Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs in adults: Beyond current classification.

BACKGROUND: Hypersensitivity reactions (HSRs) to nonsteroidal anti-inflammatory drugs (NSAIDs) are a significant clinical issue. Several classifications have been proposed to categorize these reactions, including the current European Academy of Allergy and Clinical Immunology/European Network for Drug Allergy (EAACI/ENDA) classification. This study aimed to evaluate the applicability of this classification in a real-world clinical setting. METHODS: We conducted a national multicenter study involving patients from nine hospitals in four major urban centers in Turkey. All patients had a suggestive clinical history of hypersensitivity reactions to NSAIDs. Researchers collected data using a structured form and classified reactions based on the EAACI/ENDA classification. Oral provocation tests with several NSAIDs were performed using a single-blind challenge per EAACI/ENDA guidelines. RESULTS: Our retrospective study included 966 adult patients with a history of hypersensitivity to NSAIDs. The most common triggers were Acetylsalicylic Acid (ASA), paracetamol, and metamizole. The most prevalent acute NSAID hypersensitivity group was NSAID-induced urticaria/angioedema (NIUA) (34.3%). However, 17.3% of patients did not fit neatly into the current EAACI/ENDA classification. Notably, patients with underlying asthma or allergic rhinoconjunctivitis exhibited unusual reactions, such as urticaria and/or angioedema induced by multiple chemical groups of NSAIDs, blended mixed reactions, and isolated periorbital angioedema in response to multiple chemical groups of NSAIDs. CONCLUSIONS: While the EAACI/ENDA classification system stratifies NSAID-induced hypersensitivity reactions into five distinct endotypes or phenotypes, it may not fully capture the diversity of these reactions. Our findings suggest a need for further research to refine this classification system and better accommodate patients with atypical presentations.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

BACKGROUND: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. METHODS: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs), and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2-month intervals (Group 3). RESULTS: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom, and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p < 0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). CONCLUSION: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Positive perception of COVID-19 vaccination in HAE: No significant impact of vaccination on disease course.

Background: There are some adverse effects with coronavirus disease 2019 (COVID-19) vaccines, but the impact of COVID-19 vaccination on attacks in hereditary angioedema (HAE) is not well defined. Objective: We aimed to investigate the influence of COVID-19 vaccination on the course of HAE. Method: The COVID-19 vaccination status was determined in 140 adult patients with HAE. The number and severity of attacks recorded from patients' diaries were evaluated at four different periods, comprising 1 month before the first dose, the period between the first and the second doses of COVID-19 vaccine in all the patients, the period between the second dose and the third doses in those who received three doses, and 1 month after the last vaccination dose. The disease and attack severities were assessed with the disease severity score (DSS) and 10-point visual analog scale, respectively. The patients were divided into two main groups as group 1 (those who had at least two doses of COVID-19 vaccines [n = 114]) and group 2 (those who had no vaccination [n = 26]). Only Sinovac and Biontech, which were only approved in Turkey. Results: The mean ± standard deviation DSS was significantly higher in the patients who experienced an attack after vaccination within 48 hours (6.61 ± 1.88 versus 4.14 ± 1.69; p < 0.001). Long-term prophylaxis was less common in the patients with an increased number of attacks (n = 5 (27.8%) versus n = 54 (56.3%); p = 0.027). The number of patients with less than a high school education was higher in group 2 (n = 23 [88.5%]) than in group 1 (n = 26 [3.1%]) (p < 0.001). The number of patients who had concerns about the triggering of a vaccine-induced HAE attack or about the possible vaccine adverse effects was higher in group 2 (n = 26 [100%]) than in group 1 (n = 74 [64.9%]). Conclusion: It seems that COVID-19 vaccination does not increase HAE attacks regardless of the type of the vaccines. We recommend that HAE activity should be under control before COVID-19 vaccination, and the patients should be well informed about the safety of the vaccines.

Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study.

Background: There are no well-defined data that help predict the recurrence risk of urticaria after omalizumab cessation in elderly patients with chronic spontaneous urticaria (CSU). Objective: We aimed to evaluate the effectiveness and safety of omalizumab and to determine the possible predictive factors for recurrence after omalizumab cessation in the elderly with CSU. Methods: A total of 193 patients with CSU treated with omalizumab were included and divided into two groups according to age: group 1, ages 18-64 years (n = 127), and group 2, ages ≥ 65 years (n = 66). Demographics, clinical features, immunoglobulin G (IgG) anti-thyroid peroxidase antibody (anti-TPO), serum total IgE were analyzed. The IgG anti-TPO/total IgE ratio was calculated. Pretreatment 7-day urticaria activity scores, medication scores, and urticaria control test results were compared with those after treatment periods. Adverse effects were also evaluated. Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. Omalizumab was ceased after 24 weeks in 40.9% and in 73.1% in group 1 and group 2, respectively (p < 0.001). CSU recurred after omalizumab discontinuation in 9 and 15 patients in group 1 and in group 2, respectively (p < 0.001). The median baseline IgG anti-TPO was higher in patients with recurrent CSU in group 2 than in those in group 1 (p = 0.002). In group 2, the cutoff values of IgG anti-TPO and the IgG anti-TPO/total IgE ratio were 54.83 IU/mL and 0.45 for recurrence, respectively. Conclusion: Omalizumab is effective and safe in elderly patients with CSU. The serum baseline IgG anti-TPO level and the IgG anti-TPO/total IgE ratio could serve as predictors of recurrence in CSU after omalizumab cessation in elderly patients.

Clinical effects of intranasal corticosteroids on nasal symptoms in subjects with chronic rhinitis during COVID-19.

Background: The clinical effects of intranasal corticosteroids (INC) on nasal symptoms and the clinical course of coronavirus disease 2019 (COVID-19) in subjects with chronic rhinitis (CR) seem unclear. Objective: To evaluate the clinical effects of INCs on nasal symptoms in subjects with CR and with COVID-19. Methods: In subjects with CR and diagnosed with COVID-19 at four tertiary centers, quality of life and nasal symptoms were assessed by using the 22-item Sino-Nasal Outcome Test (SNOT-22) and the visual analog scale (VAS), respectively. In subjects with allergic rhinitis, nasal symptoms were also assessed on the total symptom score-6 (TSS-6) scale. The subjects were then allocated into two groups according to whether or not they used INCs while infected with the severe acute respiratory syndrome coronavirus 2 (group 1 and group 2, respectively). The subjects in group 2 were divided into two subgroups according to the use of antihistamines and/or leukotriene receptor antagonist or not (group 2a and group 2b, respectively). All the scores were compared before and during COVID-19 among the three groups. Results: A total of 71 subjects (21 in group 1, 24 in group 2a, and 26 in group 2b) were enrolled. The total scores of the SNOT-22 increased remarkably in all the groups during the infection when compared with the pre-COVID-19 scores (p < 0.001 in each group). However, the difference between the pre-COVID-19 and COVID-19 values revealed a lower decrease in the senses of smell and/or taste in group 1 than in group 2a and group 2b (p = 0.015, adjusted p = 0.045; and p = 0.001, adjusted p = 0.002, respectively). There were no significant differences in other COVID-19 findings, VAS, and TSS-6 scores among the groups (all p > 0.05). Conclusion: INCs in subjects with CR seemed protective against the decrease in smell and/or taste observed during COVID-19 and do not aggravate the clinical course of COVID-19.

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic.

BACKGROUND: Mast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. METHODS: Mental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV-19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. RESULTS: The mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. CONCLUSIONS: Fear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

Impact of anxiety, stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency.

BACKGROUND: Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP). METHODS: This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status. RESULTS: 139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0-45) and 6 (min-max: 0-10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05). CONCLUSIONS: This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

Paucigranulocytic asthma: Do sputum macrophages matter?

Background: Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features have not been adequately studied. In this study, we aimed to display the characteristics of PGA. Method: A total of 116 non-smoking adult patients with asthma (80% women; mean ± standard deviation age, 39 ± 12.9 years) admitted to three tertiary centers were included. Their demographic and clinical features, allergy status, biochemical results, scores of Asthma Control Test (ACT), spirometry, and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. Results: Four phenotypes, according to induced sputum cell counts, were detected: eosinophilic asthma (EA) (22.4%), mixed granulocytic asthma (MGA) (6.9%), neutrophilic (NA) (7.8%), and PGA (62.9%). In the sputum, macrophages were higher in the PGA group compared with the other groups (PGA versus NA and PGA versus MGA, p < 0.001; and PGA versus EA, p =0 .030). The atopy rate between phenotypes was the same. Although the forced expiratory volume in the first second of expiration (FEV1) was similar in four groups, the ratio of FEV1 to the forced vital capacity ratio was higher (p = 0.013) and FEV1 reversibility was lower in the patients with PGA than the corresponding values in other phenotypes (p = 0.015). Low reversibility was comparable both in patients with PGA who were inhaled corticosteroid (ICS) naive and in patients on ICS treatment. Although insignificant, the FeNO values and blood eosinophil counts were higher in the MGA and EA groups, whereas these were the lowest in the PGA group. The uncontrolled asthma ratio was low in PGA (16%), whereas it was 11% for NA, 25% for MG, and 23% in EA. Conclusion: Macrophages are predominant in sputum of patients with PGA. Besides a lower uncontrolled asthma ratio, lower FEV1 reversibility is a prominent characteristic of this phenotype.

Effects of Perennial Allergen Immunotherapy in Allergic Rhinitis in Patients with/without Asthma: A-Randomized Controlled Real-Life Study.

BACKGROUND: There have been very few studiesin real-life settingscomparing the treatment effects of allergen immunotherapy (AIT) and pharmacotherapy for perennial allergic rhinitis (AR). OBJECTIVE: This study was performed to compare AIT and pharmacotherapy in terms of their effects on the symptom control and quality of life (QOL) of AR patients with/without asthma. METHODS: A total of 250 patients diagnosed with AR with/without asthma were included and assigned to the immunotherapy (AIT plus pharmacological treatment) or control (pharmacological treatment only) group. Clinical and medication scores, QOL scores, and lung function (forced expiratory volume in one second as a percentage; FEV1%) were measured at baseline and 3 years after the start of treatment. RESULTS: This study showed that there was clinical improvement in AR symptoms in the AIT group, whereas standard pharmacotherapy alone had no significant effect on nasal symptoms. The QOL and satisfaction scores, as evaluated with a visual analogue scale (VAS), were further improved compared to the pharmacotherapy group. There was a significant improvement in medication scores in both AIT groups. According to our results, while total asthma scores and asthma control test scores were significantly improved in the HDM AIT group, they did not change in the Parietaria pollen AIT group. In our study FEV1% was increased compared to the baseline value in the AIT group, but it was not statistically significant. On the other hand, FEV1% remained without any improvement in patients on standard pharmacotherapy. CONCLUSION: Perennial AIT was found to be superior to pharmacotherapy in decreasing symptoms as well as in improving QOL scores in AR patients with/without asthma. HDM AIT was more effective for asthma symptoms than Parietaria pollen AIT.

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients.

AIM: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. METHOD: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. RESULTS: The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and ß-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. CONCLUSION: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

Prevalence of atopy and allergic rhinitis in patients with adult non-cystic fibrosis bronchiectasis

Background/aim: Non-cystic fibrosis bronchiectasis (non-CF BR) is common in developing countries.Limited data are available regarding the impact of atopy, and no data are available regarding allergic rhinitis in patients with adult bronchiectasis.The aim of this study was to evaluate the prevalence of atopy and allergic rhinitis in the clinical conditions of patients with BR. Materials and methods: The study enrolled 101 patients who were diagnosed with non-CF BR using high-resolution computed chest tomography. Allergic rhinitis (AR) was defined by skin prick test (SPT) positivity and the presence of any nasal symptoms (watery runny nose, nasal obstruction, nasal itching, and sneezing). Results: The mean age of patients was 48 ± 15 years (range 18­82); 55 (54.5%) patients were female. SPT positivity was detected in 37 (36.6%) cases. AR was detected in 32 (31.7%) patients with non-CF BR. AR was related to dyspnea (P = 0.04) and number of admissions to an emergency department in the previous year (P = 0.01). Forced expiratory volume in 1 s and forced vital capacity in patients with and without AR were different (P = 0.01 and P = 0.01, respectively). AR was correlated with number of admissions to an emergency department in the last year (r = 0.417, P = 0.005). Conclusion: We concluded that atopy was detected in more than one-third of adult non-CF BR patients. This study demonstrated that non-CF BR patients might have AR; it might be important to be aware of nasal symptoms in non-CF BR patients.

Management of Hypersensitivity Reactions to Proton Pump Inhibitors: A Retrospective Experience.

BACKGROUND: We previously reported perfect specificity and low sensitivity of skin tests in proton pump inhibitor (PPI)-induced immediate hypersensitivity reactions in a prospective multicenter study. Here, in a retrospective study, we aimed to further evaluate the diagnostic workup procedures and characteristics of the patients with suspected PPI hypersensitivity. METHODS: This national multicenter study was conducted as a retrospective chart review of patients with a history of PPI-induced immediate hypersensitivity reaction. A total of 60 patients were included. Results of diagnostic workup procedures (standardized skin-prick, intradermal, and oral-provocation tests with PPIs) and the characteristics of the patients were analyzed. RESULTS: Lansoprazole was the most commonly suspected drug with 41 patients (68.3%), followed by pantoprazole in 12 patients (20.0%), esomeprazole in 6 (10.0%), rabeprazole in 4 (6.7%), and omeprazole in 1 (1.7%). Anaphylaxis (40 patients, 66.7%) was the most common clinical presentation followed by urticaria (17 patients, 28.3%). Diagnostic skin tests with the culprit PPI were positive in 13/26 patients (50.0%). Diagnostic oral-provocation tests were negative in 6/8 patients; 5 of these 6 patients had skin test results with the culprit PPI, and all were negative. Ten patients had at least 1 cross-reactivity. Extensive cross-reactivity (between >2 PPIs) was detected in 4 patients. CONCLUSIONS: Lansoprazole was the most frequently implicated drug and anaphylaxis was the most frequent manifestation of PPI-induced hypersensitivity reactions. Physicians should be aware of the possible cross-reactivity among PPIs; however, a safe, alternative PPI can usually be detected by a thorough drug allergy workup.

The prevalence of Hymenoptera venom allergy in adults: the results of a very crowded city in Euroasia.

BACKGROUND: There are scarce data about the prevalence of Hymenoptera venom allergy in the general population. The aim of this study was to determine the prevalence of Hymenoptera venom allergy in the general adult population of Istanbul. METHODS: A total of 17,064 randomly selected telephone numbers were contacted and 11,816 (69.25%) individuals who agreed to participate completed a questionnaire. Those who disclosed hypersensitivity reactions due to Hymenoptera stings in this initial survey were called again and given another questionnaire. Those who were suspected of experiencing hypersensitivity reactions to Hymenoptera stings were invited for a clinical investigation with in vivo and in vitro diagnostic tests. RESULTS: According to the first questionnaire, a total of 1171 (9.9%; 95% CI: 9.38-10.47%) were suspected of having a hypersensitivity to Hymenoptera stings. 51.75% (n: 606) answered the second questionnaire and 21% (n: 128) of these were still suspected of having a hypersensitivity to Hymenoptera stings (1.1%; 95% CI: 0.9-1.29%). The confirmed prevalence of hypersensitivity to Hymenoptera stings according to skin tests and in vitro sIgE levels was 0.2% (95% CI: 0.14-0.30%). Nearly all of the participants with systemic reactions were admitted to the emergency department, although only one tenth of them received adrenaline in the emergency room. 2.3% carried an adrenaline injector, whereas none of the patients received venom immunotherapy. CONCLUSIONS: The prevalence of Hymenoptera sting reactions in our geographical region is comparable with other European studies. There is a need to increase the awareness of adrenaline in the emergency management of insect sting anaphylaxis and venom immunotherapy in the prophylaxis.

A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option.

Investigation of Antiproliferative Effects of Combinations of White and Black Garlic Extracts with 5-Fluorouracil (5-FU) on Caco-2 Colorectal Adenocarcinoma Cells.

Garlic is rich in bioactive compounds that are effective against colon cancer cells. This study tests the antioxidant and antiproliferative effects of cold-extracted white and black garlic extracts. Black garlic extracted in water (SSU) exhibits the highest antioxidant activity, phenolic content, and flavonoid content, while black garlic extracted in ethanol (SET) shows the lowest values. Caspase-3 activity is notably higher in the white garlic extracted in methanol (BME), white garlic extracted in methanol combines with 5-FU, black garlic extracted in ethanol (SET), black garlic extracted in ethanol combines with 5-fluorouracil (5-FU), and 5-FU treatments compare to the control group (p > 0.05). BME+5-FU displays the highest caspase-8 activity (p < 0.05). A decrease in NF-κB levels is observed in the SET+5-FU group (p>0.05), while COX-2 activities decrease in the BME, SET+5-FU, SET, and 5-FU groups (p>0.05). Wound healing increases in the BME, BME+5-FU, SET+5-FU, and 5-FU groups (p < 0.05). In conclusion, aqueous black garlic extract may exhibit pro-oxidant activity despite its high antioxidant capacity. It is worth noting that exposure to heat-treated food and increased sugar content may lead to heightened inflammation and adverse health effects. This study is the first to combine garlic with chemo-preventive drugs like 5-FU in Caco-2 cells.

Does Breast Feeding Protect Mothers From Obesity?

BACKGROUND: Hepatosteatosis, which we frequently observe today with change in lifestyle, is often unnoticed, but preventable and reversible; if not prevented, it can lead to serious comorbidities. There is contradicting evidence in the literature; we believe that breastfeeding has a protective effect on hepatosteatosis. In this cross-sectional study we conducted, we aimed to examine the relationship between breastfeeding duration, metabolic parameters and fatty liver. METHODS: We examined the data of 135 patients aged 20-40 years who have had at least one pregnancy and were admitted to our polyclinic. Forty-five healthcare staff who never breastfed were included in the control group. Measurements of height and weight were taken, and number of children and total breastfeeding time were questioned. Blood values were measured to calculate insulin resistance, non-alcoholic fatty liver disease (NAFLD) fibrosis score and Fibrosis-4 (FIB-4) score. RESULTS: Consequently, there was no significant correlation between total breastfeeding time and body mass index (BMI), NAFLD fibrosis score, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value and hemoglobin A1C (HbA1C). When two groups were formed as patients breastfeeding for less than six months and patients breastfeeding for more than six months, a significant difference in BMI was observed between these two groups (p: 0.02). There was a significant relationship between BMI and NAFLD (p: 0.00) and HOMA-IR (p: 0.00). It was observed that there was a significant difference between BMI FIB-4 and NAFLD fibrosis scores of the control group and breastfed group. CONCLUSIONS: Lactation should be maintained for at least six months for maternal health together with the baby's health, and more comprehensive studies should be conducted for long-term data.

Monitoring recurrent angioedema: Findings from the Turkish angioedema control test validation study.

BACKGROUND: Determination of control level in recurrent angioedema (RAE) is necessary to guide management. Here, we validated a Turkish version of the angioedema control test (AECT) for 4-week (AECT-4wk) and for 3-month (AECT-3mth) and assessed their utility in monitoring RAE. METHOD: The recommended structured translation process for patient-reported outcome measures was completed. The final versions were administered to 51 patients with mast cell-mediated angioedema (MMAE) and 38 patients with hereditary angioedema, and the minimal clinically important difference (MCID) was determined. Additionally, anchor surveys comprising angioedema activity score for 28 days (AAS-28 day), visual analog score for angioedema control, Likert scale for the control level from the patient's perspective (LS-AEC), angioedema quality of life, short form-12 (SF-12) and patients' assessment of treatment sufficiency were applied. RESULTS: The Turkish AECT versions showed good convergent validity with a substantial correlation with anchor tools and known-group validity. Excellent internal consistency and reproducibility were observed. Equal or more than 10 of 16 points scored with the AECT-4wk and AECT-3mth identified patients with well-controlled disease. The disease activity, control and burden parameters were consistent with the disease control level defined depending on the cut-off point 10 of AECT. Three-point changes in AECT-4wk and -3 mt could detect MCID in disease control in all patients. CONCLUSIONS: Turkish AECT versions are valid and reliable tools for assessing and monitoring disease control in patients with RAE. The use of the Turkish versions of the AECT in routine patient care, clinical trials and angioedema research is recommended.

The first successful desensitization protocol in exenatide allergy: a case report.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are important treatment options in obese patients with type 2 diabetes. To date, few immediate allergic reactions due to GLP-1 receptor agonists were reported. One report revealed that a patient with a level 1 anaphylaxis according to Brighton Criteria due to an exendin based GLP-1 receptor agonist was able to tolerate liraglutide (Human GLP-1 analogue), the alternative GLP-1 receptor agonist. Since exenatide is the only available GLP-1 receptor agonist covered by insurance in Turkey, a drug desensitization protocol, the only therapeutic method in hypersensitivity reactions used in case of absence of an alternative drug, was considered. Here, we report a successful desensitization protocol for the first time in two obese diabetic patients with an immediate hypersensitivity to exenatide. CASE PRESENTATION: The first patient was a 47 year-old female. She was referred to our outpatient allergy clinic because of a generalized urticaria developed within minutes after the last dose, following a week of an exenatide BID 5 mcg/20 mcl treatment. Although the reaction was sudden onset, it did not meet the Brighton Criteria of anaphylaxis. The second patient was a 46 year-old female. She had a large local immediate injection site reaction that appeared 15 min following an exenatide BID 5 mcg/20 mcl injection. The injection site reaction was not accompanied by a systemic allergic reaction. We performed desensitization with exenatide to two patients who need GLP-1 receptor agonist treatment. Protocol was completed in 7 steps in approximately 3 h, with the aim of reaching the daily dosage of exenatide. Throughout this process, we observed that both cases tolerated the protocol without any complaints or complications. Following the protocol, the patients safely tolerated the treatment for 3 months. CONCLUSIONS: We present the first successful desensitization protocol to exenatide in both local and/or systemic immediate hypersensitivity reactions and indicate the importance of desensitization in patients who do not have alternative therapies.

Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

Introduction: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. Methods: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients' demographic and clinical characteristics were further analyzed depending on the severity of the reaction. Results: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25-75] age: 42 [33-52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1-7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1-6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5-17.0); p = 0.011, OR (CI) = 10.3 (1.6-63.3)]. Conclusion: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.