Prognostic value of inhibitors of apoptosis proteins (IAPs) and caspases in prostate cancer: caspase-3 forms and XIAP predict biochemical progression after radical prostatectomy

Background: The expression status of apoptotic regulators, such as caspases and inhibitors of apoptosis proteins (IAPs), could reflect the aggressiveness of tumors and, therefore, could be useful as prognostic markers. We explored the associations between tumor expression of caspases and IAPs and clinicopathological features of prostate cancer – clinical and pathological T stage, Gleason score, preoperative serum PSA levels, perineural invasion, lymph node involvement, surgical margin status and overall survival – and evaluated its capability to predict biochemical progression after radical prostatectomy. Methods: Protein expression of caspases (procaspase-8, cleaved caspase-8, procaspase-3, cleaved caspase-3, caspase-7 and procaspase-9) and IAPs (cIAP1/2, cIAP2, NAIP, Survivin and XIAP) was analyzed by immunohistochemistry in radical prostatectomy samples from 84 prostate cancer patients. Spearman’s test, Kaplan-Meier curves, and univariate and multivariate Cox proportional hazard regression analysis were performed. Results: cIAP1/2, cIAP2, Survivin, procaspase-8, cleaved caspase-8, procaspase-3 and caspase-7 expression correlated with at least one clinicopathological feature of the disease. Patients negative for XIAP, procaspase-3 or cleaved caspase-3 had a significantly worse prognosis. Of note, XIAP, procaspase-3 and cleaved caspase-3 were predictors of biochemical progression independent of Gleason score and pathological T stage. Conclusions: Our results indicate that alterations in the expression of IAPs and caspases contribute to the malignant behavior of prostate tumors and suggest that tumor expression of XIAP, procaspase-3 and cleaved caspase-3 may help to identify prostate cancer patients at risk of progression

The molecular signature of HIV-1-associated Lipomatosis reveals differential involvement of Brown and Beige/Brite Adipocyte cell lineages

Highly active antiretroviral therapy has remarkably improved quality of life of HIV-1-infected patients. However, this treatment has been associated with the so-called lipodystrophic syndrome, which conveys a number of adverse metabolic effects and morphological alterations. Among them, lipoatrophy of subcutaneous fat in certain anatomical areas and hypertrophy of visceral depots are the most common. Less frequently, lipomatous enlargements of subcutaneous fat at distinct anatomic areas occur. Lipomatous adipose tissue in the dorso-cervical area ('buffalo hump') has been associated with a partial white-to-brown phenotype transition and with increased cell proliferation, but, to date, lipomatous enlargements arising in other parts of the body have not been characterized. In order to establish the main molecular events associated with the appearance of lipomatosis in HIV-1 patients, we analyzed biopsies of lipomatous tissue from 'buffalo hump' and from other anatomical areas in patients, in comparison with healthy subcutaneous adipose tissue, using a marker gene expression approach. Both buffalo-hump and non-buffalo-hump lipomatous adipose tissues exhibited similar patterns of non-compromised adipogenesis, unaltered inflammation, non-fibrotic phenotype and proliferative activity. Shorter telomere length, prelamin A accumulation and SA-β-Gal induction, reminiscent of adipocyte senescence, were also common to both types of lipomatous tissues. Buffalo hump biopsies showed expression of marker genes of brown adipose tissue (e.g. UCP1) and, specifically, of 'classical' brown adipocytes (e.g. ZIC1) but not of beige/brite adipocytes. No such brown fat-related gene expression occurred in lipomatous tissues at other anatomical sites. In conclusion, buffalo hump and other subcutaneous adipose tissue enlargements from HIV-1-infected patients share a similar lipomatous character. However, a distorted induction of white-to-'classical brown adipocyte' phenotype appears unique of dorso-cervical lipomatosis. Thus, the insults caused by HIV-1 viral infection and/or antiretroviral therapy leading to lipomatosis are acting in a location- and adipocyte lineage-dependent manner

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Choroidal and retinal thickness in systemic autoimmune and inflammatory diseases: A review

To identify the risk of relapse and subclinical inflammatory stages of systemic autoimmune diseases, new tools are needed. In the recent years, choroidal thickness and retinal thickness measured with ocular coherence tomography (OCT) have been proposed as an inflammatory marker for different systemic diseases, especially for conditions with a vascular component. Our aim in this article is to review the literature regarding the role of choroidal and retinal thickness as a potential inflammatory marker in systemic autoimmune and inflammatory diseases measured by OCT. Current literature suggests that the choroid of patients thickens in active phases of inflammatory diseases with vascular involvement. This pattern is observed in lupus, systemic sclerosis, Behçet disease, spondylitis, and familial Mediterranean fever. Choroidal thickness may decrease with biological treatments, along with systemic inflammation. Repeated flares and long-term disease, however, may thin the choroid, as a result of prolonged insult to the microvasculature and subsequent atrophy. Less is known about the effect of these diseases on retinal thickness. In summary, choroidal and retinal thickness measured by OCT may be promising markers for inflammation in systemic autoimmune and inflammatory diseases; however, more studies are warranted before generalizing choroidal thickness measurements by OCT as a marker for disease activity. The role of retinal thickness is more unclear due to a lack of studies in this field.Sin financiación4.195 JCR (2019) Q1, 6/60 Ophthalmology2.002 SJR (2019) Q1, 7/125 OphthalmologyNo data IDR 2019UE

Observational Study in Real Clinical Practice of the Treatment of Non-Infectious Uveitis

Background: Uveitis is an ocular disease that is a major cause of morbidity and blindness in the developed world. Although Immunosuppressive drugs and biologic therapy have been shown to be effective in their treatment there are no clear protocols for their use. Objectives: To describe the characteristics of patients with uveitis associated with immunologic or idiopathic disease who require immunosuppressive treatment and their response in real clinical practice. Methods: Observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with uveitis associated with immunologic or idiopathic diseases attended in a multidisciplinary consultation between January 2011 and February 2022. To assess the response to treatment, we evaluated the change in visual acuity and vitritis and the presence of macular edema. Results: We included 356 patients (mean age at diagnosis 42.8 ± 15.8 years, 50% female). Of the total, 157 (44%) had a single flare and 164 (46%) more than three. The involvement was bilateral in 85 patients (24%) and anterior (73%) and idiopathic (43%) were the most frequent. Twelve percent required treatment with systemic corticosteroids and 66 patients (18.5%) immunosuppressive/biological treatment, methotrexate being the most used (55%). Ten patients of the 66 (15%) started treatment with biologics and 34 (48%) required them at some point during the disease, adalimumab being the most used. Thirty-five patients (53%) needed to change drug due to lack of response. There were no differences between different drugs in the resolution of vitritis and improvement of vision. Disappearance of macular edema was achieved in all patients treated with tocilizumab.Sin financiación27.4 Q1 JCR 20226.138 Q1 SJR 2023No data IDR 2022UE

An Observational Study in the Real Clinical Practice of the Treatment of Noninfectious Uveitis

Background: The aim of this study was to describe the characteristics of patients with uveitis associated with an immunologic or idiopathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice. Methods: An observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with noninfectious uveitis was performed. To assess the response to treatment, we evaluated the change in visual acuity, vitritis, and the presence of macular edema. Results: We included 356 patients. Overall, 12% required treatment with systemic corticosteroids, and 66 patients (18.5%) required immunosuppressive/biological treatment, with methotrexate being the most used (55%). Immunosuppressive drugs were used in 59 cases (in 56 patients, as the first choice of treatment and for 3 patients as the second choice after treatment with biologics). Treatment with biologics was the first choice in 10 patients out of 66 (15%), and 34 (48%) required them at some time during the disease, with adalimumab being the most commonly used. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement in vision. Conclusions: The use of systemic corticosteroids and immunosuppressive/biologics was necessary for a high number of patients with noninfectious uveitis. In our series, tocilizumab was significantly more effective in the resolution of macular edema.Sin financiación3.9 Q2 JCR 20220.882 Q1 SJR 2023No data IDR 2022UE

Visual acuity loss and development of ocular complications in white dot syndromes: A longitudinal analysis of 3 centers

Purpose: To compare the clinical prognosis among selected white dot syndromes (WDS) (birdshot chorioretinopathy (BRC), multifocal choroiditis, serpiginous choroidopathy (SC), and others) and to identify risk factors of poor visual prognosis. Methods: Retrospective longitudinal cohort study including 84 patients (143 affected eyes) diagnosed with WDS between 1982 and July 2017, followed up until loss of follow-up or December 2017, and recruited from three Uveitis Clinics (Madrid Community, Spain). Our main outcome measures were temporary or permanent moderate (corrected visual acuity in the Snellen scale < 20/50) or severe (< 20/200) vision losses, and development of new ocular complications. Incidence rates (IR) of the main outcome measures were estimated per 100 eye-years. Bivariate and multivariate Cox robust regression models analyzed the association of demographic- and clinical-related variables with vision loss. Results: SC exhibited the greatest IR of vision loss, even in the multivariate models. Previous events of vision loss, presence of choroidal neovascularization, and cataracts exhibited worse visual prognosis. Monotherapy with immunosuppressive drugs but not combine therapy was also associated with higher IR of visual loss. Regarding new ocular complications, BRC showed the highest IR of epiretinal membrane and macular edema. Conclusions: SC presents the worst visual prognosis. Some ocular manifestations can identify patients with WDS at risk of a worse clinical evolution.Instituto de Salud Carlos III (ISCIII), Ministerio de Sanidad, Consumo y Bienestar Social (Contrato de investigación Miguel Servet: CP12 / 03129 a LRR).2.396 JCR (2019) Q2, 23/60 Ophthalmology1.265 SJR (2019) Q1, 16/125 OphthalmologyNo data IDR 2019UE

Clinical Characteristics, Frailty, and Mortality of Residents With COVID-19 in Nursing Homes of a Region of Madrid

Objectives: To describe the clinical characteristics, 30-day mortality, and associated factors of patients living in nursing homes (NH) with COVID-19, from March 20 to June 1, 2020. Design: This is a retrospective study. A geriatric hospital-based team acted as a consultant and coordinated the care of older people living in NHs from the hospital. Setting and participants: A total of 630 patients aged 70 and older with Coronavirus Disease 2019 COVID-19 living in 55 NHs. Methods: A logistic regression was performed to analyze the factors associated with mortality. In addition, Kaplan-Meier curves were applied according to mortality and its associated factors using the log-rank Mantel-Cox test. Results: The diagnosis of COVID-19 was mainly made by clinical compatibility (N = 430). Median age was 87 years, 64.6% were women and 45.9% were transferred to be cared for at the hospital. A total of 282 patients died (44.7%) within the 30 days of first attention by the team. A severe form of COVID-19 occurred in 473 patients, and the most frequent symptoms were dyspnea (n = 332) and altered level of consciousness (n = 301). According to multiple logistic regression, male sex (P = .019), the Clinical Frailty Score (CFS) ≥6 (P = .004), dementia (P = .012), dyspnea (P < .001), and having a severe form of COVID-19 (P = .001), were associated with mortality, whereas age and care setting were not. Conclusions and implications: Mortality of the residents living in NHs with COVID-19 was almost 45%. The altered level of consciousness as an atypical presentation of COVID-19 should be considered in this population. A severe form of the disease, present in more than three-quarters of patients, was associated with mortality, apart from the male sex, CFS ≥6, dementia, and dyspnea, whereas age and care setting were not. These findings may also help to recognize patients in which the Advance Care Planning process is especially urgent to assist in the decisions about their care.Sin financiación4.367 JCR (2019) Q1, 8/51 Geriatrics & Gerontology2.054 SJR (2019) Q1, 5/109 Geriatrics and GerontologyNo data IDR 2019UE