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1.
Expert opinion on pituitary complications in immunotherapy.
Briet, C, Albarel, F, Kuhn, E, Merlen, E, Chanson, P, Cortet, C
Annales d'endocrinologie. 2018;(5):562-568
Abstract
Hypophysitis is a frequent toxic endocrine side-effect of immunotherapy. Prevalence is higher with anti-CTLA-4 antibodies (4-20%) or in association with PD-1 inhibitors (8%). Diagnosis is presumptive, based on poorly specific clinical symptoms (usually, headache and asthenia) and/or hyponatremia and/or at least one pituitary deficit and/or abnormal imaging. Visual disorder or polyuropolydipsic syndrome are exceptional. In decreasing order of frequency, deficits are thyrotropic (86-100%), gonadotropic (85-100%) or corticotropic (50-73%); somatotropin deficit or abnormal prolactin level are rarer. Pituitary MRI in acute phase shows variable moderate increase in pituitary volume, ruling out differential diagnoses, especially pituitary metastasis. Treatment of corticotropin deficiency requires systematic emergency replacement therapy, with the usual modalities, while treatment of other deficits depends on clinical status and progression. Thyrotropin and gonadotropin deficits usually recover, but corticotropin deficiency persists over the long term, requiring education and specialized endocrinologic follow-up. Onset of hypophysitis does not contraindicate continuation of immunotherapy and does not usually require high dose synthetic glucocorticoids.
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Enteral immunonutrition versus enteral nutrition for gastric cancer patients undergoing a total gastrectomy: a systematic review and meta-analysis.
Cheng, Y, Zhang, J, Zhang, L, Wu, J, Zhan, Z
BMC gastroenterology. 2018;(1):11
Abstract
BACKGROUND Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes. METHODS Four electronical databases (Medline, EMBASE, Scopus and Cochrane library) were used to search articles in peer-reviewed, English-language journals. Mean difference (MD), Relative risk (RR), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The analysis was carried out with RevMan 5.3. RESULTS Seven studies involving 583 patients were eligible for the pooled analysis. EIN, when beyond a 7-day time-frame post-operatively (D ≥ 7), increased level of CD4+ (SMD = 0.99; 95% CI, 0.65-1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02-0.67; P = 0.04), the IgM (SMD = 1.15; 95% CI, 0.11-2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI, 0.55-1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32-1.06; P = 0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33-1.14; P = 0.0004). However, those increased effects were not obvious within a 7-day time-frame post-operatively (D < 7). The levels of CD8+ and other serum proteins except proalbumin were not improved both on D ≥ 7 and D < 7. Clinical outcomes such as systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40 to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14-0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and length of hospitalization (LHS) were not improved no matter what time after surgery. CONCLUSIONS EIN was found to improve the cellular immunity, modulate inflammatory reaction and reduce postoperative complication for GC patients undergoing radical gastrointestinal surgery. Exclusion of grey literature and non-English language studies was the key limitation in this study.
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How to predict and improve prognosis of food allergy.
Dahdah, L, Pecora, V, Riccardi, C, Fierro, V, Valluzzi, R, Mennini, M
Current opinion in allergy and clinical immunology. 2018;(3):228-233
Abstract
PURPOSE OF REVIEW The prevalence of food allergy is increasing. More children are being diagnosed with food allergies, and it is taking longer to outgrow them, among those who develop tolerance. The aim of this review is to draw the profile of the persistent food allergic, so that prevention strategies can be developed and active treatment set up. RECENT FINDINGS Many determinants are involved in food allergy prognosis: ethnicity and sex, type of food, innate immune system, eliciting dose, sensitization status and other biomarkers determination, gut microbiome composition, and the presence of comorbidities. Once identified, a persistent food allergy could be conveyed to active treatments, such as oral immunotherapy or the use of biologics, always taking into account their experimental nature. SUMMARY A better understanding of prognostic factors and phenotypes of food allergy is crucial in decision-making when it comes to food allergy prevention and management. A good classification of the allergic patient allows to determine the degree of exclusion diets and the timing of the reintroduction of avoided food when possible. In the cases of persistent and severe food allergy, many promising interventions are emerging which could improve prognosis and quality of care.
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Precision immunotherapy, mutational landscape, and emerging tools to optimize clinical outcomes in patients with classical myeloproliferative neoplasms.
Mughal, TI, Lion, T, Abdel-Wahab, O, Mesa, R, Scherber, RM, Perrotti, D, Mauro, M, Verstovsek, S, Saglio, G, Van Etten, RA, et al
Hematological oncology. 2018;(5):740-748
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Abstract
Following the 47th American Society of Hematology Meeting in 2005, the late John Goldman and Tariq Mughal commenced a conference, the 1st Post-ASH Workshop, which brought together clinicians and scientists, to accelerate the adoption of new therapies for patients with myeloproliferative neoplasms (MPNs). The concept began with recognition of the CML success story following imatinib therapy, the discovery of JAK2V617F , and the demonstration that BCR-ABL1-negative MPNs are driven by abnormal JAK2 activation. This review is based on the presentations and deliberations at the XIIth Post-ASH Workshop on BCR-ABL1 positive and negative MPNs that took place on December 12 to 13, 2017, in Atlanta, Georgia, immediately following the 59th American Society of Hematology Meeting. We have selected some of the translational research and clinical topics, rather than an account of the proceedings. We discuss the role of immunotherapy in MPNs and the impact of the mutational landscape on TKI treatment in CML. We also consider how we might reduce TKI cardiovascular side effects, the potential role of nutrition as adjunctive nonpharmacologic intervention to reduce chronic inflammation in MPNs, and novel investigational therapies for MPNs.
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Diagnosis and treatment of follicular lymphoma: an update.
Bargetzi, M, Baumann, R, Cogliatti, S, Dietrich, PY, Duchosal, M, Goede, J, Hitz, F, Konermann, C, Lohri, A, Mey, U, et al
Swiss medical weekly. 2018;:w14635
Abstract
Over the last few years, there have been many changes in the management of patients with follicular lymphoma, resulting in improvements in progression-free survival and quality of life. In addition to established regimens such as radiotherapy and immunochemotherapy, new treatment options are on the horizon. Furthermore, even the use of established chemotherapy agents has evolved, with new combinations moving to the forefront of the current treatment strategy. Nevertheless, there remains an unmet need for patients who have early relapses, those who are not responsive to anti-CD20 treatment regimens and for those in whom minimal residual disease persists even after immunochemotherapy. This review provides a summary of current developments in the diagnosis, treatment and management of follicular lymphoma, focusing on the clinical issues from a Swiss perspective.
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The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy.
Gopalakrishnan, V, Helmink, BA, Spencer, CN, Reuben, A, Wargo, JA
Cancer cell. 2018;(4):570-580
Abstract
The microbiome is receiving significant attention given its influence on a host of human diseases including cancer. Its role in response to cancer treatment is becoming increasingly apparent, with evidence suggesting that modulating the gut microbiome may affect responses to numerous forms of cancer therapy. A working knowledge of the microbiome is vital as we move forward in this age of precision medicine, and an understanding of the microbiome's influence on immune responses and cancer is key. It is also important to understand factors influencing the gut microbiome and strategies to manipulate the microbiome to augment therapeutic responses.
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Treg Fragility: A Prerequisite for Effective Antitumor Immunity?
Overacre-Delgoffe, AE, Vignali, DAA
Cancer immunology research. 2018;(8):882-887
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Abstract
Inhibitory checkpoint blockade has significantly improved patient response rate across numerous tumor types. However, most patients remain unresponsive to immunotherapy, suggesting that unappreciated mechanisms of resistance exist. The tumor microenvironment (TME) is unique and composed of many suppressive cell populations that inhibit antitumor immune responses, including regulatory T cells (Tregs). The TME is nutrient poor, acidic, and hypoxic, creating a challenging microenvironment for immune cells to function and survive. Tregs suppress a wide variety of cell populations through multiple mechanisms and are tasked with limiting tissue damage. Tregs are now considered to be a barrier to effective antitumor immunity. Systemic Treg depletion is not favored because of their critical role in maintaining immune homeostasis and preventing autoimmunity. Reducing Treg function specifically within the TME may provide a more effective, targeted approach to limit the immunosuppressive environment within the tumor without inducing systemic adverse consequences. Targeting molecules that cause Treg instability, characterized by loss of critical Treg transcription factors such as Foxp3, could result in conversion into cells that cause immune pathology, tissue damage, and subsequent autoimmune side effects. Interferon-γ (IFNγ) can cause intratumoral Treg "fragility," which results in loss of suppressive activity and increased IFNγ production without loss of Foxp3 expression and gross Treg "identity." We reviewed the impact Tregs have on the TME and vice versa, and their implications for responsiveness to cancer immunotherapy. We propose that the extent to which intratumoral Tregs develop a "fragile" phenotype following immunotherapy will predict and dictate responsiveness. Cancer Immunol Res; 6(8); 882-7. ©2018 AACR.
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AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer.
Jensen-Jarolim, E, Bax, HJ, Bianchini, R, Crescioli, S, Daniels-Wells, TR, Dombrowicz, D, Fiebiger, E, Gould, HJ, Irshad, S, Janda, J, et al
Allergy. 2018;(2):328-340
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Abstract
While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines.
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Expert opinion on immunotherapy induced diabetes.
Smati, S, Buffier, P, Bouillet, B, Archambeaud, F, Vergès, B, Cariou, B
Annales d'endocrinologie. 2018;(5):545-549
Abstract
Immunotherapy often incurs side-effects, mainly involving the skin, digestive tract and endocrine system. The most frequent endocrine side-effects involve the pituitary and thyroid glands. Cases of insulin-dependent diabetes, whether autoimmune or not (type 1 or 1B) have been reported with PD-1/PD-L1 inhibitors, alone or in association with anti-CTLA-4 antibodies, and were systematically associated with sudden-onset insulinopenia, frequently leading to ketoacidosis or fulminant diabetes, requiring first-line insulin therapy. This adverse effect has not so far been reported with anti-CTLA-4 monotherapy.
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Meta-Analysis of the Risk of Immune-Related Adverse Events With Anticytotoxic T-Lymphocyte-Associated Antigen 4 and Antiprogrammed Death 1 Therapies.
Komaki, Y, Komaki, F, Yamada, A, Micic, D, Ido, A, Sakuraba, A
Clinical pharmacology and therapeutics. 2018;(2):318-331
Abstract
We assessed the risks of immune-related adverse events with anticytotoxic T-lymphocyte-associated antigen 4 (CTLA4) and antiprogrammed death 1 (PD1) therapies by meta-analysis. Twenty-one studies including 11,144 patients were found. Anti-CTLA4 therapy was associated with a significantly higher risk of overall immune-related adverse events: diarrhea, immune-related colitis, pruritus, and rash compared to control therapies (relative risk (RR) = 2.43, 2.10, 11.39, 3.88, 3.87, 95% confidence interval (CI) = 1.77-3.34, 1.52-2.45, 6.30-20.59, 2.37-6.37, 2.39-6.27, P < 0.001 for all outcomes). Anti-PD1 therapy was associated with a significantly higher risk of pruritus (RR = 4.01, 95% CI = 1.97 to 8.17, P < 0.001); however, it did not increase the risks of other adverse events. Anti-CTLA4 and anti-PD1 therapies have distinct features of immune-related adverse events. The results of our study would aid the surveillance and management of immune-related adverse events in patients receiving these therapies.