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"Latar Belakang:Penyakit COVID-19 yang disebabkan oleh virus SARS-CoV-2 bisa menyebabkan kelainan pada paru-paru berupa pulmonary intravascular coagulation, suatu koagulopati akibat infeksi. Banyak menduga keadaan ini disebabkan oleh cytokine strorm yang salah satu komponen utamanya adalah IL-6. Sampai saat ini belum diketahui hubungan antara IL-6 dengan koagulopati pada penyakit ini.Tujuan:Kami ingin megetahui apakah IL-6 memiliki korelasi dengan pertanda koagulopati d-Dimer, fibrinogen, dan prothrombin time, serta apakah IL-6 memiliki korelasi dengan ferritin sebagai acute phase reactant. Kami juga ingin mengetahui apakah IL-6, ferritin, fibrinogen, d-Dimer, dan PT berkorelasi dengan perburukan subjek COVID-19 derajat sedang dan berat.Metode:Kami melakukan penelitian kohort prospektif pada pasien COVID-19 derajat sedang dan berat di suatu rumah sakit khusus yang menangani perawatan pasien COVID-19 mulai dari Juni 2020 sampai Januari 2021. Kami melakukan pemeriksaan serial IL-6, d-Dimer, fibrinogen, ferritin dan prothrombin time (PT), serta observasi keadaan pasien tersebut saat masuk rawat dan pada hari ke 14 hari atau sebelum hari ke 14 jika terjadi perbaikan, perburukan, atau pulang; mana yang lebih dahulu terjadi. Penelitian ini sudah mendapat persetujuan dari Panitia Tetap Etik Penelitian Kedokteran FKUI-RSUPN Cipto Mangunkusumo.Hasil:Selama Juni 2020 sampai dengan Januari 2021 kami temukan sebanyak 374 pasien COVID-19 derajat sedang dan berat. Tujuh puluh tiga subjek masuk kriteria inklusi 61 orang termasuk kategori berat, dan 12 orang sedang. Jumlah pasien perburukan adalah 35 dari 61 pasien derajat berat, dan 1 dari 12 pasien derajat sedang. Uji korelasi Spearman antara IL-6 dengan ferritin, d-Dimer, fibrinogen, dan PT berturut-turut koefisien korelasinya 0,08 (p=0,5), -0,13 (p=0,27), 0,01 (p=0,91), 0,03 (p=0,77). Uji korelasi Spearman antara ferritin dengan d-Dimer, fibrinogen, dan PT berturut-turut 0,17 (p=0,14), 0,05 (p=0,63), dan 0,07 (p=0,51). ROC yang memiliki luas lebih dari 60% adalah selisih d-Dimer dan selisih IL-6 (74,77% dan 71,32%).Kesimpulan:Tidak ditemukan korelasi antara IL-6 dengan d-Dimer, fibrinogen, PT. Ferritin tidak berkorelasi dengan d-Dimer, fibrinogen dan PT. IL-6 tidak berkorelasi dengan ferritin. Perubahan IL-6 dan d-Dimer dapat memprediksi perburukan pada pasien COVID-19 derajat sedang dan berat.

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COVID-19 disease caused by the SARS-CoV-2 virus can cause abnormalities in the lungs in the form of pulmonary intravascular coagulation, a coagulopathy due to infection. Many suspect this situation is caused by cytokine storm, one of the main components of which is IL-6. Until now, there is no known relationship between IL-6 and coagulopathy in this disease.

Objectives:

We wanted to know whether IL-6 correlated with markers of d-Dimer coagulopathy, fibrinogen, and prothrombin time, and whether IL-6 correlated with ferritin as an acute phase reactant. We also wanted to find out whether IL-6, ferritin, fibrinogen, d-Dimer, and PT correlated with moderate and severe worsening of COVID-19 subjects.

Methods:

We conducted a prospective cohort study of moderate and severe COVID-19 patients in a specialized hospital that treats COVID-19 patients from June 2020 to January 2021. We performed serial tests of IL-6, d-Dimer, fibrinogen, ferritin and prothrombin time (PT), as well as observing the patient's condition at the time of admission and on day 14 or before day 14 if there is improvement, worsening, or discharge; whichever happens first. This research has been approved by the Permanent Committee of Medical Research Ethics FKUI-RSUPN Cipto Mangunkusumo.

Results:

During June 2020 to January 2021, we found 374 moderate and severe COVID-19 patients. Seventy-three subjects entered the inclusion criteria, 61 people were included in the heavy category, and 12 people were moderate. The number of deteriorating patients was 35 of 61 severe grade patients, and 1 of 12 moderate grade patients. Spearman correlation test between IL-6 and ferritin, d-Dimer, fibrinogen, and PT, respectively, the correlation coefficients were 0.08 (p=0.5), -0.13 (p=0.27), 0.01 ( p=0.91), 0.03 (p=0.77). Spearman correlation test between ferritin and d-Dimer, fibrinogen, and PT was 0.17 (p=0.14), 0.05 (p=0.63), and 0.07 (p=0.51) . ROCs that have areas of more than 60% are the d-Dimer-difference and IL-6-difference (74.77% and 71.32%).

Conclusions:

No correlation was found between IL-6 and d-Dimer, fibrinogen, PT. Ferritin did not correlate with d-Dimer, fibrinogen and PT. IL-6 was not correlated with ferritin. Changes in IL-6 and d-Dimer can predict worsening in moderate and severe COVID-19 patients."

"Since the very beginning of critical care medicine, much attention has been paid to the risk of bleeding, but only recently the risk of thrombosis has been recognized in critical patients; in fact, current laboratory investigations aimed to monitor blood coagulation are more focused on the assessment of the hemorrhagic than of the thrombotic risk. Since mid-90s, many studies have detected powerful pro-thrombotic actions of endogenous mediators in sepsis and other inflammatory conditions, including trauma and postoperative status. Unfortunately, the related complication are both hard to detect and extremely harmful. The volume provides a full coverage of the hemocoagulative problems in anesthesia and intensive care, taking into consideration the physiology and monitoring of hemostasis, its relation with sepsis, and the specific aspects of the various critical conditions, from trauma to burns, to heart and transplant surgery or acute renal failure."

"Gangguan koagulasi merupakan komplikasi yang umum terjadi pada pasien kanker kolorektal dan dikaitkan dengan risiko morbiditas dan mortalitas. Terapi antikoagulan pada pasien kanker kolorektal dengan gangguan koagulasi cukup sulit dilakukan akibat berbagai risiko. Pencarian kandidat biomarker sebagai potensi target terapi diperlukan untuk mengembangkan strategi pengobatan baru yang dapat menurunkan risiko efek samping pengobatan. Dataset microarray GSE52060 berisi data profil gen 23 sel tumor pasien kanker kolorektal dan 23 sel mukosa normal dari pangkalan data GEO dianalisis menggunakan GEO2R untuk identifikasi gen dengan ekspresi berbeda bermakna (DEG) dengan standar |log2(Fold Change)| > 2 dan p < 0,05. DEG yang memenuhi kriteria kemudian dilakukan analisis anotasi fungsi gen dengan analisis ontologi gen (GO) dan jalur KEGG. Analisis GEO2R menunjukkan terdapat 299 DEG antara sel tumor dan sel mukosa normal yang terdiri dari 221 gen yang mengalami down-regulasi dan 78 gen yang mengalami up-regulasi. Hasil analisis DEG oleh GO menunjukkan DEG cukup signifikan terjadi pada gen-gen yang terlibat dalam transport bikarbonat, transport anion, dan aktivitas carbonic anhydrase (CA). Hasil analisis DEG oleh jalur KEGG menunjukkan 23 DEG cukup signifikan pada berbagai jalur fisiologis maupun patologis dan memiliki hubungan dengan gangguan koagulasi pada lima jalur. Terdapat 23 gen yang memiliki potensi sebagai kandidat biomarker untuk pasien kanker kolorektal dengan gangguan koagulasi.

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Coagulation disorders are common complications in colorectal cancer patients and are associated with the risk of morbidity and mortality. Anticoagulant therapy in colorectal cancer patients with coagulation disorders is difficult to carry out due to various risks and side effects. The search for biomarker candidates as potential targets for therapy is necessary to develop new treatment strategies that can reduce the risk of treatment side effects. The GSE52060 microarray dataset contains gene profile data of 23 tumor cells and 23 normal mucosal cells taken from colorectal cancer patients from the GEO database. The data was analyzed using GEO2R for identification of differentially expressed genes (DEGs). DEGs that met the criteria were then subjected to gene function annotation analysis using gene ontology (GO) analysis and KEGG pathways analysis. GEO2R analysis showed that there were 299 DEGs between tumor cells and normal mucosal cells consisting of 221 downregulated genes and 78 upregulated genes. The results of DEG analysis by GO showed that DEGs were enriched in bicarbonate transport, anion transport and carbonic anhydrase (CA) activity. The results of DEG analysis by the KEGG pathway showed that 23 DEGs were quite significant in various physiological and pathological pathways and had a connection with coagulation disorders in five pathways. Twenty-three genes have been identified as potential biomarkers for colorectal cancer patients with coagulation disorders."