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"[ABSTRAKLatar Belakang: Pada anak dengan penyakit jantung bawaan (PJB) yangmenjalani operasi jantung terbuka, sepsis merupakan salah satu komplikasipascaoperasi. Lama prosedur pintas jantung paru, usia, status gizi, timektomi, danvariasi genetik, seperti polimorfisme toll-like receptor (TLR) 2 dan tollinteractingprotein (TOLLIP) dapat memengaruhi respons imun. Informasimengenai peran faktor tersebut terhadap kejadian sepsis dan respons imunpascaoperasi jantung terbuka masih terbatas.Tujuan: Mengetahui peran polimorfisme TLR2, TOLLIP, dan faktor lainnyaterhadap kejadian sepsis dan respons imun pascaoperasi jantung terbuka untukmemperoleh strategi paling tepat dalam penanganan kasus bedah jantung padaanak.Metodologi: Studi longitudinal dengan non-probability consecutive samplingdilakukan pada anak <1 tahun yang menjalani operasi jantung terbuka.Pemeriksaan polimorfisme TLR2 Arg677Trp, TLR2 N199N, TOLLIP rs5743867,sel CD4 dan CD8 yang menyekresikan IFN-γ intraselular, sel Dendritik yangmengekspresikan TLR2, dan sel NK. Pasien menjalani operasi jantung terbuka.Setelah operasi, pasien dimonitor untuk menilai sepsis dan respons imunpascaoperasi.Hasil: Dari 108 subjek yang terlibat, 21,3% diantaranya mengalami sepsis.Seluruh subjek adalah mutan TLR2 Arg677Trp, 92,6% pasien adalah mutan TLR2N199N, dan 52,8% pasien adalah mutan TOLLIP rs5743867. Polimorfisme TLR2N199N dan timektomi total tidak diikutkan dalam model analisis multivariat.Polimorfisme TOLLIP rs5743867 (p = 0,358) menurunkan resiko sepsis, lamaprosedur pintas jantung paru ≥90 menit (p = 0,002), usia neonatus (p = 0,032), dangizi buruk (p = 0,558) meningkatkan risiko sepsis pascaoperasi. Jumlah responsimun bervariasi antara kategori, namun secara umum komponen respons imunlebih rendah pada pasien yang mengalami sepsis dibanding pada pasien yang tidakmengalami sepsis.Simpulan: Lama prosedur pintas jantung paru dan usia neonatus secara signifikanmemengaruhi risiko dan kecepatan sepsis pascaoperasi. Peran polimorfisme TLR2N199N dan TOLLIP rs5743867 terhadap kejadian sepsis dan respons imunpascaoperasi memerlukan studi komprehensif lebih lanjut.

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ABSTRACTBackground: Sepsis is one of the complications in children with congenital heartdefect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immuneresponse. Information regarding those factors in the development of sepsis andimmune response after open heart surgery is still limited.Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as wellas other risk factors, in the development of sepsis and immune response followingopen heart surgery to develop the best strategy in open heart surgery in children.Methods: Longitudinal study with consecutive sampling were done in children <1year old who underwent open heart surgery. Blood sample was obtained to checkfor TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIPrs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,TLR2 expression in Dendritic cells, and NK cells. Patient then underwent openheart surgery. Thymectomy was done as indicated and CPB time was recorded.After surgery, patient was monitored for signs of sepsis and immune response waschecked.Results: Out of 108 patients involved in this study, 21.3% developedpostoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIPrs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199Npolymorphism and thymectomy were not included in multivariate analysis.TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPBtime ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =0.558) increased the risk of postoperative sepsis. Immune response?s counts varyin each category, but were generally lower in patients who developedpostoperative sepsis.Conclusion: Cardiopulmonary bypass time and neonates significantly influencedthe risk and hazard of postoperative sepsis. Further investigation on the role ofTLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to providemore comprehensive explanation on the development of postoperative sepsis andthe immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heartdefect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immuneresponse. Information regarding those factors in the development of sepsis andimmune response after open heart surgery is still limited.Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as wellas other risk factors, in the development of sepsis and immune response followingopen heart surgery to develop the best strategy in open heart surgery in children.Methods: Longitudinal study with consecutive sampling were done in children <1year old who underwent open heart surgery. Blood sample was obtained to checkfor TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIPrs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,TLR2 expression in Dendritic cells, and NK cells. Patient then underwent openheart surgery. Thymectomy was done as indicated and CPB time was recorded.After surgery, patient was monitored for signs of sepsis and immune response waschecked.Results: Out of 108 patients involved in this study, 21.3% developedpostoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIPrs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199Npolymorphism and thymectomy were not included in multivariate analysis.TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPBtime ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =0.558) increased the risk of postoperative sepsis. Immune response?s counts varyin each category, but were generally lower in patients who developedpostoperative sepsis.Conclusion: Cardiopulmonary bypass time and neonates significantly influencedthe risk and hazard of postoperative sepsis. Further investigation on the role ofTLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to providemore comprehensive explanation on the development of postoperative sepsis andthe immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heartdefect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immuneresponse. Information regarding those factors in the development of sepsis andimmune response after open heart surgery is still limited.Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as wellas other risk factors, in the development of sepsis and immune response followingopen heart surgery to develop the best strategy in open heart surgery in children.Methods: Longitudinal study with consecutive sampling were done in children <1year old who underwent open heart surgery. Blood sample was obtained to checkfor TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIPrs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,TLR2 expression in Dendritic cells, and NK cells. Patient then underwent openheart surgery. Thymectomy was done as indicated and CPB time was recorded.After surgery, patient was monitored for signs of sepsis and immune response waschecked.Results: Out of 108 patients involved in this study, 21.3% developedpostoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIPrs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199Npolymorphism and thymectomy were not included in multivariate analysis.TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPBtime ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =0.558) increased the risk of postoperative sepsis. Immune response?s counts varyin each category, but were generally lower in patients who developedpostoperative sepsis.Conclusion: Cardiopulmonary bypass time and neonates significantly influencedthe risk and hazard of postoperative sepsis. Further investigation on the role ofTLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to providemore comprehensive explanation on the development of postoperative sepsis andthe immune response after open heart surgery;Background: Sepsis is one of the complications in children with congenital heartdefect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immuneresponse. Information regarding those factors in the development of sepsis andimmune response after open heart surgery is still limited.Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as wellas other risk factors, in the development of sepsis and immune response followingopen heart surgery to develop the best strategy in open heart surgery in children.Methods: Longitudinal study with consecutive sampling were done in children <1year old who underwent open heart surgery. Blood sample was obtained to checkfor TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIPrs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,TLR2 expression in Dendritic cells, and NK cells. Patient then underwent openheart surgery. Thymectomy was done as indicated and CPB time was recorded.After surgery, patient was monitored for signs of sepsis and immune response waschecked.Results: Out of 108 patients involved in this study, 21.3% developedpostoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIPrs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199Npolymorphism and thymectomy were not included in multivariate analysis.TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPBtime ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =0.558) increased the risk of postoperative sepsis. Immune response?s counts varyin each category, but were generally lower in patients who developedpostoperative sepsis.Conclusion: Cardiopulmonary bypass time and neonates significantly influencedthe risk and hazard of postoperative sepsis. Further investigation on the role ofTLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to providemore comprehensive explanation on the development of postoperative sepsis andthe immune response after open heart surgery, Background: Sepsis is one of the complications in children with congenital heartdefect who underwent open heart surgery. Cardiopulmonary bypass (CPB) time,age, nutritional status, thymectomy, and genetic variants, such as toll-like receptor(TLR) 2 and toll-interacting protein (TOLLIP) polymorphism affect immuneresponse. Information regarding those factors in the development of sepsis andimmune response after open heart surgery is still limited.Objectives: To understand the role of TLR 2 and TOLLIP polymorphism, as wellas other risk factors, in the development of sepsis and immune response followingopen heart surgery to develop the best strategy in open heart surgery in children.Methods: Longitudinal study with consecutive sampling were done in children <1year old who underwent open heart surgery. Blood sample was obtained to checkfor TLR2 Arg677Trp polymorphism, TLR2 N199N polymorphism, TOLLIPrs5743867 polymorphism, the numbers of intracellular interferon γ CD4 and CD8,TLR2 expression in Dendritic cells, and NK cells. Patient then underwent openheart surgery. Thymectomy was done as indicated and CPB time was recorded.After surgery, patient was monitored for signs of sepsis and immune response waschecked.Results: Out of 108 patients involved in this study, 21.3% developedpostoperative sepsis. TLR2 Arg677Trp polymorphism was found in all patients,TLR2 N199N polymorphism was found in 92.6% of the patients, and TOLLIPrs5743867 polymorphism was found in 52.8% of the patients. TLR2 N199Npolymorphism and thymectomy were not included in multivariate analysis.TOLLIP rs5743867 polymorphism (p = 0.358) reduced the risk of sepsis, CPBtime ≥90 menit (p = 0.002), neonates (p = 0.032), and severe malnutrition (p =0.558) increased the risk of postoperative sepsis. Immune response’s counts varyin each category, but were generally lower in patients who developedpostoperative sepsis.Conclusion: Cardiopulmonary bypass time and neonates significantly influencedthe risk and hazard of postoperative sepsis. Further investigation on the role ofTLR2 N199N and TOLLIP rs5743867 polymorphism are necessary to providemore comprehensive explanation on the development of postoperative sepsis andthe immune response after open heart surgery]"

"ABSTRAKLatar Belakang: Cheilitis angularis adalah penyakit inflamasi yang dipicu oleh faktor genetik, lingkungan dan agen infektif. Gen Toll Like Receptor 2 (TLR2) merupakan komponen penting dalam respon imun innate. Tujuan: Penelitian ini bertujuan untuk menganalisis distribusi polimorfisme gen Toll Like Receptor 2 (TLR2) pada cheilitis angularis dan non cheilitis angularis. Metode: 50 sampel cheilitis angularis dan 50 sampel non cheilitis angularis digunakan dalam penelitian ini. Campuran TLR2 16934 T/A dengan ddH2O, enzim polimerase dan DNA template dianalisis menggunakan teknik PCR RFLP, yang menggunakan HphI sebagai enzim restriksi, dilanjutkan dengan elektroforesis. Hasil: Genotip terbanyak yang ditemukan pada cheilitis angularis dan non cheilitis angularis adalah genotip TT. Jumlah genotip dan alel polimorfik paling banyak ditemukan pada cheilitis angularis (22% dan 13%) dibandingkan non-cheilitis angularis (12% dan 6%). Uji Continuity Correction menunjukkan tidak terdapat perbedaan bermakna antara cheilitis angularis dan non-cheilitis angularis. Kesimpulan: Terdapat hubungan antara polimorfisme gen TLR2-16934 T/A dan cheilitis angularis.

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ABSTRACT

Background: Angular cheilitis is an inflammatory disease induced by genetic, environmental and infective agent factors. Toll Like Receptor 2 (TLR2) gene is essential components for innate immunity response. Objective: This study aimed to analyzed distribution of Toll Like Receptor 2 (TLR2) gene polymorphism in angular cheilitis and non angular cheilitis. Methods: 50 samples angular cheilitis as case group and 50 samples non angular cheilitis as control group were used in this research. TLR2-16934 T/A mixed with ddH2O, polymerase enzyme and DNA template were analyzed using PCR RFLP technique, which used HphI as restriction enzyme, then followed by electrophoresis. Subsequently assessed with statistical analysis using Continuity Corrections test. Results: The most genotype found in angular cheilitis and non angular cheilitis was TT genotype. The amount of polymorphic genotype and allele were recorded greater in angular cheilitis (22% and 13%) than non-angular cheilitis (12% and 6%). Continuity Corrections test showed no significant differences between angular cheilitis and non ngular cheilitis (p-value=0,287). Conclusion: There is an association between TLR2-16934 T/A gene polymorphism and angular cheilitis."

"Antiretroviral therapy (ART) given to HIV patients to improve their immune response that damaged by HIV infection. Some patients with ART experience Immune Restoration Disease (IRD) as worsening of clinical symptoms from certain pathogens infection. The incidence of IRD concided with an increased number of CD4+ T cells. Hepatitis C virus can also infect HIV patients and may also lead to HCV IRD. The immunopathogenecity of IRD has not known yet. This study aims to look at the function of dendritic cells producing IL-12 and IFNα, and IFNγ-producing T cell responses in incidence of HCV IRD. Research subjects were 50 patients with HIV/HCV who were initiating antiretroviral therapy (ART) for up to 6 months of therapy. There are 9 people with HCV IRD who compared with non HCV IRD patients. Blood specimens were collected from study subjects at months 0, 1, 3 and 6 after ART. Then PBMC isolation was done and used for flowsitometri and ELISpot analysis.

The results showed that the percentage of myeloid (mDC) and plasmacytoid dendritic cells (pDC) did not differ between HCV IRD patients and non-HCV IRD patients. It appears that the percentage of IL-12-producing mDC did not correlate significantly with IFNγ- producing T cells both in HCV IRD and non-IRD HCV patients. The percentage of IL-12-producing mDC in HCV IRD patients were lower than in non-IRD patients (p=0.003). While percentage of IFNα-producing pDC and IFNγ- producing T cells did not differ significantly between the two groups of patients. Antibody response to HCV proteins (core, NS3, NS4, and NS5) did not differ between HCV IRD and non-HCV IRD patients. The role of dendritic cells and T cell responses in HCV IRD incidence have not clearly seen.

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Terapi antiretroviral (ART) diberikan kepada pasien HIV akan memperbaiki respon imun tubuh yang rusak karena infeksi HIV. Beberapa pasien dengan ART mengalami sindrom pulih imun atau Immune Restoration Disease (IRD) berupa perburukan gejala klinis dari infeksi patogen tertentu. Kejadian sindrom pulih imun ini terjadi bersamaan dengan peningkatan jumlah sel T CD4+. Virus Hepatitis C yang menjadi patogen penyerta pada pasien HIV juga menjadi penyebab sindrom pulih imun. Belum diketahui dengan jelas imunopatogenesitas dari sindrom pulih imun ini. Penelitian ini bertujuan untuk melihat fungsi sel dendritik penghasil IL-12 dan IFNα, serta respon sel T penghasil IFNγ pada kejadian sindrom pulih imun HCV. Subyek penelitian adalah 50 pasien HIV/HCV yang sedang memulai terapi antiretroviral (ART). Terdapat 9 orang pasien dengan sindrom pulih imun HCV yang dibandingkan dengan pasien tanpa sindrom pulih imun HCV. Spesimen darah lengkap dikumpulkan dari subyek penelitian pada bulan ke-0, 1, 3 dan 6 setelah ART. Kemudian dilakukan isolasi PBMC dan analisis flowsitometri dan ELISpot.

Hasil penelitian menunjukkan bahwa persentase sel dendritik mieloid (mDC) dan plasmasitoid (pDC) tidak berbeda antara pasien dengan dan tanpa sindrom pulih imun HCV. Persentase sel mDC penghasil IL-12 tidak berkorelasi secara signifikan dengan jumlah sel T penghasil IFNγ baik pada pasien dengan maupun tanpa sindrom pulih imun HCV. Pasien dengan sindrom pulih imun HCV memiliki persentase sel mDC penghasil IL-12 yang lebih rendah dibandingkan pasien tanpa sindrom pulih imun HCV (p=0,003). Sedangkan persentase sel pDC penghasil IFNα dan jumlah sel T penghasil IFNγ tidak berbeda secara signifikan antara kedua kelompok pasien. Respon antibodi terhadap protein HCV (core, NS3, NS4 dan NS5) pun tidak berbeda antara kedua kelompok pasien. Disimpulkan bahwa belum terlihat adanya peran dari sel dendritik dan respon sel T terhadap kejadian sindrom pulih imun HCV."

"Latar Belakang: Sepsis merupakan salah satu masalah kesehatan di rumah sakittermasuk di ruang Intensive Care Unit (ICU) dan angka kematiannya masih tetaptinggi meskipun dengan tatalaksana yang maksimal dan biaya yang besar. Kematianmerupakan hal yang sulit untuk diprediksi. Pasien yang telah diresusitasi denganbaik masih berpeluang untuk mengalami kematian karena proses disfungsi organyang terus berlanjut akibat tingginya tingkat inflamasi. Inflamasi yang tidakterkontrol memicu stress oksidasi dan necroptosis. Penelitian terakhir menunjukkankadar protein carbonyl (PCO) dan receptor-interacting protein kinase 3 (RIPK3)tinggi pada pasien sepsis dan dapat digunakan untuk memprediksi kematian.Penelitian ini bertujuan untuk menilai seberapa besar kegagalan resusitasi, kadarPCO, dan kadar RIPK3 dapat memprediksi kematian pada pasien sepsis.Metode: Rancangan penelitian ini adalah kohort prospektif di ruang resusitasi danICU RSUP. Dr. Moh. Hoesin (RSMH) Palembang. Penelitian dimulai setelahsertifikat etik dan izin lokasi diterbitkan sejak bulan Februari sampai Agustus 2019.Kriteria penerimaan meliputi pasien berusia 18 tahun atau lebih yang didiagnosissepsis. Kriteria penolakan meliputi keluarga menolak diikutsertakan dalampenelitian, pasien tidak dirawat di ICU, terlambat didiagnosis (lebih dari 24 jam),hamil dan didiagnosis mati batang otak. Kriteria pengeluaran meliputi pasienmeninggal kurang dari 4 jam setelah diagnosis ditegakkan dan pasien tidak dapatdilakukan follow up dalam waktu 28 hari. Tim peneliti yang telah dilatihsebelumnya mengidentifikasi semua pasien yang memenuhi kriteria penelitian.Semua subjek penelitian mendapatkan resusitasi standar dan diambil sampel darahuntuk diperiksakan ke laboratorium. Pasien diamati selama 28 hari: apakahmengalami kematian atau tidak. Kegagalan resusitasi didefinisikan sebagai kadar laktat ≥2 mmol/l atau reduksi laktat <20%. Data yang didapatkan dianalisis denganuji statistik yang sesuai menggunakan piranti lunak program STATA.Hasil: Didapatkan total 72 subjek penelitian, 13 dikeluarkan karena meninggalkurang dari 4 jam setelah diagnosis ditegakkan. Dari hasil analisis bivariatdidapatkan hubungan antara kegagalan resusitasi (RR 1,36; IK95% 0,965-1,916; p0,085), kadar PCO (RR 2,37; IK95% 1,348-4,194; p 0,0001), dan kadar RIPK3 (RR5,86; IK95% 2,07-16,61; p <0,0001). Dari hasil multivariat hanya didapatkan satuvariabel yang bermakna yaitu kadar RIPK3 (RR 5,39; IK95% 1,490-19,478; p0,010). Setelah dikontrol dengan variabel perancu usia, komorbiditas dan skorAPACHE II didapatkan variabel RIPK3 memiliki RR 4,64 dengan IK95% 1,233-17,479; p 0,023).Simpulan: Kegagalan resusitasi, kadar PCO dan kadar RIPK3 dapat memprediksikematian pada pasien sepsis.

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Background: Sepsis remains one of the health problems at the hospital including

intensive care unit (ICU) since its mortality is still high despite maximal efforts on

therapy. Mortality is an unpredictable event. Patients who were properly

resuscitated still have a probability of mortality because of severe inflammatory

state which may lead to ongoing organ dysfunctions. Uncontrolled inflammation

will trigger oxidative stress and necroptosis. Recent study showed that high level

of protein carbonyl (PCO) and receptor-interacting protein kinase 3 (RIPK3) in

septic patients could be used to predict mortality. This study wished to analyze the

ability resuscitation failure, PCO level and RIPK3 level to predict mortality in

septic patients.

Methods: This prospective cohort study was conducted at resuscitation room and

ICU of RSUP. dr. Moh. Hoesin (RSMH), a single tertiary teaching hospital in

Palembang, South Sumatera. This study was started after ethical and location

authorization were unleashed in February to August 2019. Inclusion criteria were

18 years old or above patients that were diagnosed with sepsis. Exclusion criteria

were patients whose family did not give any consent to participate the study,

patients that were not treated at the ICU, had a late diagnosis (>24 h), pregnant, and

diagnosed with brain dead. Drop out criteria including died <4 h after diagnosed

and patients that could not be followed in 28 days. Investigators were trained to

identified all eligible patients. Subjects had a standard resuscitation and their blood

was taken to be examined at the laboratory. Patients were observed in 28 days

whether there were any mortality or not. Failed resuscitation defined by examined

lactate level ≥ 2 mmol/l or lactate reduction<20%. Data was statistically analyzed

with STATA™.

Results: Seventy two subjects were included to the study but 13 of them were

dropped out because died within 4 h after diagnosed. From bivariate analysis, there

was an association between failed resuscitation (RR 1.36; CI95% 0.965-1.916; p

0.085), PCO level (RR 2.37; CI95% 1.348-4.194; p 0.0001), and RIPK3 level (RR

5,86; CI95% 2.07-16.61; p <0.0001). From multivariate analysis using cox

regression time constant, the only variable statistically significant was RIPK3 (RR

5.39; CI95% 1.490-19.478; p 0.010). After adjusted by confounding variables,

including age, comorbidities, and APACHE II score, RIPK3 had RR 4.64 with CI

95% 1.233-17.479; p 0.023.

Conclusions: Failed resuscitation, PCO level, and RIPK3 level can predict

mortality in sepsis patients"

"Pendahuluan: Prevalensi periodontitis di Indonesia mencapai 74,1% berdasarkan data Riskesdas tahun 2018. Bakteri penyakit periodontitis dapat menembus lebih dalam ke jaringan sekitar gigi. Hal ini dapat memicu respons host dalam upaya bertahan melawan bakteri yang menyerang, salah satunya adalah respon dari TLR-2. Salah satu obat yang memiliki kandungan antiinflamasi dan saat ini sedang banyak diperhatikan oleh masyarakat adalah propolis. Tujuan: Meneliti interaksi dan afinitas antara senyawa pada propolis dengan reseptor Toll-Like Receptor 2 melalui studi penambatan molekuler. Metode: Studi in silico dengan penambatan molekuler untuk menguji interaksi molekuler dari ligan bahan aktif propolis terhadap reseptor TLR-2. Hasil interaksi yang didapat akan dianalisis dan diintrepretasikan untuk mengetahui afinitas ikatan dari interaksi antara ligan dengan reseptor. Hasil: terdapat interaksi antara ligan bahan aktif propolis terhadap reseptor TLR-2. Kesimpulan: Propolis berpotensi menjadi agen antibakteri pada terapi periodontitis yang dapat menghambat inflamasi melalui inaktivasi TLR-2. Namun, perlu dilakukan penelitian lebih lanjut secara in vitro untuk pengamatan lebih lanjut terkait interaksi yang terjadi.

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Background: The prevalence of periodontitis in Indonesia reached 74.1%. (Riskesdas, 2018). Periodontitis bacteria can penetrate deep into the gum. This can trigger a host response in an effort to defend against invading bacteria, including responses from TLR-2. Propolis has been shown to have antiinflammatory properties and is currently getting a lot of attention from the public. Purpose: To examine the interaction and affinity between compounds in propolis and the Toll-Like Receptor 2 receptor through molecular docking studies. Methods: To investigate the molecular interactions of propolis active ingredient ligands on the TLR-2 receptor, a molecular docking was conducted. The interaction results obtained will be analyzed and interpreted to determine the binding affinity of the interaction between the ligand and the receptor. Results: There is an interaction between the ligand of the active ingredient of propolis and the TLR-2 receptor. Conclusions: Propolis has the potential to be an antibacterial agent in periodontitis therapy that can inhibit inflammation through inactivation of TLR-2. However, further research needs to be carried out with in vitro studies to further observe the interactions that may occur."

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Latar Belakang: Menurut data Riset Kesehatan Dasar (Riskesdas) 2018, prevalensi penyakit periodontitis menduduki peringkat kedua terbanyak setelah karies gigi, yaitu sebesar 74,1% di Indonesia. Periodontitis merupakan penyakit inflamasi yang dihubungkan dengan kerusakan jaringan periodontal. Dalam perjalanan periodontitis, TLR-4 berperan penting dalam respon imun dan patogenesis inflamasi periodontitis karena dapat mengenali bakteri gram negatif lipopolisakarida (LPS). Propolis merupakan salah satu zat alami berupa produk resin yang memiliki banyak aktivitas biologis, salah satunya antiinflamasi. Tujuan: Mengetahui interaksi molekuler senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 pada terapi periodontitis melalui studi penambatan molekuler. Metode: Studi eksperimental komputasional secara in silico menggunakan perangkat Autodock Tools 1.5.6 dan BIOVIA Discovery Studio Visualizer 2021 untuk menguji interaksi dan afinitas ikatan dari ligan propolis terhadap reseptor target TLR-4. Hasil interaksi akan dianalisis untuk menilai konformasi terbaik dari suatu molekul dan afinitas pengikatannya. Penambatan molekuler dilakukan dengan menambatkan 7 senyawa propolis yang berpotensi sebagai antiinflamasi terhadap TLR-4 sebagai reseptor yang berperan dalam proses inflamasi. Hasil: Terdapat interaksi molekuler ikatan antara ligan propolis dengan reseptor TLR-4. Dari ketujuh ligan propolis yang diuji, senyawa Adhyperforin memiliki afinitas terbaik dibandingkan ligan propolis lainnya. Kesimpulan: Senyawa bioaktif pada propolis dapat berinteraksi terhadap reseptor TLR-4 melalui uji penambatan molekuler dan dapat berpotensi menjadi agen antiinflamasi terhadap TLR-4 yang dapat digunakan sebagai kandidat obat untuk terapi periodontitis. Namun, perlu dilakukan penelitian lebih lanjut untuk membuktikan sifat senyawa bioaktif pada propolis yang dapat bertindak sebagai agen antiinflamasi yang baik untuk terapi periodontitis.

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Background: According to 2018 Basic Health Survey (Riskesdas) data, periodontitis is the second most frequent condition after dental caries, which reached a prevalence of 74.1% in Indonesia. Periodontitis is an inflammatory condition associated with the destruction of periodontal tissue. TLR-4, which recognizes gram-negative bacterial lipopolysaccharides (LPS), plays a crucial role in the immune response and inflammatory pathogenesis of periodontitis. Propolis is a natural product in the form of resin that has many biological activities, one of which is anti-inflammatory. Purpose: To investigate the molecular interactions of propolis compounds that have anti-inflammatory potential against TLR-4 in periodontitis therapy through molecular docking studies. Methods: In silico computational experimental study using Autodock Tools 1.5.6 and BIOVIA Discovery Studio Visualizer 2021 to test the interaction and binding affinity of propolis ligands towards the TLR-4 target receptor. The interaction results will be analyzed to assess the best conformation of a molecule and its binding affinity. Molecular docking was performed by targeting 7 propolis compounds that have anti-inflammatory potential against TLR-4 as a receptor that plays a role in the inflammatory process. Results: There is a binding interaction between propolis ligands and TLR-4 receptor. Of the seven propolis ligands tested, the compound Adhyperforin had the best affinity compared to other propolis ligand. Conclusions: Bioactive compounds in propolis can interact with TLR-4 receptors through molecular docking tests and can potentially become anti-inflammatory agents against TLR-4 that can be used as drug candidates for periodontitis therapy. However, further research is needed to prove the nature of bioactive compounds in propolis that can act as good anti-inflammatory agents for periodontitis therapy.

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"Latar belakang: Sepsis pascabedah jantung terbuka merupakan kondisi yang jarang terjadi tetapi memiliki mortalitas yang cukup tinggi. Gejala sepsis yang muncul pascabedah seringkali sulit dibedakan dengan kondisi inflamasi sistemik sehingga menimbulkan keterlambatan dalam menegakkan diagnosis maupun overtreatment pada pasien. Presepsin merupakan salah satu penanda sepsis yang mulai banyak digunakan terutama pada populasi dewasa. Penelitian ini bertujuan untuk melihat peran presepsin dalam menegakkan diagnosis sepsis pascabedah jantung terbuka pada anak.Tujuan: Untuk menguji performa diagnostik presepsin sebagai penanda sepsis pada anak pascabedahjantung terbuka dibandingkan dengan prokalsitonin (PCT).Metode: Studi potong lintang terhadap 49 pasien anak pascabedah jantung terbuka yang dirawat di RSCM. Penelitian ini mencari nilai batas optimal presepsin untuk mendiagnosis sepsis pascabedah jantung terbuka pada anak yaitu pada hari pertama dan ketiga pascabedah, kemudian membandingkannya dengan prokalsitonin. Analisis kurva ROC dikerjakan untuk menentukan nilai batas optimal presepsin.Hasil: Kadar presepsin hari pertama (T1) dan ketiga (T3) lebih tinggi pada subyek dengan sepsis daripada subyek yang tidak sepsis (median 415 pg/mL vs. 141,5 pg/mL pada hari pertama dan 624 pg/mL vs. 75,9 pg/mL pada hari ke tiga). Titik potong presepsin pada T1 dengan nilai 404 pg/mL memiliki performa untuk mendiagnosis sepsis dengan AUC 0,752 sedangkan presepsin T3 dengan nilai 203,5 pg/mL dengan AUC 0,945 yang lebih baik dibandingkan T1.Simpulan: Presepsin dapat dijadikan suatu modalitas untuk memberikan nilai tambah dan pertimbangan bagi klinisi untuk menegakkan diagnosis sepsis pada pasien anak pascabedah jantung terbuka.

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Background: Postoperative open-heart sepsis is a rare condition but has a fairly high mortality. Symptoms of sepsis that appear postoperatively are often difficult to distinguish from systemic inflammatory conditions, causing delays in establishing diagnosis and overtreatment in patients. Presepsin is one of the markers of sepsis that is starting to be widely used, especially in the adult population. This study is to identify the role of presepsin for diagnosing sepsis in post open-heart surgery in pediatric population.

Aim: To perform diagnostic test of presepsin as sepsis screening markers compares to procalcitonin (PCT) in post open-heart surgery.

Methods: Cross-sectional study of 49 postoperative open-heart pediatric patients treated at RSCM. This study looked for optimal cut-off values of presepsin for diagnosing open-heart postoperative sepsis in children on the first and third postoperative days, then compared it with procalcitonin. ROC curve analysis is performed to determine the optimal limit value of presepsin.

Result: First (T1) and third day (T3) PSP levels were higher in subjects with sepsis than non- sepsis (median 415 pg/mL vs. 141.5 pg/mL on first day and 624 pg/mL vs. 75.9 pg/mL on third day). ). T1 presepsin cut off 404 pg/ml had AUC of 0.772, while T3 presepsin cut off 203.5 og/ml had better AUC of 0.945. T3 is better for diagnosing sepsis.

Conclusion: Presepsin can be used as a modality to provide added value and consideration for clinicians to establish the diagnosis of sepsis in pediatric patients after open-heart surgery."

"ABSTRAKStunting merupakan kondisi malnutrisi pada anak yaitu tinggi badan menurut usia lebih dari minus 2 simpang baku. Indonesia menempati urutan kelima di dunia. Stunting berkorelasi dengan asupan makanan terutama protein, IGF-1 dan protein pengikat Insulin like Growth Factor Binding Protein IGFBP-3 , dan Zinc Zn . Kualitas protein dinilai dari profil asam amino bebas plasma Plasma Free Amino Acid = PFAA dan kuantitas dinilai dari jumlah asupan protein harian. Beberapa penelitian menemukan kadar IGF-1 dipengaruhi oleh polimorfisme SNP rs5742612, rs35767 dan rs35766. Penelitian ini bertujuan untuk menganalisis peran profil PFAA, IGF-1, IGFBP-3, polimorfisme IGF-1, Insulin, dan Zn pada anak.Penelitian ini merupakan studi comparative cross sectional dilakukan di RS Cipto Mangunkusumo, Lembaga Biomolekular Eijkman, dan Labkesda DKI Jakarta. Subjek penelitian adalah anak usia 1 ndash;3 tahun berasal dari UPTD Puskesmas Jatinegara dibagi menjadi 2 kelompok yaitu 101 anak stunted dan 101 anak nonstunted.Pada penelitian ini didapatkan kadar 8 dari 9 AA esensial, 2 AA esensial kondisional, dan 2 AA nonesensial lebih rendah bermakna kelompok stunted dibandingkan nonstunted. Profil PFAA yaitu jumlah anak di bawah nilai rujukan berbeda bermakna antara kelompok stunted dan nonstunted. Terdapat korelasi 8 AA esensial, 1 AA esensial kondisional, dan 2 AA nonesensial dengan tinggi badan anak. Pada kelompok anak stunted, IGF-1, IGFBP-3, insulin, Zn, energi total dan protein lebih rendah bermakna dari kelompok anak nonstunted. Terdapat korelasi bermakna AA esensial dengan IGF-1 dan IGFBP-3. Polimorfisme rs35766 genotipe AG kodominan memiliki pengaruh terhadap kadar IGF-1 pada kelompok nonstunted. Faktor yang memengaruhi kejadian stunting adalah energi atau protein, IGF-1 yang berinteraksi dengan genotipe kodominan AG, IGFBP-3, dan Zn.Simpulan: PFAA, IGF-1 yang berinteraksi dengan SNP rs35766 genotipe kodominan AG, memiliki pengaruh terhadap kejadian stunting. Perlu penelitian lebih lanjut mengenai pemberian pola makan yang tepat untuk mencegah dan mengatasi anak stunted. Kata kunci: AA esensial, AA nonesensial, IGFBP-3, insulin, PFAA, stunting, Zn

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ABSTRACTStunting is a malnourished condition in children defined by height for age is under minus 2 standard deviation. Indonesia ranked fifth in world for this condition. Stunting mainly corelates with low protein intakes, IGF-1 and its binding protein Insulin-like Growth Factor Binding Protein/IGFBP-3 , and zinc Zn . Plasma free amino acid profile PFAA measures quality of protein intake, whilst its quantity measured by daily protein intake records. Previous studies found IGF-1 level affected by single nucleotide polymorphism SNP on rs5742612, rs35767 and rs35766. This study aims to analyze the role of PFAA, IGF-1, IGFBP-3, and IGF-1 polymorphism, insulin, and Zn in children.This study is a comparative cross-sectional study held in Cipto Mangunkusumo National General Hospital, Eijkman Institute for Molecular Biology, and Jakarta Provincial Public Health Laboratory. Subjects were children age 1 ndash;3 years old from Jatinegara Region Public Health Centre divided into two groups of 101 stunted children and 101 non-stunted children.Eight essential AA levels, 2 conditional essential AAs, 2 nonessential AAs were significantly lower in stunted groups than non-stunted. There was significant difference of profile PFAA below normal range between stunted and non-stunted group. Eight essential amino acids, 1 conditional essential amino acid, and 2 non-essential amino acid correlate with children rsquo;s height. IGF-1, IGFBP-3, insulin, Zn, total energy, and protein were significantly lower in stunted children compare to non-stunted children. Significant correlations found for all essential amino acids with IGF-1 and IGFBP-3. The rs35766 AG codominant polymorphism affects IGF-1 level in non-stunted group. Factors affects stunting condition were total energy or protein intake, IGF-1 that interacts with AG codominant genotype, IGFBP-3, and Zn.Conclusion: PFAA and IGF-1 that interacts with SNP rs35766 AG codominant genotype affect stunting. Further study needed to determine appropriate dietary habit for stunting prevention and treatsment. Keywords: Essential amino acid, IGFBP-3, insulin, non-essential amino acid, plasma free amino acid profile, stunting, zinc"

"Kejadian Systemic Inflammatory Response Syndrome (SIRS) pasca bedah jantung terbuka masih merupakan salah satu komplikasi yang banyak ditemukan. Salah satu faktor risikonya adalah durasi pintas jantung. Studi kohort retrospektif dilakukan terhadap 187 pasien bedah jantung terbuka di RSUPN Cipto Mangunkusumo tahun 2014-2015. Subjek dibedakan menjadi 2 kelompok berdasarkan durasi pintas jantung (durasi >60 menit dan ≤60 menit). Sebanyak 107 (57,2%) pasien mengalami SIRS dalam 24 jam pasca operasi. Kejadian SIRS ditemukan pada 75 (65,8%) pasien dari kelompok durasi >60 menit dan 32 (43,8%) pasien dari kelompok durasi ≤60 menit. Melalui analisis multivariat regresi logistik, didapatkan hubungan bermakna (p<0,05) antara durasi CPB dan SIRS dengan OR2,04 (IK95% 1,05-3,93). Durasi CPB merupakan faktor risiko independen dari kejadian SIRS pasca bedah jantung terbuka.

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Sytemic inflammatory Response Syndrome (SIRS) is a major complication foundat patient following open heart surgery. One of the risk factors is the duration of the cardiopulmonary bypass. A historical cohort study had been done on 187 postcardiac surgery patients in RSUPN Cipto Mangunkusumo. The subjects were divided into 2 separate groups based on the duration of cardiopulmonary bypass (duration >60 minutes and ≤60 minutes). There were 107 (57.2%) patients having SIRS within 24 hours following the surgery. SIRS was found on 75 (65.8%) patients from group with duration >60 minutes and 32 (43.8%) patients from group with duration ≤60 minutes. Through logistic regression multivariate analysis, there was a significant difference (p<0.05) with OR 2.04 (CI95% 1.05-3.93) between two groups. Therefore, duration of cardiopulmonary bypass was an independent risk factor of post open heart surgery SIRS."

"Latar belakang: Peningkatan suhu tubuh ekstrim menyebabkan denaturasi protein,terhentinya reaksi enzimatik, hilangnya aktivitas dan integritas membran, sertamemicu terjadinya kerusakan sel. Peningkatan suhu tubuh juga mempengaruhiterjadinya efek inotropik dan kronotropik positif pada jantung. Diperkirakan bahwapajanan panas dapat meningkatkan ekspresi protein Transient Receptor PotentialVanilloid 1 (TRPV1), Heat Shock Factor 1 (HSF1) dan Heat Shock Protein 70(Hsp70) pada kardiomiosit berperan penting dalam proses termotoleran danaklimatisasi terhadap panas serta berguna sebagai mekanisme adaptasi secara sistemikdan seluler. Tujuan dari penelitian adalah untuk menganalisis ekspresi TRPV1, HSF1,dan Hsp70 pada jantung sebagai respons protektif terhadap pajanan panas.Metode: Penelitian bersifat eksperimental in vivo menggunakan hewan coba tikusjenis Sprague Dawley (SD) berumur 12 minggu dengan berat badan 200-300 gram dilaboratorium hewan Balitbangkes Kemenkes RI, pada Oktober-Desember 2014.Sebanyak 28 ekor tikus jantan dengan n=4 pada tiap kelompoknya, dibagi dalamkelompok Kontrol (K) dan kelompok Perlakuan (P). Kelompok perlakuan terdiri dari6 subkelompok (kelompok hari ke-1,3,7,10,14 dan 21) mendapatkan pajanan panas didalam hyperthermic chamber bersuhu (45oC ± 0.3oC) dan kelembaban relatif (70% ±3%) selama 60 menit. Dilakukan pengukuran berat badan, suhu kulit, suhu rektal danfrekuensi denyut jantung. Perubahan morfologi kardiomiosit diamati menggunakanpewarnaan Hematoksilin-Eosin. Ekspresi TRPV1, HSF1 dan Hsp70 diperiksamenggunakan metode imunohistokimia dan ELISA.Hasil: Penelitian menunjukan pajanan panas 45oC; kelembaban relative 70% selama60 menit menyebabkan penurunan berat badan sejak hari ke-1 hingga hari ke-21perlakuan. Terjadi peningkatan suhu kulit, suhu rektal dan heart rate yang puncaknyaterjadi pada hari ke-7, dan menurun mulai pada hari ke-10 sampai pada hari ke-21meskipun intensitas pajanan panas tetap sama. Hal tersebut menandakan mekanismeaklimatisasi dan proses termotoleransi telah terjadi pada hari ke-7 perlakuan. Terjadipenambahan ukuran lebar kardiomiosit dan peningkatan berat pada jantung seiringlamanya pajanan panas, Hasil ini menunjukkan terjadinya hipertrofi jantung namuntidak disertai adanya fibrosis. Secara molekuler melalui pemeriksaan Imunohistokimiadan ELISA pada kardiomiosit menunjukkan ekspresi TRPV1, HSF1 dan Hsp70 yangbersifat sebagai protein protektif dan kardioprotektor cenderung mengalamipeningkatan sejak hari ke-1 sampai pada hari ke-7 perlakuan dan cenderung menurunpada hari ke-10 sampai dengan hari ke-21. Perubahan kadar ekspresi TRPV1, HSF1dan Hsp70 sejalan dengan perubahan yang terjadi pada suhu kulit, suhu rektal danheart rate.Kesimpulan: Pajanan panas pada tubuh memberikan pengaruh pada jantung berupaterjadinya hipertrofi konsentris disertai adanya peningkatan ekspresi TRPV1, HSF1dan Hsp70 yang berperan penting sebagai protein protektif dan kardioprotektorBackground: Increased extreme body temperature causes protein denaturation,cessation of enzymatic reactions, loss of membrane activity and integrity, and triggerscellular damage. Increased body temperature also affects the occurrence of positiveinotropic and chronotropic effects on the heart. It is postulated that increase inexpression Transient Receptor Potential Vanilloid 1 (TRPV1), Heat Shock Factor 1(HSF1), Heat Shock Protein 70 (Hsp70) in cardiomyocytes is activated by extremetemperatures and has an important role in thermotolerance and heat acclimatizationprocesses -and as a mechanism of systemic and cellular adaptation. The aim of thestudy was to analyze the expression of TRPV1, HSF1, and Hsp70 on cardiac muscleas a protective response to heat exposure.Methods: This in vivo experimental research was conducted using Sprague-Dawley(SD) rats (age 12 weeks, 200-300 gram) in animal laboratory National Institute ofHealth Research and Development, Indonesian Ministry of Health, October-December2014. A total of 28 male rats with n = 4 in each group, divided into Control group (K)and Treatment group (P). The treatment group consisted of 6 sub-groups (i.e.1,3,7,10,14 and 21 days) received heat exposure in hyperthermic chamber at (45oC ±0.3oC) and (70% ± 3%) with relative humidity of 60 minutes. Body weight, skintemperature, rectal temperature and heart rate were measured. Changes incardiomyocyte morphology were observed using Hematoxylin-Eosin staining.Expressions of TRPV1, HSF1 and Hsp70 were examined using immunohistochemicaland ELISA methods.Results: The results of this study showed that heat exposure at 45oC;70% RH for 60minutes resulted in weight loss from day 1st to day 21st of the treatment. Peakselevation in skin temperature, rectal temperature and heart rate were reached at day7th, and decreased gradually from day 10th to day 21st even though the intensity ofheat exposure was unchanged. This indicated the mechanism of acclimatization andthermotolerance process had occurred on the 7th day of heat treatment. There wasincreased in the size of the cardiomyocyte width and heart weight along with theduration of heat exposure. These results indicated the occurrence of heart hypertrophybut not accompanied by fibrosis. Molecular aspects on cardiomyocytes throughImmunohistochemistry and ELISA showed TRPV1, HSF1 and Hsp70 expression asprotective proteins and cardioprotectors, which tended to increase from day 1st to 7thday of treatment and decrease gradually on day 10th to day 21st. Changes inexpression levels of TRPV1, HSF1 and Hsp70 coincided with changes in skintemperature, rectal temperature and heart rate.Conclusion: Heat exposure to the body induced the development of heart hypertrophyand coincided with the increased expression of TRPV1, HSF1 and Hsp70 which act asa protective protein and cardioprotector."