Utility of the Serum Protein Electrophoresis in the Opportunistic Screening for the Deficiency of Alpha-1 Antitrypsin.

BACKGROUND: A deficiency in alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic priority issue. We investigated the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. METHODS: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those patients displaying concentrations below 100 mg/dL. RESULTS: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, with 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 patients (91%). Heterozygous mutations were detected in seven patients; three had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), two had the c.863A>T mutation (p.Glu288Val; Pi*S), one had the c.221_223delTCT mutation (p.Phe76del; Pi*Malton), and the last one had the c.1066G>A (p.Ala356Thr) mutation, which was not previously described. Finally, one patient had the c.863A>T mutation in homozygosis, whereas two double heterozygous patients c.863A>T/c.1096G>A were detected. CONCLUSIONS: An altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency.

Screening for late-onset Pompe disease in Internal Medicine departments in Spain.

BACKGROUND: The screening of high-risk populations using dried blood spots (DBS) has allowed the rapid identification of patients with Pompe disease, mostly in Neurology departments. The aim of the study was to determine the prevalence of late-onset Pompe disease (LOPD) among patients not previously diagnosed or tested for this entity despite presenting possible signs or symptoms of the disease in Internal Medicine departments in Spain. METHODS: This epidemiological, observational, cross-sectional, multicenter study included a single cohort of individuals with clinical suspicion of LOPD seen at Internal Medicine departments in Spain. The diagnosis of LOPD was initially established on the basis of the result of DBS. If decreased enzyme acid-alpha-1,4-glucosidase (GAA) activity was detected in DBS, additional confirmatory diagnostic measurements were conducted, including GAA activity in lymphocytes, fibroblasts, or muscle and/or genetic testing. RESULTS: The diagnosis of LOPD was confirmed in 2 out of 322 patients (0.6%). Reasons for suspecting LOPD diagnosis were polymyositis or any type of myopathy of unknown etiology (in one patient), and asymptomatic or pauci-symptomatic hyperCKemia (in the other). The time between symptom onset and LOPD diagnosis was 2.0 and 0.0 years. Both patients were asymptomatic, with no muscle weakness. Additionally, 19.7% of the non-LOPD cases received an alternative diagnosis. CONCLUSIONS: Our study highlights the existence of a hidden population of LOPD patients in Internal Medicine departments who might benefit from early diagnosis and early initiation of potential treatments.

Current clinical spectrum of common variable immunodeficiency in Spain: The multicentric nationwide GTEM-SEMI-CVID registry.

Common variable immunodeficiency (CVID) constitutes a heterogenic group of primary immunodeficiency disorders with a wide-ranging clinical spectrum. CVID-associated non-infectious morbidity constitutes a major challenge requiring a full understanding of its pathophysiology and its clinical importance and global variability, especially considering the broad clinical, genetic, and regional heterogeneity of CVID disorders. This work aimed to develop a nationwide, multicenter, retrospective study over a 3-year period describing epidemiological, clinical, laboratory, therapeutic, and prognostic features of 250 CVID patients in Spain. The mean diagnostic delay was around 10 years and most patients initially presented with infectious complications followed by non-infectious immune disorders. However, infectious diseases were not the main cause of morbimortality. Non-infectious lung disease was extraordinarily frequent in our registry affecting approximately 60% of the patients. More than one-third of the patients in our cohort showed lymphadenopathies and splenomegaly in their follow-up, and more than 33% presented immune cytopenias, especially Evans' syndrome. Gastrointestinal disease was observed in more than 40% of the patients. Among biopsied organs in our cohort, benign lymphoproliferation was the principal histopathological alteration. Reaching 15.26%, the global prevalence of cancer in our registry was one of the highest reported to date, with non-Hodgkin B lymphoma being the most frequent. These data emphasize the importance of basic and translational research delving into the pathophysiological pathways involved in immune dysregulation and diffuse lymphocytic infiltration. This would reveal new tailored strategies to reduce immune complications, and the associated healthcare burden, and ensure a better quality of life for CVID patients.

Úlcera atípica en paciente con infecciones pulmonares de repetición: estudio de un caso / Atypical ulcer in patient with recurrent pulmonary infections: a case study

Presentamos el caso de un varón de 76 años, con antecedentes de hipertensión arterial (HTA), enfermedad pulmonar obstructiva crónica (EPOC), dislipemia, insuficiencia cardiaca, taquicardia paroxística supraventricular y septoplastia, con úlcera dolorosa en cara posterior de la pierna izquierda de dos semanas de evolución, sin clínica previa de claudicación ni pulsos distales en extremidades inferiores (EEII). Se descartaron úlceras mediante anamnesis, claudicometría, arteriografía y biopsia. Se diagnosticó de déficit mixto de inmunoglobulinas e infección sistémica por Aspergillus. Se estableció tratamiento con itraconazol e inmunoglobulinas y mejoró el estado general y de la úlcera

We present the case of a 76-year-old man, with a history of arterial hypertension (AHT), chronic obstructive pulmonary disease (COPD), dyslipidemia, heart failure, supraventricular paroxysmal tachycardia, septoplasty, with a painful ulcer on the left leg (two weeks of evolution), no previous clinical manifestation of claudication and no distal pulses in lower extremities. Ulcers were ruled out by anamnesis, claudicometry, arteriography and biopsy. Then, a mixed immunoglobulin deficit was diagnosed with a systemic infection by Aspergillus. Treatment with itraconazole andm immunoglobulins was established, improving the general condition and the ulcer

The Importance of a Multidisciplinary Approach in the Management of a Patient with Type I Gaucher Disease.

Managing the multisystemic symptoms of type I Gaucher Disease (GD) requires a multidisciplinary team approach that includes disease-specific treatments, as well as supportive care. This involves a range of medical specialists, general practitioners, supportive care providers, and patients. Phenotype classification and the setting of treatment goals are important for optimizing the management of type I GD, and for providing personalized care. The ability to classify disease severity using validated measurement tools allows the standardization of patient monitoring, and the measurement of disease progression and treatment response. Defining treatment goals is useful to provide a benchmark for assessing treatment response and managing the expectations of patients and their families. Although treatment goals will vary depending on disease severity, they include the stabilization, improvement or reversal (if possible) of clinical manifestations. Enzyme replacement therapy (ERT) is the standard care for patients with type I GD, but a novel substrate reduction therapy (SRT), Eliglustat, has demonstrated safety and efficacy in selected patients. To ensure that treatment goals are being achieved, regular and comprehensive follow up are necessary.

Relationship Between Glucocerebrosidase Activity and Clinical Response to Enzyme Replacement Therapy in Patients With Gaucher Disease Type I.

The quantification of enzyme activity in the patient treated with enzyme replacement therapy (ERT) has been suggested as a tool for dosage individualization, so we conducted a study to evaluate the relationship between glucocerebrosidase activity and clinical response in patients with Gaucher disease type I (GD1) to ERT. The study included patients diagnosed with GD1, who were being treated with ERT, and healthy individuals. Markers based on glucocerebrosidase activity measurement in patients' leucocytes were studied: enzyme activity at 15 min. post-infusion (Act75 ) reflects the amount of enzyme that is distributed in the body post-ERT infusion, and accumulated glucocerebrosidase activity during ERT infusion (Act75-0 ) indicates the total drug exposure during infusion. The clinical response was evaluated based on criteria established by Pastores et al. and Gaucher Severity Score Index. Statistical analysis included ROC analysis and area under the curve test. Act75 and Act75-0 were found to be moderate predictive markers of an optimal clinical response (area under the ROC of Act75 was 0.733 and Act75-0 was 0.817). Act75-0 showed statistical significance in its discriminative capacity (p < 0.05) for obtaining an optimal response to ERT. The cut-off point was 58% (RR = 1.800; 95% CI: 1.003-3.229; p < 0.05). Moreover, Act75 showed a significant and inverse correlation with the Gaucher Severity Score Index, and Act75 and Act75-0 presented a significant correlation with residual enzyme activity at diagnosis. Markers based on glucocerebrosidase activity have a good correlation with clinical response to ERT. Therefore, it could provide supporting clinical data for dose management in GD1 patients.

Amiloidosis cardiaca secundaria a la mutación familiar Glu54Gln del gen de la transtiretina / Cardiac involvement secondary to a familial form of transthyretin amyloidosis resulting from the Glu54Gln mutation

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Lymphomatosis cerebri mimicking iatrogenic Creutzfeldt-Jakob disease.

Lymphomatosis cerebri (LC) is a rare variant of primary central nervous system lymphoma (PCNSL) whereby individual lymphoma cells infiltrate the cerebral white matter without causing a mass effect. The disease characteristically presents as a rapidly progressive dementia, which opens an ample differential diagnosis of toxic, metabolic, neurodegenerative and infective causes. Other presentations also include changes in personality, myoclonus and psychotic symptoms. Here we report a patient who presented with a rapidly progressive dementia with a unique surgical history of a dural mater graft in the 1970s. The diagnosis of iatrogenic Creutzfeldt-Jakob disease (iCJD) was initially considered. However, the patient's clinical status deteriorated rapidly with no response to symptomatic treatment and she died 2 months after symptom onset. A diagnosis of T-type LC was reached at autopsy.

Shock séptico por Rhodococcus equi en paciente con leucemia mielomonocítica crónica / Septic Shock Due to Rhodococcus equi in a Patient With Chronic Myelomonocytic Leukemia

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Cystatin C and NT-proBNP as prognostic biomarkers in Fabry disease.

Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the α-galactosidase A gene. It is characterized by the deposition of the incompletely metabolized substrate globotriaosylceramide in several cell types and multisystem involvement. Major morbidity results from renal, cardiac and cerebrovascular pathology, mediated by endothelial dysfunction. We examined the potential utility of Cystatin C and natriuretic peptides as biomarkers in FD, and evaluated serum levels in 89 FD patients with varying degrees of disease severity. The results revealed that as a prognostic marker, Cystatin C is a good and cost effective indicator of early renal dysfunction and/or heart failure in FD. It is also more useful than serum creatinine in detecting mild renal damage and small decreases in glomerular filtration. In addition, the natriuretic peptide NT-proBNP, was elevated in patients with FD and cardiac involvement, and found to be an adequate detection marker, not only of cardiac involvement, but also of diastolic dysfunction.

Presentación atípica de poliangeítis microscópica / Atypical presentation of microscopic polyangiitis

La poliangeítis microscópica es una vasculitis sistémica que afecta a pequeños vasos, con afectación renal y pulmonar. A continuación se presenta el caso clínico de un paciente con manifestación atípica de esta enfermedad, que debutó con afectación del sistema nervioso central, en forma de déficit motor (AU)

Microscopic polyangiitis is a systemic vasculitis that affects small caliber vessels, with renal and lung compromise. We present the case of a patient with an atypical presentation of this disease and an onset characterized by central nervous system affection in the form of a motor deficit (AU)

[Atypical presentation of microscopic polyangiitis]. / Presentación atípica de poliangeítis microscópica.

Microscopic polyangiitis is a systemic vasculitis that affects small caliber vessels, with renal and lung compromise. We present the case of a patient with an atypical presentation of this disease and an onset characterized by central nervous system affection in the form of a motor deficit.

Desarrollo y proceso de mejora de la vía clínica "neumonía adquirida en la comunidad con ingreso hospitalario" en un hospital de ámbito comarcal / Experience in the development and implementation of a clinical pathway for community-acquired pneumonia in a district hospital

Introducción: La neumonía adquirida en la comunidad es una enfermedad frecuente y la variabilidad clínica en su manejo es notable. El objetivo de este trabajo es exponer el desarrollo y el proceso de mejora de la vía clínica de la neumonía adquirida en la comunidad con ingreso hospitalario en nuestro hospital. Material y método: El diseño de la vía clínica de la neumonía adquirida en la comunidad con ingreso hospitalario fue realizado por un equipo de profesionales médicos y de enfermería implicados en la atención del paciente hospitalizado. Para su elaboración se empleó la mejor evidencia científica disponible, adaptada a las características del centro, y la valoración de los profesionales. Tras un estudio piloto, cuyos resultados se exponen, se procedió a la modificación de la vía clínica propuesta, su implantación y la recogida de indicadores. Resultados: La vía clínica de la neumonía adquirida en la comunidad con ingreso hospitalario se ha elaborado para incluir a todos los pacientes que ingresan con este diagnóstico y no cumplen ningún criterio de exclusión. Se ha estimado una estancia media bruta de 6 días. La vía clínica engloba aspectos médicos y de enfermería y tiene 3 fases: ingreso, mejoría y alta; también incluye indicadores de evaluación y una encuesta de satisfacción Conclusiones: El consenso de los profesionales implicados y la revisión de las mejores evidencias científicas ha permitido el desarrollo de la vía clínica de los pacientes con neumonía adquirida en la comunidad con ingreso hospitalario. Pretendemos que su uso se extienda a la totalidad de los pacientes hospitalizados por este motivo, para así disminuir la variabilidad clínica, reducir la estancia y mejorar la calidad asistencial y la satisfacción del paciente

Introduction: Community-acquired pneumonia is a common illness, and there remains wide clinical variability in its management. The aim of the present article was to present the development and implementation of a clinical pathway for community-acquired pneumonia in our hospital. Material and method: A team of specialists in internal medicine and nurses reached a consensus on a clinical pathway for patients admitted with community-acquired pneumonia. The best scientific evidence available was adapted to the hospital's characteristics and to the health professionals' preferences. After a pilot phase, the clinical pathway was modified, implemented and evaluated. Results: The pathway was designed to include all patients admitted with community-acquired pneumonia without exclusion criteria. A total length of hospital stay of 6 days was estimated. The clinical pathway developed combines both medical and nursing aspects and begins with an admission phase followed by an improvement phase and a discharge phase. The clinical pathway also includes indicators of outcome and a satisfaction survey. Conclusions: Consensus and review of the best scientific evidence allowed the development and implementation of a clinical pathway for community-acquired pneumonia. We aim to extend the use of this pathway to all patients admitted for this cause, thus reducing unjustified clinical variability and length of hospital stay, and improving quality of care and patient satisfaction