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"klerosis sistemik atau skleroderma adalah suatu penyakit jaringan ikat yang dimediasi imun yang ditandai dengan fibrosis kulit dan organ dalam serta vaskulopati. Penyebab kematian utama pada sklerosis sistemik adalah penyakit paru interstisial. Pengobatan penyakit paru interstisial pada sklerosis sistemik saat ini belum memuaskan. Herba ciplukan (Physalis angulata) merupakan salah satu terapi alternatif yang potensial dan terbukti dapat memperbaiki fibrosis kulit pada pasien sklerosis sistemik namun data pada manifestasi paru belum ada. Penelitian ini bertujuan untuk menilai efek herba ciplukan dalam mencegah dan memperbaiki inflamasi dan fibrosis paru pada model tikus sklerosis sistemik dan mencari dosis optimal ciplukan untuk memperbaiki fibrosis. Penelitian ini terbagai dalam 2 tahap yaitu tahap kuratif fibrosis (tahap 1) dan tahap preventif inflamasi dan fibrosis (tahap 2). Pada tahap 1, 33 tikus (Rattus norvegicus) galur Sprague-Dawley 10−12 minggu dibagi dalam 6 kelompok yaitu kelompok yang mendapat bleomisin dan ciplukan (dosis 50,100,150, dan 200 mg/kg), bleomisin dan salin, dan kontrol negatif. Bleomisin diberikan subkutan per hari selama 14 hari dan ciplukan atau salin diberikan mulai hari ke-21 selama 30 hari lalu hewan diterminasi. Fibrosis dinilai dengan derajat fibrosis dan luas fibrosis pada histopatologi, kadar hidroksiprolin, TGF-β dan MMP13 jaringan paru. Pada tahap 2, 36 ekor tikus dibagi dalam 6 kelompok yaitu 2 kelompok yang mendapat bleomisin dan ciplukan (50 dan 100 mg/kgBB) dan 2 kelompok bleomisin dan salin. Tiga kelompok diterminasi di H14 dan 3 kelompok di H51. Pada tahap 2, bleomisin dan ciplukan diberikan bersamaan selama 14 hari pertama. Luaran yang dinilai di H14 adalah kadar IL-6 paru, jumlah leukosit dari BAL dan skor inflamasi paru secara histopatologi. Luaran yang dinilai di H52 adalah derajat fibrosis dan luas fibrosis, kadar hidroksiprolin, TGF-β dan MMP13 paru. Kadar IL-6, TGF-β dan MMP 13 dinilai dengan ELISA dari jaringan paru, Hidroksiprolin dinilai dari jaringan paru dengan metode kolorimetri. Pada tahap 1 terdapat perbedaan luas fibrosis yang secara statistik bermakna antara kelompok yang mendapat ciplukan dosis 100, 150, dan 200 mg/kgBB dibandingkan kelompok bleomisin. Tidak terdapat perbedaan skor fibrosis antara kelompok yang mendapat ciplukan 50, 100, dan 150 mg/kgBB dengan kontrol negatif. Tidak terdapat perbedaan hidroksiprolin antara kelompok yang mendapat ciplukan dengan kontrol negatif. Tidak terdapat perbedaan kadar TGF-β dan MMP13 yang secara statistik bermakna antar kelompok. Pada tahap 2 penelitian tidak didapatkan perbedaan kadar IL-6, jumlah leukosit cairan BAL dan skor inflamasi yang bermakna antar kelompok dan tidak terdapat perbedaan skor fibrosis, luas fibrosis, kadar hidroksiprolin, TGF-β dan MMP13 antar kelompok. Sebagai simpulan ekstrak ciplukan memiliki efek kuratif untuk menurunkan luas fibrosis paru dengan dosis optimal 100 mg/kgBB. Ciplukan tidak memiliki efek preventif terhadap inflamasi dan fibrosis.

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Systemic sclerosis or scleroderma is an immune mediated connective tissue disease which is manifested by fibrosis on skin and internal organ and vasculopathy. Interstitial lung disease (ILD) is the main cause of death of systemic sclerosis however the treatment of ILD in systemic sclerosis is still unsatisfactory. Ciplukan (Physalis angulata) herb is a potential alternative treatment for systemic sclerosis and has been proven to improve skin sclerosis in systemic sclerosis patients however the study on its effect on lung has been lacking. The aim of this study is to evaluate the effect of ciplukan herb for treating and preventing inflammation and fibrosis in systemic sclerosis animal model and to find out its optimal dose in improving lung fibrosis. This study was done in 2 stages. For the first stage (treatment of fibrosis), 33 Sprague-Dawley rats aged 10−12 weeks were divided into 6 groups (4 groups were given bleomycin and ciplukan extract dose 50,100,150, and 200 mg/kgBW, respectively, bleomycin and saline and negative control). Bleomycin was given subcutaneously daily for 14 days and ciplukan or saline were given from day 21 until the next 30 days and then the animals were sacrificed. At the end of observation, degree of fibrosis and width of fibrosis from lung histopathology, hydroxyproline, TGF-β, and MMP13 levels were analyzed. For the second stage (prevention), 36 rats were divided into 6 groups (bleomycin and ciplukan dose 50 and 100 mg/kgBW, and bleomycin only). Three groups were sacrificed after 14 days of observation for evaluation of IL-6 level in lung tissue, leucocyte count on BAL fluid and inflammation score. Three groups were sacrificed after 51 days observation and were analyzed for degree of fibrosis and width of fibrosis from lung histopathology, hydroxyproline, TGF-β, and MMP13 levels. For the second stage, bleomycin and ciplukan were given simultaneously for 14 days. IL-6, TGF-β, and MMP13 levels were measured using ELISA methods while hydroxyproline was analyzed using colorimetric method. From the stage 1, there was a significant reduction in width of lung fibrosis on groups receiving bleomycin and ciplukan dose 100, 150, and 200 mg/kgBW compared with bleomycin group. There was no difference of fibrosis score among groups who received ciplukan 50,100, and 150 mg/kgBW compared to the negative control. There was no difference of hydroxyproline among groups who received ciplukan compared with negative control. There was no difference of TGF-β, and MMP13 levels among groups. From the stage 2, there were no difference of IL-6 levels, BAL leukocyte count and inflammation score among groups after 14 days and no difference of fibrosis score, extension of fibrosis, hydroxyproline, TGF-β and MMP13 levels among groups after 51 days observation. As a conclusion, ciplukan herb has a role as a treatment of fibrosis to reduce extent of lung fibrosis with optimal dose of 100 kg/BW but shows no effect on prevention of lung inflammation and lung fibrosis."

"klerosis sistemik atau skleroderma adalah suatu penyakit jaringan ikat yang dimediasi imun yang ditandai dengan fibrosis kulit dan organ dalam serta vaskulopati. Penyebab kematian utama pada sklerosis sistemik adalah penyakit paru interstisial. Pengobatan penyakit paru interstisial pada sklerosis sistemik saat ini belum memuaskan. Herba ciplukan (Physalis angulata) merupakan salah satu terapi alternatif yang potensial dan terbukti dapat memperbaiki fibrosis kulit pada pasien sklerosis sistemik namun data pada manifestasi paru belum ada. Penelitian ini bertujuan untuk menilai efek herba ciplukan dalam mencegah dan memperbaiki inflamasi dan fibrosis paru pada model tikus sklerosis sistemik dan mencari dosis optimal ciplukan untuk memperbaiki fibrosis. Penelitian ini terbagai dalam 2 tahap yaitu tahap kuratif fibrosis (tahap 1) dan tahap preventif inflamasi dan fibrosis (tahap 2). Pada tahap 1, 33 tikus (Rattus norvegicus) galur Sprague-Dawley 10−12 minggu dibagi dalam 6 kelompok yaitu kelompok yang mendapat bleomisin dan ciplukan (dosis 50,100,150, dan 200 mg/kg), bleomisin dan salin, dan kontrol negatif. Bleomisin diberikan subkutan per hari selama 14 hari dan ciplukan atau salin diberikan mulai hari ke-21 selama 30 hari lalu hewan diterminasi. Fibrosis dinilai dengan derajat fibrosis dan luas fibrosis pada histopatologi, kadar hidroksiprolin, TGF-β dan MMP13 jaringan paru. Pada tahap 2, 36 ekor tikus dibagi dalam 6 kelompok yaitu 2 kelompok yang mendapat bleomisin dan ciplukan (50 dan 100 mg/kgBB) dan 2 kelompok bleomisin dan salin. Tiga kelompok diterminasi di H14 dan 3 kelompok di H51. Pada tahap 2, bleomisin dan ciplukan diberikan bersamaan selama 14 hari pertama. Luaran yang dinilai di H14 adalah kadar IL-6 paru, jumlah leukosit dari BAL dan skor inflamasi paru secara histopatologi. Luaran yang dinilai di H52 adalah derajat fibrosis dan luas fibrosis, kadar hidroksiprolin, TGF-β dan MMP13 paru. Kadar IL-6, TGF-β dan MMP 13 dinilai dengan ELISA dari jaringan paru, Hidroksiprolin dinilai dari jaringan paru dengan metode kolorimetri. Pada tahap 1 terdapat perbedaan luas fibrosis yang secara statistik bermakna antara kelompok yang mendapat ciplukan dosis 100, 150, dan 200 mg/kgBB dibandingkan kelompok bleomisin. Tidak terdapat perbedaan skor fibrosis antara kelompok yang mendapat ciplukan 50, 100, dan 150 mg/kgBB dengan kontrol negatif. Tidak terdapat perbedaan hidroksiprolin antara kelompok yang mendapat ciplukan dengan kontrol negatif. Tidak terdapat perbedaan kadar TGF-β dan MMP13 yang secara statistik bermakna antar kelompok. Pada tahap 2 penelitian tidak didapatkan perbedaan kadar IL-6, jumlah leukosit cairan BAL dan skor inflamasi yang bermakna antar kelompok dan tidak terdapat perbedaan skor fibrosis, luas fibrosis, kadar hidroksiprolin, TGF-β dan MMP13 antar kelompok. Sebagai simpulan ekstrak ciplukan memiliki efek kuratif untuk menurunkan luas fibrosis paru dengan dosis optimal 100 mg/kgBB. Ciplukan tidak memiliki efek preventif terhadap inflamasi dan fibrosis.

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Systemic sclerosis or scleroderma is an immune mediated connective tissue disease which is manifested by fibrosis on skin and internal organ and vasculopathy. Interstitial lung disease (ILD) is the main cause of death of systemic sclerosis however the treatment of ILD in systemic sclerosis is still unsatisfactory. Ciplukan (Physalis angulata) herb is a potential alternative treatment for systemic sclerosis and has been proven to improve skin sclerosis in systemic sclerosis patients however the study on its effect on lung has been lacking. The aim of this study is to evaluate the effect of ciplukan herb for treating and preventing inflammation and fibrosis in systemic sclerosis animal model and to find out its optimal dose in improving lung fibrosis. This study was done in 2 stages. For the first stage (treatment of fibrosis), 33 Sprague-Dawley rats aged 10−12 weeks were divided into 6 groups (4 groups were given bleomycin and ciplukan extract dose 50,100,150, and 200 mg/kgBW, respectively, bleomycin and saline and negative control). Bleomycin was given subcutaneously daily for 14 days and ciplukan or saline were given from day 21 until the next 30 days and then the animals were sacrificed. At the end of observation, degree of fibrosis and width of fibrosis from lung histopathology, hydroxyproline, TGF-β, and MMP13 levels were analyzed. For the second stage (prevention), 36 rats were divided into 6 groups (bleomycin and ciplukan dose 50 and 100 mg/kgBW, and bleomycin only). Three groups were sacrificed after 14 days of observation for evaluation of IL-6 level in lung tissue, leucocyte count on BAL fluid and inflammation score. Three groups were sacrificed after 51 days observation and were analyzed for degree of fibrosis and width of fibrosis from lung histopathology, hydroxyproline, TGF-β, and MMP13 levels. For the second stage, bleomycin and ciplukan were given simultaneously for 14 days. IL-6, TGF-β, and MMP13 levels were measured using ELISA methods while hydroxyproline was analyzed using colorimetric method. From the stage 1, there was a significant reduction in width of lung fibrosis on groups receiving bleomycin and ciplukan dose 100, 150, and 200 mg/kgBW compared with bleomycin group. There was no difference of fibrosis score among groups who received ciplukan 50,100, and 150 mg/kgBW compared to the negative control. There was no difference of hydroxyproline among groups who received ciplukan compared with negative control. There was no difference of TGF-β, and MMP13 levels among groups. From the stage 2, there were no difference of IL-6 levels, BAL leukocyte count and inflammation score among groups after 14 days and no difference of fibrosis score, extension of fibrosis, hydroxyproline, TGF-β and MMP13 levels among groups after 51 days observation. As a conclusion, ciplukan herb has a role as a treatment of fibrosis to reduce extent of lung fibrosis with optimal dose of 100 kg/BW but shows no effect on prevention of lung inflammation and lung fibrosis."

"Latar Belakang: Jumlah kasus KPKBSK diperkirakan 85% dari seluruh kasus kanker paru dan 40% diantaranya adalah jenis adenokarsinoma. Sebanyak 10%-30% pasien adenokarsinoma mengalami mutasi EGFR dan mendapatkan terapi EGFR-TKI. Mayoritas pasien KPKBSK memiliki respons dan toleransi baik terhadap terapi EGFR- TKI tetapi sebagian kecil pasien mengalami penyakit paru interstisial akibat EGFR- TKI. Penelitian ini bertujuan untuk mengetahui proporsi gambaran penyakit paru interstisial pada pasien KPKBSK dengan terapi EGFR-TKI di RSUP Persahabatan.Metode: Penelitian ini merupakan penelitian observasional analitik dengan pendeketan kohort retrospektif yang dilakukan bulan Januari 2021 hingga Juni 2022. Subjek penelitian adalah pasien KPKBSK yang mendapatkan terapi EGFR-TKI. Subjek penelitian dipilih sesuai kriteria inklusi dan eksklusi. Pengambilan data melalu data sekunder berupa rekam medis dan hasil CT scan toraks pasien yang kontrol di poliklinik onkologi RSUP Persahabatan.Hasil: Pada penelitian ini diperoleh 73 subjek penelitian, pasien KPKBSK dengan mutasi EGFR yang mendapatkan terapi EGFR-TKI di RSUP Persahabatan. Sebanyak 12 dari 73 subjek penelitian mengalami gambaran ILD yang dievaluasi berdasarkan CT scan toraks RECIST I dan II dengan karakteristik jenis kelamin laki-laki (22,2%), kelompok usia 40-59 tahun (19,4%), perokok (24,1%), indeks brinkman berat (42,9%) dan mendapatkan terapi afatinib (26,1%). Proporsi gambaran ILD pada pasien KBPKBSK dengan terapi EGFR-TKI adalah opasitas retikular (58,3%), parenchymal band (33,3%), ground-glass opacities (25%), traction bronchiectasis (25%) dan crazy paving pattern (8,3%). Hasil analisis bivariat dan multivariat menunjukkan tidak terdapat perbedaan antara faktor-faktor seperti jenis kelamin, usia, jenis EGFR-TKI, riwayat merokok, indeks brinkman, riwayat penyakit paru dan tampilan status terhadap gambaran ILD.Kesimpulan: Gambaran ILD pada pasien KPKBSK dengan terapi EGFR-TKI meliputi opasitas retikular, parenchymal band, ground-glass opacities, traction bronchiectasis dan crazy paving pattern. Tidak terdapat perbedaan bermakna secara statistik antara faktor-faktor yang memengaruhi terhadap gambaran ILD.

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Background: The number of cases of NSCLC is estimated around 85% of all lung cancer cases and 40% among them are adenocarcinoma. Approximately 10%-30% of adenocarcinoma patients have EGFR mutations and receive EGFR-TKI therapy. The majority of NSCLC patients have a good response and tolerance to EGFR-TKI therapy, but a small group of patients experience EGFR-TKI induced interstitial lung disease. This study aims to determine the proportion of features of interstitial lung disease ini NSCLC patients treated with EGFR-TKI at Persahabatan Hospital.

Methods: This study was an analytic observational with a retrospective cohort approach that was conducted from January 2021 until June 2022. The subject were NSCLC patients who received EGFR-TKI treatment. The inclusion and exclusion criteria were used to determine which subjects will be included in the study. Data collection through secondary data from medical record and chest CT scan results of patients controlled at oncology polyclinic at Persahabatan Hospital.

Result : In this study, there were 73 subjects of NSCLC with EGFR mutations and received EGFR-TKI therapy at Persahabatan Hospital. There were 12 out of 73 subjects had ILD features which were evaluated based on RECIST I and II chest CT scan with predominant of male (22.2%), age group 40-59 years old (19.4%), smokers (24.1%), severe Brinkman index (42.9%) and received afatinib (26.1%). The proportion of ILD features in NSCLC patients with EGFR-TKI therapy are reticular opacities (58.3%), parenchymal bands (33.3%), ground-glass opacities (25%), traction bronchiectasis (25%) and crazy paving pattern (8.3%). The results of bivariate and multivariate analyzes showed that there was no differences between factors such as sex, age, type of GEFR-TKI, smoking history, Brinkman index, history of lung disease and performance status with features of ILD.

Conclusion: Features of ILD in NSCLC patients with EGFR-TKI therapy include reticular opacities, parenchymal bands, ground-glass opacities, traction bronchiectasis and crazy paving pattern. There is no statistically significa"