EFOMP Malaga Declaration 2023: An updated vision on Medical Physics in Europe.

In 2006, the European Federation of Organisations for Medical Physics (EFOMP) adopted the "Malaga Declaration". The declaration asserted the fundamental role of Medical Physics professionals in the radiation protection of patients, workers, general public, carers and comforters and research participants in hospitals. However, since that time the Medical Physics profession has evolved in Europe and new regulations and documentation have been issued, such as directive 2013/59/Euratom and the "European Guidelines on Medical Physics Expert" (RP174). EFOMP has published updated core-curricula and strived towards the recognition of the profession at the European level. In view of this, an update of the original Malaga Declaration was deemed necessary, to define the future vision that will guide the actions of the Federation in the years to come. This Declaration, which has been approved by the national member organizations of EFOMP in April 2023, is much broader than the original Malaga version. This is expected considering the rapid evolution of medical device technology over the last 17 years. The Radiation Protection Expert in hospital settings should be an MPE, since the latter has the highest level of radiation protection knowledge and training. Given the passion and energy that animated the debate, which led to the updating of the Malaga Declaration, we are confident that it represents a solid basis for the development of our profession in Europe which is in consonance with the aspirations of us all.

Development and validation of the food allergy severity score.

BACKGROUND: The heterogeneity and lack of validation of existing severity scores for food allergic reactions limit standardization of case management and research advances. We aimed to develop and validate a severity score for food allergic reactions. METHODS: Following a multidisciplinary experts consensus, it was decided to develop a food allergy severity score (FASS) with ordinal (oFASS) and numerical (nFASS) formats. oFASS with 3 and 5 grades were generated through expert consensus, and nFASS by mathematical modeling. Evaluation was performed in the EuroPrevall outpatient clinic cohort (8232 food reactions) by logistic regression with request of emergency care and medications used as outcomes. Discrimination, classification, and calibration were calculated. Bootstrapping internal validation was followed by external validation (logistic regression) in 5 cohorts (3622 food reactions). Correlation of nFASS with the severity classification done by expert allergy clinicians by Best-Worst Scaling of 32 food reactions was calculated. RESULTS: oFASS and nFASS map consistently, with nFASS having greater granularity. With the outcomes emergency care, adrenaline and critical medical treatment, oFASS and nFASS had a good discrimination (receiver operating characteristic area under the curve [ROC-AUC]>0.80), classification (sensitivity 0.87-0.92, specificity 0.73-0.78), and calibration. Bootstrapping over ROC-AUC showed negligible biases (1.0 × 10-6 -1.23 × 10-3 ). In external validation, nFASS performed best with higher ROC-AUC. nFASS was strongly correlated (R 0.89) to best-worst scoring of 334 expert clinicians. CONCLUSION: FASS is a validated and reliable method to measure severity of food allergic reactions. The ordinal and numerical versions that map onto each other are suitable for use by different stakeholders in different settings.

The TNF-α (-238 G/A) polymorphism could protect against development of severe sepsis.

Primary responses in sepsis-mediated inflammation are regulated by pro-inflammatory cytokines. Variations in the cytokine genes might modify their transcription or expression, plasma cytokines levels and response to sepsis. Activation protein-1 (AP-1) and NF-κB regulate cytokines gene expression in sepsis. A total of 90 severely septic and 91 non-infected patients were prospectively studied. IL-1α (-889 C/T), IL-1ß (+3954 C/T), IL-6 (-174 G/C), TNF-α (-238 G/A), TNF-α (-308G/A), IL-8 (-251A/T) and IL-10 (-1082 G/A) SNPs, plasma IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-13, IFN-γ, TNF-α and monocyte chemoattractant protein 1 (MCP-1) levels, and AP-1 and NF-κB gene expression by neutrophils were assessed. A allele carriers of TNF-α (-238 G/A) SNP were less frequent among septic patients. IL-6, IL-8, IL-10, TNF-α and MCP-1 levels were higher, and AP-1 and NF-κB gene expressions lower in septic patients. Sepsis was independently associated with higher fibrinogen, neutrophils counts and IL-8 levels, lower prothrombin, absence of the variant A allele of the TNF-α (-238 G/A) SNP, and haemodynamic failure. Death was independently associated with a higher APACHE II score, higher IL-8 levels, and the diagnosis of sepsis. TNF-a (-238 G/A) SNP could protect against sepsis development. Higher IL-8 levels are predictive of sepsis and mortality.

Life-Threatening Sublingual Hematoma after Mandibular Implant Placement - A Case Report.

RATIONALE: Sublingual hematoma is a potentially lethal complication following mandibular implant placement. Due to the scarce cases reported, the management is controversial. In this article, a case is discussed focusing on the different treatment options to establish an orientative guideline. PATIENT CONCERNS: A patient with sublingual hematoma following implant surgery was urgently referred. Despite no active bleeding, breathing difficulty due to oropharyngeal obstruction and oxygen saturation decrease were present. DIAGNOSIS: Stable sublingual hematoma with respiratory distress, based on clinical findings and observation. TREATMENT: Under local anaesthesia, percutaneous tracheostomy without previous intubation was performed for airway preservation. No surgical approach for the hematoma was made. OUTCOMES: Uneventful recovery with spontaneous resolution of the hematoma in few days. TAKEAWAY LESSONS: Anatomic knowledge of this area and proper surgical planning are required to avoid this complication. Regarding management, airway preservation is mandatory. Surgical approach for the bleeding source will depend on hematoma progression.

Dose accuracy improvement on head and neck VMAT treatments by using the Acuros algorithm and accurate FFF beam calibration.

BACKGROUND: The purpose of this study was to assess dose accuracy improvement and dosimetric impact of switching from the anisotropic analytical algorithm (AA) to the Acuros XB algorithm (AXB) when performing an accurate beam calibration in head and neck (H&N) FFF-VMAT treatments. MATERIALS AND METHODS: Twenty H&N cancer patients treated with FFF-VMAT techniques were included. Calculations were performed with the AA and AXB algorithm (dose-to-water - AXBw- and dose-to-medium - AXBm-). An accurate beam calibration was used for AXB calculations. Dose prescription to the tumour (PTV70) and at-risk-nodal region (PTV58.1) were 70 Gy and 58.1 Gy, respectively. A PTV70_bone including bony structures in PTV70 was contoured. Dose-volume parameters were compared between the algorithms. Statistical tests were used to analyze the differences in mean values and the correlation between compliance with the D95 > 95% requirement and occurrence of local recurrence. RESULTS: AA systematically overestimated the dose compared to AXB algorithm with mean dose differences within 1.3 Gy/2%, except for the PTV70_bone (2.2 Gy/3.2%). Dose differences were significantly higher for AXBm calculations when including accurate beam calibration (maximum dose differences up to 2.8 Gy/4.1% and 4.2 Gy/6.3% for PTV70 and PTV70_bone, respectively). 80% of AA-calculated plans did not meet the D95 > 95% requirement after recalculation with AXBm and accurate beam calibration. The reduction in D95 coverage in the tumour was not clinically relevant. CONCLUSIONS: Using the AXBm algorithm and carefully reviewing the beam calibration procedure in H&N FFF-VMAT treatments ensures (1) dose accuracy increase by approximately 3%; (2) a consequent dose increase in targets; and (3) a dose reporting mode that is consistent with the trend of current algorithms.

Single-dose oral challenges to validate eliciting doses in children with cow's milk allergy.

BACKGROUND: There is increasing interest in the use of eliciting doses (EDs) to inform allergen risk management. The ED can be estimated from the distribution of threshold doses for allergic subjects undergoing food challenges within a specified population. Estimated ED05 values for cow's milk (the dose expected to cause objective allergic symptoms in 5% of the milk-allergic population) range from 0.5 mg to 13.9 mg cow's milk protein. We undertook a single-dose challenge study to validate a predicted ED05 for cow's milk of 0.5 mg protein. METHODS: Participants were recruited from 4 clinical centres. Predetermined criteria were used to identify patients reacting to 0.5 mg cow's milk protein (approximately 0.015 mL of fresh cow's milk). Children over 1 year underwent formal challenge to cow's milk to confirm clinical reactivity. RESULTS: 172 children (median age 6.0 (IQR 0.7-11) years, 57% male) were included in this analysis. Twelve (7.0%, 95% CI 3.7%-11.9%) children experienced objective symptoms that met the predetermined criteria. One participant had mild anaphylaxis that responded to a single dose of adrenaline, the remainder experienced only mild symptoms with no treatment required. We did not identify any baseline predictors of sensitization that were associated with objective reactivity to the single-dose challenge using 0.5 mg cow's milk protein. CONCLUSIONS: These data support an estimated ED05 for cow's milk of 0.5 mg protein. Values for ED05 above 0.5 mg for cow's milk protein proposed for allergen risk management need to be reviewed.

Dosimetric impact of failing to apply correction factors to ion recombination in percentage depth dose measurements and the volume-averaging effect in flattening filter-free beams.

PURPOSE: To examine whether it is essential to apply correction factors for ion recombination (kS) to percentage depth dose (PDD) measurements and to the volume-averaging effect (kvol) to ensure accurate absolute dose calibration for flattening filter-free (FFF) beams for the most commonly used ionization chambers. METHODS: We surveyed medical physicists worldwide (n = 159) to identify the five most common ionization chamber combinations used for absolute and relative reference dosimetry of FFF beams. We then assessed the overall absolute dose calibration error for FFF beams of the Artiste Siemens and TrueBeam Varian linear accelerators resulting from failing to apply correction factors kS in the PDD(10) and the volume-averaging effect (kvol) to such chamber combinations. RESULTS: All the chamber combinations examined-the Farmer PTW 30013 ionization chamber used for absolute dosimetry, and the PTW 31010, PTW 30013, IBA CC04, IBA CC13, and PTW 31021 ionization chambers used for PDD curves measurements-showed non-negligible errors (≥0.5%). The largest error (1.6%) was found for the combination of the Farmer PTW 30013 chamber with the IBA CC13 chamber, which was the most widely used chamber combination in our survey. CONCLUSIONS: Based on our findings, we strongly recommend assessing the impact of failing to apply correction factors kS in the PDD(10) and kvol prior to using any chamber type for FFF beam reference dosimetry purposes.

Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

Immediate reactions with glatiramer acetate: Diagnosis of allergy and desensitization protocols.

PURPOSE OF REVIEW: Diverse adverse events have been associated with administration of glatiramer acetate (GA), mainly local reactions at the injection site. Other, less frequent generalized reactions include isolated postinjection reactions and anaphylaxis, which may lead to discontinuation of GA. RECENT FINDINGS: Close collaboration between the allergy and neurology departments is needed to study adverse reactions to GA. The allergy study should include a detailed history and skin prick and intradermal tests with GA and, if possible, determination of specific IgE levels. Furthermore, the implication of other drugs should be ruled out. SUMMARY: An accurate diagnosis of reactions to GA is essential if we are to confirm or rule out allergy to GA. When an allergy diagnosis is confirmed or firmly suspected based on clinical evidence, desensitization protocols are increasingly seen as safe methods for reintroduction of GA.

Assessment of ion recombination correction and polarity effects for specific ionization chambers in flattening-filter-free photon beams.

PURPOSE: To investigate ion recombination correction and polarity effects in four ion chamber models in flattening-filter-free (FFF) beams to (1) evaluate their suitability for reference dosimetry; (2) assess the accuracy of the two-voltage technique (TVA) against the Bruggmoser formalism; and (3) examine the influence of the accelerator type on the recombination correction. METHODS: Jaffé plots were created for a variety of microchambers, small-volume and Farmer-type chambers to obtain kS, the recombination correction factor, using two different types of accelerators. These values were plotted against dose-per-pulse and Jaffé plots for opposite polarities were created to determine which chambers meet the AAPM TG-51 addendum recombination and polarity specifications. RESULTS: Nearly all small-volume chambers exhibited reference-class behavior with respect to ion recombination and polarity effects. The microchambers exhibited anomalous recombination and polarity effects, precluding their use for reference dosimetry in FFF beams. For the reference-class chambers, agreement between TVA-determined kS values and Jaffé and Bruggmoser formalisms-determined kS values was within 0.1%. No significant differences were found between the kS values obtained with the two different accelerators used in this work. CONCLUSIONS: This study stresses the need to characterize ion recombination correction and polarity effects for small-volume chambers and microchambers on an individual chamber basis and with the more rigorous criteria of the AAPM TG-51 addendum. Furthermore, the study demonstrated the suitability of the TVA method for chambers that exhibit reference-class behavior in FFF beams. Finally, this work has shown that the recombination correction does not depend on the type of accelerator but on its dose-per-pulse.

Oral Food Challenge in Food Protein-Induced Enterocolitis Syndrome by Fish: Is There Any Room for Improvement?

BACKGROUND: Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food hypersensitivity usually due to cow's milk or soy. Among the solid foods, rice is one of the most causative foods worldwide, but it varies depending on the geographic area. In the Mediterranean countries, fish is one of the most important triggers of FPIES. There is not a specific biological marker for the disease that allows us to confirm the diagnosis or to predict when tolerance to the offending food has been achieved, so all patients with a FPIES diagnosis undergo an oral food challenge (OFC) at least once. The OFC is a risky procedure and many patients develop severe symptoms. OBJECTIVE: We sought to evaluate the safety of a new OFC protocol in children with fish-FPIES. METHODS: A retrospective study was performed over a 22-year period (1996-2018). We compared two methodologies used in the OFC: Method 1 that consisted in giving several doses during the same day versus Method 2 that consisted in giving a unique dose per day on 2 or three non-consecutive days. RESULTS: A total of 75 positive OFC with fish done in 40 children were included. Forty-three (57.3%) OFC were performed following Method 1 and 32 (42.7%) with Method 2.The severity of the symptoms of the OFC done with Method 1 was mostly moderate (41.9%) followed by severe (39.5%) and mild (18.6%). The adverse reactions with Method 2 were mostly mild (68.8%) and only 18.8 and 12.5% presented moderate or severe symptoms, respectively. CONCLUSIONS: OFC performed in children with fish-FPIES are risky and many patients develop moderate or severe symptoms after this procedure. We propose a new protocol that has demonstrated to improve safety.

Multi-omics analysis points to altered platelet functions in severe food-associated respiratory allergy.

BACKGROUND: Prevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, along with inflammation progression, treatment is increasingly complex and expensive. Profilin sensitization constitutes a good model to study the progression of allergic inflammation. Our aim was to identify the underlying mechanisms and the associated biomarkers of this progression, focusing on severe phenotypes, using transcriptomics and metabolomics. METHODS: Twenty-five subjects were included in the study. Plasma samples were analyzed using gas and liquid chromatography coupled to mass spectrometry (GC-MS and LC-MS, respectively). Individuals were classified in four groups-"nonallergic," "mild," "moderate," and "severe"-based on their clinical history, their response to an oral challenge test with profilin, and after a refinement using a mathematical metabolomic model. PBMCs were used for microarray analysis. RESULTS: We found a set of transcripts and metabolites that were specific for the "severe" phenotype. By metabolomics, a decrease in carbohydrates and pyruvate and an increase in lactate were detected, suggesting aerobic glycolysis. Other metabolites were incremented in "severe" group: lysophospholipids, sphingosine-1-phosphate, sphinganine-1-phosphate, and lauric, myristic, palmitic, and oleic fatty acids. On the other hand, carnitines were decreased along severity. Significant transcripts in the "severe" group were found to be downregulated and were associated with platelet functions, protein synthesis, histone modification, and fatty acid metabolism. CONCLUSION: We have found evidence that points to the association of severe allergic inflammation with platelet functions alteration, together with reduced protein synthesis, and switch of immune cells to aerobic glycolysis.

EFOMP policy statement 16: The role and competences of medical physicists and medical physics experts under 2013/59/EURATOM.

On 5 December 2013 the European Council promulgated Directive 2013/59/EURATOM. This Directive is important for Medical Physicists and Medical Physics Experts as it puts the profession on solid foundations and describes it more comprehensively. Much commentary regarding the role and competences has been developed in the context of the European Commission project "European Guidelines on the Medical Physics Expert" published as Radiation Protection Report RP174. The guidelines elaborate on the role and responsibilities under 2013/59/EURATOM in terms of a mission statement and competence profile in the specialty areas of Medical Physics relating to medical radiological services, namely Diagnostic and Interventional Radiology, Radiation Oncology and Nuclear Medicine. The present policy statement summarises the provisions of Directive 2013/59/EURATOM regarding the role and competences, reiterates the results of the European Guidelines on the Medical Physics Expert document relating to role and competences of the profession and provides additional commentary regarding further issues arising following the publication of the RP174 guidelines.

Síndrome de apneas-hipopneas y narcolepsia. Descripción de una serie hospitalaria / Sleep apnoea-hypopnoea syndrome and narcolepsy. Description of a series of hospital patients

Introducción. Los trastornos del sueño son muy prevalentes en la población general; sin embargo, la asociación de síndrome de apneas-hipopneas (SAHS) en pacientes con narcolepsia se ha descrito en pocas ocasiones. Se revisan los trastornos del sueño encontrados en pacientes con narcolepsia, la prevalencia de SAHS asociado a estos pacientes y su respuesta a los tratamientos. Pacientes y métodos. Análisis descriptivo retrospectivo observacional de 25 pacientes, con diagnóstico de narcolepsia, atendidos en nuestro centro desde octubre de 2012 hasta diciembre de 2016. Resultados. De 470 pacientes valorados en la consulta monográfica de neurología, hemos diagnosticado a 25 pacientes con narcolepsia (5,31%); el 65% eran hombres, y el 35%, mujeres. Edad media en el momento del diagnóstico: 40 años. El 60% presenta otros trastornos del sueño asociados, el más frecuente es el SAHS (36%). La eficacia del tratamiento con presión aérea positiva continua nasal (CPAP) es del 66% en los pacientes con SAHS con indicación de CPAP. Conclusiones. El 60% de los pacientes con narcolepsia asocia un segundo trastorno del sueño (mayor que la incidencia de coexistencia en la población general, del 20-25% de los pacientes), y los descritos también son los más frecuentes en la población general (SAHS, síndrome de piernas inquietas, movimientos periódicos de las piernas). El 36% de los pacientes con narcolepsia asocia SAHS. De ellos, en el 78% se ha conseguido un control de eventos respiratorios adecuado; el 57% se ha controlado con CPAP y el 43% restante no ha precisado CPAP por corrección de eventos con otros métodos (AU)

Introduction. Sleep disorders are highly prevalent among the general population, although very few cases of sleep apnoea-hypopnoea syndrome (SAHS) have been reported in patients with narcolepsy. This study reviews the sleep disorders found in patients with narcolepsy, the prevalence of SAHS associated with these patients and their response to the different treatments. Patients and methods. We conducted an observation-based retrospective descriptive analysis of 25 patients diagnosed with narcolepsy, who were treated in our centre between October 2012 and December 2016. Results. Of 470 patients evaluated in the specialised neurology consultation unit, 25 patients were diagnosed with narcolepsy (5.31%); 65% were males and the remaining 35% were females; the mean age at the time of diagnosis was 40 years. 60% presented other associated sleep disorders, the most frequent being SAHS (36%). The efficacy rate of treatment with continuous positive airway pressure (CPAP) is 66% in patients with SAHS with an indication of CPAP. Conclusions. Altogether, 60% of patients with narcolepsy have a second associated sleep disorder (greater than the incidence of coexistence in the general population, of 20-25% of patients), and those reported are also the most frequent among the general population (SAHS, restless legs syndrome, periodic limb movement disorder). 36% of patients with narcolepsy have SAHS as an associated condition. Of these, 78% have reached a suitable degree of control over respiratory events; 57% have achieved control with CPAP, and the remaining 43% did not require CPAP for event correction with other methods (AU)

Differences in the Anaphylactic Response between C3H/HeOuJ and BALB/c Mice.

BACKGROUND: Anaphylaxis is a severe and potentially lethal allergic reaction whose incidence is increasing. Murine models can elucidate the underlying mechanisms and pave the way for appropriate therapeutic options. However, differences in strains and protocols hamper comparisons of data between researchers. We performed a parallel study of clinical and immune responses with 2 strains of mice, BALB/c and C3H/HeOuJ, in an allergen-induced systemic anaphylaxis protocol. Both strains have been widely used in allergy models, although they have not been compared in an intraperitoneal systemic model. METHODS: Groups of 5-week-old female BALB/c and C3H/HeOuJ mice were intraperitoneally sensitized with peanut in the presence of adjuvants. Specific immunoglobulin (sIg) G1, sIgG2a, sIgE, total IgE, histamine release, and specific stimulated splenocyte cytokines, interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, and interferon (IFN)-γ, were assessed. At week 6, mice were intraperitoneally challenged with peanut. Anaphylaxis was evaluated by recognition of clinical symptoms and changes in body temperature. RESULTS: All peanut-sensitized mice induced sIg and developed anaphylactic symptoms upon challenge. Nonetheless, the C3H/HeOuJ strain demonstrated earlier and persistently higher sIgG1 and sIgG2a production, elevated sIgE, and more severe clinical symptoms and histamine release than the BALB/c strain. In contrast, BALB/c exhibited higher release of IL-4, IL-5, IL-10, IL-13, and IFN-γ. CONCLUSIONS: Both models are suitable for studying anaphylaxis. Consequently, they could be used in research on the pathogenesis and therapy of anaphylaxis. However, according to the type of study performed, differences in the specific clinical, humoral, and cellular responses to antigens have to be considered.

Características, notación y sintaxis para el diseño de indicadores claves de proceso (KPI) en sistemas de adecuación de la demanda de laboratorio: el ejemplo de las recomendaciones de no hacer de AEBM-ML / Characteristics, function and syntax for the design of key performance indicators (KPI) in laboratory adjustment of the demand systems: The example of the “not to do” recommendations of the AEBM-ML

La Medicina del Laboratorio constituye un área de conocimiento multidisciplinar en continuo cambio, siendo responsabilidad de las sociedades científicas el compendiar y difundir los últimos avances científicos, así como proporcionar herramientas para su interpretación. El establecimiento de protocolos, guías y recomendaciones constituye una actividad esencial, pero estas acciones deben ir acompañadas de la definición de indicadores claves de procesos. Los indicadores claves de procesos permiten evaluar y hacer un seguimiento del correcto cumplimiento de los objetivos propuestos, así como actuar a modo de herramienta de mejora a través de la intercomparación entre laboratorios (benchmarking). La reciente publicación realizada por la Asociación Española de Biopatología Médica-Medicina del Laboratorio Decisiones inteligentes desde el laboratorio: de elegir sabiamente a no hacer constituye, en este sentido, un buen ejemplo. Elaborada en el seno del proyecto «Compromiso por la Calidad de las Sociedades Científicas en España» promovido por el Ministerio de Sanidad, Servicios Sociales e Igualdad, propone un total de 19 recomendaciones avaladas por un panel constituido por 26 expertos. Cada una de estas recomendaciones se acompaña de un conjunto de indicadores de proceso para evaluar el cumplimento y eficiencia de su implementación. Considerando como punto de partida la metodología y sistema de notación empleados en la citada monografía para el diseño de indicadores claves de procesos, constituye una guía de diseño útil para la evaluación de cualquier proceso de adecuación y uso efectivo del laboratorio (AU)

Laboratory Medicine is an area of multidisciplinary knowledge in continuous change. The scientific societies have the responsibility for summarising and disseminating the latest scientific advances, as well as providing tools for their interpretation. The establishment of protocols, guidelines and recommendations is an essential activity of these societies, but these actions must be accompanied by the definition of key performance indicators. The key performance indicators enable the objectives to be correctly fulfilled. Moreover, these indicators are an improvement tool based on the intercomparison between laboratories (benchmarking). Thus, the recent publication by the Spanish Medical Biopathology Society-Laboratory Medicine (Asociación Española de Biopatología Médica-Medicina del Laboratorio) entitled "Intelligent decisions since laboratory: from choose wisely till not to do" (Decisiones inteligentes desde el laboratorio: de elegir sabiamente a no hacer) is a good example. This publication, prepared within the framework of the "Commitment to Quality by the Spanish Scientific Societies" project, proposed by the Ministry of Health, makes 19 recommendations proposed by an expert panel of 26 laboratory professionals. Each recommendation includes several indicators to evaluate the compliance and effectiveness of their implementation. Taking the methodology and function used in the Spanish Medical Biopathology Association-Laboratory Medicine document for the design of key performance indicators as a basis, it becomes a useful guide for designing the evaluation of any adjustment process and its effective use in the laboratory (AU)

Endothelial (NOS3 E298D) and inducible (NOS2 exon 22) nitric oxide synthase polymorphisms, as well as plasma NOx, influence sepsis development.

INTRODUCTION: Nitric oxide (NO) influences susceptibility to infection and hemodynamic failure (HF) in sepsis. NOS3 and NOS2 SNPs might modify plasma nitrite/nitrate (NOx) levels, sepsis development, hemodynamics and survival. METHODS: 90 severely septic and 91 non-infected ICU patients were prospectively studied. NOS3 (E298D), NOS3 (-786 T/C), NOS3 (27 bp-VNTR), and NOS2A (exon 22) SNPs and plasma NOx levels were assessed. RESULTS: 21 patients (11.6%) died, 7 with sepsis. TT homozygotes and T allele carriers of NOS3 (E298D) and AG carriers of the NOS2A (exon 22) SNPs were more frequent among septic compared to non-infected ICU patients (p < 0.05). Plasma NOx was higher in septic, especially in septic with hemodynamic failure (HF) or fatal outcome (p < 0.006). Plasma NOx was higher in carriers of the T allele of the NOS3 (E298D) SNP (p = 0.006). Sepsis independently associated with HF, increased NOx, peripheral neutrophils, and fibrinogen levels, decreased prothrombin and the presence of the NOS3 (E298D) and NOS2A (exon 22) SNPs. A low APACHE II score was the only variable associated with sepsis survival. NOx was independently associated with sepsis, HF, decreased neutrophils and higher APACHE. CONCLUSIONS: NOS3 (E298D) and NOS2A (exon 22) SNPs, individually and in combination, and plasma NOx, associated with sepsis development. NOx associated with HF and fatal outcome.

Role of plasma matrix-metalloproteases (MMPs) and their polymorphisms (SNPs) in sepsis development and outcome in ICU patients.

Matrix-metalloproteases (MMPs) and their tissue-inhibitors (TIMPs), modulated by different single nucleotide polymorphisms (SNPs), are critical in sepsis development. Ninety ICU severely septic and 91 ICU uninfected patients were prospectively studied. MMP-1 (-1607 1G/2G), MMP-3 (-1612 5A/6A), MMP-8 (-799 C/T), MMP-9 (-1562 C/T), and MMP-13 (-77A/G) SNPs were genotyped. Plasma MMPs (-1, -2, -3, -8, -9, -10, -13) and TIMPs (-1,-2,-4) were measured. AA homozygotes and A allele carriers of MMP-13 (-77 A/G) and 1G2G carriers of the MMP-1 (-1607 1G/2G) SNPs frequencies were different between septic and uninfected patients (p < 0.05), as well as plasma MMP-3, -8, -9 -10 and TIMP-2 levels (p < 0.04). No differences in MMPs levels among MMP-13 or MMP-1 SNPs genotypes carriers were observed. The area under the ROC curve for MMP-8 in the diagnosis of sepsis was 0.87 (95% CI 0.82-0.92), and that of CRP was 0.98 (0.94-0.998), whereas the area of MMP-9 in the detection of non-septic state was 0.73 (0.65-0.80), p < 0.0001 for all curves. Sepsis associated with increased MMP-8 and decreased MMP-9 levels in multivariate analysis (p < 0.0002). We report for the first time an association between MMP-13 and MMP-1 SNPs and sepsis. An independent association of MMP-8 and MMP-9 levels with sepsis was also observed.

Current use of equations for estimating glomerular filtration rate in Spanish laboratories.

INTRODUCTION: In 2006 the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) and the Spanish Society of Nephrology (S.E.N.) developed a consensus document in order to facilitate the diagnosis and monitoring of chronic kidney disease with the incorporation of equations for estimating glomerular filtration rate (eGFR) into laboratory reports. The current national prevalence of eGFR reporting and the degree of adherence to these recommendations among clinical laboratories is unknown. METHODS: We administered a national survey in 2010-11 to Spanish clinical laboratories. The survey was through e-mail or telephone to laboratories that participated in the SEQC’s Programme for External Quality Assurance, included in the National Hospitals Catalogue 2010, including both primary care and private laboratories. RESULTS: A total of 281 laboratories answered to the survey. Of these, 88.2% reported on the eGFR, with 61.9% reporting on the MDRD equation and 31.6% using the MDRD-IDMS equation. A total of 42.5% of laboratories always reported serum creatinine values, and other variables only when specifically requested. Regarding the way results were presented, 46.2% of laboratories reported the exact numerical value only when the filtration rate was below 60mL/min/1.73m2, while 50.6% reported all values regardless. In 56.3% of the cases reporting eGFR, an interpretive commentary of it was enclosed. CONCLUSIONS: Although a high percentage of Spanish laboratories have added eGFR in their reports, this metric is not universally used. Moreover, some aspects, such as the equation used and the correct expression of eGFR results, should be improved.

Extreme concentrations of high density lipoprotein cholesterol affect the calculation of low density lipoprotein cholesterol in the Friedewald formula and other proposed formulas.

OBJECTIVES: To investigate the effect of extreme levels of high density lipoprotein cholesterol (HDL-C) in the calculation of low density lipoprotein cholesterol (LDL-C) using Friedewald's formula (FF) and other formulas proposed recently. DESIGN AND METHODS: Lipoprotein profile was performed in 2603 samples with HDL-C ≤ 20 mg/dL and 1953 samples with HDL-C ≥ 100 mg/dL. RESULTS: Wilcoxon's and Student's t-tests showed significant differences (p<0.001) between calculated LDL-C by different formulas and direct determination in the two groups of HDL-C values. Passing-Bablok regression and Bland-Altman plot showed disagreement for the four formulas studied, except for Vujovic formula in the HLD-C ≥ 100 mg/dL group. CONCLUSIONS: Our results suggested that none of the formulas under analysis should be used for estimating LDL-C in samples with extreme HDL-C concentrations due to absence of statistical correlation with LDL-C direct measurement.