Epidermal biomarkers of the skin barrier in atopic and contact dermatitis.

Dysfunction of the skin barrier plays a critical role in the initiation and progression of inflammatory skin diseases, such as atopic dermatitis and contact dermatitis. Epidermal biomarkers can aid in evaluating the functionality of the skin barrier and understanding the mechanisms that underlay its impairment. This narrative review provides an overview of recent studies on epidermal biomarkers associated with the function and integrity of the skin barrier, and their application in research on atopic dermatitis and contact dermatitis. The reviewed studies encompass a wide spectrum of molecular, morphological and biophysical biomarkers, mainly obtained from stratum corneum tape strips and biopsies. Lipids, natural moisturizing factors, and structural proteins are the most frequently reported molecular biomarkers. Additionally, corneocyte surface topography and elasticity show potential as biomarkers for assessing the physical barrier of the skin. In contact dermatitis studies, biomarkers are commonly employed to evaluate skin irritation and differentiate between irritant and allergic contact dermatitis. In atopic dermatitis, biomarkers are primarily utilized to identify differences between atopic and healthy skin, for predictive purposes, and monitoring response to therapies. While this overview identifies potential biomarkers for the skin barrier, their validation as epidermal biomarkers for atopic dermatitis and contact dermatitis has yet to be established.

Influence of subscapularis tendon reattachment after reverse shoulder arthroplasty: clinical findings and ultrasonographic evaluation of the subscapularis at 89 months mean follow-up.

BACKGROUND: Reverse shoulder arthroplasty (RSA) is commonly used to treat rotator cuff arthropathy. In the deltopectoral approach for RSA, the subscapularis tendon is (partly) detached. The clinical effects of subscapularis reattachment are still under debate. An observational study was performed to evaluate the clinical effects of subscapularis tendon reattachment on the mid- to long-term following RSA. METHODS: In this study, 40 patients for a total of 46 shoulders with a reverse shoulder prosthesis participated. Constant Murley Score (CMS), Oxford Shoulder Score (OSS), Range of Motion (ROM) and abduction and internal rotation strength were measured. The integrity of the subscapularis tendon at follow-up was assessed using ultrasound. Outcomes were compared between three groups: repair and intact at follow-up, repair and not intact, and no repair. RESULTS: Mean follow-up was 89 months with a minimum of three years. CMS, OSS, ROM and strength did not differ between groups. One-third of the initially reattached subscapularis tendons were still present at follow-up. No dislocations were reported. CONCLUSION: This study showed no clinical effects of subscapularis reattachment after reverse shoulder arthroplasty on the mid- to long-term.

Required distal mesorectal resection margin in partial mesorectal excision: a systematic review on distal mesorectal spread.

BACKGROUND: The required distal margin in partial mesorectal excision (PME) is controversial. The aim of this systematic review was to determine incidence and distance of distal mesorectal spread (DMS). METHODS: A systematic search was performed using PubMed, Embase and Google Scholar databases. Articles eligible for inclusion were studies reporting on the presence of distal mesorectal spread in patients with rectal cancer who underwent radical resection. RESULTS: Out of 2493 articles, 22 studies with a total of 1921 patients were included, of whom 340 underwent long-course neoadjuvant chemoradiotherapy (CRT). DMS was reported in 207 of 1921 (10.8%) specimens (1.2% in CRT group and 12.8% in non-CRT group), with specified distance of DMS relative to the tumor in 84 (40.6%) of the cases. Mean and median DMS were 20.2 and 20.0 mm, respectively. Distal margins of 40 mm and 30 mm would result in 10% and 32% residual tumor, respectively, which translates into 1% and 4% overall residual cancer risk given 11% incidence of DMS. The maximum reported DMS was 50 mm in 1 of 84 cases. In subgroup analysis, for T3, the mean DMS was 18.8 mm (range 8-40 mm) and 27.2 mm (range 10-40 mm) for T4 rectal cancer. CONCLUSIONS: DMS occurred in 11% of cases, with a maximum of 50 mm in less than 1% of the DMS cases. For PME, substantial overtreatment is present if a distal margin of 5 cm is routinely utilized. Prospective studies evaluating more limited margins based on high-quality preoperative magnetic resonance imaging and pathological assessment are required.

Jejunal closed-loop obstruction without prior abdominal surgery during COVID-19 ICU admittance: A case report.

INTRODUCTION: and importance: Closed-loop obstruction is a specific case of small bowel obstruction in which two sites of the bowel obstruct at one adjacent location. This can result in strangulation with high mortality. This condition is most often observed after abdominal surgery. The exact underlying pathology in patients without prior abdominal surgery is still largely unclear, and only scarce literature on the role of COVID-19 or long-term prone position is available. CASE PRESENTATION: A 74-year-old male patient without prior abdominal surgery was presented to the emergency department with pulmonary and gastro-intestinal symptoms of COVID-19. The patient was known to have diverticulosis of colon and sigmoid. After a complicated ICU course, the patient developed a jejunal closed loop obstruction, and a diagnostic laparoscopy was performed. Fixation of the omentum to the retroperitoneum was released, without observation of further adhesions, bowel torsion or ischemic bowel. Further abdominal course was uncomplicated, however, unfortunately the patient died following pulmonary deterioration. CLINICAL DISCUSSION: The differential diagnosis of small bowel obstruction is extensive; however, adhesions are most often observed. In patients without prior surgery, also adhesions are observed, mainly caused by earlier infections. There might be a role for abdominal COVID-19 infection and prolonged prone position in the emergence of adhesions; however, literature is lacking. Alternatively, asymptomatic diverticulitis might have led to adhesion formation. CONCLUSION: Closed loop obstructions in patients without prior abdominal surgery are uncommon and post-infectious abdominal status might cause adhesions. It is unclear whether abdominal manifestations of COVID-19 and prolonged prone position can also cause adhesions and, thereby, small bowel obstructions.

Variations in respiratory rate do not reflect changes in tidal volume or minute ventilation after major abdominal surgery.

Monitoring of postoperative pulmonary function usually includes respiratory rate and oxygen saturation measurements. We hypothesized that changes in postoperative respiratory rate do not correlate with changes in tidal volume or minute ventilation. In addition, we hypothesized that variability of minute ventilation and tidal volume is larger than variability of respiratory rate. Respiratory rate and changes in tidal volume and in minute ventilation were continuously measured in 27 patients during 24 h following elective abdominal surgery, using an impedance-based non-invasive respiratory volume monitor (ExSpiron, Respiratory Motion, Waltham, MA, US). Coefficients of variation were used as a measure for variability of respiratory rate, tidal volume and minute ventilation. Data of 38,149 measurements were analyzed. We found no correlation between respiratory rate and tidal volume or minute ventilation (r2 = 0.02 and 0.01). Mean respiratory rate increased within the first 24 h after abdominal surgery from 13.9 ± 2.5 to 16.2 ± 2.4 breaths/min (p = 0.008), while tidal volume and minute ventilation remained unchanged (p = 0.90 and p = 0.18). Of interest, variability of respiratory rate (0.21 ± 0.06) was significantly smaller than variability of tidal volume (0.37 ± 0.12, p < 0.001) and minute ventilation (0.41 ± 0.12, p < 0.001). Changes in postoperative respiratory rate do not allow conclusions about changes in tidal volume or minute ventilation. We suggest that postoperative alveolar hypoventilation may not be recognized by monitoring respiratory rate alone. Variability of respiratory rate is smaller than variability in tidal volume and minute ventilation, suggesting that adaptations of alveolar ventilation to metabolic needs may be predominately achieved by variations in tidal volume.

Effectiveness of a Tailored Work-Related Support Intervention for Patients Diagnosed with Gastrointestinal Cancer: A Multicenter Randomized Controlled Trial.

Purpose The aim of this research was to study the effectiveness on return to work (RTW) of an early tailored work-related support intervention in patients diagnosed with curative gastrointestinal cancer. Methods A multicenter randomized controlled trial was undertaken, in which patients were assigned randomly to the intervention or the control group (usual care). The intervention encompassed three psychosocial work-related support meetings, starting before treatment. Five self-reported questionnaires were sent over twelve months of follow-up. Primary outcome was days until RTW (fulltime or partial) and secondary outcomes included work status, quality of life, work ability, and work limitations. Descriptive analysis, Kaplan-Meier analysis, relative risk ratio and linear mixed models were applied. Results Participants (N = 88) had a mean age of 55 years; 67% were male and the most common cancer type was colon cancer (66%). Of the participants, 42 were randomized to the intervention group. The median time from sick leave until RTW was 233 days (range 187-279 days) for the control group, versus 190 days (range 139-240 days) for the intervention group (log-rank p = 0.37). The RTW rate at twelve months after baseline was 83.3% for the intervention group and 73.5% for the control group. Work limitations did statistically differ between the groups over time (p = 0.01), but quality of life and work ability did not. Conclusion Patients in the intervention group seem to take fewer days to RTW, albeit not to a statistically significant extent.Trial registration Trial NL4920 (NTR5022) (Dutch Trial Register https://www.trialregister.nl ).

Invasive fungal infections in patients treated with Bruton's tyrosine kinase inhibitors.

Bruton's tyrosine kinase (BTK) inhibitors are increasingly used in untreated and previously treated chronic lymphocytic leukaemia (CLL) patients. Invasive fungal infections (IFI) were rarely observed in patients treated for CLL in the pre-BTK era. In this article, we describe two patients with CLL who developed an IFI during treatment with the BTK inhibitor ibrutinib. The atypical presentation and the serious course of this complication are described.

[Psychosis as an evolutionary adaptive mechanism to environmental changes; A plea for a functional explanatory model]. / Psychose als evolutionair adaptief mechanisme bij omgevingsverandering; pleidooi voor een functioneel verklaringsmodel.

BACKGROUND: From an evolutionary perspective it is remarkable that psychotic disorders, mostly occurring during fertile age and decreasing fecundity, maintain in the human population.
AIM: To argue the hypothesis that psychotic symptoms may not be viewed as an illness but as an adaptation phenomenon.
METHOD: Philosophical consideration and literature study.
RESULTS: Until now, biomedical research has not unraveled the definitive etiology of psychotic disorders. Findings are inconsistent and show non-specific brain anomalies and genetic variation with small effect sizes. However, compelling evidence was found for a relation between psychosis and stressful environmental factors, particularly those influencing social interaction. Psychotic symptoms may be explained as a natural defense mechanism or protective response to stressful environments. This is in line with the fact that psychotic symptoms most often develop during adolescence. In this phase of life, it is important for an individual's development to leave the familiar and safe home environment, and to build new social networks. This could cause symptoms of 'hyperconsciousness' and calls on the capacity for social adaptation. This mechanism can become out of control due to different underlying brain vulnerabilities and external stressors, leading to social exclusion. CONCLUSIONS There is theoretical ground to consider psychotic symptoms as an evolutionary maintained phenomenon. Research investigating psychotic disorders may benefit from a focus on underlying general brain vulnerabilities or prevention of social exclusion, instead of regarding psychotic symptoms as abnormal phenomena.

Locoregional recurrences after transanal total mesorectal excision of rectal cancer during implementation.

BACKGROUND: Transanal total mesorectal excision (TaTME) has been proposed as an approach in patients with mid and low rectal cancer. The TaTME procedure has been introduced in the Netherlands in a structured training pathway, including proctoring. This study evaluated the local recurrence rate during the implementation phase of TaTME. METHODS: Oncological outcomes of the first ten TaTME procedures in each of 12 participating centres were collected as part of an external audit of procedure implementation. Data collected from a cohort of patients treated over a prolonged period in four centres were also collected to analyse learning curve effects. The primary outcome was the presence of locoregional recurrence. RESULTS: The implementation cohort of 120 patients had a median follow up of 21·9 months. Short-term outcomes included a positive circumferential resection margin rate of 5·0 per cent and anastomotic leakage rate of 17 per cent. The overall local recurrence rate in the implementation cohort was 10·0 per cent (12 of 120), with a mean(s.d.) interval to recurrence of 15·2(7·0) months. Multifocal local recurrence was present in eight of 12 patients. In the prolonged cohort (266 patients), the overall recurrence rate was 5·6 per cent (4·0 per cent after excluding the first 10 procedures at each centre). CONCLUSION: TaTME was associated with a multifocal local recurrence rate that may be related to suboptimal execution rather than the technique itself. Prolonged proctoring, optimization of the technique to avoid spillage, and quality control is recommended.

ANTECEDENTES: La escisión total del mesorrecto por vía transanal (Transanal Total Mesorectal Excision, TaTME) se ha propuesto como abordaje quirúrgico en pacientes con cáncer de recto medio e inferior. La técnica TaTME se ha introducido en los Países Bajos mediante un proceso de formación estructurado que incluye la supervisión. Este estudio evaluó el porcentaje de recidiva local durante la fase de implementación de TaTME. MÉTODOS: Se recogieron los resultados oncológicos de los primeros 10 procedimientos realizados mediante TaTME en cada uno de los 12 centros participantes como parte de una auditoría externa de implementación del procedimiento. Se reunió una cohorte más amplia de pacientes procedentes de 4 centros para analizar los efectos de la curva de aprendizaje. El criterio de valoración principal fue la presencia de recidiva locorregional. RESULTADOS: La cohorte de implementación de 120 pacientes tuvo una mediana de seguimiento de 21,9 meses. Los resultados a corto plazo incluyeron una tasa del margen de resección circunferencial positivo del 5% y una tasa de fuga anastomótica del 17,4%. La tasa global de recidiva local en la cohorte de implementación fue del 10% (12/120) con un intervalo medio de recidiva de 15,2 (DE 7) meses. El patrón de recidiva local fue multifocal en 8 de 12 casos (67%). En la cohorte ampliada (n = 266), la tasa global de recidiva fue del 5,6% (4,0%, excluyendo a los primeros 10 pacientes). CONCLUSIÓN: TaTME se asoció con un porcentaje de recidiva local multifocal que puede relacionarse con una ejecución subóptima, más que con la técnica en sí. Se recomienda una supervisión prolongada, la optimización de la técnica para evitar la diseminación tumoral, así como un control de calidad.

Nikolay Ivanovich Pirogov (1810-1881): Anatomical research to develop surgery.

The 19th century Russian surgeon Nikolay Ivanovich Pirogov believed passionately in the importance of anatomy for surgeons. His interest in anatomy began as a medical student in Moscow. After graduating in 1828 Pirogov entered the postgraduate German-Baltic University of Dorpat (now Tartu in the Republic of Estonia) where he studied anatomy and surgery. After completing his study, he remained to research the consequences of ligation of the aorta in a series of animal experiments, which formed the core of his doctoral thesis. He wanted to determine the feasibility of aortic ligation as a treatment for patients with an aneurysm of the aorta or iliac artery. He discovered that success was only likely when the aorta was ligated between the two mesenteric arteries and the ligature gradually tightened, an approach surgically difficult in humans. Pirogov then spent 2 years at the Charité Hospital in Berlin before returning to Russia. In 1841, he was appointed Professor of Applied Anatomy and Surgery at the Imperial Medico-Surgical Academy in Saint Petersburg. He instituted the teaching of microscopy and histology to the medical curriculum and in 1846 formed the Institute for Applied Anatomy within the academy, where in addition to teaching medical students future teachers of anatomy in Russia were trained. Pirogov published extensively on anatomy, including several anatomical atlases, the most notable his three-dimensional atlas of topographical anatomy published in four volumes between 1852 and 1859. Today Pirogov's contributions to anatomy are remembered in a number of anatomical structures named after him. Clin. Anat., 33:714-730, 2020. © 2019 Wiley Periodicals, Inc.

Characterization of the Scattering and Absorption of Colored Zein Colloids in Optically Dense Dispersions.

In this research, we model the color of optically dense colloidal dispersions of dyed and undyed zein particles using results from multiple light scattering theory. These particles, as well as monodisperse silica colloids, were synthesized and characterized to obtain particle properties such as particle size, particle size distribution, refractive index, and absorption spectrum of the dye. This information was used to model the diffuse transmission of concentrated particle dispersions, which was measured using a specially designed variable path length quartz glass cuvette. For the nonabsorbing silica dispersions, a transport mean-free path throughout the visible range was obtained. Results showed a difference of less than 5% from the values calculated with a multiple scattering model using the single-particle properties as an input. For undyed zein particles, which are off-white, the deviation between the model and the experiment was about 30% because of slight absorption at wavelengths below 550 nm but <7% at higher wavelengths. From these results, it was concluded that the model correctly describes diffuse transmission and that the measurements are sensitive to absorption. Finally, this method was applied to dispersions of dyed zein particles. Here, the transport mean-free path was first determined for wavelengths at which there is no absorption, which agreed with the theory better than 4%. The modeled transport mean-free path was then used to extract the reciprocal absorption mean-free path in the remaining parts of the visible spectrum, and a reasonable agreement with the absorption spectrum of the dye solution was obtained.

Mediating Mechanisms in Cognitive Behavioral Therapy for Childhood OCD: The Role of Dysfunctional Beliefs.

Reframing cognitions is assumed to play an important role in treatment for obsessive-compulsive disorder (OCD). However, there hardly is any empirical support for this assumption, especially for children. The aim of this study was to examine if changing dysfunctional beliefs is a mediating mechanism of cognitive behavioral therapy (CBT) for childhood OCD. Fifty-eight children (8-18 years) with OCD received CBT. Dysfunctional beliefs (OBQ-CV) and OCD severity (CY-BOCS) were measured pre-treatment, mid-treatment, post-treatment, and at 16-week follow-up. Results showed that OCD severity and dysfunctional beliefs decreased during CBT. Changes in severity predicted changes in beliefs within the same time interval. Our results did not support the hypothesis that changing dysfunctional beliefs mediates treatment effect. Future studies are needed to replicate these findings and shed more light on the role of explicit and implicit cognitions in treatment for childhood OCD.

White zein colloidal particles: synthesis and characterization of their optical properties on the single particle level and in concentrated suspensions.

Growing interest in using natural, biodegradable ingredients for food products leads to an increase in research for alternative sources of functional ingredients. One alternative is zein, a water-insoluble protein from corn. Here, a method to investigate the optical properties of white zein colloidal particles is presented in both diluted and concentrated suspensions. The particles are synthesized, after purification of zein, by anti-solvent precipitation. Mean particle diameters ranged from 35 to 135 nm based on dynamic light scattering. The value of these particles as white colorant is examined by measuring their optical properties. Dilute suspensions are prepared to measure the extinction cross section of individual particles and this was combined with Mie theory to determine a refractive index (RI) of 1.49 ± 0.01 for zein particles dispersed in water. This value is used to further model the optical properties of concentrated suspensions. To obtain full opacity of the suspension, comparable to 0.1-0.2 wt% suspensions of TiO2, concentrations of 2 to 3.3 wt% of zein particles are sufficient. The optimal size for maximal scattering efficiency is explored by modeling dilute and concentrated samples with RI's matching those of zein and TiO2 particles in water. The transport mean free path of light was determined experimentally and theoretically and the agreement between the transport mean free path calculated from the model and the measured value is better than 30%. Such particles have the potential to be an all-natural edible alternative for TiO2 as white colorant in wet food products.

International practices in the dietary management of fructose 1-6 biphosphatase deficiency.

BACKGROUND: In fructose 1,6 bisphosphatase (FBPase) deficiency, management aims to prevent hypoglycaemia and lactic acidosis by avoiding prolonged fasting, particularly during febrile illness. Although the need for an emergency regimen to avoid metabolic decompensation is well established at times of illness, there is uncertainty about the need for other dietary management strategies such as sucrose or fructose restriction. We assessed international differences in the dietary management of FBPase deficiency. METHODS: A cross-sectional questionnaire (13 questions) was emailed to all members of the Society for the Study of Inborn Errors of Metabolism (SSIEM) and a wide database of inherited metabolic disorder dietitians. RESULTS: Thirty-six centres reported the dietary prescriptions of 126 patients with FBPase deficiency. Patients' age at questionnaire completion was: 1-10y, 46% (n = 58), 11-16y, 21% (n = 27), and >16y, 33% (n = 41). Diagnostic age was: <1y, 36% (n = 46); 1-10y, 59% (n = 74); 11-16y, 3% (n = 4); and >16y, 2% (n = 2). Seventy-five per cent of centres advocated dietary restrictions. This included restriction of: high sucrose foods only (n = 7 centres, 19%); fruit and sugary foods (n = 4, 11%); fruit, vegetables and sugary foods (n = 13, 36%). Twenty-five per cent of centres (n = 9), advised no dietary restrictions when patients were well. A higher percentage of patients aged >16y rather than ≤16y were prescribed dietary restrictions: patients aged 1-10y, 67% (n = 39/58), 11-16y, 63% (n = 17/27) and >16y, 85% (n = 35/41). Patients classified as having a normal fasting tolerance increased with age from 30% in 1-10y, to 36% in 11-16y, and 58% in >16y, but it was unclear if fasting tolerance was biochemically proven. Twenty centres (56%) routinely prescribed uncooked cornstarch (UCCS) to limit overnight fasting in 47 patients regardless of their actual fasting tolerance (37%). All centres advocated an emergency regimen mainly based on glucose polymer for illness management. CONCLUSIONS: Although all patients were prescribed an emergency regimen for illness, use of sucrose and fructose restricted diets with UCCS supplementation varied widely. Restrictions did not relax with age. International guidelines are necessary to help direct future dietary management of FBPase deficiency.

Chemotherapy-induced exacerbations of thyroid orbitopathy in a patient with B-cell lymphoma.

A 55-year-old woman with concurrent active thyroid orbitopathy and B-cell lymphoma developed acute exacerbation of thyroid orbitopathy after receiving Rituximab, cyclophosphamide, hydroxydaunorubicin, Prednisone (R-CHOP) chemotherapy, presenting with subtotal loss of vision and severe eyelid edema. Intravenous methylprednisolone was fully effective within several hours. Further exacerbations of her orbitopathy were seen following every subsequent chemotherapeutic treatment, but responded well to oral prednisone. This case shows that thyroid orbitopathy may severely and acutely progress after chemotherapy for concurrent B-cell lymphoma. Clinical awareness of this potential complication may prevent blindness in this rare subset of patients.

Dietary practices in propionic acidemia: A European survey.

BACKGROUND: The definitive dietary management of propionic acidaemia (PA) is unknown although natural protein restriction with adequate energy provision is of key importance. AIM: To describe European dietary practices in the management of patients with PA prior to the publication of the European PA guidelines. METHODS: This was a cross-sectional survey consisting of 27 questions about the dietary practices in PA patients circulated to European IMD dietitians and health professionals in 2014. RESULTS: Information on protein restricted diets of 186 PA patients from 47 centres, representing 14 European countries was collected. Total protein intake [PA precursor-free L-amino acid supplements (PFAA) and natural protein] met WHO/FAO/UNU (2007) safe protein requirements for age in 36 centres (77%). PFAA were used to supplement natural protein intake in 81% (n = 38) of centres, providing a median of 44% (14-83%) of total protein requirement. Seventy-four per cent of patients were prescribed natural protein intakes below WHO/FAO/UNU (2007) safe levels in one or more of the following age groups: 0-6 m, 7-12 m, 1-10 y, 11-16 y and > 16 y. Sixty-three per cent (n = 117) of patients were tube fed (74% gastrostomy), but only 22% received nocturnal feeds. CONCLUSIONS: There was high use of PFAA with intakes of natural protein commonly below WHO/FAO/UNU (2007) safe levels. Optimal dietary management can only be determined by longitudinal, multi-centre, prospective case controlled studies. The metabolic instability of PA and small patient cohorts in each centre ensure that this is a challenging undertaking.

Dietary practices in isovaleric acidemia: A European survey.

BACKGROUND: In Europe, dietary management of isovaleric acidemia (IVA) may vary widely. There is limited collective information about dietetic management. AIM: To describe European practice regarding the dietary management of IVA, prior to the availability of the E-IMD IVA guidelines (E-IMD 2014). METHODS: A cross-sectional questionnaire was sent to all European dietitians who were either members of the Society for the Study of Inborn Errors of Metabolism Dietitians Group (SSIEM-DG) or whom had responded to previous questionnaires on dietetic practice (n = 53). The questionnaire comprised 27 questions about the dietary management of IVA. RESULTS: Information on 140 patients with IVA from 39 centres was reported. 133 patients (38 centres) were given a protein restricted diet. Leucine-free amino acid supplements (LFAA) were routinely used to supplement protein intake in 58% of centres. The median total protein intake prescribed achieved the WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Centres that prescribed LFAA had lower natural protein intakes in most age groups except 1 to 10 y. In contrast, when centres were not using LFAA, the median natural protein intake met WHO/FAO/UNU [2007] safe levels of protein intake in all age groups. Enteral tube feeding was rarely prescribed. CONCLUSIONS: This survey demonstrates wide differences in dietary practice in the management of IVA across European centres. It provides unique dietary data collectively representing European practices in IVA which can be used as a foundation to compare dietary management changes as a consequence of the first E-IMD IVA guidelines availability.