BACKGROUND:Immunotherapy based on anti-PD1 inhibitors has significantly improved survival in advanced melanoma. However, a significant proportion of patients do not benefit, and predicting response to immunotherapy remains an area of unmet need. Our group previously defined an immune signature able to predict response to anti-PD1 inhibitors in this scenario. METHODS:In this study, we analyzed two cohorts of patients with advanced melanoma treated with anti-PD1 inhibitors: the GEM cohort, previously used to validate our immune signature, and Campbell's cohort, which contains data about different immunotherapy schemes. Using the 107 genes that compose our immune signature and consensus clustering, samples were classified as immune-low or immune-high. Then, CIBERSORTx and Ecotyper were used to estimate the proportion of each immune cell type and carcinoma ecotypes in both cohorts. RESULTS:We confirmed that the immune-low group includes mostly patients who do not response to anti-PD1 inhibitors. We also studied the distribution of carcinoma ecotypes in the immune-high and immune-low groups defined by our immune classification. Ecotypes CE9 and CE10 clustered in the immune-high group, with good response to treatment. The use of combination immunotherapy improved response rate both in immune-low and immune-high tumors. The immune-high group contained a higher number of CD8 T cells, B memory cells and T follicular helper cells. CONCLUSIONS:Our immune-based classification defines an immune-low group of tumors with poor response to anti-PD1 inhibitors. This immune classification is related to carcinoma ecotypes. Finally, a use of a combo scheme improves the rates of response both in immune-high and low groups but in the case of immune-low tumors, our results suggests that a combo treatment approach could be an adequate strategy and should be further explored in these patients. Altogether, our results support the utility of our immune signature in the prediction of response to anti-PD1 inhibitors in advanced melanoma.
PURPOSE:This study aimed to evaluate the rate and severity of allergic events associated with the use of indocyanine green (ICG) in sentinel lymph node biopsy (SLNB) for patients with early-stage vulvar cancer. The research question focused on whether ICG administration poses a significant risk of allergic reactions, especially in patients with a history of allergies to iodinated contrast. METHODS:We conducted a retrospective study after prospective multicenter recruitment endorsed by the Spanish Investigational Network Gynecologic Oncology Group. Data on patient demographics, history of allergic reactions, and ICG administration were collected. A systematic literature review was performed to assess existing studies on ICG-related allergic reactions in SLNB. RESULTS:Among the 75 patients, 66 (75%) have been exposed to iodinated contrasts and 2 (3%) had a documented iodinated contrast allergy with a mild reaction. There were no intraoperative complications. During the postoperative period, there were only minor complications (15 (20.0%) grade I and 13 (17.3%) grade II of Clavien-Dindo classification), and none associated with the injection of ICG or allergen-based that could be related. The systematic review of 11 studies involved 206 patients and 354 groins. The history of allergy to iodinated contrast was not recorded in any of them. We observed no patients with adverse reactions related to this tracer after peritumoral injection. CONCLUSION:Our findings suggest that peritumoral ICG injection for SLNB in early-stage vulvar cancer could be safe. This study reinforces the potential for ICG to be a reliable tracer in vulvar cancer staging.
Abstract Background and Objective Cushing disease (CD) is characterized by impaired glucocorticoid negative feedback. In rare cases, patients exhibit glucocorticoid-induced positive feedback (GIPF), which may represent a distinct corticotroph adenoma phenotype. We aimed to investigate the prevalence, clinical and biochemical features, and surgical outcomes of GIPF in a large multicenter cohort. Design Retrospective cohort study from the SPAIN-CUSHING registry. Methods We included 139 patients with CD who had complete overnight 1-mg dexamethasone suppression test. GIPF was defined as a paradoxical cortisol response, corresponding to an increase of at least 25% in serum cortisol levels after dexamethasone compared with baseline. Clinical, biochemical, and radiological characteristics as well as surgical outcomes were compared between groups. Recurrence was evaluated in patients undergoing transsphenoidal surgery, with recurrence-free survival assessed by Kaplan–Meier analysis. Results Thirteen patients (9.3%) showed GIPF. These patients had lower BMI (26.4 vs 29.8 kg/m², P = .032), higher urinary free cortisol expressed as the upper limit of normal ratio (4.7 vs 2.8 ULN, P = .047), and a markedly greater ACTH response to desmopressin (525.0 vs 63.1 pg/mL, P = .022). Tumor size, proportion of macroadenomas, and cavernous sinus invasion did not differ. Despite this, after surgery remission was significantly lower in GIPF (28.6% vs 70.2%, P = .036), and Kaplan–Meier analysis showed reduced recurrence-free survival in GIPF patients (log-rank P = .04). Clinical phenotypes and comorbidities were otherwise similar. Conclusions GIPF occurs in up to 9% of patients with CD and is associated with poorer surgical outcomes and lower remission rates. This phenotype likely represents a distinct subtype of corticotroph adenoma, highlighting the need for closer follow-up and molecular characterization.
A standardized classification system was developed to harmonize the documentation of pharmaceutical interventions throughout the pharmacotherapeutic process in intensive care units caring for critically ill adult patients. The Intensive Care and Critical Patient Pharmacists Group (FarMIC) created an initial proposal, which was evaluated in a first phase through one week of intervention recording. After analyzing 168 interventions, modifications were made to improve applicability. In a subsequent phase, volunteer hospital pharmacists used the adapted classification for another week, documenting an additional 562 interventions. The analysis of discrepancies and suggestions allowed the consensus of a final classification comprising 35 types of interventions related to issues in indication, effectiveness, safety, and other aspects such as pharmacist consultations, therapeutic drug monitoring, and nutritional support. This classification provides a homogeneous framework that facilitates the standardization of pharmaceutical interventions in critically ill patients and promotes data comparability across centers.
