Direct bilirubin and the neutrophil-to-monocyte ratio timely predict intensive care unit admission in patients with severe acute respiratory syndrome coronavirus-2 infection (COVID-19)

Objective: Intensive care units (ICUs) collapsed under the global wave of coronavirus disease 2019 (COVID-19). Thus, we designed a clinical decision-making model that can help predict at hospital admission what patients with COVID-19 are at higher risk of requiring critical care. Method(s): This was a cross-sectional study in 119 patients that met hospitalization criteria for COVID-19 including less than 30 breaths per minute, peripheral oxygen saturation < 93%, and/or >= 50% lung involvement on imaging. Depending on the need for critical care, patients were retrospectively assigned to ICU and non-ICU groups. Demographic, clinical, and laboratory parameters were collected at admission and analyzed by classification and regression tree (CRT). Result(s): Forty-five patients were admitted to ICU and 80% of them were men older than 57.13 +/- 12.80 years on average. The leading comorbidity in ICU patients was hypertension. The CRT revealed that direct bilirubin (DB) > 0.315 mg/dl together with the neutrophil-to-monocyte ratio (NMR) > 15.90 predicted up to correctly in 92% of the patients the requirement of intensive care management, with sensitivity of 93.2%. Preexisting comorbidities did not influence on the tree growing. Conclusion(s): At hospital admission, DB and NMR can help identify nine in 10 patients with COVID-19 at higher risk of ICU admission.Copyright © 2022 Sociedad Medica del Hospital General de Mexico.

Evaluation of Neutrophil Percentage to Albumin Ratio as Predictor of Mortality in Patients with Covid-19

Background: Inflammatory acute respiratory syndrome (SARS) is caused by the COV-2 virus. Neutrophils have been implicated in the pathophysiology of the COVID-19 pandemic since its inception, particularly in individuals with advanced disease. This is confirmed by a large number of studies. Method(s): The study included 200 patients, of whom 100 were in the critical group (group 1) and 100 were in the non-critical group (group 2). White blood cell (WBC) percentage, neutrophil count, albumin, and demographic information were recorded. Neutrophil percentage x 100 /Albumin (g/dl) was used to construct the neutrophil count to albumin ratio (NPAR). To determine whether the measure may be utilized as a predictor for mortality, the NPAR is then compared between groups 1 and 2, as well as between discharge and mortality groups. Result(s): Age and gender had no statistically significant differences in either group. There were no significant variations in the median (IQR) values of neutrophil count (89 vs 91.25), WBC (15.65 vs 14.9), and NPAR (41.3 vs 43.7) between the two groups. Significant differences in albumin (3.330.521 vs. 3.10.51) were identified between the critical and non-critical groups. Conclusion(s): According to our research, the COVID-19 patients' NPAR is a poor predictor of mortality. More study is still required to verify and elucidate the clinical implications of these findings.Copyright © 2023 Lahore Medical And Dental College. All rights reserved.

Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial

Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objective(s): This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Method(s): This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital's ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Result(s): The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 +/- 4.67 vs. 27.37 +/- 6.99 /min) and D-dimer (186.37 +/- 410.23 vs. 1339.04 +/- 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) <= 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusion(s): Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.Copyright © 2023, Author(s).

Comparison of demographic features and laboratory parameters between COVID-19 deceased patients and surviving severe and critically ill cases.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has been far more devastating than expected, showing no signs of slowing down at present. Heilongjiang Province is the most northeastern province of China, and has cold weather for nearly half a year and an annual temperature difference of more than 60ºC, which increases the underlying morbidity associated with pulmonary diseases, and thus leads to lung dysfunction. The demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province, China with such climatic characteristics are still not clearly illustrated. AIM: To illustrate the demographic features and laboratory parameters of COVID-19 deceased patients in Heilongjiang Province by comparing with those of surviving severe and critically ill cases. METHODS: COVID-19 deceased patients from different hospitals in Heilongjiang Province were included in this retrospective study and compared their characteristics with those of surviving severe and critically ill cases in the COVID-19 treatment center of the First Affiliated Hospital of Harbin Medical University. The surviving patients were divided into severe group and critically ill group according to the Diagnosis and Treatment of New Coronavirus Pneumonia (the seventh edition). Demographic data were collected and recorded upon admission. Laboratory parameters were obtained from the medical records, and then compared among the groups. RESULTS: Twelve COVID-19 deceased patients, 27 severe cases and 26 critically ill cases were enrolled in this retrospective study. No differences in age, gender, and number of comorbidities between groups were found. Neutrophil percentage (NEUT%), platelet (PLT), C-reactive protein (CRP), creatine kinase isoenzyme (CK-MB), serum troponin I (TNI) and brain natriuretic peptides (BNP) showed significant differences among the groups (P = 0.020, P = 0.001, P < 0.001, P = 0.001, P < 0.001, P < 0.001, respectively). The increase of CRP, D-dimer and NEUT% levels, as well as the decrease of lymphocyte count (LYMPH) and PLT counts, showed significant correlation with death of COVID-19 patients (P = 0.023, P = 0.008, P = 0.045, P = 0.020, P = 0.015, respectively). CONCLUSION: Compared with surviving severe and critically ill cases, no special demographic features of COVID-19 deceased patients were observed, while some laboratory parameters including NEUT%, PLT, CRP, CK-MB, TNI and BNP showed significant differences. COVID-19 deceased patients had higher CRP, D-dimer and NEUT% levels and lower LYMPH and PLT counts.

Markers of Inflammation Predict PostThrombectomy Mortality in Acute Stroke

Objective: To further characterize the relationship between markers of inflammation and outcome in patients undergoing mechanical thrombectomy for acute stroke. Background: Inflammation and infection after ischemic stroke are known to exacerbate tissue injury and worsen clinical outcome. Thrombectomy has become standard of care in stroke, but little data exist regarding how inflammation affects outcome after thrombectomy. Design/Methods: We performed retrospective chart review of stroke patients who underwent mechanical thrombectomy at 2 tertiary academic centers between December 2018 and November 2020. The relationship between discharge mortality, admission WBC count, admission neutrophil percentage, peak WBC count, and fever (peak temperature >38°C) were analyzed using the Wilcoxon rank sum test, Student's t-test, and Fisher's exact test. Multivariable analysis was performed to test for independent predictors of discharge mortality. Analyses were performed for the entire cohort, then repeated in a cohort excluding COVIDpositive patients. Results: Of 254 patients who had thrombectomy for acute stroke, 42 (16.5%) died prior to discharge. Mortality was associated with admission WBC count (10.7 [8.9-14] vs. 8.6 [7-12], p=0.0064), admission neutrophil percentage (78% ± 11 vs. 70% ± 14, p=0.0001), peak WBC count (17 [13-22] vs. 12 [8.9-15], p<0.0001), and fever (71% vs. 29%, p<0.0001). In multivariable analysis, admission WBC count (OR 14, CI 1.5-158, p=0.024), neutrophil percentage (OR 1.04, CI 1.0-1.1, p=0.039), peak WBC count (OR 343, CI 27-5702, p<0.0001) and fever (OR 8.6, CI 3.6-23, p<0.0001) were significantly predictive of discharge mortality after controlling for age, admission NIHSS and post-thrombectomy ASPECTS score. Fifteen patients tested positive for COVID-19. In analyses excluding these patients, peak WBC count and fever remained independent predictors of discharge mortality. Conclusions: Elevated markers of inflammation during hospitalization predict discharge mortality in patients who undergo mechanical thrombectomy for acute stroke. Further study is warranted to investigate causation and identify opportunities to improve quality of care in this patient population.

Common Symptom, Rare Etiology: A Case Metastatic Cancers of Unknown Primary Origin Presenting with Epistaxis and Gingival Bleeding

Introduction: Epistaxis and gingival bleeding are among the most common presentation to the emergency department for patients with thrombocytopenia. Here, we present a case who was admitted to the emergency department with thrombocytopenia and was diagnosed with metastatic cancer of unknown primary origin. Case Report: A 26-year-old male patient was admitted to the emergency department with gingival bleeding and epistaxis. The body temperature was 38.3 °C. Petechial rash, ecchymosis or organomegaly was not detected on physical examination. Laboratory results revealed thrombocytopenia as 31 × 103 (159-388 × 103/μL). Although hemoglobin and leukocyte counts were normal, no band or precursor cell was observed in the patient's peripheral blood smear. There was no history of weight loss, night sweats, arthritis, malar rash, photosensitivity, contact with ticks, animals, or a COVID-19 patient. Serological tests performed for infections such as HIV, EBV, HCV, Crimean-Congo hemorrhagic fever were negative. Bone marrow biopsy was performed due to the unexplained cytopenia, reported as "signet ring cell metastatic adenocarcinoma". Gastrointestinal system endoscopy was performed to detect primary cancer. A biopsy was taken from the antrum and corpus revealed gastritis. An FDG PET-CT was revealed heterogeneously pathologically increased FDG attitude in all axial and appendicular bones. Despite all the modalities of diagnosis, the origin was not found and the patient was transferred to the oncology department for treatment with a diagnosis of cancer of unknown origin with bone marrow infiltration. Conclusion: Bone marrow metastases should be kept in mind in patients presenting with thrombocytopenia.

The neutrophil percentage-to-albumin ratio is related to the occurrence of diabetic retinopathy.

BACKGROUND: Among patients with diabetic retinopathy (DR), no proof was available to confirm the prognostic significance of the neutrophil percentage-to-albumin ratio (NPAR). We hypothesized that NPAR plays a role in the incidence of DR in diabetic patients. METHODS: We extracted all diabetes mellitus (DM) data from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2018, NPAR was expressed as neutrophil percentage/albumin. Multivariable logistic regression and generalized additive model were utilized for the purpose of examining the correction between NPAR levels and DR. Subgroup analysis of the associations between NPAR and DR was carried out to investigate if the impact of the NPAR varied among different subgroups. RESULTS: An aggregate of 5850 eligible participants were included in the present research. The relationship between NPAR levels and DR was positive linear. In the multivariate analysis, following the adjustment for confounders (gender, white blood cell, age, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, body mass index, iron, glucose, basophils percent, total bilirubin, creatinine, and chloride), higher NPAR was an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00-1.39; 1.24, 1.04-1.48). For the purpose of sensitivity analysis, we found a trend of consistency (p for trend: 0.0190). The results of the subgroup analysis revealed that NPAR did not exert any statistically significant interactions with any of the other DR risk variables. CONCLUSIONS: Elevated NPAR is associated with an elevated risk of occurrence of DR in diabetic patients.

Identification of Early Features to Differentiate Hospitalized Children Admitted for Suspected MIS-C from Alternative Diagnoses

Background. Multi-system inflammatory syndrome in children (MIS-C) is a rare consequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). MIS-C shares features with common infectious and inflammatory syndromes and differentiation early in the course is difficult. Identification of early features specific to MIS-C may lead to faster diagnosis and treatment. We aimed to determine clinical, laboratory, and cardiac features distinguishing MIS-C patients within the first 24 hours of admission to the hospital from those who present with similar features but ultimately diagnosed with an alternative etiology. Methods. We performed retrospective chart reviews of children (0-20 years) who were admitted to Vanderbilt Children's Hospital and evaluated under our institutional MIS-C algorithm between June 10, 2020-April 8, 2021. Subjects were identified by review of infectious disease (ID) consults during the study period as all children with possible MIS-C require an ID consult per our institutional algorithm. Clinical, lab, and cardiac characteristics were compared between children with and without MIS-C. The diagnosis of MIS-C was determined by the treating team and available consultants. P-values were calculated using two-sample t-tests allowing unequal variances for continuous and Pearson's chi-squared test for categorical variables, alpha set at < 0.05. Results. There were 128 children admitted with concern for MIS-C. Of these, 45 (35.2%) were diagnosed with MIS-C and 83 (64.8%) were not. Patients with MIS-C had significantly higher rates of SARS-CoV-2 exposure, hypotension, conjunctival injection, abdominal pain, and abnormal cardiac exam (Table 1). Laboratory evaluation showed that patients with MIS-C had lower platelet count, lymphocyte count and sodium level, with higher c-reactive protein, fibrinogen, B-type natriuretic peptide, and neutrophil percentage (Table 2). Patients with MIS-C also had lower ejection fraction and were more likely to have abnormal electrocardiogram. Conclusion. We identified early features that differed between patients with MIS-C from those without. Development of a diagnostic prediction model based on these early distinguishing features is currently in progress.

HEMATOBIOCEMICAL AND HISTOPATHOLOGICAL STUDIES ON THE EFFECTS OF RAJ NIRWAN BATI (A NOVEL ALLOVEDIC DRUG) IN WISTAR RATS

Objective: To see the effects of Raj Nirwan Bati (RNB) on the hematobiochemical parameters, coagulation tests, and histopathological changes in the lungs, liver, kidneys and spleen and also to evaluate the immunomodulatory activity of RNBin Wistar rats. Methods: A total of 24 adult albino Wistar rats (of bodyweight 200-250 g) of either sex were divided into 3 groups. In the normal control group (n=8), no drug was administered and in the rest of the groups (A and B), RNB@ 26 mg/kg body weight./day and 260 mg/kg body weight/day respectively were administered orally for a period of 14 d. The blood samples were collected from the jugular vein at zero d (before drug administration) and after the 14th d of drug administration in both groups (A and B). The organ samples (lungs, liver, kidneys, and spleen) were collected after euthanizing the rats using Ketamine anesthesia overdose intraperitoneally (IP) after the 14th d of drug administration. White Blood Cells (WBC), Red Blood Cells (RBC), Hemoglobin (Hb), Hematocrit (HCT), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin(MCH), Mean Corpuscular Hemoglobin Concentration(MCHC), number of platelets, Differential Leucocyte Count(DLC) i.e. the percentage of neutrophils, lymphocytes, eosinophils, monocytes and basophils, neutrophil adhesion percentage, Prothrombin test (PT), Activated Partial Thromboplastin Time (APTT), fibrinogen, D-dimer, Lactate Dehydrogenase (LDH), urea, creatinine, Aspartate Amino Transferase (AST), Alanine amino Transferase (ALT), Alkaline Phosphatase (ALP), C-Reactive Protein (CRP) were evaluated and histological examination of organs were done. Results: After statistical analysis, it was found that the decrease in TLC, RBC, Hb, HCT, and LDH in Wistar rats after RNB intervention in Group A as compared to that of before RNB intervention, was found to be statistically significant (P=0.001, P=0.002, P=0.001, P=0.039, and P=0.008). On the other hand, an increase was observed in MCV, Urea, Creatinine and ALT values in the Wistar rats after RNB intervention in Group ‘A’ as compared to that of before RNB intervention and this increase in values was statistically significant (P=0.007, P=0.001, P<0.001 and P=0.038). After RNB intervention in Group B, the increase in MCH, fibrinogen concentration, and monocytes percentage, was found to be statistically significant (P=0.004, P=0.033, and P=0.001) as well as the decrease in PT and APTT was statistically significant (P=0.007and P=0.002). After comparing the Mean Hematobiochemical and coagulation test parameters in the rats of Group A and Group B, after RNB intervention, it was observed that the concentration of Urea, Creatinine, APTT, and D-dimer were less in Group B as compared to that of Group A and this difference was statistically significant(P<0.001, P<0.001, P<0.001 and P=0.022). Histologically the findings in the lungs of group B were more distortion of lung architecture, most of the alveoli become collapse and make emphysematous changes, more diffuse inflammatory infiltrate within interalveolar septa and around bronchioles as compared to Group A. In the liver of group B rats, the histological findings were mild to moderate distortion of lobular architecture, healthy hepatocytes with more activation of kupffer cells as well as larger and more aggregates of inflammatory cells as compared to group A. Histological findings of kidneys in group A and group B rats were similar to that of control group rats. Conclusion: The results suggest that the RNB is having an immunomodulatory effect. It might be helpful in the restoration of coagulation factors and can help treat the COVID patients. No harmful effects on the lungs, liver, kidney, and spleen were seen. These findings may act as baseline data for planning further clinical trials in human study subjects to evaluate the effects on various comorbidities.

Dynamic alterations of immunophenotype, C reactive protein and interleukine-6 levels in peripheral blood of severe COVID-19 patients

Introduction. Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a coronavirus disease 2019 (COVID-19) characterized by a "cytokine storm"-increased activity of immune cells with the elevated production of inflammatory cytokines leading to respiratory failure. Additionally, the course of pneumonia is characterized by an increased content of C reactive protein. Leukocytosis, leukopenia and lymphopenia are also commonly present in COVID-19 patients. Fine alterations of the immune cells subpopulations and cytokines level in COVID-19 patients are little known. This work aimed to determine the immunophenotype of peripheral blood cells subpopulations and to study the mentioned underlying changes in IL-6 and CRP levels in patients with COVID-19 pneumonia. Methods. Blood count with Erythrocyte Sedimentation Rate (ESR) was completed by routine blood assay. CRP and IL-6 levels were measured by ELISA. Immunophenotype of subpopulations of peripheral blood cells was acquired by multiparametric fluorescence flow cytometry. Results. Blood parameters comparison in 14 hospitalized severe COVID-19 patients showed that WBC count increased on day 7 and steadily decreased by day 28, while the percentage of neutrophils decreased gradually from the time of admission to full-recovery state. The percentage and count of lymphocytes regularly increased. The percentage of monocytes had a trend to rising but not statistically significant. The red blood cells count, ESR, and platelet count were not altered during COVID-19 progression. On initial admission, 35.7 % of COVID-19 patients had leucopenia, while 14.3 % of patients had leukocytosis on day 7. Lymphopenia occurred in 76.9 % of patients on day 0 and was not present on day 28. Changes in CRP levels were statistically significant over the duration of COVID-19 progression and recovery (p=0.003;n=15). The maximum CRP value was at day 0 but reached a normal range on day 28. The Il-6 level did not change significantly over 28 days of observation demonstrating a steady twice higher level in COVID-19 patients compared to healthy donors (p=0.934;n=8). The population of CD45+ cells was significantly lower in COVID-19 patients than in the healthy donors group (p=0.009;n=12). Despite it grew gradually from day 0 to 28, it did not reach the normal value at full-recovery state. The population of CD3+ cells was higher than the normal ranges at the first assessment, then dropped on day 7 but return to elevated levels on days 14 and 28 (p=0.008;n=12). Changes in the CD19+ cells count were significantly lower than those of the healthy volunteers during the period of observations (p=0.007;n=12). There were decreases in CD16+CD56+ cells counts over each time of assessment compared to healthy donors, but not statistically significant. Conclusion. The understanding of the dynamic changes of lymphocyte populations, cytokines production in COVID-19 patients will provide an in-depth knowledge of the COVID-19 pneumonia progression.