 and 21. At day 21, all tumors were collected for further histologic analyses (Ki-67 and CD31 staining), whereas tumor dimensions were measured by calipers. The Ktrans values in the 0.5 mm-thick peripheral tumor region were calculated, and the changes in Ktrans during the 3 days posttherapy were compared to tumor volume changes, bioluminescent signal changes, and histologic findings. The Ktrans changes in the peripheral tumor region after 3 days of therapy were linearly correlated with 21-day decreases in tumor volume (p < .001), bioluminescent signal (p  =  .050), microvessel densities (p  =  .002), and proliferating cell densities (p  =  .001). This study supports the clinical use of DCE-MRI for pancreatic cancer patients for early assessment of an anti-epidermal growth factor receptor therapy combined with chemotherapy.

Extracelluar matrix metalloproteinase as a novel target for pancreatic cancer therapy.

The objective of this study was to evaluate extracellular matrix metalloproteinase (EMMPRIN) as a novel target in orthotopic pancreatic cancer murine models. MIA PaCa-2 human pancreatic tumor cells were implanted in groups 1 and 3-7, whereas MIA PaCa-2 EMMPRIN knockdown cells were implanted in group 2. Dosing with anti-EMMPRIN antibody started immediately after implantation for groups 1-3 (residual tumor model) and at 21 days after cell implantation for groups 4-7 (established tumor model). Groups 3, 5, and 7 were treated with anti-EMMRPIN antibody (0.2-1.0 mg) twice weekly for 2-3 weeks, whereas the other groups served as the control. In the residual tumor model, tumor growth of anti-EMMPRIN-treated group was successfully arrested for 21 days (15 ± 4 mm(3)), which was significantly lower than that of the EMMPRIN knockdown group (80 ± 15 mm(3); P=0.001) or the control group (240 ± 41 mm(3); P<0.001). In the established tumor model, anti-EMMPRIN therapy lowered tumor volume increase by approximately 40% compared with the control, regardless of the dose amount. Ki67-expressed cell density of group 5 was 939 ± 150 mm(-2), which was significantly lower than that of group 4 (1709 ± 145 mm(-2); P=0.006). Microvessel density of group 5 (30 ± 6 mm(-2)) was also significantly lower than that of group 4 (53 ± 5 mm(-2); P=0.014), whereas the microvessel size of group 5 (191 ± 22 µm(2)) was significantly larger than that of group 4 (113 ± 26 µm(2); P=0.049). These data show the high potential of anti-EMMPRIN therapy for pancreatic cancer and support its clinical translation.

Differential sensitivity of TOMAL subtests and index scores to pediatric traumatic brain injury.

The objective of the present study was to examine and compare the subtest, index, and factor scores of the Test of Memory and Learning (TOMAL), using receiver-operating characteristic curves, to investigate their sensitivity and specificity to traumatic brain injury (TBI) in children and adolescents. One hundred and fifty participants who had sustained TBI were compared to 150 controls matched on age and gender from the TOMAL's standardization sample. Results indicated that the greatest area under the curve (AUC) was for the Object Recall (OR) subtest score, the Composite Memory Index (CMI), and the attention factor score. The optimal CMI cutoff score for a TBI diagnosis was 83. When factor scores were compared, the attention factor and two verbal factors had significantly larger AUCs than the three nonverbal factors. These findings suggest that the OR subtest and CMI are most sensitive to TBI, and that when components were broken into factors with no overlapping subtests, attention and verbal memory were optimal for classifying TBI.

MYSTAT: A compact potentiostat/galvanostat for general electrochemistry measurements.

An open-source potentiostat/galvanostat instrument design is introduced that provides the ability to take accurate measurements over a current range of ±200 mA and a potential range of ±12 V. The improved capability of the instrument compared to the previously published design upon which it is based makes it suitable for performing a wider range of electrochemical measurements including the ability to use larger working electrodes, study of high current density processes, study of electrochemistry in nonaqueous solutions and use in high voltage processes such as electrophoretic deposition. The instrument can be controlled from any computer capable of running the Python programming language, including a low-cost Raspberry Pi. Unlike many commercial potentiostat designs, the instrument is completely open-source, giving researchers the ability to modify the hardware and software as needed for custom measurement techniques. The low cost makes the instrument attractive for research and teaching laboratories in which multiple electrochemical measurements need to be carried out in parallel.

Autoimmune Hemolytic Anaemias in Pregnancy: Experience in a Tertiary Care Hospital in South India.

BACKGROUND: Autoimmune hemolytic anaemia is very rare and there is limited data regarding their pregnancy outcomes. Hence we aimed to study the maternal and perinatal outcomes in pregnancies with autoimmune hemolytic anaemias (AIHA). METHODS: A retrospective descriptive study of pregnant women with AIHA, who delivered at SJMCH between January 2011 and January 2016 was carried out. Their antenatal and labour records were reviewed and demographic details noted.The primary outcome measures studied were-the prevalence of AIHA, gestational age at delivery, antepartum, intrapartum and postpartum complications, mode of delivery and requirement of transfusion of blood and blood products. The secondary outcome measures studied included neonatal outcomes such as low birth weight, intrauterine growth restriction and need for intensive care. The data is presented as descriptive statistics, including means and percentage. RESULTS: The prevalence of AIHA was (18/12,420) 0.14%. The mean gestational age at delivery was 34 weeks; 100%, 77% and 50% had antenatal, intra partum or postpartum complications, respectively. 44% had preeclampsia, 38% intrauterine growth restriction and 16% preterm labour. 83% required additional drugs for treatment of AIHA.72% had vaginal delivery; 28% had caesarean delivery; 33% were transfused antenatally and 22% postnatally; 50% of the babies were preterm and required intensive care, 66% had low birth weight. There was no maternal mortality. CONCLUSION: Multidisciplinary approach, early diagnosis and detection of autoimmune hemolytic anaemia and complications, good antenatal care, judicious transfusions and delivery at tertiary care centre are the keys to successful outcomes.

Preparing Teachers to Teach in K-12 Blended Environments: A Systematic Mapping Review of Research Trends, Impact, and Themes.

Despite evidence concerning the widespread growth of K-12 blended teaching and the impact that emergency remote teaching during the COVID-19 pandemic has had on the spread of K-12 online and blended teaching, we could find no systematic reviews focused on preparing K-12 teachers for blended teaching. Previous literature reviews, such as those from Halverson et al. (2012) and Drysdale et al. (2013), have noted the lack of research focused on K-12 blended teaching contexts. This systematic mapping review (Grant & Booth, 2009) of 88 K-12 blended teacher preparation articles focused on identifying trends in author impact according to citation count and number of publications, journal impact according to number of publications, prevalence of research methods, and prevalence of research themes according to research questions and findings. The analysis provides a valuable snapshot of current literature, sets a foundation for a deeper thematic analysis of K-12 blended teacher preparation literature, and identifies some potential areas for future K-12 blended teaching research.

Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients.

Background: Early biomarkers of progression to severe dengue are urgently required to enable effective patient management and control treatment costs. Innate immune cells, which comprise the earliest responders to infection and along with the cytokines and chemokines they secrete, play a vital role in orchestrating the subsequent adaptive immune response and have been implicated in the enhancement of infection and "cytokine storm" associated with dengue severity. We investigated the early innate immune cytokine profile of dengue patients during acute phase of disease in a prospective blinded study that included subjects with acute dengue and febrile controls from four major hospitals in Bengaluru, India along with healthy controls. We used intracellular cytokine staining and flow cytometry to identify innate immune biomarkers that can predict progression to severe dengue. Results: Dengue infection resulted in enhanced secretion of multiple cytokines by all queried innate immune cell subsets, dominated by TNF-α from CD56+CD3+ NKT cells, monocyte subsets, and granulocytes along with IFN-γ from CD56+CD3+ NKT cells. Of note, significantly higher proportions of TNF-α secreting granulocytes and monocyte subsets at admission were associated with mild dengue and minimal symptoms. Dengue NS1 antigenemia used as a surrogate of viral load directly correlated with proportion of cytokine-secreting innate immune cells and was significantly higher in those who went on to recover with minimal symptoms. In patients with secondary dengue or those with bleeding or elevated liver enzymes who revealed predisposition to severe outcomes, early activation as well as efficient downregulation of innate responses were compromised. Conclusion: Our findings suggested that faulty/delayed kinetics of innate immune activation and downregulation was a driver of disease severity. We identified IFN-γ+CD56+CD3+ NKT cells and IL-6+ granulocytes at admission as novel early biomarkers that can predict the risk of progression to severity (composite AUC = 0.85-0.9). Strong correlations among multiple cytokine-secreting innate cell subsets revealed that coordinated early activation of the entire innate immune system in response to dengue virus infection contributed to resolution of infection and speedy recovery.