RESUMEN
The role of immunosuppression among coronavirus disease 2019 (COVID-19) patients has not been elucidated and management may be challenging. This observational study included confirmed COVID-19 patients. The primary endpoint was the development of moderate-severe acute respiratory distress syndrome (ARDS). Time to moderate-severe ARDS, the need for mechanical or noninvasive ventilation (MV/NIV), death, and a composite of death or MV/NIV were secondary endpoints. Of 138 patients included, 27 (19.6%) were immunosuppressed (IS) and 95 (68.8%) were male, with a median (IQR) age of 68 (54-78) years. A significantly lower proportion of IS patients (25.9%) compared to non-IS patients (52.3%) developed moderate-severe ARDS, in both unadjusted (0.32; 95% CI, 0.13-0.83; p = .017) and adjusted (aOR, 0.25; 95% CI, 0.08-0.80; p = .019) analyses. After stratifying by pathologies, only IS patients with autoimmune diseases remained significant (aOR 0.25; 95% CI, 0.07-0.98; p = .046). Nonsignificant trends toward a longer time to moderate or severe ARDS, a lower need for MV/NIV, and a lower risk of death or MV/NIV were detected among IS. In our cohort of COVID-19 patients, nonsevere immunosuppression was associated with a lower risk of moderate-severe ARDS, especially among AD. This suggests a potential protective effect from a hypothesized hyper-inflammatory response.
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COVID-19/inmunología , Síndrome de Dificultad Respiratoria/inmunología , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/virología , Estudios de Cohortes , Coinfección , Femenino , Hospitalización , Humanos , Terapia de Inmunosupresión , Masculino , Persona de Mediana Edad , Proyectos Piloto , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/virología , Estudios Retrospectivos , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , España/epidemiologíaRESUMEN
KCNJ10 encodes the inward-rectifying potassium channel (Kir4.1) that is expressed in the brain, inner ear, and kidney. Loss-of-function mutations in KCNJ10 gene cause a complex syndrome consisting of epilepsy, ataxia, intellectual disability, sensorineural deafness, and tubulopathy (EAST/SeSAME syndrome). Patients with EAST/SeSAME syndrome display renal salt wasting and electrolyte imbalance that resemble the clinical features of impaired distal tubular salt transport in Gitelman's syndrome. A key distinguishing feature between these two conditions is the additional neurological (extrarenal) manifestations found in EAST/SeSAME syndrome. Recent reports have further expanded the clinical and mutational spectrum of KCNJ10-related disorders including non-syndromic early-onset cerebellar ataxia. Here, we describe a kindred of three affected siblings with early-onset ataxia, deafness, and progressive spasticity without other prominent clinical features. By using targeted next-generation sequencing, we have identified two novel missense variants, c.488G>A (p.G163D) and c.512G>A (p.R171Q), in the KCNJ10 gene that, in compound heterozygosis, cause this distinctive EAST/SeSAME phenotype in our family. Electrophysiological characterization of these two variants confirmed their pathogenicity. When expressed in CHO cells, the R171Q mutation resulted in 50% reduction of currents compared to wild-type KCNJ10 and G163D showed a complete loss of function. Co-expression of G163D and R171Q had a more pronounced effect on currents and membrane potential than R171Q alone but less severe than single expression of G163D. Moreover, the effect of the mutations seemed less pronounced in the presence of Kir5.1 (encoded by KCNJ16), with whom the renal Kir4.1 channels form heteromers. This partial functional rescue by co-expression with Kir5.1 might explain the lack of renal symptoms in the patients. This report illustrates that a spectrum of disorders with distinct clinical symptoms may result from mutations in different parts of KCNJ10, a gene initially associated only with the EAST/SeSAME syndrome.
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Pérdida Auditiva Sensorineural/genética , Discapacidad Intelectual/genética , Mutación Missense , Canales de Potasio de Rectificación Interna/genética , Convulsiones/genética , Anciano , Animales , Células CHO , Cricetulus , Femenino , Pérdida Auditiva Sensorineural/fisiopatología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Discapacidad Intelectual/fisiopatología , Persona de Mediana Edad , Linaje , Fenotipo , Convulsiones/fisiopatologíaRESUMEN
INTRODUCTION: An increased incidence of stroke in HIV-infected patients has already been reported, suggesting that HIV infection may be a cerebrovascular risk factor. The objective of this study was to assess temporal trends in the proportion of HIV infection among patients with stroke in Spain. METHODS: Data were obtained from the minimum basic dataset (MBDS) of all patients hospitalized in Spain between 1997 and 2012 with a primary or secondary diagnosis of stroke. The annual proportion of HIV infection and time trends (stratifying by type of stroke and HIV stage) were calculated, and predictors of HIV infection and the social and economic impact of HIV-infected (HIV+) and non-infected (HIV-) patients were analyzed. RESULTS: Of 857,371 patients hospitalized with an incident stroke, 2134 (0.25%) had HIV infection. A 2.5% year-on-year increase (OR 1.025, 95% CI 1.015-1.036, p<0.0001) of the proportion of HIV-infected patients was observed due to an increase in the asymptomatic stage of the infection (per year OR 1.077, 95% CI 1.057-1.097, p<0.0001), as the proportion of patients with AIDS remained stable. Factors independently associated with HIV infection and stroke were active smoking, stimulating drugs and hepatitis C virus (HCV) infection. A higher mortality rate, longer hospital stay and a higher cost per hospitalized patient was observed among HIV+ patients. CONCLUSIONS: From 1997 to 2012, there was an increase in the proportion of HIV infection among patients hospitalized with stroke irrespective of the classical vascular risk factors, reinforcing the role of HIV infection as a cerebrovascular risk factor.
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Infecciones por VIH , Accidente Cerebrovascular , Infecciones por VIH/epidemiología , Humanos , Estudios Retrospectivos , España/epidemiología , Accidente Cerebrovascular/epidemiologíaRESUMEN
INTRODUCTION: Substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is frequent in Parkinson's disease (PD), while lenticular nucleus hyperechogenicity (LN+) and 3rd ventricle enlargement (3V+) are typical of Atypical Parkinsonisms (AP). However, there are no studies assessing the diagnostic yield of all TCS biomarkers in the three AP (progressive supranuclear palsy, PSP, multiple system atrophy, MSA, corticobasal degeneration, CBD). Previous references lack homogeneous criteria and data are incomprehensive. METHODS: Analysis of TCS performed in routine clinical practice in AP and PD patients from two tertiary hospitals. Expert recommendations were strictly followed. Previous literature was critically analysed. RESULTS: 155 AP (98 PSP, 40 MSA, 14 CBD), 254 PD, 145 control subjects were included. We confirmed good sensitivity for SN+ in PD (80%), but specificity was lower than reported (61%). LN+ and 3V + had moderate sensitivity for AP and PSP diagnosis respectively (65%, 63%), but specificity was higher than reported (87%, 91%). We confirmed high specificity and positive predictive value of the combination SN/LN (98%, 93% AP; 83%, 86% PD). The combinations of two or three echofeatures, previously unreported, showed high specificity but lower sensitivity (SN/3V: 75% sensitivity, 87% specificity PD; 42% sensitivity, 98% specificity PSP) (SN + LN+: 79% sensitivity, 86% specificity CBD) (SN/3V/LN: 67% sensitivity, 89% specificity PD; 29% sensitivity, 99% specificity PSP; 41% sensitivity, 95% specificity MSA; 57% sensitivity 91% specificity CBD). CONCLUSIONS: We present a large comprehensive study of TCS, confirming its usefulness and certain limitations in AP diagnosis. Adherence to consensus criteria is critical to implement TCS for clinical and research purposes.
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Cuerpo Estriado/diagnóstico por imagen , Trastornos Parkinsonianos/diagnóstico por imagen , Sustancia Negra/diagnóstico por imagen , Tercer Ventrículo/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/normas , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: HHV7 reactivation has been occasionally reported as a cause of encephalitis or myelitis in transplant recipients, but to our knowledge it has never been associated with neurological disease in HIV-infected patients. We report a case of acute myelitis in an HIV-infected patient, with sustained HHV-7 DNA amplification in cerebrospinal fluid (CSF) and a favourable response to foscarnet. CASE REPORT: A 40 year-old man with HIV infection was admitted with asymmetric hypoesthesia in legs and paraparesis. He was receiving treatment with efavirenz, emtricitabine and tenofovir, his CD4 count was 580/mm3 and HIV viral load was undetectable. Magnetic resonance imaging showed a focal central hyperintensity on T2 and STIR sequences, on the torathic spinal cord, with slight enhancement after intravenous gadolinium. All microbiological studies were negative except for HHV-7 DNA amplification in CSF. With a diagnosis of idiopathic transverse myelitis, treatment with high-dose intravenous methylprednisolone was initiated. However, paraparesis continued worsening, and a second CSF obtained 12 days after the first one resulted again in HHV-7 amplification. RESULTS: The patient was treated with a 2 week course of foscarnet, and a rapid neurological improvement was noted. After treatment, PCR for HHV-7 in CSF was negative. Neurological exam was normal one month after treatment initiation. CONCLUSION: HHV-7 reactivation may cause neurological disease in patients with HIV infection. Foscarnet is an effective treatment in HHV-7 associated myelitis.