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Introduction We performed cost-effectiveness and cost-utility analyses of the modified International Consortium on Acute Promyelocytic Leukemia protocol in Mexico for the treatment of acute promyelocytic leukemia Acute Promyelocytic Leukemia. Methods We performed a three-state Markov analysis: stable disease (first line complete response [CR]), disease event (relapse, second line response and CR) and death. The modified IC-APL protocol is composed of three phases: induction, consolidation and maintenance. Cost and outcomes were used to calculate incremental cost-effectiveness ratios (ICERs); quality-adjusted life-years were used to calculate incremental cost-utility ratios (ICURs). Results The CR was achieved in 18 patients (90%), treated with the IC-APL protocol as the first-line option; one patient (5%) died in induction, another one never achieved CR (5%); of the 18 patients that achieved CR, 1 relapsed (5.5%). The median treatment cost of the IC-APL protocol was $21,523 USD. The average life-year in our study was 7.8 years, while the average quality-adjusted life-year (QALY) was 6.1 years. When comparing the ICER between the IC-APL and the all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) protocols, we found the different costs of $6497, $19,133 and $17,123 USD in Italy, the USA and Canada, respectively. In relation to the ICUR, we found the different costs to be $13,955 and $11,979 USD in the USA and Canada, respectively. Conclusion Taking into account the similar response rates, lower cost and easy access to the modified IC-APL regimen, we consider it a cost-effective and cost-utility protocol, deeming it the treatment of choice for our population.

The hepatitis B (HBV) vaccine is recommended in unvaccinated adults with cirrhosis, despite its low efficacy. We aimed to evaluate the response to a double-dose/accelerated vaccine schedule in patients with cirrhosis admitted into a hepatology ward. All patients with cirrhosis admitted to the hepatology ward without exclusion criteria were offered the HBV HBVAXPRO 40mcg vaccine at months 0, 1 and 2. Non-responders received a second cycle. We evaluated 468 patients and only 19% were seroprotected against HBV. In 196 patients without exclusion criteria for HBV vaccination, the per protocol response rate (anti-HBs >10 U/ml) was 23% after a first cycle and 59% after a second cycle. The overall response per intention to treat was only 23%. We have not identified predictors of response. Only one patient had a mild adverse event. Most patients with cirrhosis admitted in the hepatology ward are unprotected against HBV. Although a second HBV vaccination cycle increases the response rate, the poor overall response reinforces the implementation of HBV vaccination before the development of cirrhosis.

Tursiops truncatus gephyreus is only found in the inshore waters of the Southwestern Atlantic Ocean. They are organized in small socially, structured groups, which lead to low genetic variability and high anthropogenic threats. Currently, the information about their reproductive biology and management is still insufficient. Thus, this study aims to present novel information recorded for 20 years regarding reproductive parameters in a small population of captive T. t. gephyreus. Three of the animals involved were found stranded in La Plata River estuary and, the other two were born at the oceanarium. Thirteen semen evaluations showed high-quality semen with a low percentage of sperm abnormalities. Twelve pregnancies and parturitions were observed. There was a clear calving seasonality during austral spring and summer. The duration of phase-2 of labor was approximately 80 min, being the caudal presentation the most frequent. The average inter-birth interval (IBI) was about 33 months. This is the first report that closely monitored parturition, IBI, and seminal evaluation in this species. Information gathered during this program will allow the development of adequate conservation plans for free-ranging populations.

Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53-65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.

Complications of cirrhosis are the main cause of hospital admissions in liver units. In areas where HCV is prevalent, most of these admissions are attributable to HCV-related cirrhosis (HCV-cirrhosis). This study assessed the impact of direct-acting antivirals (DAA) in the profile of patients with liver disease admitted to a referral liver unit from a university hospital.We registered hospital admissions resulting from cirrhosis to the Liver Unit of the Hospital Clinic of Barcelona, from 2011 to 2014 (pre-DAA period) and from 2015 to 2019 (post-DAA period).From a total of 14,865 hospital admissions, 10,053 resulted from cirrhosis (corresponding to 6,272 patients). The number and proportion of hospital admissions because of HCV-cirrhosis remained stable during the period 2011-2014 (525 per year, 48.8% of the total), but decreased progressively after 2015 (p0.001), reaching300 (27.1%) admissions in 2019. Similarly, HCV-cirrhosis accounted for 3,885 inpatient days per year (44.9%) during the pre-DAA period and decreased steadily after 2015 (p0.001), reaching only 1,909 inpatient days (22%) in 2019. The figures for intensive care unit admissions followed a similar pattern. By means of a slope analysis (binomial regression model), we predicted that HCV-cirrhosis hospital admissions will be residual by 2025 (2.3%, 95% CI 0-10.9%). By contrast, we observed a significant increase in hospital admissions because of metabolic-associated fatty liver disease (5-fold) and autoimmune hepatitis (4-fold) during the study period.In summary, our data showed a profound reduction in HCV-cirrhosis hospitalisation burden since 2015, coincident with the wide use of DAAs in Spain. Our predictions suggest that, by 2025, HCV-cirrhosis will be a marginal cause of hospital admissions for patients with liver disease.Over the past few years, the wide use of antiviral drugs that cure HCV has had a significant effect on patients being admitted to hospital. Most patients with HCV and cirrhosis are treated (and often cured) in the community and, thus, the number of hospital admissions because of severe forms of HCV has decreased drastically. HCV is no longer the first cause of admission into liver units and, in only a few years from now, it is likely to be only a residual cause of hospitalisation.

Background Since 2006 breast cancer has been the leading cause of death by cancer in Mexican women. Recently several studies have shown the relationship of neutrophil-lymphocyte index (NLI) and breast cancer as a predictor of overall survival (OS) and disease-free survival (DFS). Methods The study included 2711 patients of the Institute of Breast Diseases (FUCAM) treated since April 2006 to March 2011. The NLI and its relation with OS and DFS were evaluated. A receiver operating characteristic curve was used to obtain the cut-off point of greater sensitivity and specificity for the NLI. A multivariate analysis was used to analyze the clinical parameters of prognostic factor. Results 342 patients were included for the analysis. The follow-up time average of 80.1 months and the mean of NLI was 2.1. In this model, sensitivity was 66.7% (95% CI: 46–64) p = 0.04. The Kaplan–Meier analysis was applied to evaluate OS and the DFS of all patients according to the NLI, comparing two groups: ≤2.1 and ≥ 2.1. No differences were reported between these groups. In triple negative patients (n = 32), patients with NLI > 2.1 had a shorter DFS in comparison to patients with NLI 2.1 pretreatment, lymph node stage and Ki-67 were correlated independently with the DFS. Conclusions Our study suggests that there is a relationship between the NLI and the breast cancer DFS; especially in triple negative subtypes.

Chronic hepatitis C virus (HCV) infection impairs HCV CD8+ T-cell responses, while it could influence immune responses towards unrelated viruses/vaccines (e.g. cytomegalovirus, CMV, and influenza, Flu). The aim of our study was to delineate whether restoration of these virus-specific CD8+ T cells occurs after direct-acting antiviral (DAA) therapies and particularly in patients with cirrhosis. We performed longitudinal analysis (baseline, week 4, follow-up [FU] 12 and FU48) of virus-specific CD8+ T cells by multicolour flow cytometry in HCV-cirrhotic patients undergoing DAA therapy (n = 26) after in vitro expansion with immunodominant HCV, CMV and Flu epitopes restricted by HLA-A*02. HCV noncirrhotic patients (n = 9) and healthy individuals (n = 10) served as controls. We found that the proliferative capacity of HCV-specific CD8+ T cells increased from baseline up to FU48 in a significant proportion of cirrhotic and noncirrhotic patients. Nevertheless, these cells remained poor cytokine producers in both patient groups, regardless of the down-regulation of inhibitory co-regulatory receptors in HCV-cirrhotic patients at FU48. Likewise, high expression levels of these exhaustion markers were detected in CMV-/Flu-specific CD8+ T cells in HCV-cirrhotic patients at all time points, albeit without affecting their proliferative capacity or cytokine production. We conclude that DAA therapies induce restoration of the proliferative capacity of HCV-specific CD8+ T cells. However, these cells remain phenotypically and functionally impaired. Contrarily, the 'exhausted' phenotype in CMV-/Flu-specific CD8+ T cells in HCV-cirrhotic patients did not associate with their functions. Larger studier with longer follow-up may elucidate whether this complex interplay influences the outcome of cirrhotic patients.

Background Hepatitis C virus (HCV) is a risk factor for porphyria cutanea tarda (PCT), a rare disease originating in the liver characterised by overproduction of porphyrins. Although hepatitis C infection is highly prevalent among patients with porphyria, only a minority of hepatitis C patients develop PCT. Aims To explore the presence of porphyrin abnormalities in a cohort of asymptomatic hepatitis C-infected patients and the impact of anti-viral therapy. Methods Eighty-four consecutive patients with HCV infection treated with direct-acting antivirals after 1 January 2018 were longitudinally evaluated for the presence of porphyrin abnormalities. Those patients with biochemical abnormalities at baseline were additionally evaluated at follow-up. Porphyrins in urine were screened by fluorometry and isomer separation was performed by liquid chromatography. Results In five patients, all of them asymptomatic, porphyrin profile abnormalities were detected: three presented significant increased urinary porphyrins with a typical PCT profile, and two showed normal levels of urinary porphyrins, but abnormal porphyria-like profiles. Urine evaluation after hepatitis C cure showed complete normalisation of the urinary porphyrins in all patients, confirming the biochemical cure of the disease. Conclusions We document the existence of rare cases of hepatitis C-infected patients with significant uroporphyrinuria in the absence of dermatological manifestations. Anti-viral therapy normalises the biochemical disorder, preventing patients from presenting PCT associated complications.

It is important to know which patients with hepatitis C are likely to develop liver-related complications after achieving a sustained virological response (SVR) to direct-acting antiviral (DAA) therapy. We aimed to describe the incidence of liver-related events in a population of patients with HCV-associated compensated advanced chronic liver disease (cACLD) who achieved SVR and to identify non-invasive parameters that predict the occurrence of liver-related events.This 2-center prospective study included 572 patients with cACLD who had been treated with DAAs and had achieved SVR. Patients had liver stiffness measurement (LSM) ≥10 kPa at baseline and had never decompensated (Child-Pugh class A). Laboratory work-up and LSM were performed at baseline and at 1 year of follow-up.The median follow-up was 2.8 years during which 32 patients (5.6%) presented with a liver-related event. The incidence rate (IR) of portal hypertension-related decompensation was 0.34/100 patient-years. These patients all had baseline LSM20 kPa, and LSM did not improve during follow-up in 4 out of 5 of them. Hepatocellular carcinoma (HCC) occurred in 25 patients (IR 1.5/100 patient-years). Albumin levels at follow-up (hazard ratio [HR] 0.08; 95% CI 0.02-0.25) and LSM10 kPa at follow-up (HR 0.33; 95% CI 0.11-0.96) were independently associated with the risk of HCC. Combining both predictors identified 2 groups with differing risk of HCC occurrence: those with LSM ≥20 kPa at follow-up or those with LSM between 10-20 kPa and albumin levels4.4 g/dl were at the highest risk (IR ≥1.9/100 patient-years). Visual nomograms predicting HCC risk based on LSM and albumin at 1 year of follow-up were constructed.In patients with HCV-related cACLD who have achieved SVR with DAAs, HCC is the most frequent liver-related event. Both albumin levels and LSM are useful for stratifying patients based on their risk of developing HCC during follow-up.New oral antivirals can cure chronic hepatitis C infection, however patients with advanced chronic liver disease are still at risk of presenting with liver-related complications. The most frequent complication after oral antiviral therapy in asymptomatic patients with advanced chronic liver disease was liver cancer. The use of simple parameters such liver stiffness and albumin levels after treatment can help to identify patients at higher or lower risk of liver cancer.

Background and aims Recent studies have found an increase in the seroprevalence of hepatitis E virus (HEV) infection in patients with autoimmune hepatitis (AIH). We aimed to assess the prevalence of positive anti-HEV IgM and IgG, and HEV-RNA in a cohort of patients with AIH, to determine the impact of positive HEV serology on patient outcome, and to evaluate the role of hypergammaglobulinemia and positive autoantibodies in the presence of positive anti-HEV serology. Methods One hundred and five patients tested for HEV infection between 2014 and 2018 were included in the study: 50 with chronic AIH (more than 1 year on treatment), and 55 with an acute hepatitis (30 patients with acute AIH and 25 with non-AIH). Results Seroprevalence of HEV was higher in patients with acute AIH (17% vs 10% in patients with chronic AIH and 8% in patients with non-AIH). Patients with acute AIH and positive anti-HEV IgG were older (58 vs 40; P = .006), had higher IgG levels (27 g/dL vs 13 g/dL; P = .03) and antismooth muscle antibodies (ASMA) titres (1:160 vs 1:80; P = .045), and were more likely to have another autoimmune disease (60% vs 16%; P = .03). At the time of HEV testing, anti-HEV IgG positive patients had significantly higher serum IgG levels (17 g/L vs 11 g/L; P = .009), ANA (1:160 vs 1:60; P = .026) and ASMA titres (1:80 vs 1:40; P = .021). Conclusion Seroprevalence of HEV in patients with AIH in Catalonia does not differ from that of the general population. The higher HEV seroprevalence in patients with acute AIH with higher levels of gammaglobulins and high antibody titres suggest the presence of cross-reactivity between HEV and liver antigens.

Hepatitis E virus (HEV) and hepatitis A virus (HAV) are both secreted in feces. Despite HEV transmission in Europe is mainly zoonotic, person-to-person transmission has not been completely excluded. Men who have sex with men (MSM) constitute a high-risk group for HAV mostly due to oral sex. We investigated the potential transmission of HEV during an acute hepatitis A (AHA) outbreak mainly affecting MSM. One hundred and two patients were diagnosed with AHA. Sixty-nine (68%) self-reported to be MSM, 75% of whom had high-risk sexual behaviors and 46% had suffered previous sexually transmitted diseases. We collected serum from 85 (83%) patients during AHA. HEV-IgG seroprevalence was not different among MSM (7%) compared with non-MSM (8%) patients. Two patients had positive anti-HEV-IgM, but all samples tested negative for HEV-RNA. These results suggest that HEV does not spread by sexual contact or person-to-person in our area.

Background: Antimalarial drugs were widely used as experimental therapies against COVID-19 in the initial stages of the pandemic. Despite multiple randomized controlled trials demonstrating unfavorable outcomes in both efficacy and adverse effects, antimalarial drugs are still prescribed in developing countries, especially in those experiencing recurrent COVID-19 crises (India and Brazil). Therefore, real-life experience and pharmacovigilance studies describing the use and side effects of antimalarials for COVID-19 in developing countries are still relevant.Objective: To describe the adverse effects associated with the use of antimalarial drugs in hospitalized patients with COVID-19 pneumonia at a reference center in Mexico City.Methods: We integrated a retrospective cohort with all adult patients hospitalized for COVID-19 pneumonia from March 13th, 2020, to May 17th, 2020. We compared the baseline characteristics (demographic and clinical) and the adverse effects between the groups of patients treated with and without antimalarial drugs. The mortality analysis was performed in 491 patients who received optimal care and were not transferred to other institutions (210 from the antimalarial group and 281 from the other group).Results: We included 626 patients from whom 38% (n = 235) received an antimalarial drug. The mean age was 51.2 ± 13.6 years, and 64% were males. At baseline, compared with the group treated with antimalarials, the group that did not receive antimalarials had more dyspnea (82 vs. 73%, p = 0.017) and cyanosis (5.3 vs. 0.9%, p = 0.009), higher respiratory rate (median of 28 vs. 24 bpm, p < 0.001), and lower oxygen saturation (median of 83 vs. 87%, p < 0.001). In the group treated with antimalarials, 120 patients had two EKG evaluations, from whom 12% (n = 16) prolonged their QTc from baseline in more than 50 ms, and six developed a ventricular arrhythmia. Regarding the trajectories of the liver function tests over time, no significant differences were found for the change in the mean value per day between the two groups. Among patients who received optimal care, the mortality was 16% (33/210) in those treated with antimalarials and 15% (41/281) in those not receiving antimalarials (RR 1.08, 95% 0.75–1.64, and adjusted RR 1.12, 95% CI 0.69–1.82).Conclusion: The adverse events in patients with COVID-19 treated with antimalarials were similar to those who did not receive antimalarials at institutions with rigorous pharmacological surveillance. However, they do not improve survival in patients who receive optimal medical care.

Background Chronic hepatitis delta is a severe liver disease with rapid progression to cirrhosis. The impact of hepatitis delta virus (HDV)-RNA on disease progression and interferon treatment in a real-world cohort has been barely explored. Aim To assess the development of clinical events in a cohort of chronic hepatitis delta patients according to the presence or absence of HDV-RNA METHODS: Multicentre study at four academic hospitals in Spain included anti-HDV-positive patients with compensated liver disease with a follow-up ≥12 months. Results Among 2888 HBsAg-positive subjects, 151 (5.2%) tested positive for anti-HDV, and 118 were included (58% men; median age, 49 years; 73% detectable HDV-RNA and 30% cirrhosis, most often in subjects with HDV-RNA). After a median follow-up of 8 years, subjects with initially detectable HDV-RNA were more prone to developing cirrhosis (31% vs 0%, P = .002) and/or liver decompensation (28% vs 3%, P = .019). Mortality rate was 0.44 per 1000 person-months. The probability of a clinical event was 6%, 25%, and 80% according to initial baseline-event-anticipation score. HDV-RNA became undetectable in 21 (24%) subjects either due to interferon or spontaneously (48% vs 52%, P = .29). Liver decompensation was reduced in interferon-treated patients (13% vs 38%, P = .026). Conclusions Subjects with persistently positive HDV-RNA had a worse prognosis in terms of clinical events. Baseline-event-anticipation score is useful in predicting the risk of developing liver decompensation and hepatocellular carcinoma. Interferon was beneficial in reducing liver decompensation, even in the absence of virological response.

In some areas of the world, antiviral therapy for chronic hepatitis C (CHC) is not available for all patients. The optimal interval for liver stiffness measures (LSM) and noninvasive scores to assess fibrosis progression has not been studied. We evaluated the usefulness of consecutive LSM, APRI, FIB-4 and Forns scores to predict disease progression.Patients with CHC and at least two annual LSM within 3 years were followed for a minimum of 5 years. Noninvasive scores were assessed. Evolution of LSM and scores were expressed as change/year (Delta).623 non-cirrhotic patients were included. Median baseline LSM was 6.6 kPa (IQR 5.4-8.4). During a median follow-up of 6 years, 61(9.7%) patients developed cirrhosis. Baseline LSM ≥ F2 and Forns ≥ 6.9 were the main predictors of cirrhosis (C-index 0.97). The addition of Delta variables did not improve its prediction. In patients with mild fibrosis (F0-1), progression to ≥F2 occurred in 80 (23%) within the first 3 years. Baseline BMI ≥ 24 kg/mBaseline LSM and Forns are highly predictive of cirrhosis development. In patients with mild CHC, BMI 24 and LSM 5.9, the likelihood of progression is very low, allowing for a significant spacing of noninvasive assessments over time.

We read the letter of Giraldez-Gallego et al. Our data show that hepatitis B vaccination in patients with advanced cirrhosis leads to a poor response despite the implementation of a double dose accelerated schedule (starting at the hospital admission) and the nursing effort to reinforce the vaccination compliance after discharge(1) . The reasons for a lower response to vaccination in liver transplantation (LT) candidates were not clear, as we explained in our discussion. We did not find a direct correlation between the MELD score and the immunogenicity, but it is relevant to notice that LT candidates had worse MELD score (12[8-16]) compared with the remaining population (9[6-10], p

Background: Whether or not inhalation of airborne desert dust has adverse health effects is unknown. The present study, based on a systematic review and meta-analysis, was carried out to assess the influence desert dust on cardiovascular mortality, acute coronary syndrome, and heart failure. Methods: A systematic search was made in PubMed and Embase databases for studies published before March 2020. Studies based on daily measurements of desert dust were identified. The meta-analysis evaluated the impact of desert dust on cardiovascular events the same day (lag 0) of the exposure and during several days after the exposure (lags 1 to 5). The combined impact of several days of exposure was also evaluated. The incidence rate ratio (IRR) with 95% confidence intervals (CI) was calculated using the inverse variance random effects method. Results: Of the 589 identified titles, a total of 15 studies were selected. The impact of desert dust on the incidence of cardiovascular mortality was statistically significant (IRR = 1.018 (95%CI 1.008–1.027); p < 0.001) in lag 0 of the dust episode, in the following day (lag 1) (IRR = 1.005 (95%CI 1.001–1.009); p = 0.022), and during both days combined (lag 0–1) (IRR = 1.015 (95%CI 1.003–1.028); p = 0.014). Conclusions: The inhalation to desert dust results in a 2% increase (for every 10 µg/m3) in cardiovascular mortality risk., This study was made within the setting of project VARDUST-SAL (PGC2018-099166-B-I00), funded by the Spanish State Research Agency (Agencia Estatal de Investigación), the Spanish Ministry of Science, Innovation and University (Ministerio de Ciencia, Innovación y Universidad), and the European Regional Development Fund.

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions.

Aim. To assess procedural and long-term efficacy and safety of two alternative methods for appendage closure, conscious sedation with standard transoesophageal echo and procedure guided by rotational angiography. Background. Demand for appendage closure is increasing, and a reasonable time-response should be given to nonvalvular atrial fibrillation patients not suitable to receive anticoagulation. General anesthesia and the need for an anesthesiologist are limiting factors to improve procedure availability; it is time to introduce simpler approaches. Methods. Single center experience in appendage closure during 9 years, using three different procedural approaches: general anesthesia with echo guidance, conscious sedation with echo guidance, and rotational angiography guidance. Conscious sedation and rotational angiography-guided procedures were performed in the absence of an anesthesiologist. Procedural characteristics and follow-up events were recorded. Results. 260 consecutive appendage closure procedures were reviewed: 155 were performed under general anesthesia (59.6%), 71 were performed with conscious sedation (27.3%), and 34 were rotational angiography guided (13.1%). Device success rate for procedures guided by rotational angiography was significantly lower than that for general anesthesia and conscious sedation (91.2% versus 100% versus 98.6%, p = 0.001 ) because there was a greater need to recapture and change device size. However, final procedural success was high and without difference between approaches (98.8% versus 97.2% versus 100%, for general anesthesia, conscious sedation, and rotational angiography, respectively); with a median follow-up of 17 months (CI 95% 13–23 month) (637.9 patients-year), there was no difference among approaches for thromboembolic (1.3 versus 1.8 versus 1.8) and major bleeding events (3.2 versus 2.8 versus 1.8), respectively. Conclusions. Appendage closure performed, either with conscious sedation with echo guidance or rotational angiography guided, is feasible, with no difference in procedural success and follow-up events compared with general anesthesia and without the limitation of the need for an anesthesiologist on-site.

A significant proportion of patients infected with SARS‐CoV‐2 develop severe respiratory symptoms due to an excessive immune response. Treatment of this condition may include immunosuppressive therapies, such as IL‐6 receptor antagonists and corticosteroids, which poses a risk for patients with active or past hepatitis B virus (HBV) infection. In this prospective cohort study we analyzed the risk of HBV reactivation in patients with severe COVID‐19 and resolved HBV infection undergoing immunosuppressive therapy. From March 15thto April 30th2020, 600 patients with severe COVID‐19 were admitted into our Hospital and treated with immune‐modulators. Data regarding HBV infection was available in 484, of whom 69 (14%) were HBsAg negative/anti‐HBc positive. For these patients, HBV reactivation prophylaxis with entecavir was strongly recommended. Complete follow‐up was available in 61 patients: 72% were male, median age was 67 years, and anti‐HBs was >10 IU/mL in 72%. The immunosuppressive drug most used was tocilizumab (72%). Despite HBV prophylaxis recommendation, 38 (62%) patients received entecavir and 23 (38%) did not. Baseline features of both groups were similar. At follow‐up, we found no cases of HBsAg seroreversion and only 2 (3%) patients (no prophylaxis group) had detectable serum HBV‐DNA (

Background and Aim Accurate information on the epidemiology of hepatitis C and B infection is mandatory to establish a national/regional plan. We aim to update the prevalence of hepatitis C and B infection in Catalonia using point-of-care tests to analyze the risk factors related and to implement a linkage-to-care circuit. Methods This is a community-based study. A random list of adult individuals was retrieved from censuses of primary care centers. Point-of-care tests for anti-hepatitis C virus (HCV) and HBV surface antigen (HBsAg) and a questionnaire for risk factor assessment were performed. Positive results were validated and a circuit for linkage-to-care was established. Results A total of 3328 individuals were included. The anti-HCV and HBsAg overall prevalence were lower than expected [1.02%, 95% confidence interval (CI) 0.65-1.39; and 0.52%, 95% CI 0.26-0.77, respectively]. Anti-HCV positive subjects were mostly (88%) autochthonous. The prevalence increased with age; only 12% were under age 40. The associated risk factors were drug use, blood transfusion, relative with HCV, and diabetes. Notably, the prevalence of active infection was only 0.49% (95% CI 0.23-0.74), 40% less than previously reported, reflecting the impact of direct acting antiviral therapy. Differently, HBsAg positive subjects were mostly foreign migrants (53%) with no other risk factors. Despite the implementation of a linkage-to-care circuit, one third of HBsAg positive subjects were lost. Conclusions The prevalence of HCV infection was lower than previously reported, showing a strong impact of direct acting antiviral therapy in the last years. Because of hepatitis B universal vaccination, HBV infection in Catalonia is mainly associated with migrant population. Linkage-to-care in patients with hepatitis B was challenging and warrants additional efforts.

Epidemiological studies found that increases in the concentrations of airborne particulate matter (PM) smaller than 10 microns diameter (PM10) in the ambient air due to desert dust outbreaks contribute to global burden of diseases, primarily as a result of increased risk of cardiovascular morbidity and mortality. No studies have investigated the possible association between desert dust inhalation and airway inflammation in patients with ischemic heart disease (IHD). Induced sputum was collected in 38 patients and analysed to determine markers of airway inflammation (Transforming Growth Factor-β1 [TGF-β1] and hydroxyproline) concentrations. For the purpose of the investigation, PM10 and reactive gases concentrations measured in the European Air Quality Network implemented in the Canary Islands were also used. We identified Saharan desert dust using meteorology and dust models. Patients affected by smoking, chronic obstructive pulmonary disease (COPD), asthma, pulmonary abnormalities, acute bronchial or pulmonary disease were excluded. The median of age of patients was 64.71 years (56.35–71.54) and 14 (38.84%) of them were women. TGF-β1 and hydroxyproline in sputum were highly associated to PM10 inhalation from the Saharan desert. According to a regression model, an increase of 1 µg/m3 of PM10 concentrations due to desert dust, results in an increase of 3.84 pg/gwt of TGF-β1 (R2 adjusted= 89.69%) and of 0.80 μg/gwt of hydroxyproline (R2 adjusted= 85.28%) in the sputum of patients. The results of this study indicate that the exposure to high PM10 concentrations due to Saharan dust events are associated with intense inflammatory reaction in the airway mucosae of IHD-patients.

Introduction Hemophagocytic lymphohistiocytosis (HLH) is a disorder caused by severe immune activation. There are no specific criteria to establish the diagnosis in adults; however, the HLH-04 criteria are among the most commonly used. The HScore is a non-validated tool that can also be useful for HLH diagnosis. Patients and Methods We describe the prognostic factors and outcomes of 64 adults diagnosed with HLH in a reference medical center in Mexico City. We included patients ≥ 18 years with HLH, diagnosed and treated at our institution from 1998 to 2016. Results The median age was 35 years (range, 18-77 years). The underlying cause of HLH was lymphoma in 33 (51.56%) patients (MA-HLH). Cutaneous involvement was more frequent in MA-HLH (33.33%), when compared with patients with non-malignancy associated HLH (NM-HLH) (9.68%) (P = .022). Neurologic symptoms were more frequent in NM-HLH (25.81%) versus MA-HLH (6.06%) (P = .032). After a median follow-up of 14 months (range, 0-216 months), 30-day mortality was 26.56%. Three-year overall survival (OS) was higher for patients with MA-HLH compared with patients with NM-HLH (41% vs. 22.5%; P = .046). Multivariate analysis showed that the presence of nosocomial infection and neurologic symptoms were statistically significant predictors of inferior OS (P = .034 and P = .033, respectively). Conclusion In this series of adults with HLH, patients with nosocomial infections and neurologic symptoms had a statistically significant worse OS. In the largest series in Latin America, the most common cause of HLH was T-cell lymphoma. In our population, NM-HLH presented a higher mortality.

Due to the fact that mitochondrial defects and oxidative stress have been related with obesity and breast cancer is more aggressive in women with obesity, we investigated if postmenopausal Mexican-Mestizo women with breast cancer presented somatic mutations in the sequence of the ATP6 and/or ND3 genes. Twenty one postmenopausal Mexican-Mestizo women with breast cancer who underwent mastectomy or breast conserving surgery were studied. Height and weight were used to calculate body mass index. DNA from tumor tissue samples and blood leukocytes was amplified by polymerase chain reaction and sequenced the ATP6 and ND3 mitochondrial genes. Ages ranged from 46 to 82. According to World Health Organization criteria among the 21 women, 7 had a normal BMI, 7 were overweight and 7 had obesity. In regard to the molecular study, after sequencing the coding region of ATP6 and ND3 genes of the DNA obtained from both leukocytes and tumor tissue, we did not find somatic mutations. All of the changes that we found in both genes were polymorphisms: in ATP6, we identified in ten patients 3 non-synonymous nucleotide changes and in ND3 we observed that six patients presented polymorphisms, three of them were synonymous and two non-synonymous. To our knowledge, this constitutes the first report where the complete sequence of the ATP6 and ND3 genes has been analyzed in postmenopausal Mexican-Mestizo women with breast cancer and diverse BMI. Our results differ with those reported in Caucasian and Asian populations, possibly due to ethnic differences.

Musculoskeletal symptoms are the most common extraintestinal manifestations of inflammatory bowel disease (IBD). An essential step in the management of these patients is to establish referral algorithms through the use of appropriate screening tools. Our objective was to evaluate the performance of two simple questionnaires to detect inflammatory arthritis (IA) in patients with IBD. Two questionnaires, one for detecting axial IA and the other for peripheral IA, were tested among 112 IBD unselected consecutive patients of both sexes, aged 18–45 years. The study period was from January to December 2016. Each questionnaire was composed of three simple questions. If the patient answered affirmatively at least to two of the three questions, the questionnaire was considered positive. Clinical diagnosis of IA based on an expert’s opinion was the reference gold standard. To obtain a weighted value of sensitivity and specificity, likelihood ratio (LR) values were calculated. Twenty-seven percent of the patients were considered positive responders to the axial questionnaire while 32% were considered positive responders to the peripheral questionnaire. Twenty-four patients (21.4%) were diagnosed with axial IA, whereas 26% had peripheral IA. The axial questionnaire yielded a sensitivity of 87.5% (67.6–97.3), specificity of 89.8% (81.5–92.2) and LR+ of 8.6 (4.5–16.2). For the peripheral questionnaire, these values were 82.8% (64.2–94.2), 87.4% (79–93.3), and 6.6 (3.8–11.4), respectively. Both questionnaires showed an adequate screening capacity for IA in patients with IBD. Their specificity, together with their simplicity, can make them suitable detection tools in gastroenterology and general medicine consultations.

Background And Aims Acute hepatitis A is transmitted mainly via the fecal-oral route and/or contaminated aliment. Furthermore, several outbreaks in the men who have sex with men (MSM) population classified hepatitis A as a sexually transmitted disease (STD). We aimed to clarify an ongoing hepatitis A outbreak in Barcelona with respect to patients’ characteristics and viral phylogenetic analysis. Methods We prospectively analyzed 46 cases of hepatitis A infection that were registered in our hospital between January and June 2017. We evaluated demographics data, risk factors, presenting symptoms, sexual orientation, comorbidities and further STD infections. The phylogenetic correlation of the current circulating viruses among them and other hepatitis A strains was assessed by sequencing of the VP1/P2A region. Results Most patients were male (44, 96%) with median age 33.5 years (range 28-50). Thirty-one (67%) were MSM and 18 (39%) required hospitalization. Molecular phylogenetic analyses revealed that all patients were infected by hepatitis A subgenotype IA strains. Moreover, current strains comprised 3 distinct clusters, previously reported in ongoing outbreaks in the United Kingdom, Berlin and Netherlands. However, these strains were phylogenetically diverse to those previously reported in Barcelona metropolitan region. Conclusions Ongoing hepatitis A outbreak in Barcelona affects primarily the MSM community and is phylogenetically linked to current hepatitis A outbreaks described in other European countries. Due to the high admission rate, these outbreaks may impact the admission pattern of referral liver units. Control measures, e.g. vaccinations programs tailored to the MSM community, must be taken to control further spreading. This article is protected by copyright. All rights reserved.

OBJECTIVES: Interferon-free therapies have an improved safety and efficacy profile. However, data in elderly patients, who have frequently advanced liver disease, associated comorbidities, and use concomitant medications are scarce. The im of this study was to assess the effectiveness and tolerability of all-oral regimens in elderly patients in real-life clinical practice. METHODS: Retrospective analysis of hepatitis C virus (HCV) patients aged >= 65 years receiving interferon-free regimens within the Spanish National Registry (Hepa-C). RESULTS: Data of 1,252 patients were recorded. Of these, 955 (76%) were aged 65-74 years, 211 (17%) were aged 75-79 years, and 86 (7%) were aged >= 80 years at the start of antiviral therapy. HCV genotype-1b was predominant (88%) and 48% were previous non-responders. A significant proportion of patients had cirrhosis (922; 74%), of whom 11% presented decompensated liver disease. The most used regimens were SOF/LDV (33%), 3D (28%), and SOF/SMV (26%). Ribavirin was added in 49% of patients. Overall, the sustained virological response (SVR12) rate was 94% without differences among the three age categories. Albumin = 75 years (2.59 (1.16-5.83); P = 0.02) and albumin = 75 years) or those with advanced liver disease (albumin

Background Breast cancer is the most common among women in our country, and its treatment is based on prognostic factors to categorise patients into different risk groups. In this study, the clinical and pathological features that play a role as a prognostic factor in a representative population with breast cancer in Mexico are described. Material and methods A descriptive analysis of the clinical and pathological features of women diagnosed with breast cancer, in a period from June 2005 to May 2014; registered in a database and calculated by simple frequencies. Results A total of 4411 patients were included, the average age at diagnosis was 53 years, 19.7% were diagnosed by mammography screening program and 80.3% derived from any signs or symptoms. Regarding the stages at diagnosis, 6.8% were carcinoma in situ, 36% at early stages (I and IIA), 45% locally advanced (IIB to IIIC), 7.7% metastatic and 3.9% unclassifiable. A 79% were ductal histology, lobular 7.8% and the rest, other types. Of ductal carcinomas, 9.1% were grade I, 54.1% grade II, and 34.6% grade III. Regarding the biological subtypes, 65.7% were luminal, 10.9% luminal Her positive, 8.7% pure Her 2 positive and 14.6% triple negative. Conclusion In the present study, we described the clinical and pathologic features of a group of Mexican women with breast cancer that might reflect a national landscape, and represent the prognostic factors to determine groups of risk and treatment decisions.

Introduction Patients with similar local advanced breast cancer (LABC) could respond different to neoadjuvant chemotherapy (NC). Luminal HER2(-) tumors have pathologic complete response (pCR) by 5-7%. Ki67, tumor grade and hormonal receptors, could be helpful but not enough to choice between NC vs. initial surgery. Response to drugs depends on enzymes involved in absorption, distribution, metabolism and elimination (ADME); the drug-metabolizing enzyme and transporter platform (DMET), could identify 1936 single nucleotide polymorphism (SNP) from 225 genes involved in ADME proccess. Objective To identify predictive factors to pCR in patients with Luminal HER2(-) LABC underwent NC, to distinguish wish patients could have a real benefit from NC. Material and Methods This is a prospective nested case control study (1:4) with LABC patients, pure invasive ductal carcinoma Luminal HER2(-) subtypes, and sequential NC (anthracyclines and taxanes). Cases were defined as patients with pCR (Residual Cancer Burden=0), and controls those without pCR. SNPs were evaluated from DNA of leucocytes using DMET microarrays by Affymetrix. Bivariate analyses were used as appropriate. Microarrays were processed by the DMET analyzer console. OR and 95%CI were used to test association between pCR and variables with a non-conditional logistic regression analysis; p value ≤0.05 was considered statistically significant (two-sided). Results From 2005 to 2014, of 3762 treated patients, 287 women met inclusion criteria. We included 117 patients, 21 cases and 96 controls. Patients with pCR were 5 years younger than controls (45.4 vs 49.4), have more grade-3 tumors, (66.7 vs 22.3%), more Luminal B subtypes (90.5 vs 64.6%), lower expression of estrogen receptor (60 vs 80%) and higher Ki67 expression (65 vs 12%), all with p≤0.05. No differences in toxicity existed between groups. In an initial screening procedure, 13 SNPs were identified, but only 4 SNPs (4 genes) are known to participate in ADME of antineoplastic agents. All pCR cases did not have the C/C allelic variant in the rs2072671 SNP (CDA gene); while in rs1883322 SNP (PPARD gene) all had T/T variant SNPs identified in DMET microarray known to participate with antineoplastic agentsGENESNPAllelic variantpCR, n=21No pCR, n=96pDPYDrs17376848T/T13 (61.9%)83 (86.4%)0.007 C/T8 (38.1%)11 (11.4%) CDArs2072671A/A6 (28.5%)51 (53.1%)0.013 A/C15 (71.4%)36 (37.5%) C/C09 (9.3%) PPARDrs1883322T/T21 (100%)69 (71.8%)0.022 C/T022 (22.9%) C/C05 (5.2%) GSTM3rs7483A/A7 (33.3%)20 (20.8%)0.024 A/G13 (61.9%)43 (44.7%) G/G1 (4.7%)33 (34.3%) pCR= pathologic complete response After logistic regression analysis, pCR predictive factors were the presence of grade-3 tumors OR=6.66 (95%CI=1.67-26.56), Ki67 ≥14% OR=15.45 (95%CI=1.71–138.86), premenopausal status OR=6.540 (95%CI=1.50–28.38) and A/A or A/G allele in rs7483 SNP (GSTM3 gene) OR=19.16 (95%CI=1.97–185.93). Conclusions Genetic variability encoded in the DMET-chip, could be helpful as a predictive factor of pCR in patients with Luminal HER2(-) LABC, but only in combination with other factors such as grade-3 tumors, elevated Ki67, and premenopausal status. Citation Format: Ruvalcaba-Limon E, Rodriguez-Cuevas S, Hidalgo-Miranda A, Villa-Romero A, Bautista-Piña V, Rebollar-Vega R, Fernandez-Lopez JC, Morales-Vasquez F. Predictive factors of pathologic complete response to neoadjuvant chemotherapy in patients with Luminal HER2(-) local advanced breast cancer using the DMET microarray [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-18.

Background: Breast cancer is the most prevalent cancer in Mexico and is the leading oncologic death cause among women older than 25 years-old. Its incidence has steadily increased during the last decades. Unfortunately, most of the patients are diagnosed in advanced stages, increasing the cost of the treatment and mortality. Through this study, we analyse the annual economic impact of breast cancer in Mexico. Materials and methods: Data from Mexican official statistics from 2014 were obtained. The rate of population covered by the public health system, the mean income per capita, the age for retirement, the funds used in public hospitals according to clinical stages, the mean age for diagnosis and the mean age of death by breast cancer in Mexico and the mean cost of a funeral service were obtained. We calculate the direct costs including the funds used for diagnosis and treatment of the patients with breast cancer in the public hospitals. The indirect costs were obtained calculating the mean per capita income lost due to death by breast cancer, the number of deaths before 65 years-old (Age for retirement in Mexico) and the mean cost for funeral services. Costs for breast cancer treatment were also obtained according to the funds for early stages (0 – IIA), locally-advanced stages (IIB – IIIC) and metastatic stages (IV). Results were compared between groups. Results: In 2014, around 20,500 new cases of breast cancer were diagnosed in Mexico. Among them, 15,826 patients (77.2%) were treated in public health institutions. From these patients, 38.7% were diagnosed in early stages, 51% in locally-advanced stages and 9.6% in stage IV. Only 22% were diagnosed during screening mammography. In 2014, funds for early stages amounted to US $44,077, 959; for locally-advanced stages to US $120,727,505 and for metastatic stages to US $ 192,623,862. The total fund for breast cancer, including diagnosis and treatment, was US $ 304, 747,165. Treatments for locally advanced stages were 107.8% higher compared to early stages (US $14,958 / 7,197). It has been demonstrated that the mean age of breast cancer diagnosis in Mexico is 53 years-old, while the mean age of death due to this disease is 58 years-old. Age for retirement is 65 years and 76% of the breast cancer patients appeared in this group of age or younger. The mean per capita income is US $22 and the cost for funeral was US $1,968 approximately. The mean Overall-Survival rate for breast cancer in Mexico is 83.1%, so the mortality rate is 16.9%, so 2044 patients died due to breast cancer in 2014. The economic loss for the families amounted to US $120,647,834: US$116, 624,822 for the loss of the per capita income and US $4,023,012 for the cost for funeral services. Conclusions: Breast cancer has a great economic impact in both the government and the patient, especially in advanced stages. It is extremely important to improve the mammographic screening programs in Mexico and reduce the time of care. Initiation of annual screening mammography starting at 40 years-old should be a mandatory policy in order to increase the rate of diagnosis of breast cancer at early stages. In the near future, there will not be sufficient economic resources for treating breast cancer in Mexico, if new and strict policies are not carried out. Citation Format: Sherwell-Cabello S, Maffuz-Aziz A, Rodríguez-Cuevas S. Economic impact of breast cancer in Mexico [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-15.

Objective There is scarce data with regard to the effectiveness and safety of direct-acting antivirals and possible drug-drug interactions between antiviral therapy and the multiple drugs frequently assumed by older patients. The aim is to evaluate the impact of comorbidities and drug-drug interactions on the efficacy and tolerability of direct-acting antivirals in this population. Methods Observational retrospective study of patients at least 65 years old receiving all-oral antiviral therapy between April 2015 and March 2016. Results Two hundred sixty-one patients were identified. Age distribution: 65-74 (73.9%), 75-79 (18.4%) and ≥80 (7.7%) years. Average age was 71 years, 38.7% were male, and 90% of patients took concomitant medication (43% patients taking ≥ 5 medicines). Predicted clinically significant drug-drug interactions were present in 72.8% of patients. The sustained viral response 12 weeks after end of treatment was 96.9%. Patients with serious adverse events received more concomitant drugs and all of them presented a clinical risk group ≥06/5. Conclusions Direct antiviral agents are highly effective also in older patients with advanced liver disease, comorbidities and concomitant medications. Serious adverse events increased with the number of concomitant medications and the severity of comorbidity. A clinical risk group score ≥06/5 may help to decide the indication of antiviral therapy in this difficult-to-treat population.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by inflammation and tissue damage mediated by the immune system. Respiratory manifestations are common in SLE, appearing in up to 50% of patients throughout their lives. Furthermore, it is associated with higher mortality. Objectives: To describe the prevalence and characteristics of pulmonary involvement in patients with SLE Methods: Observational, descriptive, cross-sectional, retrospective study performed in patients with SLE in follow-up by the Rheumatology Department of Valme Hospital. The following information is collected from medical records; age, sex, mean age at diagnosis, characteristics of pleuropulmonary involvement and ANA and antiDNA positivity. Results: We studied 165 patients with SLE, with mean age of 37.01 +/- 14.65 years, predominance of the female patients 153 (92.72%). Thirty eight of them had pulmonary involvement (23.03%), with a total of 47 episodes related to lung manifestations. Mean age at diagnosis was 39.70 +/- 15.50 years. Below is shown information about lung involvement: Eleven patients (28.94%) presented pulmonary involvement at the time of diagnosis; pleuritis (10.63%) and only one case of interstitial lung disease, varicella pneumonia, shrinking lung syndrome, pulmonary embolism (PE) and bronchiolitis obliterans with organizing pneumonia. Two patients (4.24%) died due to severe respiratory failure secondary to bilateral pneumonia. Three of the 5 patients with PE were diagnosed with antiphospholipid syndrome secondary to SLE. Regarding treatment, most of patients who required hospitalization were in basic treatment with synthetic DMARDs (78.57% in monotherapy and 21.43% with double therapy) and only 2 patients with biologic DMARDs (Rituximab and etanercept). Six patients had no treatment because the pulmonary event was at time of diagnosis, 2 patients were with antiaggregating therapy and there was no information registered in two patients (episode before 1997). 91.10% of the patients presented positive for ANA, of which 37.14% (13 patients) also presented positive antiDNA. No information was collected about autoimmunity in one patient (2.12%). Conclusion: Pulmonary involvement in SLE is prevalent, although a significant proportion may remain asymptomatic. The little prevalence of pulmonary manifestations in our series might be due to low mean age, according to the result of a recent systematic review where analysed more than 10000 patients and concluded pulmonary manifestations are more frequent in late-onset SLE. The differential diagnosis is broad and the infectious cause, the main cause of mortality in patients with SLE, must always be ruled out. References: [1] 10.1016/j.semarthrit.2018.01.010 [2] 10.1016/j.reuma.2018.03.012 [3] 10.1186/s13075-018-1776-8 [4] 10.1097/BOR.0000000000000531 Acknowledgement: None Disclosure of Interests: NAHIA PLAZA: None declared, MARIA JOSE PEREZ: None declared, Sergio Rodriguez Montero: None declared, CARMEN TRAPERO: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen

Background The infection of a native or prosthetic heart valve usually occurs in patients with structural valvular anomalies that predispose to turbulent flows. Manifestations such as arthralgia, arthritis or back pain appear in up to 40% of patients, which acts as a confounding factor when this infection occurs in patients with rheumatic diseases. On the other hand, in the latter patients, noninfectious endocarditis has been described, which adds even more complexity to the diagnosis. Objectives To describe the characteristics of endocardial lesions in patients with rheumatic diseases. Methods Patients attending clinics at the Department of Rheumatology were analyzed to determine how many of them required hospitalization for causes directly related to endocardial lesion, from January 2015 until December 2018. The following information was recorded: age, sex, type of rheumatic disease, duration of the disease, immunosuppressive treatment, characteristics of endocardial lesions, complications of endocardial lesions, and cardiovascular risk factors. Results All patients were identified from an electronic database. Results regarding to demographic and clinical data are as follows: Conclusion The spectrum of endocardial involvement in patients with rheumatic diseases is variable. In this case review, we found lesions of different origin: infectious, thrombotic and tumoral. The appearance of fever of unknown origin in patients with rheumatic diseases, requires ruling out an endocarditis, needing transesophageal echocardiography in case the transthoracic study, which is less sensitive, is negative. It is striking the case of patient 3, a systemic sclerosis with calcinosis in limbs, whose endocardial wart, was studied histologically, revealing in its composition mainly calcium and fibrin. We have not found a bibliographic reference of calcium endocarditis in systemic sclerosis. In conclusion, patients with rheumatic diseases can develop infectious endocarditis, but also thrombotic valvular vegetations, as well as myxomas whose consequences, from their clinical debut, may pose life-threatening situations for the patient. The presence of fever, stroke or embolic events in these patients should put us on the track of an underlying endocardial involvement. References [1] Am J Med (2007) 120, e1-e2 [2] World J Cardiol 2014 September 26; 6(9): 993-1005 [3] Rev Esp Enferm Metab oseas 2002;11(2): 50-58 Disclosure of Interests Sergio Rodriguez Montero: None declared, Consuelo Ramos Giraldez Speakers bureau: Sanofi, NAHIA PLAZA: None declared, Jose Luis Marenco Speakers bureau: abbie, pfizer, novartis, janmsen

Objective To explore the clinical and epidemiological characteristics of chronic obstructive pulmonary disease (COPD) patients with Aspergillus spp. isolation from respiratory samples, and to identify which factors may help us to distinguish between colonisation and infection. Methods A retrospective cohort study was performed. All patients with COPD and respiratory isolation of Aspergillus spp. over a 12-year period were included. Patients were assigned to 2 categories: colonisation and pulmonary aspergillosis (PA), which includes the different clinical forms of aspergillosis. A binary logistic regression model was performed to identify the predictive factors of PA. Results A total of 123 patients were included in the study: 48 (39.0%) with colonisation and 75 (61.0%) with PA: 68 with probable invasive pulmonary aspergillosis and 7 with chronic pulmonary aspergillosis. Spirometric stages of the GOLD classification were not correlated with a higher risk of PA. Four independent predictive factors of PA in COPD patients were identified: home oxygen therapy (OR: 4.39; 95% CI: 1.60–12.01; p = 0.004), bronchiectasis (OR: 3.61; 95% CI: 1.40–9.30; p = 0.008), hospital admission in the previous three months (OR: 3.12; 95% CI: 1.24–7.87; p = 0.016) and antifungal therapy against Candida spp. in the previous month (OR: 3.18; 95% CI: 1.16–8.73; p = 0.024). Conclusions Continuous home oxygen therapy, bronchiectasis, hospital admission in the previous three months and administration of antifungal medication against Candida spp. in the previous month were associated with a higher risk of pulmonary aspergillosis in patients with COPD.

Introduction and objectives: There is current controversy regarding the benefits of percutaneous recanalization (PCI) of chronic total coronary occlusions (CTO). Our aim was to determine acute and follow-up outcomes in our setting. Methods: Two-year prospective registry of consecutive patients undergoing PCI of CTO in 24 centers. Results: A total of 1000 PCIs of CTO were performed in 952 patients. Most were symptomatic (81.5%), with chronic ischemic heart disease (59.2%). Previous recanalization attempts had been made in 15%. The mean SYNTAX score was 19.5 +/- 10.6 and J-score was > 2 in 17.3%. A retrograde procedure was performed in 92 patients (9.2%). The success rate was 74.9% and was higher in patients without previous attempts (82.2% vs 75.2%; P = .001), those with a J-score 20 mm, and blunt proximal cap were independent predictors of failed recanalization. The rate of procedural complications was 7.1%, including perforation (3%), myocardial infarction (1.3%), and death (0.5%). At 1-year of follow-up, 88.2% of successfully revascularized patients showed clinical improvement (vs 34.8%, P < .001), which was associated with lower mortality. At 1-year of follow-up, the mortality rate was 1.5%. Conclusions: Compared with other national registries, patients in the Iberian registry undergoing PCI of a CTO showed similar complexity, success rate, and complications. Successful recanalization was strongly associated with functional improvement, which was related to lower mortality. (C) 2018 Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Cardiologia.

Vascular calcification is a major risk for cardiovascular disease and implies the transformation of smooth muscle cells to an osteoblastic phenotype as a consequence of dysregulation of calcium and phosphate metabolism. Fibroblast growth factor (FGF) 23 is the most potent phosphate regulator. Observational studies suggest that high levels of FGF23 are related to cardiovascular morbidity and mortality. In this work, we determined the levels of both the intact and the carboxi-terminal fragments of circulating FGF23 in 133 patients with established cardiovascular disease, the expression of FGF23, its receptors 1 and 3, and its co-receptor Klotho in vascular fragments of aorta, carotid and femoral in 43 out of this group of patients, and in a control group of 20 organ donors. Patients with atherosclerosis and vascular calcification presented increased levels of FGF23 respect to the control group. Vascular immunoreactivity for FGF23 was also significantly increased in patients with vascular calcification as compared to patients without calcification and to controls. Finally, gene expression of FGF23 and RUNX2 were also higher and directly related in vascular samples with calcification. Conversely, expression of Klotho was reduced in patients with cardiovascular disease when comparing to controls. In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone.

IntroductionHepatitis C virus (HCV) infection is known to be associated with neuropsychiatric manifestations as part of the disease. Previous neuroimaging studies showed brain connectivity dysfunction among HCV-infected patientsObjectivesTo assess, by MR in resting state, the potential structural and connectivity changes before (BL) and after HCV eradication (FU12) with direct-acting antivirals (DAA), along with clinical parameters.Methods Twenty-one HCV-patients, aged≤55 years, without psychiatric history, nor advanced liver disease, and eligible for DAA, and 25 healthy controls were included. Evaluations were performed at BL and FU12. Brain volume and local gyrification index (LGI) were assessed in MR-T1, and functional connectivity by seed-based analysis (left insula). Depression (MADRS/PHQ9) and neurotoxicity symptomatology (NRS) were assessed. We compared patients between BL/FU12, and controls by means of paired/independent T-test analysis.ResultsSubstained virologycal response was obtained in all patients (100%). Depressive and neurotoxicity symptomatology improved after cure (pConclusionsNeuropsychiatric symptomatology improved after cure. Left insula is altered among HCV-patients in structured and connectivity (mainly occipital areas). After cure differences with controls were reduced, suggesting a partial restoration of brain connectivity.

Hepatitis C recurrence after liver transplantation is universal and increases morbidity and mortality in these patients. The development of new direct antiviral agents against the hepatitis C virus is a major treatment advance. Pre-transplant treatment avoids graft infection and sometimes improves liver function, allowing the patient to be withdrawn from the transplant waiting list. Delaying treatment until the postpostransplant period may be advisable in patients with advanced cirrhosis. Generally, antiviral therapy after liver transplantation is provided in patients with histological evidence of the disease. In these patients, treatment is more effective in the initial stages of the disease. The choice of antiviral therapy in these patients is based on the degree of liver function, the presence of renal failure, and potential drug-drug interactions.

Objective Evaluate whether the meterological parameters affecting revenues in patients with ST-segment and non-ST-segment elevation ACS. Design A prospective cohort study was carried out. Setting Coronary Care Unit of Hospital Universitario de Canarias. Patients We study a total of 307 consecutive patients with a diagnosis of ST-segment and non-ST-segment elevation ACS. We analyze the average concentrations of particulate smaller than 10 and 2.5 μm diameter, particulate black carbon, the concentrations of gaseous pollutants and meteorological parameters (wind speed, temperature, relative humidity and atmospheric pressure) that were exposed patients from one day up to 7 days prior to admission. Interventions None. Variables of interest Demographic, clinical, atmospheric particles, concentrations of gaseous pollutants and meterological parameters. Results A total of 138 (45%) patients were classified as ST-segment and 169 (55%) as non-ST-segment elevation ACS. No statistically significant differences in exposure to atmospheric particles in both groups. Regarding meteorological data, we did not find statistically significant differences, except for higher atmospheric pressure in ST-segment elevation ACS (999.6 ± 2.6 vs. 998.8 ± 2.5 mbar, p =.008). Multivariate analysis showed that atmospheric pressure was significant predictor of ST-segment elevation ACS presentation (OR: 1.14, 95% CI: 1.04–1.24, p =.004). Conclusions In the patients who suffer ACS, the presence of higher number of atmospheric pressure during the week before the event increase the risk that the ST-segment elevation ACS.

Proliferating trichilemmal tumors (PTTs) are benign adnexal skin neoplasms that arise from the outer root sheath of the hair follicle. These tumors are most commonly observed on the scalp and occur, most of the time, in elderly women. Malignant transformation of these neoplasms is a rare event; less than 50 cases have been reported in the English medical literature. We present the case of a 39-year-old Hispanic woman with a tumor located on the skin of one of her breasts that in her third surgical procedure the histologic examination revealed the presence of a malignant proliferating trichilemmal tumor (MPTT). Furthermore, a review of the medical literature and a discussion of the clinical and pathologic features of this rare entity are provided.

Background Cell energy during ischemia/reperfusion depends on mechanisms including adenosine diphosphate degradation, oxygen species and cytokine liberation, neutrophil infiltration, and endothelial dysfunction. Preconditioning—a brief ischemic episode that confers a state of protection against subsequent ischemia-reperfusion injury—involves NO and adenosine production, reduction in oxygen species liberation, and preservation of microcirculation. During hypoxia, constitutive NO production assures adequate oxygen delivery and reduced energy loss. The aim was to determine the role of ischemic preconditioning in the stimulation of constitutive endothelial nitric oxide (NO) production and its effect on energy charge, radical oxygen species generation, cytokine liberation, and neutrophil infiltration during reperfusion. Materials and Methods Rats were assigned to one of four groups depending on the preconditioning protocol: hepatic ischemia/reperfusion, or hepatic ischemia/reperfusion and ischemic preconditioning, for 5, 10, or 20 min. A portosystemic shunt was established between the portal and left jugular veins during ischemia. Results Preconditioning produced rises in plasma nitrites, but no rise in inducible nitric oxide synthase gene expression. A 5 or 10 min preconditioning period allowed for higher energy charge, bile production, and glutathione levels, with less lipoperoxide, alanine aminotransferase, tumor necrosis factor-α, and interleukin-1 production and neutrophil infiltration, compared with 20 min or control. Survival was 80% in the G10 group, 70 in G5, 10 in GC, and 0% in the G20 group. Conclusions Ten-min liver preconditioning improves survival and prevents energy loss during hepatic ischemia/reperfusion by stimulating constitutive NO production, maintaining glutathione concentrations and reducing oxygen species and proinflammatory cytokine generation as well as neutrophil infiltration.

Patients with hepatitis C virus-associated cryoglobulinemic vasculitis (HCV-CV) have high rates of clinical remission after treatment with direct-acting antivirals (DAAs), but circulating cryoglobulins persist, and vascular disorders reappear in some patients shortly after DAA treatment ends. We performed a prospective study to assess the long-term clinical and immune system effects of HCV eradication with DAAs in 46 patients with HCV-CV and 42 asymptomatic patients with circulating cryoglobulins. A median of 24 months after DAA treatment (range, 17-41 months), 66% of patients with HCV-CV and 70% of asymptomatic patients with circulating cryoglobulins had an immunologic response, with comparable reductions in cryocrit from 2.6% to 0% (P.05). However, 20% of patients still had positive test results for cryoglobulins after DAA therapy. Among patients with HCV-CV, 42 (91%) had a clinical response, in that their Birmingham Vasculitis Activity Score (version 3) decreased from 7 to 0 (P.01). Nevertheless, within 2 years after a sustained viral response to DAA therapy, 5 patients with HCV-CV (11%, 4 with cirrhosis) had relapses of vasculitis that included severe organ damage and death.

The sentinel lymph node (SLN) is frequently the first node in the lymphatic basin that receives drainage from an anatomic region and is immunologically responsible for that region. Sentinel lymph node biopsy (SLNB) remains the standard of care for the assessment of clinically negative axillary lymph nodes in patients with invasive breast carcinomas. Accurate diagnosis of a SLNB can direct the surgeon with regard to the need for axillary dissection (AD), and it can affect post-operative treatment decisions, including decisions about radiation therapy. Furthermore, an accurate negative diagnosis on SLNB can spare the patient the increased risk of lymphedema that accompanies AD or post-operative treatments. Its relatively low false negative rate of 5–10% and high sensitive rate of 90–95% in the detection of cancer to the lymph node basin has made this minimally invasive operation a standard. The idea that the SLN serves as a limited target sample of the axillary lymph nodes aroused an interest and trend toward increased inspection of the sentinel lymph node for detection of metastatic carcinoma by the pathologist though serial sections and/or immunohistochemistry.

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.