The polygenic basis of relapse after a first episode of schizophrenia

Little is known about genetic predisposition to relapse. Previous studies have linked cognitive and psychopathological (mainly schizophrenia and bipolar disorder) polygenic risk scores (PRS) with clinical manifestations of the disease. This study aims to explore the potential role of PRS from major mental disorders and cognition on schizophrenia relapse. 114 patients recruited in the 2EPs Project were included (56 patients who had not experienced relapse after 3 years of enrollment and 58 patients who relapsed during the 3-year follow-up). PRS for schizophrenia (PRS-SZ), bipolar disorder (PRS-BD), education attainment (PRS-EA) and cognitive performance (PRS-CP) were used to assess the genetic risk of schizophrenia relapse.Patients with higher PRS-EA, showed both a lower risk (OR=0.29, 95% CI [0.11–0.73]) and a later onset of relapse (30.96± 1.74 vs. 23.12± 1.14 months, p=0.007. Our study provides evidence that the genetic burden of neurocognitive function is a potentially predictors of relapse that could be incorporated into future risk prediction models. Moreover, appropriate treatments for cognitive symptoms appear to be important for improving the long-term clinical outcome of relapse

Comisionamiento del sistema integrado de radiocirugía Varian ICVI.

La radiocirugía es una técnica de radioterapia compleja que requiere altos niveles de precisión debido a la elevada dosis entregada de forma hipofraccionada sobre un pequeño volumen rodeado por estructuras de riesgo. Para resguardar dichas estructuras y generar alto gradiente de dosis, la técnica puede ser administrada mediante colimadores cónicos, los cuales conforman campos considerados pequeños. Trabajar con dichos campos implica dificultades dosimétricas, por lo cual se han desarrollado nuevos protocolos. Se comisionó el sistema de radiocirugía ICVI de Varian, que incluye colimadores cónicos de 4 mm, 5 mm, 7,5 mm, 10 mm, 12,5 mm, 15 mm y 17,5 mm, a ser usado en un acelerador TrueBeam STx® con energías 6 MV y 10 MV, con y sin filtro aplanador. Se midieron perfiles, curvas de dosis en profundidad y output factors, tal como lo requiere el software de planificación Eclipse™ Cone Planning. Se utilizaron detectores Edge™, microDiamond™ y Diodo E™, así como el fantoma 3D Scanner™, y los resultados se compararon con los datos de referencia del fabricante. Los perfiles y curvas de dosis en profundidad calculados se validaron utilizando diferentes criterios gamma. También se realizó un estudio End-to-End con el fantoma StereoPhan™ y la cámara de ionización PinPoint® 3D. Los conos iguales o mayores a 7,5 mm mostraron concordancia dentro del 2% entre lo medido y lo calculado. Se requiere otro método de validación para los conos más chicos

Evaluation of the validity of the HPV viral load compared to conventional techniques for the detection of high-grade anal intraepithelial lesions in men with HIV who have sex with men

Background The incidence of high-grade anal intraepithelial lesions (HSILs) has increased in recent years among men who have sex with men with human immunodeficiency virus (HIV). This work evaluated the validity of the human papilloma virus viral load (HPV-VL) versus cytological and qualitative HPV results to detect HSILs. Methods From May 2017 to January 2020, 93 men who have sex with men and HIV were included in an anal cancer screening program from the Infectious Diseases Unit at a tertiary-care hospital in Alicante (Spain). The gold-standard for the screening of anal HSILs is the anal biopsy using high-resolution anoscopy. The diagnostic methods compared against gold-standard were HPV-16-VL, HPV-18-VL, and HPV-16-18-VL co-testing, anal cytology, and qualitative HPV detection. The receiver operating characteristic (ROC) curve and cut-off points for HPV-VL were calculated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen’s Kappa coefficient (κ) were also calculated. Results The mean patient age was 44.6 ± 9.5 years. All of them received antiretroviral treatment, 96.8% had an HIV viral load of 6.2 copies/cell was detected in the HSIL biopsy samples (p = 0.007), showing a sensitivity of 100% and a specificity of 46.2%. HPV-18-VL and HPV16-18-VL co-testing showed a sensitivity of 75% and 76.9% and a specificity of 72.7% and 61.3%, respectively. The highest PPV was 50% obtained with the cytology and HPV-18-VL. The HPV-16-VL showed a NPV of 100%, followed by 88.9% in the HPV-18-VL and 87% in the abnormal cytology. Cohen’s Kappa coefficient were: HPV-18-VL (κ = 0.412), abnormal cytology (κ = 0.353) and HPV-16-VL (κ = 0.338). Conclusions HPV-VL testing improved the detection sensitivity but not the specificity for HSIL biopsies compared to anal cytology and the qualitative detection of HPV. In men who have sex with men and HIV the HPV-VL could be an useful tool for diagnosis of HSILs in anal cancer screening programs. Further studies will be needed to evaluate the clinical implications of HPV-VL in these programs

Association of Hypertension with All-Cause Mortality among Hospitalized Patients with COVID-19

It is unclear to which extent the higher mortality associated with hypertension in the coronavirus disease (COVID-19) is due to its increased prevalence among older patients or to specific mechanisms. Cross-sectional, observational, retrospective multicenter study, analyzing 12226 patients who required hospital admission in 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics of survivors versus non-survivors. The mean age of the study population was 67.5 ± 16.1 years, 42.6% were women. Overall, 2630 (21.5%) subjects died. The most common comorbidity was hypertension (50.9%) followed by diabetes (19.1%), and atrial fibrillation (11.2%). Multivariate analysis showed that after adjusting for gender (males, OR: 1.5, p = 0.0001), age tertiles (second and third tertiles, OR: 2.0 and 4.7, p = 0.0001), and Charlson Comorbidity Index scores (second and third tertiles, OR: 4.7 and 8.1, p = 0.0001), hypertension was significantly predictive of all-cause mortality when this comorbidity was treated with angiotensin-converting enzyme inhibitors (ACEIs) (OR: 1.6, p = 0.002) or other than renin-angiotensin-aldosterone blockers (OR: 1.3, p = 0.001) or angiotensin II receptor blockers (ARBs) (OR: 1.2, p = 0.035). The preexisting condition of hypertension had an independent prognostic value for all-cause mortality in patients with COVID-19 who required hospitalization. ARBs showed a lower risk of lethality in hypertensive patients than other antihypertensive drugs.Ye