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Purpose: The quality, rather than the quantity, of carbohydrate intake may play a major role in the etiology of obesity-related cancers (ORCs). We assessed the association between a previously defined carbohydrate quality index (CQI) and the risk of developing ORCs in the "Seguimiento Universidad de Navarra" (SUN) cohort., Methods: A total of 18,446 Spanish university graduates [mean age 38 years (SD 12 years), 61% women, mean BMI 23.5 kg/m 2 (SD 3.5 kg/m 2 )], with no personal history of cancer, were followed-up. Baseline CQI was assessed summing quintiles of four previously defined criteria: high dietary fiber intake, low glycemic index (GI), high whole-grain: total-grain carbohydrates ratio and high solid carbohydrates: total carbohydrates ratio. Participants were classified into tertiles of their total CQI. Incident ORCs were confirmed by an oncologist using medical records and by querying the National Death Index blindly to dietary exposures., Results: During a median follow-up of 13.7 years, 269 incident cases of ORC were confirmed. A higher CQI was inversely associated with ORC incidence [multivariable-adjusted hazard ratio (HR) for the upper (T3) versus the lowest tertile (T1) of 0.68 (95% CI: 0.47-0.96), p for trend = 0.047]. Particularly, higher dietary fiber intake was inversely associated with ORC, HR T3 vs. T1 =0.57 (95% CI 0.37-0.88 p for trend = 0.013)., Conclusion: In this prospective Mediterranean cohort, an inverse association between a better global quality of carbohydrate intake and the risk of ORCs was found. Strategies for cancer prevention should promote a higher quality of carbohydrate intake., (© 2024. The Author(s).)

Background: Anaphylaxis is the most acute and life-threatening manifestation of allergic disorders. Currently, there is a need to improve its medical management and increase the understanding of its molecular mechanisms. This study aimed to quantify the extravasation underlying human anaphylactic reactions and propose new theragnostic approaches., Methods: Molecular determinations were performed in paired serum samples obtained during the acute phase and at baseline from patients presenting with hypersensitivity reactions. These were classified according to their severity as Grades 1, 2 and 3, the two latter being considered anaphylaxis. Tryptase levels were measured by ImmunoCAP, and serum protein concentration was quantified by Bradford assay. Human serum albumin (HSA) and haemoglobin beta subunit (HBB) levels were determined by Western blot and polyacrylamide gel electrophoresis, respectively., Results: A total of 150 patients were included in the study. Of them, 112 had experienced anaphylaxis (83 and 29 with Grade 2 and 3 reactions, respectively). Tryptase diagnostic efficiency substantially improved when considering patients' baseline values (33%-54%) instead of the acute value threshold (21%). Serum protein concentration and HSA significantly decreased in anaphylaxis (p < .0001). HSA levels dropped with the severity of the reaction (6% and 15% for Grade 2 and 3 reactions, respectively). Furthermore, HBB levels increased during the acute phase of all hypersensitivity reactions (p < .0001)., Conclusions: For the first time, the extravasation underlying human anaphylaxis has been evaluated based on the severity of the reaction using HSA and protein concentration measurements. Additionally, our findings propose new diagnostic and potential therapeutic approaches for this pathological event., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Lipid transfer proteins (LTPs) syndrome is an important cause of multiple plant food allergy in the Mediterranean area. The effectiveness of sublingual immunotherapy (SLIT) with the LTP Pru p 3 extract has been little investigated in the real-world setting. This study aimed to investigate the outcome of Pru p 3 SLIT in real-life patients with LTP syndrome with/without concurrent reactions to peanut and/or nuts., Methods: This was a prospective real-life study including all patients diagnosed with LTP allergy and treated with Pru p 3 SLIT between 2011 and 2018 in a tertiary hospital in Spain. Patients underwent open oral food challenge (OFC) tests for unpeeled peach and nuts/peanuts 1 year after the treatment started to assess food tolerance. A control group of patients diagnosed with LTP allergy who refused treatment with immunotherapy were included. Severity of symptoms and diet avoidance was recorded in both groups., Results: Twenty-nine patients with a median age of 24.7 years (range 5.5-43.1) were included: 100% were allergic to fruit; 72%, to peanut and/or nuts; 19 had a history of severe systemic reactions. Seven patients discontinued therapy; 3 (10%), due to adverse events. One year after SLIT start, 16 (73%) patients had negative OFC to peach; 95%, after 2 years; 69% had negative OFC to nuts/peanuts. The control group included 13 patients: 53.8% experienced reactions with new foods; severity of symptoms increased significantly (p < 0.001), and diet restrictions were maintained in this group., Conclusions: SLIT with Pru p 3 shows a good safety profile, and avoid dietary restrictions in patients with LTP syndrome treated in the real-life setting., (© 2021 S. Karger AG, Basel.)

Introduction: Polcalcins belong to the family of calcium-binding proteins. They are ubiquitous in the plant kingdom and highly conserved, which leads to these panallergens showing a high degree of inter-cross-reactivity. They are responsible for allergic polysensitization, and therefore, their diagnosis is necessary for correct selection of immunotherapy. The objectives were to develop a method to purify native polcalcin with intact allergenic properties and to validate its use for diagnosis of polcalcin sensitization., Methods: Ole e 3 was purified by immunoaffinity chromatography using anti-rChe a 3 polyclonal antibodies and identified by mass spectrometry. Calcium-binding assays were performed in immunoblot and ELISA assays. Diagnostic capacity of Ole e 3 was analyzed by ELISA and compared to ImmunoCAP with sera from a pollen-sensitized population. Cross-reactivity with other polcalcins was investigated by ImmunoCAP inhibition., Results: Immunogenicity of purified Ole e 3 was not affected by the addition of calcium. However, the presence of a calcium chelator agent completely inhibited IgG binding by immunoblot and produced a 32.3% reduction in IgE binding by ELISA. Ole e 3 enabled diagnosis of polcalcin-sensitized patients, and a good correlation was revealed with ImmunoCAP. A 50% inhibition in IgE binding was obtained with 2.8 ng of Ole e 3 for rBet v 4 and 3.9 ng for rPhl p 7., Discussion/conclusion: Native Ole e 3 was purified by maintaining its allergenic properties. This innovative method enables obtaining this active native allergen to be used for in vivo diagnosis of polcalcin sensitization., (© 2021 S. Karger AG, Basel.)

Background: Anaphylaxis includes mast cell (MC) activation, but less is known about downstream mechanisms (ie, vascular permeability controlled by endothelial cells [ECs]). The TNF-like weak inducer of apoptosis (TWEAK) and its sole receptor, fibroblast growth factor-inducible molecule 14 (Fn14), belong to the TNF superfamily and are involved in proinflammatory responses., Objective: We sought to investigate the role of TWEAK/Fn14 axis in anaphylaxis., Methods: In vivo vascular permeability and mouse models of passive systemic anaphylaxis (PSA) and active systemic anaphylaxis were applied to wild-type (WT), TWEAK- and Fn14-deficient mice (TWEAK -/- and Fn14 -/- , respectively). Primary bone marrow-derived mast cells (BMMCs) and ECs from WT and Fn14 -/- or TWEAK -/- mice were studied. The TWEAK/Fn14 axis was also investigated in human samples., Results: Mice with PSA and active systemic anaphylaxis had increased Fn14 and TWEAK expression in lung tissues and increased serum soluble TWEAK concentrations. TWEAK and Fn14 deficiencies prevent PSA-related symptoms, resulting in resistance to decreased body temperature, less severe reactions, and maintained physical activity. Numbers of MCs after PSA are similar between genotypes in different tissue regions, such as ear skin and the trachea, tongue, peritoneum, lungs, and bone marrow. Moreover, in vitro studies revealed no differences in degranulation or mediator release between WT and Fn14 -/- BMMCs after IgE-FcεRI stimulation. In vivo and in vitro histamine and platelet-activating factor administration increases Fn14 receptor expression in lungs and ECs. Moreover, Fn14 deficiency in ECs maintained in vitro impermeability when stimulated by mediators or activated BMMCs but not by TWEAK -/- BMMCs, indicating that Fn14 is crucial for endothelial barrier function. TWEAK/Fn14 deletion or TWEAK-blocking antibody prevented histamine/platelet-activating factor-induced vascular subcutaneous permeability. Circulating soluble TWEAK levels were increased in patients with anaphylaxis, and plasma from those patients increased Fn14 expression in ECs., Conclusion: The TWEAK/Fn14 axis participates in anaphylactic reactions. Inhibition of TWEAK/Fn14 interaction could be efficacious in anaphylaxis therapy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Breast cancer (BC) is the most commonly diagnosed cancer, and diet is suspected to play a role in its development. Dietary factors may mediate this process through modulation of inflammation, though findings from previous studies have not been consistent. We aimed to longitudinally assess the association between the dietary inflammatory index (DII ® ), a frequently used method to assess the inflammatory potential of the diet, and incident BC., Methods: We included 10,713 middle-aged, Spanish female university graduates from the SUN cohort. DII ® scores were derived from a validated 136-item food-frequency questionnaire, and it was based on scientific evidence on the relationship between diet and inflammatory biomarkers. Diagnosis of BC was reported by the participant or, if deceased, by the next of kin or identified from death certificates. Self-reports of BC were confirmed by revision of medical reports by an experienced oncologist. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between quartiles of DII ® and incident BC., Results: After 10.3 years of median follow-up, we identified 100 confirmed and 168 probable incident BC cases. The multivariable-adjusted HR for participants in the 4th quartile to the 1st quartile was 1.44 (95% CI 0.76-2.72; p-trend: 0.339) when confirmed cases were analyzed, and 1.20 (95% CI 0.72-1.99; p-trend: 0.757) for the probable cases. We neither observed statistically significant differences in regard to menopausal status., Conclusions: The apparent increase in risk between DII ® scores and BC in our cohort was not statistically significant, which could be partly explained by the small number of observed cases., (Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Polyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression. In vivo and in vitro studies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project - a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10·3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3 v. T1 0·31 (95 % CI 0·13, 0·77; Ptrend=0·010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.

Profilins are small actin-binding proteins found in eukaryotes and involved in cell development, cytokinesis, membrane trafficking, and cell motility. From an allergenic point of view, profilins are panallergens usually involved in allergic polysensitization, although they are generally recognized as minor allergens. The objectives of this study were to identify and characterize the profilin from Plantago lanceolata pollen and to investigate the cross-reactivity between profilins from different pollen allergenic sources. Profilins from P. lancelolata (Pla l 2) and palm tree pollen (Pho d 2) were purified by affinity chromatography, deeply characterized and identified by mass spectrometry. Pla l 2 allergenicity was confirmed by immunoblot with serum samples from a patient population sensitized to profilin. Immunoblot inhibition was performed to study IgG reactivity between different pollen profilins. IgE cross-reactivity was demonstrated by ImmunoCAP inhibition. Pla l 2 is the second P. lanceolata allergen included in the IUIS Allergen Nomenclature database. Four peptides from purified Pla l 2 were identified with percentages of homology with other pollen profilins between 73 and 86%. Eighty-six percent (21/24) of the patient population recognized Pla l 2. The allergenic relatedness between Pla l 2, Pho d 2 and six pollen profilins was confirmed, and IgE cross-reactivity of Pla l 2 with rBet v 2 and rPhl p 12 was demonstrated. Pla l 2 is the profilin from P. lanceolata. The demonstrated allergenicity of this protein and its cross-reactivity with other pollen profilins support its use in profilin diagnostic assays., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The introduction of molecular diagnoses has provided evidence of the existence of several different allergenic profiles in grass-sensitised individuals, reflecting the large number of allergens involved. This methodology has become a potent tool for a correct diagnosis and for the selection of the most appropriate immunotherapy. Based on these concepts, the objectives of this study were to determine the sensitisation profile of a grass-allergic population, and to treat them with specific immunotherapy., Methods: Patients suffering from rhinitis and/or asthma associated with grass pollen were recruited. The active group was treated with depigmented-polymerised allergenic extract of mixed grass pollen. sIgE and sIgG4 to Phleum pratense, and to its individual components (Phl p 1, 2, 4, 5b, 6, 7, 11 and 12) were determined at the beginning and end of the study., Results: The inclusion criteria were fulfilled by 139 individuals (36 in the control group and 103 in the active group). Phl p 1 (96.4%) and Phl p 4 (91.2%) were the most recognised allergens, and 15.3% of individuals had positive IgE to cross-reactive carbohydrate determinants. Levels of antigen-specific IgG4 increased significantly after treatment, and the IgE/IgG4 ratio decreased significantly in all allergens after receiving allergen-specific immunotherapy. Non-significant differences were observed in the control group., Conclusions: A high percentage of sensitisation to Phl p 4 was observed. Immunological efficacy was studied by measuring sIgG4 levels and the IgE/IgG4 ratio before and after treatment. Sensitisation profiles should be taken into consideration to prepare the most appropriate immunotherapy containing all the relevant and needed allergens., (© 2014 S. Karger AG, Basel.)

Taxanes, docetaxel and paclitaxel, represent important antineoplastic agents with broad spectra of antitumor activity. The authors developed and validated a high-performance liquid chromatography method with ultraviolet detection for quantifying both taxanes in human plasma. The assay uses liquid-liquid extraction as sample treatment and an isocratic mobile phase and reversed-phase chromatography to determine docetaxel with paclitaxel as internal standard and vice versa. The lower limit of quantification was 0.015 mg/L. The assay had good recovery (87.96+/-14.05 and 90.57+/-9.63 for docetaxel and paclitaxel respectively) and precision: the within-day and between-days relative standard deviation of the mean for docetaxel (0.015-3 mg/L) and paclitaxel was always <10%. The method presented has been fully validated following the U.S. Food and Drug Administration requirements and has been successfully applied for the pharmacokinetic investigation of docetaxel or paclitaxel.

Objective: The aim of this study was to evaluate the clinical utility of FDG-PET for detecting recurrent disease in patients with ovarian cancer., Material and Methods: Twenty-one FDG-PET studies performed in 19 patients who had previously undergone surgery and chemotherapy for ovarian cancer were reviewed retrospectively. In a maximum interval of one week regarding the FDG-PET study, computed tomography (CT) was performed and CA-125 levels were measured. In 16 cases the relapse suspicion was due to elevation of the tumor marker CA125 and in 5 cases it was due to CT. PET images were obtained at 45 min after the intravenous injection of 370 MBq of FDG. The results of the visual interpretation were compared with the CA125 levels and the images of the CT, and related to the definitive diagnosis. Recurrence was confirmed in 19/21 cases, by means of pathological findings (11 cases) and clinical follow-up for a median of 11 months in the others., Results: Recurrence was confirmed in 16 cases with increased CA-125 and the tumor marker was true-negative in 2 disease free cases, but there were 3 false-negative results (sensitivity of 84 % and accuracy of 86 %). CT correctly identified 9 cases with recurrence, but it was false-negative in 10 cases and false-positive in 2 disease free patients (sensitivity of 47 % and accuracy of 43 %). FDG-PET correctly detected the 19 cases with recurrence but it was false-positive in 2 cases with a sensitivity of 100 % and accuracy of 90 %. In 3 patients with CA125 false-negative and 10 patients with false-negative CT, FDG-PET was positive and recurrence was confirmed., Conclusion: These preliminary results suggest that in the follow-up of patients with ovarian cancer FDG-PET could detect recurrence with higher accuracy than CT, and even with higher sensitivity than the tumor marker CA125, being useful at the same time to locate the recurrence when the tumor marker is positive.

Thirty previously untreated patients with advanced germ cell testicular tumours received PVB or BEP. Four patients with bulky disease underwent debulking surgery before initiating chemotherapy and two between cycles of treatment. Twenty-seven (90%) complete responses, two (6.7%) partial responses and one (3.3%) no changes were observed. Both partial remissions were rendered disease-free with surgical removal of residual disease. Four patients presented tumour progression with PVB or BEP, three of whom developed a non-germ cell malignancy within the germ cell tumour. One toxic death and three patients with radiological evidence of reversible interstitial pneumonitis attributed to bleomycin were observed. With a median follow-up time of 38.5 months, range 2.5 to 130 months, 83.3% of the patients are alive and free of disease. Actuarial overall survival is 85.6%. This study confirms once again the high percentage of curability of this disease.