Ex vivo effect of JAK inhibition on JAK-STAT1 pathway hyperactivation in patients with dominant-negative STAT3 mutations.

PURPOSE: STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted treatment with Janus-kinase (JAK) inhibitors shows promising results in treating STAT1 GOF-associated symptoms while management of DN STAT3 patients has been largely supportive. We here assessed the impact of ruxolitinib on the JAK-STAT1/3 pathway in DN STAT3 patients' cells. METHODS: Using flow cytometry, immunoblot, qPCR, and ELISA techniques, we examined the levels of basal STAT1 and phosphorylated STAT1 (pSTAT1) of cells obtained from DN STAT3, STAT1 GOF patients, and healthy donors following stimulation with type I/II interferons (IFNs) or interleukin (IL)-6. We also describe the impact of ruxolitinib on cytokine-induced STAT1 signaling in these patients. RESULTS: DN STAT3 and STAT1 GOF resulted in a similar phenotype characterized by increased STAT1 and pSTAT1 levels in response to IFNα (CD3+ cells) and IFNγ (CD14+ monocytes). STAT1-downstream gene expression and C-X-C motif chemokine 10 secretion were higher in most DN STAT3 patients upon stimulation compared to healthy controls. Ex vivo treatment with the JAK1/2-inhibitor ruxolitinib reduced cytokine responsiveness and normalized STAT1 phosphorylation in DN STAT3 and STAT1 GOF patient' cells. In addition, ex vivo treatment was effective in modulating STAT1 downstream signaling in DN STAT3 patients. CONCLUSION: In the absence of effective targeted treatment options for AD-HIES at present, modulation of the JAK/STAT1 pathway with JAK inhibitors may be further explored particularly in those AD-HIES patients with autoimmune and/or autoinflammatory manifestations.

Extracellular Vesicles as Biomarkers in Liver Disease.

Extracellular vesicles (EVs) are membrane-derived vesicles released by a variety of cell types, including hepatocytes, hepatic stellate cells, and immune cells in normal and pathological conditions. Depending on their biogenesis, there is a complex repertoire of EVs that differ in size and origin. EVs can carry lipids, proteins, coding and non-coding RNAs, and mitochondrial DNA causing alterations to the recipient cells, functioning as intercellular mediators of cell-cell communication (auto-, para-, juxta-, or even endocrine). Nevertheless, many questions remain unanswered in relation to the function of EVs under physiological and pathological conditions. The development and optimization of methods for EV isolation are crucial for characterizing their biological functions, as well as their potential as a treatment option in the clinic. In this manuscript, we will comprehensively review the results from different studies that investigated the role of hepatic EVs during liver diseases, including non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcoholic liver disease, fibrosis, and hepatocellular carcinoma. In general, the identification of patients with early-stage liver disease leads to better therapeutic interventions and optimal management. Although more light needs to be shed on the mechanisms of EVs, their use for early diagnosis, follow-up, and prognosis has come into the focus of research as a high-potential source of 'liquid biopsies', since they can be found in almost all biological fluids. The use of EVs as new targets or nanovectors in drug delivery systems for liver disease therapy is also summarized.

Gene Therapy for Neuronopathic Mucopolysaccharidoses: State of the Art.

The need for long-lasting and transformative therapies for mucopolysaccharidoses (MPS) cannot be understated. Currently, many forms of MPS lack a specific treatment and in other cases available therapies, such as enzyme replacement therapy (ERT), do not reach important areas such as the central nervous system (CNS). The advent of newborn screening procedures represents a major step forward in early identification and treatment of individuals with MPS. However, the treatment of brain disease in neuronopathic MPS has been a major challenge to date, mainly because the blood brain barrier (BBB) prevents penetration of the brain by large molecules, including enzymes. Over the last years several novel experimental therapies for neuronopathic MPS have been investigated. Gene therapy and gene editing constitute potentially curative treatments. However, despite recent progress in the field, several considerations should be taken into account. This review focuses on the state of the art of in vivo and ex vivo gene therapy-based approaches targeting the CNS in neuronopathic MPS, discusses clinical trials conducted to date, and provides a vision for the future implications of these therapies for the medical community. Recent advances in the field, as well as limitations relating to efficacy, potential toxicity, and immunogenicity, are also discussed.

Analgesic effect of postoperative laparoscopic-guided transversus abdominis plane (TAP) block, associated with preoperative port-site infiltration, within an enhanced recovery after surgery protocol in one-anastomosis gastric bypass: a randomized clinical trial.

BACKGROUND: The use of ultrasonography to assist needle placement during transverse abdominal plane (TAP) technique has provided direct visualization of surround anatomical musculature and facial planes. However, the increased girth in patients undergoing bariatric surgery is challenging to visualize via ultrasonography which may lead to poor postoperative analgesia. OBJECTIVE: The aim of the study is to investigate whether the addition of postoperative laparoscopic-guided TAP block as part of a multimodal analgesic regimen within the ERAS protocol compared to no block provides better postoperative analgesia in patients undergoing one-anastomosis gastric bypass surgery. PATIENTS AND METHODS: A prospective clinical trial was performed. Patients were randomized into two groups: patients undergoing postoperative laparoscopic-guided TAP (TAP-lap) and patients not receiving TAP-lap (Control). Multimodal analgesia included preoperative port-site infiltration with Bupivacaine 0.25% in both groups and systemic Acetaminophen. Pain quantification as measured by visual analogic scale (VAS) was assessed at 6 and 24 h after surgery, and 24-h postoperative opioid consumption. RESULTS: One hundred and forty patients were included, 70 in each group. The mean operation time was 78.5 ± 14.4 min in TAP-lap and 75.9 ± 15.6 min in Control (NS). The mean postoperative pain, as measured by VAS, 6 h after surgery was 23.1 ± 11.3 mm in TAP-lap and 41.8 ± 16.2 mm in Control (p = 0.001). 24 h after surgery was 16.6 ± 11.4 mm in TAP-lap and 35.4 ± 12.7 mm in Control (p = 0.001). Morphine rescues were necessary in 14.2% in Control and 2.8% in TAP-lap (p = 0.035). CONCLUSION: Laparoscopic-guided TAP block as part of a multimodal analgesia regimen can reduce postoperative pain and opioid consumption, without increasing operative time.

A Simple Method for the Determination of Triazines from Seawater in Accordance with the Directive 2013/39/EU.

Since the Directive 2013/39/EU included terbutryn to the list of priority substances of all water bodies, a previous method based on dispersive liquid-liquid micro-extraction (DLLME) for the determination of triazines in seawater has been modified. The main change consisted on the use of tandem mass spectrometry instead of diode array as detection technique. Due to the higher sensitivity of mass detector, sample volume was reduced and extraction solvent volume was optimized. The optimum extraction conditions were 5 mL of sample, 50 µL of 1-octanol and an agitation step instead of disperser solvent. The obtained analytical recoveries (73%-101% with relative standard deviations below 4%) meeting the requirements. The limits of quantification (between 0.016 and 0.021 µg L-1) were more than 10 times lower than the limit set by the European Directive 2013/39/EU for terbutryn (0.34 µg L-1). The proposed method was applied to the determination of the target compounds in seawater samples from A Coruña (Galicia, NW of Spain).

Long-term follow-up after sleeve gastrectomy versus Roux-en-Y gastric bypass versus one-anastomosis gastric bypass: a prospective randomized comparative study of weight loss and remission of comorbidities.

BACKGROUND: One-Anastomosis Gastric Bypass (OAGB) has exponentially increased in the last decade, as it is associated with very low complications, mortality, readmissions and reoperations rates, and shows excellent short- and long-term benefits of weight loss and resolution of comorbidities. The aim of this study was to compare the effect of SG, RYGB, and OAGB, on short- and long-term weight loss and comorbidities resolution. METHODS: A prospective randomized clinical study of all morbidly obese patients undergoing SG, RYGB, and OAGB, as primary bariatric procedures, was performed. Patients were randomly assigned into 3 groups: those patients undergoing SG, those ones undergoing RYGB and those ones undergoing OAGB. BMI, excess BMI loss (EBMIL) and remission of type 2 diabetes (T2DM), hypertension (HT), and dyslipidemia (DL) were assessed. RESULTS: 600 patients were included in the study, 200 in each group. Follow-up rate at 5 years postoperatively was 91% in SG group, 92% in RYGB, and 90% in OAGB. OAGB achieves significantly greater EBMIL than RYGB and SG at 1, 2, and 5 years (p < 0.001, respectively). At 5 years, OAGB achieves significantly greater remission of T2DM (p = 0.027), HT (p = 0.006), and DL (p < 0.001) than RYGB and SG. RYGB did not show significant superiority than SG in short- and long-term remission of T2DM and HT, but achieves greater remission of DL (p < 0.001). CONCLUSION: OAGB achieves superior mid- and long-term weight loss than RYGB and SG. There are no significant differences in weight loss between SG and RYGB at 1, 2, and 5 years. OAGB achieves better short- and long-term resolution rates of DM, HT, and DL than SG and RYGB. RYGB and SG obtain similar T2DM and HT remissions, but RYGB reaches significantly greater rates of DL remission. ClinicalTrials.gov Identifier: NCT03467646.

Relationship between pressure ulcer risk based on Norton Scale and on the "Eating/Drinking" need assessment.

AIM: To study the relationship between pressure ulcer risk evaluated by the Norton Scale and inadequate fulfilment of Need 2 (Eating/Drinking) from the 14-need classification designed by Virginia Henderson. BACKGROUND: Assessing nutritional status and skin condition to implement preventive measures are important nursing interventions. Our hospital's standard procedure requires recording Norton Scale and Henderson Eating/Drinking Assessment results. METHODS: This was a descriptive cross-sectional study, analysing case histories of 219 patients in medical/surgical wards for >24 hr with nursing care recorded in the GACELA Care computer application. Patient sociodemographic variables and evaluation concepts from the Norton Scale and Eating/Drinking were studied. RESULTS: A statistically significant relationship (p < 0.05; 95% CI: 0.61, 2.83) was seen between inadequate Eating/Drinking need fulfilment and increased pressure ulcer risk. Pressure ulcer risk was generally low in the sample, with mainly no or minimum risk (77.3%); the oldest age group had the highest risk. Self-care autonomy was the most frequently assessed item in Eating/Drinking (42%). CONCLUSIONS: A relationship was found between Norton Scale risk results and Eating/Drinking need assessment results. The greater the pressure ulcer risk, the more likely was inadequate need satisfaction (poor nutritional status). IMPLICATIONS: To help identify pressure ulcer risk, nurses should assess patients' eating independence. Safeguarding nutritional status and preventing pressure ulcers are nursing skills associated with quality nursing care.

Reaching consensus on communication of critical laboratory results using a collective intelligence method.

BACKGROUND: There is no consensus in the literature about what analytes or values should be informed as critical results and how they should be communicated. The main aim of this project is to establish consensual standards of critical results for the laboratories participating in the study. Among the project's secondary objectives, establishing consensual procedures for communication can be highlighted. METHODS: Consensus was reached among all participating laboratories establishing the basis for the construction of the initial model put forward for consensus in conjunction with the clinicians. A real-time Delphi, methodology "health consensus" (HC), with motivating and participative questions was applied. The physician was expected to choose a numeric value within a scale designed for each analyte. RESULTS: The medians of critical results obtained represent the consensus on critical results for outpatient and inpatient care. Both in primary care and in hospital care a high degree of consensus was observed for critical values proposed in the analysis of creatinine, digoxin, phosphorus, glucose, international normalized ratio (INR), leukocytes, magnesium, neutrophils, chloride, sodium, calcium and lithium. For the rest of critical results the degree of consensus obtained was "medium high". The results obtained showed that in 72% of cases the consensual critical value coincided with the medians initially proposed by the laboratories. CONCLUSIONS: The real-time Delphi has allowed obtaining consensual standards for communication of critical results among the laboratories participating in the study, which can serve as a basis for other organizations.

Complement C3F allotype synthesized by liver recipient modifies transplantation outcome independently from donor hepatic C3.

Complement component 3 (C3) presents both slow (C3S) and fast (C3F) variants, which can be locally produced and activated by immune system cells. We studied C3 recipient variants in 483 liver transplant patients by RT-PCR-HRM to determine their effect on graft outcome during the first year post-transplantation. Allograft survival was significantly decreased in C3FF recipients (C3SS 95% vs C3FS 91% vs C3FF 83%; P=.01) or C3F allele carriers (C3F absence 95% vs C3F presence 90%, P=.02). C3FF genotype or presence of C3F allele independently increased risk for allograft loss (OR: 2.38, P=.005 and OR: 2.66, P=.02, respectively). C3FF genotype was more frequent among patients whose first infection was of viral etiology (C3SS 13% vs C3FS 18% vs C3FF 32%; P=.04) and independently increased risk for post-transplant viral infections (OR: 3.60, P=.008). On the other hand, C3FF and C3F protected from rejection events (OR: 0.54, P=.03 and OR: 0.63, P=.047, respectively). Differences were not observed in hepatitis C virus recurrence or patient survival. In conclusion, we show that, independently from C3 variants produced by donor liver, C3F variant from recipient diminishes allograft survival, increases susceptibility to viral infections, and protects from rejection after transplantation. C3 genotyping of liver recipients may be useful to stratify risk.

Association of early kidney allograft failure with preformed IgA antibodies to ß2-glycoprotein I.

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti-ß2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.

Nonspecific (Heterologous) Protection of Neonatal BCG Vaccination Against Hospitalization Due to Respiratory Infection and Sepsis.

BACKGROUND: Bacille Calmette-Guerin (BCG) vaccination has been suggested to have nonspecific beneficial effects in children from developing countries, reducing morbidity and mortality caused by unrelated pathogens. OBJECTIVE: We aimed to assess the heterologous protective effects of BCG vaccination against respiratory infection (RI) and sepsis not attributable to tuberculosis in children born in Spain. METHODS: We conducted a retrospective epidemiological study using data from the Official Spanish Registry of Hospitalizations (CMBD-HA) to identify differences in hospitalization rates (HR) in BCG-vaccinated children (Basque Country, where neonatal BCG is part of the immunization schedule and has a 100% coverage) as compared to non-BCG-vaccinated children (from the rest of Spain, where BCG is not used). RESULTS: A total of 464 611 hospitalization episodes from 1992 to 2011 were analyzed. The HR due to RI not attributable to tuberculosis in BCG-vaccinated children was significant lower compared to non-BCG-vaccinated children for all age groups, with a total preventive fraction (PF) of 41.4% (95% confidence interval: 40.3-42.5; P-value <.001). According to age group, PF was 32.4% (30.9-33.9; P-value <.001) for children under 1 year old, 60.1% (58.5-61.7; P-value <.001) for children between 1 and 4 years old, 66.6% (62.8-70.2; P-value <.001) for children between 5 and 9 years old, and 69.6% (63.3-75.0; P-value <.001) for children between 10 and 14 years old. The HR due to sepsis not attributable to tuberculosis in BCG-vaccinated children under 1 year of age was also significantly lower, with a PF of 52.8% (43.8-60.7; P-value <.001). CONCLUSIONS: BCG vaccination at birth may decrease hospitalization due to RI and sepsis not related to tuberculosis through heterologous protection.

[Prevalence of performing and prescribing physical exercise in patients diagnosed with anxiety and depression]. / Prevalencia de realización y prescripción de ejercicio físico en pacientes diagnosticados de ansiedad y depresión.

OBJECTIVE: To estimate the prevalence of physical exercise practice in patients diagnosed with anxiety and/or depression. DESIGN: Cross-sectional, observational study. LOCATION: Sabugo and la Magdalena primary care centers in Avilés. PARTICIPANTS: Patients aged 18 to 75 years diagnosed with anxiety and/or depression, consumers of psychoactive drugs in the three months previous to the realization of the study. We selected 376 patients by simple random sampling stratified by health center, making them a telephone survey. MAIN MEASUREMENTS: Age, sex, physical exercise realization, type and duration of exercise, diagnosis of anxiety and/or depression, exercise prescription, prescriber health personnel and use of psychotropic medication. RESULTS: 294 participants (78.19% of selected) with a mean age of 55.33 years (55.32±12.53 SD) and 78.2% were female. 60.9% were diagnosed with anxiety, 59.5% with depression and 20.4% both diagnoses. 62.9% used antidepressants, benzodiazepines 76.9% and 39.79% both treatments. 58.5% (95%CI: 52.70-64.31) performed exercise of which 44.77% did it 3-5 times/week. The mean duration was 1.24h each time (95%CI: 0.53-1.96). The physical exercise was prescribed to the 59.18% (95%CI: 53.39-64.97); 90.23% by the family physician, 63.22% primary care nurse, 17.24% psychiatrist and 5.17% psychologist. The adherence to the prescription was 59.77% (95%CI: 52.20-67.34). CONCLUSIONS: The percentage of anxious and/or depressed patients who practiced exercise is similar to the general population but should be higher. The exercise prescription by health personnel is insufficient.

Assessment of nurses' level of knowledge of the management of chronic wounds.

BACKGROUND: Chronic wounds are a challenge and a major cause of morbidity. A wound is considered chronic if healing does not occur within the expected time frame depending on the etiology and location of the wound. OBJECTIVE: To assess the level of knowledge about chronic wound management of postgraduate nurses in different areas of the health system and their previous satisfaction with the training received during their undergraduate studies. DESIGN: Cross-sectional study of a health system of 95,000 inhabitants and 557 nursing professionals working in it. PARTICIPANTS: Nurses working in the study health system and in areas with care for patients with chronic wounds in social, primary and hospital care. RESULTS: Survey results described a low knowledge of chronic wound management in general. Data on knowledge according to area of work showed that nurses in primary care had the highest knowledge of wound etiology. Nurses working in health and social care were most knowledgeable in diagnostic knowledge. Hospital nurses showed the lowest knowledge overall. A relationship was observed when nurses had a master's degree followed by an expert with better knowledge in the test. In addition, nurses reported little training in chronic wounds during their university studies (69.73 %, n = 106). CONCLUSIONS: Therefore, a review of this point should be considered to improve the management of chronic wounds and their correct approach among nursing students. A review of continuing and even specialised training needs in the clinical care setting should also be considered.

False positive elevation in serum creatinine: a case report.

Background: Paraproteins can interfere with several substances, producing erroneous laboratory measurements. The diagnosis of kidney disease in patients with hematological disorders has important prognosis implications. An elevated creatinine with no other signs of kidney disease should prompt the idea of a spurious creatinine. Communication between the clinical team and the laboratory is key. Case presentation: In this case, we present a 68-year-old woman with an elevated creatinine and an IgM lambda paraprotein. Interestingly, there were no other signs of chronic kidney disease besides the creatinine value, with no albuminuria or microhematuria. A kidney biopsy showed normal parenchyma and ruled out the possibility of paraprotein-related damage. The monoclonal component and creatinine levels raised parallelly during follow-up while maintaining normal urea levels. This prompted the hypothesis of a falsely elevated creatinine. It was confirmed with a normal glomerular filtration rate determined by a radioisotope, a cystatin C measurement and a reduction in creatinine when diluting the sample. Conclusion: It is important to consider the possibility of a falsely elevated creatinine in patients with paraproteinemia and no other signs of kidney disease to avoid unnecessary diagnostic tests and for the prognostic implications.

Prospective, Randomized, Double-Blind Parallel Group Nutritional Study to Evaluate the Effects of Routine Intake of Fresh vs. Pasteurized Yogurt on the Immune System in Healthy Adults.

The immune system is affected by the dietary products humans intake. Immune system regulation by nutrition has uses in the clinical context, but it can also benefit healthy populations by delaying or preventing the emergence of immune-mediated chronic illnesses. In this study, the purpose was to describe and compare the modulator effects on the immune system of the routine ingestion of fresh vs. pasteurized yogurt. A unicentral, prospective, randomized, double-blind, parallel group 8-week nutritional study was carried out comparing the ingestion of 125 g of the products in healthy adults three times a day. A complete battery of in vitro tests on the activity of the immune system, processes and phenomena was performed. Exclusive immune-modulatory effects of fresh yogurt with respect to base line were found in terms of increased systemic IgM (primary immune responses), increased synthesis of IFN-gamma upon stimulation (Th1) and increased peripheral T cells (mainly "naive" CD4s). In the three interventions, we observed an increased phagocytic activity and burst test in granulocytes, together with increased secretion of IL-6, IL-1 ß and IL-8 (pro-inflammatory) and increased CD16 expression (FcR favoring phagocytosis) in granulocytes. Overall, it is concluded that regardless of bacteria being alive or thermally inactivated, yogurt has common effects on the innate system, but the presence of live bacteria is necessary to achieve a potentiating effect on the specific immune response.

Development of a dispersive liquid-liquid microextraction method for the determination of plastic additives in seawater.

A method using dispersive liquid-liquid microextraction (DLLME) prior to high performance liquid chromatography-diode array detection (HPLC-DAD) was developed to determine seven additives from the plastics industry (butylated hydroxytoluene, diisodecyl phthalate, irgafos 168, lawsone, quercetin, triclosan and vitamin E) in seawater samples. These compounds can reach seawater due to direct discharge from wastewater treatment plants and leaching from plastics and microplastics. The extraction was performed using 25 mL of seawater, 500 µL of 1-octanol (extraction solvent) and a stirring step instead of dispersive solvent. Additive concentrations were determined by LC-DAD on a C18 column with a mobile phase of acetonitrile and phosphoric acid aqueous solution (pH 3.5) by gradient elution. The analytical recoveries ranged from 82 to 93% for all compounds, except for lawsone (60%). Repeatability and intermediate precision were adequate with RSD < calculated values following the Horwitz equation at the concentration levels evaluated (0.06 and 0.24 mg L-1). All additives exhibited linear matrix calibration curves (R2 > 0.99). Detection limits ranged from 0.009 to 0.028 mg L-1 and quantification limits ranged from 0.027 to 0.084 mg L-1. Finally, the application of the method to real samples verified the method as accurate and applicable to seawater.

Changes in Adhesion and the Expression of Adhesion Molecules in PBMCs after Aneurysmal Subarachnoid Hemorrhage: Relation to Cerebral Vasospasm.

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by extravasation of blood to the subarachnoid space after rupture of the cerebral vessels. After bleeding, the immune response is activated. The role of peripheral blood mononuclear cells (PBMCs) in this response is a current subject of research. We have analysed the changes in PBMCs of patients with aSAH and their interaction with the endothelium, focusing on their adhesion and the expression of adhesion molecules. Using an in vitro adhesion assay, we observed that the adhesion of PBMCs of patients with aSAH is increased. Flow cytometry analysis shows that monocytes increased significantly in patients, especially in those who developed vasospasm (VSP). In aSAH patients, the expression of CD162, CD49d, CD62L and CD11a in T lymphocytes and of CD62L in monocytes increased. However, the expression of CD162, CD43, and CD11a decreased in monocytes. Furthermore, monocytes from patients who developed arteriographic VSP had lower expression of CD62L. In conclusion, our results confirm that after aSAH, monocyte count and adhesion of PBMCs increase, especially in patients with VSP, and that the expression of several adhesion molecules is altered. These observations can help predict VSP and to improve the treatment of this pathology.

A newborn Screening Programme for Inborn errors of metabolism in Galicia: 22 years of evaluation and follow-up.

BACKGROUND: There is a notable lack of harmonisation in newborn screening (NBS) programmes worldwide. The Galician programme for early detection of inborn errors of metabolism (IEM) was one of the first NBS programmes in Europe to incorporate mass spectrometry (July 2000). This programme currently screens for 26 IEMs in dried blood and urine samples collected 24-72 h after birth. RESULTS: In its 22-year history, this programme has analysed samples from 440,723 neonates and identified 326 cases of IEM with a prevalence of 1:1351. The most prevalent IEMs were hyperphenylalaninaemia (n = 118), followed by medium chain acyl-CoA dehydrogenase deficiency (MCADD, n = 26), galactosaemia (n = 20), and cystinurias (n = 43). Sixty-one false positives and 18 conditions related to maternal pathologies were detected. Urine samples have been identified as a useful secondary sample to reduce the rate of false positives and identify new defects. There were 5 false negatives. The overall positive value was 84.23%. The fatality rate over a median of 12.1 years of follow-up was 2.76%. The intelligence quotient of patients was normal in 95.7% of cases, and school performance was largely optimal, with pedagogic special needs assistance required in < 10% of cases. Clinical onset of disease preceded diagnosis in 4% of cases. The age at which first NBS report is performed was reduced by 4 days since 2021. CONCLUSIONS: This study highlights the benefits of collecting urine samples, reduce NBS reporting time and expanding the number of IEMs included in NBS programmes.