Latar belakang.Wound dehiscenceadalah salah satu komplikasi bedah abdominal yang jarang ditemui, namun sering menyebabkan kematian, meningkatkan lama rawat, biaya, dan risiko infeksi berat dengan akibat kematian. Malnutrisi dianggap sebagai salah satu faktor yang berkontribusi terhadap kejadian dehiscencetersebut. Tujuan.Menilai angka kejadiandehiscencebedah mayor pada anak yang berbeda status gizi, risiko relatif serta faktor lain yang mempengaruhi risiko dehiscence.Metode. Penelitian kohort prospektif pada 262 kasus bedah abdominal mayor pada anak. Pasien yang memenuhi kriteria dibagi 2 kelompok yaitu menderita malnutrisi dan tidak. Tata laksana dilakukan sesuai standar Bagian Bedah Anak RSAB Harapan Kita. Pengamatan dilakukan selama periode perioperatif sampai pulang dari rumah sakit. Dihitung angka kejadian, risiko relatif, dan faktor atribusi dehiscence. Pengolahan data dan analisis menggunakan SPSS versi 11.5 dan Open Epi Hasil.Angka kejadian dehiscence2,7% (7/262), satu pasien gizi baik (0,8%), gizi kurang 2/7(1,7%), gizi buruk 4/4(100%). Terjadi pada hari kelima pasca operasi (kisaran 3-7hari). Lama rawat 25 hari (14-73) vs10 hari (1-10) tidak dehiscence. Meninggal dunia 1/7dehiscence. Risiko dehiscencemeningkat secara bermakna pada gizi buruk vsgizi baik (RR136, IK95% 19,3-958,6, p=0,000). Hipoalbumin vsnormal (RR23,6, IK95% 5,8-95,4, p=0,000). Anemia vsnormal (RR18,6, IK95% CI3.7-91.9, p=0,000). Sepsis vsnormal (RR10,7, IK95% 2,5-45,5, p=0,000). Faktor atribusi dehiscence99,3% karena gizi buruk, hipoalbumin 96,6%, sepsis 90,7%, gizi kurang 59%. Kesimpulan.Status gizi buruk, hipoalbumin, dan sepsis berperan hampir seratus persen terhadap kejadian dehiscencepada anak. Saran, perlu dilakukan skoring risiko tinggi dehiscencepada anak yang akan menjalani bedah mayor.

In the tumor microenvironment, ATP released by dying cells is converted to adenosine, a well-established potent suppressor of immune cell activity. The immune suppressive function of extracellular adenosine is mediated through two G-protein coupled receptors known as A2A and A2B. Both receptors are expressed on many types of immune cells. While A2B has traditionally been considered of less relevance compared to A2A due to lower affinity to its ligand adenosine, recent evidence suggests a specific role of A2B in immune suppressive myeloid cells in cancer. To determine whether a small molecule inhibitor which blocks both adenosine receptors on immune cells can be used as an immunotherapy to enhance anti-tumor immune responses, we initiated a discovery campaign to identify dual antagonist inhibitors of A2A and A2B. INCB106385 is a potent, selective and orally bioavailable dual antagonist of A2A and A2B receptors. In vitro, INCB106385 potently binds to both A2A and A2B receptors in the single-digit nanomolar range and antagonizes downstream signaling as measured by cAMP production in A2A and A2B expressing cells. In functional studies, INCB106385, in the presence of 50μM AMP, restores effector T cell activity as measured by interferon gamma (IFNγ) production. In vivo, INCB106385 inhibited both the downstream effector pCREB and tumor growth in CT26 and B16-F10 syngeneic tumor models. Furthermore, in in vitro and in vivo combination studies, INCB106385 and anti-PD-1/PD-L1 CPIs demonstrated an increase in T cell function and anti-tumor activity compared to the single agent treatment groups. These data suggests that inhibition of the adenosine pathway is non-redundant to current checkpoint inhibitor therapies and can be an effective combination strategy to enhance anti-tumor immune activities. In summary, the data presented in this study demonstrate that INCB106385 is a potent, selective and orally bioavailable A2A/A2B dual antagonist that can overcome the immune-suppressive effects of high levels of adenosine in the tumor microenvironment. INCB106385 can promote anti-tumor immunity as a monotherapy and in combination with anti-PD-1/PD-L1 treatment. Citation Format: Hui Wang, Alexandra Alexandra, Michael Hansbury, Jennifer Mason, Jennifer Harris, Christina Stevens, Christopher Maddage, Xiaodi Ren, Mingming Gao, Kerri Kurzeja-Lipinski, Gengjie Yang, Patricia Conlen, Kristine Stump, Patricia Feldman, Pramod Thekkat, Luping Lin, Maryanne Covington, Swamy Yeleswaram, Chao Qi, Xiaozhao Wang, Wenqing Yao, Sunkyu Kim, Susan Wee, Yingnan Chen, Holly Koblish. Discovery and characterization of INCB106385: a novel A2A/A2B adenosine receptor antagonist, as a cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB157.

Background: Long-gap Esophageal Atresia (LGEA) remains one of the most challenging congenital conditions. When primary anastomoses attempts had failed, esophageal replacement (ER) is indicated in these patients. Some infants with LGEA are born with other congenital anomalies, such as rectourethral fistula. In this study, we reported our experience in managing newborn with LGEA and rectourethral fistula. Case: A 1-day-old male neonate complained of unable to swallow any breast milk and presence of feces-like discharge from external urethral orifice within 24 hours after birth. Oral gastric tube was unable to pass into the stomach and x-ray examination revealed curled gastric tube in esophagus, and there wasn’t any bubble seen from patient’s stomach. Patient then was diagnosed with long gap esophageal atresia without fistula. Esophageal replacements using left colon interposition technique was performed as closing and final procedure.  Gastrostomy tube insertion, sigmoid colostomy, and cervical esophagostomy were immediately performed. Posterior sagittal anorectoplasty (PSARP) for patient’s recto-urethral fistula were performed six months after sigmoid colostomy. Patient was hospitalized with total of 32 days and gastric feeding tube can be removed three months after surgery. Conclusion: colon interposition can be safely used in long gap esophageal atreasia although patient had undergone previous colostomy repair. Long-term follow up will be needed. Further large-scale studies regarding this matter are necessary and hopefully comprehensive treatment can be established in the future.