Impact of asthma on severe food-induced allergic reactions: a systematic review and meta-analysis.

Summary: Background. Food allergy can range from mild to severe, life-threatening reactions with various symptoms and organ involvement. The impact of asthma on severe food-induced allergic reactions is not completely understood. In the hypothesis that asthma increases the risk of severe food-induced allergic reactions, the aim of this study is to compare the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. Methods. We performed a systematic research on electronic databases, including PubMed, Scopus, and Web of Science. Observational studies, studies reporting medical characteristics of patients diagnosed with food allergy, and studies reporting medical history of patients with allergic reactions were included. The primary outcome was the incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma. The protocol of this review was registered in PROSPERO (CRD42023448293). Results. Eight studies with a total of 90,367 patients met the inclusion criteria and were included, with a total population of 28,166 of patients with food allergy. The incidence of severe food-induced allergic reactions in patients with history of asthma compared with patients without history of asthma was increased (OR = 1.28; 95% CI 1.03-1.59; p = 0.03; I2 = 59%). Conclusions. Individuals with both food allergy and asthma are at high risk of severe, potentially fatal allergic reactions. Healthcare professionals should prioritize prevention and management strategies for these subjects.

The role of skin tests with polyethylene glycol and polysorbate 80 in the vaccination campaign for COVID-19: results from an Italian multicenter survey.

Summary: Background. International guidelines suggested skin tests with Polyethylene-glycol (PEG) and polysorbate 80 (PS-80), to investigate a possible hypersensitivity to these excipients either to identify subjects at risk of developing allergic reactions to Covid-19 vaccines, or in patients with suspected IgE mediated hypersensitivity reactions (HR) to the Covid-19 vaccine. The main purpose of this study was to investigate the prevalence of PEG and PS sensitization in patients with a clinical history of HR to drugs containing PEG/PS and in patients with a suspected Covid-19 vaccine immediate HR. Methods. This was a multicenter retrospective study conducted by allergists belonging to 20 Italian medical centers. Skin testing was performed in 531 patients with either a clinical history of suspected hypersensitivity reaction (HR) to drugs containing PEG and/or PS-80 (group 1:362 patient) or a suspected HR to Covid-19 vaccines (group 2: 169 patient), as suggested by the AAIITO/SIAAIC guidelines for the "management of patients at risk of allergic reactions to Covid-19 vaccines" [1]. Results. 10/362 (0.02%) had positive skin test to one or both excipients in group 1, 12/169 (7.1%) in group 2 (p less than 0.01). In group 2 HRs to Covid-19 vaccines were immediate in 10/12 of cases and anaphylaxis occurred in 4/12 of patients. Conclusions. The positivity of skin test with PEG and or PS before vaccination is extremely rare and mostly replaceable by an accurate clinical history. Sensitization to PEG and PS has to be investigated in patients with a previous immediate HR to a Covid-19 vaccine, in particular in patients with anaphylaxis.

Hypersensitivity reactions to iodinate contrast media in Italy: a retrospective study. Characteristics of patients and risk factors.

SUMMARY: Objective. The purpose of the study was to describe the characteristics of patients experiencing hypersensitivity reactions (HRs) to iodinated contrast media (ICM) in a large Italian population and to investigate potential risks factors in order to obtain a risk stratification, helpful in the management of these patients. Methods. Data of 407 patients investigated in 9 Italian Allergy Centers for suspected HRs to ICM were analyzed and compared with a control group of 152 subjects that tolerated one or more ICM-enhanced examinations. The univariate and multivariate logistic regression model was used to evaluate associated factors. Results. The mean age of reactive patients was 61 years and 60% were female; 67% of patients reported immediate reactions and 35% experienced the reaction, more frequently with immediate onset, at the first examination in life. Iomeprol, iopromide and iodixanol were the most frequent culprit agents and 20% of patients showed a positive skin test result. Previous adverse reactions to ICM were reported by 15.6% of patients, whereas 35% of subjects experienced the reaction, more frequently immediate, after the first ICM-enhanced examination in their life. The multivariate analysis showed that male gender and age > 65 were associated with ICM reactions as protective factors [ORadja = 0.51; 95% CI: 0.33-0.77 and ORadja = 0.60; 95% CI: 0.39-0.92 respectively]. Cardio-vascular disease [ORadja = 2.06; 95% CI: 1.22-3.50)], respiratory allergy [ORadja = 2.30; 95% CI: 1.09-4.83)] and adverse drug reactions [ORadja = 1.99; 95% CI: 1.05-3.77)] were identified as risk factors for ICM reactions. Food allergy was not significantly associated with reactions [ORadja = 1.51; 5% CI: 0.41-5.56]. Conclusions. This is the largest study on Italian patients experiencing hypersensitivity reactions to ICM. Most results are in line with other studies, showing some association with factors that could influence the incidence of hypersensitivity reactions but not allowing an easy risk stratification.

Septal Ablation Versus Surgical Myomectomy for Hypertrophic Obstructive Cardiomyopathy.

PURPOSE OF REVIEW: Patients with hypertrophic cardiomyopathy (HCM) who have left ventricular outflow tract obstruction (LVOTO) often experience severe symptoms and functional limitation. Relief of LVOTO can be achieved by two invasive interventions, i.e., surgery myectomy and alcohol septal ablation (ASA), leading in experienced hands to a dramatic improvement in clinical status. Despite extensive research, however, the choice of the best option in individual patients remains challenging and poses numerous clinical dilemmas. RECENT FINDINGS: Invasive strategies have been recently incorporated in recommendations for the diagnosis and treatment of HCM on both sides of the Atlantic. These guidelines are based on a bulk of well-designed but retrospective studies as well as on expert opinions. Evidence now exists that adequate evaluation and management of HCM requires a multidisciplinary team capable of choosing the best available options. Management of LVOTO still varies largely based on local expertise and patient preference. Following the trend that has emerged for other cardiac diseases amenable to invasive interventions, the concept of a "HCM heart team" is coming of age.

SLCO1B1 Gene Polymorphisms (rs2306283 and rs4149056) and Statin-Induced Myopathy in Jordanian Diabetics.

BACKGROUND: The use of statins to lower high serum cholesterol levels may be associated with a number of adverse reactions, including severe myopathy. The solute carrier organic anion transporter 1B1 (SLCO1B1) gene, which encodes the organic anion-transporting polypeptide OATP1B1, is related to the intracellular transport of statins. The aim of this research was to study the association of rs2306283 and rs4149056 genetic polymorphism of the SLCO1B1 gene with the development of statin-induced myopathy in Jordanian diabetics receiving statins. METHODS: We included 413 patients attending the Diabetes Clinics of the National Center for Diabetes, Endocrinology and Genetics, Amman, Jordan. The study was approved by the Institutional Review Board of NCDEG. Myopathy was defined as the elevation of creatine kinase more than 3 times the upper limit of normal. Every subject signed an informed consent form and donated 3-5 mL of venous blood. Genome DNA was extracted from lymphocytes of peripheral blood. Genotypes were identified using the Tetra Amplification Refractory Mutation System of SLCO1B1. RESULTS: The minor allele frequencies of rs2306283 [G] and rs4149056 [C] were 0.38 and 0.23, respectively. The two SNPs followed the Hardy-Weinberg equilibrium. The development of SIM was significantly associated with the homozygous and heterozygous minor allele genotype of rs4149056 (CC and CT), and the homozygous wild type allele genotype of rs2306283 (AA). There was no linkage disequilibrium between the two SNPs in the studied subgroups. CONCLUSION: Genetic polymorphism in the SLCO1B1 Gene is a risk factor for the development of SIM in Jordanian patients.

The Effect of Pomegranate Juice on the Expression of Some Murine UDP-Glucuronosyltransferases Genes.

BACKGROUND: Food-drug interactions may lead to suppression or induction of drug metabolizing enzymes. Pomegranate is a commonly used fruit in folk medicine all over the world. Data concerning the effect of pomegranate on the activity of UDP-glucuronosyltransferases (UGTs) is scarce. OBJECTIVE: The purpose of this work was to investigate the effect of pomegranate juice ingestion on the transcription of ugt2b1, ugt2a3, and ugt1a9 in the liver and small intestine of male mice. METHODS: Pomegranate juice was administered to 10 male mice for 14 days in drinking bottles instead of water. Ten control mice received water in the drinking bottles. On the 15th day, the mice were sacrificed and the liver and the small intestine were removed. The small intestine was divided into 3 parts. Total mRNA was extracted from samples of these specimens, and cDNA was synthesized by quantitative real-time polymerase chain reaction (RT-PCR) using specific primers for each ugt gene. RESULTS: The ugt1a9 mRNA level was reduced by 2.25-fold in the liver and by 6-, 1.5-, and 3-folds in the first, second and third part of the small intestine, respectively. The ugt2b1 mRNA level in the liver and the third part of the small intestine was not affected, while it was reduced by 3.7- and 3-folds in the first and second parts of the small intestine, respectively. The ugt2a3 mRNA level was not affected in the liver and the 3 parts of the small intestine. CONCLUSION: Some ugt mRNA levels may be reduced by the ingestion of pomegranate juice, which may reduce the metabolism of their drug substrates. The consequences may be an accumulation of such drugs in the body and enhanced toxicity.

Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic LHCGR Gene Mutation.

Purpose: Testotoxicosis is an autosomal dominant form of limited gonadotropin-independent precocious puberty in boys. It is caused by a heterozygous constitutively activating mutation of the LHCGR gene encoding the luteinizing/hormone receptor (LHR). Some twenty mutations of the LHCGR gene have been reported. Most of them are constitutive mutations isolated from blood leukocyte DNA, although others are somatic, found only in testicular tumoural tissue. In all the previously reported cases of these somatic mutations, the tumour, whether a nodular Leydig cell adenoma or hyperplasia, was easily visible on testicular ultrasonography. The aim of this study was to describe an unusual presentation of a patient with the clinical and hormonal characteristics of testotoxicosis but no well-circumscribed lesion at testicular ultrasonography.Materials and Methods: Molecular analysis of the LHCGR gene was performed by direct sequencing of DNA extracted from peripheral leucocytes and testicular biopsy.Results: Molecular analysis didn't find any LHR mutation in blood, whereas it revealed for the first time a somatic D578H mutation in testicular tissue despite no evidence of a nodular aspect at testis ultrasonography.Conclusions: This observation underlines the need to look for a somatic LHCGR gene mutation from the testicular biopsies of all boys with testotoxicosis with no constitutive LHCGR gene mutation identified from blood DNA, even in the absence of circumscribed testicular lesion at ultrasonography. In addition, based on the known link between LHR mutations and testicular tumourigenesis, yearly ultrasound monitoring of the testes should be considered for these patients.

The prognostic value of quantitative diffusion-weighted MRI after pediatric cardiopulmonary arrest.

OBJECTIVES: The prognostic value of quantitative diffusion-weighted magnetic resonance imaging (DWI MRI) in predicting neurologic outcomes after pediatric cardiopulmonary arrest (CPA) has not been determined. The aim of this study was to identify a DWI MRI threshold for brain volume percent that correlates with neurologic outcome in children who remain comatose or display significant neurologic deficits immediately after resuscitation from CPA. METHODS: This single-center retrospective study analyzed DWI MRIs of pediatric patients who remained neurologically impaired after CPA. Any MRI obtained within 2 weeks after CPA was analyzed. The apparent diffusion coefficient (ADC) value of each voxel within the brain was determined. Percentage brain volume with voxels below each ADC threshold between 300 and 1200 × 10-6 mm2/s with a step of 50 were calculated. Area under the receiver operating characteristics curve (AUC) was used to identify optimal DWI MRI thresholds for brain volume percent most predictive of poor neurologic outcome. The primary outcome measure was neurologic outcome 6-months after CPA based on Pediatric Cerebral Performance Category (PCPC) score. Poor neurologic outcome was defined as PCPC score of 3-6, or a worsening from baseline score ≥1 if baseline PCPC score was ≥3. RESULTS: Twenty-six patients were included in this study. The median age was 8.5 years (2.2-14) and median time from CPA to MRI was 4 days (2-7). Two ADC thresholds for brain volume percent had the largest AUC for predicting poor neurologic outcome. An ADC threshold of <600 × 10-6 mm2/s in ≥7% of brain volume; and <650 × 10-6 mm2/s in ≥11% of brain volume both demonstrated a specificity of 1.0 (0.76-1.0, 95% CI) and a sensitivity of 0.8 (0.44-0.96, 95% CI) for poor outcome. CONCLUSIONS: In pediatric patients who remain comatose or have significant neurologic deficits after CPA, quantitative DWI MRI correlates with neurologic outcome. Both an ADC threshold of <600 × 10-6 mm2/s in ≥7% of brain volume and <650 × 10-6 mm2/s in ≥11% of brain volume are highly specific for predicting poor neurologic outcome. A prospective trial to validate these thresholds is needed.

The Cape Town Declaration on Access to Cardiac Surgery in the Developing World.

Twelve years after cardiologists and cardiac surgeons from all over the world issued the 'Drakensberg Declaration on the Control of Rheumatic Fever and Rheumatic Heart Disease in Africa', calling on the world community to address the prevention and treatment of rheumatic heart disease (RHD) through improving living conditions, to develop pilot programmes at selected sites for control of rheumatic fever and RHD, and to periodically review progress made and challenges that remain, RHD still accounts for a major proportion of cardiovascular diseases in children and young adults in low- and middle-income countries, where more than 80% of the world population live. Globally equal in prevalence to human immunodeficiency virus infection, RHD affects 33 million people worldwide. Prevention efforts have been important but have failed to eradicate the disease. At the present time, the only effective treatment for symptomatic RHD is open heart surgery, yet that life-saving cardiac surgery is woefully absent in many endemic regions. In this declaration, we propose a framework structure to create a co-ordinated and transparent international alliance to address this inequality.

In vivo percutaneous microwave ablation in kidneys: Correlation with ex vivo data and ablation work.

PURPOSE: To compare diameters of in vivo microwave ablation (MWA) performed in swine kidneys with ex vivo diameters, and to correlate with ablation work (AW), a new metric reflecting total energy delivered. MATERIAL AND METHODS: Eighteen in vivo MWA were performed in 6 swine kidneys successively using one or two antennas (MicroThermX®). Ablation consisted in delivering power (45-120W) for 5-15minutes. Ex vivo diameters were provided by the vendors and obtained on bovine liver tissue. AW was defined as the sum of (power)*(time)*(number of antennas) for all phases of an ablation (in kJoules). Kidneys were removed laparoscopically immediately after ablation. After sacrifice, ablations zones were evaluated macroscopically, and maximum diameters of the zones were recorded. Wilcoxon sum rank test and Pearson's correlation were used for comparisons. RESULTS: For a single antenna (n=12), the in vivo diameters ranged from 12 to 35mm, and 15-49mm for 2 antennas (n=6). The in vivo diameters remained shorter than ex vivo diameters by 8.6%±30.1 on 1 antenna and 11.7%±26.5 on 2 antennas (P=0.31 and 0.44, respectively). AW ranged from 13.5 to 108kJ. Diameters increased linearly with AW both with 1 and 2 antennas, but only moderate correlations were observed (r=0.43 [95% confidence interval: -0.19; 0.81], P=0.16; and 0.57 [-0.44; 0.95], P=0.24, respectively). CONCLUSION: Although diameters after in vivo renal MWA increased linearly with AW, the moderate correlation and wide standard deviations observed may justify a careful imaging monitoring during treatment delivery and settings adaptation, if needed, for optimal ablation.

Histamine release positive test associates with disease remission in chronic spontaneous urticaria: a proof-of-concept study.

SUMMARY: Background. Histamine release (HR) test has previously been shown to predict the presence of endogenous histamine-releasing factors in chronic spontaneous urticaria (CSU). Objectives and methods. Twenty CSU patients unresponsive to antihistamine treatment were enrolled in order to evaluate the correlations between HR test results and demographic features, quality of life, disease activity, clinical course, and autologous serum and plasma skin tests (ASST and APST). Results. All patients with positive HR test (9/9, 100%) had a more severe disease activity at onset (urticaria activity score, UAS > 2) when compared to negative HR test patients (5/11; p = 0.04). Quality of life questionnaire's results were not substantially different between HR positive and negative subgroups at baseline (p > 0.05), and results of HR test and ASST/APST did not co-segregate (p > 0.05). After 12 months, patients with a positive HR test had a significant reduction of disease activity (p = 0.003) whereas patients with a negative HR test did not (p > 0.05), leading to disease remission and antihistamine treatment withdrawal in 67% (6/9) of positive HR test patients versus 18% (2/11) of negative HR test patients (p = 0.027). Conclusions. Positive HR test may predict spontaneous CSU remission at 12 months.

CT and MR imaging features of mucinous tubular and spindle cell carcinoma of the kidneys. A multi-institutional review.

Mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney is a recently identified renal malignancy. Diagnosis of this rare subtype of renal tumour can be challenging for pathologists, and as such, any additional data would be helpful to improve diagnostic reliability. As imaging features of this new and rare sub-type have not yet been clearly described, the purpose of this study was to describe the main radiologic features on computed tomography (CT) and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective review of pathology and imaging databases. Using a combination of CT/MRI features, diagnosis of MTSCC could be suggested in many cases. A combination of slow enhancement with plateau on dynamic contrast-enhanced CT/MRI, intermediate to high T2 signal intensity contrasting with low apparent diffusion coefficient values on MRI appeared evocative of this diagnosis. KEY POINTS: • A slow enhancement with plateau is observed either on CT or MRI. • High T2 signal components but low apparent coefficient diffusion are evocative. • T2-weighted imaging features depend on the mucin components of the tumour.

Tubulocystic renal cell carcinoma: a new radiological entity.

UNLABELLED: Tubulocystic renal cell carcinoma (TC-RCC) is a recently identified renal malignancy. While approximately 100 cases of TC-RCC have been reported in the pathology literature, imaging features have not yet been clearly described. The purpose of this review is to describe the main radiologic features of this rare sub-type of RCC on ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), based jointly on the literature and findings from a multi-institutional retrospective HIPAA-compliant review of pathology and imaging databases. Using a combination of sonographic and CT/MRI features, diagnosis of TC-RCC appeared to be strongly suggested in many cases. KEY POINTS: • Tubulocystic renal cell carcinoma is a new entity with typical imaging features • Diagnosis of tubulocystic renal cell carcinoma can be suggested preoperatively by imaging • Cystic renal lesions with high echogenicity may correspond to tubulocystic carcinoma.

Association of rs7041 and rs4588 Polymorphisms of the Vitamin D Binding Protein and the rs10741657 Polymorphism of CYP2R1 with Vitamin D Status Among Jordanian Patients.

AIM: Previous studies have shown a high prevalence of vitamin D deficiency among Jordanians despite adequate exposure to sunlight, suggesting the presence of other causes for this deficiency. The aim of this study was to identify the relationship between 25-hydroxyvitamin D [25-(OH) VD] status and the nonsynonymous single-nucleotide polymorphisms (SNPs) (rs7041 and rs4588) of the GC gene, which encodes the vitamin D binding protein, and one SNP (rs10741657) near the CYP2R1 gene. METHODS: Blood samples from 381 subjects (74 males and 307 females, 18-60 years of age) were obtained from the "National Center for Diabetes, Endocrinology and Genetics" (Amman, Jordan). The subjects were classified as "apparently healthy" if they did not suffer from chronic diseases and as "unhealthy" if they suffered from certain chronic diseases. Subjects' genotypes for GC; rs7041 and rs4588; CYP2R1; rs10741657 were determined by the polymerase chain reaction-restriction fragment length polymorphism assay method. RESULTS: Apparently, healthy subjects had significantly higher 25-(OH) VD levels than unhealthy patients. In apparently healthy subjects, the rs10743657 genotypes containing the variant allele A (AA, GA) were associated with higher 25-(OH) VD levels than the homozygous wild-type genotype (GG). The genotypes containing the variant allele of rs7041 (TT, TG) and rs4588 (AA, AC) were associated with lower 25-(OH) VD levels than the wild-type genotypes (GG and CC, respectively). Haplotype analysis of rs7041 and rs4588 revealed that the haplotypes GC1S and GC1S/S were associated with 25-(OH) VD sufficiency, whereas haplotypes GC1F/S, GC1F/2, GC1S/2, GC2, and GC2/2 were associated with 25-(OH) VD deficiency. In unhealthy patients, only the homozygous genotype of the variant allele of rs7041 (TT) was associated with higher 25-(OH) VD levels, which is the reverse of what had been observed in apparently healthy subjects. CONCLUSIONS: The rs70141657G/A of CYP2R1 and rs7041T/G and rs4588C/A of vitamin D binding protein genetic polymorphisms were associated with increased risk of vitamin D deficiency among apparently healthy Jordanians.

Proposal of a skin tests based approach for the prevention of recurrent hypersensitivity reactions to iodinated contrast media.

The purpose of the present work is to evaluate the efficacy of an approach that combines clinical history, skin tests results, and premedication, in preventing recurrent hypersensitivity reactions to iodinated contrast media (ICM). Skin Prick tests, Intradermal tests, and Patch tests were performed in 36 patients with a previous reaction to ICM. All patients underwent a second contrast enhanced radiological procedure with an alternative ICM selected on the basis of the proposed approach. After alternative ICM re-injection, only one patient presented a mild NIR. The proposed algorithm, validated in clinical settings where repeated radiological exams are needed, offers a safe and practical approach for protecting patients from recurrent hypersensitivity reactions to ICM.

Multiparametric magnetic resonance imaging for the differentiation of low and high grade clear cell renal carcinoma.

PURPOSE: To retrospectively evaluate the ability of magnetic resonance (MR) imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC). MATERIALS AND METHODS: MR images from 80 consecutive pathologically proven RCC (57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps were reviewed independently. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated and compared to pathological grade and size. The Fuhrman scoring system was used. Low grade (score ≤ 2) and high grade (score ≥ 3) tumours were compared using univariate and multivariate analyses. RESULTS: No associations between grade and imaging factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there was a significant association between the grade and parenchymal WiI (WiI2) (P = 0.02) or ADCr (P = 0.03). A significant association between tumour grade and size (P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate analysis. CONCLUSIONS: Multiparametric MRI can be used to accurately differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman grade (≥ 3) RCCs were larger, had lower parenchymal wash-in indices and lower ADC ratios than low grade. KEY POINTS: • Fuhrman grade of clear cell RCC can be differentiated with multiparametric MR imaging. • Fuhrman grade significantly differed for size, parenchymal wash-in index and ADC ratio. • No significant associations were found for papillary and chromophobe renal cell carcinoma.