Immunoregulatory effects of AFP domains on monocyte-derived dendritic cell function

<p>Abstract</p> <p>Background</p> <p>Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function.</p> <p>Results</p> <p>As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DR^high/CD11c^highand CD80⁺/CD86^highmolecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70).</p> <p>Conclusions</p> <p>D2- and D3- but not D1-AFP extensively suppresses the MDDC function. All the recombinant AFP proteins impaired the ability of MDDC to secrete IL-12.</p

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Terapi Nutrisi Pada Nefropati Diabetik, Gagal Jantung Kronik Nyha III, Karsinoma Serviks, Post Operasi Urs Bilateral, Replace Dj Stent

Nefropati Diabetik or Diabetic Kidney Disease (DKD) adalah Perubahan struktural dan fungsional patologis spesifik yang terlihat pada ginjal pasien Diabetes Mellitus (DM). Nefropati diabetik menyebabkan berbagai Perubahan pada kapiler dan arteri, penebalan membran endotel, trombosis dan inflamasi. Kondisi ini terlihat setelah satu atau dua tahun menderita DM. Diabetes mellitus juga dapat berkontribusi pada gagal jantung kronik dengan mekanisme sistemik, miokard, dan seluler. Semua faktor inilah yang dapat menyebakan malnutrisi. Ini adalah laporan kasus dari seorang wanita berusia 50 tahun, dengan keluhan tidak ada asupan oral yang didiagnosis dengan moderate protein energy malnutrition, nefropati diabetik, gagal jantung kronik NYHA III dengan karsinoma serviks dan pasca operasi URS Bilateral, Replace DJ Stent. Terapi nutrisi diberikan 720 kkal, ditingkatkan bertahap menjadi 2000 kkal sesuai kemampuan dan kondisi pasien, dengan komposisi 0,8-1 g / kg BB ideal / hari protein dan ekstrak ikan gabus, 45-50% karbohidrat dan 41-47% lemak diikuti dengan suplementasi seng (20 mg / hari), vitamin B kompleks, dan kurkumin. Terjadi peningkatan asupan energi dari 245 kkal menjadi 2.142,6 kkal diikuti dengan peningkatan hasil laboratorium seperti penurunan ureum / kreatinin (114 / 3,2 menjadi 84 / 2,05 mg / dl, penurunan leukosit (14.000 menjadi 7200 / µl), penurunan asam urat (13,1 hingga 7,3) mg / dl, penurunan kadar gula darah (199 menjadi 162 g / dl), peningkatan hemoglobin (6,7 hingga 8,2 g / dl), peningkatan kadar natrium (128 hingga 131 mmol / l) Kesimpulan: Terapi gizi yang adekuat selama 16 hari dapat memperbaiki kondisi, status metabolisme dan kualitas hidup pasien

Analisis Faktor Risiko Kanker Payudara pada RSU. Bahteramas Kota Kendari Provinsi Sulawesi Tenggara Tahun 2017

Menurut American Cancer Society (ACS) (2011) kanker payudara adalah tumor ganas yang menyerangsel-sel payudara.. Penelitian ini bertujuan untuk mengetahui faktor risiko status Menopouse, Riwayat lamapemberian ASI dan Merokok terhadap kejadian kanker payudara di RSU Bahteramas Kota Kendari ProvinsiSulawesi Tenggara Tahun 2016. Penelitian ini menggunakan rancangan penelitian analitik observasionalmenggunakan desain case control study dengan prosedur non matching. Populasi dalam penelitian ini 90pasien kanker payudara dengan jumlah sampel sebanyak 27 kasus dan 27 kontrol, pengambilan sampelmenggunakan teknik purposive sampling. statistik menggunakan uji Chi-squre pada tingkat kepercayaan 95%( =0,05). Hasil penelitian ini menunjukan bahwa perempuan dengan riwayat lama pemberian ASI(OR=7.188:95%CI 1.949– 26.511 ) merupakan Faktor Risiko kanker payudara. Dari hasil penelitian jugadiperoleh penyebab perempuan tidak memberikan ASI diantaranya adanya puting payudara yang tidakterbentuk sempurna, produksi ASI yang tidak lancar dan kesibukkan luar rumah yang menyebabkan tidakmemberikan ASI kepada anak. Sedangkan status menopouse (OR=2,841:95%CI 0,500-16.138) dan statusmerokok (OR=1,429:95%CI 04421– 4,627) bukan merupakan faktor resiko yang bermakna terhadap kejadiankanker payudara di RSU Bahteramas Kota Kendari Provinsi Sulawesi Tenggara