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A review of neurotoxicities associated with immunotherapy and a framework for evaluation.

Immuno-oncology agents, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T (CAR-T) cell therapies, are increasing in use for a growing list of oncologic indications. While harnessing the immune system against cancer cells has a potent anti-tumor effect, it can also cause widespread autoimmune toxicities that limit therapeutic potential. Neurologic toxicities have unique presentations and can progress rapidly, necessitating prompt recognition. In this article, we review the spectrum of central and peripheral neurologic immune-related adverse events (irAEs) associated

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… Additionally, headache is a presenting symptom of hypophysitis, which is categorized as an endocrine rather than neurologic irAE. 24 Main categories of reported CNS irAE syndromes include encephalitis, myelitis, demyelinating disease (including optic neuritis), meningitis, and vasculitis. 10 Encephalitis … MRI brain is also recommended, which can show leptomeningeal enhancement but is also important for ruling out other etiologies (e.g., vascular events, metastasis, hypophysitis). 24 , 32 Supportive CSF findings include pleocytosis (median WBC count 143, range 20–705 cells/uL in a 13-case series), elevated …

Emerging treatment options for the management of Hodgkin's lymphoma: clinical utility of nivolumab.

Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell. Enhancing antitumor immune response by targeting PD-1 with the monoclonal antibody

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… autoimmunity and, as could be anticipated, patients treated with nivolumab have demonstrated autoimmune reactions following treatment, termed immune-related AEs (IRAEs). 78 These IRAEs include acute hepatitis, colitis, dermatitis, pneumonitis, pancreatitis, and autoimmune endocrine disorders, including hypophysitis … treated with nivolumab to date, and clinicians should monitor thyroid function through routine thyroid-stimulating hormone measurement during treatment. 64 , 68 – 70 Although less commonly observed with PD-1 inhibitors than with CTLA-4 inhibitors, providers should be aware of the potential for autoimmune hypophysitis …

Демографическая точность в онкологических оврагах, клинических и генетических детерминантах системной терапии.

Токсичность при лечении сдерживает применение эффективных методов лечения рака, однако ее клинические и генетические детерминанты по-прежнему недостаточно четко определены. Мы разработали подход, основанный на большой языковой модели, для производства MSK-Tox, панракорного ресурса, фиксирующего частотность, временнóсть и сорт токсичности для антираковой терапии в большей степени, чем 50,000 Пациенты. Анализ six Репрезентативные неблагоприятные явления - пневмонит, адренальная недостаточность, токсичность для печени, колит, гипертироидизм и гипотироидозные отдельные токсические ландшафты, опред

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… For adrenal insufficiency, a further prompt was applied to positive batches to distinguish primary adrenal insufficiency, arising from direct adrenal injury, from secondary (central) adrenal insufficiency arising from hypophysitis ( Supplementary Note 3 ). … This distinction cannot be made from the detection call alone and is mechanistically relevant in the immune checkpoint inhibitor setting, where hypophysitis is a recognized cause of central adrenal insufficiency. Gold standard dataset description. …

Nuclear receptors Nor1 and NGFI-B/Nur77 play similar, albeit distinct, roles in the hypothalamo-pituitary-adrenal axis.

Studies in Nur77-deficient mice have shown that the basal regulation of hypothalamic and pituitary functions as well as the adrenocortical steroidogenesis in these animals is normal. This indicates that Nur77-related orphan receptors may substitute Nur77 functions in the hypothalamo-pituitary-adrenal axis by a compensatory mechanism. Nor1 is the most recently cloned member of the NGFI-B/Nur77 subfamily, and its properties are still largely unknown. We demonstrate here that Nor1 is expressed in the pituitary gland and adrenal cortex, and that ACTH and angiotensin II (AngII) treatment of adrenal

Changes in bone turnover markers in patients without bone metastases receiving immune checkpoint inhibitors: An exploratory analysis.

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome. A series of 4

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… Immune checkpoint inhibitor-associated hypophysitis World Health Organisation VigiBase report analysis Eur J Cancer 113 2019 10 13 30954881 10.1016/j.ejca.2019.03.002 8 Raschi E. Mazzarella A. Antonazzo I.C. …

Renal Involvement in Cancer Patients Undergoing Oncology Therapies: Implications for Personalized Treatment Strategies.

Introduction: Oncological therapies have significantly improved patient outcomes but are increasingly associated with renal toxicity, which can markedly influence therapeutic decisions. Integrating early identification of kidney injury into clinical workflows is essential for personalized medicine, allowing treatment tailoring based on individual risk profiles. Aim: To evaluate the incidence of acute kidney injury (AKI) and chronic kidney Disease (CKD); assess indices of renal function recovery in patients who developed AKI; and investigate the incidence of renal immune-related adverse events

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… Among the drugs most frequently associated with SIADH are platinum derivatives, alkylating agents (particularly cyclophosphamide), targeted therapies, immunotherapies, and vinca alkaloids [ 27 ], while immunotherapy may also induce hypophysitis [ 3 ]. …

Oncologic Emergencies: Immune-Based Cancer Therapies and Complications.

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse

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… common agents: anti-PD-1/PD-L1 therapy and anti-CTLA-4 inhibitor therapy | 1 | - Asymptomatic or mild symptoms | - No treatment needed | - Follow up with oncology and obtain outpatient endocrine referral 2–3 | - Evidence of endocrine dysfunctions with weakness, fatigue | - Treat based on condition - Hypophysitis … Adrenal crisis requires hydrocortisone 100 mg IV, as well as evaluation for infection, broad-spectrum antibiotics, and IV fluids with glucose. 2 , 35 – 40 , 48 Pituitary dysfunction, or hypophysitis, typically presents with symptoms of hypothyroidism but may also present with arthralgias, vision changes …

Автоантифиды острова во взрослом возрасте с перитуарной и оварской автономностью: последствия для типа 1 Скрининг диабета.

ЦЕЛЬ: Тип 1 диабет представляет собой хроническое аутоиммунное заболевание, характеризующееся постепенным разрушением поджелудочной клетки β-клеток и ранним появлением излетных автоантител (Islet-AAb) на предсимптомных этапах. Учитывая растущий интерес к скринингу и профилактике типа 1 Это исследование было направлено на оценку распространенности поджелудочной автоматической эмиссии у взрослых с другими аутентическими организмами, характерными для конкретных органов, с тем чтобы выявить потенциальные целевые группы для программ скрининга.МЕТОДЫ: Взрослые, прошедшие ранее проверку на наличие ав

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… Pituitary autoimmunity is most commonly reported in association with autoimmune thyroid diseases [ 14 ] and HLA‐DQ8, a genotype that also confers susceptibility to T1D, has been found to be frequent in patients with hypophysitis [ 27 ]. …

Diabetes Insipidus: A Pragmatic Approach to Management.

Diabetes insipidus (DI) is a disorder of water balance characterized by polyuria and polydipsia. It can occur due to genetic and acquired causes that affect the secretion or action of arginine vasopressin (AVP) or antidiuretic hormone (ADH).Markedly increased thirst and urination are not only quite distressing but also increases the risk of volume depletion and hypernatremia in severe situations. A careful diagnosis of the type of DI and its etiology is based on careful clinical evaluation, measurement of urine and serum osmolality, and water deprivation test. Management includes the correctio

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… Autoimmune – lymphocytic neurohypophysitis, xanthogranulomatous hypophysitis. Drugs and toxins – ethanol, snake venom, phenytoin Idiopathic. Acquired DI results when more than 80% of AVP-secreting neurons have been damaged. …

The Continuum of Thyroid Disorders Related to Immune Checkpoint Inhibitors: Still Many Pending Queries.

BackgroundUntil more data are available to shed light on the thyroid disorders related to immune checkpoint inhibitors (ICPi) implemented for the treatment of hematological malignancies, the decision-making is guided by pertinent data derived mostly from solid tumors.MethodsThe present review provides a comprehensive and updated overview of the thyroid disorders related to ICPi, namely to inhibitors of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death (PD) 1 (PD-1), and the ligand of the latter (PD-L1).ResultsWith the increasing recognition of ir thyroid disorders, many outstand

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… Another systematic review and meta-analysis showed that the hyperthyroidism of any grade ranks second among endocrine irAEs, following hypophysitis, affecting 100 patients (2.5%), while the hypothyroidism of any grade ranks third, affecting nine patients (0.2%). …

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust

[Polycystic ovary syndrome of extra-ovarian origin. Review].

An established fact in the polycystic ovarian syndrome (POS) is an abnormal ovarian steroidogenesis. Though this suggest an intrinsic ovarian defect, the syndrome could also be influenced by factors outside the ovaries. Although of unknown etiology, the POS is one of the most frequent endocrine disorders in the gynecologic practice. The disorder is characterized by ultrasound findings of enlarged polycystic ovaries, hyperandrogenism, menstrual disorders, obesity and including the appearance of infertility. There are a series of mechanisms involved in the extraovarian androgen increase in patie

Impact of Glucocorticoid Use in Oncology in the Immunotherapy Era.

Thanks to their anti-inflammatory, anti-oedema, and anti-allergy properties, glucocorticoids are among the most widely prescribed drugs in patients with cancer. The indications for glucocorticoid use are very wide and varied in the context of cancer and include the symptomatic management of cancer-related symptoms (compression, pain, oedema, altered general state) but also prevention or treatment of common side effects of anti-cancer therapies (nausea, allergies, etc.) or immune-related adverse events (irAE). In this review, we first give an overview of the different clinical situations where

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… Conversely, Faje et al., reported that the use of low-dose GCs to treat ipilimumab-induced hypophysitis was associated with longer survival, compared to high-dose GCs [ 154 ]. 3.3. … High-Dose Glucocorticoids for the Treatment of Ipilimumab-Induced Hypophysitis Is Associated with Reduced Survival in Patients with Melanoma Cancer 2018 124 3706 3714 10.1002/cncr.31629 29975414 155. Opzoomer J.W. Sosnowska D. Anstee J.E. Spicer J.F. Arnold J.N. …

Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy.

Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy. Serum sPDL1 was measured

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… Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. Journal of immunotherapy (Hagerstown, Md: 1997) 2007;30(8):825. doi: 10.1097/CJI.0b013e318156e47e. 12. Ott PA, Hodi FS, Robert C. …

Acupuncture in Multiple Myeloma Peripheral Neuropathy: A Systematic Review.

BackgroundPeripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN. This study aimed to conduct a comprehensive analysis of the literature to assess the effectiveness and safety of acupuncture as a treatment for MMPN.MethodsThe PubMed, Web of Science, MEDLINE, Cochrane Library, and Embase databases were comprehensively searched fr

Предварительная обработка сигнатуры эндокринного недоедания прогнозируют клиническую пользу от PD-1/PD-L1 Блокирование гематологовых магнатов.

Гематологические заболевания создают значительное бремя для здоровья людей во всем мире, а запрограммированная клеточная смертность protein-1 (В тыс.PD-1)/запрограммированный смертельный лиганж клеток 1 (В тыс.PD-L1) ингибиторы, революционизирующие лечение в подтипах, таких, как классическая лимфома Ходжкина (cHL) и первичная медистинальная лимфома В-клеток (PMBCL), достигающая высоких объективных показателей ответов (ORR). Однако эффективность варьируется в широких пределах, при этом успех в множестве миеломы ограничен.< 10% ORR) и лейкемии, подчеркивая необходимость лучшего прогнозирования,

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… Hypophysitis-induced secondary adrenal insufficiency (common irAE, incidence 5–15% with combination CTLA-4/PD-1 blockade) paradoxically does not worsen prognosis when promptly replaced with physiologic hydrocortisone, suggesting that supra-physiologic GC doses, not cortisol deficiency per se , drive …

Budesonide treatment for microscopic colitis from immune checkpoint inhibitors.

BackgroundImmune checkpoint inhibitors (CPIs) are effective against a variety of malignancies but can be limited by inflammatory toxicities such as enterocolitis. Enterocolitis is typically treated with systemically active glucocorticoids. Endoscopy can stratify patients by the severity of mucosal inflammation, including identifying patients with colitis in the absence of visible mucosal changes: microscopic colitis. Whether patients with CPI microscopic colitis could be managed differently from colitis with more severe mucosal involvement is unclear. The objective of this study was to describ

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… High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer. 2018;124(18):3706–3714. doi: 10.1002/cncr.31629. 19. Garcia-Neuer M, Marmarelis ME, Jangi SR, et al. …

Current and Future Role of Medical Imaging in Guiding the Management of Patients With Relapsed and Refractory Non-Hodgkin Lymphoma Treated With CAR T-Cell Therapy.

Chimeric antigen receptor (CAR) T-cells are a novel immunotherapy available for patients with refractory/relapsed non-Hodgkin lymphoma. In this indication, clinical trials have demonstrated that CAR T-cells achieve high rates of response, complete response, and long-term response (up to 80%, 60%, and 40%, respectively). Nonetheless, the majority of patients ultimately relapsed. This review provides an overview about the current and future role of medical imaging in guiding the management of non-Hodgkin lymphoma patients treated with CAR T-cells. It discusses the value of predictive and prognos

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… Machine Learning Defined Diagnostic Criteria for Differentiating Pituitary Metastasis From Autoimmune Hypophysitis in Patients Undergoing Immune Checkpoint Blockade Therapy. Eur J Cancer (2019) 119:44–56. 10.1016/j.ejca.2019.06.020 28. …

CNS Toxicity of Immunotherapy.

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… Toxicity | Toxicity grade | Imaging Features | Symptoms Hypophysitis | 3–4 [ 33 ] | MRI: Enlargement of pituitary gland/stalk and hypoenhancing nodules; heterogeneous enhancement [ 31 ] | Headaches, dizziness, diplopia, loss of peripheral vision and fatigue, nausea/vomiting [ 31 ] hyponatremia (diabetes …

The Rising Era of Immune Checkpoint Inhibitors in Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases characterized by ineffective hematopoiesis and a wide spectrum of manifestations ranging from indolent and asymptomatic cytopenias to acute myeloid leukemia (AML). MDS result from genetic and epigenetic derangements in clonal cells and their surrounding microenvironments. Studies have shown associations between MDS and other autoimmune diseases. Several immune mechanisms have been identified in MDS, suggesting that immune dysregulation might be at least partially implicated in its pathogenesis. This has led to rigorous inves

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… In their attempt to augment the immune response, PD-1 inhibitors can breach immunologic tolerance by upregulating autoreactive T-cells causing immune mediated reactions such as rash, pneumonitis, colitis, thyroiditis, hepatitis, nephritis, uveitis, adrenalitis, facial nerve paresis, hypophysitis, aseptic …