Comparison of treatment modalities for non-tuberculous mycobacterial cervicofacial lymphadenitis in children.

PURPOSE: We aim to compare the different treatment modalities of non-tuberculous cervicofacial lymphadenitis in children, by means of a retrospective study conducted in the University Hospitals of Leuven of patients treated between 2012 and 2022. METHODS: For this retrospective cohort study, data were collected and pseudonimised from 52 patients with non-tuberculous cervicofacial lymphadenitis, who were treated in our hospital between January 2012 and December 2022, either conservatively, antibiotically, surgically, or with a combination of these options. We only included patients who were considered immunocompetent. All of the included patients were below 10 years at time of treatment. We collected data regarding time to resolution and adverse effects, i.e., skin discoloration, excessive scar formation, fistula formation, persistence of adenopathies after treatment, need for additional treatment, facial nerve paresis/paralysis, or systemic side-effects due to antibiotic treatment. RESULTS: The mean time to resolution (in days) when looking at primary treatments, was shortest in partial excisions (16), followed by complete excisions (19), antibiotic therapy (129), incision and drainage (153), curettage (240), and finally conservative management (280). Taking into account isolated treatments (i.e., both primary and adjuvant), we also observed consistently faster time to resolution in surgical and antibiotic treatments when compared to conservative treatment. Antibiotic therapy (p = 0.003), incision and drainage (p = 0,004) were associated with a significantly higher need for adjuvant treatment. Curettage was associated with a higher incidence of fistula formation (p = 0,006) and higher number of adjuvant treatments (p = 0,002). CONCLUSIONS: This study shows a faster resolution of nontuberculous mycobacterial cervicofacial lymphadenitis in children when treated surgically, more specifically when treated with partial or complete lymph node excision. Antibiotic treatment also leads to faster resolution than conservative management. There was a low rate of complications, and no permanent facial nerve damage was reported.

The European TREatment of ATopic eczema (TREAT) Registry Taskforce survey: prescribing practices in Europe for phototherapy and systemic therapy in adult patients with moderate-to-severe atopic eczema.

BACKGROUND: For many years dermatologists have had access to few therapies for patients with moderate-to-severe atopic eczema (AE). New promising therapies are entering the market but conventional phototherapies and systemic therapies have more well-known safety profiles, lower costs and wider availability. OBJECTIVES: To provide insight into current prescribing practices of conventional phototherapy and systemic immunomodulatory therapies for adults with chronic AE, and the factors influencing these prescribing practices, before biologics and other novel therapeutics become routine clinical practice. METHODS: In this exploratory study dermatologists were invited to participate in an online survey via a mailing list of the European Academy of Dermatology and Venereology and national societies. Data were collected on participant characteristics (including clinical practice data), the use of phototherapies and systemic therapies, and factors influencing their use. RESULTS: From 30 European countries, 238 out of 361 dermatologists willing to participate (65·9%) completed the survey, with 229 meeting the inclusion criteria. For phototherapy (prescribed by 84·7%), most preferred narrowband ultraviolet B as first line (80·9%) and psoralen plus ultraviolet A as second (21·6%). For systemic therapy (prescribed by 95·2%) ciclosporin (54·1%), oral corticosteroids (32·6%) and methotrexate (30·7%) were used first line. Dermatologists relied mostly on personal experience for prescribing phototherapy and systemic therapy. Azathioprine and mycophenolic acid were prescribed by only 135 (59·0%) and 85 (37·1%) participants in total, mostly due to a lack of personal experience. CONCLUSIONS: This study provides insight into prescribing practices for conventional phototherapy and systemic therapy in Europe and shows that off-label therapies are also preferred as first-line choice of systemic therapy.

TREatment of ATopic eczema (TREAT) Registry Taskforce: protocol for a European safety study of dupilumab and other systemic therapies in patients with atopic eczema.

BACKGROUND: A long-term prospective observational safety study is essential to characterize fully the safety profile of systemic immunomodulating therapies for patients with atopic eczema. The TREatment of ATopic eczema (TREAT) Registry Taskforce offers a large platform to conduct such research using national registries that collect the same data using a predefined core dataset. OBJECTIVES: To present a protocol for a safety study comparing dupilumab with other systemic immunomodulating therapies in children and adults with moderate-to-severe atopic eczema, to assess the long-term safety risk of these therapies in a routine clinical care setting. METHODS: We describe a registry-embedded international observational prospective cohort study. Adult and paediatric patients who start treatment with dupilumab or another systemic immunomodulating agent for their atopic eczema will be included. The primary end point is the incidence of malignancies (excluding nonmelanoma skin cancer) compared between the treatment groups. Secondary end points include other serious adverse events and adverse events of special interest, such as eye disorders and eosinophilia. CONCLUSIONS: This protocol delineates a safety study for dupilumab in adult and paediatric patients with atopic eczema, using a standardized methodological approach across several national registries. The protocol could also be used for other novel systemic immunomodulating therapies, and could provide licensing and reimbursement authorities, pharmaceutical companies and clinicians with safety evidence from a routine clinical care setting. What's already known about this topic? There is a need for long-term data on the safety of systemic immunomodulating therapies in patients with atopic eczema. Regulatory bodies, such as the European Medicines Agency, increasingly stipulate the collection of such data as part of the licensing agreement for new treatments, to assess the new agent's long-term safety profile against established therapies. Large numbers of patients with a long duration of follow-up are necessary in order to detect rare events like malignancies. What does this study add? The TREAT Registry Taskforce offers a platform to conduct such research with a network of multiple national atopic eczema research registries. We present a protocol for an investigator-initiated multicentre safety study comparing dupilumab with other systemic immunomodulating therapies in adults and subsequently adolescents and children with moderate-to-severe atopic eczema. This protocol can be used as a framework for similar studies for other novel systemic immunomodulating therapies across both adult and paediatric populations.

The current extent of and need for shared decision making in atopic dermatitis and psoriasis in the Netherlands: an online survey study amongst patients and physicians.

BACKGROUND: In shared decision making (SDM), patients and physicians work together to choose the best treatment option for an individual patient. Atopic dermatitis (AD) and psoriasis are particularly suitable for SDM, considering that the best treatment option depends on a patient's preferences and values (preference-sensitive decisions). Currently, it is unknown to what extent SDM is applied in treatment decisions for these diseases in the Netherlands. OBJECTIVES: Primary, to assess the current extent of SDM in AD and psoriasis in the Netherlands amongst patients and dermatologists. Secondary, to assess the degree to which patients and physicians endorse SDM, to explore which characteristics are related to their preference to be involved in SDM and to identify which barriers and facilitators for SDM they perceive. METHODS: Two similar online surveys, one for patients with AD or psoriasis and one for (resident) dermatologists, were carried out. The surveys comprised validated questionnaires (shared decision making questionnaire (SDM-Q; range 0-100), Control Preference Scale) and study-specific statements mainly regarding barriers and facilitators for SDM. RESULTS: The responses of 219 patients and 147 physicians were analysed. Dermatologists experienced significantly more SDM than patients (SDM-Q 82 vs 55; P < 0.01). Most patients and dermatologists prefer to share treatment decisions. Mainly facilitators for SDM were perceived, including the positive perception of patients and dermatologists regarding SDM. The perceived barriers included lack of continuity of care by the same physician and lack of time. CONCLUSION: Despite the dermatologists' optimistic perspective, patients experience a limited extent of SDM and physicians should be aware of this gap. Improvement of SDM in AD and psoriasis is needed. The positive attitude of patients and dermatologists towards the process and outcome of SDM is important facilitators, while barriers were mainly perceived on an organizational level.

TREatment of ATopic eczema (TREAT) Registry Taskforce: consensus on how and when to measure the core dataset for atopic eczema treatment research registries.

BACKGROUND: Comparative, real-life and long-term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate-to-severe atopic eczema (AE) is limited. Such data must come from well-designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling. OBJECTIVES: To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE. METHODS: Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face-to-face consensus meetings, one teleconference and via e-mail. The frequency of follow-up visits was determined by an expert survey. RESULTS: A total of 16 experts from seven countries participated in the 'how to measure' consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow-up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined. CONCLUSIONS: This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long-term effectiveness and safety of phototherapy and systemic therapy used in patients with AE. What's already known about this topic? Comparable, real-life and long-term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed. There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling. What does this study add? Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries. This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data. What are the clinical implications of this work? The data collected through this core dataset will help to gain better insights into the long-term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice. Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment-related adverse events that require large patient numbers).

Effect of previous vaccination with pneumococcal conjugate vaccine on pneumococcal polysaccharide vaccine antibody responses.

During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced.

[Bronchopulmonary infections caused by atypical pathogens in children : Myth or reality?] / Les infections broncho-pulmonaires à germes atypiques chez l'enfant : Mythe ou réalité ?

Mycoplasma pneumoniae and Chlamydia pneumoniae are the most common atypical pathogens seen in respiratory infections in children. Currently, the management of atypical pneumonia due to these pathogens is blurry. The clinical features are hardly specific ; it appears that M. pneumoniae respiratory infect ions are associated with chest pain and the absence of wheezing, however, further confirmations are needed. Hoarseness is frequently seen with C. pneumoniae infection. Co-infections with viruses, bacteria or even between M. pneumoniae and C. pneumoniae can be frequent. Infection with either of these bacteria seems to increase the incidence of asthma. PCR appears to be the most sensitive and specific for rapid diagnosis of M. pneumoniae and C. pneumoniae infections, however, it cannot dif ferentiate asymptomatic carriage from infection. Serodiagnosis can be helpful. This requires two serum samples taken with several weeks interval. Macrolides are the classical antibiotics used for treatment of these pathogens. In vivo efficacy of antibiotic treatment of M. pneumoniae remains unclear. Resistance to macrolides in M. pneumoniae treatment has been described. In conclusion, there is still a lack in scientific literature of high level evidences and clear consensus in the management of suspicious infection due to M. pneumoniae and C. pneumoniae.

Les germes atypiques les plus fréquemment rencontrés dans les infections respiratoires chez l'enfant sont Mycoplasma pneumoniae ou Chlamydia pneumoniae. La prise en charge des bronchopneumopathies atypiques à ces deux germes reste actuellement floue. La symptomatologie est pauvre, aucun signe clinique spécifique n'a pu être à ce jour identifié. Il semblerait que les infections respiratoires à M. pneumoniae sont associées à des douleurs thoraciques ou à une absence de wheezing même si cela reste à confirmer. Les infections à C. pneumoniae seraient plus souvent associées à des laryngites. Les co-infections virales, bactériennes ou entre les deux germes atypiques, M. pneumoniae et le C. pneumoniae, ne sont pas rares. Une infection par une de ces deux bactéries augmenterait l'incidence de l'asthme. Le diagnostic par PCR semble être la méthode diagnostique la plus spécifique et la plus sensible, autant pour le M. pneumoniae que pour le C. pneumoniae. Cependant, elle ne permet pas de différencier les infections des portages asymptomatiques. Le diagnostic par sérologie peut être utile mais nécessite deux échantillons à quelques semaines d'intervalle. Les macrolides sont la classe d'antibiotique classiquement utilisées dans le traitement des infections à ces deux germes. L'ef ficacité du traitement antibiotique pour le M. pneumoniae est actuellement remis en doute par certaines études. Des résistances au traitement du M. pneumoniae par macrolide sont décrites. En conclusion, il manque encore de littérature scientifique à hauts niveaux de preuve et de concensus clairs dans la prise en charge des suspicions d'infection à M. pneumoniae et C. pneumoniae.

Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency.

Polysaccharide antibody deficiency is characterized by a poor or absent antibody response after vaccination with an unconjugated pneumococcal polysaccharide vaccine. Allohaemagglutinins (AHA) are antibodies to A or B polysaccharide antigens on the red blood cells, and are often used as an additional or alternative measure to assess the polysaccharide antibody response. However, few studies have been conducted to establish the clinical significance of AHA. To investigate the value of AHA to diagnose a polysaccharide antibody deficiency, pneumococcal polysaccharide antibody titres and AHA were studied retrospectively in 180 subjects in whom both tests had been performed. Receiver operating characteristic curves for AHA versus the pneumococcal vaccine response as a marker for the anti-polysaccharide immune response revealed an area under the curve between 0·5 and 0·573. Sensitivity and specificity of AHA to detect a polysaccharide antibody deficiency, as diagnosed by vaccination response, were low (calculated for cut-off 1/4-1/32). In subjects with only low pneumococcal antibody response, the prevalence of bronchiectasis was significantly higher than in subjects with only low AHA (45·5 and 1·3%, respectively) or normal pneumococcal antibody response and AHA (2·4%). A logistic regression model showed that low pneumococcal antibody response but not AHA was associated with bronchiectasis (odds ratio 46·2). The results of this study do not support the routine use of AHA to assess the polysaccharide antibody response in patients with suspected immunodeficiency, but more studies are warranted to clarify the subject further.

Long-term bleeding events after mechanical aortic valve replacement in patients under the age of 60.

BACKGROUND: Although younger patients are supposed to be less susceptible to bleeding complications of mechanical aortic valve replacement (mAVR) than older patients, there is a relative paucity of data on this subject. Therefore, it remains uncertain whether younger patients are really at a lower risk of these complications than older patients. METHODS: Incidence rates of bleeding events during 15 years of follow-up after mAVR were compared between 163 patients under 60 (group I), 122 patients between 60 and 65 (group II), and 145 patients over 65 (group III) years of age at operation. The target international normalised ratio (INR) was 3.0-4.0. RESULTS: During 15 years of follow-up, the annual incidence rate of major bleeding events (excluding haemorrhagic stroke) was lower in the youngest as compared with the oldest group (3.0 versus 4.7 %, respectively; p = 0.030). However, the annual incidence rate of haemorrhagic stroke was as high in the youngest as in the two older groups (0.6 versus 0.7 % and 0.7 %, respectively; p = 0.928). CONCLUSIONS: With a target INR of 3.0-4.0, patients under 60 years of age are at equally high risk of haemorrhagic stroke after mAVR as older patients. This finding confirms the relevance of a lower target INR as used in international guidelines.

[Interceptive treatment of maxillary hypoplasia with the use of bone anchors. A review of the literature]. / Interceptieve behandeling van een maxillaire hypoplasie met behulp van botankers. Een literatuuronderzoek.

A Class III malocclusion is mainly caused by a hypoplastic maxilla and therefore the treatment is principally aimed at stimulating the growth of the maxilla. Disadvantages of conventional treatment methods are that treatment effects are mainly dentoalveolar rather than skeletal and that there is often an increase in the height of the lowerface. Moreover, patients are not always cooperative about wearing extra-oral appliances. Because of these disadvantages, a new treatment approach has been developed which makes use of skeletal anchoring. In this new technique, called 'bone anchored maxillary protraction, bone anchors are placed on both sides of the maxilla and the mandibula, onto which Class III elastics are attached. The literature shows that good results have been achieved with this method. Disadvantages of this method are that the placement of the bone anchors requires a surgical procedure and that complications, like the loosening or breaking of the anchors, can occur.

High-calorie refeeding in adolescents with anorexia nervosa: a narrative review.

Background and objectives: Recent studies about refeeding in anorexia nervosa (AN) suggest starting with a high calorie diet. This narrative review aims to understand the initial refeeding management in hospitalized children and adolescents with AN and to develop a practical protocol. Methods: We performed a comprehensive database search in June 2023 for abstracts published between January 2010 and May 2023 in different databases: Pubmed, The Cochrane Library and Embase with the terms refeeding syndrome, energy intake, diet therapy, weight restoration, hypophosphatemia, nutritional rehabilitation, anorexia nervosa, restrictive eating disorders, child, adolescent and young adult. Results: Fifteen papers were included in this review. Twelve studies were retrospective or observational. Only 3 randomized controlled trials were found. Initial energy intake varies within a wide range between 500 and 2800 kcal per day but generally begins with higher calories than current recommendations. Only hypophosphatemia was often described without clinical refeeding syndrome. Initial weight restoration was better with high calorie refeeding (HCR). Length of stay was shorter with HCR in some studies. Long term outcomes were unknown. Only two studied severely malnourished patients (< 70 % mBMI). Conclusion: In adolescents with AN and with a low risk of RS, high calorie refeeding is possible under close medical monitoring and with prompt electrolyte correction. Robust studies with a unified protocol are needed to confirm the safety of high calorie refeeding especially in severely malnourished adolescents with AN.

Maturation of CD4+ regulatory T lymphocytes and of cytokine secretions in infants born prematurely.

PURPOSE: To characterize the maturation of CD4(+) regulatory T lymphocytes (Treg) and of cytokine productions in preterm infants during their first 16 months of life. METHODS: The proportions of CD4(+) Treg cells, their phenotypic characteristics, and the mitogen-induced cytokine productions by peripheral blood mononuclear cells (PBMC) were analysed in 26 very-preterm infants from 2 to 16 months of age, and compared to results obtained for 17 cord blood mononuclear cells (CBMC) from very-preterm infants, 12 from term infants and to blood samples from 40 adults. RESULTS: High proportion of CD25(+/high)CD4(+) Treg cells was found at birth in preterm CB with a gradual decreased afterwards. However, their percentage at 16 months of age was still higher than in term CB. In contrast to adults, preterm infants were characterized by excellent linear correlations between the proportions of CD25(+/high)CD4(+) and CD25(+/high)FoxP3(+) CD4(+) or CD25(+/high)CD127(low) CD4(+) or CD25(+/high)FoxP3(+)CD127(low) CD4(+)T lymphocytes. CD45RO(+) and HLA-DR(+) expressions were very low on preterm Treg and progressively increased with age. Functionally, preterm compared to term CBMC secreted in response to phytohaemagglutinin lower IFN-γ, higher IL-5 and similar IL-12p70, IL-10, IL-2 and IL-13 concentrations. IFN-γ, IL-12p70 and IL-10 productions were at 16 months still lower than those obtained for adults CONCLUSION: Preterm differed from term CBMC both by their proportion and phenotype of CD4(+) Treg lymphocytes and by their cytokine secretions. Maturation occurred during infancy with similar IFN-γ secretion but with persistently higher proportion of CD4(+) Treg cells in 1 year preterm infants compared to term neonates.

CFTR biomarkers: time for promotion to surrogate end-point.

In patients with cystic fibrosis, cystic fibrosis transmembrane conductance regulator (CFTR) biomarkers, such as sweat chloride concentration and/or nasal potential difference, are used as end-points of efficacy in phase-III clinical trials with the disease modifying drugs ivacaftor (VX-770), VX809 and ataluren. The aim of this project was to review the literature on reliability, validity and responsiveness of nasal potential difference, sweat chloride and intestinal current measurement in patients with cystic fibrosis. Data on clinimetric properties were collected for each biomarker and reviewed by an international team of experts. Data on reliability, validity and responsiveness were tabulated. In addition, narrative answers to four key questions were discussed and agreed by the team of experts. The data collected demonstrated the reliability, validity and responsiveness of nasal potential difference. Fewer data were found on reliability of sweat chloride concentration; however, validity and responsiveness were demonstrated. Validity was demonstrated for intestinal current measurement, but further information is required on reliability and responsiveness. For all three end-points, normal values were collected and further research requirements were proposed. This body of work adds useful information to support the promotion of CFTR biomarkers to surrogate end-points and to guide further research in the area.

Association of fetal cranial shape with shoulder dystocia.

OBJECTIVE: To evaluate whether fetal cranial shape is related to shoulder dystocia. METHODS: We compared shoulder dystocia cases (n = 18) with controls (normal vaginal deliveries, n = 18) in a retrospective matched-pairs observational study. Subjects were matched for known maternal and fetal risk factors and then evaluated for fetal biometric differences, which were measured by ultrasound near delivery. We tested multivariable risk models to predict shoulder dystocia by logistic regression. RESULTS: Cases had a smaller estimated occipitofrontal diameter (OFD) (P = 0.02) and a larger biparietal diameter/estimated OFD ratio (P = 0.003). A multivariable model including estimated fetal weight, estimated OFD, maternal weight and diabetes mellitus had sensitivity and specificity of 86% and 95%, respectively, and positive and negative likelihood ratios of 18.9 and 0.15, respectively. Estimated OFD significantly increased the predictive value of the model. CONCLUSION: A small estimated OFD is a risk factor for shoulder dystocia in the presence of other significant risk factors. A multivariable model including estimated OFD can predict shoulder dystocia in a clinically useful range.

ECFS standards of care on CFTR-related disorders: Diagnostic criteria of CFTR dysfunction.

The spectrum of disorders involving CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction correlates with a continuous gradient of CFTR function defined by the combination of two allelic CFTR variants. CFTR-related disorders are clinical entities with features of cystic fibrosis (CF) and evidence for presence of CFTR dysfunction but not meeting criteria for diagnosis of CF. Individuals with CFTR-RDs demonstrate a wide range of CFTR activity and are still under-recognized or misclassified. The level of CFTR dysfunction may be measured in vivo (sweat testing, nasal potential difference measurements) and/or by ex vivo tests (intestinal current measurement), or indirectly indicated by CFTR variants, as alteration in sequence of the CFTR gene translates into CFTR dysfunction. CFTR bioassays can aid in the diagnosis of individuals with CF, but we lack parameters to differentiate CF from CFTR-RD. In the era of the CFTR modulators and their potential clinical benefit, it is of utmost importance to diagnose CFTR-RD as unambiguously as possible. We therefore propose the following to define compatible CFTR dysfunction in a person with a suspected diagnosis of CFTR-RD : (1) evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (2) One CFTR variant known to reduce CFTR function and evidence of CFTR dysfunction in vivo or ex vivo in at least two different CFTR functional test types, or (3) Two CFTR variants shown to reduce CFTR function, with at most one CF-causing variant.

Standards of care guidance for sweat testing; phase two of the ECFS quality improvement programme.

More than five decades after the introduction of the quantitative pilocarpine iontophoresis technique, surveys still highlight inconsistencies in the performance and reporting of sweat tests in Europe. The sweat test remains key for the Cystic Fibrosis (CF) diagnostic pathway for all age groups, as it reflects the basic pathophysiological defect in the sweat gland. It is also critical following newborn screening as a confirmatory diagnostic step. Despite its importance, sweat test quality is variable whether performed in the laboratory or as a point of care test. The ECFS DNWG aims to improve sweat test performance, taking into account the barriers and issues identified in the European survey; the previous step in the ECFS sweat test project. This manuscript proposes a grading of sweat test guidance from "acceptable" to "optimal", aiming to pragmatically improve quality while taking into account local situations, especially in resource-limited settings.

Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis.

A recent American registry analysis in cystic fibrosis (CF) children showed less lung function decline after starting inhaled corticosteroid (ICS) use. We therefore examined the influence of ICS treatment on lung function in Belgian CF patients. Data from patients ≥ 6 yrs of age were eligible, provided entries on lung function, height and ICS use were available in two consecutive years. Data after oral steroid use or transplant were excluded. 852 subjects contributed data with 2,976 data pairs analysed, 44.9% concerning years of ICS use. Yearly % predicted decline in forced expiratory volume in 1 s (FEV1) was 1.07% lower during ICS use (p = 0.001). Subgroup analysis for age revealed that the lower FEV1 decline rate during ICS use was only statistically significant in children 6-12 yrs of age (2.56%; p = 0.0003). Baseline FEV(1) was lower by 5.89% (p < 0.0001) in ICS users for all age groups combined, but there was no difference in baseline lung function in the children 6-12 yrs of age. In 6-12-yr-old children with CF, baseline lung function was similar in ICS users and nonusers, but annualised FEV1 decline was 2.56% pred lower in ICS users. Our data therefore support recent American findings.

Preserved hyperaemic response in supraclavicular ultrasonography demonstrates function on demand of the LIMA to LAD string sign graft after CABG.

AIM: To correlate supraclavicular ultrasonography with angiographically patent and string sign left internal mammary artery (LIMA) to left anterior descending artery (LAD) grafts. METHODS: Sixteen patients with a single LIMA anastomosis to the LAD were prospectively entered in a follow-up study. The supraclavicular ultrasonography of the LIMA origin was studied preoperatively and at 5.3+/-3.6 months and 1.7+/-0.4 year postoperatively. At the late postoperative ultrasonography electrocardiographically controlled hyperemic response was also studied for 6 min. Control angiography was performed at 1.5+/-0.8 year. Differences within groups were tested with a paired t-test and between groups with an unpaired t-test. RESULTS: Control angiography showed in 13 patients (group I) a patent LIMA graft and in 3 patients (group II) a string sign LIMA graft. Preoperative blood velocities were not significantly different between groups. Postoperatively, both groups revealed higher diastolic and lower systolic blood velocities compared to preoperative values. The blood velocities at rest did not change in group I and all velocities decreased in group II in time postoperatively. The blood velocities in maximal hyperemic response increased significantly within the groups and were not significantly different between the groups. No ischemia could be detected electrocardiographically during hyperemic response and no patient presented angina. CONCLUSIONS: Both groups showed a shift towards coronary type diastolic blood velocities at rest and at hyperaemic response. Significant hyperemic response was also present in string sign LIMA grafts and demonstrates response capacity to increased myocardial oxygen demand.

Biological variability of the sweat chloride in diagnostic sweat tests: A retrospective analysis.

BACKGROUND: The sweat test is the current gold standard for the diagnosis of cystic fibrosis (CF). CF is unlikely when sweat chloride (Clsw) is lower than 30mmol/L, Clsw>60 is suggestive of CF, with intermediate values between 30 and 60mmol/L. To correctly interpret a sweat chloride value, the biological variability of the sweat chloride has to be known. METHODS: Sweat tests performed in two centers using the classic Gibson and Cooke method were retrospectively reviewed (n=5904). Within test variability of Clsw was measured by comparing results from right and left arm collected on the same day. Between test variability was calculated from subjects with sweat tests performed on more than one occasion. RESULTS: Within test variability of Clsw calculated in 1022 subjects was low with differences between -3.2 (p5) and +3.6mmol/L (p95). Results from left and right arm were classified differently in only 3 subjects. Between test variability of Clsw in 197 subjects was larger, with differences between -18.2mmol/L (p5) and +14.1mmol/L (p95) between repeat tests. Changes in diagnostic conclusion were seen in 55/197 subjects, the most frequent being changing from indeterminate to 'CF unlikely' range (48/102). CONCLUSION: Variability of sweat chloride is substantial, with frequent changes in diagnostic conclusion, especially in the intermediate range.

Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations.

INTRODUCTION: Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial. METHODS: In subjects with G551D at least 12years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial. RESULTS: Mean overall sweat chloride value (all patients, all tests, n=1062) was 100.8mmol/L (SD 12.7mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9mmol/L (95% CI 7.4-10.6) and within-subject SD was 8.1mmol/L (95% CI 7.5-8.7). Limits of repeatability for repeat measurements were -19.7 to +21.6mmol/L using values from one arm, and -13.3 to 11.8mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. CONCLUSION: Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.