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"Latar Belakang: Proses inflamasi dengan respons maladaptif merupakan mekanisme terjadinya disfungsi multiorgan dan kematian pada sepsis. Heparin merupakan sediaan yang digunakan secara luas untuk terapi gangguan koagulasi, secara in-vitro heparin juga memiliki pengaruh sebagai antiinflamasi melalui penurunan aktivitas nuclear factor kappa B (NFkB) dan tumor necrosis factor alpha (TNF-. Penggunan heparin pada sepsis, khususnya sebagai antiinflamasi, masih merupakan kontroversi dan memerlukan penelitian lebih lanjut.Tujuan Penelitian: Tujuan primer penelitian ini adalah mengetahui pengaruh terapi heparin terhadap konsentrasi NFkB, inhibitor kappa B kinase beta (IKK dan TNF-pada pasien sepsis berat Tujuan sekunder adalah menilai pengaruh terapi heparin terhadap mortalitas dan perbaikan disfungsi organ.Metode: Uji klinis acak tersamar ganda membandingkan terapi heparin tidak terfraksinasi, dosis 10 unit/kg berat badan/24 jam, infus kontinu selama 72 jam, dengan plasebo. Kriteria inklusi adalah: subjek usia 18 tahun atau lebih dengan sepsis berat awitan maksimal 48 jam dan bersedia berpartisipasi dalam penelitian. Seleksi subjek dilakukan secara konsekutif dengan alokasi subjek secara acak. Pemantauan terhadap respons klinis dilakukan dengan menilai mortalitas 14 hari serta perbaikan skor APACHE II. Analisis intention to treat (ITT) dilakukan terhadap subjek yang telah mendapat terapi heparin minimal selama 24 jam, pada subjek yang melengkapi seluruh protokol penelitian dilakukan analisis per-protocol (PP).Hasil: Sebanyak 115 subjek telah diinklusi dan dirandomisasi, 58 subjek mendapat heparin dan 57 subjek plasebo. Rentang usia 21 hingga 82 tahun dengan rerata 51 tahun. Analisis ITT dan PP dilakukan terhadap masing-masing 46 dan 22 subjek kelompok heparin dan 50 dan 28 subjek kelompok kontrol. Tidak didapatkan perbedaan yang bermakna konsentrasi NFkBterfosforilasi dan IKK terfosforilasi kelompok heparin dibandingkan kontrol. Didapatkan penurunan konsentrasi TNF-pada kelompok heparin dibandingkan kontrol walaupun secara statistik belum bermakna. Didapatkan penurunan mortalitas pada analisis PP (RR 0,212 [IK 95% 0,053 - 0,815], p = 0,008), dengan ARR 33,8 % dan NNT 3. Terdapat kecenderungan perbaikan disfungsi organ pada kelompok heparin, walaupan secara statistik belum menunjukkan kemaknaan.Simpulan: Terapi heparin memberikan pengaruh terhadap proses inflamasi pada pasien sepsis berat, terlihat dari penurunan konsentrasi TNF-, walaupun pada pengujian statistik tidak didapatkan perbedaan bermakna. Tidak didapatkan pengaruh terapi heparin terhadap penurunan konsentrasi IKKdanNFkB. Heparin memberikan manfaat terhadap penurunan mortalitas, terutama pada subjek yang mendapat heparin selama 72 jam. Pada pengamatan selama 72 jam, heparin belum telihat memberikan pengaruh terhadap perbaikan disfungsi organ.

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Background. Multiple organ dysfunction and mortality in sepsis are developed as the consequence of the inflammation with maladaptive host response. Heparin has been widely used as an anticoagulant treatment. Based on in vitro evaluation, heparin has an antiinflammatory property by reducing the activity of nuclear factor kappa B (NFkB) and tumor necrosis factor alpha (TNF-. However, the effect of heparin as the anti-inflammatory agent is still controversial. To ascertain the anti-inflammatory effects of heparin in sepsis, further study is needed.Objectives. The primary aim of this study was to determine the effect of heparin in severe sepsis based on the concentration of NFkB, Inhibitor kappa B kinase beta (IKK), and TNF-. Secondary objective was to determine the effect of heparin on mortality rate and improvement of organ dysfunction.Methods. A randomized, double-blind, clinical trial was conducted to compare the unfractionated heparin (UFH) treatment, in dosage of 10 units/ kg BW for 24 hours, continuous infusion for 72 hours, in comparison to placebo. The inclusion criteria were subject 18 years old or above, with severe sepsis in maximum 48 hours after onset and agreed to participate in this study. Furthermore, subjects were consecutively selected and randomly allocated. Clinical responses were monitored by evaluating the 14-days mortality rate and improvement of APACHE II score. Subjects who had received heparin treatment for at least 24 hours were analyzed by intention to treat (ITT), while others who had completed all the protocol, were analyzed by per protocol (PP).Results. There were 115 subjects included and randomly assigned to heparin (n = 58) and placebo (n = 57) groups. The range of age was 21 to 82 years, mean of age was 51 years. ITT and PP analysis were conducted to 46 and 22 subjects in heparin group; 50 and 28 subjects in control group respectively. There were no significant differences in concentration of Phosphorylated-NFkB and Phosphorylated-IKK in both groups. The concentration of TNF-decreased in heparin groups, although statistically was not significant. The 14 days mortality rate reduced in PP analysis (RR 0.212 [95% CI 0.053 – 0.815], p = 0.008), with ARR 33.8 % and NNT 3. Moreover, there are trend of organ dysfunction improvement in heparin group, yet not statistically significant.Conclusion. Heparin treatment has an impact on inflammatory process in severe septic patients; as shown in the reduction of the TNF- concentration, although was not significant statistically. There was no clear impact of heparin treatment on IKK and NFkB concentration. Moreover, heparin shows benefit in reducing the mortality, especially in subjects who has received heparin for 72 hours. No benefit on improvement of organ dysfunction was shown in 72-hour monitoring of heparin treatment."

"Sepsis merupakan respons inflamasi sistemik pejamu terhadap infeksi. Respons inflamasi dimediasi oleh sitokin yang akan dilepaskan ke sirkulasi. Pelepasan sitokin akan menyebabkan terjadinya aktivasi koagulasi melalui peningkatan ekspresi tissue factor (TF) dan penurunan inhibitor alamiah, serta penurunan fibrinolisis. Tissue factor (TF) merupakan inisiator penting pada proses koagulasi, yang diekspresikan di sirkulasi darah oleh monosit aktif. Aktivasi TF selain menyebabkan aktivasi koagulasi juga dapat memodulasi inflamasi pada pasien sepsis berat. Heparin selain sebagai antikoagulan, berperan sebagai antiinflamasi. Berdasarkan fungsi heparin sebagai antiinflamasi dan peranan TF dalam inflamasi, ingin diteliti apakah pemberian heparin dapat menurunkan aktivitas TF yang diekspresikan monosit pada keadaan inflamasi.Penelitian ini bertujuan untuk mengetahui perbedaan aktivitas TF monosit pada orang sehat dan pasien sepsis berat dan perbedaan aktivitas TF monosit pada pasien sepsis berat dengan pemberian heparin in vitro dibandingkan dengan kelompok tanpa heparin.Penelitian ini merupakan penelitian eksperimental dengan menggunakan sampel 10 orang pasien sepsis berat dan 5 orang sehat. Darah sitrat dipisahkan sel mononuklear darah tepi (peripheral blood mononuclear cell/ PBMC) dengan teknik Ficoll-Paque, dan isolat monosit diperoleh dari PBMC menggunakan Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolat monosit dipisahkan menjadi tiga kelompok, yaitu kelompok pertama langsung diperiksa aktivitas TF, kelompok kedua diinkubasi 6 jam dengan heparin 0.1 IU, dan kelompok ketiga diinkubasi 6 jam tanpa heparin. Isolat monosit kemudian dibuat lisat sel dan supernatan diukur aktivitas TF (Actichrome TF).Hasil penelitian menunjukkan terdapat perbedaan bermakna aktivitas TF monosit pada pasien sepsis berat dibandingkan orang sehat (p=0.002). Aktivitas TF monosit pada pasien sepsis berat yang mendapat heparin 0.1 IU berbeda bermakna setelah jam ke-6 dibandingkan tanpa heparin (p=0.003).

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Sepsis is a host systemic inflammatory response to infection. Inflammatory response is mediated by cytokines released into circulation. Cytokine leads to coagulation activation by elevating tissue factor (TF) expression, reducing natural inhibitors, and impeding fibrinolysis. TF is an important initiator in coagulation process, expressed in blood circulation by active monocytes. TF activates coagulation and modulates inflammation in severe septic patients. Heparin acts as anticoagulant and antiinflammatory agent. Based on heparin as antiinflammatory agent and role of TF in inflammation, heparin can decrease TF activity expressed on monocyte in inflammation.

This study aims to find the difference between monocyte TF activities in healthy people and severe septic patients, and also between monocyte TF activities in severe septic patients receiving heparin in vitro and without heparin group.

This study is a laboratory experiment using 10 samples from severe septic patients and 5 healthy samples. Peripheral blood mononuclear cells (PBMCs) are separated from citrate blood using Ficoll-Paque technique. Monocyte isolation is performed using Monoclonal Antibody Cell Sorter (MACS) microbeads. Monocyte isolate is divided into three groups, first group is measured for TF activity directly, second group is incubated 6 hours with heparin 0.1 IU, and third group is incubated without heparin. Cell lysate is processed from monocyte isolate and supernatant is measured for activity TF (Actichrome TF).

The result shows a significant difference between monocyte TF activity in severe septic patients compared to healthy people (p = 0.002). Monocyte TF activity in severe septic patients with heparin 0.1 IU/mL in the 6th hour is also significantly different than without heparin group (p = 0.003)."

"Kelahiran preterm masih merupakan masalah global. Penyebab kelahiran preterm bersifat multifaktor, di antaranya adalah proses inflamasi dan status nutrisi yang dipengaruhi oleh mikronutrien seperti seng, vitamin A dan D. Penelitian ini bertujuan mengetahui pengaruh seng, AtRA dan 25(OH)D pada regulasi respons inflamasi pada kelahiran preterm melalui pemeriksaan MyD88, TRIF, NFκB dan IL-1β. Desain kuasi eksperimental dilakukan selama periode Januari-Juni 2017 di RSUPN-CM dan RS Budi Kemuliaan, Jakarta. Subjek dibagi menjadi kelompok aterm (n=25), pretem kontrol (n=27), dan preterm perlakuan (n=26). Kelompok preterm perlakuan diberikan secara oral seng 50 mg/hari, beta-carotene 25.000 IU, dan vitamin D₃ 50.000 IU/minggu. Seluruh subjek dilakukan wawancara, pengukuran konsentrasi seng, AtRA dan 25(OH)D serum dan plasenta, serta kadar MyD88, TRIF, NFκB dan IL-1β plasenta. Pada kelompok aterm konsentrasi AtRA serum dan plasenta lebih tinggi dibandingkan kelompok lain. Pada kelompok preterm perlakuan, tidak didapatkan adanya perbedaan bermakna konsentrasi seng, AtRA dan 25(OH)D serum sebelum dan sesudah perlakuan. Ekspresi NFκB dan TRIF lebih rendah pada kelompok aterm dan preterm kontrol, dibandingkan kelompok preterm perlakuan. Konsentrasi IL-1β ditemukan paling tinggi pada kelompok aterm. Konsentrasi seng, AtRA dan 25(OH)D plasenta memiliki korelasi positif sedang dengan IL-1β.Simpulan: Konsentrasi seng, AtRA dan 25(OH)D plasenta yang rendah berhubungan dengan lebih tingginya ekspresi MyD88, TRIF, NFκB dan IL-1β pada kelahiran preterm. Pemberian seng, beta-carotene dan vitamin D₃ berhubungan dengan IL-1β yang lebih rendah.

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Preterm birth is still a global burden. Inflammation process and nutritional status are among its multifactorial etiology which is affected by micronutrient such as vitamin A, D and zinc. Quasi-experimental design was conducted to know the role of zinc, beta-carotene and vitamin D₃ towards inflammatory regulator of preterm birth during January-June 2017 in RSUPN-CM and Budi Kemuliaan Hospital, Jakarta. Subjects were classified into term (n=25), control preterm (n=27), and experimental preterm group (n=26). Subjects in experimental preterm group were given orally zinc 50 mg/day, beta-carotene 25,000 IU and vitamin D₃ 50,000 IU/week. Nutrient intake interview, measurement of zinc, AtRA and 25(OH)D level in serum and placenta was performed in all subjects, also placental concentration of MyD88, TRIF, NFκB dan IL-1β. The term group had higher AtRA concentration in serum and placenta. No significant difference of serum zinc, AtRA and 25(OH)D concentration was found in treated group before and after intervention. The term and control preterm groups had lower expression of NFκB and TRIF compared to the experimental group. The concentration of IL-1β was highest among term group. Placental concentration of zinc, AtRA and 25(OH) had moderate positive correlation with IL-1β.Conclusion: Lower placental concentrations of zinc, AtRA and 25(OH)D relate to higher expression of MyD88, TRIF and NFκB. The supplementation of zinc, beta-carotene and vitamin D₃ relate to lower expression of IL-1β."

"Sepsis dikenal secara luas sebagai sindrom klinis yang merupakan hasil dari respon sistemik yang hebat terhadap infeksi dan melibatkan gangguan pada berbagai organ penderitanya Sepsis merupakan penyebab kematian tersering pada pasien yang dirawat di unit perawatan intensif Proses inflamasi dengan respon maladaptif terhadap proses tersebut merupakan mekanisme terjadinya disfungsi organ multipel dan kematian pada sepsis. Heparin juga diketahui dapat memodulasi proses inflamasi, namun belum banyak penelitian yang menjelaskan dosis heparin sebagai antiinflamasi. Penelitian ini ingin mengkaji lebih jauh pengaruh dosis heparin terhadap aktivasi faktor transkripsi Nuclear Factor Kappa Beta (NFkB) melalui pengukuran terhadap kadar NFkB sub unit p65 dan produksi sitokin proinflamasi Tumor Necrosis Factor Alpha (TNF-?) untuk memberikan dasar ilmiah mengenai penggunaan dosis heparin sebagai antiinflamasi pada pasien dengan sepsis berat. Penelitian ini merupakan eksperimental laboratorik dengan menggunakan sampel dari 5 orang sukarelawan sehat dan 10 orang pasien sepsis berat. Sel mononuklear darah tepi (peripheral blood mononuclear cells/PBMC) dari darah vena diperoleh dengan teknik Ficoll-hypaque. Fraksi non-monosit dari PBMC menggunakan Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolasi monosit diresuspensi pada medium Roswell Park Memorial Institute (RPMI) yang disuplementasi dengan 10% fetal bovine serum (FBS). Sel kemudian dipaparkan dengan heparin 0.1 IU/ml (1?g/ml), 1 IU/ml (10 ?g/ml), dan 10 IU/ml (100 ?g/ml), sedangkan kontrol tidak diberi perlakuan. Setelah diinkubasi pada 37°C dan 5% CO2 selama 6 jam dan 24 jam, pelet sel diukur NFkB sedangkan supernatan diukur TNF-? dengan metode ELISA. Hasil penelitian menunjukkan kadar NFkB sub unit 65 dan produksi TNF-? pada kultur monosit pasien sepsis berat yang mendapat heparin ditemukan secara signifikan lebih rendah daripada kontrol. Heparin dosis rendah 0.1 IU/ml (1?g/ml), secara signifikan menurunkan aktivasi NF?B dan produksi TNF-? lebih besar. Penelitian ini menunjukkan bahwa heparin menghambat aktivasi NFkB sehingga menurunkan produksi sitokin TNF-?. Heparin dengan dosis rendah menunjukkan pengaruh sebagai antiinflamasi lebih besar. Hasil yang diperoleh diharapkan memberikan pemahaman baru mengenai pengaruh dosis heparin sebagai anti-inflamasi pada pasien sepsis berat.

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Sepsis is a severe systemic response to infection, based on the Systemic Inflammatory Response Syndrome (SIRS) plus infection proven or clinically suspected infection, with evidence of organ failure due to hypo-perfusion. Anti-inflammatory therapy is one of the important therapeutic modality and applied potential as sepsis therapy. Inflammatory process with a maladaptive response to this process is the mechanism for the occurrence of multiple organ dysfunction and mortality in sepsis. Bacterial lipopolysaccharide binds to CD14 receptors and toll-like receptor (TLR) on the surface of monocytes and activates intracellular signal transduction involving beta-Kinase Inhibitor Kappa/IKKB that activates Nuclear Factor Kappa-Beta (NFkB) enter the nucleus and initiate transcription of RNA that encodes the production of cytokines TNF-?. Heparin has long been known as an anticoagulant, but also known to modulate the inflammatory process. This study want to examine further role of heparin as an anti-inflammatory to provide a scientific basis for the use of heparin in sepsis. Peripheral blood mononuclear cells (peripheral blood mononuclear cells/PBMC) of patients with severe sepsis obtained by Ficoll-Hypaque technique. Non-monocyte fraction of PBMC were removed using a Monoclonal Antibody Cell Sorter (MACS) microbeads. Isolation of monocytes resuspended in Roswell Park Memorial Institute medium (RPMI) supplemented with 10% fetal bovine serum (FBS). Cells then exposed to 0.1 IU heparin (1 ?g/ml), 1 IU (10 ug/ml), and 10 IU (100 ?g/ml), whereas controls did not. After incubation at 37°C and 5% CO2 for 6 hours and 24 hours, each sample is aspirated into micro centrifuge tube and rotated at a speed of 400 g for 5 min. Cell pellet was measured for NFkB and supernatant measured for TNF-?. Both were measured by ELISA. The results showed NFkB activation and TNF-? production in cultured monocytes severe sepsis patients who received heparin found to be significantly lower than controls. Low-dose heparin 0.1 IU (1?g/ml), significantly decreased the activation of NFkB and TNF-? production a lot more. This study demonstrates how heparin interfere an inflammatory response in severe sepsis patients monocytes through interrupt NFkB activation that decrease the production of cytokines TNF-?. The results are expected to provide new insights into the role of heparin as an anti-inflammatory in patients with severe sepsis."

"Pendahuluan: Heparin dapat digunakan sebagai terapi bagi pasien COVID-19. Namun, indikasi dan efeknya masih berbeda di berbagai penelitian. Oleh karena itu, penelitian ini bertujuan untuk menilai efektivitas pemberian heparin dalam menurunkan keparahan gejala klinis. Metode :Studi retrospektif dilakukan dari rekam medis pasien COVID-19 kondisi sedang-berat yang dirawat di Rumah Sakit Universitas Indonesia (RSUI). Parameter yang diperiksa adalah kondisi klinis pasien (tingkat mortalitas dan total lama perawatan), kadar D-dimer, dan trombosit pada dua kelompok, kelompok yang diberikan heparin dan yang tidak. Hasil:Penelitian ini menyertakan 110 subjek penelitian. Terdapat tingkat mortalitas yang lebih tinggi pada kelompok heparin dibandingkan kontrol (45,3% vs 5 10,9%; p<0,01). Hal ini dapat disebabkan perbedaan derajat sedang dan berat. Mayoritas kelompok heparin berkondisi berat (58,1% vs 28,2%) jika dibandingkan kontrol. Pada pengecekan laboratorium, heparin menurunkan kadar D-dimer (790 ke 500 vs 725 ke 4.475 µg/L) dan trombosit (366 ke 208x103 vs 217 ke 318x103/µL)secara signifikan (p<0,01). Kesimpulan: Kelompok heparin memiliki tingkat mortalitas yang tinggi akibat tingkat kondisi yang lebih berat, tetapi kadar D-dimer dan trombosit menurun dibandingkan kelompok kontrol.

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Introduction: Heparin can be used as therapy for COVID-19 patients. However, the indications and effects still differ in various studies. Therefore, this study aims to assess the effectiveness of heparin administration in reducing the severity of clinical symptoms. Methods: A retrospective study was conducted from medical records of moderate-severe COVID-19 patients treated at the University of Indonesia Hospital (RSUI). The parameters examined were the patient's clinical condition (mortality rate and total length of treatment), D-dimer levels, and platelets in two groups, those given heparin and those not. Results: This study included 110 research subjects. There was a higher mortality rate in the heparin group compared to controls (45.3% vs 5 10.9%; p<0.01). This is due to the difference in moderate and severe degrees. The majority of the heparin group had severe conditions (58.1% 28.2%) when compared to controls. In laboratory tests, heparin reduced the levels of D-dimer (790 to 500 vs 725 to 4,475 µg/L) and platelets (366 to 208x103 vs 217 to 318x103/µL) significantly (p<0.01). Conclusion: The heparin group had a high mortality rate due to more severe conditions, but D-dimer and platelet levels decreased compared to the control group"

"Batu ginjal merupakan salah satu penyakit urologi tersering di Indonesia dan dipengaruhi oleh berbagai faktor inflamasi, faktor klinis dan demografi, namun, 50% faktor predisposisi batu ginjal diketahui juga dipengaruhi oleh faktor genetik. Namun, sampai saat ini, belum ada studi yang menganalisis faktor risiko kejadian batu ginjal dari segi polimorfisme gen, sitokin inflamasi, klinis, dan demografi secara komprehensif, serta belum diketahui mekanisme keseluruhan faktor-faktor tersebut dalam menyebabkan batu ginjal. Oleh sebab itu, penelitian ini dibuat untuk menjelaskan mekanisme faktor risiko tersebut terhadap kejadian batu ginjal sebagai pencegahan terjadinya batu ginjal. Penelitian dilakukan di RSUPN Dr. Cipto Mangunkusumo dengan desain kasus kontrol sejak Maret 2021 hingga Maret 2024 dengan jumlah 308 subjek, yaitu 154 subjek kelompok kasus dan 154 subjek kelompok kontrol sehat. Pada setiap pasien dilakukan pencatatan dan evaluasi terhadap data demografi, pemeriksaan biokimia dan polimorfisme genetik dievaluasi dari sampel darah, ekspresi gen sitokin inflamasi dan urinalisis dari sampel urin pagi, serta pemerikaan urin 24 jam. Asupan cairan dinilai menggunakan kuesioner Liq-In7. Analisis bivariat dan multivariat dilakukan menggunakan SPSS versi 20 sedangkan analisis jalur dilakukan menggunakan JASP 0.19.1.0. Dari penelitian didapatkan usia lebih tua, peningkatan kadar kreatinin darah, peningkatan kadar kalsium urin, kondisi ISK, genotipe GT gen CaSR rs1801725, genotipe CT gen CLDN14 rs219780, genotipe AG dan GG gen VDR rs2228570, genotipe CT gen VDR rs1544410, dan genotipe CT gen ALPL rs1256328 berhubungan dengan peningkatan risiko kejadian batu ginjal. Peningkatan kadar sitrat urin dan genotipe AG gen CaSR rs1042636 menurunkan risiko batu ginjal. Selain itu, rerata asupan cairan lebih rendah, asam urat urin lebih rendah, asam urat serum lebih tinggi, dan proporsi Genotipe CT gen VDR rs731236 dan pekerja kantor lebih rendah didapatkan pada kelompok kasus secara bermakna, namun tidak termasuk dalam faktor risiko independen berdasarkan hasil multivariat. Upregulation ekspresi IL-8 juga didapatkan pada kelompok kasus. Pada analisis jalur, varian gen VDR rs2228570, CLDN14 rs219780, CaSR rs1801725, kreatinin serum, dan usia lebih dominan memiliki efek positif langsung terhadap batu ginjal. Di sisi lain, varian gen VDR rs1544410 memiliki efek positif tidak langsung yang lebih dominan terhadap batu ginjal melalui kalsium urin. Prediktor batu ginjal dengan sistem skoring menggunakan beberapa variabel telah dikembangkan dengan sensitivitas dan spesifisitas yang baik. Dengan mengidentifikasi faktor risiko terkait batu ginjal yang dapat dan tidak dapat dimodifikasi bisa menjadi target utama dalam pencegahan primer batu ginjal.

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Kidney stones are among the most common urological diseases in Indonesia, influenced by various inflammatory, clinical, and demographic factors, but 50% of the predisposition is also attributed to genetic factors. To date, no comprehensive studies have analyzed kidney stone risk factors by considering genetic polymorphisms, inflammatory cytokines, clinical, and demographics factors. Moreover, the comprehensive mechanisms by which these risk factors contribute to kidney stone formation remain unclear. Therefore, this study was conducted to elucidate how these risk factors contribute to kidney stone occurrence, aiming to prevent kidney stones. The study was conducted at Dr. Cipto Mangunkusumo Hospital using a case-control design from March 2021 to March 2024, involving 308 subjects, comprising 154 cases and 154 healthy controls. Demographic data were collected through subject interviews. Biochemical and genetic polymorphism analyses were performed using blood samples, while inflammatory cytokine gene expression and urinalysis were evaluated from morning urine samples. Twenty-four-hour urine samples were utilized to analyze the levels of dissolved molecules and urine pH. Fluid intake was assessed using the Liq-In7 questionnaire. Bivariate and multivariate analysis was conducted using SPSS version 20, whereas path analysis was performed using JASP 0.19.1.0. The study identified that older age, increased serum creatinine levels, increased urinary calcium levels, urinary tract infections, the GT genotype of the CaSR rs1801725 gene, the CT genotype of the CLDN14 rs219780, the AG and GG genotypes of the VDR rs2228570, the CT genotype of the VDR rs1544410, and the CT genotype of the ALPL rs1256328 were associated with an increased risk of kidney stone. In contrast, higher urinary citrate levels and the AG genotype of the CaSR rs1042636 gene were associated with a reduced risk of kidney stones. Furthermore, the case group showed significantly lower mean fluid intake, lower urinary uric acid levels, higher serum uric acid levels, and a lower proportion of the CT genotype of the VDR rs731236 gene and office workers. However, these variables were not identified as independent risk factors based on multivariate analysis. IL-8 expression was also observed to be upregulated in the case group. Path analysis revealed that the VDR rs2228570, CLDN14 rs219780, and CaSR rs1801725 genetic variants, serum creatinine, and age, predominantly exerted direct positive effects on kidney stone. Conversely, the VDR rs1544410 genetic variant had a more pronounced indirect positive effect through urinary calcium levels. Scoring systems for kidney stone prediction, incorporating these variables, had been developed with good sensitivity and specificity. Identifying modifiable and non-modifiable risk factors related to kidney stones could serve as critical targets for primary prevention strategies."

"Insidens insufisiensi adrenal pada pasien renjatan sepsis dilaporkan sekitar 40-65. Sitokin IL-1 dan IL-6 dapat menstimulasi sekresi kortisol sedangkan TNF-? serta MIF berperan dalam menghambat pembentukan kortisol. Penelitian ini bertujuan untuk mengetahui peran IL-1, IL-6, TNF-? dan MIF dalam terjadinya insufisiensi adrenal relatif pada renjatan sepsis.Penelitian eksperimental dilakukan di laboratorium FKH IPB berlangsung selama 6 bulan April-September 2015 . Model anak babi yang dipakai berumur 6-8 minggu dengan berat badan 5-10 kg. Pemilihan sampel dengan consecutive sampling dengan total n = 20. Anak babi diberikan infus endoktoksin dengan dosis 50 ug/kg BB. Sampel darah untuk analisis IL-1, IL-6, TNF-?, MIF, ACTH, kortisol, 17 OHP, DHEA, androstenedion diambil sebelum pemberian endotoksin dan tiap 15 menit hingga terjadi renjatan sepsis, kemudian dilakukan uji synacthen. Pemeriksaan imunohistokimia dilakukan pada kelenjar adrenal, hipofisis, dan hipotalamus.Dari 19 anak babi yang dianalisis mengalami renjatan sepsis dalam waktu 60 menit. Karakteristik sampel tidak berbeda bermakna antara kedua kelompok. Kadar IL-6 pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-45 0,65 0,5-4,32 pg/dL vs. 0,54 0,51-0,61 pg/dL , p = 0,008 . Kadar IL-1 antara kelompok IAR dibandingkan kelompok tanpa IAR tidak berbeda bermakna. Kadar TNF-? pada kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada menit ke-15 1862,5 327,9-4511,14 pg/dL vs. 155,38 24,67-394,10 pg/dL , p = 0,002 dan menit ke-30 4295,76 246,9-5913,37 pg/dL vs. 422,90 101,05-4129,42 pg/dL , p = 0,007 . Kadar MIF kelompok IAR dibandingkan dengan kelompok tanpa IAR berbeda bermakna pada saat renjatan sepsis 25,28 18,45-30,64 ng/dL vs. 11,30 7,1-15,14 ng/dL p = 0,003 . Pemeriksaan imunohistokimia hanya pada hipotalamus yang menunjukkan pewarnaan terhadap IL-1, IL-6, TNF-? dan MIF pada kelompok dengan IAR. Pada renjatan sepsis dan insufisiensi adrenal relatif kadar TNF-? meningkat pada menit-menit awal, kemudian kadar IL-6 meningkat kemudian serta terakhir kadar MIF meningkat pada saat renjatan sepsis. Kadar IL-1 tidak terdapat perbedaan antara kedua kelompok. Kata kunci: IL-1, IL-6, insufisiensi adrenal relatif, MIF, renjatan sepsis, TNF-?

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Incidence of adrenal insufficiency in septic shock ranged between 40 ndash 65 . The mechanism of relative adrenal insufficiency in septic shock is caused by inflammatory mediators. This study aimed to identify the role of IL 6, IL 1 in stimulating ACTH and cortisol release, and the role of TNF and MIF in inhibiting the level of ACTH and cortisol in septic shock with relative adrenal insufficiency RAI in order to develop guidelines for relative adrenal insufficiency marker.Experimental study was conducted in Veterinary Faculty, Bogor Agricultural Institute for 6 months Apri ndash September 2015 . Piglet models Sus scrofa aged 6 ndash 8 weeks weighing 5 ndash 10 kg. Consecutive sampling was used with total 20 piglets. Piglet models were given 50 ug kg endotoxin infusion Escherichia coli O111 B4 Sigma chemical, St. Louis, MO, USA . Blood sample for analysis of IL 1, IL 6, TNF , MIF, ACTH, cortisol, 17 OHP, DHEA, androstenedione was collected before endotoxin administration and every 15 minutes until septic shock occurred. Piglet models were monitored using PiCCO monitor. Stimulation test was then performed using synthetic corticotropin Synacthen and blood sample was collected again along with immunohistochemistry examination of the adrenal, pituitary and hypothalamus glands.From 19 study subjects analized, all subject had septic shock in 60 minutes. Study subject characteristics in each group were similar. The level of IL 6 at 45 minutes had a significant different compared to the group without RAI 0.65 0.5 ndash 4.32 pg dL vs. 0.54 0.51 ndash 0.61 pg dL , p 0.008 . The level of IL 1 during septic shock were not significantly different between both groups. The level of TNF in RAI group had significant different compared to the group without RAI at 15 minutes 1862.5 327.9 ndash 4511.14 pg dL vs. 155.38 24.67 ndash 394.10 pg dL , p 0.002 and at 30 minutes 4295.76 246.9 ndash 5913.37 pg dL vs. 422.90 101.05 ndash 4129.42 pg dL , p 0.007 The level of MIF in group with RAI during septic shock had a significant different compared to the group without RAI t 25.28 18.45 ndash 30.64 ng dL vs. 11.30 7.1 ndash 15.14 ng dL , p 0.003 . Immunohisto chemistry staining of IL 1, IL 6, TNF , and MIF was observed only in the hypothalamus glands of the RAI group. In septic shock and relative adrenal insufficiency, TNF increased in earlier minutes, then IL 6 increased and later MIF increased in septic shock condition. IL 1 level had no difference increment for both group.Keywords IL 1, IL 6, MIF, relative adrenal insufficiency, septic shock, TNF"

"ABSTRAKBerbagai studi terkini menunjukkan hubungan antara vitamin D dan sepsis. Vitamin D berperan sebagai stimulator produksi peptida antimikroba dan mencegah inflamasi yang berlebihan. Insufisiensi dan defisiensi vitamin D berhubungan dengan risiko terjadinya sepsis. Saat ini belum terdapat data mengenai hubungan status vitamin D dengan pasien infeksi tanpa sepsis, sepsis, dan sepsis berat. Tujuan penelitian ini dilakukan untuk mendapatkan hubungan antara proporsi status vitamin D dengan pasien infeksi tanpa sepsis, sepsis, dan sepsis berat.Desain penelitian potong lintang, terdiri dari 60 pasien infeksi terbagi menjadi kelompok infeksi tanpa sepsis, sepsis, dan sepsis berat masing-masing 20 pasien. Diagnosis sepsis berdasarkan modifikasi SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 2001. Status vitamin D ditetapkan menurut rekomendasi Holick. Pada ketiga kelompok tersebut dicatat data karakteristik subjek dan dilakukan pemeriksaan 25(OH)D.Status vitamin D pada subjek penelitian ini didapatkan sebanyak 5 (8,33%) orang insufisiensi dan 55 (91,67%) orang defisiensi vitamin D Proporsi insufisiensi pada kelompok infeksi tanpa sepsis adalah 5%, sepsis 10%, dan sepsis berat 10%. Proporsi defisiensi pada kelompok infeksi tanpa sepsis adalah 95%, sepsis 90%, dan sepsis berat 90%. Didapatkan perbedaan tidak bermakna proporsi insufisiensi dan defisiensi vitamin D pada kelompok infeksi tanpa sepsis, sepsis, dan sepsis berat.Kami menyimpulkan status vitamin D tidak berhubungan dengan beratnya sepsis. Proporsi insufisiensi dan defisiensi pada pasien infeksi tanpa sepsis, sepsis, dan sepsis berat masing-masing didapatkan 5% dan 95%; 10% dan 90%; 10% dan 90%.

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ABSTRACTRecent studies have shown that there is a relationship between vitamin D and sepsis. Vitamin D has a a role as a potent stimulator of antimicrobial peptides and prevent an over reaction of the inflammatory response. Insufficiency and deficiency of vitamin D have been associated with sepsis event. Nevertheless, there is no data about the relationship between vitamin D status with infection without sepsis, sepsis, and severe sepsis patient. The aim of this study was to obtain the relationship between proportions of vitamin D with infection without sepsis, sepsis, and severe sepsis patient.This was a cross-sectional study, 60 patients with infection were divided into groups of infection without sepsis, sepsis, and severe sepsis, each consisted of 20 patients. Diagnosis of sepsis was based on modified SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference 2001. Vitamin D status was defined according to Holick recommendations. Baseline characteristics of subjects were recorded and 25(OH)D concentrations were measured in subjects of each groups.According to status of Vitamin D, 5 (8,33%) subjects were insufficiency and 55 (91,67%) were deficiency. The proportions of vitamin D insufficiency at infection without sepsis group were 5%, sepsis 10%, and severe sepsis 10%. The proportions of vitamin D deficiency at infection without sepsis group were 95%, sepsis 90%, and severe sepsis 90%. The proportions of insufficiency and deficiency at infection without sepsis, sepsis, and severe sepsis patient were not significantly different (p > 0.05).It is concluded that vitamin D status were not related to infection severity. The proportions of vitamin D insufficiency and deficiency at infection without sepsis, sepsis, and severe sepsis, i.e. 5% and 95%; 10% and 90%; 10% and 90%, respectively."

"Latar belakang. Acute respiratory distress syndrome (ARDS) merupakan salah satu komplikasi fatal sepsis berat. Penggunaan cairan koloid sebagai cairan resusitasi dapat menurunkan kejadian ARDS lebih banyak karena memiliki berat molekul yang lebih tinggi dibandingkan cairan kristaloid. Peningkatan extravascular lung water (EVLW), kadar interleukin-8 (IL-8) dan vascular cell adhesion molecule-1 (VCAM-1) telah diteliti sebagai indikator penting yang berperan dalam patogenesis ARDS. Penelitian pada hewan coba diharapkan dapat memberikan penjelasan yang lebih baik mengenai patofisiologi ARDS yang kompleks dan sulit dimengerti. Tujuan. Mengungkap pengaruh cairan koloid atau kristaloid terhadap kejadian ARDS pada model hewan coba babi dengan sepsis berat, serta menganalisis pengaruh cairan kristaloid atau koloid terhadap peningkatan EVLW, IL-8, dan VCAM-1. Metode. Penelitian ini merupakan studi eksperimental acak tersamar ganda, dilakukan di Laboratorium Bedah Eksperimental, Fakultas Kedokteran Hewan, Institut Pertanian Bogor, dengan menggunakan babi (Sus scrofa) yang sehat berusia 2-3 bulan, berat badan 8-12 kg. Subjek dialokasikan secara acak menjadi dua kelompok, yaitu yang mendapatkan cairan resusitasi koloid atau kristaloid. Setelah pemberian endotoksin 50 μg/kg, tanda klinis ARDS, EVLW, IL-8, dan VCAM-1 dipantau saat sepsis, sepsis berat, 1 jam, dan 3 jam pasca-resusitasi cairan. Tiga jam pasca-resusitasi, dilakukan eutanasia pada babi, kemudian spesimen jaringan paru diambil untuk pemeriksaan histopatologi. Hasil Utama. ARDS kategori ringan lebih banyak terdapat pada kelompok koloid, sedangkan ARDS kategori sedang lebih banyak pada kelompok kristaloid. Rerata skor cedera paru pada kelompok koloid lebih rendah dibandingkan dengan kristaloid (0,4 vs. 0,7; p=0,001). Peningkatan EVLW lebih sedikit terjadi pada kelompok koloid dibandingkan dengan kristaloid pada 1 jam (1,0 vs. 3,0 mL/kgbb; p=0,030) dan 3 jam pasca-resusitasi (2,7 vs. 6,3 mL/kgbb; p=0,034). Pada kedua kelompok, kadar IL-8 meningkat secara bermakna setelah pemberian endotoksin (103,1 vs. 3854,5 pg/mL; p=0,012 pada kelompok koloid dan 125,0 vs. 4419,3 pg/mL; p=0,003 pada kelompok kristaloid). Nilai kadar IL-8 dan VCAM-1 tidak berbeda bermakna antara kedua kelompok. Simpulan. Penggunaan cairan koloid sebagai cairan resusitasi tidak menurunkan kemungkinan kejadian ARDS dibandingkan kristaloid. Cairan koloid berhubungan dengan peningkatan EVLW dan skor cedera paru yang lebih rendah dibandingkan dengan cairan kristaloid, tetapi tidak pada kadar IL-8 dan VCAM-1.

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Background. Acute respiratory distress syndrome (ARDS) is a fatal complication of severe sepsis. Due to its higher molecular weight, the use of colloids in fluid resuscitation may be associated with fewer cases of ARDS compared to crystalloids. Extravascular lung water (EVLW) elevation and levels of interleukin-8 (IL-8) and vascular cell adhesion molecule-1 (VCAM-1) have been studied as indicators playing a role in the pathogenesis of ARDS. The use of animal models may provide a better understanding of the complex and poorly understood pathophysiology of ARDS.

Objectives. To determine the effects of colloid or crystalloid fluid resuscitation on the incidence of ARDS, elevation of EVLW, and levels of IL-8 and VCAM-1, in swine models with severe sepsis.

Methods. This was a randomized trial conducted at the Laboratory of Experimental Surgery, School of Veterinary Medicine, Institut Pertanian Bogor, using healthy swine (Sus scrofa) models aged 2 to 3 months with a body weight of 8 to 12 kg. Subjects were randomly allocated to receive either colloid or crystalloid fluid resuscitation. After administration of 50 μg/kgbw of endotoxin, clinical signs of ARDS, EVLW, IL-8, and VCAM-1 were monitored during sepsis, severe sepsis, and one- and three hours after fluid resuscitation. Three hours after resuscitation, euthanasia was performed on the animal and the lung tissue specimen was taken for histopathological examination.

Results. Mild ARDS was more prevalent in the colloid group, while moderate ARDS was more frequent in the crystalloid group. Mean lung injury score was lower in colloid compared to crystalloid group (0.4 vs. 0.7; p=0.001). The increase in EVLW was lower in the colloid compared to the crystalloid group both at one hour (1.0 vs. 3.0 mL; p=0.030) and three hours post-resuscitation (2.7 vs. 6.3 mL/kg; p=0.034). In both groups, IL-8 levels were significantly higher after endotoxin administration (103.1 vs. 3854.5 pg/mL; p=0.012 in the colloid group and 125.0 vs. 4419.3 pg/mL; p=0.003 in the crystalloid group). There was no significant difference in IL-8 and VCAM-1 levels between the two groups.

Conclusion. The use of colloids in fluid resuscitation does not decrease the probability of ARDS events compared to crystalloids. Compared to crystalloids, colloids are associated with a lower increase in EVLWI and a lower mean lung injury score, but not with IL-8 or VCAM-1 levels."

"ABSTRAKLuka kaki diabetik (LKD) merupakan komplikasi kronik diabetes yang meningkatkan mortalitas danmorbiditas, serta menurunkan kualitas hidup. Komplikasi makro dan mikrovaskular/mikrosirkulasimempunyai pengaruh besar terhadap kejadian LKD dan proses penyembuhannya. Kondisimikrosirkulasi dapat dinilai melalui pemeriksaan transcutaneous perfusion oxygen (TcPO2). Kondisimikrosirkulasi dipengaruhi oleh HbA1c, glukosa darah sewaktu, neuropati, fibrinogen, PAI-1,hsCRP, indeks MMP-9, indeks TcPO2, dan indeks TcPCO2, yang akan memengaruhi terbentuknyajaringan granulasi.Penelitian ini bertujuan untuk mengetahui peran HbA1c, GDS, neuropati, fibrinogen, PAI-1, hsCRP,indeks MMP-9, terhadap indeks TcPO2, indeks TcPCO2, dan indeks granulasi, serta mengetahuiperan serta indeks TcPO2 dan indeks TcPCO2 terhadap indeks granulasi pada luka kaki diabetik.Sebanyak 68 subjek LKD tanpa penyakit arteri perifer di RS dr. Cipto Mangukusumo dan beberaparumah sakit jejaring, pada Desember 2015?Desember 2016, diberikan perawatan standar dandipantau setiap minggu sebanyak 4 kali. Pada pemantauan ke-1, ke-2, dan ke-3, dilakukandokumentasi LKD, pengambilan darah vena sebanyak 7,7 mL untuk pemeriksaan fibrinogen, PAI-1,hsCRP, MMP-9, dan TIMP-1, darah arteri sebanyak 2 mL untuk pemeriksaan analisis gas darah,serta pemeriksaan TcPO2 dan TcPCO2 dengan menggunakan TCM TOSCA/CombiM monitoringsystems buatan Radiometer. Pada pemantauan ke-4, hanya dilakukan dokumentasi LKD.Pengukuran luas luka dan jaringan granulasi dinilai berdasarkan hasil dokumentasi fotografi denganmenggunakan program ImageJ. Penilaian neuropati menggunakan pemeriksaan interval RR dankecepatan hantar saraf. Data laboratorium lainnya diperoleh dari data sekunder rekam medis.Kemudian dilakukan analisis data dengan menggunakan path analysis (analisis lajur) pada datarepetitif dan SPSS pada data nonrepetitif.Berdasarkan analisis didapatkan hubungan antara peningkatan glukosa darah sewaktu, fibrinogen,dan PAI-1 dengan penurunan indeks TcPO2. Didapatkan juga hubungan antara beratnya neuropatimotorik dan sensorik, peningkatan glukosa darah sewaktu, fibrinogen, PAI-1, dan hsCRP denganpenurunan indeks granulasi. Tetapi, indeks granulasi tidak dipengaruhi oleh indeks TcPO2. IndeksTcPCO2 tidak memiliki hubungan terhadap semua variabel tersebut, kecuali hsCRP dan indeksTcPCO2 tidak memengaruhi indeks granulasi.Indeks TcPO2 pada LKD dipengaruhi oleh kadar glukosa darah sewaktu, fibrinogen, dan PAI-1,tetapi tidak memengaruhi tumbuhnya jaringan granulasi. Tumbuhnya jaringan granulasi dipengaruhioleh glukosa darah sewaktu, neuropati motorik dan sensorik, peningkatan kadar fibrinogen, PAI-1,dan hsCRP. Selain itu, indeks TcPCO2 tidak memengaruhi indeks granulasi

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ABSTRACTDiabetic foot wounds/ulcer (DFU) is chronic complication of diabetes, which increasesmortality and morbidity, and lower quality of life. Macro and microvascular/microcirculationcomplications has a great influence on DFU and healing process. Microcirculation condition canbe seen from transcutaneous perfusion oxygen (TcPO2). The growth of granulation tissue in thehealing process is determined by microcirculation condition, among others influenced byHbA1c, random blood glucose, neuropathy, fibrinogen, PAI-1, hsCRP, MMP-9 index, TcPO2index, and TcPCO2 index.This study aimed to investigatethe role of HbA1c, random blood glucose, sensory, motoric, andautonomy neuropathy, fibrinogen, PAI-1, hsCRP, MMP-9 index, TcPO2 index, TcPCO2 index,and granulation index, as well as the relationship between TcPO2 index, TcPCO2 index andgranulation index in diabetic foot wounds.As much as 68 subjects DFU without peripheral arterial disease, in Cipto MangunkusumoReferral National Hospital, on December 2015?December 2016, were given standardmanagementof diabetic foot ulcer and monitored once a week for four times. In the 1st, 2nd, and3rd monitoring, DFU was documented, then 7.7 mL of venous blood was taken for fibrinogen,PAI-1, hsCRP, MMP-9, and TIMP-1 examination, also 2 mL arterial blood for blood gasanalysis, and then examination of TcPO2 and TcPCO2was performed using TCM4TOSCA/CombiM monitoring systems made by Radiometer. In the 4th monitoring, only DFUwas documented. Wound and granulation size was measured through photographicdocumentation using ImageJ program. Neuropathy was diagnosed based on RR interval andnerve conduction velocity study. Other laboratory data were obtained from medical records. Thedata were analysed by path analysis for repetititive data and SPSS for nonrepetitive data.From analysis, there is a significant correlation between the increasing random blood glucose(RBG), fibrinogen, and PAI-1 with the decreasing of TcPO2, also found a significantrelationship between the severity of sensory and motoric neuropathy, the increasing levels ofRBG, fibrinogen, PAI-1, and hsCRP with the decreasing of granulation index. But, TcPO2 indexdoes not influence granulation index. TcPCO2 index does not have significant correlation withall these variables, except hsCRP. Moreover, TcPCO2 index also does not influence granulationindex.TcPO2 index of DFU is affected by RBG, fibrinogen, PAI-1, but does not affect the growth ofgranulation tissue. Granulation tissue?s growing is influenced by the sensory and motoricneuropathy, increased levels of fibrinogen, PAI-1, and hsCRP. Furthermore, TcPCO2 index doesnot influence granulation?s growth."