Recurrent bacteremia and endocarditis due to Staphylococcus capitis in a patient with Bowen's disease: a case report.

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.

Expanding the genetic and phenotypic spectrum of congenital myasthenic syndrome: new homozygous VAMP1 splicing variants in 2 novel individuals.

We report the cases of two Spanish pediatric patients with hypotonia, muscle weakness and feeding difficulties at birth. Whole-exome sequencing (WES) uncovered two new homozygous VAMP1 (Vesicle Associated Membrane Protein 1) splicing variants, NM_014231.5:c.129+5 G > A in the boy patient (P1) and c.341-24_341-16delinsAGAAAA in the girl patient (P2). This gene encodes the vesicle-associated membrane protein 1 (VAMP1) that is a component of a protein complex involved in the fusion of synaptic vesicles with the presynaptic membrane. VAMP1 has a highly variable C-terminus generated by alternative splicing that gives rise to three main isoforms (A, B and D), being VAMP1A the only isoform expressed in the nervous system. In order to assess the pathogenicity of these variants, expression experiments of RNA for VAMP1 were carried out. The c.129+5 G > A and c.341-24_341-16delinsAGAAAA variants induced aberrant splicing events resulting in the deletion of exon 2 (r.5_131del; p.Ser2TrpfsTer7) in the three isoforms in the first case, and the retention of the last 14 nucleotides of the 3' of intron 4 (r.340_341ins341-14_341-1; p.Ile114AsnfsTer77) in the VAMP1A isoform in the second case. Pathogenic VAMP1 variants have been associated with autosomal dominant spastic ataxia 1 (SPAX1) and with autosomal recessive presynaptic congenital myasthenic syndrome (CMS). Our patients share the clinical manifestations of CMS patients with two important differences: they do not show the typical electrophysiological pattern that suggests pathology of pre-synaptic neuromuscular junction, and their muscular biopsies present hypertrophic fibers type 1. In conclusion, our data expand both genetic and phenotypic spectrum associated with VAMP1 variants.

Incorporación del dietista-nutricionista en un hospital universitario: declaración de postura de la Comisión de Nutrición del Hospital Universitario La Paz / Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz

El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares deatención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estadonutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid.El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que,actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva,habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes,los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedadrenal crónica, entre otras.(AU)

The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized carethat provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid.The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians usenutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hyper-tension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.(AU)

Identifying Factors That Influence Physical Activity and Healthy Aging Among Older Latino Adults.

BACKGROUND: For older Latinos, some benefits of leisure-time physical activity (LTPA) include enhanced cognitive functioning, decreased loneliness, and reduced premature mortality. Despite LTPA benefits, adults ≥50 years are one of the most inactive age groups in the United States. METHODS: This qualitative study aimed to add to the limited evidence of LTPA in older Latino adults by exploring the barriers and facilitators for fitness class uptake and park use. Guided by a Social-Ecological Model of Health and Social Determinants of Health theoretical and a phenomenological research design, qualitative research data were collected via 27 personal interviews with Latino adults using a semistructured interview guide. Participants were recruited using purposive sampling strategies in collaboration with community partners. Bicultural data collectors conducted the semistructured interviews over Zoom. Thematic analysis was performed using Dedoose, following an inductive and deductive approach. RESULTS: The main barriers to fitness class attendance and park use were family and/or work commitments, perceived safety, and perceived discrimination. Conversely, the critical facilitators for participation were socialization into a group, social connectedness with group members, fitness instructor characteristics, and exercise history. CONCLUSIONS: Findings from this study hold important implications for the design of fitness programming and park-based recreation, including the need to increase the cultural diversity of recreation staff and culturally relevant programming. Future research is needed on time poverty related to family/work commitments and whether discriminatory practices at fitness centers, like ageism and race/ethnicity, influence physical activity behavior.

Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz.

Introduction: The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized care that provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid. The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians use nutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hypertension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.

Introducción: El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares de atención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estado nutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid. El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que, actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva, habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes, los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedad renal crónica, entre otras.

Surgical vs. transcatheter aortic valve replacement in patients over 75 years with aortic stenosis: sociodemographic profile, clinical characteristics, quality of life and functionality.

Background: Aortic valve stenosis (AVS) affects 25% of the population over 65 years. At present, there is no curative medical treatment for AVS and therefore the surgical approach, consisting of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR), is the treatment of choice. Methodology: The aim of this study was to analyze the sociodemographic and clinical characteristics, quality of life and functionality of a sample of patients with AVS over 75 years of age, who underwent TAVR or SAVR, applying standard clinical practice. A prospective multicenter observational study was conducted in two hospitals of the Spanish National Health System. Data were collected at baseline, 1, 6 months and 1 year. Results: In total, 227 participants were included, with a mean age of 80.6 [SD 4.1]. Statistically significant differences were found in terms of quality of life, which was higher at 1 year in patients who underwent SAVR. In terms of functionality, SAVR patients obtained a better score (p < 0.01). However, patients who underwent TAVR began with a worse baseline situation and managed to increase their quality of life and functionality after 1 year of follow-up. Conclusion: The individualized choice of TAVR or SAVR in patients with AVS improves patients' quality of life and function. Moreover, the TAVR procedure in patients with a worse baseline situation and a high surgical risk achieved a similar increase in quality of life and functionality compared to patients undergoing SAVR with a better baseline situation.

Influence of baseline characteristics and stratification level of patients living with HIV on pharmaceutical interventions developed according to the Capacity-Motivation-Opportunity methodology.

OBJECTIVE: In recent years the therapeutic approach to patients with HIV has gone from being multidisciplinary to multidimensional, being vital to know the different aspects that define patients in order to outline the best care interventions for each patient. The aim of this study was to determine the influence of the individual characteristics (demographic and clinical, pharmacotherapeutic and HIV infection control data) of patients with HIV being followed up using the Capacity-Motivation-Opportunity methodology on the pharmaceutical interventions performed. METHODS: A single-centre prospective observational study was conducted between February 2019 and January 2020. Patients with HIV aged ≥18 years on antiretroviral treatment and who were receiving pharmaceutical care based on the Capacity-Motivation-Opportunity methodology were included. Demographic, clinical and pharmaceutical variables and HIV infection control data were registered at baseline. To identify the independent variables associated with pharmaceutical interventions, a univariate logistic regression was performed. RESULTS: Sixty-five patients were included in the study. A total of 129 pharmaceutical care consultations were performed and 909 pharmaceutical interventions were carried out: 503/909 (55.3%) capacity interventions, 381/909 (41.9%) motivation interventions, 25/909 (2.8%) opportunity interventions. The educational level had a significant influence on the opportunity (p=0.025) and transversal training interventions performed (p=0.001). A relationship was found between the antiretroviral therapy received and the development of safety interventions (p=0.037). The presence of polypharmacy significantly influenced concomitant review and validation (p=0.030) and motivation interventions (p=0.041). Adherence of ≥95% had a significant influence on the motivation interventions carried out (p=0.038). Stratification significantly influenced adherence interventions (p=0.033). The sex and age of the patients, as well as their toxic habits, presence of comorbidities, CD4+ cell count and HIV viral load, did not significantly influence the pharmaceutical interventions performed (p>0.05). CONCLUSIONS: Our study has elucidated the pharmaceutical interventions carried out in a pharmaceutical care consultation for patients with HIV based on the Capacity-Motivation-Opportunity model and ascertained the individual characteristics (demographic and clinical, pharmacotherapeutic and HIV infection control data) that may have conditioned them.

A novel de novo variant in CASK causes a severe neurodevelopmental disorder that masks the phenotype of a novel de novo variant in EEF2.

We report a 9-year-old Spanish boy with severe psychomotor developmental delay, short stature, microcephaly and abnormalities of the brain morphology, including cerebellar atrophy. Whole-exome sequencing (WES) uncovered two novel de novo variants, a hemizygous variant in CASK (Calcium/Calmodulin Dependent Serine Protein Kinase) and a heterozygous variant in EEF2 (Eukaryotic Translation Elongation Factor 2). CASK gene encodes the peripheral plasma membrane protein CASK that is a scaffold protein located at the synapses in the brain. The c.2506-6 A > G CASK variant induced two alternative splicing events that account for the 80% of the total transcripts, which are likely to be degraded by NMD. Pathogenic variants in CASK have been associated with severe neurological disorders such as mental retardation with or without nystagmus also called FG syndrome 4 (FGS4), and intellectual developmental disorder with microcephaly and pontine and cerebellar hypoplasia (MICPCH). Heterozygous variants in EEF2, which encodes the elongation factor 2 (eEF2), have been associated to Spinocerebellar ataxia 26 (SCA26) and more recently to a childhood-onset neurodevelopmental disorder with benign external hydrocephalus. The yeast model system used to investigate the functional consequences of the c.34 A > G EEF2 variant supported its pathogenicity by demonstrating it affects translational fidelity. In conclusion, the phenotype associated with the CASK variant is more severe and masks the milder phenotype of EEF2 variant.

First splicing variant in HECW2 with an autosomal recessive pattern of inheritance and associated with NDHSAL.

We report the clinical and genetic features of a Caucasian girl who presented a severe neurodevelopmental disorder with drug-resistant epilepsy, hypotonia, severe gastro-esophageal reflux and brain magnetic resonance imaging anomalies. WES uncovered a novel variant in homozygosis (g.197092814_197092824delinsC) in HECW2 gene that encodes the E3 ubiquitin-protein ligase HECW2. This protein induces ubiquitination and is implicated in the regulation of several important pathways involved in neurodevelopment and neurogenesis. Furthermore, de novo heterozygous missense variants in this gene have been associated with neurodevelopmental disorder with hypotonia, seizures, and absent language (NDHSAL). The homozygous variant of our patient disrupts the splice donor site of intron 22 and causes the elimination of exon 22 (r.3766_3917+1del) leading to an in-frame deletion of the protein (p.Leu1256_Trp1306del). Functional studies showed a twofold increase of its RNA expression, while the protein expression level was reduced by 60%, suggesting a partial loss-of-function mechanism of pathogenesis. Thus, this is the first patient with NDHSAL caused by an autosomal recessive splicing variant in HECW2.

MLIP causes recessive myopathy with rhabdomyolysis, myalgia and baseline elevated serum creatine kinase.

Striated muscle needs to maintain cellular homeostasis in adaptation to increases in physiological and metabolic demands. Failure to do so can result in rhabdomyolysis. The identification of novel genetic conditions associated with rhabdomyolysis helps to shed light on hitherto unrecognized homeostatic mechanisms. Here we report seven individuals in six families from different ethnic backgrounds with biallelic variants in MLIP, which encodes the muscular lamin A/C-interacting protein, MLIP. Patients presented with a consistent phenotype characterized by mild muscle weakness, exercise-induced muscle pain, variable susceptibility to episodes of rhabdomyolysis, and persistent basal elevated serum creatine kinase levels. The biallelic truncating variants were predicted to result in disruption of the nuclear localizing signal of MLIP. Additionally, reduced overall RNA expression levels of the predominant MLIP isoform were observed in patients' skeletal muscle. Collectively, our data increase the understanding of the genetic landscape of rhabdomyolysis to now include MLIP as a novel disease gene in humans and solidifies MLIP's role in normal and diseased skeletal muscle homeostasis.

New subtype of PCH1C caused by novel EXOSC8 variants in a 16-year-old Spanish patient.

We report the case of a 16-year-old Spanish boy with cerebellar and spinal muscular atrophy, spasticity, psychomotor retardation, nystagmus, ophthalmoparesis, epilepsy, and mitochondrial respiratory chain (MRC) deficiency. Whole exome sequencing (WES) uncovered three variants (two of them novel) in a compound heterozygous in EXOSC8 gene (NM_181503.3:c.[390+1delG];[628C>T;815G>C]) that encodes the exosome complex component RRP43 protein (EXOSC8). In order to assess the pathogenicity of these variants, expression experiments of RNA and protein for EXOSC8 were carried out. The c.[390+1delG] variant produces the elimination of exon 7 (r.[345_390del]; p.[Ser116LysfsTer27]) and a decrease of the RNA expression in relation to the other allele (p.[Pro210Ser;Ser272Thr]). Furthermore, total mRNA expression is reduced by 30% and the protein level by 65%. EXOSC8 is an essential protein of the exosome core, a ubiquitously expressed complex responsible for RNA processing and degradation. Recessive mutations in EXOSC8 cause pontocerebellar hypoplasia type 1C (PCH1C), and currently, only two homozygous variants in this gene have been described. However, unlike PCH1C-affected individuals with EXOSC8 variants, our patient presents a normal supratentorial cerebral tissue (neither corpus callosum hypoplasia nor hypomyelination) with a less severe phenotype and longer survival. In conclusion, our data expand both genetic and phenotypic spectrum associated with EXOSC8 variants.

Characterization of a complex phenotype (fever-dependent recurrent acute liver failure and osteogenesis imperfecta) due to NBAS and P4HB variants.

We report the clinical, biochemical and genetic findings from a Spanish boy of Caucasian origin who presented with fever-dependent RALF (recurrent acute liver failure) and osteogenesis imperfecta (OI). Whole-exome sequencing (WES) uncovered two compound heterozygous variants in NBAS (c.[1265 T > C];[1549C > T]:p.[(Leu422Pro)];[(Arg517Cys)]), and a heterozygous variant in P4HB (c.[194A > G];[194=]:p.[(Lys65Arg)];[(Lys65=)]) that was transmitted from the clinically unaffected mother who was mosaic carrier of the variant. Variants in NBAS protein have been associated with ILFS2 (infantile liver failure syndrome-2), SOPH syndrome (short stature, optic nerve atrophy, and Pelger-Huët anomaly syndrome), and multisystem diseases. Several patients showed clinical manifestations affecting the skeletal system, such as osteoporosis, pathologic fractures and OI. Experiments in the patient's fibroblasts demonstrated that mutated NBAS protein is overexpressed and thermally unstable, and reduces the expression of MGP, a regulator of bone homeostasis. Variant in PDI (protein encoded by P4HB) has been associated with CLCRP1 (Cole-Carpenter syndrome-1), a type of severe OI. An increase of COL1A2 protein retention was observed in the patient's fibroblasts. In order to study if the variant in P4HB was involved in the alteration in collagen trafficking, overexpression experiments of PDI were carried out. These experiments showed that overexpression of mutated PDI protein produces an increase in COL1A2 retention. In conclusion, these results corroborate that the variants in NBAS are responsible for the liver phenotype, and demonstrate that the variant in P4HB is involved in the bone phenotype, probably in synergy with NBAS variants.

Deterioro cognitivo subagudo como comienzo de una angeítis primaria del sistema nervioso central / Subacute cognitive impairment as clinical presentation of primary angiitis of the central nervous system

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Caracterización de los inmunofenotipos linfocitarios de sangre periférica en pacientes con cáncer / Characterization of peripheral blood lymphocytes immunophenotype in cancer patients

Introducción: La determinación de los inmunofenotipos linfocitarios en sangre periférica forma parte de la evaluación del estado general del sistema inmunitario. Estos exámenes ofrecen informaciones sobre la distribución, concentración y funcionabilidad de las células inmunitarias, lo cual contribuye a establecer pronósticos en el cáncer y predicciones a las respuestas terapéuticas. Objetivo: Evaluar la distribución de las concentraciones linfocitarias circulantes en sangre periférica de pacientes con cáncer. Métodos: Se realizó un estudio analítico en 154 pacientes con cáncer, atendidos en el Instituto de Oncología y Radiobiología de La Habana, durante los años 2017 a 2019. Se empleó la citometría de flujo multiparamétrica para identificar los inmunofenotipos linfocitarios. Este procedimiento se realizó antes de comenzar cualquier tratamiento inmunoterapéutico. Resultados: Los pacientes con cáncer mostraron mayor heterogeneidad en la distribución de las poblaciones linfocitarias respecto a los controles. En los pacientes la mediana de los linfocitos totales y de las subpoblaciones linfocitarias CD3+, CD4+, CD8+ y CD19+ fueron significativamente menores. Los linfocitos T dobles positivos (CD4/CD8) se encontraron elevados significativamente. No se hallaron diferencias entre sexos. La edad se asoció negativamente con las concentraciones de las poblaciones T en tumores sólidos, y con T y B en los linfomas. En el cáncer de próstata se obtuvieron los valores más bajos de poblaciones linfocitarias. Conclusiones: Los pacientes con cáncer tienen menor concentración de linfocitos en sangre periférica que los controles sanos. Las células más afectadas fueron las subpoblaciones T y los linfocitos B. La edad se asoció negativamente con las concentraciones sanguíneas de linfocitos, lo cual pudiera estar en relación con la inmunosenescencia(AU)

Introduction: Determination of lymphocytic immunophenotypes in peripheral blood is part of the evaluation of the general state of the immune system. These tests provide information about the distribution, concentration, and functionality of immune cells, which helps establish prognoses in cancer and predictions of therapeutic responses. Objective: To evaluate the distribution of circulating lymphocyte concentrations in peripheral blood of cancer patients. Methods: An analytical study was carried out with 154 cancer patients treated at the Institute of Oncology and Radiobiology in Havana, from 2017 to 2019. Multiparametric flow cytometry was used to identify lymphocyte immunophenotypes. This procedure was performed before beginning any immunotherapeutic treatment. Results: Cancer patients showed greater heterogeneity in the distribution of lymphocyte populations compared to control patients. The median for total lymphocytes and the lymphocyte subpopulations of CD3+, CD4+, CD8+ and CD19+ were significantly lower in patients. CD4+ CD8+ double-positive T lymphocytes were found to be significantly elevated. No sex differences were found. Age was negatively associated with the concentrations of T-cells populations in solid tumors, and with T- and B-cells populations in lymphomas. In prostate cancer, the lowest values ​​of lymphocyte populations were obtained. Conclusions: Cancer patients have a lower concentration of lymphocytes in peripheral blood than healthy patients in the control group. The most affected ones were the T-cells subpopulations and B lymphocytes. Age was negatively associated with blood levels of lymphocytes, which could be related to immunosenescence(AU)

MAST1 variant causes mega-corpus-callosum syndrome with cortical malformations but without cerebellar hypoplasia.

We report the case of a Caucasian Spanish origin female who showed severe psychomotor developmental delay, hypotonia, strabismus, epilepsy, short stature, and poor verbal language development. Brain magnetic resonance imaging scans showed thickened corpus callosum, cortical malformations, and dilated and abnormal configuration of the lateral ventricles without hydrocephalus. Whole-exome sequence uncovered a de novo variant in the microtubule associated serine/threonine kinase 1 gene (MAST1; NM_014975.3:c.1565G>A:p.(Gly522Glu)) that encodes for the MAST1. Only 12 patients have been identified worldwide with 10 different variants in this gene: six patients with mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations; two patients with microcephaly and cerebellar hypoplasia; two patients with autism, one patient with diplegia, and one patient with microcephaly and dysmorphism. Our patient shows a new phenotypic subtype defined by mega-corpus-callosum syndrome with cortical malformations without cerebellar hypoplasia. In conclusion, our data expand the phenotypic spectrum associated to MAST1 gene variants.