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Theresia Santi
"Golongan usia anak merupakan golongan usia yang paling ringan terdampak infeksi COVID-19. Salah satu kemungkinan penyebab keadaan tersebut adalah perlindungan dari efek nonspesifik vaksinasi rutin yang diterima anak sebelumnya. Vaksinasi rutin yang diterima anak dapat memodulasi sistem imun anak terhadap infeksi lain di luar target imunisasi yang dituju melalui mekanisme imunitas heterolog. Bukti-bukti penelitian terdahulu menimbulkan hipotesis antigen vaksin DTP berpotensi menimbulkan imunitas heterolog dengan SARS-CoV-2. Hal ini berdasarkan kemiripan epitop antara antigen SARS-CoV-2 dengan antigen pada vaksin DTP. Belum diketahui bagaimana pengaruh vaksinasi DT booster terhadap respons imun (antibodi S-RBD SARS-CoV-2 dan IFN-ɤ-sel T spesifik SARS-CoV-2) pascavaksinasi COVID-19 inaktif pada anak usia 6–7 tahun. Penelitian ini bertujuan mengetahui pengaruh pemberian vaksinasi DT booster pada anak yang mendapat vaksinasi COVID-19 inaktif terhadap respons imun humoral dan selular anak.
Studi potong lintang dilakukan dengan didahului tahapan pengambilan data pada orang tua subjek penelitian di wilayah Senen, Jakarta Pusat. Pengambilan data menggunakan kuesioner yang disebarkan secara luring kepada orang tua melalui guru sekolah anaknya. Dari kuesioner didapatkan data status vaksinasi anak, yang dibedakan dalam 4 kelompok yaitu COVID+/DT+, COVID+/DT–, COVID–/DT+ dan COVID–/DT–, dan diukur antibodi S-RBD, IFN-ɤ-sel T spesifik SARS-CoV-2 dan IgG antidifteri.
Hasil penelitian menunjukkan 113 dari 154 subjek penelitian (73,4%) telah memiliki status relative immune terhadap difteri, dengan hasil IgG antidifteri > 0,1 IU/mL. Terdapat imunitas heterolog vaksinasi DT booster terhadap COVID-19 dengan adanya perbedaan bermakna kadar antibodi S-RBD SARS-CoV-2 antara anak yang sudah mendapat vaksin DT booster dibanding yang belum (1182 U/mL vs. 612,5 U/mL, p = 0,026), dan perbedaan bermakna IFN-ɤ-sel T spesifik SARS-CoV-2 pada anak COVID+/DT+ dibanding COVID+/DT– (560,87 mIU/mL vs. 318,03 mIU/mL, p = 0,03). Tidak didapatkan korelasi antara IgG antidifteri dan S-RBD SARS-CoV-2. Selain hasil penelitian data laboratorium, didapatkan pula data keinginan orang tua untuk vaksinasi COVID-19 bagi anaknya adalah sebesar 69,7%.
Disimpulkan vaksin DT booster dapat berperan menguatkan respons imun spesifik SARS-CoV-2 pada anak yang menerima vaksin COVID-19 inaktif.

Corona Virus Disease 2019 (COVID-19) in children tends to be mild. A possible cause is existing protection from the routine vaccination previously received by children. Routine vaccinations can modulate the child's immune system against other pathogen, presumably through a mechanism of heterologous immunity. Previous research had suggested that the Diphtheria-Tetanus-Pertussis (DTP) vaccine antigen has potential to incite heterologous immunity towards SARS-CoV-2, due to similarities between SARS-CoV-2 epitopes and various epitopes found within the DTP vaccine. It was not known whether the Diphtheria-Tetanus (DT) vaccination could modulate the SARS-CoV-2-specific immune response among children aged 6–7 years who received inactivated COVID-19 vaccine.
This study thus aimed to assess the impact of DT booster immunization in SARS-CoV-2-specific humoral and cellular immune responses among children who received two doses of CoronaVac.
A cross-sectional study was performed on children aged 6–7 years old in the Senen area, Central Jakarta. This study was started with data collection from parents of eligible subjects using questionnaire that was distributed to parents via their children’ school teachers. Based on the collected demographic data and the child's vaccination status, eligible subjects were further screened. The participating subjects were subsequently classified into 4 groups, i.e., COVID+/DT+, COVID+/DT-, COVID-/DT+ and COVID-/DT-. Blood collections were performed to determine anti-diphtheria toxoid antibodies, anti-S-RBD antibodies and SARS-CoV-2-specific T cell-produced IFN-ɤ.
The results showed that 113 of 154 subjects (73.4%) had relative immune-status against diphtheria as the result of the anti–diphtheria toxoid antibodies was > 0.1 IU/mL. There was a heterologous immunity of DT booster and COVID-19 vaccine, as there was significant difference in anti-S-RBD antibody titers between the group with DT booster compared to non-DT booster (1182 U/mL vs. 612.5 U/mL, p = 0.026), and a significant difference in IFN-ɤ concentration between the group of COVID+/DT+ and COVID+/DT- (560.87 mIU/mL vs. 318.03 mIU/mL, p = 0.03). No correlation was found between anti-diphtheria and anti-S-RBD antibodies. In addition, our data indicated that parental intention to vaccinate their children against COVID-19 in the Senen area was 69.7%.
In conclusion, our results suggested that DT booster vaccine might able to enhance SARS-CoV-2-specific immune responses among children who received inactivated COVID-19 vaccine.
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Jakarta: Fakultas Kedokteran Universitas Indonesia, 2024
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UI - Disertasi Membership  Universitas Indonesia Library
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Ari Prayitno
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Pneumonia karena Streptococcus pneumoniae merupakan penyebab utama kematian balita yang sebenarnya dapat dicegah dengan vaksinasi. Penelitian ini bertujuan menilai efektivitas Pneumococcal Conjugate Vaccine-13 (PCV13) dengan imunisasi dasar 2 dosis dan 1 dosis penguat (jadwal 2 + 1).

Penelitian kohort prospektif dilakukan di tiga Kabupaten Nusa Tenggara Barat pada bulan November 2017–Juni 2019. Subjek adalah bayi usia dua bulan, dibagi menjadi kelompok PCV13 dan kontrol. Vaksinasi PCV13 dilakukan oleh Dinas Kesehatan Provinsi NTB pada bulan Oktober 2017. Subjek dilakukan usap nasofaring 4 kali saat berusia 2, 4, 12, dan 18 bulan, kemudian spesimen dikultur, diidentifikasi serotipe, dan diuji kepekaannya terhadap antibiotik.

Proporsi S. pneumoniae pada usia 2 bulan adalah 22,9% pada kelompok vaksin dan 19,1% pada kontrol. Evaluasi pada usia 12 bulan menunjukkan kolonisasi S. pneumoniae lebih tinggi dibandingkan usia 2 bulan pada kedua kelompok (chi square, p < 0,01). Kolonisasi S. pneumoniae serotipe vaksin PCV13 (serotipe VT) pada kelompok vaksin menurun pada usia 18 bulan diikuti kenaikan serotipe yang tidak terdapat di vaksin PCV13 (serotipe NVT). Pada kontrol serotipe VT meningkat dengan bertambahnya usia (chi square, p < 0,05). PCV13 menurunkan kolonisasi S. pneumoniae serotipe 6A/6B (serotipe dominan). Pola kepekaan terhadap antibiotik tidak berubah dengan bertambahnya usia pada kedua kelompok. Disimpulkan pemberian PCV13 dengan jadwal 2 + 1 efektif menurunkan kolonisasi S. pneumoniae serotipe VT di nasofaring.

 

Kata kunci:    kepekaan terhadap antibiotik, kolonisasi nasofaring, perubahan serotipe, pneumonia, proporsi


Pneumonia caused by Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths in children under five years old. The study aims to assess the effectiveness of the Pneumococcal Conjugate Vaccine-13 (PCV13) administration with 2 primary doses and 1 booster (2 + 1 schedule).

This prospective cohort study was conducted in three districts of West Nusa Tenggara from November 2017–June 2019. The subjects were 2-month-old babies, divided into the group that was given PCV13 and the control group. PCV13 administered by West Nusa Tenggara Health Office in October 2017. Four nasopharyngeal swabs were collected at the age of 2, 4, 12, and 18 months old. S. pneumoniae was identified by culture and optochin test, then serotyping and antibiotic susceptibility test were performed by multiplex PCR and disk diffusion tools respectively.

The proportion of S. pneumoniae in 2 months old was 22.9% in the vaccine group and 19.1% in the control group. Evaluation in 12 months old showed higher colonization than in 2 months old (chi-square, p < 0.01). Colonization of vaccine-type serotypes in the vaccine group decreased at the age of 18 months followed by an increase in non-vaccine serotype. In the control group, vaccine-type increased with increased age (chi-square, p < 0.05). The PCV13 lowered the 6A/6B serotype (dominant serotype). Antibiotic susceptibility patterns did not change with increased age in both groups. In conclusion, the administration of PCV13 with a 2 + 1 schedule is effective to reduce the colonization of S. pneumoniae vaccine-type serotypes in the nasopharynx.

 

 

Keywords: antibiotic susceptibility, nasopharyngeal colonization, pneumonia, prevalence, serotype changes

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Depok: Fakultas Kedokteran Universitas Indonesia, 2020
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UI - Disertasi Membership  Universitas Indonesia Library
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Bobby Setiadi Dharmawan
"Pencegahan parut ginjal di kemudian hari pada tata laksana PNA belum memuaskan. Mekanisme vitamin E dalam menekan inflamasi dan sebagai antioksidan pada tata laksana anak dengan febrile UTI belum diteliti. Penelitian ini menelaah efek inhibisi vitamin E terhadap IL-6, IL-8, dan MDA urin. Efek perancu seperti usia, ASI, riwayat ibuprofen, dan infeksi E. coli, juga diteliti. Uji klinis acak tersamar ganda (n = 40) dilakukan di RS Fatmawati pada anak berusia 6?60 bulan dengan febrile UTI. Kelompok kasus diberikan 40 UI DL-α- tocopherol dan kelompok kontrol diberikan saccharum lactis selama 10 hari. Kedua kelompok mendapat terapi antibiotik yang sama. Pemantauan demam, leukosit darah, IL-6, IL-8, dan MDA urin dilakukan pada H0, H3 dan H10. Analisis IL-6 dan IL-8 dan MDA urin dilakukan di Laboratorium Biokimia FKUI. Kadar IL-6 urin lebih rendah pada kelompok vitamin E. Vitamin E menurunkan IL-8 urin namun tidak berbeda bermakna dibanding plasebo. Vitamin E tidak terbukti menurunkan demam lebih baik dibanding plasebo. Leukosit darah pada kelompok vitamin E lebih menurun dibanding kelompok plasebo, namun keduanya dalam batas normal. Perubahan MDA urin kedua kelompok tidak berbeda. Pemberian ASI menurunkan IL-6 dan IL-8 urin secara bermakna. Riwayat ibuprofen meningkatkan IL-6 dan IL-8 urin secara bermakna. Infeksi E. coli lebih meningkatkan MDA urin dibanding uropatogen lain. Manfaat penambahan vitamin E pada tata laksana febrile UTI masih perlu diteliti lebih lanjut.

Prevention of subsequent renal scarring in APN treatment has not been encouraging. The mechanism of vitamin E in suppressing inflammation and as an anti-oxidant in pediatric febrile UTI patients has not been studied. This study aimed to examine the inhibitory effects of vitamin E on urinary IL-6, IL-8, and MDA. Confounding effects of age, breastfeeding, previous treatment with ibuprofen, and E. coli infection were studied. A randomized double blind placebo controlled clinical trial (n = 40) was conducted in Fatmawati Hospital on 6 to 60 months old subjects with febrile UTI. The intervention group received 40 IU DL- α-tocopherol while the control received saccharum lactis as placebo for 10 days. Both groups were treated with antibiotics equally. Fever monitoring as well as blood leukocyte, urinalysis, and urinary IL-6, IL-8, and MDA were performed on day 0, day 3 and day 10. Analyses of urinary IL-6, IL-8 and MDA levels were conducted at Biochemistry Laboratory of Faculty of Medicine University of Indonesia. Urinary IL-6 levels were lower in the vitamin E group. Vitamin E suppressed urinary IL-8 but this result was not statistically significant compared to that of the placebo group. Vitamin E was not proven to reduce fever better than placebo. Leukocyte was lower in the vitamin E group compared to the placebo group, but both counts were within normal limit. Changes of urinary MDA levels between the two groups was statistically insignificant. Breastfeeding significantly lowered urinary IL-6 and IL-8 levels. Ibuprofen withdrawal significantly increased urinary IL-6 and IL-8 levels. E. coli infection increased urinary MDA more than any other uropathogens. The supplementation of vitamin E in the treatment of febrile UTI in children needs to be further investigated."
Jakarta: Fakultas Kedokteran Universitas Indonesia, 2016
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UI - Disertasi Membership  Universitas Indonesia Library
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Bina Akura
"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-?

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"
Depok: Universitas Indonesia, 2017
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UI - Disertasi Membership  Universitas Indonesia Library
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Eka Nurfitri
"ABSTRAK
Inflamasi sistemik pada renjatan sepsis dapat menyebabkan insufisiensi adrenal. Kadar asam lemak bebas ALB yang tinggi diketahui menyebabkan inflamasi steril dan menghambat adrenocorticothropic hormone dan sekresi kortisol. Pemberian hidrokortison pada renjatan sepsis diharapkan memperbaiki hemodinamik, menurunkan ketergantungan terhadap obat vasoaktif dan memperbaiki disfungsi organ.Penelitian bersifat studi eksperimental yang bertujuan menilai pengaruh ALB dan pemberian hidrokortison terhadap hemodinamik, kadar laktat, cedera paru dan kadar kortisol darah pada renjatan sepsis model anak babi. Penelitian dilaksanakan di Divisi Bedah dan Radiologi Departemen Klinik Reproduksi dan Patologi Fakultas Kedokteran Hewan Institut Pertanian Bogor FKH IPB pada April -September 2015 dan telah disetujui oleh Komisi Etik Hewan FKH IPB.Delapan model anak babi Sus scrofa berusia 6-8 minggu dengan berat 5-10 kg dibagi dalam 2 kelompok, yaitu kelompok lipid dan kelompok kontrol. Kelompok lipid diberi lipid 20 sebanyak 3 gram/kgbb intravena dan kelompok kontrol tanpa pemberian lipid sebelum induksi sepsis. Pengukuran parameter hemodinamik dengan Pulse Contour Cardiac Output PiCCO . Pengukuran kadar laktat dengan i-Stat. Cedera paru ditentukan dengan pengukuran extravascular lung water index EVLWI dan rontgen toraks. Tes synacthen dilakukan untuk mengetahui adanya insufisiensi adrenal relatif IAR .Pengaruh ALB terhadap hemodinamik dinilai dengan rerata cardiac index 60 menit setelah pemberian hidrokortison yang berbeda bermakna [2,14 0,06 l/menit/m2 vs. 2,75 0,04 l/menit/m2 p 0,002 ]. Jumlah cairan dan obat vasoaktif yang dibutuhkan kelompok lipid untuk mempertahankan mean arterial blood pressure > 65 mmHg lebih banyak dibandingkan kelompok kontrol. Kadar laktat meningkat sebelum induksi sepsis pada kelompok lipid [2,28 0,52 vs. 1,28 0,45 mmol/L p 0,001 ]. Bersihan laktat pada kelompok lipid lebih buruk dibandingkan kelompok kontrol. Extravascular lung water index kelompok lipid lebih tinggi bermakna dibanding kelompok kontrol setelah 60 menit resusitasi [21 4,04 mL/kg vs. 12,38 2,32 mL/kg p 0,004 ]. Gambaran radiologi efusi pleura dan edema pulmonal terjadi pada seluruh model anak babi kelompok lipid. Insufisiensi adrenal relatif terjadi pada 7 model anak babi di kelompok lipid dan 4 di kelompok kontrol.Kesimpulan penelitian ini adalah kadar ALB yang tinggi memperberat inflamasi dan merupakan faktor risiko terjadinya IAR. Kata kunci: Asam lemak bebas, cedera paru, hemodinamik, hidrokortison insufisiensi adrenal relatif, laktat, renjatan sepsis, sepsis.
ABSTRACT
Cortisol deficiency is associated with increased morbidity and mortality during critical illness. Dysregulation of immune system in septic shock triggers adrenal insufficiency. Free fatty acid FFA is known to induced sterile inflammation and inhibit adrenocorticothropic hormone and cortisol secretion. Hydrocortisone administration is expected to improve hemodynamic, decrease dependency of vasoactive drugs and improve organ dysfunction in septic shock.The aim of this study is to find out the effect of FFA and hydrocortisone administration on hemodynamic parameters, lactate, lung injury and blood cortisol levels in septic shock piglet models, conducted in April September 2015 in the Division of Surgery and Radiology School of Veterinary Medicine, Institut Pertanian Bogor IPB and has been approved by the Animal Ethics Committee of School of Veterinary Medicine IPB. Sixteen piglet models Sus scrofa entered the study. The piglets were 6 8 weeks old, weighing 5 10 kg divided into two groups, lipids and control groups. Administration of 3 g kg BW of lipid 20 were performed intravenously before sepsis induction for lipid group. Hemodynamic measurement by Pulse Contour Cardiac Output PiCCO by Picco. Lactate measurement by i Stat. Lung injury was determined by Extravascular lung water index EVLWI and chest X ray. Synacthen test to determine relative adrenal insufficiency RAI .FFA influences was shown on cardiac index 60 min after adminstration of hydrocortisone in lipid group 2.14 0.06 L min m2 and control group 2.75 0.04 L min m2 p 0.002 . Lipid group require fluids and vasoactive drugs more than the control grup to maintain mean arterial blood pressure 65 mmHg. Lactate levels before induction of sepsis lipid group 2.28 0,52 mmol L and control group 1.28 0.45 mmol L p 0.001 . Lactate clearance in lipid group was worse than the control group. Extravascular lung water index at 60 minutes after resuscitation in lipid group 21 4.04 mL kg and control group 12.38 2.32 mL kg p 0.004 . Pleural effusion and pulmonary edema were found in all piglet models in lipid group. Relative adrenal insufficiency occured to 7 piglet model in lipid gorup and 4 in control group.Conclusion High level FFA aggravate inflammation in septic shock and is a risk factor for RAI. Hydrocortisone administration improve circulation and lactate levels. Keywords FFA, hemodynamic, hydrocortisone, lactate, lung injury, relative adrenal insufficiency, sepsis, septic shock"
2017
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UI - Disertasi Membership  Universitas Indonesia Library