Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

Phase angle and cellular health: inflammation and oxidative damage.

Phase angle is a composite measure that combines two raw bioelectrical impedance analysis measures: resistance and reactance. Phase angle has been considered an indicator of cellular health, integrity, and hydration. As inflammation and oxidative stress can damage cellular structures, phase angle has potential utility in early detecting inflammatory and oxidative status. Herein, we aimed to critically review the current understanding on the determinants of phase angle and its relationship with markers of inflammation and oxidative stress. We also discussed the potential role of phase angle in detecting chronic inflammation and related adverse outcomes. Several factors have been identified as predictors of phase angle, including age, sex, extracellular to intracellular water ratio, and fat-free mass. In addition to these factors, body mass index (BMI) also seems to influence phase angle. Available data also show that lower phase angle values are correlated (negligible to high correlation coefficients) with higher c-reactive protein, tumour necrosis factor-α, interleukin-6, and interleukin-10 in studies involving the general and aging populations, as well as patients with chronic conditions. Although fewer studies have evaluated the relationship between phase angle and markers of oxidative stress, available data also suggest that phase angle has potential to be used as an indicator (for screening) of oxidative damage. Future studies including diverse populations and bioelectrical impedance devices are required to confirm the validity and accuracy of phase angle as a marker of inflammation and oxidative stress for clinical use.

Positive drug provocation with beta-lactam antibiotics in children: A single test may not be enough.

BACKGROUND: Drug provocation tests (DPTs) are considered the gold standard for diagnosing beta-lactam allergy. However, positive results tend to be mild and difficult to interpret. This study aimed to describe pediatric patients with a presumedly positive or inconclusive DPT, assess the decision to repeat the DPT, and describe its outcome. METHODS: Retrospective review of all presumedly positive or inconclusive DPTs performed in six pediatric allergy clinics from 2017 to 2019. We describe the interpretation of results, focusing on the decision to repeat the DPT and its outcome. RESULTS: Of 439 children challenged with a beta-lactam, 26 (5.9%) with a presumedly positive or inconclusive result were included in this study. Most were girls (n = 16, 61.5%), and the median age was 5 years (range 1-13). The initial DPT used amoxicillin (n = 13, 50.0%), amoxicillin-clavulanic acid (n = 12, 46.2%), or cefadroxil (n = 1, 3.8%). Reactions were early (n = 11, 42.3 %), delayed (n = 14, 53.8 %), or not registered (n = 1, 3.8 %), but mild in all cases. A second confirmatory DPT was proposed in 19 patients (73.1%) and performed in 17 patients (65.4%). Nine DPTs were performed from 1 day to 4 months after the first DPT, and the remaining eight took place 6 months to 2 years later. Fifteen children tolerated the drug in the second DPT: 88.2% of those reevaluated and 57.5% of the whole study group. CONCLUSION: The positive predictive value of DPT may be lower than expected. Given the mildness of observed reactions, a second confirmatory DPT is warranted within a few weeks or months.

Dysphagia Perception Among Community-Dwelling Older Adults from a Municipality in Southern Brazil.

To analyse the prevalence of dysphagia perception and associated factors among community-dwelling older adults in Pelotas, Brazil. A total of 1447 community-dwelling individuals aged 60 and older participated in a cross-sectional population-based study carried out in 2014. Dysphagia perception was assessed using the following question: "Do you have swallowing difficulties? (Yes/No)". Independent variables included sociodemographic, behavioural and health characteristics. Poisson regression was used to obtain prevalence ratios. Dysphagia perception prevalence was 8.1%, higher among women (PR 1.63, 95% CI 1.07; 2.46) and in subjects older than 80 years (PR 1.88, 95% CI 1.16; 3.03). Older adults with 1-7 years of schooling were more likely to present dysphagia (PR 1.62; 95% CI 1.09; 2.40). Those who did not use dental prosthesis (PR 1.85; 95% CI 1.08; 3.16), who presented dry mouth sensation (PR 4.10; 95% CI 2.59; 6.51) and multimorbidity (PR 30.0; 95% CI 4.09; 219.45) were more likely to present dysphagia perception. The participants who consumed alcohol were 60% less likely to report dysphagia perception (PR 0.43; 95% CI 0.22; 0.86). One out of twelve older adults presented dysphagia perception, and associations with sociodemographic characteristics and other health problems were found. Early identification of dysphagia should be a public health and clinical concern.

Objective and Self-Reported Physical Activity and Risk of Falling Among Community-Dwelling Older Adults From Southern Brazil.

This study evaluated prospective associations between self-reported and objectively measured physical activity (PA) and risk of falls among older adults. A cohort study started in 2014 with 1,451 community-dwelling older adults living in Pelotas, Brazil. Leisure-time PA was obtained by the International Physical Activity Questionnaire and 7-day raw accelerometer data evaluated for total, light PA, and moderate to vigorous PA. In 2016-2017, participants recorded their falls in the previous 12 months. Around 23% of the 1,161 participants followed-up in 2016-2017 experienced a fall in the last 12 months. Participants who did not spend any time in self-reported leisure-time PA at baseline had on average 34% higher risk of falls, and individuals in the lowest tertile for moderate to vigorous PA had on average 51% higher risk of falls compared to those in the highest tertile. Low levels of self-reported and objectively measured moderate to vigorous PA were related to higher risk of falling among Brazilian older adults.

Body mass index and mortality among community-dwelling elderly of Southern Brazil.

This study aims to measure the association between body mass index (BMI), comparing two different classifications, and mortality among community-dwelling elderly considering myopenia in Pelotas, Brazil. This is a longitudinal study started in 2014, we followed 1451 elderly people (≥ 60 years) enrolled in the "COMO VAI?" study. BMI was classified according to the World Health Organization (WHO) and the classification with specific cutoff points for older adults. Myopenia was measured by calf circumference (≤33 cm for women and ≤34 cm for men). Cox proportional-hazards models were used to test associations controlling for sociodemographic and behavioral characteristics and number of morbidities. Nearly 10% (N = 145) of the elderly died during almost three years of follow-up. We observed a L-shaped relation between BMI and mortality. Elderly with underweight had a higher mortality risk compared to those with adequate BMI in both classifications. According to the WHO classification, overweight elderly presented protection for mortality (HR: 0.58; 95% CI 0.38-0.87) when compared to those with adequate BMI. Among elderly with myopenia, overweight by WHO continued to protect against mortality, although not significantly, while those with the specific classification underweight presented a higher risk of death compared to those with normal weight (HR: 2.09; 95% CI 1.06-4.14). In conclusion the underweight increased the risk of death in community-dwelling elderly people during a follow-up of three years. The specific classification seemed to be more adequate to indicate risk of mortality in this population. Higher BMI protect against mortality when muscle mass was not considered.

Pacifier Biosensor: Toward Noninvasive Saliva Biomarker Monitoring.

Wearable sensors for noninvasive monitoring of physiological parameters is a growing technology in the clinical field. Especially in neonates, the development of portable and nonharmful monitoring devices is urgently needed because they cannot provide any feedback about discomfort or health complaints. However, in infant monitoring, only wearable sensors measuring physical parameters for vital signs have been developed. Here, we describe the first chemical wearable sensor for newborn monitoring. This fully integrated pacifier operates as a portable wireless device toward noninvasive chemical monitoring in the infant's saliva. The infant's mouth movements on the pacifier result in efficient saliva pumping and promote unidirectional flow from the mouth to the electrochemical chamber. The integrated electrochemical detection chamber, containing the enzymatic biosensor, is located outside of the oral cavity. The capabilities of the platform were studied for glucose detection in diabetic adults and compared to their blood levels with good correlation, demonstrating the sensor's good performance. This baby-friendly device integrates saliva sampling with electrochemical sensing, along with miniaturized wireless electronics on a single pacifier platform. Such integration simplifies the infant's health monitoring in a real-time and selective fashion, representing the first wearable sensor focusing on chemical saliva sensing in newborns. This initial demonstration of glucose monitoring introduces new possibilities for metabolites monitoring in infants and neonates using saliva as a noninvasive sample.

Relationship between Sarcopenia and mTOR Pathway in Patients with Colorectal Cancer: Preliminary Report.

Sarcopenia is a syndrome characterized by loss of muscle mass and strength that impacts clinical outcomes and mortality in cancer patients. Although the molecular pathways involved in sarcopenia are not fully elucidated, the decrease in protein synthesis rate appears to be one of the most important events. The objective of this study was to investigate the relationship between sarcopenia and mTOR signaling pathway in patients undergoing colorectal resection surgery. Three groups of patients were assessed: 1) the control group (no cancer, no sarcopenia), 2) the cancer non-sarcopenic group and 3) the cancer sarcopenic group. All individuals were evaluated in relation to presence of sarcopenia and mTOR signaling pathway. Sarcopenia was evaluated by the combination of low muscle mass and low muscle strength, measured using computerized tomography images, and hand grip strength, respectively. Rectus abdominis muscle biopsy was performed at the time of surgery. mTOR pathway was analyzed by MILLIPLEX Map Kit Phospho/total mTOR 2-Plex Magnetic Bead Panel. Results were presented by phosphor/total mTOR ratio. Independent T test, Kruskal-Wallis test, and Dunn-Bonferroni post hoc were performed for statistical analysis and P < 0.05 was considered. Thirty-six patients and five controls were evaluated. A total of 13 cancer patients (36.1%) had sarcopenia. The phospho/total mTOR ratio was different between the control group (0.167 MFI) and the cancer non-sarcopenic group (0.055 MFI) (P = 0.026) as well as between the control group (0.167 MFI) and the cancer sarcopenic group (0.0049 MFI) (P = 0.041). No difference was observed on the median phospho/total mTOR ratio between the cancer groups (P > 0.05). More research is needed to extrapolate these results.

Disposable carbon nanotube scaffold films for fast and reliable assessment of total α1-acid glycoprotein in human serum using adsorptive transfer stripping square wave voltammetry.

Alpha-1-acid glycoprotein (AGP) is a serum glycoprotein whose levels are increased two or three times during disease or injury. This makes it a potential biomarker for inflammatory bowel diseases and sepsis. Consequently, fast, simple, and cheap analytical methods for prognosis, diagnosis, and follow-up of these diseases are demanded. In this work, we propose a simple electrochemical approach based on carbon nanotubes scaffold films (CNSFs) for total AGP determination in serum samples. Firstly, AGP is labeled with an electrochemical tag (osmium(VI) complex), and then the total amount of AGP is quantified by adsorptive transfer stripping square wave voltammetry (AdTSWV). Multi-walled carbon nanotubes scaffold films (MWSFs) yielded the best analytical performance in terms of sensitivity with a good limit of detection of 0.6 mg L-1 for AGP determination in serum samples, in less than 20 min. A simplified AGP calibration and its sequential serum sample analysis strategy with good accuracy (81%) and excellent reproducibility (RSD < 1%) was additionally proposed to meet the point-of-care/needs requirements. Graphical abstract Multi-walled carbon nanotubes scaffold films for total AGP determination on disposable platforms integrating single-point calibration and sequential sample analysis.

Exploring the complexity: the interplay between the angiotensin-converting enzyme insertion/deletion polymorphism and the sympathetic response to hemodialysis.

Patients on hemodialysis (HD) are at increased risk for arrhythmias and sudden cardiac death. Autonomic nervous system (ANS) dysfunction seems to participate in the arrhythmogenic process. Genetic factors have an impact on ANS modulation, but the specific role of the insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) has not been investigated. Since the D allele increases gene expression, it is a candidate polymorphism to interact with the ANS. The aim of the present study was to compare the behavior of heart rate variability (HRV) during HD, as a surrogate for ANS response to stressors, between the ACE genotypes. In a sample of patients with chronic kidney disease I/D ACE genotypes were assessed with PCR and HRV was measured before, in the second hour, and after a HD session. HRV parameters in the time and frequency domains were analyzed by repeated-measures mixed models according to the time of measurement and ACE polymorphism. HRV parameters in the frequency domain presented significantly different variations during the HD session between patients with or without the D allele. Only patients with the II genotype presented an increase in low-frequency normalized units and in the low frequency-to-high frequency ratio throughout HD. Patients with the II genotype seemed to have a more physiological response to the volemic and electrolytic changes that occur during HD, with greater sympathetic activation than patients with ID and DD genotypes. NEW & NOTEWORTHY Adding to the effort to understand the complexity of cardiovascular system regulation, we have found that the autonomic nervous system response to the acute volume removal during hemodialysis may be different between angiotensin-converting enzyme insertion/deletion polymorphisms. To our knowledge, this is the first time that this specific interaction was analyzed during a volume removal intervention.

Factors Associated with Sarcopenia in Patients with Colorectal Cancer.

Introduction; Sarcopenia are frequently observed in cancer patients and was associated with poor prognosis. Objectives; to determine the association of nutritional status, body composition, and clinic parameters with sarcopenia in patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional study of 197 patients with CRC. The sarcopenia elements, including lumbar skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The SMI was assessed by computed tomography at third lumbar vertebra. Phase angle (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient-generated subjective global assessment (PG-SGA) were also evaluated. Univariate and multivariate analysis of factors associated with sarcopenia were performed. Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG-SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb, PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia in patients with CRC.

Electrochemical detectors based on carbon and metallic nanostructures in capillary and microchip electrophoresis.

Carbon and metallic-based nanostructures have been progressively implemented as innovative electrochemical detectors in CE and microchip electrophoresis (ME). For both type of nanomaterials and toward selected examples, this review details the impact of these nanomaterials for enhanced detection performance in CE, ME, and paper-based microfluidic devices. The analytical performance and the analytical potential in real world applications is also presented and discussed.

A requiem for BMI in the clinical setting.

PURPOSE OF REVIEW: Quetelet reported in the nineteenth century that body weight varies across adults with the square of height. Quetelet's index, now known as BMI, is accepted by most health organizations as a first-level measure of body fat and as a screening tool for diagnosing excess adiposity. Modern imaging methods now, however, indicate that BMI has limited predictive value for estimating body fat and lean mass at the individual level. The use of BMI as a measure of body composition in the clinical setting should therefore be challenged. RECENT FINDINGS: Recent studies enrolling cancer and surgical patients reported discrepant outcomes when BMI was used as a body composition surrogate. Sarcopenia, loss of muscle mass and function, which affects the elderly and those with chronic and acute diseases, is not accurately diagnosed with BMI. The distribution of adipose tissue is not characterized by BMI, specific measures of which have greater predictive value for metabolic impairments and clinical outcomes. SUMMARY: BMI, as the traditional tool for assessing malnutrition and obesity, is not appropriate to accurately differentiate between important body weight components and therefore should not be used for making clinically important decisions at the individual patient level.

Vertically-Oriented and Shape-Tailored Electrocatalytic Metal Nanowire Arrays for Enzyme-Free Galactosemia Rapid Diagnosis.

Metallic catalytic nanowires such as nickel and copper nanowires (NWs) for electrochemical detection of carbohydrates involved in metabolic rare diseases are proposed. NWs were electrodeposited using a polycarbonate membrane template, which was cut with the desired shape, stuck in double-sided adhesive tape, pasted into a non-conductive substrate and in situ removed. This simple and versatile approach allowed to obtain NWs vertically oriented (v-NWs), which are contained in the double-sided adhesive tape, becoming highly versatile. The high specific surface of working electrode in which the transduction is supported exclusively by the nanomaterial yielded a high analytical performance [extremely low fouling for galactose (RSD<2 %; n=25)]. Likewise, v-NWs exhibited a superior analytical performance with respect to commercial sputtered thick-film electrodes showing also a clear advantage related with the price, as well as with non-need clean room facilities. The analytical potency of the new approach was clearly demonstrated towards the fast and reliable diagnosis of galactosemia using precious newborn urine samples compared to standard clinical diagnosis. These results revealed new opportunities for future enzyme-free diagnosis and development of future point-of-care applications.

Correction: Microchip in situ electrosynthesis of silver metallic oxide clusters for ultra-FAST detection of galactose in galactosemic newborns' urine samples.

Correction for 'Microchip in situ electrosynthesis of silver metallic oxide clusters for ultra-FAST detection of galactose in galactosemic newborns' urine samples by Laura García-Carmona et al., Analyst, 2016, 141, 6002-6007.

Nutritional and functional factors as prognostic of surgical cancer patients.

PURPOSE: We evaluated phase angle, sarcopenia, and handgrip strength as prognostic factors of postoperative morbimortality in patients with cancer. METHODOLOGY: We conducted a prospective study with 60 oncology patients admitted for elective surgery between November 2015 and May 2016. We calculated the standardized phase angle (SPA) and the skeletal mass index of the subjects based on their bioelectrical impedance tests. Handgrip strength (HGS) was measured using a hydraulic dynamometer. Diagnosis of sarcopenia followed the criteria of the European Working Group on Sarcopenia in Older People. The nutritional status of each subject was evaluated through the Patient-Generated Subjective Global Assessment. Evaluation of postoperative complications followed the Clavien-Dindo classification. We also evaluated the duration of hospital stay. Outcomes were postoperative complications and duration of hospital stay. RESULTS: The prevalence of malnutrition was 28.3%, and the prevalence of sarcopenia was 18.6%. The SPA was significantly lower among those who had severe postoperative complications or long hospital stays, while HGS and sarcopenia showed no relationship with these outcomes. Malnutrition was also related to postoperative outcomes. CONCLUSION: SPA can be considered a prognostic factor in postoperative morbimortality for patients with cancer.

Microchip in situ electrosynthesis of silver metallic oxide clusters for ultra-FAST detection of galactose in galactosemic newborns' urine samples.

This work describes for the first time the coupling of microfluidic chips (MC) to electrosynthetized silver metallic oxide clusters (AgMOCs). As an early demonstration of this novel approach, the ultrafast detection of galactose in galactosemic newborns' urine samples is proposed. AgMOCs were in situ electrosynthetized on integrated microchip platinum electrodes using a double pulse technique and characterized in full using scanning electronic microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) and electrochemical techniques revealing the presence of silver oxides and electrocatalysis towards galactose as a galactosemia biomarker. Galactose detection in galactosemic newborns' urine samples proceeded in less than 30 s, differentiating between ill and healthy urine samples and requiring negligible urine sample consumption. The significance of the newborns' urine samples confirmed the analytical potency of the MC-AgMOCs approach for future implementation of screening for rare disease diagnosis such as galactosemia.

Enzyme-based microfluidic chip coupled to graphene electrodes for the detection of D-amino acid enantiomer-biomarkers.

An electrochemical microfluidic strategy for the separation and enantiomeric detection of D-methionine (D-Met) and D-leucine (D-Leu) is presented. These D-amino acids (D-AAs) act as biomarkers involved in relevant diseases caused by Vibrio cholerae. On a single layout microfluidic chip (MC), highly compatible with extremely low biological sample consumption, the strategy allowed the controlled microfluidic D-AA separation and the specific reaction between D-amino acid oxidase (DAAO) and each D-AA biomarker avoiding the use of additives (i.e., cyclodextrins) for enantiomeric separation as well as any covalent immobilization of the enzyme into the wall channels or on the electrode surface such as in the biosensor-based approaches. Hybrid polymer/graphene-based electrodes were end-channel coupled to the microfluidic system to improve the analytical performance. D-Met and D-Leu were successfully detected becoming this proof-of-the-concept a promising principle for the development of point-of-care (POC) devices for in situ screening of V. cholerae related diseases.

Gold Nanoparticles-based Extraction-Free Colorimetric Assay in Organic Media: An Optical Index for Determination of Total Polyphenols in Fat-Rich Samples.

In this work, a rapid and simple gold nanoparticle (AuNPs)-based colorimetric assay meets a new type of synthesis of AuNPs in organic medium requiring no sample extraction. The AuNPs synthesis extraction-free approach strategically involves the use of dimethyl sulfoxide (DMSO) acting as an organic solvent for simultaneous sample analyte solubilization and AuNPs stabilization. Moreover, DMSO works as a cryogenic protector avoiding solidification at the temperatures used to block the synthesis. In addition, the chemical function as AuNPs stabilizers of the sample endogenous fatty acids is also exploited, avoiding the use of common surfactant AuNPs stabilizers, which, in an organic/aqueous medium, rise to the formation of undesirable emulsions. This is controlled by adding a fat analyte free sample (sample blank). The method was exhaustively applied for the determination of total polyphenols in two selected kinds of fat-rich liquid and solid samples with high antioxidant activity and economic impact: olive oil (n = 28) and chocolate (n = 16) samples. Fatty sample absorbance is easily followed by the absorption band of localized surface plasmon resonance (LSPR) at 540 nm and quantitation is refereed to gallic acid equivalents. A rigorous evaluation of the method was performed by comparison with the well and traditionally established Folin-Ciocalteu (FC) method, obtaining an excellent correlation for olive oil samples (R = 0.990, n = 28) and for chocolate samples (R = 0.905, n = 16). Additionally, it was also found that the proposed approach was selective (vs other endogenous sample tocopherols and pigments), fast (15-20 min), cheap and simple (does not require expensive/complex equipment), with a very limited amount of sample (30 µL) needed and a significant lower solvent consumption (250 µL in 500 µL total reaction volume) compared to classical methods.

Multidimensional carbon allotropes as electrochemical detectors in capillary and microchip electrophoresis.

The main multidimensional carbon allotropes could be classified into carbon nanotubes as 1D material, graphene as 2D material, as well as graphite and diamond as 3D carbon materials. Along with this review, a discussion using these four structures as electrochemical detectors in CE and ME will permit us to explore the recent advances in this field.