International Recommendations Research Articles

Rapid analysis of amatoxins in human urine by means of affinity column chromatography and liquid chromatography-high-resolution tandem mass spectrometry

Analysis of amatoxins is of great importance as these cyclic peptides contribute to a high number of fatalities each year. Development of analytical approaches needs to focus on rapid, sensitive, and reliable methods. By establishing an affinity column chromatography-based assay using the monoclonal amanitin antibody AMA9G3 and liquid chromatography (LC) coupled to high-resolution mass spectrometry (HRMS) for the trace detection of α-, β-, and γ-amanitin in human urine samples to confirm ingestion, we report the first approach that extents the current status of amatoxin analysis. The presented procedure allows detection of amatoxins in human urine down to 1 ng/mL. The method was successfully validated qualitatively for α- and γ-amanitin according to international recommendations. A proof of concept was performed by analyzing 37 urine samples after suspected amatoxin consumption submitted for regular clinical toxicological analysis. Using this antibody-based enrichment strategy, acute amatoxin intoxications can be determined within 90 min and due to the high sensitivity and selectivity, a comparable approach using target specific antibodies may also be used for other toxicological relevant peptides.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

Rotation or change of biotherapy after TNF blocker treatment failure for axial spondyloarthritis: the ROC-SpA study, a randomised controlled study protocol

IntroductionAxial spondyloarthritis (axSpA) is a chronic inflammatory disease characterised by inflammatory low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as a first treatment in axSpA. In case of inadequate...

Pregnancy outcomes among women with inflammatory bowel disease: A UK tertiary centre experience.

Optimal management of inflammatory bowel disease (IBD) in pregnancy is associated with better pregnancy outcomes. We describe management of IBD during pregnancy and maternal and fetal outcomes of patients from a tertiary UK IBD centre. This is a retrospective observational cohort study of all pregnancies occurring between 2015 and 2021 in a large tertiary IBD centre in the UK. IBD activity and management prior to, during and after pregnancy were recorded along with pregnancy and neonatal outcomes. Associations between IBD-focused interventions and any adverse pregnancy outcomes, as well as the association between IBD severity and treatments and adverse maternofetal outcomes were assessed. Pregnancies in 130 women with IBD were included for analysis. The mean maternal age at delivery was 30.5 (± 4.7) years. At conception, 73 women (56.2%) were in clinical remission and 24 (18.4%) were treated with a biologic agent. Active disease during pregnancy, measured by physician global assessment, was less frequent in women who were in clinical remission at conception, compared to those not in remission at conception (16/73 21.9% vs. 39/49 79.6%; data insufficient for eight women). Active IBD at conception was associated with pre-term birth (p = 0.04). Maternal corticosteroid use in any trimester was associated with low birth weight (T1 p = 0.02; T2 p = 0.005; T3 p = 0.007). Active disease (p = 0.008) and steroid use in the third trimester (p = 0.05) were both associated with neonatal infections up to sixmonths after birth. Women in clinical remission at the time of conception have favorable outcomes, consistent with prospective observational studies. Our observations emphasize the importance of high quality IBD care for women pre and post-partum in line with international recommendations.

Minor surgical procedures during immune tolerance induction in people with hemophilia A and inhibitors: results from the Brazilian Immune Tolerance (BrazIT) study cohort

IntroductionSurgeries are implicated in the development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) in hemophilia A individuals with immune tolerance induction (ITI) treatment being the recommended therapy to eradicate these inhibitors. We evaluated the association of surgical procedures performed during ITI and treatment outcome. MethodsPatients were treated according to the Brazilian ITI Protocol with outcomes being defined as successful (i.e., recovered responsiveness to exogenous FVIII) and failed (i.e., unresponsiveness to exogenous FVIII thus requiring bypassing agents for bleeding control). Surgical procedures during induction therapy were managed following international recommendations. ResultsTreatment success rate was 68.7 % in 163 patients; 33 (20.2 %) were submitted to 43 (96 %) minor and two major surgeries. Personal, hemophilia, inhibitor, and treatment characteristics were similar between patients submitted to surgical procedures or not while on ITI; the success rates were 72.7 % and 67.7 % (p-value = 0.577), respectively. ConclusionNo association was found between having a minor surgical procedure and ITI treatment outcome.

The role of unsaturated fatty acids in depression treatment - international clinical guidelines and recommendation of psychiatric associations

The role of unsaturated fatty acids in depression treatment - international clinical guidelines and recommendation of psychiatric associations

Is per capita fish consumption in Latin America aligned with international recommendations for a healthy diet?

The World Health Organization (WHO) is urging Latin American countries to prioritize the prevention of chronic noncommunicable diseases. Diet is a crucial factor in determining one’s health, and healthy eating recommendations emphasize the consumption of fish at least twice a week due to its protein, vitamin, mineral, and essential fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This review was designed to compare the status of fish consumption as a source of EPA and DHA fatty acids in some Latin American countries (namely Brazil, Chile, Colombia, and Ecuador), and comparisons with international recommendations within a healthy diet could contribute to the WHO’s call for a focus on preventing the aforementioned diseases in the region. A comprehensive literature search was conducted from January to October 2022 using PubMed, Scopus, EBSCO, and government compendia. Keywords included “fish,” “consumption,” “fatty acids,” “nutrients,” and “Latin America;” and “fish,” “chronic non-communicable diseases,” “all-cause mortality,” “obesity,” “cancer,” “neurodegenerative diseases,” “metabolic diseases,” “diabetes,” “polycystic ovary syndrome,” and “metabolic syndrome.” In countries such as Chile, Brazil, and Colombia, per capita fish consumption falls below WHO’s recommended levels, and the most commonly eaten species do not contain sufficient polyunsaturated fatty acids to provide an optimal intake of EPA and DHA. It is therefore recommended that each country review its dietary guidelines and fish recommendations based on the most commonly consumed species to ensure that their populations obtain the recommended intake of EPA and DHA fatty acids and thus the benefits related to the prevention of chronic noncommunicable diseases.

Value of troponin and NT-proBNP to screen for cardiac amyloidosis after carpal tunnel syndrome surgery

BackgroundEarly diagnosis of cardiac amyloidosis (CA) is crucial due to the promising effect of disease-modifying treatment. This calls for screening strategies to identify CA patients with so-called “red flags”, such as carpal tunnel syndrome (CTS). ObjectivesThis study aims to assess Troponin-T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) as predictors for CA in patients with a history of surgery for bilateral carpal tunnel syndrome, a population suitable for systematic screening. MethodsSubjects with a history of surgery for bilateral CTS 5–15 years prior, identified using national registries were investigated for CA as per international recommendations. Sensitivity, specificity, positive and negative predictive values were assessed, and receiver operating curves were generated using logistic regression. ResultsAmong the 250 participants, 12 were diagnosed with CA, all with wild-type transthyretin amyloidosis. Elevated TnT levels (≥13 ng/L) were found in all CA patients and 25.6% (±2.8) of non-CA patients. The negative predictive value (NPV) of TnT <13 ng/L was 100%. For NT-ProBNP the NPV was 99.1% when age dependent cutoff levels were used. A combination of both biomarkers yielded an NPV of 99.1% and sensitivity of 99.7%. Early disease (Mayo or NAC stage 1) was found in 83% of identified patients with CA. ConclusionThis study demonstrates the utility of TnT and NT-ProBNP as negative predictors to exclude CA in a screening population with a history of surgery for CTS.

Prophylactic phenylephrine infusion versus treatment with vasopressor bolus as needed during non-urgent cesarean delivery and neonatal acidemia: a retrospective cohort study (2016–2021)

IntroductionProphylactic vasopressor administration reduces spinal hypotension during cesarean delivery, however the effects of vasopressor administration on neonatal acidemia remain uncertain. We examined the occurrence of neonatal acidemia in the setting of non-urgent cesarean delivery and compared outcomes between cases receiving prophylactic phenylephrine infusion versus cases treated with boluses of phenylephrine. MethodsRetrospective cohort study with ethical approval, comparing non-urgent cesarean delivery cases performed under spinal anesthesia (2016 to 2021), receiving either prophylactic phenylephrine infusion or boluses as needed.Data were collected from anesthesia and labor ward electronic medical records. Records with missing pH or missing blood pressure data were excluded. The independent variable was prophylactic phenylephrine administration, a strategy implemented following international recommendations in 2018. The main outcome was neonatal acidemia, defined as umbilical artery pH < 7.1. The secondary outcome was maternal hypotension, defined as at least one systolic blood pressure (SBP) measurement below 100 mmHg or below 80% baseline. ResultsA total of 4392 patients were included in the final analysis; 1318 (30.0%) received prophylactic phenylephrine infusion. Neonatal acidemia (umbilical artery pH < 7.1) occurred in 28 (2.1%) cases receiving prophylactic phenylephrine versus 50 (1.6%) treated with boluses as needed (p = 0.188). Prophylactic phenylephrine infusion was not associated with occurrence of neonatal acidemia (aOR 0.83; 95% CI 0.52 to 1.33, p = 0.435). Prophylactic phenylephrine infusion was associated with a reduced spinal hypotension rate when defined as SBP < 100 mmHg (OR 0.47; 95% CI 0.37 to 0.57; p < 0.001), with similar results when hypotension was defined as a drop below 80% or 90% of baseline SBP. ConclusionIn this pragmatic study, prophylactic phenylephrine infusion was associated with a reduction in maternal spinal hypotension, but not reduced neonatal acidemia.

One Health Priorities: Advancing Veterinary Public Health in Latin America and the Caribbean.

One Health (OH) is an integrative approach to human, animal, and environmental health and can be used as a comprehensive indicator for comparative purposes. Although an OH index has been proposed for comparing cities, states, and countries, to date, no practical study has compared countries using this approach. Accordingly, this study aimed to assess OH initiatives using a survey with a veterinary public health focus. The questionnaire contained 104 quantitative questions and was sent to representatives of governmental institutions of 32 countries in the Americas. After exclusion criteria were considered, a total of 35 questionnaires from 17 countries were analyzed, with country names remaining undisclosed during the statistical analyses to protect potentially sensitive information. Principal component analysis (PCA) of health parameters in Latin America and the Caribbean (LAC) as a function of country perception (self-vector) showed that food safety was ranked higher than public policies (p = 0.009), and that both (p = 0.003) were ranked higher than institutional routines related to zoonosis programs. National policies in accordance with international standards, regulations, recommendations, and guidelines was considered the standout topic for public policy, with higher-ranking topics including standard. Meanwhile, challenging topics included tools, preparedness, governance, and research. Food safety showed both strengths and challenges in the coordination of its activities with other sectors. Food safety communication was scored as a strength, while foodborne diseases prevention was ranked as a challenge. Institutional routines for zoonosis maintained both strong and challenging topics in the execution and implementation of attributions and daily routine. Thus, the survey showed that topics such as access to and compliance with international guidelines and intercountry integration were ranked higher than in-country articulation, particularly among food safety, zoonoses, and environmental institutions.

Widespread service fragmentation for patients and families with tuberous sclerosis complex (TSC) in the Republic of Ireland

BackgroundTuberous sclerosis complex (TSC) is a rare approximate 1:6000 birth incidence, a genetic disease with a wide variability of physical and neuropsychiatric symptoms. Patients require lifelong care from multiple healthcare specialities, for which International and United Kingdom (UK) TSC consensus recommendations exist. Personalised care delivered by a centralised coordinated team of TSC experts is recommended. There is no such service for the estimated 600 TSC patients in the Republic of Ireland (ROI) and there is a paucity of information regarding the healthcare of this group.PurposeEvaluate the baseline care of patients with TSC attending epilepsy services in the Republic of Ireland (ROI) against UK TSC consensus recommendations.MethodsPatients with a diagnosis of TSC attending 12 adult and paediatric epilepsy centres in the ROI were identified. Clinical audits measured the baseline care of a subset of these patients against UK, TSC clinical recommendations. Data was anonymised and analysed at Trinity College Dublin.ResultsOne hundred thirty-five TSC patients attending twelve epilepsy centres were identified. Adults (n = 67) paediatric (n = 68). The care of 83 patients was audited (n = 63 ≥ 18 years) and (n = 20 < 18 years). Many baseline tests were completed, however, they required intra or interhospital referral. Care appears fragmented and there was no evidence of formal disease surveillance plans.ConclusionsThe number of TSC patients attending epilepsy services is lower than expected (n = 135). Specialist services and treatments for TSC are available through informal referral pathways. Although UK, TSC consensus baseline recommendations are roughly adhered to, care is fragmented. Increased coordination of care could benefit disease management.

Development and psychometric validation of a patient safety assessment tool in German Radiation Oncology: the PaSaGeRO Study protocol

IntroductionEnsuring patient safety in radiation oncology is crucial for delivering high-quality healthcare. Patient safety indicators (PSIs) provide a mechanism for identifying, quantifying and evaluating risks and the effectiveness of safety...

Quality-of-care standards in adult type 3 intestinal failure caused by benign disease: A European society of clinical nutrition and metabolism (ESPEN) position paper

BackgroundOutcomes related to chronic intestinal failure (CIF) vary significantly within and between countries. While there are extensive European Society of Clinical Nutrition and Metabolism (ESPEN) guidelines on the delivery of optimal care in CIF, there are no international consensus recommendations on the structure or resources required, nor on the process and appropriate outcome measures for delivering such quality care in CIF. AimThe aim of this position paper is therefore to devise ESPEN-endorsed, internationally agreed quality of care standards, covering the resources, systems and standards that centres should aim for in order to deliver optimal CIF care. MethodsMembers of the Home Artificial Nutrition-CIF Special Interest Group of ESPEN proposed an initial set of quality-of-care standards which was submitted to voting amongst clinicians from international CIF centres using a modified Delphi process, with participants rating each proposed statement as ‘essential’, ‘recommended’ or ‘not required’. Any statement receiving 80% of more ‘not required’ responses was excluded. ResultsAll 30 proposed standards relating to the structure, 18 relating to the process and 16 to the outcome measures of CIF care were deemed to be essential or recommended in more than 80% of respondents. ConclusionThis is the first paper to determine and describe internationally-agreed quality of care standards in CIF, which are now aimed at forming the basis for all CIF teams to develop and monitor their service, while also informing policymakers and payers on the infrastructure required for the optimal approach to multi-disciplinary team CIF care delivery. The recording of standardised outcomes should also allow internal and external benchmarking of care delivery within and between CIF centres.

Glycaemia and ischaemia-reperfusion brain injury in patients with ischaemic stroke treated with mechanical thrombectomy (GLIAS-MT): an observational, unicentric, prospective study protocol

IntroductionPoststroke hyperglycaemia is an independent risk factor for poorer outcomes in patients treated with mechanical thrombectomy (MT) and is associated with a lower probability of functional recovery and higher mortality...

Formula-led methods using first morning fasting spot urine to assess usual salt intake: a secondary analysis of PURE study data.

Observational studies that assess the relationship between salt intake and long-term outcomes require a valid estimate of usual salt intake. The gold-standard measure in individuals is sodium excretion in multiple nonconsecutive 24-h urines. Multiple studies have demonstrated that random spot urine samples are not valid for estimating usual salt intake; however, some researchers believe that fasting morning spot urine samples produce a better measure of usual salt intake than random spot samples. We have used publicly available data from a PURE China validation study to compare estimates of usual salt intake from morning spot urine samples and four published formulae with mean of two 24-h urine samples (reference). We estimated the mean and 95% confidence interval of absolute and relative error for each formula-led method and the degree to which estimates were able to be classified into the correct quartile of intake. Bland-Altman plots were used to test the level of agreement. The results show that compared with the reference method, all formulae-led estimates from spot urine collections have high error rates: both random and systematic. This is demonstrated for individual estimates, as well as by quartiles of reference salt intake. This study conclusively demonstrates the unsuitability of morning spot urine formula-led estimates of usual salt intake. Our findings support international recommendations to not conduct, fund, or publish research studies that use spot urine samples with estimating equations to assess individuals' salt intake in association with health outcomes.

Continuous glucose monitoring metrics in people with liver glycogen storage disease and idiopathic ketotic hypoglycemia: A single-center, retrospective, observational study

BackgroundCohort data on continuous glucose monitoring (CGM) metrics are scarce for liver glycogen storage diseases (GSDs) and idiopathic ketotic hypoglycemia (IKH). The aim of this study was to retrospectively describe CGM metrics for people with liver GSDs and IKH. Patients and methodsCGM metrics (descriptive, glycemic variation and glycemic control parameters) were calculated for 47 liver GSD and 14 IKH patients, categorized in cohorts by disease subtype, age and treatment status, and compared to published age-matched CGM metrics from healthy individuals. Glycemic control was assessed as time-in-range (TIR; ≥3.9 - ≤7.8 and ≥ 3.9 - ≤10.0 mmol/L), time-below-range (TBR; <3.0 mmol/L and ≥ 3.0 - ≤3.9 mmol/L), and time-above-range (TAR; >7.8 and > 10.0 mmol/L). ResultsDespite all patients receiving dietary treatment, GSD cohorts displayed significantly different CGM metrics compared to healthy individuals. Decreased TIR together with increased TAR were noted in GSD I, GSD III, and GSD XI (Fanconi-Bickel syndrome) cohorts (all p < 0.05). In addition, all GSD I cohorts showed increased TBR (all p < 0.05). In GSD IV an increased TBR (p < 0.05) and decreased TAR were noted (p < 0.05). In GSD IX only increased TAR was observed (p < 0.05). IKH patient cohorts, both with and without treatment, presented CGM metrics similar to healthy individuals. ConclusionDespite dietary treatment, most liver GSD cohorts do not achieve CGM metrics comparable to healthy individuals. International recommendations on the use of CGM and clinical targets for CGM metrics in liver GSD patients are warranted, both for patient care and clinical trials.

Biological variation of methylmalonic acid in urine in spanish population

Background-AimMethylmalonic acid (MMA) is currently the best biomarker of functional vitamin B12 deficiency. However, for a correct interpretation of the patient’s results it is necessary to know its biological variation (BV).No BV data are available for urine MMA values, as measured by mass spectrometry. Hence, the aim of this study was to estimate the within- and between-person coefficients of variation (CVw, CVg) for MMA in a healthy population, and the associated index of individuality (II), as well as to define quality specifications based on BV and the reference change value (RCV). MethodsRandom urine samples from 34 healthy volunteers were collected over four consecutive weeks. Samples were stored at –80 °C until analysis in a single analytical run. MMA excretion was quantified by tandem liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results were normalized to urine creatinine.The coefficients of variation were estimated by CV-ANOVA. Confidence intervals (95 %) were calculated. Quality specifications were defined according to international recommendations. ResultsA total of 128 samples were included. The coefficients of variation were CVw = 35.7 % (26.1–45.3) and CVg = 67.7 % (58.3–77.0). The associated II was 0.5 and the RCV was 88.1 %. ConclusionConsidering the II obtained, MMA in urine has high individuality, therefore, RCV is better to evaluate serial clinical results. Our results will contribute to a better clinical interpretation of this biomarker and will represent a great aid when defining analytical performance specifications for this magnitude.

White and wholewheat bread consumption and the risk of exposure to acrylamide and 5-hydroxymethylfurfural

This study used a green validated method to evaluate the risk of exposure of individuals of different ages to acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) by consuming white and wholewheat bread. Recoveries of AA and 5-HMF were 100.7% and 100.1%, respectively, while uncertainty was 2.3% and 6.2%. Levels of AA ranged from 617.22 to 3151.8 μg/kg while levels of 5-HMF ranged from 180.5 to 648.2 μg/kg. Female adolescents were almost 2-fold exposed to AA when they consumed 100% wholewheat bread (2.93 μg/kg bw/day) by comparison with white bread (1.72 μg/kg bw/day). Estimated daily exposure to AA was 1.5-fold higher than international recommendations. These findings raise concern for health risks associated with exposure to processing contaminant as the result of bread consumption, especially made from whole grains. Since development of those compounds is inevitable during breadmaking, it is crucial to standardize processing conditions and recipes to mitigate it.

Ozone therapy in musculoskeletal medicine: a comprehensive review

Musculoskeletal disorders encompass a wide range of conditions that impact the bones, joints, muscles, and connective tissues within the body. Despite the ongoing debate on toxicity and administration, ozone demonstrated promise in managing several musculoskeletal disorders, modulating pain and inflammation. A literature search was conducted. The research design, methods, findings, and conclusions of the studies were then examined to evaluate the physiological effects, clinical application, controversies, and safety of the application of ozone in musculoskeletal medicine. Ozone application demonstrates considerable therapeutic applications in the management of musculoskeletal disorders, including fractures, osteoarthritis, and chronic pain syndromes. Despite these advantages, studies have raised concerns regarding its potential toxicity and emphasized the importance of adhering to stringent administration protocols to ensure safety. Additionally, heterogeneities in patient reactions and hazards from oxidizing agents were observed. Given its anti-inflammatory and analgesic qualities, ozone therapy holds potential in the management of several musculoskeletal disorders. Additional high-quality research with long follow-up is required to refine indications, efficacy and safety profile. Finally, for wider clinical acceptability and utilization, the development of international recommendations is essential.

Extraskeletal Ewing sarcoma of the extremities and trunk: a retrospective analysis of a mono-institutional series.

Introduction Extra-skeletal Ewing sarcoma is a rare malignant tumor, and current international recommendations indicate systemic and local treatment like bone Ewing sarcoma; to the best of our knowledge, very few studies tried to explore the clinical and genetic characteristics of this tumor and the most appropriate treatment strategy remains uncertain. Methods We reviewed 35 extra-skeletal Ewing sarcoma (EEwS) cases enrolled at Rizzoli Orthopedic Institute in Bologna, Italy between 1988-2022. We performed RNA sequencing in 18 Ewing sarcoma cases, including 12 bone Ewing sarcomas (BEwS) and 6 EEwS. We analyzed overall survival (OS), local relapse-free survival (LRFS), and metastasis-free survival (MFS) and the risk factors associated to survival. Results Unsupervised Hierarchical clustering showed no differences in the transcriptional profile between EEwS and BEwS. Five-year OS was 67% (95%CI 47-80), 5-year LRFS was 61% (95% CI 43-75), and 5-year MFS was 55% (95% CI 38-70). Recurrent tumors, larger than 8 cm, and elevated LDH serum value resulted to be a negative prognostic factor. Conclusions The founding of a genetic profile indistinguishable between EEwS and BEwS, confirms the view that includes the two subgroups in the same tumor entity and supports the use of a single therapeutic approach for Ewing sarcoma independently from the site of origin. Statistical evaluation showed that size bigger than 8cm, elevated LDH, and recurrent tumors had a worse prognosis, suggesting a risk-stratification method for identifying patients for specific therapy treatment. However, larger, multicentre, prospective trials are called for to validate our findings.