Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.

BACKGROUND: Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials. METHODS: We recruited 3 patients receiving Sebelipase alfa 5 mg/kg twice weekly. We measured LAL activity in leukocytes and plasma oxysterol concentration in two patients and LAL activity in fibroblasts in one patient. Clinical follow up was also assessed. RESULTS: Analyses of LAL activity and oxysterols demonstrate that there is short-lived enzyme activity post-dosing which is associated with the release of stored lipids. Clinical data demonstrate that 5 mg/kg twice weekly dosing is well tolerated and effective. CONCLUSION: 5 mg/kg twice weekly dosing with Sebelipase alfa rescues severely ill infants with WD by increasing substrate clearance. There is biologically relevant lipid accumulation in the 'trough' periods before the next dosing, even with this intensive regimen.

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.

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.

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.

Occult cancer in patients with unprovoked venous thromboembolism: A nested case-control study.

OBJECTIVES: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies. METHODS: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants. RESULTS: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%). CONCLUSIONS: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies.

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.

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.

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.

Handling of lipemic samples in the clinical laboratory.

Interferences in the clinical laboratory may lead physicians misinterpret results for some biological analytes. The most common analytical interferences in the clinical laboratory include hemolysis, icterus and lipemia. Lipemia is defined as turbidity in a sample caused by the accumulation of lipoproteins, mainly very-low density lipoproteins (VLDL) and chylomicrons. Several methods are available for the detection of lipemic samples, including the lipemic index, or triglyceride quantification in serum or plasma samples, or mean corpuscular hemoglobin (MCHC) concentration in blood samples. According to the European Directive 98/79/CE, it is the responsibility of clinical laboratories to monitor the presence of interfering substances that may affect the measurement of an analyte. There is an urgent need to standardize interference studies and the way interferences are reported by manufacturers. Several methods are currently available to remove interference from lipemia and enable accurate measurement of biological quantities. The clinical laboratory should establish a protocol for the handling of lipemic samples according to the biological quantity to be tested.

Discrepancies in Lipemia Interference Between Endogenous Lipemic Samples and Smoflipid®-Supplemented Samples.

Background: Manufacturers evaluate lipemia-induced interference using Intralipid®, but it does not contain all lipoprotein types. The aim of this study was to evaluate lipemiainduced interference in biochemical parameters from endogenous lipemic samples and SMOFlipid® supplemented samples, in order to assess if SMOFlipid® can be used in lipemic interference studies. Methods: Serum pools were supplemented with SMOFlipid® to achieve 800 mg/dL and 1500 mg/dL triglyceride concentration, and analyzed for 25 biochemical parameters both before and after the supplementation. In another independent phase, lipemic serum pools were prepared choosing patient samples of 800 mg/dL and 1500 mg/dL triglyceride concentration. These lipemic serum pools were ultracentrifugated in order to remove lipids. Biochemical parameters were analyzed before and after ultracentrifugation. The bias between SMOFlipid®-supplemented samples and endogenous lipemic samples were compared. The bias between the lipemic and non-lipemic samples were compared with the reference change value. Results: At 800 mg/dL triglyceride concentration, we found that total protein and transferrin had been affected only in endogenous lipemic serum samples. Magnesium and creatinine had been affected only in SMOFlipid®-supplemented samples. At 1500 mg/dL triglyceride concentration, we found that total protein, amylase, ferritin and glucose had lipemic interference only in endogenous lipemic samples, and chloride only in SMOFlipid®-supplemented samples. Conclusions: The use of SMOFlipid®-supplemented samples does not provide suitable data to estimate lipemia-induced interference. Thus, interference studies should be performed using a wide variety of lipemic patient samples that represent the heterogeneity of the lipoprotein particles size.

Mixed-mode chromatography of mixed functionalized analytes as the homologues of benzalkonium chloride. Application to pharmaceutical formulations.

In this work, a retention behavior based on mixed-mode reversed-phase (RP)/hydrophilic interaction liquid chromatography (HILIC) was observed for benzalkonium chloride (BAK) using a core-shell column functionalized with biphenyl groups. Although in the literature, the U-shaped retention was reported for polar compounds in mixed functionalized phases, in the present work, the behavior was dependent upon the chemical structure of the analyte with mixed functionality (ammonium group, a benzyl group and an alkyl chain) and on the high selectivity of the chromatographic column. The bimodal retention was observed for the four BAK homologues using a content of acetonitrile from 65 to 95% in the mobile phase. The data were adjusted to polynomial equations which allow for modeling and predicting the U-shaped retention. The salt concentration (50 and 100 mM), anion (formate and acetate) and cation (ammonium and triethylammonium) of the salt, pH (4 and 5) in the mobile phase were studied in order to understand their influence on the two retention modes. Significant electrostatic interactions were involved in the two retention modes, especially with a content of acetonitrile higher that 90%. Linear relationships between the retention factors of the four homologues were found in a wide range of %acetonitrile when the salt and triethylamine concentration, pH and nature of salt were changed. The differences found on the retention of the homologues, when increasing the alkyl chain length, were more significant in the RP mode due to predominant hydrophobic interactions. A pH decrease and a salt concentration increase caused a retention decrease for both modes. A decrease on of the retention was observed when acetate anion was replaced by formate anion. The different order of the polynomial equations according to the used mobile phase confirmed its relevant role in the interactions with the analytes and stationary phase. A mobile phase was selected (85% acetonitrile, pH 4 and 100 mM ammonium formate) for the BAK determination in cutaneous, otic and ophthalmic formulations with different active pharmaceutical ingredients and excipients. Low sample volume (500 µL) and short analysis time (<5 min) were some of the advantages of the proposed method. In addition, good analytical performance (R2 > 0.999, % RSD <4.5% for intra-day precision and <5.8% for inter-day precision, and recoveries in the 92-105% range) was obtained.

Prevalence and Characterization of Psychological Trauma in Patients with Fibromyalgia: A Cross-Sectional Study.

Background: Preliminary evidence suggests that psychological trauma, especially childhood trauma, is a risk factor for the onset of fibromyalgia (FM). Objective: The main objective of this study consisted of evaluating the prevalence and detailed characteristics of psychological trauma in a sample of patients with FM, the chronology of trauma across the lifespan, and its clinical symptoms. We also calculated whether childhood trauma could predict the relationship with different clinical variables. Method: Eighty-eight females underwent an interview to assess sociodemographic data, psychiatric comorbidities, level of pain, FM impact, clinical symptoms of anxiety, depression, insomnia, quality of life, and psychological trauma. Results: The majority of participants (71.5%) met the diagnostic criteria for current post-traumatic stress disorder (PTSD). Participants reported having suffered traumatic events throughout their lifespan, especially in childhood and early adolescence, in the form of emotional abuse, emotional neglect, sexual abuse, and physical abuse. Traumatic events predict both poor quality of life and a level of pain in adulthood. All patients showed clinically relevant levels of anxiety, depression, insomnia, suicidal thoughts, and pain, as well as somatic comorbidities and poor quality of life. Pain levels predicted anxiety, depression, dissociation, and insomnia symptoms. 84% of the sample suffered one or more traumatic events prior to the onset of pain. Conclusions: Our data highlight the clinical complexity of patients with FM and the role of childhood trauma in the onset and maintenance of FM, as well as the high comorbidity between anxiety, depression, somatic symptoms, and FM. Our data also supports FM patients experiencing further retraumatization as they age, with an extremely high prevalence of current PTSD in our sample. These findings underscore the need for multidisciplinary programs for FM patients to address their physical pain and their psychiatric and somatic conditions, pay special attention to the assessment of psychological trauma, and provide trauma-focused interventions. Trial registration: ClinicalTrials.gov NCT04476316. Registered on July 20th, 2020.

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.

Changes in the Bone Mineral Density after Sleeve Gastrectomy vs. Roux-En-Y Gastric Bypass 2 Years after Surgery.

The aim of this study was to compare the analytical and densitometric changes 2 years after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A retrospective study of a prospectively collected database was performed. Morbidly obese patients undergoing RYGB or SG, as primary bariatric procedures, were included. Weight loss; analytical levels of parathormone (PTH), vitamin D, and calcium; and densitometric parameters were investigated. In total, 650 patients were included in the study, and 523 patients (80.5%) underwent RYGB and 127 (19.5%) SG. There were no significant differences in excess weight loss at 24 months between both groups. When comparing preoperative and postoperative values, a significantly greater increase in PTH values was observed in the RYGB group, whereas there were no significant differences in calcium and vitamin D levels. The mean t-score values decreased after surgery at all the locations and in both groups. The reduction in the t-score was significantly greater in the RYGB group at the femoral trochanter and lumbar spine. A decrease in bone mineral density (BMD) was observed after both techniques. The mean BMD decrease was significantly greater in the femoral trochanter and lumbar spine after RYGB.

Rapid Molecular Diagnosis of Genetically Inherited Neuromuscular Disorders Using Next-Generation Sequencing Technologies.

Neuromuscular diseases are genetically highly heterogeneous, and differential diagnosis can be challenging. Over a 3-year period, we prospectively analyzed 268 pediatric and adult patients with a suspected diagnosis of inherited neuromuscular disorder (INMD) using comprehensive gene-panel analysis and next-generation sequencing. The rate of diagnosis increased exponentially with the addition of genes to successive versions of the INMD panel, from 31% for the first iteration (278 genes) to 40% for the last (324 genes). The global mean diagnostic rate was 36% (97/268 patients), with a diagnostic turnaround time of 4-6 weeks. Most diagnoses corresponded to muscular dystrophies/myopathies (68.37%) and peripheral nerve diseases (22.45%). The most common causative genes, TTN, RYR1, and ANO5, accounted for almost 30% of the diagnosed cases. Finally, we evaluated the utility of the differential diagnosis tool Phenomizer, which established a correlation between the phenotype and molecular findings in 21% of the diagnosed patients. In summary, comprehensive gene-panel analysis of all genes implicated in neuromuscular diseases facilitates a rapid diagnosis and provides a high diagnostic yield.

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.

The LINCE Project: A Pathway for Diagnosing NCL2 Disease.

Introduction: Neuronal Ceroid Lipofuscinosis (NCL) comprises a clinically and genetically heterogeneous group of 13 neurodegenerative lysosomal storage disorders. Neuronal Ceroid lipofuscinosis type 2 disease (NCL2), caused by the deficient lysosomal enzyme tripeptidyl peptidase 1 (TPP1), is the only one with an approved enzyme replacement treatment (ERT). Early initiation of ERT appears to modify significantly the natural history of the disease. We aimed to shorten the time to diagnosis of NCL2. Methods: In March 2017, we started per first time in Spain a selective screening program, the LINCE project, in pediatric patients with clinical symptoms compatible with NCL2 disease. The program covered the whole country. We distributed kits to pediatricians with the necessary material to assess patients. All samples in this study were received within one week of collection. Enzymatic activity determined on dried blood spots was the main method used to screen for TPP1 and palmitoyl protein thioesterase 1 (PPT1) for the differential diagnosis with neuronal ceroid lipofuscinosis type 1 (NCL1). Results: Over a period of three years, we received 71 samples. The analysis was minimally invasive, relatively cheap and fast-executing. Three cases identified as a direct result of the selective screening strategy were confirmed by genetic study of NCL2 disease with a median age of 4.5 years. Our screening method has a specificity of 100%, and, with the absence to date of false negatives. We did not detect any NCL1-positive cases. Conclusions: LINCE proved to be a simple, useful, and reliable tool for the diagnosis of NCL2, enabling clinicians to diagnose NCL2 faster. The presence of NCL2-positive cases in our population and availability of treatment may facilitate the inclusion of NCL2 in neonatal screening programs for early diagnosis.

Dynamic profiles and predictive values of some biochemical and haematological quantities in COVID-19 inpatients.

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in some hospitalized patients has shown some important alterations in laboratory tests. The aim of this study was to establish the most relevant quantities associated with the worst prognosis related to COVID-19. MATERIALS AND METHODS: This was a descriptive, longitudinal, observational and retrospective study, in a cohort of 845 adult inpatients from Bellvitge University Hospital (L'Hospitalet de Llobregat, Barcelona, Spain). A multivariate regression analysis was carried out in demographic, clinical and laboratory data, comparing survivors (SURV) and non-survivors (no-SURV). A receiver operating characteristic analysis was also carried out to establish the cut-off point for poor prognostic with better specificity and sensibility. Dynamic changes in clinical laboratory measurements were tracked from day 1 to day 28 after the onset of symptoms. RESULTS: During their hospital stay, 18% of the patients died. Age, kidney disease, creatinine (CREA), lactate-dehydrogenase (LD), C-reactive-protein (CRP) and lymphocyte (LYM) concentration showed the strongest independent associations with the risk of death in the multivariate regression analysis. Established cut-off values for poor prognosis for CREA, LD, CRP and LYM concentrations were 75.0 µmol /L, 320 U/L, 80.9 mg/L and 0.69 x109/L. Dynamic profile of laboratory findings, were in agreement with the consequences of organ damage and tissue destruction. CONCLUSIONS: Age, kidney disease, CREA, LD, CRP and LYM concentrations in COVID-19 patients from the southern region of Catalonia provide important information for their prognosis. Measurement of LD has demonstrated to be very good indicator of poor prognosis at initial evaluation because of its stability over time.

Clinical Efficacy and Safety of Fanhdi®, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients. METHODS: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi®, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis. RESULTS: Seventy-two eligible patients, type 1, 2, 3 VWD (25%/38.9%/36.1%) were treated for spontaneous and traumatic bleeding (140 episodes, n = 41 patients), to prevent surgical bleeding (69 episodes, n = 43 patients); and for secondary long-term prophylaxis (18 programs, n = 13 patients). Replacement therapy with pdVWF/FVIII showed an excellent to good clinical efficacy in 96.7% of the bleeding episodes, 100% during surgical procedures and 100% during prophylaxis. No adverse events (AEs), nor serious AEs related to the product were observed. CONCLUSIONS: Fanhdi® was effective, safe and well tolerated in the management of bleeding episodes, the prevention of bleeding during surgeries, and for secondary long-term prophylaxis in VWD patients.