Diagnóstico diferencial de la debilidad muscular

Algoritmo con el diagnóstico diferencial de la debilidad muscularDepartamento de Medicina, Dermatología y Toxicologí

Enfermedad ósea de Paget: 1877-2023. Etiología y abordaje de una enfermedad en transición epidemiológica

Producción CientíficaLa enfermedad ósea de Paget se caracteriza por la alteración, en una o varias localizaciones óseas, del equilibrio entre formación y resorción ósea. Este desequilibrio da lugar a un hueso ensanchado, desorganizado, en muchos casos con una densidad ósea aumentada, aunque más frágil. Existiría una predisposición genética para su desarrollo, que explicaría entre un 5 y un 40% de los casos, sobre la que actuarían distintos factores ambientales. La enfermedad ósea de Paget fue considerada clásicamente la segunda enfermedad metabólica ósea más frecuente. Sin embargo, durante las últimas décadas presenta un marcado descenso tanto de la incidencia como de la gravedad clínica, lo que ha llevado a especular sobre la disminución o desaparición de la influencia de algún factor ambiental. Este descenso en la incidencia no debe servir como excusa para el abandono de su estudio, sino ser la razón para tratar de entender mejor su patogenia

PPAR gamma pro12Ala polymorphism and type 2 diabetes: a study in a spanish cohort

Type 2 diabetes (T2D) is a disease whose occurrence is increasing prevalent in westernized civilizations and is responsible for the proliferation in the morbidity and total mortality of patients with cardiovascular diseases, worldwide. However, the complexity in the treatment and prevention of T2D arises from the intricacy of the many physical and biological factors involved in its etiology. Impaired pathways for insulin signaling have been implicated as one the many factors in the development of T2D Individual peroxisome proliferator-activated receptors (PPARs) have previously exhibited associations with alterations of lipid profiles, fat tissue and T2D and displayed complications derived from high levels of glucose. However, PPARgamma has not yet been associated with the development or developmental pathways of T2D. We performed an observational study a Spanish cohort in order to better understand the association between the SNP PPARgamma polymorphism Pro12Ala in our patients and the incidence of T2D and other cardiovascular complications. We study did not find a statistically significant relationship between the Pro12Ala and T2D development in our cohort, future observations will help us to know the association with vascular disease in patients with T2D

Paradoxical Deterioration During Anti-Tuberculous Therapy in Non-HIV-Infected Patients with Pleural Tuberculosis: A Pragmatic Approach

We report a case of paradoxical deterioration. A male patient diagnosed with pleural tuberculosis, but who was not infected with human immunodeficiency virus (HIV), experienced clinical deterioration 3 weeks after the initiation of anti-tuberculous treatment. After other diagnoses were ruled out, a paradoxical response to treatment was established and the patient was started on systemic corticosteroids. Paradoxical response to treatment should be considered in patients with clinical deterioration after they start on anti-tuberculous treatment

Diagnosis and management of Paget’s disease of bone in adults: A clinical guideline

An evidence-based clinical guideline for the diagnosis and management of Paget's disease of bone (PDB) was developed using GRADE methodology, by a Guideline Development Group (GDG) led by the Paget's Association (UK). A systematic review of diagnostic tests and pharmacological and nonpharmacological treatment options was conducted that sought to address several key questions of clinical relevance. Twelve recommendations and five conditional recommendations were made, but there was insufficient evidence to address eight of the questions posed. The following recommendations were identified as the most important: 1) Radionuclide bone scans, in addition to targeted radiographs, are recommended as a means of fully and accurately defining the extent of metabolically active disease in patients with PDB. 2) Serum total alkaline phosphatase (ALP) is recommended as a first-line biochemical screening test in combination with liver function tests in screening for the presence of metabolically active PDB. 3) Bisphosphonates are recommended for the treatment of bone pain associated with PDB. Zoledronic acid is recommended as the bisphosphonate most likely to give a favorable pain response. 4) Treatment aimed at improving symptoms is recommended over a treat-to-target strategy aimed at normalizing total ALP in PDB. 5) Total hip or knee replacements are recommended for patients with PDB who develop osteoarthritis in whom medical treatment is inadequate. There is insufficient information to recommend one type of surgical approach over another. The guideline was endorsed by the European Calcified Tissues Society, the International Osteoporosis Foundation, the American Society of Bone and Mineral Research, the Bone Research Society (UK), and the British Geriatric Society. The GDG noted that there had been a lack of research on patient-focused clinical outcomes in PDB and identified several areas where further research was needed

Características epidemiológicas de las nuevas infecciones causadas por el VIH comparadas con los casos de sida. La epidemia de VIH/sida en el País Vasco

ResumenObjetivoDescribir las características epidemiológicas de los nuevos diagnósticos de infección por el VIH en el período 1997- 2001 y comparlas con los casos de sida (1991-2001).MétodosSe han recogido retrospectivamente los datos de las nuevas infecciones por el VIH ocurridas en el País Vasco (1997-2001) y se han comparado con los casos de sida (1991- 2001).ResultadosSe han diagnosticado 912 nuevas infecciones por el VIH. El diagnóstico de VIH coincidió con el de sida en 299 (32,8%) de las nuevas infecciones. Las relaciones heterosexuales han sido el mecanismo de transmisión más frecuente, seguido de la transmisión por vía parenteral y las relaciones homosexuales y bisexuales, con diferencias significativas (p < 0,001) respecto a los casos de sida.ConclusionesLa transmisión sexual ha reemplazado al consumo de drogas por vía parenteral como mecanismo más frecuente de transmisión del VIH. Hay un alto porcentaje de pacientes con diagnóstico simultáneo de VIH y sida. Estos datos indican la necesidad de realizar nuevas estrategias de prevención.SummaryObjectiveTo describe the epidemiological characteristics of new cases of HIV infection diagnosed from 1997-2001 and compare them with AIDS cases (1991-2001).MethodsData were retrospectively collected on new cases of HIV infection detected in the Basque Country (1997-2001) and were compared with AIDS cases (1991-2001).ResultsA total of 912 new cases of HIV infection were diagnosed. In 299 of the new cases (32.8%), HIV and AIDS were diagnosed simultaneously. The most common mechanism of transmission was heterosexual transmission, followed by intravenous and homo/bisexual transmission. Significant epidemiological differences (p < 0.001) were found with regard to AIDS cases.ConclusionsSexual transmission has replaced intravenous drug use as the most common mechanism of HIV transmission. A large percentage of patients were simultaneously diagnosed with HIV and AIDS, indicating the need for new prevention strategies

Epigenetic analysis of Paget's disease of bone identifies differentially methylated loci that predict disease status

Paget’s disease of bone (PDB) is characterized by focal increases in disorganized bone remodeling. This study aims to characterize PDB-associated changes in DNA methylation profiles in patients’ blood. Meta-analysis of data from the discovery and cross-validation set, each comprising 116 PDB cases and 130 controls, revealed significant differences in DNA methylation at 14 CpG sites, 4 CpG islands, and 6 gene-body regions. These loci, including two characterized as functional through expression quantitative trait-methylation analysis, were associated with functions related to osteoclast differentiation, mechanical loading, immune function, and viral infection. A multivariate classifier based on discovery samples was found to discriminate PDB cases and controls from the cross-validation with a sensitivity of 0.84, specificity of 0.81, and an area under curve of 92.8%. In conclusion, this study has shown for the first time that epigenetic factors contribute to the pathogenesis of PDB and may offer diagnostic markers for prediction of the disease

Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID ‐19 pneumonia: An open‐label randomised trial

Producción CientíficaBackground: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. Methods: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. Results: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, −8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, −18.9% [95% CI, −31.8 to - 5.6%]; p = 0.007). Conclusions: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation

Targeted Inactivation of Rin3 Increases Trabecular Bone Mass by Reducing Bone Resorption and Favouring Bone Formation

AbstractCommon genetic variants at the RIN3 locus on chromosome 14q32 predispose to Paget’s disease of bone (PDB) but the mechanisms by which they do so are unknown. Here, we analysed the skeletal phenotype of female mice with targeted inactivation of the mouse Rin3 gene (Rin3−/−) as compared with wild-type littermates. The Rin3−/− mice had higher trabecular bone volume (BV/TV%) compared with wild type. Mean ± standard deviation values at the distal femur at 8 weeks were 9.0 ± 2.5 vs. 7.0 ± 1.5 (p = 0.002) and at 52 weeks were 15.8 ± 9.5 vs. 8.5 ± 4.2 (p = 0.002). No differences were observed in femoral cortical bone parameters with the exception of marrow diameter which was significantly smaller in 52-week-old Rin3−/− mice compared to wild type: (0.43 mm ± 0.1 vs. 0.57 mm ± 0.2 (p = 0.001). Bone histomorphometry showed a lower osteoclast surface / bone surface (Oc.S/BS%) at 8 weeks in Rin3−/− mice compared to wild type (24.1 ± 4.7 vs. 29.7 ± 6.6; p = 0.025) but there were no significant differences in markers of bone formation at this time. At 52 weeks, Oc.S/BS did not differ between genotypes but single labelled perimeter (SL.Pm/B.Pm (%)) was significantly higher in Rin3−/− mice (24.4 ± 6.4 vs. 16.5 ± 3.8, p = 0.003). We conclude that Rin3 negatively regulates trabecular bone mass in mice by inhibiting osteoclastic bone resorption and favouring bone formation. Our observations also suggest that the variants that predispose to PDB in humans probably do so by causing a gain-in-function of RIN3.</jats:p

Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19

Objective To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Methods Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Results Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p.298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. Conclusion There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses