The Influence of the Socioeconomic Status and the Density of the Population on the Outcome After Peripheral Artery Disease.

BACKGROUND: Low socioeconomic status (SES) and living in a rural environment are associated with poorer health and a higher number of amputations among the population at large. The purpose of this study is to determine the influence of low SES and of the degree of urbanization on the short-term and long-term results of patients after revascularization for peripheral artery disease. METHODS: An observational retrospective follow-up study of 770 patients operated on for peripheral artery disease at three university centers in north-western Spain from January 2015 to December 2016. The events studied were Rutherford classification of severity upon admission, direct amputation, amputations in the follow-up period, new revascularization procedures, major adverse cardiovascular events (MACE), and overall mortality. Mean personal income and income of the household associated with the street in which each patient lived and the degree of urbanization in three areas as per Eurostat criteria: densely populated areas, intermediate density areas, and thinly populated areas. Comorbidity, surgical, and follow-up variables were also collected. Descriptive analysis and Cox regression were used. Approval was obtained from the regional ethics committee. RESULTS: Median follow-up was 47.5 months. MACE occurred in 21.5% of the series and overall mortality was 47.0%. Living in a thinly populated area is associated with a lower risk of MACE (adjusted subhazard ratio = 0.60; 95% confidence interval [CI]: 0.39-0.91). Overall survival is lower in intermediate density area patients (adjusted Hazard Ratio = 1.46; 95% CI: 1.07-2.00). The third quartile of mean personal and household income is associated with a higher risk of major amputation at follow-up (adjusted Odds Ratio 1.92, 95% CI: 1.05-3.52 and adjusted Odds Ratio 1.93, 95% CI: 1.0.3-3.61, respectively). CONCLUSIONS: Patients who live in a densely populated area run a higher risk of MACE. SES is neither associated with worse outcomes after surgery nor with MACE in long-term follow-up.

A Model for Prediction of In-Hospital Mortality in Patients with Subarachnoid Hemorrhage.

BACKGROUND: Despite being a rare cause of stroke, spontaneous subarachnoid hemorrhage (SAH) is associated with high mortality rates. The prediction models that are currently being used on SAH patients are heterogeneous, and few address premature mortality. The aim of this study was to develop a mortality risk stratification score for SAH. METHODS: A retrospective study was carried out with 536 patients diagnosed with SAH who had been admitted to the intensive care unit (ICU) at the University Hospital Complex of A Coruña (Spain) between 2003 and 2013. A multivariate logistic regression model was developed to predict the likelihood of in-hospital mortality, adjusting it exclusively for variables present on admission. A predictive equation of in-hospital mortality was then computed based on the model's coefficients, along with a points-based risk-scoring system. Its discrimination ability was also tested based on the area under the receiver operating characteristics curve and compared with previously developed scores. RESULTS: The mean age of the patients included in this study was 56.9 ± 14.1 years. Most of these patients (73.9%) had been diagnosed with aneurysmal SAH. Their median length of stay was 7 days in the ICU and 20 days in the general hospital ward, with an overall in-hospital mortality rate of 28.5%. The developed scales included the following admission variables independently associated with in-hospital mortality: coma at onset [odds ratio (OR) = 1.87; p = 0.028], Fisher scale score of 3-4 (OR = 2.27; p = 0.032), Acute Physiology and Chronic Health Evaluation II (APACHE II) score within the first 24 h (OR = 1.10; p < 0.001), and total Sequential Organ Failure Assessment (SOFA) score on day 0 (OR = 1.19; p = 0.004). Our predictive equation demonstrated better discrimination [area under the curve (AUC) = 0.835] (bootstrap-corrected AUC = 0.831) and calibration properties than those of the HAIR scale (AUC = 0.771; p ≤ 0.001) and the Functional Recovery Expected after Subarachnoid Hemorrhage scale (AUC = 0.814; p = 0.154). CONCLUSIONS: In addition to the conventional risk factors for in-hospital mortality, in our study, mortality was associated with the presence of coma at onset of the condition, the physiological variables assessed by means of the APACHE II scale within the first 24 h, and the total SOFA score on day 0. A simple prediction model of mortality was developed with novel parameters assessed on admission, which also assessed organ failure and did not require a previous etiological diagnosis.

Results in liver transplantation using grafts from donors after controlled circulatory death: A single-center experience comparing donor grafts harvested after controlled circulatory death to those harvested after brain death.

BACKGROUND: In recent years, interest in donation after cardiac death (DCD) has increased. Although DCD liver transplantation (LT) has demonstrated satisfactory long-term outcomes, different studies have shown poorer patient and graft survival after DCD than after donation after brain death (DBD). This study aimed to evaluate the results of LT using controlled DCD (cDCD) donors, specifically the incidence of primary non-function and ischemic cholangiopathy (IC), and to compare these results with those of LT using DBD in the same time period. METHODS: Between June 2012 and July 2018, we performed 66 transplants using cDCD and 258 with DBD grafts. RESULTS: The incidence of IC was similar in both groups (2% in DBD, 1.5% in DCD; P = .999). No significant differences were found for overall graft and patient survival rates between the groups at 1 and 2 years post-transplantation. CONCLUSIONS: This study provided evidence that cDCD donors exhibit excellent graft and patient survival outcomes. When the warm ischemia time is <30 minutes and cold ischemia time is <6 hours, the graft and patient survival rates and the incidence of IC in DCD are similar to those in DBD, even when using donors without age restrictions.

Mitochondrial DNA haplogroups influence the risk of incident knee osteoarthritis in OAI and CHECK cohorts. A meta-analysis and functional study.

OBJECTIVE: To evaluate the influence of the mitochondrial DNA (mtDNA) haplogroups in the risk of incident knee osteoarthritis (OA) and to explain the functional consequences of this association to identify potential diagnostic biomarkers and therapeutic targets. METHODS: Two prospective cohorts contributed participants. The osteoarthritis initiative (OAI) included 2579 subjects of the incidence subcohort, and the cohort hip and cohort knee (CHECK) included 635, both with 8-year follow-up. The analysis included the association of mtDNA haplogroups with the rate of incident knee OA in subjects from both cohorts followed by a subsequent meta-analysis. Transmitochondrial cybrids harbouring haplogroup J or H were constructed to detect differences between them in relation to physiological features including specific mitochondrial metabolic parameters, reactive oxygen species production, oxidative stress and apoptosis. RESULTS: Compared with H, the haplogroup J associates with decreased risk of incident knee OA in subjects from OAI (HR=0.680; 95% CI 0.470 to 0.968; p<0.05) and CHECK (HR=0.728; 95% CI 0.469 to 0.998; p<0.05). The subsequent meta-analysis including 3214 cases showed that the haplogroup J associates with a lower risk of incident knee OA (HR=0.702; 95% CI 0.541 to 0.912; p=0.008). J cybrids show a lower free radical production, higher cell survival under oxidative stress conditions, lower grade of apoptosis as well as lower expression of the mitochondrially related pro-apoptotic gene BCL2 binding component 3 (BBC3). In addition, J cybrids also show a lower mitochondrial respiration and glycolysis leading to decreased ATP production. CONCLUSIONS: The physiological effects of the haplogroup J are beneficial to have a lower rate of incident knee OA over time. Potential drugs to treat OA could focus on emulating the mitochondrial behaviour of this haplogroup.

Characterization of chronic HCV infection in Northwest Spain: Impact of the treatment strategic plan of the Spanish National Health Service on HCV cure.

The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.

A replication study and meta-analysis of mitochondrial DNA variants in the radiographic progression of knee osteoarthritis.

OBJECTIVE: To conduct a replication study and meta-analysis involving the study of mtDNA variants in the radiographic progression of OA in different cohorts worldwide, including Cohort Hip and Cohort Knee (CHECK), the OA Initiative and a cohort from Spain. METHODS: The influence of the haplogroups in the rate of radiographic progression at 96 months in 431 subjects from CHECK was assessed in terms of Kellgren and Lawrence (KL) grade. Progression was defined as a change from KL ⩾ 1 at baseline to any higher grade during the follow-up. Extended Cox proportional hazard models were used to analyse the influence of mtDNA variants in the rate of radiographic knee OA progression. A subsequent meta-analysis of 1603 subjects following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted to combine the data of individual studies. A sensitivity analysis was performed to validate the stability of the results. RESULTS: CHECK subjects carrying the haplogroup T showed the lowest rate of radiographic knee OA progression [hazard ratio (HR) 0.645 (95% CI 0.419, 0.978); P < 0.05]. When pooled, subjects within the superhaplogroup JT showed the same trend [HR 0.707 (95% CI 0.501, 0.965); P < 0.05]. BMI [HR 1.046 (95% CI 1.018, 1.073); P < 0.05] and bilateral OA [HR 2.266 (95% CI 1.733, 2.954); P < 0.05] at baseline are risk factors for radiographic knee OA progression as well. In the meta-analysis there was a reduced rate of radiographic progression in subjects with haplogroup T [HR 0.612 (95% CI 0.454, 0.824); P = 0.001] or in the superhaplogroup JT [HR 0.765 (95% CI 0.624, 0.938); P = 0.009]. Sensitivity analysis revealed that the results were robust. CONCLUSION: The mtDNA variants in the superhaplogroup JT associate with a reduced rate of radiographic OA progression. The mtDNA polymorphisms in the superhaplogroup JT emerge as potential complementary genetic biomarkers for disease progression.

Trends in hospital admissions, re-admissions, and in-hospital mortality among HIV-infected patients between 1993 and 2013: Impact of hepatitis C co-infection.

BACKGROUND: New patterns in epidemiological characteristics of people living with HIV infection (PLWH) and the introduction of Highly Active Antiretroviral Therapy (HAART) have changed the profile of hospital admissions in this population. The aim of this study was to evaluate trends in hospital admissions, re-admissions, and mortality rates in HIV patients and to analyze the role of HCV co-infection. METHODS: A retrospective cohort study conducted on all hospital admissions of HIV patients between 1993 and 2013. The study time was divided in two periods (1993-2002 and 2003-2013) to be compared by conducting a comparative cross-sectional analysis. RESULTS: A total of 22,901 patient-years were included in the analysis, with 6917 hospital admissions, corresponding to 1937 subjects (75% male, mean age 36±11 years, 37% HIV/HCV co-infected patients). The median length of hospital stay was 8 days (5-16), and the 30-day hospital re-admission rate was 20.1%. A significant decrease in hospital admissions related with infectious and psychiatric diseases was observed in the last period (2003-2013), but there was an increase in those related with malignancies, cardiovascular, gastrointestinal, and chronic respiratory diseases. In-hospital mortality remained high (6.8% in the first period vs. 6.3% in the second one), with a progressive increase of non-AIDS-defining illness deaths (37.9% vs. 68.3%, P<.001). The admission rate significantly dropped after 1996 (4.9% yearly), but it was less pronounced in HCV co-infected patients (1.7% yearly). CONCLUSIONS: Hospital admissions due to infectious and psychiatric disorders have decreased, with a significant increase in non-AIDS-defining malignancies, cardiovascular, and chronic respiratory diseases. In-hospital mortality is currently still high, but mainly because of non-AIDS-defining illnesses. HCV co-infection increased the hospital stay and re-admissions during the study period.

Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

OBJECTIVES: The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA <50 copies/mL) on ART. METHODS: Newly diagnosed (2004-13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan-Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. RESULTS: A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524-11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA <20 copies/mL) [HR 3.813 (95% CI 0.675-21.535)]. Moreover, only HIV-infected patients with at least three consecutive detected, but not quantified, HIV-RNA determinations showed a higher probability of virological rebound with >200 copies/mL [33.7% at 24 and 60 months versus <5% for other HIV-RNA values; HR 6.943 (0.728-66.261), P = 0.092]. CONCLUSIONS: Blips are frequent (22.7%) among HIV-infected patients with sustained virological suppression on ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL).

Long-term clinical experience with darunavir (2007-2015) in a large cohort of HIV-infected patients in Spain.

The clinical experience with the protease inhibitor darunavir/ritonavir (DRV/r) was retrospectively evaluated in a cohort of 173 HIV+ patients who initiated antiretroviral treatment including DRV/r (period 2007-2015). The 43.2% had a CD4 nadir ≤100 cells/mm3 , 64.1% were treatment-experienced, and 36.5% had failed to >3 lines of antiretroviral therapy. Nonetheless, the rate of virological suppression (HIV-RNA <50 copies/ml) in naïve patients was 63%, 66.7%, and 63.6% at 48, 96, and 144 weeks, respectively. The rate of virological suppression in treatment-experienced patients was 62.7%, 78.7%, and 79.1% at 48, 96, and 144 weeks, respectively. No differences were observed according to the immunovirological status neither dosage of DRV/r. Most of them (82.6%) maintained DRV/r treatment. Causes for DRV/r discontinuation were mainly gastrointestinal and cutaneous adverse events (10.5%), switch to simplification treatment strategies (3.5%) and virological failure (1.7%). These findings demonstrate the prolonged efficacy and tolerability of DRV/r even in multi-treated HIV+ patients with an unfavorable immunovirological status. J. Med. Virol. 88:2125-2131, 2016. © 2016 Wiley Periodicals, Inc.

Predicting mortality in burn patients with bacteraemia.

OBJECTIVE: To determine factors associated with mortality in burn patients with bacteraemia. BACKGROUND: Previous studies have shown the negative impact of bacteraemia on the prognosis of burn patients, but only a few of these have analysed variables intervening in the clinical progress of these patients. METHODS: A retrospective study of adult burn patients (n = 73) with bacteraemia (103 episodes) in a Burns Unit during the 2000-2013 period. The study collected demographic variables, and comorbidity, injury-related and clinical data related to bacteraemia. Variables related to hospital mortality were analysed using a multiple logistic regression model. RESULTS: The cumulative incidence of bacteraemia was 4.4 episodes/100 patients. The mean age was 53.3 ± 19.2 years (65.8 % male). The median total body surface area (TBSA) was 35 %, while 50.7 % of the population had inhalation syndrome. The mean SOFA score at the onset of bacteraemia was 2.7 ± 3.8. The most common pathogen was Pseudomonas aeruginosa (17.5 %). The mortality rate was 24.7 %. The variables that were significantly associated with mortality were age (OR = 1.13), TBSA (OR = 1.05), SOFA score at the onset of bacteraemia (OR = 1.53) and recurrent bacteraemia (OR = 41.6). CONCLUSION: In addition to conventional risk factors, recurrence and organ dysfunction at the onset of bacteraemia are also associated with mortality, while the pathogen involved is not a prognostic factor.

Rhabdomyolysis and acute kidney injury in patients with traumatic spinal cord injury.

BACKGROUND: Patients with acute traumatic spinal cord injuries (SCIs) exhibit factors that, in other populations, have been associated with rhabdomyolysis. PURPOSE: The aim of the study is to determine the incidence of rhabdomyolysis in patients with acute traumatic SCI admitted to the Intensive Care Unit (ICU), as well as the development of secondary acute kidney injury and associated factors. STUDY DESIGN AND SETTING: This was an observational, retrospective study. PATIENT SAMPLE: All adult patients admitted to the ICU with acute traumatic SCI who presented rhabdomyolysis, diagnosed through creatine phosphokinase (CPK) levels >500 IU/L. OUTCOME MEASURES: Incidence of rhabdomyolysis and subsequent renal dysfunction was calculated. MATERIALS AND METHODS: Data about demographic variables, comorbidity, rhabdomyolysis risk factors, and variables involving SCI, severity scores, and laboratory parameters were obtained from clinical records. Multivariate logistic regression was used to identify renal injury risk factors. RESULTS: In 2006-2014, 200 patients with acute SCI were admitted to ICU. Of these, 103 had rhabdomyolysis (incidence = 51.5%; 95% confidence interval [CI]: 44.3%-58.7%). The most typical American Spinal Injury Association classification was A (70.3%). The injury severity score was 30.3 ± 12.1 and sequential organ failure assessment (SOFA) score was 5.6 ± 3.3 points. During their stay, 57 patients (55.3%; 95% CI: 45.2%-65.4%) presented renal dysfunction (creatinine ≥1.2 mg/dL). In the multivariate analysis, variables associated with renal dysfunction were creatinine at admission (odds ratio [OR] = 9.20; P = 0.006) and hemodynamic SOFA score the day following admission (OR = 1.33; P = 0.024). Creatinine was a better predictor of renal dysfunction than the peak CPK value during the rhabdomyolysis (area under the receiver operating characteristic curve: 0.91 vs. 0.63, respectively). CONCLUSIONS: Rhabdomyolysis is a frequent condition in patients with acute traumatic SCI admitted to the ICU, and renal dysfunction occurs in half of the cases. Creatinine values should be requested starting at the admission while neither the peak CPK values nor the hemodynamic SOFA scores could be used to properly discriminate between patients with and without renal dysfunction.

Tracheostomy in the management of patients with thermal injuries.

OBJECTIVE: To assess the use and clinical impact of tracheostomy in burn patients. SUMMARY BACKGROUND DATA: The role of tracheostomy in the management of burn patients is controversial, with only a few recent studies conducted in this population. METHODS: Retrospective study of all adult burn patients who underwent a tracheostomy in a Burns Unit between 1995 and 2013. These were compared with a control group (1:1) who underwent orotracheal intubation. Hospital records were reviewed to obtain demographic and clinical information, including those related to respiratory support and tracheostomy. The McNemar's Chi-square and Signed-Rank Tests were used to study differences in morbimortality between both groups. RESULTS: A total of n = 20 patients underwent tracheostomy (0.9% of admissions, 56.0 ± 19.5 years, 60.0% women). The most common indication was long-term ventilation (75%), 24.6 ± 19.7 days after admission. Thirteen patients were successfully decannulated with a fatal complication observed in one case. Patients in the tracheostomy group were found to require longer-term mechanical ventilation (43.2 vs. 20.4 days; P = 0.004), with no differences in respiratory infection rates (30.0% vs. 31.6%; P = 0.687) or mortality (30.0% vs. 42.1%; P = 0.500). Ventilator weaning times (15.7 vs. 3.3 days; P = 0.001) and hospital stays (99.1 vs. 53.1 days; P = 0.030) were longer in the tracheostomy group, with no differences in duration of sedation. CONCLUSIONS: Tracheostomy may be a safe procedure in burn patients and is not associated with higher rates of mortality or respiratory infection. Tracheostomy patients showed longer mechanical ventilation times and higher morbidity, probably not attributable to tracheostomy.

Association of urinary excretion rates of uric acid with biomarkers of kidney injury in patients with advanced chronic kidney disease.

BACKGROUND: The potential influence of hyperuricemia on the genesis and progression of chronic kidney disease (CKD) remains controversial. In general, the correlation between blood levels of uric acid (UA) and the rate of progression of CKD is considered to be modest, if any, and the results of relevant trials oriented to disclose the effect of urate-lowering therapies on this outcome have been disappointing. Urinary excretion rates of UA could reflect more accurately the potential consequences of urate-related kidney injury. METHOD: Using a cross-sectional design, we investigated the correlation between different estimators of the rates of urinary excretion of UA (total 24-hour excretion, mean urinary concentration, renal clearance and fractional excretion)(main study variables), on one side, and urinary levels of selected biomarkers of kidney injury and CKD progression (DKK3, KIM1, NGAL, interleukin 1b and MCP)(main outcome variables), in 120 patients with advanced CKD (mean glomerular filtration rate 21.5 mL/minute). We took into consideration essential demographic, clinical and analytic variables with a potential confounding effect on the explored correlations (control variables). Spearman's rho correlation and nonlinear generalized additive regression models (GAM) with p-splines smoothers were used for statistical analysis. MAIN RESULTS: Multivariate analysis disclosed independent correlations between urinary UA concentrations, clearances and fractional excretion rates (but not plasma UA or total 24-hour excretion rates of UA), on one side, and the scrutinized markers. These correlations were more consistent for DKK3 and NGAL than for the other biomarkers. Glomerular filtration rate, proteinuria and treatment with statins or RAA axis antagonists were other independent correlates of the main outcome variables. CONCLUSIONS: Our results support the hypothesis that urinary excretion rates of UA may represent a more accurate marker of UA-related kidney injury than plasma levels of this metabolite, in patients with advanced stages of CKD. Further, longitudinal studies will be necessary, to disclose the clinical significance of these findings.

Exposure to paracetamol and asthma symptoms.

BACKGROUND: Paracetamol is one of the factors that have been associated with the observed increase in asthma prevalence in the last few years. The influence of environmental or genetic factors in this disease may be different in some countries than in others. The purpose of this study was to analyse the relationship between the paracetamol consumption and asthma prevalence in our community. METHODS: A cross-sectional study was conducted on more than 20,000 children and adolescents in Galicia, Spain. The International Study of Asthma and Allergies in Childhood methodology was used to collect the information on asthma symptoms in children, paracetamol consumption, body mass index (BMI), pets in the home, education level of the mother and parental asthma and smoking habits. The influence of paracetamol consumption on the prevalence of asthma symptoms was calculated using logistic regression, adjusted for the other parameters included in the study. RESULTS: After adjusting for gender, BMI, having a cat or dog, maternal education, parental asthma and smoking, in 6- to 7-year-old children, the consumption of paracetamol during the first year of life is associated with asthma [odds ratio (OR) 2.04 (1.79-2.31) for wheezing at some time]. Paracetamol consumption in the previous year leads to a significant increase in the probability of wheezing at some time [OR 3.32 (2.51-4.41)] in young children and adolescents [OR 2.12 (1.68-2.67)]. CONCLUSIONS: Paracetamol consumption is associated with a significant increase in asthma symptoms. The effect is greater the more often the drug is taken.

Surgical treatment for necrotizing enterocolitis: a new score to extreme surveillance.

BACKGROUND: The time to perform a surgical intervention in necrotizing enterocolitis remains a challenge for the pediatric surgeon. We design a novel score system to predict infants in high risk for the development of surgical necrotizing enterocolitis. METHODS: A total of 124 consecutively patients diagnosed of NEC at the University Hospital of A Coruña, Spain were included in the study. Associations were analyzed by bivariate and multivariate analysis. We applied multivariate logistic regression modeling to identify factors that could provide accurate risk of surgical NEC. We include not only analytical and radiological parameters or physical examination, but we also analyzed prenatal, sociodemographic, perinatal and peripartum variables that conditioned the presence of predispose factors, which could determine the debut of this entity and in its progression. RESULTS: Patients requiring surgical treatment have presented an antecedent of respiratory distress (worsening of the ventilatory requirements) in the perinatal period, they present higher values of glycemia at diagnosis of the illness, debut with coagulopathy and have in laboratory findings marked neutrophilia. CONCLUSIONS: Our score system obtained by combining several parameters could detect infants at risk of developing severe necrotizing enterocolitis improving the morbidity and mortality associated with delay in the surgical treatment.

Brachytherapy for the treatment of recurrent prostate cancer after radiotherapy or radical prostatectomy.

What's known on the subject? and What does the study add? The curative treatment of prostate cancer includes surgery, external beam radiation or interstitial radiation. However, a high percentage of patients may develop recurrent disease, which is often localised. The possibilities of treatment in these cases, including surgery or adjuvant radiotherapy, are not well defined. Brachytherapy is a well established first-line treatment option. We review and update the use of brachytherapy in the treatment of recurrences post-radiotherapy, brachytherapy or radical prostatectomy as an alternative to surgery and radiotherapy, with a focus on functional and oncological outcomes. Salvage therapeutic options following radical prostatectomy or radiotherapy for patients with local relapse of prostate cancer include radical prostatectomy, radiotherapy, brachytherapy or cryotherapy. Salvage radical prostatectomy following radiotherapy failure is associated with a 5-year PSA relapse-free rate of 30-40%. Biochemical relapse-free survival rates after salvage radiotherapy following radical prostatectomy failure range from 10% to 77% after a follow-up of 22-60 months. A number of studies have evaluated salvage brachytherapy for radiotherapy failure and 5-year biochemical disease-free survival (bDFS) rate results reported are of the order of 20-87%; one study reported a 10-year bDFS rate of 54%. Fewer studies in small numbers of patients and with shorter follow-up have been conducted on brachytherapy for radical prostatectomy failure and bDFS rates reported include 25.8% at a median of 29 months to 70% at a median of 20 months. The side-effects were as expected for brachytherapy. A newer initiative conducted in Spain in a larger series of 42 patients with failure following radical prostatectomy involves brachytherapy with RAPID Strand™(125) I seeds and real-time placement. The 5-year bDFS rate was 88.6% and cancer-specific survival was 97%; complication rates were low. Optimization of salvage brachytherapy is under way and involves accurate placement of seeds, dose optimization and optimal patient selection.

Evaluation of the adenocarcinoma-associated gene AGR2 and the intestinal stem cell marker LGR5 as biomarkers in colorectal cancer.

We aim to estimate the diagnostic performances of anterior gradient homolog-2 (AGR2) and Leucine-rich repeat-containing-G-protein-coupled receptor 5 (LGR5) in peripheral blood (PB) as mRNA biomarkers in colorectal cancer (CRC) and to explore their prognostic significance. Real-time PCR was used to analyze AGR2 and LGR5 in 54 stages I-IV CRC patients and 19 controls. Both mRNAs were significantly increased in PB from CRC patients compared to controls. The area under the receiver-operating characteristic curves were 0.722 (p = 0.006), 0.376 (p = 0.123) and 0.767 (p = 0.001) for AGR2, LGR5 and combined AGR2/LGR5, respectively. The AGR2/LGR5 assay resulted in 67.4% sensitivity and 94.7% specificity. AGR2 correlated with pT3-pT4 and high-grade tumors. LGR5 correlated with metastasis, R2 resections and high-grade. The progression-free survival (PFS) of patients with high AGR2 was reduced (p = 0.037; HR, 2.32), also in the stage I-III subgroup (p = 0.046). LGR5 indicated a poor prognosis regarding both PFS (p = 0.007; HR, 1.013) and overall survival (p = 0.045; HR, 1.01). High AGR2/LGR5 was associated with poor PFS (p = 0.014; HR, 2.8) by multivariate analysis. Our findings indicate that the assessment of AGR2 and LGR5 in PB might reflect the presence of circulating tumor cells (CTC) and stem cell like CTC in CRC. Increased AGR2 and LGR5 are associated with poor outcomes.

PROCOAC (PROspective COhort of A Coruña) description: Spanish prospective cohort to study osteoarthritis.

INTRODUCTION AND OBJECTIVE: The use of well characterized osteoarthritis (OA) cohorts is mandatory for the study and knowledge of this disease. Currently, there is no prospective cohort in this pathology in Spain. The objective of this work is to describe the first osteoarthritis cohort in Spain, PROCOAC (Cohort PROspectiva de A Coruña). METHODS: The Unit of Rheumatology of the University Hospital of A Coruña started a prospective follow-up study in 2006. The patient inclusion criteria were: I) Patients older than 55 years who underwent an abdominal x-ray to study both hips II) Patients diagnosed with radiographic hand OA according to ACR criteria III) Patients diagnosed with radiographic knee or hip OA according to ACR criteria. Follow-up was performed every two years collecting clinical, analytical, genetic and radiographic information. RESULTS: The cohort consists of 937 patients, 873 have radiographic knee OA, 783 hip OA and 679 hand OA. The mean age of the population is 63.9±8.9 years and the average BMI is 29.6±5.1. More than half of the population has high blood pressure and 17% diabetes. The predominant osteoarthritis in the hand is nodular (78.1%), followed by trapeziometacarpal (55.3%) and erosive (18.4%). Twenty-one point four percent and 43.1% are healthy at knee and hip level respectively; observing a grade 1 in 26% and 37%; a grade 2 in 26.7% and 11.5%; a grade 3 in 14.9% and 4%; and a grade 4 in 9.4% and 3.7% respectively. Of the population, 44.1% has only 1 joint affected, 39.9% has 2 and 13.4% has 3 joints affected. Age (OR=1.11; p<.001), BMI (OR=1.11; p=.002) and total WOMAC (OR=1.03; p=.005) are the only risk factors if we compare the involvement of a single location versus three. A discrepancy between pain and radiographic damage at the joint level was also detected in patients with KL≤2 grade, and therefore a significantly higher percentage of patients with knee OA experienced pain (66.1%) compared to patients with OA hip (21.1%) (p<.001). CONCLUSIONS: The PROCOAC cohort is an instrument that allows studies of incidence and progression in hand, knee and hip OA; as well as determining factors that are associated with the different OA phenotypes.

Impact of a Home Telehealth Program After a Hospitalized COPD Exacerbation: A Propensity Score Analysis.

INTRODUCTION: Currently there is lack of data regarding the impact of a home telehealth program on readmissions and mortality rate after a COPD exacerbation-related hospitalization. OBJECTIVE: To demonstrate if a tele-monitoring system after a COPD exacerbation admission could have a favorable effect in 1-year readmissions and mortality in a real-world setting. METHODS: This is an observational study where we compared an intervention group of COPD patients treated after hospitalization that conveyed a telehealth program with a followance period of 1 year with a control group of patients evaluated during one year before the intervention began. A propensity-score analyses was developed to control for confounders. The main clinical outcome was 1-year all-cause mortality or COPD-related readmission. RESULTS: The analysis comprised 351 telemonitoring patients and 495 patients in the control group. The intervention resulted in less mortality or readmission after 12 months (35.2% vs. 45.2%; hazard ratio [HR] 0.71 [95% CI=0.56-0.91]; p=0.007). This benefit was maintained after the propensity score analysis (HR=0.66 [95% CI=0.51-0.84]). This benefit, which was seen from the first month of the study and during its whole duration, is maintained when mortality (HR=0.54; 95% CI=[0.36-0.82]) or readmission (subdistribution hazard ratio [SHR] 0.66; 95% CI=[0.50-0.86]) are analyzed separately. CONCLUSION: Telemonitoring after a severe COPD exacerbation is associated with less mortality or readmissions at 12 months in a real world clinical setting.

Mitochondrial DNA (mtDNA) haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis.

BACKGROUND: Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA) haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2) and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. METHODS: We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI), age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. RESULTS: Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p < 0.001). Even in those OA patients with higher OA severity (K/L grade IV), the serum levels of this antioxidant enzyme appeared more significantly increased than in OA patients with lower K/L grade (p < 0.001). The mtDNA haplogroups showed an influence on serum levels of catalase (p = 0.054), being carriers of the mtDNA haplogroup J those who showed higher serum levels than non-J carriers (p = 0.057). CONCLUSIONS: The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase.