Association of Thymidylate Synthase Polymorphisms with Acute Pancreatitis and/or Peripheral Neuropathy in HIV-Infected Patients on Stavudine-Based Therapy

Altres ajuts: Fondo de Investigaciones Sanitarias (FIS 02/1280, 05/1591, 07/0976, 08/00256), Fundación para la Prevención del SIDA en España (FIPSE 36610, 36572/06), and Red de Investigación en SIDA (RIS RD06/006/0022)Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy. We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student's t test, Pearson's correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done. Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10-5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33-6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23-7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; OR = 0.34 [95%CI: 0.08 to 1.44], OR = 3.38 [95%CI: 1.33 to 8.57], OR = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm 3 (OR = 0.38; 95%CI: 0.17-0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18-0.85, P = 0.018). Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients

Effects of ezetimibe on cholesterol metabolism in HIV-infected patients with protease inhibitor-associated dyslipidemia: a single-arm intervention trial

BACKGROUND: The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe. METHODS: Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol > 3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured. RESULTS: Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p = .002), LDL-cholesterol (-20.4%, p = .003), non-HDL-cholesterol (-13.4%, p = .002) and apolipoprotein B (-9.1%, p = .021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p = .001; sitosterol-to-cholesterol ratio -41.9%, p = .001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p = .005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged. CONCLUSIONS: The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy

Catatonia and Cognitive Impairments : A Systematic Review

Catatonia is an underdiagnosed and undertreated neuropsychiatric syndrome characterized by catalepsy, negativism, mutism, muscular rigidity, and mannerism, often accompanied by autonomic instability and fever. Although there is growing interest in studying cognitive impairments before and after catatonia, little is known about the cognitive features of the syndrome. This systematic review was registered at PROSPERO (CRD42022299091). Using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach, we searched PubMed, ScienceDirect, and PsycArticles using a combination of the terms "Catatonia" and "Cognitive impairment" and "Executive function" and "Frontal lobe" and "Parietal lobe." Studies included original research articles enrolling patients with catatonic syndrome according to specified criteria. Fourteen studies were deemed relevant for inclusion. The abstraction form included age, assessment during acute episode, associated diagnosis, assessment procedure, and cognitive domains. Outcome measures were extracted. Executive functions and visuospatial abilities proved to be the most investigated domains. A great heterogeneity has been observed in the assessment tools used among the 14 evaluated studies. Findings showed that catatonic patients had worse performance than healthy and non-catatonic psychiatric patients in frontal and parietal cortical functions. Because of the small number of studies in such heterogeneous areas and significant methodological limitations, the results should be regarded with caution. Future research assessing cognitive impairments on catatonic patients is needed. [], identifier [CRD42022299091]

Liver steatosis induces portal hypertension regardless of fibrosis in patients with NAFLD: A proof of concept case report

Esteatosi hepàtica; Hipertensió portalLiver steatosis; Portal hypertensionEsteatosis hepática; Hipertensión portalNo financial support was received for data analysis or writing assistance. JRE is a PhD student at Universitat Autònoma de Barcelona, Spain. JMP reports having received consulting fees from Boehringer Ingelheim, MSD and Novo Nordisk. He has received speaking fees from Gilead, Intercept, and Novo Nordisk, and travel expenses from Gilead, Rubió, Pfizer, Astellas, MSD, CUBICIN, and Novo Nordisk. He has received educational and research support from Madrigal, Gilead, Pfizer, Astellas, Accelerate, Novartis, Abbvie, ViiV, and MSD. Funds from European Commission/EFPIA IMI2 853966-2, IMI2 777377, H2020 847989, and ISCIII PI19/01898 (PI22/01770). JG has received consulting fees from Boehringer Ingelheim, speaking fees from Echosens and travel expenses from Gilead and Abbie. Funds from ISCIII PI18/00947 and PI21/00691. All other authors: nothing to disclose

Association of thymidylate synthase polymorphisms with acute pancreatitis and/or peripheral neuropathy in HIV-infected patients on Stavudine-Based Therapy

BACKGROUND: Low expression thymidylate synthase (TS) polymorphism has been associated with increased stavudine triphosphate intracellular (d4T-TP) levels and the lipodystrophy syndrome. The use of d4T has been associated with acute pancreatitis and peripheral neuropathy. However, no relationship has ever been proved between TS polymorphisms and pancreatitis and/or peripheral neuropathy. METHODS: We performed a case-control study to assess the relationship of TS and methylene-tetrahydrofolate reductase (MTHFR) gene polymorphisms with acute pancreatitis and/or peripheral neuropathy in patients exposed to d4T. Student's t test, Pearson's correlations, one-way ANOVA with Bonferroni correction and stepwise logistic regression analyses were done. RESULTS: Forty-three cases and 129 controls were studied. Eight patients (18.6%) had acute pancreatitis, and 35 (81.4%) had peripheral neuropathy. Prior AIDS was more frequent in cases than in controls (OR = 2.36; 95%CI 1.10-5.07, P = 0.0247). L7ow expression TS and MTHFR genotype associated with increased activity were more frequent in patients with acute pancreatitis and/or peripheral neuropathy than in controls (72.1% vs. 46.5%, OR = 2.97; 95%CI: 1.33-6.90, P = 0.0062, and 79.1% vs. 56.6%, OR = 2.90, 95%CI: 1.23-7.41, P = 0.0142, respectively). Independent positive or negative predictors for the development of d4T-associated pancreatitis and/or peripheral neuropathy were: combined TS and MTHFR genotypes (reference: A+A; P = 0.002; ORA+B = 0.34 [95%CI: 0.08 to 1.44], ORB+A = 3.38 [95%CI: 1.33 to 8.57], ORB+B = 1.13 [95%CI: 0.34 to 3.71]), nadir CD4 cell count >200 cells/mm(3) (OR = 0.38; 95%CI: 0.17-0.86, P = 0.021), and HALS (OR = 0.39 95%CI: 0.18-0.85, P = 0.018). CONCLUSIONS: Low expression TS plus a MTHFR genotype associated with increased activity is associated with the development of peripheral neuropathy in d4T-exposed patients

Correlation between Clinical and Immunological Variables and Humoral Response to SARS-CoV-2 Vaccination in Adult Patients with Antibody Deficiency Disorders

Altres ajuts: Generalitat de Catalunya's Department de salut (SLD015); Consorcio Centro de Investigación Biomédica en Red (CB-2021)Background. Prophylactic vaccination has proven to be the most effective strategy to fight the COVID-19 pandemic. Methods. This was a prospective observational cohort study involving 30 predominantly antibody deficiency disorders (ADD)-afflicted adult patients on immunoglobulin replacement therapy vaccinated with three doses of the mRNA-1273 COVID-19 vaccine, and 10 healthy controls. Anti-RBD IgG antibodies were determined in plasma samples collected just before the first dose of mRNA-based COVID-19 vaccine and on weeks 4, 8, 24, and 28 following the first vaccination. Patients were categorized based on the levels of anti-RBD antibodies determined on w8 as non-, low-, and responders. Chi-square and Kruskal-Wallis tests were used to see if any variables correlated with humoral response levels. Any adverse effects of the mRNA-based vaccine were also noted. Results. The COVID-19 vaccine was safe and well-tolerated. The humoral response elicited at w8 after vaccination depended on the type of ADD, the type of immunoglobulin deficiency, the presence of granulomatous lymphocytic interstitial lung disease, recent use of immunosuppressive drugs, and the switched memory B cells counts. The third vaccine dose boosted humoral response in previous responders to second dose but seldom in non-responders. Conclusions: The humoral response of patients with predominant ADD depends mostly on the type of immunodeficiency and on the frequency of B and T cell populations

Cost-effectiveness analysis of an active search to retrieve HCV patients lost to follow-up (RELINK-C strategy) and the impact of COVID-19

Acord transformatiu CRUE-CSICAltres ajuts: Gilead Science

The Renal Range of the κ/λ sFLC Ratio: Best Strategy to Evaluate Multiple Myeloma in Patients With Chronic Kidney Disease

Background: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD. Methods: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90). Results: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/ min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson. Conclusions: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/ min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies

Bases per a la Gestió del Paisatge de la Serra de Tramuntana : 13 propostes i 55 projectes

Màster Oficial en Estudis Territorials i de la Població. Departament de Geografia, Universitat Autònoma de Barcelona, Programa troncal 2013-2014, Gener 2014Coordinació projecte Troncal: Oriol Nel·lo ColomMòduls docents: Ordenació, Planejament i Gestió del Territori: Oriol Nel·lo Colom, Rufí Cerdán Heredia -- Temes Avançats: Enric Mendizàbal Riera, Albert Pèlachs Mañosa -- Sistemes d'Informació Geogràfica, Planejament i Paisatge: Anna Badia Perpinyà, Albert Pèlachs Mañosa -- Ciutat i Espais Metropolitans: Àngel Cebollada Frontera, Carles Donat MuñozCoordinació continguts: Esteve Dot JutglaConferenciants: Vicent Maria Rosselló Verger, Juli Esteban Noguera, Ricard Pié Ninot, Xavier Campillo Besses, Pere Sala Martí, Joan Nogué FontConferenciants de Mallorca: Miquel Grimalt (Director del Departament de Ciències de la Terra, Universitat de les Illes Balears), Onofre Rullan (Departament de Ciències de la Terra, Universitat de les Illes Balears), Jaume Mateu (Departament de Ciències de la Terra,Universitat de les Illes Balears), Maria Lluïsa Dubon (geògrafa), Bartomeu Deyà (Director gerent del Consorci Serra de Tramuntana Patrimoni Mundial), Miquel Rayó (escriptor), Sebastià Torrens (fotògraf), Joan Sastre (escriptor), Vicenç Sastre (escriptor)Redactors: Grup1: Sara González Pérez, Antón Magarolas Navarro, Ilaria Sanna -- Grup2: Giulia Garolla, Alberto Innocenti, Javier Martín Úceda, Dalila Serusi -- Grup 3: Francesco Finotto, Maria Lidmäe, Sara Serilli, María Torres Bagur -- Grup 4: Giulia Battiston, Sergi Del Olmo Parisi, Elena Vettoretti, Rafael Vicente Salar -- Grup 5: Roberta Fadda, Daniela Pinna, Gloria Veloz, Francesc Vila Palà -- Grup 6: Fernanda Avellaneda Viteri, Giulia Cubadda, Xavier Delclòs Alió, Francesco Luigi FerrariEl Màster d'Estudis Territorials i de la Població és un programa de postgrau del Departament de Geografia de la Universitat Autònoma de Barcelona que té per objectiu la formació de professionals en el camp de la demografia, el planejament i l'ordenació del territori. En el seu itinerari d'Estudis Territorials, el programa ofereix una orientació essencialment aplicada, de tal manera que inclou un exercici troncal en el que els participants elaboren, en equip, amb finalitats didàctiques i sota la direcció dels docents, un document de planejament que compta amb tots els elements d'una proposta professional de planejament. Enguany, el tema escollit per a l'exercici troncal ha estat el reconeixement territorial i la redacció d'una proposta per a la gestió del paisatge de la Serra de Tramuntana de Mallorca. El document que teniu a les mans és el resultat de l'exercici, en el qual 23 alumnes, procedents de 4 països diversos, dividits en 6 equips, i sota la direcció de 10 professors, han redactat efectivament unes Bases per a la Gestió del Paisatge de la Serra de Tramuntana. El document resultant, conté, tal com s'ha indicat, tots els elements propis d'un document d'ordenació del territori: Memòria, Valoració, Diagnosi, Objectius, Propostes i Projectes. D'acord amb les característiques del programa, l'exercici s'ha realitzat a partir d'una voluntat d'integració dels continguts, transversalitat de les propostes, contextualització dels ensenyaments teòrics i un mètode aplicat, en el que han tingut un paper central el treball de camp i el treball en grup. Per això, s'han integrat els quatre mòduls que configuren el primer semestre del Màster en un sol programa i calendari d'ensenyaments i activitats, d'acord amb allò que figura en el Quadern Troncal que podreu trobar al final d'aquest volum