HLA-E and NKG2A Mediate Resistance to M. bovis BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is the primary treatment for non-muscle-invasive bladder cancer (NMIBC), known to stimulate inflammatory cytokines, notably interferon (IFN)-γ. We observed that prolonged IFN-γ exposure fosters adaptive resistance in recurrent tumors, aiding immune evasion and tumor proliferation. We identify HLA-E and NKG2A, part of a novel NK and T cell checkpoint pathway, as key mediators of resistance in BCG-unresponsive NMIBC. IFN-γ enhances HLA-E and PD-L1 expression in recurrent tumors, with an enrichment of intra-tumoral NKG2A-expressing NK and CD8 T cells. CXCL9 + macrophages and dendritic cells and CXCL12-expressing stromal cells likely recruit CXCR3/CXCR4-expressing NK and T cells and CXCR7 + HLA-E HIGH tumor cells. NK and CD8 T cells remain functional within BCG-unresponsive tumors but are inhibited by HLA-E and PD-L1, providing a framework for combined NKG2A and PD-L1 blockade strategy for bladder-sparing treatment of BCG-unresponsive NMIBC.

Nut Consumption and Depression: Cross-Sectional and Longitudinal Analyses in Two Cohorts of Older Adults.

OBJECTIVES: To assess the cross-sectional and longitudinal associations between nut consumption and depression in two cohorts of older adults. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: The first cohort (Seniors-ENRICA-I or SE-I) included a representative sample of Spanish noninstitutionalized adults aged ≥65 years interviewed in 2010 and 2013. The second cohort (SE-II) included individuals from the Madrid region, Spain, aged ≥65 years interviewed in 2017 and in 2019. Nut consumption was estimated with a validated computer-based diet history. Depression was defined as self-reported physician-diagnosed depression or the use of antidepressants. Logistic regression models were adjusted for the main confounders. The DerSimonian and Laird random-effect method was used to meta-analyze the results from both studies. A participant-level pooled analysis was conducted to examine the robustness of our analyses. RESULTS: The SE-I included 2278 individuals (233 prevalent cases) in the cross-sectional analysis and 1534 (108 incident cases) in the longitudinal analysis; the corresponding figures for SE-II were 2726 (407 prevalent cases) and 1566 (74 incident cases). In the meta-analysis of cross-sectional results from the two studies, compared to consuming <1 serving (30 g) of nuts/week, the odds ratio (95% confidence interval) for depression was 0.90 (0.64, 1.16) for consuming 1 to <3 servings/week and 0.92 (0.70, 1.13) for consuming ≥3 servings/week; the corresponding figures for the longitudinal results were 0.90 (0.41, 1.38) and 0.66 (0.35, 0.97). CONCLUSION: Nut consumption was associated with a lower risk of depression in a pooled longitudinal analysis using data from two cohorts of older adults. Nuts should be recommended as part of a healthy diet in older adults.

Meningococcal knee arthritis serogroup W-135. Case report

N. Meningitidis serogroup (A, B, C), are main causers of disease. Serogroup W-135 incidence is lower nowadays and, although it is increasing, is such an uncommon infection in adults. We report a case of a monoarthritis knee due to Neisseria meningitidis (W- 135) in an inmunocompetent 50 year-old male

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Correlation between Streptococcus bovis bacteremia and density of cows in Galicia, northwest of Spain.

BACKGROUND: There are few data on the epidemiology of infections caused by Streptococcus bovis (Sb). Some studies suggest that both residence in rural areas and contact with livestock could be potential risk factors. METHODS: We performed a retrospective study for the period 2005-2016 of all cases of bacteremia caused by Sb in Galicia (a region in the northwest of Spain). The association between the incidence rate of Sb bacteremia and the number of cattle by province and district was analyzed. RESULTS: 677 cases were included with a median age of 76 years, 69.3% males. The most frequent infections were endocarditis (234 cases, 34.5%), primary bacteremia (213 cases, 31.5%) and biliary infection (119 cases, 17.5%). In 252 patients, colon neoplasms were detected (37.2%). S. gallolyticus subsp. gallolyticus was the predominant species (52.3%). Mortality was 15.5% (105 cases). The annual incidence rate was 20.2 cases/106 inhabitants and was correlated with the density of cattle (p < 0.001), but not with rurality. When comparing the two provinces with a strong predominance of rural population, but with important differences in the number of cattle, such as Orense and Lugo, with 6% and 47.7% of Galician cattle, respectively, the rates were very different: 15.8 and 43.6 cases/106, respectively, with an RR of 2.7 (95% CI, 2.08-3.71). Some districts of the province of Lugo had rates higher than 100 cases/106 inhabitants. CONCLUSIONS: Our study shows a significant correlation between the rates of Sb bacteremia and cattle density, suggesting a possible transmission of Sb from cows to people.

Acquired hepatocerebral degeneration: clinical characteristics and MRI findings.

OBJECTIVE: To determine the prevalence of acquired hepatocerebral degeneration (AHD), its clinical and neuroimaging characteristics and response to treatments. BACKGROUND: Acquired hepatocerebral degeneration is a chronic encephalopathy with predominant motor signs in the context of severe liver disease. Its clinical picture is not well defined, and its prevalence and risk factors are not well known. METHODS: Review of a database of 1000 patients with cirrhosis to identify cases of AHD. Clinical and neuroimaging data, follow-up and response to treatments, including liver transplantation, were recorded. RESULTS: Eight patients with AHD were identified. Its prevalence was 0.8% of patients with cirrhosis. The main risk factor for AHD was the presence of portosystemic shunts. Movement disorders, especially a combination of parkinsonism and cerebellar signs were observed in all patients. All AHD cases showed on MRI T1-weighted images hyperintensities in the globus pallidus, and 75% had extrapallidal involvement as well. Antiparkisonian drugs and treatments to prevent acute encephalopathies were ineffective. Three patients who underwent liver transplantation did not experience neurological improvement. Persistence of portosystemic shunts was demonstrated in two cases. CONCLUSIONS: Acquired hepatocerebral degeneration is a chronic encephalopathy which occurs in ∼1% of patients with liver cirrhosis and seems related to portosystemic shunts. Its is characterized by a combination of parkinsonism and cerebellar signs. MRI pallidal and extrapallidal lesions are seen in most patients, probably reflecting intracerebral deposits of manganese. Liver transplant did not improve the neurological signs in our patients, perhaps because of the persistence of portosystemic shunts.

Meningitis con múltiples lesiones intracraneales / Meningitis with intracranial multiple lesions

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Miocarditis por virus varicela-zoster en el adulto / Varicella-zoster myocarditis in an adult

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Síndrome miasteniforme de Eaton-Lambert. Revisión y presentación de un caso / Lambert-Eaton myasthenic syndrome. Review and a case report

El síndrome miasteniforme de Eaton-Lambert (SMEL) es un trastorno autoimmune presináptico de la transmisión neuromuscular, que se manifiesta clínicamente por debilidad muscular proximal, principalmente de los miembros inferiores, disfunción autosómica y reflejos osteotendinosos disminuidos. Presentamos el caso clínico de un paciente diagnosticado inicialmente de una polineuropatía crónica diabética, que tras la realización de un nuevo estudio electrofisiológico es diagnosticado de SMEL. Se revisan los principales aspectos sobre la enfermedad expuestos en la literatura médica, con particular énfasis en la importancia que tiene un correcto estudio electrofisiológico para el diagnóstico y el papel de la rehabilitación en el tratamiento de estos pacientes

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune presynaptic disorder of neuromuscular transmission, clinically manifest by proximal muscle weakness, principally involving the lower limbs, autonomic dysfunction and depressed deep tendon reflexes. We present the clinical case of a patient initially diagnosed of chronic diabetic polyneuropathy, who was diagnosed of LEMS after new electrophysiological testing. We review the main aspects on the disease presented in the literature, with special emphasis on the importance of an appropriate electrophysiological study to confirm diagnosis and the role of the rehabilitation in the treatment of these patients

Infección por VIH, consumo de drogas y rendimiento neuropsicológico / HIV-1 infection, use of drugs and neuropsychologic efficiency

Introducción: El abuso de sustancias ha sido considerado como un factor explicativo del deterioro neuropsicológico. Sin embargo, persisten dudas sobre la distinción entre efectos directos o indirectos e incluso sobre la interacción entre el efecto del VIH y el consumo de sustancias. El objetivo de esta investigación consistió en estudiar el efecto del consumo de drogas y la seropositividad al VIH-1 sobre el rendimiento neuropsicológico. Método: Tras obtener el consentimiento informado fueron reclutados 113 suetos, integrados en cuatro grupos (34 seropositvos exconsumidores de drogas por vía parenteral; 33 seropositivos en programas de mantenimiento con metadona; 19 seronegativos exconsumidores de drogas por vía parenteral; y 27 seronegativos sin antecedentes de consumo. A todos ellos se les aplicó una batería neuropsicológica integrada diseñada ad hoc, una entrevista semiestructurada sobre aspectos sociodemográficos, toxicológicos, neuropsiquiátricos y clínico-biológicos y una evaluación de la sintomatología ansioso-depresiva. Resultados: los sujetos seropositivos en metadona presentan mayores tasas de prevalencia del deterioro que el resto de los grupos (c2 = 32.22, p ,000). Conclusiones: El consumo de drogas y la seropositividad son factores que se asocian al bajo rendimiento neuropsicológico. Además, la situación respecto al consumo explica diferencias en los niveles de ejecución y tasas de deterioro neuropsicológico, siendo los sujetos en programas de mantenimiento con metadona los que presentan los peores niveles de ejecución, así como las tasas más elevadas de afectación neuropsicológica

Introduction: The abuse of substances has been considered as an explanatory factor of the neuropsychologic failure. However, doubts persist on the distinction among direct or indirect efects and even on the interaction between the effect of the HIV and the use of substances. The objective of this investigation consisted on studying the effect of the use of drugs and the seropositivity to the HIV-1 on the neuropsychologic efficiency. Method: After obtaining the informed consentiment 113 patients they were recruited, integrated in four groups (34 seropositives ex-UDPP; 33 seropositives in maintenance programs with methadone; 19 seronegatives; and 27 seronegatives without previous use of drugs. To all they were applied a neuropsychologic battery designed ad hoc, an semistructured interview about sociodemographical, toxicological, neuropsychiatric and clinical-biological aspects and an evaluation of the ansious-depressive symptomatology. Results: The seropositive patients in methadone present bigger rates of prevalence of the damage that the rest of the groups (X2 = 32.22, p .000). Conclusions: The abuse of drugs and the seropositivity are factors that associate to the decrease neuropsychologic efficiency. Also, the situation regarding the abuse explains differences in the execution levels and rates of neuropsychologic damage, being the patients in maintenance programs with methadone those that present the worst execution levels, as well as the highest rates in neuropsychologic affectation

Infección por VIH-1 y enfermedad inflamatoria intestinal / HIV-1 infection and inflammatory bowel disease

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Quiste sinovial como causa de lumbociática. Revisión y presentación de un caso / Synovial cyst as cause of lumbar sciatic picture. Review and presentation of one case

La lumbociática representa un síntoma muy frecuente en una consulta de Rehabilitación y puede ser atribuida a diferentes etiologías. Los quistes sinoviales lumbares son una etiología poco frecuente, pero que no debemos olvidaren el diagnóstico diferencial. Estas lesiones están íntimamente relacionadas con las articulaciones facetarias y sudegeneración; su localización preferente es a nivel de L4-L5 y la técnica diagnóstica de elección será la resonancia magnética. La cirugía es la mejor alternativa si existe dolor persistente y sintomatología neurológica. Se presenta un caso de una mujer de 52 años de edad, sin antecedentes de interés, que acudió a la consulta de Rehabilitación por un cuadro de lumbociática de 3 meses de evolución que no respondía al tratamiento farmacológico pautado. Se prescribe tratamiento rehabilitador ante sospecha de protrusión discal. Se objetiva un quiste sinovial lumbar en la resonancia magnética. Debido a la persistencia de la sintomatología, la paciente fue subsidiaria de cirugía y presentó muy buena evolución

Lumbar sciatic picture represents a very frequent symptom in a Rehabilitation out-patient clinic and maybe attributed to different etiologies. Lumbar synovial cysts(LSC) are a rare etiology, but we must not forget it in the differential diagnosis. These lesions are closely related with facet articulations and their degeneration; its preferential site isL4-L5 level and the diagnostic technique of choice would be Magnetic Resonance Imaging (MRI). Surgery is the best alternative if there is persistent pain and neurological symptoms. We present a case of a 52 year old woman, without background of interest, who came to the Rehabilitation out-patient clinic due to a lumbal-sciatic picture of three months evolution that did not respond to the drug treatment prescribed. Rehabilitation treatment was prescribed due to the suspicion of disc protrusion. A lumbar synovial cyst was seen in the MRI. Due to the persistence of the symptoms, the patients underwent surgery, presenting good evolution

[HIV-1 infection, use of drugs and neuropsychologic efficiency]. / Infección por VIH, consumo de drogas y rendimiento neuropsicológico.

INTRODUCTION: The abuse of substances has been considered as an explanatory factor of the neuropsychologic failure. However, doubts persist on the distinction among direct or indirect effects and even on the interaction between the effect of the HIV and the use of substances. The objective of this investigation consisted on studying the effect of the use of drugs and the seropositivity to the HIV-1 on the neuropsychologic efficiency. METHOD: After obtaining the informed consent 113 patients they were recruited, integrated in four groups (34 seropositives ex-UDPP; 33 seropositives in maintenance programs with methadone; 19 seronegatives; and 27 seronegatives without previous use of drugs. To all they were applied a neuropsychologic battery designed ad hoc, an semistructured interview about sociodemographical, toxicological, neuropsychiatric and clinical-biological aspects and an evaluation of the anxious-depressive symptomatology. RESULTS: The seropositive patients in methadone present bigger rates of prevalence of the damage that the rest of the groups (X2 = 32.22, p < .000) and lower rates of execution in all the studied factors. Also, it is observed that the seropositive patients as group present lower execution levels and higher rates of damage. Also, all the groups had lower levels of execution that the people seronegative non consumers (F = 15.661, p > .000). CONCLUSIONS: The abuse of drugs and the seropositivity are factors that associate to the decrease neuropsychologic efficiency. Also, the situation regarding the abuse explains differences in the execution levels and rates of neuropsychologic damage, being the patients in maintenance programs with methadone those that present the worst execution levels, as well as the highest rates in neuropsychologic affectation.

[Disseminated Mycobacterium chelonae infection during HIV. ]. / Infection disséminée à Mycobacterium chelonae au cours de l'infection à VIH.

INTRODUCTION: An atypical mycobacterium, Mycobacterium chelonae is a saprophyte germ in the environment, but rarely pathogenic. A few disseminated infections can be noted in immunodepressed patients. OBSERVATION: A 30 year-old man infected by HIV was hospitalised for deterioration in his general status of health with, on clinical examination, pallor, several superficial lymph nodes and hepatosplenomegaly. A biopsy of an axillary node and the liver revealed numerous granulomas with many atypical M. chelonae-like mycobacteria. Adapted treatment led to complete remission. DISCUSSION: Immunodepression facilitates the occurrence of M. chelonae infections, often of severe evolution and leading to dissemination. This mycobacterium is resistant to many antibiotics.

[Antimicrobial susceptibility of the bloodstream infections: a study in a nonteaching hospital]. / Estudio de sensibilidad antibiótica en las bacteriemias de un hospital secundario.

BACKGROUND: To try established antimicrobial susceptibility patterns and frequency of both nosocomial and community-acquired bloodstream infections and and to try identified the prognostic factors that can be modified. MATERIAL AND METHODS: A prospective study of 310 bloodstream infections with clinical significance detected in a non teaching hospital over period from October 2000-2001. A blood culture were identified by Bact-Alert system and the confirmation was performed by MicroScan system; an antimicrobial susceptibility test was performed by reference microdilution methods as described by NCCLS. We studied sentinel antimicrobial/organism combinations with potential clinical importance. Data were computerized using SPSS. Qualitative variables were compared using the X2 test or the Fisher exact test, and quantitative variables with t Student or ANOVA. RESULTS: Gram positive and Candida were frequently recovered in nosocomial bloodstreams. The proportion of oxacillin-resistant S. aureus isolates was 24% and the penicillin resistant pneumococci was 14%. Vancomycin was universal active against gram positive. Gram negatives were often recovered in community bloodstream. The proportion of EBSL E. coli isolates was < 2% and the proportion of multiresistance Pseudomonas aeruginosa was higher among UCI isolates. An independent risk factors for death identified after multivariate analysis was the inappropriate antimicrobial therapy OR 2.6. CONCLUSIONS: Ongoing surveillance of microbial pathogens and their resistance profiles is essential on local scale and permit the selection of appropriate antibiotic therapy which would be reduce the mortality.

Estudio de sensibilidad antibiótica en las bacteriemias de un hospital secundario / Antimicrobial susceptibility of the bloodstream infections: a study in a nonteaching hospital

Objetivo: Conocer los patógenos prevalentes y los patrones de resistencia de las bacteriemias nosocomiales y adquiridas. Material y métodos: Estudio prospectivo de 310 bacteriemias "significativas" detectadas en un hospital no universitario en el periodo octubre 2000-2001. Los hemocultivos se detectaron por el sistema Bact-Alert y la identificación definitiva se efectuó con el sistema MicroScan, con estudio de sensibilidad por el método de microdilución de referencia (NCLSS). Se estudiaron combinaciones "centinela" con relevancia clínica. El análisis estadístico utilizó el programa SPSS. El análisis univariante utilizó para variables cuantitativas t Student y para cualitativa test X2 o t Fisher. Resultados: Los gram positivos y las levaduras predominaron en las nosocomiales. Hubo un 24 por ciento de MARSA y un 14 por ciento de neumococos penicilina resistentes. La vancomicina mantuvo una sensibilidad universal. Los gram negativos dominaron en las comunitarias, E. coli (40 por ciento) con una prevalencia de EBSL < 2 por ciento. Destacamos las tasas de multiresistencia para P. aeruginosa en las unidades de agudos. Un análisis de regresión logística reveló al tratamiento empírico inadecuado como un factor independiente de mortalidad (OR 2,6). Conclusiones: La necesidad de un sistema de vigilancia que permita conocer la prevalencia y resistencia de los microorganimos locales y establecer terapéuticas empíricas adecuadas que permitan reducir la mortalidad (AU)