Network pharmacology and in silico investigation on Saussurea lappa for viral respiratory diseases

Respiratory viral diseases are prevalently affecting people of all ages, requiring extensive study into herbal medicine as a potential solution. Therefore, this study aimed to identify the Saussurea lappa (S. lappa) compounds and explain the molecular mechanisms against respiratory viral diseases. The molecular mechanisms of the compound against respiratory viral diseases was determined through network pharmacological methods using Cytoscape 3.10.0, GeneCards, OMIM, STRING 11.0, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The interaction of compounds with NFĸB and TNF were analyzed using molecular docking with dexamethasone as a control through PyRx Autodock Vina 9.0 and Biovia Discovery Studio. The results showed that S. lappa compounds activated defense mechanisms against viral infection, impacting genes associated with SARS-CoV-2 disease, and activating NF-κB and NRF2 signaling pathways. The molecular docking results, supporting the network pharmacology finding, indicated that the syrigaresinol compound, with several NF-ĸB binding residues, inhibited the inflammatory pathway by blocking the protein signal. Saussureamine A and C, with lower binding affinities for TNFα, showed higher effectiveness compared to dexamethasone, showing their potential to reduce inflammation. In addition, syrigaresinol and saussureamine A and C showed potential for reducing inflammation. These results showed the potential of S. lappa as an herb for defense against SARS-CoV-2

Analisis Faktor Koagulasi : Korelasi Fibrinogen dengan Rendahnya Derajat Oksigenasi pada Pasien COVID-19

Background: Hipercoagulable state is a one complication of COVID-19. The exact mechanism are still unclear, however hyperfibrinogenemia is considered one of the mechanisms for COVID-19 coagulopathy. Objective : To analyze the parameters of coagulation factors of COVID-19 patients and its correlation with degree of oxygenation Methods: We conducted an observational analytic, cross sectional, single-center study  including  25 laboratory-confirmed patients in Dr. Saiful Anwar General Hospital, Malang, Indonesia from April-Juni 2020. Statistical analysis performed to determine coagulation factors like fibrinogen, D-dimer, thrombocyte  and its relationship to disease severity and correlation with degree of oxygenation measured by PaO2/FiO2. Result: Subjects consisted of 12 patients (48%) in the mild-moderate group and 13 patients (52%) in severe group. D-dimer with mean 1,30 mg/L (0,43 mg/L - 4,08 mg/L) increased in 11 patients (91,67%) in mild-moderate group and 11 patients (84,61%) in severe group with mean 11,42 mg/L (0,34 mg/L – 66,30 mg/L). Fibrinogen with mean 399,73 mg/dL  (235,10 mg/dL -529 mg/dL) increased in 7 patients (58,33%) in mild-moderate and 10 patients (76,92%) in severe group with mean 444,31 mg/dL (284,7 mg/dL – 543,0 mg/dL). Statistical analysis revelaed that D-dimer associated with disease severity (p=0,039) and fibrinogen was inversely correlated with degree of oxygenation measured by PaO2/FiO2 ratio with moderate correlation strength (p = 0.019; Pearson correlation = -4,67). Conclusion: High level of fibrinogen correlated with decrease of oxygenation and D-dimer associated with disease severity in hospitalized patients, suggested increasing coagulable factors such as fibrinogen and D-dimer may be the main keys developing severe condition in COVID-19 patients

Respiratory Parameter Has A Great Impact in Determining Sepsis Condition in COVID-19 Patients at Saiful Anwar Hospital Malang: Case Report

To describe Sequential Organ Failure Assessment (SOFA) Score parameters which have a great impact in the condition of sepsis in Corona Virus Disease-19 (COVID-19) patients and comorbidities that aggravate the patient's condition, we conducted a prospective cohort study in adult patients with sepsis and confirmed COVID-19 cases. We conducted a prospective cohort study in confirmed COVID-19 patients with sepsis who were admitted at Saiful Anwar Hospital Malang at March 10th–April 21st 2020. Diagnosis of sepsis is based on the Surviving Sepsis Campaign-III criteria. We found 6 COVID-19 confirmed patients with sepsis. There is an increased respiratory parameter in SOFA Score in these patients. Therefore, respiratory parameter of the SOFA score has a great impact in determining sepsis condition among confirmed COVID-19 patients. Keywords: COVID-19, Sepsis, SOFA Scor

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis

Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting

Correction: Epidemiology and outcomes of early-onset AKI in COVID-19-related ARDS in comparison with non-COVID-19-related ARDS: insights from two prospective global cohort studies (Critical Care, (2023), 27, 1, (3), 10.1186/s13054-022-04294-5)

Following publication of the original article [1], the authors identified that the collaborating authors part of the collaborating author group CCCC Consortium was missing. The collaborating author group is available and included as Additional file 1 in this article

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND: The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS: In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS: Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS: Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group