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Introduction: Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event., Methods: Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation., Results: Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44-3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5-4.45)., Conclusion: Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The largest outbreak of human leishmaniasis in Europe took place in Fuenlabrada, Spain, between 2009 and 2017. The University Hospital "12 de Octubre" in Madrid serves the population residing in three districts of Madrid located just north of the outbreak area (Villaverde, Usera, and Carabanchel). Villaverde and Usera are connected by rail to the outbreak area, unlike Carabanchel. We performed a retrospective study including all cases of leishmaniasis diagnosed between 2011 and 2020. Fifty-one cases were documented. In the districts connected by rail to the outbreak area, a higher-than-expected incidence was observed (13.45-15.55 versus 5.2 per 100,000 inhabitants). Apart from the linear distance from the place of residence to the railway tracks, no differences in terms of demographics or risk factors were detected between the populations of the districts. We hypothesize that the direct connection with the outbreak area by rail could explain the higher incidence observed in Villaverde and Usera.

Background: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT., Methods: A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation., Results: The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups., Conclusions: A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)

Strongyloides stercoralis hyperinfection syndrome has been observed in immunosuppressed coronavirus disease 2019 (COVID-19) patients. Detecting and treating asymptomatic Strongyloides infection in individuals from endemic areas can effectively prevent hyperinfection. Unfortunately, many clinicians are unaware of this neglected infection. Therefore, we aimed to evaluate whether including Strongyloides screening in COVID-19 management protocols would encourage this practice. To accomplish this, we conducted a retrospective single-center study at 'Hospital Universitario 12 de Octubre' in Madrid, Spain, comparing two consecutive cohorts. The first cohort comprised all Latinx patients over 18 years old who were admitted for COVID-19 between March 1 st and April 30 th , 2020. The second cohort consisted of Latinx patients admitted between July 1 st and December 31 st , 2020, following an amendment to the COVID-19 management protocol that recommended screening for strongyloidiasis in at-risk patients. We identified 559 and 795 patients in the first and second periods, respectively. The percentage of individuals screened increased significantly from 8.8% to 51.6% after the screening recommendation was included in the protocol (odds ratio [OR] 11.08, 95% confidence interval [CI] 8.01-15.33). In both periods, the screening rate was significantly higher among those receiving immunosuppression than those who did not receive steroids and/or tocilizumab. No other factors influenced the screening rate. In conclusion, including strongyloidiasis screening recommendations in COVID-19 management protocols led to its increased implementation. However, the overall screening rate remained low, emphasizing the need for further efforts to enhance screening practices.

Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Invasive fungal infection, particularly intraabdominal candidiasis, exerts a negative impact on the outcome of pancreas transplant recipients (PTRs). Optimal antifungal prophylaxis in this context remains unclear., Methods: We performed a single-centre retrospective study to compare the incidence of invasive candidiasis during the first 6 post-transplant months in a cohort of 218 PTRs over two periods in which different agents for antifungal prophylaxis were used: fluconazole (Fluco-Px) from March 1995 to June 2012, and micafungin followed by fluconazole (Mica-Px) from July 2012 to December 2018., Results: A total of 152 and 66 PTRs received Fluco-Px and Mica-Px. Mean age was 39.7 ± 7.8 years, 56.4% (123/218) were males, and 85.3% (186/218) underwent simultaneous pancreas-kidney transplantation. Invasive candidiasis occurred in 21.7% (33/152) of PTRs under Fluco-Px compared to 24.2% (16/66) of those under Mica-Px (p-value = .681). Median time from transplantation to infection was 8 days (interquartile range [IQR]: 6-16) under Fluco-Px versus 6.5 (IQR: 3.3-15.8) under Mica-Px (p-value = .623). Non-albicans Candida species comprised 27.5% (11/40) and 25.0% (4/16) of episodes under Fluco-Px and Mica-Px respectively (p-value = .849). Surgical site infection was the most common form in both groups (82.5% [33/40] and 87.5% [14/16]; p-value = .954). Multivariable analysis identified cold ischaemia time of the pancreas and kidney grafts, surgical reintervention and insulin requirement after transplantation as risks factor for invasive candidiasis., Conclusion: This retrospective study did not reveal a significant benefit from the initial use of micafungin-based antifungal prophylaxis over fluconazole among PTRs in terms of invasive candidiasis., (© 2022 Wiley-VCH GmbH.)

Background: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients., Methods: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models., Results: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively)., Conclusion: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission., Competing Interests: Conflicts of interest All the authors declare no potential conflict of interest regarding this study., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Agar-plate culture (APC) remains the most sensitive parasitological technique for S. stercoralis diagnosis. Although it was first described three decades ago, the time of incubation of the plates is neither a commonly described feature nor usually standardized. The aim of the study was to analyze the required time to detect S. stercoralis larvae in APC., Methods: A prospective laboratory-based study including all patients with at least one positive APC was performed. The plates were incubated at room temperature for 7 days. Clinical, analytical and parasitological features including results of the direct visualization of the stool (DV) after formalin-ether concentration and time-to-detection (TTD) of the larvae in APC were recorded., Results: A total of 141 samples from 75 patients had a positive APC. In 49 of them (65.3%) three or more stool samples were processed for direct visualization (DV) and APC. Of these 49 patients, 8 (16.3%) were also diagnosed with DV and 41 (83.7%) were diagnosed only with APC. In 38 samples from 23 (30.7%) patients, the TTD was below 2 days, while in 27 samples from 13 (17.3%) patients, the larvae were detected on the 6th and 7th day., Conclusion: Direct visualization failed to detect S. stercoralis in most of the patients that were diagnosed with APC. Incubation periods below 2 and 5 days would miss an important percentage of infections. At least 7 days of incubation of the APC are required to detect presumably low-burden chronic infections in non-endemic countries., (Copyright © 2021. Published by Elsevier B.V.)

Background and objectives : Influenza vaccination rates among medical students (MSs) are below the standards recommended in hospitals where influenza vaccination is not mandatory. We carried out a comparative study in two Spanish university hospitals to reassert this fact and evaluated the impact on vaccination rates of a specific program aimed at promoting influenza vaccination among MSs. Methods : A descriptive cross-sectional study was performed describing influenza vaccination rates and motivations for vaccination during the 2017/18 campaign among MSs in two hospitals affiliated to the same university. We subsequently performed a community-based intervention study during the 2018/19 campaign evaluating the impact of a strategy for promoting influenza vaccination, comparing the hospital where the intervention took place (hospital A) with the one where it did not take place (hospital B). Results : During de 2017/18 campaign the overall influenza vaccination rate was 44.8%, with no differences between hospitals A and B (difference: 3.9%; 95% CI: -4.36-12.16; p -value = .4). During the 2018/19 campaign, vaccination rate increased to 76.4% in hospital A, with significant differences compared with the previous campaign in the same hospital (29.8%; OR 5.00; 95% CI: 3.14-8.3; p -value = .0001) and with that observed in hospital B in the same campaign (21.1%; 95% CI: 13.38-28.82; p -value <.001). Conclusions : Influenza vaccination rates among MSs in two Spanish university affiliated hospitals were below the recommended standards. A new reproducible strategy for promoting influenza vaccination with a specific approach toward MSs achieved a significant improvement in vaccination rate.

Objectives: The World Health Organization recommends routinely screening HIV-infected patients with CD4 + T-cell counts <100/μL for cryptococcal infection to prevent cryptococcal meningitis (CM), based on studies in Sub-Saharan Africa where the prevalence of positive cryptococcal antigen (CrAg+) is ≥ 3% in this subgroup. Data about such prevalence in Spain are unavailable and rare in other European countries. Thus, the Spanish AIDS Study Group guidelines do not recommend routinely screening. We aim to determine the prevalence and outcomes of cryptococcal infection in this subgroup of patients in Spain., Methods: We determined CrAg using a lateral flow assay in banked plasma from participants in the cohort of the Spanish AIDS Research Network. Eligible patients had CD4 + T-cell counts ≤100/μL at the time of plasma collection and a follow-up >4 weeks, unless they died., Results: We included 576 patients from June 2004 to December 2017. Of these, 43 were CrAg+ for an overall prevalence of 7.5%. There were no differences depending on birthplace. The CrAg+ was independently associated with a higher mortality at eight weeks (hazard ratio (HR) 5.36, 95% confidence interval (CI) 1.46-19.56) and 6 months (HR 3.12, 95% CI 1.19-8.21). CM was reported in 10 of the 43 CrAg+ patients. There were no cases among negatives. Five patients had CM when the plasma was collected and five developed it during the follow-up. The number of subjects needed to screen to anticipate the diagnosis of one CM case was 114., Conclusions: The CrAg+ prevalence among HIV-infected patients with CD4 + T-cell counts ≤100/μL diagnosed in Spain, both immigrants and native-born Spanish, is >7%. Consequently, the Spanish AIDS Study Group guidelines have to be updated and recommend routine screening for cryptococcal infection in these patients. Future studies should explore whether this recommendation could be firmly applied to other European populations., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The role of combination immunomodulatory therapy with systemic corticosteroids and tocilizumab (TCZ) for aged patients with COVID-19-associated cytokine release syndrome remains unclear., Methods: A retrospective single-center study was conducted on consecutive patients aged ≥65 years who developed severe COVID-19 between 03 March and 01 May 2020 and were treated with corticosteroids at various doses (methylprednisolone 0.5mg/kg/12h to 250mg/24h), either alone (CS group) or associated with intravenous tocilizumab (400-600mg, one to three doses) (CS-TCZ group). The primary outcome was all-cause mortality by day +14, whereas secondary outcomes included mortality by day +28 and clinical improvement (discharge and/or a ≥2 point decrease on a 6-point ordinal scale) by day +14. Propensity score (PS)-based adjustment and inverse probability of treatment weights (IPTW) were applied., Results: Totals of 181 and 80 patients were included in the CS and CS-TCZ groups, respectively. All-cause 14-day mortality was lower in the CS-TCZ group, both in the PS-adjusted (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.17-0.68; P=0.002) and IPTW-weighted models (odds ratio [OR]: 0.38; 95% CI: 0.21-0.68; P=0.001). This protective effect was also observed for 28-day mortality (PS-adjusted HR: 0.38; 95% CI: 0.21-0.72; P=0.003). Clinical improvement by day +14 was higher in the CS-TCZ group with IPTW analysis only (OR: 2.26; 95% CI: 1.49-3.41; P<0.001). The occurrence of secondary infection was similar between both groups., Conclusions: The combination of corticosteroids and TCZ was associated with better outcomes among patients aged ≥65 years with severe COVID-19., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

To investigate risk factors for invasive aspergillosis (IA) after kidney transplantation (KT), we conducted a systematic search in PubMed and EMBASE to identify studies published until June 2020. We included case-control or cohort design studies comprising KT recipients with a diagnosis of IA, defined according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria, and assessed risk factors for the development of IA. Random-effect models meta-analysis served to pool data. We identified eleven case-control studies (319 IA cases and 835 controls). There was an increased risk of IA among recipients with underlying chronic lung diseases (odds ratio [OR] = 7.26; 95% confidence interval [CI] = 1.05-50.06) and among those with diabetic nephropathy (OR = 1.65; 95% CI = 1.10-2.48). Requiring posttransplant hemodialysis (OR = 3.69; 95% CI = 2.13-6.37) or surgical reintervention (OR = 6.28; 95% CI = 1.67-23.66) were also associated with an increased risk. Moreover, a positive link was identified between IA and posttransplant bacterial infection (OR = 7.51; 95% CI = 4.37-12.91), respiratory tract viral infection (OR = 7.75; 95% CI = 1.60-37.57), cytomegalovirus infection or disease (OR = 2.67; 95% CI = 1.12-6.32), and acute graft rejection (OR = 3.01; 95% CI = 1.78-5.09). In contrast, receiving a kidney from a living donor was associated with a reduced risk (OR = 0.65; 95% CI = 0.46-0.93). KT recipients that accumulate several of these conditions should be closely monitored and a low threshold of suspicion for IA should be maintained. Future studies should explore the benefit of mold-active prophylaxis to this subgroup of KT recipients at highest risk., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Coronavirus disease 2019 (COVID-19) can lead to a massive cytokine release. The use of the anti-interleukin-6 receptor monoclonal antibody tocilizumab (TCZ) has been proposed in this hyperinflammatory phase, although supporting evidence is limited. We retrospectively analyzed 88 consecutive patients with COVID-19 pneumonia that received at least one dose of intravenous TCZ in our institution between 16 and 27 March 2020. Clinical status from day 0 (first TCZ dose) through day 14 was assessed by a 6-point ordinal scale. The primary outcome was clinical improvement (hospital discharge and/or a decrease of ≥2 points on the 6-point scale) by day 7. Secondary outcomes included clinical improvement by day 14 and dynamics of vital signs and laboratory values. Rates of clinical improvement by days 7 and 14 were 44.3% (39/88) and 73.9% (65/88). Previous or concomitant receipt of subcutaneous interferon-β (adjusted odds ratio [aOR]: 0.23; 95% confidence interval [CI]: 0.06-0.94; P = .041) and serum lactate dehydrogenase more than 450 U/L at day 0 (aOR: 0.25; 95% CI: 0.06-0.99; P = .048) were negatively associated with clinical improvement by day 7. All-cause mortality was 6.8% (6/88). Body temperature and respiratory and cardiac rates significantly decreased by day 1 compared to day 0. Lymphocyte count and pulse oximetry oxygen saturation/FiO 2 ratio increased by days 3 and 5, whereas C-reactive protein levels dropped by day 2. There were no TCZ-attributable adverse events. In this observational single-center study, TCZ appeared to be useful and safe as immunomodulatory therapy for severe COVID-19 pneumonia., (© 2020 Wiley Periodicals LLC.)

Background: Which are the consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in liver transplant (LT) recipients?, Methods: We attempted to address this question by reviewing our single-center experience during the first 2 months of the pandemics at a high incidence area., Results: Nineteen adult patients (5 females) were diagnosed by May 5, 2020. Median age was 58 (range 55-72), and median follow-up since transplantation was 83 (range 20-183) months. Cough (84.2%), fever (57.9%), and dyspnea (47.4%) were the most common symptoms. Thirteen patients (68.4%) had pneumonia in x-ray/CT scan. Hydroxychloroquine was administered in 11 patients, associated with lopinavir/ritonavir and interferon β in 2 cases each. Immunomodulatory therapy with tocilizumab was used in 2 patients. Immunosuppression (IS) was halted in one patient and modified in only other two due to potential drug interactions. Five (26.3%) patients were managed as outpatient. Two patients (10.5%) died, 10 (52.6%) were discharged home, and 2 (10.5%) were still hospitalized after a median follow-up of 41 days from the onset of symptoms. Baseline IS regimen remained unchanged in all surviving recipients, with good liver function., Conclusions: Our preliminary experience shows a broad spectrum of disease severity in LT patients with COVID-19, with a favorable outcome in most of them without needing to modify baseline IS., (© 2020 Wiley Periodicals LLC.)

Hepatic sinusoidal obstruction syndrome (SOS) is a life-threatening complication with high mortality rate. Even if it is more commonly described after hematopoietic stem-cell transplant, hepatic-SOS may occur following the use of certain chemotherapeutic agents. Mitomycin-C has been previously identified as a causal agent when administered intravenously at high doses. We report herein the first case of hepatic-SOS due to intravesical instillation of mitomycin-C, after a traumatic urinary catheterization with significant hematuria. Although this procedure is usually considered safe, without the systemic side effects related to intravenous administration of the drug, clinicians must be aware of its potential risks to facilitate an early diagnosis, avoid a delay in the withdrawal of the causative drug and set up an appropriate therapy as soon as possible.

Objective: To analyse the ocular manifestations of patients with GPA, their treatment and outcome., Methods: Retrospective cohort study performed at the National Referral Center for Vasculitis, Cochin Hospital, Paris (France), from January 2005 to December 2015. Among 308 patients with a new diagnosis of GPA in accordance with the American College of Rheumatology classification criteria and/or revised Chapel Hill nomenclature definitions, we identified those with ocular involvement and a subsequent follow up in our center., Results: The prevalence of ocular involvement in our GPA series was 38.6%; 63 patients were analysed with a median follow-up of 50.5 months (IQR: 17.8-82.8). Scleritis (18 patients, 28.6%) and episcleritis (18 patients, 28.6%) were the most common ophthalmologic manifestations, followed by orbital disease (13 patients, 20.6%). Bilateral involvement and visual acuity loss was seen in 29.1% and 16.7% of patients, respectively. Ocular involvement was the first GPA manifestation in 9 patients (14.3%), concomitant with systemic manifestation in 36 (57.1%), and occurred only during follow-up in 18 (28.6%). The indication for GPA treatment was suggested by ocular involvement in 12 patients (19.0%), by systemic features in 40 (63.5%) and by both ocular and systemic involvement in 11 (17.5%). Remission of ocular involvement was achieved in 51 patients (80.9%). In the remaining 12 (19.1%), symptoms persisted or even worsened, finally leading to rituximab (RTX) therapy in 8 of them (66.7%). Altogether, when used as first line or for refractory disease, ocular remission was achieved in 11 of the 12 cases (91.7%) treated with RTX versus 34 of the 47 cases (72.3%) treated with CYC (P = .260). Eye disease relapsed in 14 patients (22.2%). RTX allowed achievement of remission in 8 of them (57.1%). In the remaining six, other immunosuppressive drugs were used., Conclusions: Scleritis and episcleritis are the most common ocular manifestations in GPA, most of the time associated with other systemic manifestations. In >40% of cases, ocular manifestations were refractory to initial treatment or recurrent and led to RTX prescription, which appeared to be useful in these situations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Functional status linked to a poor outcome in a broad spectrum of medical disorders. Barthel Activities of Daily Life Index (BADLI) is one of the most extended tools to quantify functional dependence. Whether BADLI can help to predict outcomes in elderly patients with acute venous thromboembolism (VTE) is unknown. The current study aimed to ascertain the influence of BADLI on 6-month all-cause mortality in aged patients with VTE. This is a prospective observational study. We included consecutive patients older than 75-year-old with an acute VTE between April 2015 and April 2017. We analyzed several variables as mortality predictors, including BADLI-measured functional status. Afterward, we performed a multivariate analysis, using logistic regression, to identify all-cause mortality independent predictive factors. Two hundred and two subjects were included. Thirty-five (17%) patients died in the first 6 months. The leading cause of death was cancer (59%). After multivariable logistic regression, we identified BADLI and Charlson index as independent predictors for 6-months mortality [BADLI (every decrease of 10 points) OR 1.21 95% CI (1.03-1.42) and Charlson index OR 1.71 95% CI (1.21-2.43)]. Body mass index (BMI) values were inversely related to mortality [OR 0.85 95% CI (0.75-0.95)]. In conclusion, BADLI, BMI, and Charlson index scores are independent predictive factors for 6-month all-cause mortality in old patients with VTE.

The incidence of visceral leishmaniasis (VL) after solid organ transplantation (SOT) is increasing. The optimal therapy for post-transplant VL remains unclear, as relapses after liposomal amphotericin B (L-AmB) are common. Miltefosine has been shown to be effective for treating VL in immunocompetent patients, although data in the specific population of SOT recipients are lacking. In the setting of an outbreak of leishmaniasis occurring in Southwest Madrid, we reviewed our experience in 6 SOT recipients with persistent or relapsing VL who received a 28-day course of miltefosine (2.5 mg/kg/day) as salvage therapy. All patients had been treated previously with L-AmB as first-line therapy. The incident episode of VL occurred at a median of 14 months after transplantation. Two patients experienced persistent infection and the remaining 4 had a relapse after a median interval of 168 days since the completion of the course of L-AmB. All the patients had an apparent initial clinical improvement with miltefosine. However, VL relapsed in 3 of them (after a median interval of 46 days), which required retreatment with L-AmB-based regimens. Miltefosine therapy was followed by a prolonged secondary prophylaxis with L-AmB in the only 2 cases with sustained clinical response and ongoing immunosuppression. No adverse effects associated with miltefosine were observed. Albeit limited, our experience suggests that miltefosine monotherapy likely has a limited utility to obtain a long-lasting clinical response in complicated (persistent or relapsing) forms of post-transplant VL, although its role in association with L-AmB-based secondary prophylaxis may merit further investigation., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients., (© 2016 Steunstichting ESOT.)

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085)., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Recent studies suggest that Epstein-Barr virus DNAemia (EBVd) may act as a surrogate marker of post-transplant immunosuppression. This hypothesis has not been tested so far in lung transplant (LT) recipients., Methods: We included 63 patients undergoing lung transplantation at our center between October 2008 and May 2013. Whole blood EBVd was systematically assessed by real-time polymerase chain reaction assay on a quarterly basis. The occurrence of late complications (overall and opportunistic infection [OI] and chronic lung allograft dysfunction [CLAD]) was analyzed according to the detection of EBVd within the first 6 months post transplantation., Results: Any EBVd was detected in 30 (47.6%) patients. Peak EBVd was higher in patients with late overall infection (2.23 vs. 1.73 log10 copies/mL; P = 0.026) and late OI (2.39 vs. 1.74 log10 copies/mL; P = 0.004). The areas under receiver operating characteristic curves for predicting both events were 0.806 and 0.871 respectively. The presence of an EBVd ≥2 log10 copies/mL during the first 6 months post transplantation was associated with a higher risk of late OI (adjusted hazard ratio [aHR] 7.92; 95% confidence interval [CI] 2.10-29.85; P = 0.002). Patients with detectable EBVd during the first 6 months also had lower CLAD-free survival (P = 0.035), although this association did not remain statistically significant in the multivariate analysis (aHR 1.26; 95% CI 0.87-5.29; P = 0.099)., Conclusions: Although preliminary in nature, our results suggest that the detection of EBVd within the first 6 months after transplantation is associated with the subsequent occurrence of late OI in LT recipients., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The aim of this review was to assess the effectiveness to reduce clinical adverse events and safety of insulin administered in basal-bolus-corrector or basal-corrector regimens (BB) versus a sliding scale scheme (SS) in patients with diabetes or newly diagnosed hyperglycemia admitted to a conventional (not critical) medical or surgical hospital ward., Method: A Medline search was conducted. The Odds ratio was the main summary measure. A random effects model with the Mantel-Haenszel procedure was used., Results: A total of 957 citations were collected, of which nine were finally included in the systematic review. Patients in the BB group had better blood glucose control than those with SS. Overall, there was a nonsignificant trend to a lower risk of adverse events in the BB as compared to the SS group (OR 0.67 [95% CI 0.22 to 2.04], [I(2)=71%]). There was a nonsignificant trend to an increased risk of hypoglycemia in the BB group (OR 2.29 [95% CI 0.50 to 10.49] [I(2)=70%])., Conclusion: Despite its benefit for glycemic control during hospitalization, this review did not show that use of the BB scheme decreases clinical events in patients hospitalized in a conventional ward. Because of heterogeneity of the results, we think that clinical trials are needed addressing its effect in patient subgroups in which the BB scheme may be used safely and with longer follow-up periods., (Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)

Bacillus Calmette-Guérin (BCG) is the most effective intravesical immunotherapy for superficial bladder cancer. Although generally well tolerated, BCG-related infectious complications may occur following instillation. Much of the current knowledge about this complication comes from single case reports, with heterogeneous diagnostic and therapeutic approaches and no investigation on risk factors for its occurrence. We retrospectively analyzed 256 patients treated with intravesical BCG in our institution during a 6-year period, with a minimum follow-up of 6 months after the last instillation. We also conducted a comprehensive review and pooled analysis of additional cases reported in the literature since 1975. Eleven patients (4.3%) developed systemic BCG infection in our institution, with miliary tuberculosis as the most common form (6 cases). A 3-drug antituberculosis regimen was initiated in all but 1 patient, with a favorable outcome in 9/10 cases. There were no significant differences in the mean number of transurethral resections prior to the first instillation, the time interval between both procedures, the overall mean number of instillations, or the presence of underlying immunosuppression between patients with or without BCG infection. We included 282 patients in the pooled analysis (271 from the literature and 11 from our institution). Disseminated (34.4%), genitourinary (23.4%), and osteomuscular (19.9%) infections were the most common presentations of disease. Specimens for microbiologic diagnosis were obtained in 87.2% of cases, and the diagnostic performances for acid-fast staining, conventional culture, and polymerase chain reaction (PCR)-based assays were 25.3%, 40.9%, and 41.8%, respectively. Most patients (82.5%) received antituberculosis therapy for a median of 6.0 (interquartile range: 4.0-9.0) months. Patients with disseminated infection more commonly received antituberculosis therapy and adjuvant corticosteroids, whereas those with reactive arthritis were frequently treated only with nonsteroidal antiinflammatory drugs (p < 0.001 for all comparisons). Attributable mortality was higher for patients aged ≥65 years (7.4% vs 2.1%; p = 0.091) and those with disseminated infection (9.9% vs 3.0%; p = 0.040) and vascular involvement (16.7% vs 4.6%; p = 0.064). The scheduled BCG regimen was resumed in only 2 of 36 patients with available data (5.6%), with an uneventful outcome. In the absence of an apparent predictor of the development of disseminated BCG infection after intravesical therapy, and considering the protean variety of clinical manifestations, it is essential to keep a high index of suspicion to initiate adequate therapy promptly and to evaluate carefully the risk-benefit balance of resuming intravesical BCG immunotherapy.

Introduction: Venous thromboembolism is a common cause of morbidity and mortality. Although cirrhosis has classically been considered as an acquired bleeding diathesis, there is increasing evidence that rejects the traditional belief that these patients are naturally protected against venous thromboembolism. However, antithrombotic prophylaxis in this setting is still underused. The aim of this review is to assess if the use of heparin in cirrhotic patients is effective in the prevention of venous thromboembolism and whether its use is related to an increase in bleeding episodes., Material and Methods: We searched in MEDLINE and EMBASE, using the terms "liver cirrhosis", "heparin", "low molecular weight heparin," "venous thrombosis", "deep venous thrombosis", "hemorrhage" and "bleeding". We sought for clinical trials and observational studies performed in patients with liver cirrhosis to evaluate the efficacy or the safety of the heparin. It was used the Mantel-Haenszel method with a random effects model. Odd Ratio was the main measure of effect. The results of the pooled OR and its 95% confidence intervals were expressed in forest plots. The heterogeneity was assessed by the I(2) statistic. The statistical software RevMan was used., Results and Conclusions: The current review found that, although the use of heparin was not related to higher rates of bleeding in cirrhotic patients (pooled OR 0.87 95% CI (0.34-2.18)), it doesn´t decrease the risk of venous thromboembolism in patients receiving prophylaxis, with a pooled OR 1.65 95% (0.36 to 7.54). However, further prospective studies are needed to assess this issue., (© 2013.)