Life expectancy of people with HIV on antiretroviral therapy in Spain.

OBJECTIVE: To estimate life expectancy of people with HIV (PWH) and describe causes of death. DESIGN: Antiretroviral therapy (ART)-naive adults from the CoRIS cohort starting ART in 2004-2019. METHODS: We calculated life expectancy at age 40 for men and women according to their ART initiation period, and stratified by transmission category, CD4 + cell count and AIDS diagnosis. We estimated life expectancy in 10-year age bands using life tables constructed from mortality rates, estimated through Poisson models. RESULTS: Life expectancy increased from 65.8 [95% confidence interval (CI) 65.0-66.6] in 2004-2008 to 72.9 (72.2-73.7) in 2014-2019 in men [general population comparators (GPC): 79.1 and 81.2 years, respectively] and from 65.8 (65.0-66.6) to 72.5 (71.8-73.3) in women (GPC: 84.9 and 86.4, respectively). Non-AIDS-related deaths accounted for 68% of deaths among men and 78% among women. Life expectancy was longer when starting ART with higher CD4 + cell counts and without AIDS. For men acquiring HIV through sex with men, starting ART in 2014-2019 without AIDS, life expectancy was 75.0 (74.2-75.7) with CD4 + cell count less than 200 cells/µl, rising to 78.1 (77.5-78.8) with CD4 + cell count at least 350 cells/µl. Corresponding figures were 70.1 (69.4-70.9) and 76.0 (75.3-76.7) for men acquiring HIV heterosexually (HTX) and 61.5 (60.7-62.3) and 69.0 (68.2-69.8) for those acquiring HIV through injection drug use (IDU). For women starting ART from 2014 without AIDS, life expectancy increased from 71.7 (71.0-72.4) to 77.3 (76.7-77.9) among HTX and from 63.7 (62.9-64.5) to 70.7 (70.0-71.5) among IDU. CONCLUSION: Our findings confirm the progressive improvement of life expectancy in PWH in Spain over the last decades, supporting the insurability of PWH on suppressive ART in our current setting and time.

Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS): Assessment & validation of imaging modality performance across the NAFLD spectrum in a prospectively recruited cohort study (the LITMUS imaging study): Study protocol.

Non-alcoholic fatty liver disease (NAFLD) is the liver manifestation of the metabolic syndrome with global prevalence reaching epidemic levels. Despite the high disease burden in the population only a small proportion of those with NAFLD will develop progressive liver disease, for which there is currently no approved pharmacotherapy. Identifying those who are at risk of progressive NAFLD currently requires a liver biopsy which is problematic. Firstly, liver biopsy is invasive and therefore not appropriate for use in a condition like NAFLD that affects a large proportion of the population. Secondly, biopsy is limited by sampling and observer dependent variability which can lead to misclassification of disease severity. Non-invasive biomarkers are therefore needed to replace liver biopsy in the assessment of NAFLD. Our study addresses this unmet need. The LITMUS Imaging Study is a prospectively recruited multi-centre cohort study evaluating magnetic resonance imaging and elastography, and ultrasound elastography against liver histology as the reference standard. Imaging biomarkers and biopsy are acquired within a 100-day window. The study employs standardised processes for imaging data collection and analysis as well as a real time central monitoring and quality control process for all the data submitted for analysis. It is anticipated that the high-quality data generated from this study will underpin changes in clinical practice for the benefit of people with NAFLD. Study Registration: clinicaltrials.gov: NCT05479721.

Bilateral orbital plasmacytomas as first sign of extramedullary progression post CAR-T therapy: case report and literature review.

Background: Plasma cell leukemia (PCL) is an aggressive and rare form of plasma cell dyscrasia characterized by peripheral blood expression, poor prognosis, and high relapse rates. Extramedullary plasmacytomas are common in this entity and can affect various organs and soft tissues. Chimeric antigen receptor-T-cell (CAR-T) therapy is a novel immunotherapy for hematological malignancies with promising results. However, it is not indicated for PCL, and experience in this condition is limited. This case is a rare presentation of bilateral orbital plasmacytomas after CAR-T therapy in a patient with PCL history. Case presentation: We present the case of a 51-year-old female patient with a history of previous primary PCL treated with CAR-T therapy achieving complete response and without evidence of systemic progression. Six months after the treatment, she developed subacute proptosis and ptosis on the left eye.An orbital CT scan was performed and showed an orbital tumor in both eyes. A surgical biopsy with histological examination revealed plasma cells, consistent with a plasmacytoma. PET-CT and MRI confirmed the presence of tumors in both orbits. The patient was treated with dexamethasone and chemotherapy along with palliative radiation therapy to the left orbit which had a good response. Conclusion: Orbital involvement in multiple myeloma and PCL is rare, with plasmacytomas being more common in other parts of the body. In this report, we present a case of a patient with PCL history, treated with multiple therapeutic lines including CAR-T therapy, who presented bilateral orbital plasmacytomas as the first sign of extramedullary progression after the treatment. This case should be considered by specialist to be aware that the orbits are a possible location of extramedullary progression.

An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography.

BACKGROUND & AIMS: We conducted an individual patient data meta-analysis to establish stiffness cut-off values for magnetic resonance elastography (MRE) in staging liver fibrosis and to assess potential confounding factors. METHODS: A systematic review of the literature identified studies reporting MRE data in patients with NAFLD. Data were obtained from the corresponding authors. The pooled diagnostic cut-off value for the various fibrosis stages was determined in a two-stage meta-analysis. Multilevel modelling methods were used to analyse potential confounding factors influencing the diagnostic accuracy of MRE in staging liver fibrosis. RESULTS: Eight independent cohorts comprising 798 patients were included in the meta-analysis. The area under the receiver operating characteristic curve (AUROC) for MRE in detecting significant fibrosis was 0.92 (sensitivity, 79%; specificity, 89%). For advanced fibrosis, the AUROC was 0.92 (sensitivity, 87%; specificity, 88%). For cirrhosis, the AUROC was 0.94 (sensitivity, 88%, specificity, 89%). Cut-offs were defined to explore concordance between MRE and histopathology: ≥F2, 3.14 kPa (pretest probability, 39.4%); ≥F3, 3.53 kPa (pretest probability, 24.1%); and F4, 4.45 kPa (pretest probability, 8.7%). In generalized linear mixed model analysis, histological steatohepatitis with higher inflammatory activity (odds ratio 2.448, 95% CI 1.180-5.079, p <0.05) and high gamma-glutamyl transferase (GGT) concentration (>120U/L) (odds ratio 3.388, 95% CI 1.577-7.278, p <0.01] were significantly associated with elevated liver stiffness, and thus affecting accuracy in staging early fibrosis (F0-F1). Steatosis, as measured by magnetic resonance imaging proton density fat fraction, and body mass index(BMI) were not confounders. CONCLUSIONS: MRE has excellent diagnostic performance for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Elevated inflammatory activity and GGT level may lead to overestimation of early liver fibrosis, but anthropometric measures such as BMI or the degree of steatosis do not. IMPACT AND IMPLICATIONS: This individual patient data meta-analysis of eight international cohorts, including 798 patients, demonstrated that MRE achieves excellent diagnostic accuracy for significant, advanced fibrosis and cirrhosis in patients with NAFLD. Cut-off values (significant fibrosis, 3.14 kPa; advanced fibrosis, 3.53 kPa; and cirrhosis, 4.45 kPa) were established. Elevated inflammatory activity and gamma-glutamyltransferase level may affect the diagnostic accuracy of MRE, leading to overestimation of liver fibrosis in early stages. We observed no impact of diabetes, obesity, or any other metabolic disorder on the diagnostic accuracy of MRE.

Clinical application of Magnetic resonance elastography in hepatocellular carcinoma: from diagnosis to prognosis.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Liver fibrosis is closely correlated with liver functional reserve and the risk of HCC development. Meanwhile, malignant tumors generally have high cellularity compared to benign tumors, which results in increased stiffness. Magnetic resonance elastography (MRE) has emerged as a new non-invasive technique for assessing tissue stiffness with excellent diagnostic accuracy, not only for assessing liver fibrosis but also for measuring tumor stiffness. Recent studies provide new evidence that MRE may play an important role in the management of patients with HCC and show several novel clinical applications, such as predicting the development of HCC, differentiating between benign/malignant liver lesions (FLL) and HCC pathological grades, assessing treatment response, and predicting recurrence after treatment, although some findings are controversial. Therefore, we conducted this review to summarize these novel applications of MRE in HCC patients and also discuss their limitations and future advancement.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort.

OBJECTIVES: to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). METHODS: sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. RESULTS: the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. CONCLUSIONS: MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy. Histological inflammation and surrogate biomarkers of inflammation can overestimate liver stiffness, but only GGT was statistically significant in the multivariate analysis. Important features of NAFLD patients such as obesity, DM, or lipidic profile did not affect MRE accuracy.

Liver stiffness accuracy by magnetic resonance elastography in histologically proven non-alcoholic fatty liver disease patients: a Spanish cohort

Objectives: to evaluate the performance of magnetic resonance elastography (MRE) to stage liver fibrosis in patients with histologically confirmed nonalcoholic fatty liver disease (NAFLD) and to assess the impact of potential confounding factors in MRE diagnostic accuracy. The secondary objective was to compare MRE with other non-invasive methods for staging fibrosis such as transient elastography (TE) and non-invasive scores (APRI and FIB-4). Methods: sixty-five histologically confirmed NAFLD patients were prospectively enrolled at the Hospital Universitario Virgen del Rocío (Seville, Spain). Liver stiffness was measured by MRE, TE and non-invasive scores (APRI and FIB-4). Fibrosis was assessed by liver biopsy using the steatosis, activity and fibrosis (SAF) score. Patients were classified into three groups according to the consistency between MRE and histopathological findings: underestimation, concordance and overestimation groups. Areas under the ROC curve (AUROC) and diagnostic performance were evaluated. Results: the area under the ROC curve (AUROC) of MRE in advanced fibrosis (≥ F3) was 0.90 (0.82-0.97), while TE AUROC was 0.82 (0.72-0.93) (p = 0.22) and lower for the non-invasive test (FIB-4 0.67 and APRI 0.62). Inflammatory activity, steatosis grade and higher levels of liver biochemistry appeared to overestimate MRE results in the univariate analysis, but only gamma-glutamyl transferase (GGT) was statistically significant in the multivariate analysis (p < 0.01). Age, sex, body mass index (BMI), weight, diabetes mellitus (DM), high blood pressure (HBP), platelets or lipidic profile did not affect MRE accuracy. Conclusions: MRE is an effective and non-invasive method for detecting and staging liver fibrosis in NAFLD patients. MRE is more accurate than TE and allows the study of liver anatomy (AU)

Obstructive sleep apnoea syndrome, endothelial function and markers of endothelialization. Changes after CPAP.

STUDY OBJECTIVES: This study tries to assess the endothelial function in vivo using flow-mediated dilatation (FMD) and several biomarkers of endothelium formation/restoration and damage in patients with obstructive sleep apnoea (OSA) syndrome at baseline and after three months with CPAP therapy. DESIGN: Observational study, before and after CPAP therapy. SETTING AND PATIENTS: We studied 30 patients with apnoea/hypopnoea index (AHI) >15/h that were compared with themselves after three months of CPAP therapy. FMD was assessed non-invasively in vivo using the Laser-Doppler flowmetry. Circulating cell-free DNA (cf-DNA) and microparticles (MPs) were measured as markers of endothelial damage and the vascular endothelial growth factor (VEGF) was determined as a marker of endothelial restoration process. MEASUREMENTS AND RESULTS: After three month with CPAP, FMD significantly increased (1072.26 ± 483.21 vs. 1604.38 ± 915.69 PU, p< 0.005) cf-DNA and MPs significantly decreased (187.93 ± 115.81 vs. 121.28 ± 78.98 pg/ml, p<0.01, and 69.60 ± 62.60 vs. 39.82 ± 22.14 U/µL, p<0.05, respectively) and VEGF levels increased (585.02 ± 246.06 vs. 641.11 ± 212.69 pg/ml, p<0.05). These changes were higher in patients with more severe disease. There was a relationship between markers of damage (r = -0.53, p<0.005) but not between markers of damage and restoration, thus suggesting that both types of markers should be measured together. CONCLUSIONS: CPAP therapy improves FMD. This improvement may be related to an increase of endothelial restoration process and a decrease of endothelial damage.