Academic literature on the topic 'Orhan KOMAÇ'

Malaria teruk atau ‘severe’ kebiasaannya disebabkan oleh jangkitan Plasmodium falciparum. Jangkitan Plasmodium falciparum pada manusia boleh menyebabkan kerosakan organ, anemia teruk, komplikasi serius, koma dan kematian. Bagi tujuan memahami patogenesis malaria teruk, model haiwan digunakan dalam kajian kali ini bagi mengenal pasti sama ada gabungan hos-parasit daripada mencit ICR dengan Plasmodium berghei NK65 boleh menyebabkan jangkitan malaria teruk pada hos. Pencirian jangkitan P. berghei ANKA pernah dilakukan sebelum ini terhadap mencit ICR; walau bagaimanapun, pencirian jangkitan P. berghei NK65 secara terperinci terhadap mencit ICR dalam kajian ini adalah pertama kali dilaporkan. Inokulasi sel darah merah (RBC) terjangkit-P. berghei NK65 (2 ´ 107 parasit RBC (pRBC)/mL) dilakukan terhadap mencit ICR dengan suntikan secara intraperitoneum. Pemantauan perubahan ciri fizikal seperti berat, suhu mencit, kematian mencit, pos mortem, histologi dan aras sitokin inflamasi yang terhasil selepas jangkitan direkod untuk analisis. Strain P. berghei NK65 menghasilkan jangkitan tahap teruk terhadap mencit ICR iaitu paras parasitemia melebihi 50% pada hari ke-10 selepas jangkitan diikuti kematian. Analisis histopatologi menunjukkan jangkitan ini menyebabkan perubahan pada tisu serebrum, perlekatan leukosit pada endotelium dan pensekuesteran pRBC dalam salur darah serebrum serta pendarahan intravaskular. Selepas jangkitan, pensekuesteran pRBC dan pengumpulan pigmen malaria turut dilihat pada organ utama mencit. Tambahan lagi, edema pulmonari, pembentukan membran hialin pada peparu dan pendarahan kortikal pada ginjal dilihat pada mencit terjangkit. Sitokin proinflamasi (TNF-α, IFN-γ, dan IL-18) dan sitokin antiinflamasi (IL-10 dan IL-4) juga meningkat dalam serum mencit terjangkit. Secara rumusannya, model jangkitan mencitICR-P. berghei NK65 yang digunakan dalam kajian ini menunjukkan ciri-ciri jangkitan malaria teruk. Hasil daripada kajian ini boleh digunakan sebagai asas untuk memahami patogenesis bagi malaria teruk pada manusia dan model jangkitan malaria haiwan pada masa akan datang.

Disfungsi tiroid sering dijumpai pada populasi perempuan usia masa reproduksi. Efek disfungsi tiroid bermanifestasi pada berbagai organ dan mungkin menimbulkan komplikasi pembedahan dan kehamilan. Seorang perempuan 37 tahun dengan hipotiroid akan menjalani seksio sesarea. Kadar tiroid timulating hormone (TSH): dan tiroksin (T4) adalah 14,87 µUI/mL dan 71 nmol/L. Pasien mendapat terapi levotiroksin selama 6 minggu. Pada pemeriksaan fisik, pasien dalam keadaan umum baik. Anestesia spinal dilakukan dengan bupivakain 0,5% 7,5 mg dan fentanyl 25 µg. Bayi lahir dengan skor Apgar 8/9, hemodinamik stabil selama operasi. Pasien pulang dari rumah sakit setelah hari ke tiga operasi. Pasien hipotiroid dapat mengalami komplikasi koma miksedema, gangguan respirasi, maupun hipotensi selama pembedahan. Pembedahan elektif sebaiknya ditunda sampai kondisi eutiroid. Anestesia spinal dosis rendah, monitoring adekuat, pencegahan hipotermia, pengurangan opioid, dan terapi levotiroksin perioperatif dibutuhkan untuk mencegah komplikasi jika kondisi eutiroid belum tercapai. Sebagai kesimpulan anestesia spinal dapat dilakukan pada pasien hipotiroid yang menjalani seksio sesarea. Anesthesia for Cesarean Section in Hypothyroid Patient Abstract Thyroid disfunction is common in woman of child-bearing age population. Multiple organ are influenced with thyroid dysfunction and may contribute to complication during surgery and pregnancy. A 37-years-old female with hypothyroid was scheduled for cesarean section. Thyroid stimulating hormone (TSH) and thyroxine (T4) level was 14,87 µUI/mL and 71 nmol/L. The patient had levothyroxine therapy for 6 weeks. On physical examination, the general condition was good. She underwent spinal anesthesia with bupivacaine 0,5% 7,5 mg and fentanyl 25 µg. The baby was born with Apgar score 8/9 and the surgery was done without any complication. The patient was discharged from the hospital on the 3rd day after surgery. The hypothyroid patient may experience complication of myxedema comatous, respiratory disorder and hypotension during surgery. The elective surgery was best postponed until a euthyroid state was achieved. Low dose spinal anesthesia, adequate monitoring, hypothermia prevention, reducing opioid dose and continuing levothyroxine therapy was needed to prevent the complication if the euthyroid state was able not able to achieve. As conclusion : spinal anesthesia may be done for cesarean section in hypothyroid patient.

Abstract Introduction: COVID-19 vaccination substantially reduces morbidity and mortality associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe illness. However, despite effective COVID-19 vaccines many questions remain about the efficacy of vaccines and the durability and robustness of immune responses, especially in immunocompromised persons. The NCI-funded Serological Sciences Network (SeroNet) is a coordinated effort including 11 sites to advance research on the immune response to SARS-CoV-2 infection and COVID-19 vaccination among diverse and vulnerable populations. The goals of the Pooling Project are: (1) to conduct real-world data (RWD) analyses using electronic medical records (EMR) data from four health care systems (Kaiser Permanente Northern California, Northwell Health, Veterans Affairs-Case Western, and Cedars-Sinai) to determine vaccine effectiveness in (a) cancer patients; (b) autoimmune diseases and (c) solid organ transplant recipients (SOTR); (2) to conduct meta-analyses of prospective cohort studies from eight SeroNet institutions (Cedars-Sinai, Johns Hopkins, Northwell Health, Emory University, University of Minnesota, Mount Sinai, Yale University) to determine post-vaccine immune responses in (a) lung cancer patients; (b) hematologic cancers/hematopoietic stem cell transplant (HSCT) recipients; (c) SOTR; (d) lupus. Methods: For our RWD analyses, data is extracted from EMR using standardized algorithms using ICD-10 codes to identify immunocompromised persons (hematologic and solid organ malignancy; SOTR; autoimmune disease, including inflammatory bowel disease, rheumatoid arthritis, and SLE). We use common case definitions to extract data on demographic, laboratory values, clinical co-morbidity, COVID-19 vaccination, SARS-CoV-2 infection and severe COVID-19, and disease-specific variables. In addition, we pool individual-level data from prospective cohorts enrolling patients with cancer and other immunosuppressed conditions from across network. Surveys and biospecimens from serology and immune profiling are collected at pre-specified timepoints across longitudinal cohorts. Results: Currently, we have EMR data extracted from 4 health systems including >715,000 cancer patients, >9,500 SOTR and >180,000 with autoimmune conditions. Prospective cohorts across the network have longitudinal data on >450 patients with lung cancer, >1,200 patients with hematologic malignancies, >400 SOTR and >400 patients with lupus. We will report results examining vaccine effectiveness for prevention of SARS-CoV-2 infection, severe COVID-19 and post-acute sequelae of COVID-19 (PAS-C or long COVID) in cancer patients compared to other immunocompromised conditions. Conclusion: Our goal is to inform public health guidelines on COVID-19 vaccine and boosters to reduce SARS-CoV-2 infection and severe illness in immunocompromised populations. Citation Format: Elham Kazemain, Jane Figueiredo, Jacek Skarbinski, Russell McBride, Viviana Simon, Amy B. Karger, F. Eun-Hyung Lee, Fred R. Hirsch, Andrea Cox, Sabra Klein, Rong Fan, Stephanie Halene, David A. Zidar, James M. Crawford, Bharat Thyagarajan, Charles Gleason, Alex Mathson, Komal Srivastava, Puleng Moshele, Toby Amoss, Martin Runnstrom, Susanne Linderman, Ananda M. Rodilla, Philip C. Mack, Yu Shyr, Anna Yin, Patrick Shea, Jennifer VanOudenhove, Hinnah Siddiqui, Brigid M. Wilson, Eric P. Elkin, Crystal A. Hsiao, Yonah Ziemba, Cheryl B. Schleicher, Sharon Fox, Lawrence H. Kushi, Karen Reckamp, Akil Merchant, Noah Merin. SeroNet Pooling Project of immunocompromised populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 798.

Abstract Background: Extended release onapristone (onapristone ER) is a progesterone receptor (PR) antagonist that inhibits hormone-mediated PR activation and stabilizes PR association with corepressors, resulting in an antineoplastic effect when applied alone or in combination with antiestrogen therapy to breast cancer cells in vitro. Recent preclinical studies further suggest that onapristone adds to inhibition of cell proliferation when combined with CDK4/6 inhibitors and fulvestrant. Elevations in ctDNA can precede overt disease progression by a matter of months in metastatic breast cancer and may represent an opportunity for proactive therapeutic intervention. Trial Design: This is an investigator initiated open-label, single institution phase 1b study of onapristone ER added as escalation therapy in patients with ER+, PR+, HER2 negative MBC, who have detectable ctDNA after six months of treatment with letrozole and palbociclib in the first line. The study is supported by Context Therapeutics and will involve two stages. Stage 1 is a dose escalation/de-escalation phase of 18 patients maximum, in which the safety and recommended phase 2 dose (RP2D) will be established for onapristone ER when used in combination with letrozole and palbociclib. In stage 2, the dose expansion phase, the RP2D of onapristone will be combined with letrozole and palbociclib in 10 patients to further explore the tolerability of the regimen. ctDNA will be collected serially while patients are on this triplet therapy. Eligibility Criteria: This study will enroll patients with radiologically measurable or evaluable metastatic or unresectable ER+/PR+/HER2-negative MBC in whom a tumor-derived somatic mutation can be detected in ctDNA at a variant allele fraction of 0.5% or greater after 6 months (+/- 4 weeks) of treatment with first line letrozole and palbociclib without progression, using our in house CLIA certified MSK-ACCESS assay. Adequate organ function and functional status for enrollment are stipulated in the protocol. Specific Aims: The primary objective of this study is to define the safety, tolerability, and recommended phase 2 dose of onapristone ER used in combination with letrozole and palbociclib. Secondary objectives include to investigate ctDNA response rate of the triplet therapy regimen, to gather early data regarding the 6-month clinical benefit rate , overall response rate , and progression free survival of this triplet escalation therapy regimen in high risk ctDNA+ patients, and to evaluate the pharmacokinetics of Onapristone ER when used in combination with letrozole and Palbociclib. Exploratory objective include to describe ctDNA dynamics during antiprogestin therapy escalation in ER+ MBC, as well as the molecular features present in responders vs. non-responders using ctDNA and pre-treatment tissue. Target Accrual: The total planned cohort for the phase I dose escalation is a maximum of 18 patients across 3 dose levels, and the total planned cohort for the dose expansion is 10 patients, with an anticipated maximum total of 28 patients. We will allot for 5 additional patients to account for inevaluability during the dose escalation and expansion portions of the trial. The trial will be open to enrollment at MSKCC in July 2021. Citation Format: Joshua Z Drago, Elaine M Walsh, Mithat Gonen, Michael F Berger, Mark E Robson, Sarat Chandarlapaty, Pedram Razavi, Komal Jhaveri. Circulating tumor DNA-guided adaptive therapy escalation in ER+ MBC: A phase 1b study with letrozole, palbociclib and onapristone ER [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-04-01.

Abstract ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study with Letrozole, Palbociclib and Onapristone ER Background: Extended release onapristone (onapristone ER) is a progesterone receptor (PR) antagonist that inhibits hormone-mediated PR activation and stabilizes PR association with corepressors, resulting in an antineoplastic effect when applied alone or in combination with antiestrogen therapy to breast cancer cells in vitro. Recent preclinical studies further suggest that onapristone adds to inhibition of cell proliferation when combined with CDK4/6 inhibitors and fulvestrant. Elevations in ctDNA can precede overt disease progression by a matter of months in metastatic breast cancer and may represent an opportunity for proactive therapeutic intervention. Trial Design: This is an investigator initiated open-label, single institution phase 1b study of onapristone ER added as escalation therapy in patients with ER+, PR+, HER2 negative MBC, who have detectable ctDNA after six months of treatment with letrozole and palbociclib in the first line. The study is supported by Context Therapeutics and involves two stages. Stage 1 is a dose escalation/de-escalation phase of 18 patients maximum, in which the safety and recommended phase 2 dose (RP2D) will be established for onapristone ER when used in combination with letrozole and palbociclib. In stage 2, the dose expansion phase, the RP2D of onapristone will be combined with letrozole and palbociclib in 10 patients to further explore the tolerability of the regimen. ctDNA will be collected serially while patients are on this triplet therapy. Eligibility Criteria: This study is enrolling patients with radiologically measurable or evaluable metastatic or unresectable ER+/PR+/HER2-negative MBC in whom a tumor-derived somatic mutation can be detected in ctDNA at a variant allele fraction of 0.5% or greater after 6 months (+/- 4 weeks) of treatment with first line letrozole and palbociclib without progression, using our in house CLIA certified MSK-ACCESS assay. Adequate organ function and functional status for enrollment are stipulated in the protocol. Specific Aims: The primary objective of this study is to define the safety, tolerability, and recommended phase 2 dose of onapristone ER used in combination with letrozole and palbociclib. Secondary objectives include to investigate ctDNA response rate of the triplet therapy regimen, to gather early data regarding the 6-month clinical benefit rate, overall response rate, and progression free survival of this triplet escalation therapy regimen in high risk ctDNA+ patients, and to evaluate the pharmacokinetics of Onapristone ER when used in combination with letrozole and Palbociclib. Exploratory objective include to describe ctDNA dynamics during antiprogestin therapy escalation in ER+ MBC, as well as the molecular features present in responders vs. non-responders using ctDNA and pre-treatment tissue. Target Accrual: The total planned cohort for the phase I dose escalation is a maximum of 18 patients across 3 dose levels, and the total planned cohort for the dose expansion is 10 patients, with an anticipated maximum total of 28 patients. We will allot for 5 additional patients to account for inevaluability during the dose escalation and expansion portions of the trial. The trial is currently open to enrollment at MSKCC. Contact Information: Dragoj@mskcc.org; Jhaverik@mskcc.org Citation Format: Joshua Drago, Elaine Walsh, Mithat Gonen, Michael Berger, Mark E. Robson, Sarat Chandarlapaty, Pedram Razavi, Komal Jhaveri. ctDNA-guided Adaptive Therapy Escalation in ER+ MBC: A Phase 1b Study with Letrozole, Palbociclib and Onapristone ER [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-01-11.

Amaç: Akdeniz Üniversitesi Tıp Fakültesi hastanesi Türkiye'nin önemli organ nakil merkezlerinden biridir. Bu çalışmada erişkin yoğun bakım ünitesinde (YBÜ) beyin ölüm oranı, izlemi, donör bakımı ve organ bağışı ile ilgili deneyimlerin paylaşılması amaçlanmıştır. Gereç ve Yöntemler: Akdeniz Üniversitesi Tıp Fakültesi Anestezi ve Yoğun Bakım Ünitesinde Ocak 2003-Aralık 2016 tarihleri arasında beyin ölümü tanısı alan hastaların kayıtları retrospektif olarak incelendi. Bu kayıtlarda hastaların demografik özellikleri, başvuru tanıları, yoğun bakım koma skorları, laboratuvar değerleri, değerlendirme tetkiklerinin yöntem ve süreleri, konsültasyon süreleri ve sevk bilgileri yer almaktadır. Bulgular: Çalışmamıza 136 (%66) erkek, 71 (%34) kadın hasta dahil edildi. Başvuru tanısında intrakraniyal kanama ilk sırada yer aldı. Bunu 56 (%27,05) ile subaraknoid kanama (SAK)ve 42 (%20,28) ile intraparankimal kanama izledi. Doğrulayıcı testler arasında SPECT (tek foton emisyonlu bilgisayarlı tomografi) ilk sırada yer aldı, 70 hastada (%33,81) kullanıldı. Serebral ölüm sonrası 27 (%13.04) hastada spinal refleks gözlendi. İki hastada (%0,96) Lazarus bulgusu vardı. Yetmiş bir (%34,29) hastada sempatik fırtına gelişti. Hastaların 122'sinde (%58,93) diabetes insipidus gelişti ve tüm hastalar medikal tedavi aldı. Ayrıntılı kayıtları bulunan 207 beyin ölümü vakasının 66'sı (%31,4) organlarını bağışladı. Sonuç: Organ nakli hastalarında güven ortamı oluşturmak için ortak bir tanı protokolü gereklidir. Bu alanda daha fazla klinik araştırmaya ihtiyaç olduğunu yineliyoruz.

Abstract Objectives: Diagnosis of brainstem death and the vital organ function support in the pregnant woman to prolong gestation to attain fetal viability is still controversial. The decision is influenced by ethical and legal issue in the country. Another consideration is the hospital cost and health insurance coverage. This article purpose is to report a case and discuss the biopsychosocial aspect of this issue, so the doctors know how to decide a similar case.Methods: We reported a suspected brainstem death in pregnant women and discussed the holistic approach.Case: This case is a-38-year-old women, third pregnancy, 22 weeks of gestation, referred from the secondary hospital in a comatose condition. She was diagnosed with brainstem dysfunction due to intracranial mass and cerebral oedema. She wasn't diagnosed with brainstem death due to the electrolyte imbalance that can cause this condition. We did the multidisciplinary management approach. We decided the termination of pregnancy would only be performed if the fetus reaches 28 weeks of gestational age (with survival rate on perinatology is 31%). From the husband point of view, since the attending doctors have not declared the mother to be dead, then the husband still want to keep the mother in full life support. The patient and the fetus died on the 8th day of hospitalization. The patient was fully paid for by Indonesian Health Insurance.Conclusion: Maternal brainstem dysfunction and brainstem death during pregnancy are rare. In Indonesia, ethical and legal consideration to keep both mother and fetus are appropriate with the general social, cultural, and religious values. However, we recommend managing every single case individually with an intensive multidisciplinary approach due to the possibility of the different personal value of the patient.Keywords: brainstem dysfunction, brain death, pregnancy, fetal, ethic, legal. Abstrak Tujuan: Diagnosis kematian batang otak dan dukungan fungsi organ vital pada perempuan hamil untuk melanjutkan kehamilannya sampai janin dapat hidup jika dilahirkan masih kontrovesi. Keputusan ini dipengaruhi oleh etik dan hukum di suatu negara. Pertimbangan lainnya adalah biaya perawatan rumah sakit dan cakupan asuransi kesehatan. Artikel ini bertujuan melaporkan sebuah kasus dan mendiskusikan aspek biopsikososialnya, sehingga para dokter dapat mengambil keputusan pada kasus lain yang serupa.Metode: Kami melaporkan kasus perempuan hamil dengan kecurgaan kematian batang otak dan mendiskusikan pendekatan holistiknya.Hasil: Kasus perempuan usia 38 tahun, kehamilan ketiga, 22 minggu, dirujuk dari rumah sakit sekunder dalam kondisi koma. Pasien didiagnosis dengan disfungsi batang otak akibat massa intracranial dan edema serebri. Pasien tidak didiagnosis dengan meti batang otak karena kondisi ini masih dapat dikarenakan gangguan keseimbangan elektrolit. Kami melakukan pendekatan multidisiplin. Diputuskan terminasi kehamilan akan dilakukan hanya jika janin mencapai usia kehamilan 28 minggu (dengan harapan hidup dari perinatology 31%). Dikarenakan dokter belum mengatakan pasien sudah meninggal, suami pasien menginginkan pasien dalam topangan alat. Pasien dan janinnya meninggal pada hari ke-8 perawatan. Pembiayaan pasien dengan menggunakan BPJS.Kesimpulan: Disfungsi batang otak dan kematian batang otak selama kehamilan adalah kasus yang jarang. Di Indonesia, etik dan hukum yang berlaku untuk menjaga kehidupan ibu dan janin sesuai dengan nilai sosial, budaya, dan agama. Namun demikian, kami merekomendasikan mlakukan tata laksana setiap kasus secara individu dengan pendekatan multidisiplin dikarenakan perbedaan nilai pribadi pasien dan keluarga.Kata kunci: disfungsi batang otak, etik, hukum, janin, mati batang otak, kehamilan.