High Inflammatory Markers Research Articles

Risk factor profile of Mucormycosis in COVID 19 patients: A Case series

Coronavirus disease-19 (COVID-19)-infected patients are at risk to develop severe opportunistic infections, especially fungal infections. The incidence of mucormycosis has increased in patients who are recovering from COVID-19 and now it has become an epidemic in India. In the background of the COVID-19 pandemic, we present a case series of seven patients with mucormycosis and their risk factor profile. Six of our patients had nonketotic poorly controlled glycemic status. All patients were mild or asymptomatic as far as COVID-19 clinical symptoms are concerned, but they had high inflammatory markers such as interleukin 6 (IL-6), ferritin, and D-dimer, which are commonly seen in a cytokine storm. Hyperglycemia and COVID-19 infection were consistent features in our patients. We found that COVID-19 patients with poor glycemic control and high inflammatory markers are at high risk for mucormycosis infection. However, the duration from the diagnosis of COVID-19 and the development of symptoms of mucormycosis was varied from 1 to 12 days (mean- 5.71). There was no correlation of the level of IL-6 or D-dimer with the early onset of mucormycosis. We also did not find any correlation of mucormycosis with other proposed risk factors such as oxygen therapy, steam inhalation, or prolonged steroid therapy, since four of our patients had never received steroids in any form and three had received only mild dosages of steroid. The sample size for statistical analysis was inadequate. However, a randomized clinical trial or larger observational study is needed to establish this observation.

Outcome of COVID-19 in Patients Requiring Haemodialysis- A Retrospective Observational Study

Introduction: Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are risk factors for COVID-19 infection. Patients with kidney disease also have other co-morbidities like hypertension, diabetes mellitus, cardiovascular disease that are risk factors for poor outcome in COVID-19 infections. Severe COVID-19 has multiorgan involvement including AKI. Compared to normal population, renal failure patients with COVID-19 have extensive lung involvement, need more ventilator support, and have higher mortality. Aim: To assess outcome (mortality, recovery) and association between factors (age, gender, co-morbidities), biochemical parameters with mortality in COVID-19 patients requiring haemodialysis. Materials and Methods: It was a retrospective observational study wherein, data was collected, entered and analysed with Statistical Package for the Social Sciences (SPSS) version 19.0 using medical records of all COVID-19 patients who had renal failure (AKI or CKD) requiring haemodialysis. The study period was from June-September 2020 at Vydehi Institute of Medical Sciences and Research Centre, Bangalore, Karnataka, India. Results: Out of total 68 COVID-19 positive patients, mean age of presentation was 55.08 years and with 75% of the study population were males. Most patients presented with severe COVID-19 illness with tachypnoea and hypoxia. The AKI occurrence and mortality was noted in 44.1% and 47%, respectively. It was noted that medication usage was higher for corticosteroids, oseltamivir, vitamin C, zinc therapy. Conclusion: In the present single centre study involving COVID- 19 patients requiring haemodialysis, it was noticed that severe COVID-19 illness, presence of AKI, chronic respiratory illness and high inflammatory markers were associated with higher mortality.

Clinical and demographic characteristics of patients with coronavirus disease 2019 in Security Forces Hospital, Riyadh, Saudi Arabia

Background:Corona virus disease (COVID-19) is a global pandemic public health problem which affected more than 5 million worldwide and caused more than 500,000 deaths. Disease presentations varied from a symptomatic or mild to severe illness which leads to death.Aim:The study describes the demographic and clinical characteristics patients with coronavirus disease 2019 (COVID-19) admitted to Security Forces Hospital in Riyadh, Saudi Arabia between 15th March till 30th of June 2020.Methods:Study group studied a case series of 566 consecutive patients with COVID-19 evaluated at Security Forces Hospital in Riyadh, Saudi Arabia from 15th March and 30th June 2020.Main Outcomes:Demographic data, underlying co-morbidities, clinical presentation, and treatment were collected.Results:Demographically, COVID-19 was more prevalent in male, Saudi, nonsmokers with blood group O + ve patients. It's more common in patients with co-morbidities like diabetes and hypertension. Fever, cough, and shortness of breath are the most common presenting symptoms. ESR, CRP, LDH, and Ferretin are the commonest laboratory abnormalities found.Conclusion:Totally, 556 case series patients showed more prevalence in aged male with diabetes as co-morbidity. Fever and cough are the most presenting symptoms with high inflammatory markers.

Prevalence of lung fibrosis amongst COVID-19 patients admitted in ICU and their clinical profile: An observational study

Background: We are observing a very tough time once again fighting an invisible enemy, the novel coronavirus. A novel coronavirus spill over event, with its epicenter in Wuhan, China, has emerged as a public health emergency as an international concern today. Chest computed topography and investigating the role of inflammatory mediators plays an important role in evaluation of covid-19 and effective therapy for this infection. Materials and Methods: An observational study in patients of covid-19 admitted in Geetanjali medical college, Udaipur. After taking all necessary consent, patients were enrolled. In each patient: symptom onset, blood and radiological investigations were compared during and after covid-19 treatment. Result: In our study, 68 patients were enrolled, out of which 36 were males and 32 were females. 52 patients were aged above 60 years out of which 50 patients were having co-morbid conditions (DM, HTN, Hypothyroidism, obesity and CAD). Out of the total 68 patients included in our study, 60 patients showed deranged inflammatory markers (CRP, D-Dimer, and Lymphocytes) for more than 45 days amongst these patients. In 39 patients fibrotic changes were observed after three months in chest radiography.Conclusion: From our study we conclude that the positive predictor of pulmonary fibrosis in covid19 infection are old age, co-morbid conditions, high severity index and inflammatory markers.

COVID-19 among patients with pre-existing renal impairment: experience in a tertiary care hospital of Bangladesh

Background: Patients with chronic kidney disease (CKD) are at increased risk for infection because of immunosuppressed state. CKD is an independent risk factor for poor outcome in coronavirus disease 2019 (COVID-19). This study was designed to describe clinical and laboratory parameters of COVID-19 patients with preexisting CKD.
 Methods: This cross-sectional study was conducted in the Department of Nephrology, BIRDEM General Hospital from July to December 2020. Hospitalized adult patients with CKD not yet on dialysis, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase polymerase chain reaction (RT-PCR), irrespective of symptoms were included in this study. RT-PCR negative cases were excluded.
 Results: Total patients were 40 (mean age 58.3 years, 52.5% male). Common comorbidities were diabetes mellitus (92.5%), hypertension (67.5%) and ischaemic heart disease (27.5%). Fever, cough, shortness of breath, headache and fatigue were common presenting features. Nearly one-fifth had no COVID-related symptoms. Lymphopenia and high inflammatory markers (ESR, CRP) were common. Sixteen patients were complicated by acute kidney injury, four patients required haemodialysis and 23 had electrolyte imbalance. Most cases were mild to moderate; most were transferred to COVID-dedicated hospitals or discharged with home isolation protocols. Three patients required intensive care unit shifting and two patients died.
 Conclusion: Most CKD patients had comorbid conditions. Clinical presentation was typical in most cases. Case fatality rate was higher than Bangladeshi statistics.
 Birdem Med J 2020; 10, COVID Supplement: 23-28

Association of sleep disturbance with diabetic retinopathy.

Diabetes mellitus (DM) patients are more likely to experience sleep disturbances than normal. Sleep disturbances may contribute to the development of diabetic retinopathy (DR) by higher inflammatory markers in circulation. We investigated the association between sleep quality and DR. Institutional case control study with type 2 DM patients of <10 years duration and HbA1c ⩽8%; 70 cases with DR and 70 controls without DR (NODR) (power 0.8). Sleep quality was assessed by Pittsburg sleep quality index (PSQI) questionnaire and compared. Cronbach's alpha was 0.777 with high internal homogeneity. Global PSQI score in DR (7.44 ± 3.99; 95%CI 6.88, 9.42) was more than in NODR (4.30 ± 3.26; 95%CI 3.87, 6.45) (p < 0.001). All sleep disturbance scores were more in DR except sleep duration. Poor sleep (PSQI score>5) was more prevalent in DR (p = 0.000) and associated with increasing DR severity (p = 0.026). Normal sleep latency was recorded in 78.57% and 42.85% patients in NODR and DR respectively (p < 0.001). Severe difficulty in subjective sleep quality (p = 0.024), sleep latency (p = 0.002) and daytime dysfunction (p < 0.001) was seen more in DR. Elevated daytime dysfunction was observed with increasing DR severity (p = 0.008). The optimal cut-off for global PSQI score and sleep latency for DR was 5.5 (OR: 5.97; 95%CI 2.86, 12.47) and 25 min(OR: 4.89; 95%CI 2.32, 10.26) respectively. Sleep disturbance is positively associated with DR. Our study identifies cut off value for DR of a modifiable parameter like sleep latency. It emphasizes the need of sleep quality assessment for risk assessment of DR.

Clinical characteristics, hospital course, and outcomes among COVID-19 positive patients with mental illness in a community hospital in New York City

Background Emerging evidence suggests a definite neuropsychiatric sequela of the SARS-CoV-2 infection possibly from a direct effect of the virus on the central nervous system. Although the pathophysiology of the virus and the epidemiology of its impact are only just being unraveled, clinical characteristics, and outcomes specifically among patients with primary psychiatric disorders who are hospitalized with COVID-19 remain unclear and unreported. Methods This is a retrospective cohort study of all patients with psychiatric diagnoses who were hospitalized patients with severe SARS-CoV-2 infection in a community hospital in New York City. Results More than 80% of the cohort are African Americans. Hypertension (61.2%), morbid obesity (41.8%) and diabetes (27.6%) were the most prevalent co-morbid medical conditions. Schizophrenia (32.7%) and Major Depressive disorder (29.6%) were the most common psychiatric diagnoses reported. At triage, the most common presentations were fever (57.1%), cough (55.1%), myalgia (32.7%), fatigue (25.5%), and altered mental status (19.4%). Distinctly high infection-related inflammatory markers and cytokines were also reported with median values including CRP (85.5 mg/ml), D-dimer (2061 ng/ml), procalcitonin (1.1 ng/ml) and IL-6 (65.5 pg/ml). Conclusion Results from this study strengthen preliminary data that show an overrepresented COVID-19 burden in the African American community. This further suggests that the same holds true among a cohort of patients with psychiatric conditions hospitalized with severe COVID-19 infection. Having comorbid mental illness and older age were observed as independent factors of morbidity and mortality. The finding of elevated inflammatory markers in this cohort may account for the prolonged hospitalization and hospital course, morbidity and mortality among COVID patients with comorbid psychiatric diagnoses and requires further investigation.

Abstract 17095: Association of Cigarette and Electronic Cigarette Use Behaviors With Levels of Inflammatory and Oxidative Stress Biomarkers Among United States Adults, Path 2013-2014

Introduction: Electronic cigarette (e-cigarette) use has increased rapidly in recent years; however, the cardiovascular risks of e-cigarettes remain unclear. Using data from the Population Assessment of Tobacco and Health Survey, this study assesses the cross-sectional association of cigarette and e-cigarette use behaviors with markers of inflammation (high-sensitivity C-reactive protein [hsCRP], soluble intercellular adhesion molecule [sICAM], interleukin-6 [IL-6], fibrinogen), oxidative stress (8-isoprostane [F2PG2a]), and nicotine exposure (cotinine). Methods: We analyzed data from adults (18+ years) who provided urine and blood specimens at wave 1 (2013-2014). Biomarkers were examined as continuous and categorical variables using the clinical cut points of ≥3 mg/L for hsCRP &gt;10 ng/mL for cotinine, and the upper quartiles of fibrinogen (≥381mg/dL), IL-6 (≥2.32 pg/mL), sICAM (≥288.77 ng/mL), and 8-isoprostane (≥788 pg/mL). Progressively adjusted negative binomial and generalized structural equation models were used, as well as sensitivity checks to assess the robustness of associations. Results: Of the 7,019 participants (58.6% non-users, 1.8% current vapers, 29.7% current smokers, 9.9% dual users), 67.2% had ≥1 high inflammatory or oxidative stress marker. Current vapers had increased risk of high hsCRP (IRR 1.28; 95% CI,1.02-1.59) and sICAM (IRR 2.01; 95% CI,1.42-2.85) compared to non-users. Relative to current smokers, current vapers who were former smokers had lower risk of having ≥1 high inflammatory or oxidative stress marker (IRR 0.80; 95% CI,0.69-0.94). Dual users had higher levels of all 5 inflammatory and oxidative stress markers compared to never smokers in both continuous and categorical models, with similar levels compared to current smokers. Current smokers and dual users had higher levels of cotinine compared to exclusive vapers. Conclusions: This study suggests that current vapers may have lower levels of inflammatory and oxidative stress markers compared to current smokers, but only after complete cessation of combustible cigarettes. Our findings strengthen the need for longitudinal studies investigating the association of vaping with markers of cardiovascular risk, particularly among dual users.

Abstract 16566: Presentation and Outcome of Pediatric Multisystem Inflammatory Syndrome Temporally Associated With Sars-cov-2 Pandemic: An International Survey

Introduction: Following the SARS-CoV-2 pandemic peak, children suffering from a multiorgan inflammatory disease that often leads to shock have been reported. This condition shares features with Kawasaki disease, but its etiopathogenesis is unknown. Hypothesis: We aimed to describe presentation and hospital course for this pediatric inflammatory multisystemic syndrome associated with COVID-19 (PIMS-TS). Methods: Data were collected from a retrospective review of children from 33 participating European, Asian and American sites. Results: We included 183 patients (109 males, 59·6%) with PIMS-TS, at a mean age of 7·0 (±4·7) years. Fifty-six (30·6%) had black ethnicity and obesity was present in 48 (26·2%) cases. Overall, 114/183 (62·3%) had biological evidence of current or recent SARS-CoV-2 infection. At admission, all presented with fever, 117/183 (63·9%) with gastrointestinal symptoms and 79/183 (43·2%) with shock, that was associated with more frequent black ethnicity, higher inflammatory markers and more cardiac involvement. Twenty-seven patients (14·7%) fulfilled criteria for Kawasaki disease. They were younger with no shock, fewer gastrointestinal, cardio-respiratory and neurological symptoms. Among the remaining PIMS-TS patients, 77 (49·3%) had mainly fever and inflammation with less cardiac involvement. For the entire cohort of 183 patients, the mean duration of admission was 8·6 (±5·6) days. Inotropic support, mechanical ventilation and ECMO were indicated in 72 (39·3%), 43 (23·5%) and 4 (2·2%) patients, respectively. Three patients (1·6%) died. A shorter duration of symptoms before admission was a risk factor for worse outcome and for ECMO/death, with 63% increased risk per day reduction (95%CI 0·39-0·93, p=0·03) and with 51·4% increased risk per day reduction (95%CI 0·36-0·9, p=0·03), respectively. Conclusions: We describe the first largest international series of children with PIMS-TS. Life-threatening shock is a common presentation. A shorter duration of symptoms prior to admission characterizes the fulminant form of the disease with potentially worse outcome.

Abstract 13479: Association of Plasma Branched Chain Amino Acid With Biomarkers of Inflammation and Lipid Metabolism in Women

Introduction: We previously observed that circulating branched-chain amino acids (BCAAs) were associated with a higher risk of cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways other than type 2 diabetes (T2D) are unclear, including inflammation, dyslipidemia, and impaired glucose metabolism. Hypothesis: We hypothesized plasma BCAAs are correlated with cardiometabolic dysfunction in women, independent of shared risk factors. Methods: We conducted a cross-sectional analysis of 19,472 participants (mean age=54.9 years, SD=7.2) in the Women’s Health Study without a history of T2D, CVD, or cancer at baseline blood collection. We used multivariable linear regression models comparing quartiles of BCAAs (sum of fasting isoleucine, leucine and valine concentrations via NMR spectroscopy) with biomarkers of inflammation, lipids, and glucose metabolism, adjusting for age, body mass index, smoking, diet, and other CVD risk factors. Results: Women in the highest vs. lowest quartiles of plasma BCAAs had higher inflammatory markers including high-sensitivity C-reactive protein (hsCRP; adjusted mean: 2.7 vs. 2.0 mg/L), fibrinogen (390 vs. 384 mg/dL), GlycA (420 vs. 384 μmol/L), and soluble intercellular cell adhesion molecule-1 (sICAM-1; 350 vs. 341 ng/mL) (p&lt;0.001 for linear trends across quartiles). Similarly for lipids, women with higher BCAAs had lower HDL-c (48.8 vs. 54.7 mg/dL), and higher LDL-c (142 vs. 135 mg/dL) and triglycerides (142 vs. 114 mg/dL) (p&lt;0.001). BCAAs were positively associated with insulin resistance (lipoprotein insulin resistance [LPIR] score [54.8 vs. 40.0]) and HbA1c (5.2 vs. 5.1%). BCAAs remained associated with GlycA and hsCRP, but not fibrinogen or sICAM-1, when we further adjusted for LPIR and HbA1c, and remained associated with lipids after additional adjustment for HbA1c. Conclusions: Circulating BCAAs are concurrently associated with biomarkers of inflammation, dyslipidemia and impaired glucose metabolism indicative of an overall poorer cardiometabolic health profile. BCAAs remained positively associated with some of these pathways when adjusted for impaired glucose metabolism, suggesting elevated BCAAs may be an independent CVD risk factor in women.

An observational cohort study of bacterial co-infection and implications for empirical antibiotic therapy in patients presenting with COVID-19 to hospitals in North West London.

ObjectivesTo describe the prevalence and nature of bacterial co-infections in COVID-19 patients within 48 hours of hospital admission and assess the appropriateness of empirical antibiotic treatment they received.MethodsIn this retrospective observational cohort study, we included all adult non-pregnant patients who were admitted to two acute hospitals in North West London in March and April 2020 and confirmed to have COVID-19 infection within 2 days of admission. Results of microbiological specimens taken within 48 hours of admission were reviewed and their clinical significance was assessed. Empirical antibiotic treatment of representative patients was reviewed. Patient age, gender, co-morbidities, inflammatory markers at admission, admission to ICU and 30 day all-cause in-hospital mortality were collected and compared between patients with and without bacterial co-infections.ResultsOf the 1396 COVID-19 patients included, 37 patients (2.7%) had clinically important bacterial co-infection within 48 hours of admission. The majority of patients (36/37 in those with co-infection and 98/100 in selected patients without co-infection) received empirical antibiotic treatment. There was no significant difference in age, gender, pre-existing illnesses, ICU admission or 30 day all-cause mortality in those with and without bacterial co-infection. However, white cell count, neutrophil count and CRP on admission were significantly higher in patients with bacterial co-infections.ConclusionsWe found that bacterial co-infection was infrequent in hospitalized COVID-19 patients within 48 hours of admission. These results suggest that empirical antimicrobial treatment may not be necessary in all patients presenting with COVID-19 infection, although the decision could be guided by high inflammatory markers.

Pediatric Inflammatory Multisystem Syndrome Associated With SARS-CoV-2: A Case Series Quantitative Systematic Review.

Pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) is infrequent, but children might present as a life-threatening disease. In a systematic quantitative review, we analyzed 11 studies of PIMS-TS, including 468 children reported before July 1, 2020. We found a myriad of clinical features, but we were able to describe common characteristics: previously healthy school-aged children, persistent fever and gastrointestinal symptoms, lymphopenia, and high inflammatory markers. Clinical syndromes such as myocarditis and Kawasaki disease were present in only one third of cases each one. Pediatric intensive care unit admission was frequent, although length of stay was less than 1 week, and mortality was low. Most patients received immunoglobulin or steroids, although the level of evidence for that treatment is low. The PIMS-ST was recently described, and the detailed quantitative pooled data will increase clinicians' awareness, improve diagnosis, and promptly start treatment. This analysis also highlights the necessity of future collaborative studies, given the heterogeneous nature of the PIMS-TS.

Newly Diagnosed Acute Lymphoblastic Leukemia in a Child with COVID-19 Complicated By MIS-C: A Case Report from Kuwait

Introduction:Coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major challenge worldwide. Data reporting manifestations of COVID-19 in pediatric cancer patients are limited. This report describes the presentation and initial management challenges of a newly diagnosed child with acute lymphoblastic leukemia (ALL) with positive (+) SARS-CoV-2 complicated by multisystem inflammatory syndrome in children (MIS-C).Case Description:A previously healthy 9-year-old female had (+)SARS-CoV-2 following a 4-day history of fatigability. This was followed by a day of severe gastroenteritis (GE) necessitating a visit to Jaber Al-Ahamed Hospital (JAH), the designated COVID-19 pandemic center. Examination revealed hypovolemic shock, hepatosplenomegaly (HSM) and cervical lymphadenopathy. Patient also had significant pancytopenia and high inflammatory markers (Table).Bone marrow aspiration (BMA) - done 7 days from diagnosis of SARS-CoV-2 - was consistent with B-ALL. Transfer to National Bank of Kuwait Children's Hospital (NBKCH) - the pediatric cancer center - was delayed for 11 days given her (+)SARS-CoV-2, but once tested negative, transfer was complete. Due to logistical issues, lumbar puncture and repeat BM were delayed. She then developed new fever, abdominal pain and vomiting. Her febrile neutropenia (FN) was managed according to local protocol including antifungal therapy for prolonged FN. Five days into her FN, she developed hematemesis and septic shock. In addition to pancytopenia, she also had disseminated intravascular coagulation with further raise in CRP (Table). She also had a new maculopapular rash (Image). Infectious work-up was negative except for (+)SARS-CoV-2 (after 10 days of negativity), fulfilling criteria of MIS-C. Patient was transferred back to JAH according to local pandemic protocol. Induction chemotherapy as perUK-MRC-ALL 2011 regimen Afor standard risk ALL - with modifications given her MIS-C - was started after 22 days (Figure). On day 5 of chemotherapy, patient was clinically stable with negative SARS-CoV-2, therefore transferred back to NBKCH for continuation of leukemia management.Discussion:Although children tend to have a milder course of COVID-19, this case described a fulminant presentation initially with GE, hypovolemic shock and complicated by MIS-C, lacking any respiratory symptoms throughout her course. Until more data reporting manifestations of SARS-CoV-2 in pediatric cancer patients are available, physicians should keep high index of suspicion for leukemia in presence of pancytopenia and HSM in spite of (+)SARS-CoV-2. Prompt diagnosis of ALL is fundamental to avoid delays in treatment and consequent effects on prognosis. Logistical issues such as lack of optimum COVID-19 isolation measures in our cancer center and paucity of blood products have led to delayed initiation of chemotherapy. These cancer-related challenges have been well described.Another interesting aspect of our case is the seroconversion to (+)SARS-CoV-2 after proved negativity. It is possible that protective antibodies were not well developed as she is immunocompromised, making such patients prone to recurrent SARS-CoV-2 infection. The re-emergence of SARS-CoV-2 has led to the diagnosis of MIS-C after fulfilling other criteria. This phenomenon of negative to (+)SARS-CoV-2 seroconversion has been reported in 20-40% of MIS-C cases.Increased risk of venous thromboembolism (VTE) is linked to the hyperinflammatory state of COVID-19. Chemotherapy is also identified as an independent risk factor for VTE in malignancy. To avoid the collateral effects of these factors, modifications of the planned chemotherapy were implemented in our case to minimize the VTE risk. The high steroid dose with chemotherapy was also planned as a treatment for MIS-C, which is consistent with different modalities of MIS-C treatment offered in literature.Conclusion:Children with B-ALL may suffer from fulminant clinical course when diagnosed with COVID-19 and could be prone to recurrent SARS-CoV-2 infection. Our experience highlights the importance of optimizing isolation measures and raising awareness for need of blood products to avoid treatment delay. Further research can aid in forming recommendations to prevent management pitfalls especially with the anticipation of a second wave of this pandemic.DisclosuresNo relevant conflicts of interest to declare.

Refractory Thrombocytopenia in SLE with Evans Syndrome : A Case Report

Background: Evans syndrome (ES) is a rare autoimmune disorder of unknown etiology. It is characterized by the occurrence of two or more hematologic immune cytopenias, most often immune thrombocytopenia and autoimmune hemolytic anemia (AIHA). In this study we present a rare case of a 9-year-old girl, who was diagnosed with secondary ES associated with active systemic lupus erythematosus (SLE). Case presentation: On November 16th, 2018, a 9-year old girl, presented for the first time with recent onset of gum bleeding and decreased level of consciousness for two weeks. On examination, she was conscious but not oriented, unable to walk, showed scanty hair with oral and gum bleeding, and had multiple bruises and massive hepatosplenomegaly. No parental consanguinity, and no similar history in the family was noted. She had low platelet count (1×103 /μL), with high mean platelet volume (19 fl), anemia (HB 5.5 g/dL), with normal white blood cell count, positive direct Coombs test, and hemolysis with no malignant cells on a peripheral blood smear. Bone marrow evaluation showed hypercellularity, and increased number of megakaryocytes, with no other significant abnormalities. Her flowcytometry study was normal. Brain computed tomography (CT) revealed left subdural hematoma with elements of old brain atrophy (Photo 1), with significant dilatation of ventricular system. Chest X-ray showed mild right pleural effusion. Abdominal ultrasonography showed hepatosplenomegaly with no focal lesions, and mild-to-moderate ascites. Both antinuclear antibody and anti-phospholipid antibody tests showed positive results and C3 was low. Hepatitis and human immunodeficiency virus (HIV) serology were negative.Autoimmune lymphoproliferative syndrome gene sequence analysis was negative. The patient was diagnosed with SLE, after she fulfilled the American Rheumatology Association criteria, associated with Evans syndrome. Any planned surgery was postponed until thrombocytopenia correction, and their aim was to increase the platelet count to a level of above 100.The patient received packed red blood cells (RBCs) and platelets several times. To control her condition, several medications were tried. These medications included intravenous immunoglobulin (1 gm/kg) for two successive days, prednisolone (2 mg/kg/day); however, no improvement was observed after 10 days. Therefore, all of these medications were replaced with methylprednisolone pulse therapy (30 mg/kg for three days), with one dose of anti-D (75 mcg/kg IV). Our next choice was mycophenolate mofetil, which was stopped after finishing the course of five weeks, but the patient did not show any improvement. Moreover, platelets failed to respond to four doses of Rituximab (370 mg/m2/dose) for four weeks and to two cycles of high dose of dexamethasone 20mg/m2 for 4 days every 4 weeks. On 12/29/2018, chloroquine (4 mg/kg/day) was administered for two weeks in conjunction with cyclosporine (4 mg/kg/day). Splenectomy was an option but was not performed because her platelet levels never recovered. Her anemia started to improve on 1/9/2019 with combination of prednisolone and cyclosporine and Coombs test results were negative. On 1/23/2019, the patient was started on Eltrombopag, in a dose-escalated manner starting with 25 mg/kg/day up to 75 mg/kg/day in addition to corticosteroids. One week later, her platelet counts markedly improved (Photo 2). No major side effects were reported. On 2/12/2019, the patient underwent left side burr-hole evacuation of subdural hematoma, but her consciousness was never regained. She was maintained in intensive care unit and ventilated, but she developed multiple postoperative complication, including sepsis with high inflammatory markers and spiking fever. Her platelet count was continuously high, so the dose of Eltrombopag was decreased to 50 mg/kg/day to just keep the level between 50 and 100. Despite all of therapeutic interventions, she passed away one month later, on 3/13/2019, due to respiratory failure. Conclusion: The incidence of ES is quite rare, especially in children. Eltrombopag is a safe and effective drug for management of refractory thrombocytopenia in cases of ES associated with SLE. Figure Disclosures No relevant conflicts of interest to declare.

Metabolic comparison of polycystic ovarian syndrome and control women in Middle Eastern and UK Caucasian populations

To determine if metabolic characteristics differed in women with and without polycystic ovary syndrome (PCOS) between a Caucasian and Middle East population. Comparative cross-sectional analysis. Demographic and metabolic data from Middle Eastern women from Qatar Biobank (97 with PCOS, 622 controls) were compared to a Caucasian PCOS biobank in Hull UK (108 with PCOS, 69 controls). In both populations, PCOS women showed a worse cardiovascular risk profile of increased systolic and diastolic blood pressure, increased C-reactive protein (CRP), reduced HDL, insulin resistance as well as increased androgens compared to their respective controls without PCOS. UK women without PCOS had higher systolic and diastolic blood pressures, and increased testosterone results (p < 0.01) compared to Middle Eastern women without PCOS who had higher inflammatory markers (WBC and CRP), HDL and insulin resistance (p < 0.001). UK PCOS women had a higher body mass index, systolic and diastolic blood pressures, triglycerides (p < 0.01), whilst Middle Eastern PCOS women showed increased testosterone, free androgen index, HDL and CRP (P < 0.01). There was no difference in insulin or insulin resistance between the two PCOS cohorts. This study highlights ethnic population differences because, whilst cardiovascular risk indices were increased for both PCOS cohorts, this may be for different reasons: BMI, waist and hip measurements, systolic and diastolic blood pressure, and triglycerides were higher in the UK cohort whilst testosterone, HDL and CRP were higher in the Middle East population. Insulin resistance did not differ between the two PCOS populations despite differences in BMI.

Multisystem Inflammatory Syndrome in Children (MIS-C): New challenges of a new era

In the background of a sudden surge of coronavirus disease 2019 (COVID-19) cases, reports of themultisystem inflammatory syndrome in children from different parts of the globe are a matter ofconcern for physicians. We report a similar case presenting with persisting fever, rashes, bulbarconjunctivitis, abdominal pain, respiratory difficulty, and shock. Initial reports suggestive of highinflammatory markers, neutrophilic leucocytosis, high d-dimer, transaminitis, and found to haveCOVID 19 IgG antibodies positive in high titer. The echo at the bedside is suggestive of poor LVfunction with normal coronaries. Managed successfully in PICU with non-invasive ventilation support,ionotropy, aspirin, IVIG, and steroids and discharged. Early referral, a high index of suspicion,prompt recognition of shock, and early management by steroids and intravenous immunoglobulin(IVIG) may bring success.

COVID-19 Severity and Stroke: Correlation of Imaging and Laboratory Markers.

Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. Compared with patients with COVID-19 with outside-of-hospital stroke onset and milder or no COVID-19 symptoms (n = 45, 52.3%), patients with stroke already hospitalized for severe COVID-19 (n = 41, 47.7%) had significantly more frequent infarctions (95.1% versus 73.3%, P = .006), with multivascular distributions (56.4% versus 33.3%, P = .022) and associated hemorrhage (31.7% versus 4.4%, P = .001). Patients with stroke admitted with more severe COVID-19 had significantly higher C-reactive protein and ferritin levels, elevated D-dimer levels, and more frequent lymphopenia and renal and hepatic injury (all, P < .003). Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.

Transvaginal Stent as an Effective Drainage Route for Refractory Infection of a Pelvic Tumor

The institutional review board approved this report. A 44-year-old woman underwent total hysterectomy and radiation therapy for cervical cancer. Chemotherapy was started for local recurrence of the tumor. However, the tumor enlarged and formed fistulae with the urinary bladder and rectum (Fig 1). A percutaneous nephrostomy catheter was inserted for hydronephrosis. Persisting infection in the tumor caused by the fistulae resulted in severe anal pain and high inflammatory markers, and the patient was bedridden all day. Antibiotic therapy and percutaneous drainage of the infected tumor could not control pelvic infection.

Role of T1 Inflammatory Endotype in the Pathophysiology of Severe COVID-19

Background: Coronavirus disease (COVID-19) is a severe acute respiratory disease with approximately 5% of infected persons developing a serious disease. It is known that cytokine release is involved in its mechanism of aggravation, but the understanding of its inflammatory pathophysiology is not sufficiently advanced. Of specific importance to the development of therapeutic strategies is the understanding of its therapeutic endotype.Methods: Peripheral blood cytokines that were identified as being associated with COVID-19 in previous studies and eight inflammatory markers (IL-6, CRP, CXCL9, IL-18, CCL3, CCL17, IL-10, and VEGF) were measured in 57 COVID-19-infected individuals and their association with the patients’ condition was examined using a cluster analysis.Findings: The 8 inflammatory markers had significantly higher blood levels in patients who developed ARDS (ARDS) compared to those who did not develop ARDS during the observation period (non-ARDS). In the cluster analysis, the patient groups were classified into four clusters, of which two of the clusters had patients with high levels of IL-6 and CRP. In these clusters with high levels of IL-6 and CRP, in the clusters with high T1-inflammatory markers such as CXCL9 and IL-18, 85% of the patients had ARDS or pre-ARDS, and 65% of the patients developed AKI.Interpretation: In addition to IL-6 and CRP, which are reported as severity markers, clusters with high T1 inflammatory markers, the patients with high tissue damage have high ARDS and AKI frequency. The existence of different inflammatory endotypes was observed in the patient population with high IL-６ and CRP levels. This difference in inflammatory endotypes provides information essential for the development of therapeutic strategies for anti-inflammatory therapy. Funding: This research was funded by Sysmex Corporation.Declaration of Interests: TH, KS, KY, SY, NI, ET, and NK are employee of Sysmex corporation. TH, KS, and AN patent pending (patent for the biomarker). All other authors declare no competing interests. Ethics Approval Statement: The study complied with the requirements of the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of Kobe City Medical Centre General Hospital and the Sysmex Cooperation. Informed consent was obtained from all of the patients using the following method: In compliance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects, the study information was published on the website and patients at the opportunity to withdraw their consent at any stage of the study. Therefore, the requirement for written informed consent from the enrolled patients was waived by the ethics committee.

Immune Activation and Anemia Are Associated with Decreased Quality of Life in Patients with Solid Tumors.

Anemia often coincides with depression and impaired quality of life (QoL) in cancer patients. Sustained immune activation can lead to the development of anemia. Furthermore, it also may go along with changes in tryptophan and phenylalanine metabolism. The aim of our pilot study was to study the relationship between anemia, immune-mediated changes in amino acid metabolism, and the QoL and mood of cancer patients. Questionnaires to measure QoL and depression were completed by 152 patients with solid tumors. Hemoglobin, parameters of immune activation as well as tryptophan and phenylalanine metabolism were determined in the patients’ sera. Anemic patients (51.7%) presented with higher inflammatory markers, and a higher tryptophan breakdown with lower tryptophan concentrations. They reported an impaired QoL and had higher depression scores. Patients with an impaired QoL (65.8%) also suffered from more fatigue and impaired physical, emotional, and social functioning. They, furthermore, presented with higher concentrations of inflammatory markers (C-reactive protein (CRP) and neopterin) as well as higher tryptophan degradation (in men) and higher phenylalanine concentrations (in women). Sixty-one patients (40.1%) had (mostly mild) depression. In these patients, a higher degree of Th1 immune activation was found. The results of our study suggest that cancer-related anemia goes along with an impaired QoL, which is also associated with immune-mediated disturbances of tryptophan and phenylalanine metabolism.