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Kelainan kulit kering banyak ditemukan pada penyandang DMT2. Patogenesis kulit kering pada DMT2 dipicu oleh kondisi hiperglikemia kronik yang meningkatkan Advanced glycation end products (AGE) N(6)-carboxymethyl-lysine (CML), sitokin proinflamasi dan stres oksidatif.  Kombinasi Centella asiatica  oral  (CAo) dan topikal (CAt) diduga dapat meningkatkan efektivitas tatalaksana kulit kering DMT2. Penelitian bertujuan menganalisis efektivitas dan keamanan kombinasi CAo + CAt dalam memperbaiki kulit kering DMT2.

 

Penelitian merupakan uji klinis acak tersamar ganda di Poliklinik Metabolik Endokrin Departemen Penyakit Dalam RSCM dan 5 puskesmas di Jakarta pada bulan Juli 2018–Maret 2019. Subjek dibagi menjadi 3 kelompok, yaitu kelompok CAo + CAt, plasebo oral (Plo) + CAt, dan Plo + Plasebo topikal (Plt) masing-masing berjumlah 53 orang. Perbaikan kulit kering secara klinis diukur dengan Specified Symptom Sum Score (SRRC) dan Skin Capacitance (SCap). Perbaikan secara molekular diukur  CML, IL-1a, dan aktivitas superoksida dismutase (SOD). Keamanan kombinasi CAo + CAt dilakukan melalui penilaian efek simpang oral dan topikal.

 

Pada ketiga kelompok, median HbA1c > 7%. Glukosa darah sewaktu (GDS) kelompok CAo + CAt hari ke-15 dan 29 semakin menurun. Efektivitas kombinasi CAo + CAt dinilai melalui analisis subgrup berdasarkan nilai HbA1c dan GDS. Pada glukosa darah terkontrol baik, persentase penurunan SRRC lebih besar pada kelompok CAo + CAt vs Plo + Plt (p = 0,04). Peningkatan SCap kelompok CAo + CAt lebih besar dibandingkan Plo + Plt (p = 0,01). Pada glukosa darah terkontrol kurang baik peningkatan SOD kelompok CAo + CAt lebih besar dibandingkan Plo + Plt  (p = 0,01). Tidak terdapat korelasi antara CML, IL-1α dan SOD dengan SRRC atau SCap. Terdapat korelasi sedang sampai kuat dan arah korelasi sesuai antara CML dengan SOD (r = 0,58, p < 0,05)  dan  IL-1α dengan SOD (r = 0,70, p < 0,05) pada glukosa darah terkontrol baik. Tidak terdapat efek simpang oral dan topikal yang bermakna pada penggunaan CAo + CAt dibandingkan 2 kelompok.

 

Simpulan: Pada glukosa darah terkontrol baik, perbaikan SRRC dan SCap  kelompok CAo + CAt lebih besar dibandingkan Plo + Plt.  Pada glukosa darah terkontrol kurang baik peningkatan SOD kelompok CAo + CAt lebih besar daripada Plo + Plt. Terdapat korelasi sedang sampai kuat antara CML atau IL-1α dengan SOD pada glukosa darah terkontrol baik. Tidak terdapat efek simpang oral dan topikal yang bermakna pada kelompok CAo + CAt dibandingkan 2 kelompok.

 

Kata kunci: CML, DMT2, IL-1a, kulit kering, SCap, SOD, SRRC

 

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Dry skin is a common findings in type 2 diabetes mellitus (T2DM). The pathogenesis of dry skin in T2DM rises from chronic hyperglycemic condition which causes an increase in levels of Advanced glycation end products (AGEs)  N(6)-carboxymethyl-lysine (CML), pro-inflammation cytokines and oxidative stress. Combination of oral and topical Centella asiatica (CA) is expected to ameliorate dry skin in T2DM patients more effectively.

 

This study was a double blinded randomized clinical trial in T2DM patients with dry skin in outpatients clinic of Metabolic Endocrine, Internal Medicine Department, dr. Cipto Mangunkusumo Hospital, and 5 primary health cares in Jakarta from July 2018 to March 2019. The subjects were divided into three groups, CA oral (CAo) + CA topical (CAt) group, oral placebo (Plo) + CAt group, and Plo + topical placebo (Plt) which included 53 subjects respectively. Dry skin improvement was evaluated clinically using Specified Symptom Sum Score (SRRC) and Skin Capacitance (SCap). The molecular improvement was evaluated using levels of CML, inflammation interleukin 1-α (IL-1α) concentration, and oxidative stress superoxide dismutase (SOD).

 

In the three groups, median of HbA1c > 7%. Random blood glucose (RBG) in CAo + CAt group in day-15 and 29 were further decreased. Effectivity of CAo + CAt combination were assessed via subgroup analysis based on HbA1c and RBG. In well controlled blood glucose, on day-29, percentage of SRRC decrement was greater in  CAo + CAt compared to control group without CA (p = 0,04). SCap value in CAo + CAt group was greater than control group (p = 0,01). In the partially controlled blood glucose, increment of SOD activity of CAo + CAt group was greater than control group (p = 0,01). There was no correlation found between CML, IL-1α and SOD with SRRC nor SCap. There were medium to strong correlation between CML with SOD (r = 0,58, p < 0,05)  and IL-1α with SOD (r = 0,70, p < 0,05)  in well controlled blood glucose. Systemic and topical adverse events were not found significantly in CAo or CAt usage compared to the other two groups.

 

Conclusion: In well controlled blood glucose, improvement of SSRC and SCap in CAo + CAt were greater than Plo + Plt.  In partially controlled blood glucose,  increment of SOD in CAo + CAt was greater than Plo + Plt.  There was moderate to strong correlation between CML or IL-1 and SOD in well controlled blood glucose. There were no significant adverse events found due to CAo + CAt compared to the other 2 group in the study.

 

Keywords: CML, diabetes mellitus, dry skin, IL-1a, SCap, SOD, SRRC

 

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"Disertasi ini membahas algoritme neuromuscular taping terhadap manifestasi klinis gangguan mikrosirkulasi pada kaki dabetik. Tahapan riset meliputi kajian literatur, faktor risiko neuropati kaki diabetik, uji diagnostik, standarisasi perawatan pencegahan neuropati kaki diabetik, standarisasi NMT FANI pada perawatan neuropati kaki diabetik dan pembentukan algoritme. Desain penelitian uji diagnostik dengan cross sectional, sedangkan uji efek NMT FANI terhadap kelembapan, suhu, kapiler lipatan kuku dan nyeri neuropati dengan desain eksperimental. Instrument menggunakan moisture meter skin, thermometer infrared, capiloroscopy, biothesiometer dan LANSS. Hasil uji diagnostik menunjukan moisture meter skin (sensitifitas, spesifisitas dan akurasi 74%); capilaroscopy (sensitifitas, spesifisitas dan akurasi 73%) baik dalam mendeteksi neuropati kaki diabetik. Uji thermograph menunjukan sensitifitas 73.07% dalam mendeteksi kelainan neuropati, spesifisitas 56.42% dan akurasi 59.03%. Uji thermometer gun menunjukan sensitifitas 56.66%, spesifisitas 53.67% dan akurasi 54.21% kurang baik dalam mendeteksi neuropati kaki diabetik. NMT FANI berpengaruh secara signifikan terhadap kelembapan kulit, kapiler lipatan kulit kuku dan derajat nyeri neuropati pada kaki diabetik (p value < 0.05), sedangkan pada suhu kaki tidak berpengaruh secara signifikan (p value > 0.05). Hasil akhir algoritme tersusun dari pengkajian awal dari hasil anamnesis faktor risiko, pemeriksaan fisik dan diagnostik serta tatalaksana NMT FANI. Indikator kelembapan kulit, perubahan struktur kapiler lipatan kuku kaki dan intervensi NMT FANI perlu dimasukan dalam tatalaksana kaki diabetik.

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This dissertation discusses the neuromuscular taping algorithm against the clinical manifestations of microcirculation disorders in the diabetic foot. The research stages included a review of literature, risk factors for neuropathy of diabetic foot, diagnostic tests, standardization of preventive treatment of diabetic foot neuropathy, standardization of NMT FANI in the treatment of diabetic foot neuropathy, and algorithm formation. The study design was a cross-sectional diagnostic test, while an experimental design was employed for the NMT FANI effect test on skin moisture, temperature, nail fold capillaries, and neuropathic pain. The instruments used were a skin moisture meter, infrared thermometer, capillaroscopy, biothesiometer, and LANSS. The diagnostic test results showed that the SC skin moisture meter (sensitivity, specificity, accuracy 74%) and capillaroscopy (sensitivity, specificity, accuracy 73%) were good at detecting diabetic foot neuropathy. The thermograph test shows a sensitivity of 73.07% in detecting neuropathic disorders, a specificity of 56.42% and an accuracy of 59.03%. The thermometer gun test showed a sensitivity of 56.66%, a specificity of 53.67%, and an accuracy of 54.21% that was not good at detecting diabetic foot neuropathy. NMT FANI had a significant effect on skin moisture, nail fold capillaries, and the degree of neuropathy pain in diabetic foot (p value < 0.05), while foot temperature did not significantly influence (p value > 0.05). The end result of the algorithm is composed of a preliminary assessment of the results of the history of risk factors, physical examination, diagnostic and management of NMT FANI. Indicators of skin moisture, changes in the capillary structure of the nail folds and NMT FANI interventions need to be included in the management of diabetic foot."

"Luka diabetes merupakan komplikasi mikrovaskular yang sering dikeluhkan oleh pasien diabetes melitus (DM) tipe 2. Vaskularisasi berperan penting dalam penyembuhan luka, yang aktivitasnya diperantarai aktivitas hypoxia-inducible factor 1-alpha (HIF-1α) dan vascular endothelial growth factor (VEGF). Belum ada studi klinis yang mengevaluasi aktivitas HIF-1α dan VEGF pada manusia, khususnya pasien DM tipe 2 yang mengalami luka kaki diabetes. Tujuan penelitian adalah untuk mengevaluasi vaskularisasi jaringan, HIF-1α, dan VEGF pada luka kaki diabetes yang menjalani amputasi dan non-amputasi.Studi potong lintang dilakukan di Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo (RSCM) pada tahun 2020–2021. Subjek penelitian adalah pasien luka kaki diabetik yang dilakukan debridemen/amputasi. Kemudian diambil jaringan viabel tepi luka untuk diperiksa vaskularisasi jaringan (densitas mikrovaskular), ekspresi VEGF, serta area granulasi, di Departemen Patologi Anatomi FKUI-RSCM. Konsentrasi HIF-1α jaringan dikuantifikasi di Departemen Biokimia dan Biologi Molekuler FKUI-RSCM. Data numerik yang diperoleh diuji normalitasnya dengan uji Saphiro-Wilk. Data distribusi normal dianalisis dengan uji t tidak berpasangan. Dilakukan uji regresi logistik bila terdapat > 2 variabel independen dengan nilai p < 0,25.Dari 67 subjek terdapat 30 pasien amputasi dan 34 pasien debridemen yang dianalisis. Proporsi subjek laki-laki pada kelompok amputasi lebih tinggi dibandingkan kelompok debridemen (p = 0,041). Tidak terdapat perbedaan bermakna pada status gizi, usia, kejadian hipertensi, gagal ginjal, dan status merokok antar kedua kelompok. Profil glikemik, hematologi rutin, penanda inflamasi, kadar elektrolit, penanda fungsi hati, fungsi ginjal tidak berhubungan dengan tindakan pasien, kecuali kadar albumin. Pada analisis bivariat, kadar albumin lebih tinggi pada kelompok debridemen 2,53/0,49 dibandingkan amputasi 2,94/0,51, p = 0,002. Kelompok amputasi memiliki nilai median HIF-1α 5,77 (0,55–53,47) pg/mg protein yang jauh lebih rendah dibandingkan kelompok debridemen 26,56 (2,23–211,12) pg/mg protein (p = 0,001). Hal serupa juga ditemukan pada nilai VEGF (p < 0,001). Pasien dengan HIF-1α < 8,8065 pg/mg protein, MVD < 68,7%, VEGF < 30,443%, dan area granulasi < 33,2802% memiliki aOR 11,116 (IK 95% 1,441–85,752), 10,934 (IK 95% 1,604–74,55), 7,973 (IK 95% 1,301–48,86), 15,589 (IK 95% 1,39–174,867) untuk mengalami amputasi. Kepadatan mikrovaskular, konsentrasi HIF-1α, ekspresi VEGF, dan area jaringan granulasi lebih banyak pada pasien non-amputasi. Pasien dengan penurunan jumlah parameter tersebut memiliki risiko lebih tinggi untuk mendapat tindakan amputasi.

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Diabetic wounds are microvascular complications often complained by people with type 2 diabetes mellitus (DM). Tissue vascularization plays an essential role in wound healing, whose activity is mediated by the activity of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF). However, no clinical studies evaluate its activity in humans, especially in type 2 diabetes mellitus patients who have diabetic foot ulcers. This study attempts to evaluate whether there are differences in tissue vascularization, HIF-1 α, and VEGF in diabetic foot wounds that received amputation and non-amputation procedures.

A cross-sectional study was conducted at the Cipto Mangunkusumo National Central General Hospital (RSCM) in 2020–2021. Diabetic foot wound patients who received debridement/amputation were included in this study. Viable tissue at the wound edges was taken. The expression of VEGF, microvascular density, and area of granulated tissue were evaluated in the Department of Pathology and Anatomy, FKUI-RSCM. HIF-1 levels in tissue were quantified at the Department of Biochemistry and Molecular Biology FKUI-RSCM. All numerical data were tested for normality by the Shapiro-Wilk test. Variables with normally distributed data were analyzed by unpaired t-test. A logistic regression test was performed if there were more than two independent variables with a p-value < 0.25.

This study included 67 patients. There were 30 amputees, and 34 debridement patients included in the data analysis. The proportion of male patients in the amputation group was found to be higher than the debridement group (p = 0.041). There were no differences in nutritional status, age, the incidence of hypertension, kidney failure, and smoking status between the two groups. The glycemic profile, routine haematological findings, markers of inflammation, electrolyte levels, markers of liver function, and markers of kidney function were not found to be related to the patient's condition, except for albumin levels. In bivariate analysis, albumin levels were found to be higher in the debridement group [2.53 (0.49)] than in the amputee [2.94 (0.51)], p = 0.002. The amputee group had a median HIF-1α value of 5,77 (0,55–53,47) pg/mg protein, which was much lower than the debridement group of 26,56 (2,23–211,12) pg/mg protein (p = 0.001). Similar condition was also found in the VEGF value (p < 0.001). Patients with HIF-1α < 8.8065 pg/mg protein, MVD < 68.7%, VEGF < 30.443%, and granulation area < 33.2802% had risk odds of 11.116 (95% CI 1.441–85.752), 10.934 (95% CI 1.604–74.55), 7,973 (95% CI 1.301–48.86), 15.589 (95% CI 1.39–174.867) for amputation. Microvascular density, HIF-1α levels, VEGF expression, and granulation tissue area were higher in non-amputated patients. Patients with a decrease in these parameters have a higher risk of amputation."

"Diabetes sering menyebabkan komplikasi ulkus kaki diabetik (UKD) yang penyembuhannya terhambat pada fase inflamasi dan terjadi gangguan pada pembentukan jaringan granulasi. LL-37 memiliki aktivitas antimikrobial, memicu angiogenesis, serta migrasi dan proliferasi keratinosit. Penelitian ini menganalisis pengaruh krim LL-37 terhadap kecepatan penyembuhan UKD derajat ringan dengan mengkaji IL-1a, TNF-a, serta pola dan jumlah kolonisasi bakteri aerob.Penelitian ini adalah uji klinis buta ganda acak yang dilaksanakan Januari 2020–Juni 2021 di RSUPN dr. Cipto Mangunkusumo dan RSUP Persahabatan, Jakarta. Subjek adalah penyandang UKD tanpa infeksi atau infeksi derajat ringan, berusia 18–60 tahun, ABI 0,9–1,3, luas luka ≥ 2 cm2, kedalaman luka sampai dengan subkutis, dan tanpa infeksi sistemik. Subjek dibagi menjadi kelompok krim LL-37 dan plasebo yang dioles dua kali seminggu selama 4 minggu. Dilakukan pengamatan luka pada akhir minggu dengan metode planimetri dan fotografi digital lalu diolah dengan ImageJ. Subjek diperiksa kadar IL-1a dan TNF-a cairan luka dengan metode ELISA dan kultur bakteri aerob dari apusan luka pada setiap akhir minggu.Kadar LL-37 cairan luka pada kelompok LL-37 adalah 1,07 (0,37–4,96) ng/mg protein dan plasebo sebesar 1,11 (0,24–2,09) ng/mg protein (p = 0,44). Penurunan luas luka pada hari ke-14, ke-21, dan ke-28 dibandingkan hari ke-1 pada kelompok LL-37 lebih besar daripada plasebo, walaupun tidak bermakna. Pada kelompok LL-37 terjadi peningkatan luas jaringan granulasi yang lebih besar daripada plasebo pada semua hari, walaupun hanya bermakna pada hari ke-14 yaitu 0,95 (±1,34) cm2 pada kelompok LL-37 dibandingkan -0,24 (±1,01) cm2 pada kelompok plasebo (p = 0,020). Terjadi peningkatan indeks granulasi yang secara konsisten lebih besar dan bermakna (p < 0,05) pada kelompok LL-37 dibandingkan plasebo pada semua hari. Tidak terjadi penurunan kadar IL-1a dan TNF-a yang lebih besar pada kelompok LL-37. Pada hari ke-1, frekuensi bakteri aerob terbanyak adalah S. aureus yaitu 37,1% pada kelompok LL-37 dan 45% pada kelompok plasebo. Penurunan jumlah koloni bakteri pada kelompok plasebo lebih besar dibandingkan dengan kelompok LL-37 pada hari ke-28 dibandingkan dengan hari ke-1, walaupun tidak bermakna (p = 0,98).Simpulan: Kadar LL-37 pada UKD kedua kelompok rendah. Pemberian LL-37 mempercepat penyembuhan UKD tanpa infeksi maupun derajat ringan dengan meningkatkan indeks granulasi. Pemberian LL-37 tidak menurunkan kadar IL-1a dan TNF-a pada UKD. Pemberian LL-37 tidak memengaruhi pola dan jumlah kolonisasi bakteri aerob pada UKD.

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Diabetes often causes DFU (diabetic foot ulcer). Wound healing in DFU has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream on wound healing rate in DFU with mild infection by examining IL-1a, TNF-a, and aerobic bacteria colonization.

This study was a randomized double-blind controlled trial conducted from January 2020–June 2021 at RSUPN dr. Cipto Mangunkusumo and RSUP Persahabatan, Jakarta. Subjects were patients with uninfected DFU or DFU with mild infection according to IDSA, aged 18–60 years old, ABI 0.9–1.3, wound area ≥ 2 cm2, wound no deeper than subcutaneous layer, and without systemic infection. Subjects were divided into the LL-37 cream and placebo cream group which were applied twice a week for 4 weeks. Wounds were measured at the end of every week using planimetric method and digital photography and subsequently processed with ImageJ. The levels of IL-1a and TNF-a from wound fluid were measured using the ELISA method and aerobic bacteria culture was performed using wound swabs.

The level of LL-37 from wound fluid in the LL-37 group was 1.07 (0.37–4.96) ng/mg protein and in the placebo group was 1.11 (0.24–2.09) ng/mg protein (p = 0.44). The decrease in wound area on day 14, 21, and 28 compared to day 1 in the LL-37 group was greater than in the placebo group, although the difference was not significant. In the LL-37 group, there was a greater increase in granulation tissue area than in the placebo group on each day, although the difference was only significant on day 14 which was 0.95 (±1.34) cm2 in the LL-37 group compared to -0.24 (± 1.01) cm2 in the placebo group (p = 0.020). There was a consistently and significantly greater increase in granulation index (p < 0.05) in the LL-37 group compared to placebo group on each day. There was no greater decrease in IL-1a and TNF-a levels in the LL-37 group. On day 1, the highest frequency of aerobic bacteria was S. aureus which was 37.1% in the LL-37 group and 45% in the placebo group. The decrease in the number of bacterial colonies in the placebo group was greater than in the LL-37 group on day 28 compared to day 1, although the difference was not significant (p = 0.98).

Conclusion: The level of LL-37 in DFU was low in both groups. Administration of LL-37 accelerated the healing of uninfected DFU or DFU with mild infection by increasing the granulation index. Administration of LL-37 did not reduce the levels of IL-1a and TNF-a in DFU. Administration of LL-37 did not affect the pattern and number of colonization of aerobic bacteria in DFU."

"Luka kaki diabetes (LKD) adalah salah satu komplikasi diabetes melitus (DM). Terapi LKD adalah perawatan luka dan growth factor (GF) seperti advanced-platelet rich fibrin (A-PRF). Penyandang DM memiliki GF rendah, untuk mengoptimalkan GF yang dilepaskan oleh PRF, ditambahkan asam hialuronat (AH). Penelitian ini bertujuan menganalisis pengaruh A-PRF + AH terhadap penyembuhan LKD dengan mengkaji VEGF, PDGF, IL-6, dan indeks granulasi. Desain penelitian randomized control trial, dilaksanakan pada bulan Juli 2019 −Maret 2020 di RSPAD Gatot Soebroto dan RSUD Koja, Jakarta. Subjek penyandang LKD yang mengalami luka kronik, kriteria Wagner II, luas luka < 40 cm2. Subjek diambil berdasarkan rule of thumb dan dibagi tiga secara acak yaitu kelompok terapi topikal A-PRF + AH (n = 10), A-PRF (n = 10) dan kontrol NaCl 0,9% (n = 10). Pada kelompok A-PRF + AH dan A-PRF dilakukan pemeriksaan VEGF, PDGF, IL-6 dari usap LKD dan fibrin gel sedangkan kontrol hanya diperiksa usap LKD. Biomarker dan Indeks Granulasi (IG) diperiksa hari ke-0, ke-3, ke-7. Khusus IG pengukuran ditambah hari ke-14. Data dianalisis menggunakan SPSS versi 20 dengan uji Anova atau Kruskal Wallis. Pada kelompok A-PRF + AH, kadar VEGF usap LKD hari ke-0 adalah 232,8 meningkat menjadi 544,5 pg/mg protein pada hari ke-7. Pada kelompok A-PRF tejadi peningkatan dari 185,7 menjadi 272,8 pg/mg protein, namun kelompok kontrol terjadi penurunan dari 183,7 menjadi 167,4 pg/mg protein. Kadar PDGF usap LKD kelompok A-PRF + AH hari ke-0 adalah 1,9 pg/mg protein, meningkat menjadi 8,1 pg/mg protein hari ke-7, kelompok A-PRF dari 1,7 meningkat menjadi 5,4 pg/mg protein dan kontrol dari 1,9 meningkat menjadi 6,4 pg/mg protein. Kadar IL-6 usap LKD kelompok A-PRF + AH hari ke-0 adalah 106,4 menjadi 88,7 pg/mg protein hari ke-7, pada A-PRF dari 91,9 menjadi 48,8 pg/mg protein dan kontrol dari 125,3 menjadi 167,9 pg/mg protein. IG kelompok A-PRF + AH hari ke-0 adalah 42,1% menjadi 78,9% dan 97,7% hari ke-7 dan ke-14, pada kelompok A-PRF dari 34,8% menjadi 64,6% dan 91,6%. Kelompok kontrol dari 35,9% menjadi 66,0% dan 78,7% hari ke-7 dan ke-14. Pada kelompok A-PRF + AH dibandingkan A-PRF dan NaCl didapatkan peningkatan bermakna kadar VEGF pada hari ke-3 (p = 0,011) dan hari ke-7 (p < 0,001). Kadar IL-6 menurun bermakna (p = 0,041) pada hari ke-7 saja. Namun persentase IG meningkat bermakna pada hari ke-3 (p = 0,048), ke-7 (p = 0,012) dan hari ke-14 (p < 0,001). Disimpulkan penambahan AH pada A-PRF meningkatkan VEGF (marker angiogenesis) dan IG (tanda klinis penyembuhan luka), serta menurunkan IL-6 (marker inflamasi) secara bermakna sehingga mempercepat penyembuhan LKD.

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Diabetic foot ulcer (DFU) is one of complications of diabetes mellitus (DM). Advance wound treatment in DFU such as growth factors (GF) including Advanced-Platelet Rich Fibrin (A-PRF) topical has been developed . People with DM have low GF, so to optimize GF hyaluronic acid (AH) is added. This study analyzed the combination of A-PRF + AH combination in DFU recovery by examining VEGF, PDGF, IL-6, and granulation index (IG). The study used a randomized control design, done from July 2019−March 2020 at the Gatot Soebroto Army Hospital and Koja District Hospital, Jakarta. Subjects were DFU patients who had chronic wounds, area < 40 cm2 and Wagner II criteria. Subjects were recruited according to the rule of thumb and were randomly divided into three groups namely topical A-PRF + AH (n = 10), A-PRF (n = 10) and control NaCl 0.9% groups (n = 10). The A-PRF + AH and A-PRF groups underwent VEGF, PDGF, and IL-6 examinations of the DFS swabs and fibrin gel while the controls could only underwent the DFU swabs. Biomarkers and Granulation Index (GI) were measured on day 0, 3rd, 7th. Special GI measurements were added on day 14. Data were analyzed using SPSS version 20 with the Anova and Kruskal Wallis test. In the A-PRF + AH group the VEGF level from swab DFU day 0 was 232,8 pg/mg protein increase to 544,5 pg/mg protein on day 7. In the A-PRF group VEGF increase from 185,7 to 272,8 pg/mg protein and control decrease from 183.7 to 167.4 pg/mg protein. Increasing of PDGF levels in group A-PRF + AH day 0 was from 1,9 pg/mg protein to 8,1 pg/mg day 7, group A-PRF from 1,7 increased to 5,4 pg/mg protein and control from 1,9 to 6,4 pg/mg protein. Decreasing of IL-6 level of DFU swab in group A-PRF + AH day 0 was 106,4 pg/mg protein to 88,7 pg/mg protein day 7, in group A-PRF from 91,9 to 48,8 pg/mg protein and control from 125,3 to 167,9 pg/mg protein. The granulation index of DFU group A-PRF + AH on day 0 was 42,1% increased to 78,9% and 97,7% days 7 and 14. In the A-PRF group increased from 34,8% to 64,6 % and 91,6%. and controls from 35,9% to 66,0% and 78,7% on days 7 and 14. On the 7th day the VEGF level of the A-PRF + AH group increased significantly (p < 0.001), while IL-6 decreased and the granulation index increased significantly with p level of p = 0.041 and p = 0.012 respectively, compare with other group. It was concluded that on day 7 the AH to A-PRF increases VEGF (a marker of angiogenesis) and GI (a clinical sign of wound recovery), as well as a decrease in IL-6 (a marker of inflammation) which fully increase in DFU. "

"Burnout Syndrome (BOS) adalah kumpulan gejala akibat stres fisik maupun psikis akibat beban dan stresor pekerjaan yang tinggi. BOS memengaruhi tubuh dalam aspek psikis, neuroautonom, imunologi, maupun endokrin (PNIE). Terapi musik terbukti dapat membantu mengatasi stres psikis dan fisik. Musik tradisional dapat digunakan untuk terapi musik karena sesuai dengan latar budaya masyarakat Indonesia.Studi I merupakan penelitian kuantitatif untuk menentukan nilai baseline pada kelompok tidak burnout. Studi II merupakan studi kualitatif dengan teknik clinical expert judgement untuk menentukan model terapi musik. Studi III desain RCT dengan intervensi terapi musik pada tenaga kesehatan dengan BOS selama 4 minggu. Skor Maslach Burnout Inventory (MBI-HSS), Heart Rate Variability (HRV), endorfin, kortisol dan IgA saliva, dan kadar T-Regulator (FOXP3) serum dilakukan pada awal penelitian, minggu ke-2, ke-4, dan ke-6. Analisis data menggunakan SPSS 20, dengan nilai kemaknaan < 0,05.Pada studi I, didapatkan nilai baseline HRV sebesar 51,153 ms2 , endorfin sebesar 503 pg/mL, kortisol saliva sebesar 5,55 ng/mL, IgA saliva sebesar 0,44 mg/mL, dan FOXP3 sebesar 4%. Pada Studi II, didapatkan aransemen 20 jenis musik bergenre tradisional untuk terapi, uji coba musik terapi di laboratorium musik dan model terapi sebanyak 3 kali per minggu, durasi 10–15 menit setiap sesi, diberikan selama 4 minggu. Pada studi III didapatkan peningkatan bermakna skor MBI-HSS (p 0,022), HRV (p < 0,0001), dan kadar FOX-P3 (p 0,035) setelah intervensi terapi musik dibanding dengan kontrol. Didapatkan persistensi terapi musik terhadap skor MBI-HSS.Terapi musik terbukti memperbaiki BOS melalui jalur PNIE, sehingga dapat diaplikasikan dalam praktik sebagai terapi supportif. Perlu dilakukan penelitian lebih lanjut untuk menilai manfaat terapi musik dengan frekuensi dan durasi yang lebih panjang, serta kombinasi dengan modalitas terapi lain.

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Burnout Syndrome (BOS) is a collection of symptoms due to physical and psychological stress due to high workload and stressors. BOS affects the body in psychological, neuroautonomic, immunological, and endocrine (PNIE) aspects. Music therapy has been proven to help overcome psychological and physical stress. Traditional music can be used for music therapy because it is in accordance with the cultural background of Indonesian society.

Study I is a quantitative study to determine the baseline value in the non-burnout group. Study II is a qualitative study using clinical expert judgment techniques to determine the music therapy model. Study III RCT design with music therapy intervention in health workers with BOS for 4 weeks. Maslach Burnout Inventory (MBI-HSS) scores, Heart Rate Variability (HRV), endorphins, cortisol and salivary IgA, and serum T-Regulator (FOXP3) levels were carried out at the beginning of the study, weeks 2, 4, and 6. Data analysis using SPSS 20, with a significance value of < 0.05.

In study I, baseline HRV values were obtained at 51.153 ms2, endorphin at 503 pg/mL, salivary cortisol at 5.55 ng/mL, salivary IgA at 0.44 mg/mL, and FOXP3 at 4%. In study II, arrangements of 20 types of traditional music genres for therapy were obtained, music therapy trials in a music laboratory and therapy models were carried out 3 times per week, with a duration of 10–15 minutes per session, given for 4 weeks. In study III, there was a significant increase in MBI-HSS scores (p 0.022), HRV (p < 0.0001), and FOX-P3 levels (p 0.035) after music therapy intervention compared to control. A retention effect of music therapy on MBI-HSS scores was obtained.

Music therapy has been shown to improve BOS through the PNIE pathway, so it can be applied in practice as a supportive therapy. Further research is needed to assess the benefits of music therapy with longer frequencies and durations, as well as in combination with other therapeutic modalities."

"Luka kaki diabetes (LKD) adalah salah satu komplikasi diabetes melitus (DM). Terapi LKD adalah perawatan luka dan growth factor (GF) seperti advanced-platelet rich fibrin (A-PRF). Penyandang DM memiliki GF rendah, untuk mengoptimalkan GF yang dilepaskan oleh PRF, ditambahkan asam hialuronat (AH). Penelitian ini bertujuan menganalisis pengaruh A-PRF + AH terhadap penyembuhan LKD dengan mengkaji VEGF, PDGF, IL-6, dan indeks granulasi. Desain penelitian randomized control trial, dilaksanakan pada bulan Juli 2019 −Maret 2020 di RSPAD Gatot Soebroto dan RSUD Koja, Jakarta. Subjek penyandang LKD yang mengalami luka kronik, kriteria Wagner II, luas luka < 40 cm2. Subjek diambil berdasarkan rule of thumb dan dibagi tiga secara acak yaitu kelompok terapi topikal A-PRF + AH (n = 10), A-PRF (n = 10) dan kontrol NaCl 0,9% (n = 10). Pada kelompok A-PRF + AH dan A-PRF dilakukan pemeriksaan VEGF, PDGF, IL-6 dari usap LKD dan fibrin gel sedangkan kontrol hanya diperiksa usap LKD. Biomarker dan Indeks Granulasi (IG) diperiksa hari ke-0, ke-3, ke-7. Khusus IG pengukuran ditambah hari ke-14. Data dianalisis menggunakan SPSS versi 20 dengan uji Anova atau Kruskal Wallis.Pada kelompok A-PRF + AH, kadar VEGF usap LKD hari ke-0 adalah 232,8 meningkat menjadi 544,5 pg/mg protein pada hari ke-7. Pada kelompok A-PRF tejadi peningkatan dari 185,7 menjadi 272,8 pg/mg protein, namun kelompok kontrol terjadi penurunan dari 183,7 menjadi 167,4 pg/mg protein. Kadar PDGF usap LKD kelompok A-PRF + AH hari ke-0 adalah 1,9 pg/mg protein, meningkat menjadi 8,1 pg/mg protein hari ke-7, kelompok A-PRF dari 1,7 meningkat menjadi 5,4 pg/mg protein dan kontrol dari 1,9 meningkat menjadi 6,4 pg/mg protein. Kadar IL-6 usap LKD kelompok A-PRF + AH hari ke-0 adalah 106,4 menjadi 88,7 pg/mg protein hari ke-7, pada A-PRF dari 91,9 menjadi 48,8 pg/mg protein dan kontrol dari 125,3 menjadi 167,9 pg/mg protein. IG kelompok A-PRF + AH hari ke-0 adalah 42,1% menjadi 78,9% dan 97,7% hari ke-7 dan ke-14, pada kelompok A-PRF dari 34,8% menjadi 64,6% dan 91,6%. Kelompok kontrol dari 35,9% menjadi 66,0% dan 78,7% hari ke-7 dan ke-14. Pada kelompok A-PRF + AH dibandingkan A-PRF dan NaCl didapatkan peningkatan bermakna kadar VEGF pada hari ke-3 (p = 0,011) dan hari ke-7 (p < 0,001). Kadar IL-6 menurun bermakna (p = 0,041) pada hari ke-7 saja. Namun persentase IG meningkat bermakna pada hari ke-3 (p = 0,048), ke-7 (p = 0,012) dan hari ke-14 (p < 0,001).Disimpulkan penambahan AH pada A-PRF meningkatkan VEGF (marker angiogenesis) dan IG (tanda klinis penyembuhan luka), serta menurunkan IL-6 (marker inflamasi) secara bermakna sehingga mempercepat penyembuhan LKD.

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Diabetic foot ulcer (DFU) is one of complications of diabetes mellitus (DM). Advance wound treatment in DFU such as growth factors (GF) including Advanced-Platelet Rich Fibrin (A-PRF) topical has been developed . People with DM have low GF, so to optimize GF hyaluronic acid (AH) is added. This study analyzed the combination of A-PRF + AH combination in DFU recovery by examining VEGF, PDGF, IL-6, and granulation index (IG).

The study used a randomized control design, done from July 2019−March 2020 at the Gatot Soebroto Army Hospital and Koja District Hospital, Jakarta. Subjects were DFU patients who had chronic wounds, area < 40 cm2 and Wagner II criteria. Subjects were recruited according to the rule of thumb and were randomly divided into three groups namely topical A-PRF + AH (n = 10), A-PRF (n = 10) and control NaCl 0.9% groups (n = 10). The A-PRF + AH and A-PRF groups underwent VEGF, PDGF, and IL-6 examinations of the DFS swabs and fibrin gel while the controls could only underwent the DFU swabs. Biomarkers and Granulation Index (GI) were measured on day 0, 3rd, 7th. Special GI measurements were added on day 14. Data were analyzed using SPSS version 20 with the Anova and Kruskal Wallis test.

In the A-PRF + AH group the VEGF level from swab DFU day 0 was 232,8 pg/mg protein increase to 544,5 pg/mg protein on day 7. In the A-PRF group VEGF increase from 185,7 to 272,8 pg/mg protein and control decrease from 183.7 to 167.4 pg/mg protein. Increasing of PDGF levels in group A-PRF + AH day 0 was from 1,9 pg/mg protein to 8,1 pg/mg day 7, group A-PRF from 1,7 increased to 5,4 pg/mg protein and control from 1,9 to 6,4 pg/mg protein. Decreasing of IL-6 level of DFU swab in group A-PRF + AH day 0 was 106,4 pg/mg protein to 88,7 pg/mg protein day 7, in group A-PRF from 91,9 to 48,8 pg/mg protein and control from 125,3 to 167,9 pg/mg protein. The granulation index of DFU group A-PRF + AH on day 0 was 42,1% increased to 78,9% and 97,7% days 7 and 14. In the A-PRF group increased from 34,8% to 64,6 % and 91,6%. and controls from 35,9% to 66,0% and 78,7% on days 7 and 14. On the 7th day the VEGF level of the A-PRF + AH group increased significantly (p < 0.001), while IL-6 decreased and the granulation index increased significantly with p level of p = 0.041 and p = 0.012 respectively, compare with other group.

It was concluded that on day 7 the AH to A-PRF increases VEGF (a marker of angiogenesis) and GI (a clinical sign of wound recovery), as well as a decrease in IL-6 (a marker of inflammation) which fully increase in DFU."