Search

BACKGROUND & AIMS: Liver transplantation (LT) is one of the most complex surgical procedures. Enhanced recovery after surgery (ERAS) aims to reduce the risk of postoperative complications. When patients achieve all desirable outcomes after a procedure, they are considered to have experienced a textbook outcome (TO). METHODS: Two cohorts of patients undergoing low (n = 101) or medium risk (n = 15) LT were identified. The remaining patients (n = 65) were grouped separately. The ERAS protocol included pre-, intra-, and post-operative steps. TO was defined as the absence of complications, prolonged length of hospital stays, readmission and mortality during the first 90 days. RESULTS: One third of patients who underwent ERAS after LT experienced a TO. On multivariable analysis, age (OR, 1.05 [95% CI, 1.01-1.09]; P = .02), and having hepatocellular carcinoma (OR, 2.83 [95% CI, 1.37-6.03]; P = .005) were individually associated with a greater probability of achieving a TO. Belonging to the cohorts of medium risk or outside the selection criteria was associated with a lower probability of achieving a TO (OR, 0.46 [96% CI, 0.22-0.93]; P = .03). Patients less likely to experience TO required more hospital resources. Patients who achieved TO were more likely to remain free of chronic kidney disease (achieved TO, 83.8% [82.7-85.6]; failed TO, 67.9% [66.9-70.2]; P

Introduction Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay, improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to-discharge) before starting our liver transplant activity and then applied this protocol prospectively to every patient undergoing liver transplantation at our institution, monitoring the results periodically. We now report our first six years results. Patients and methods Prospective cohort study of all the liver transplants performed at our institution for the first six years. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and temporary portocaval shunt were strategies common to all cases. Standard immunosuppression administered included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophenolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started early. Results A total of 240 transplants were performed in 236 patients (191 male/45 female) over 74 months, mean age 56.3 +/- 9.6 years, raw MELD score 15.5 +/- 7.7. Predominant etiologies were alcohol (n = 136) and HCV (n = 82), with hepatocellular carcinoma present in 129 (54.7%). Nine patients received combined liver and kidney transplants. The mean operating time was 315 +/- 64 min with cold ischemia times of 279 +/- 88 min. Thirty-one patients (13.1%) were transfused in the OR (2.4 +/- 1.2 units of PRBC). Extubation was immediate (< 30 min) in all but four patients. Median ICU length of stay was 12.7 hours, and median post-transplant hospital stay was 4 days (2-76) with 30 patients (13.8%) going home by day 2, 87 (39.9%) by day 3, and 133 (61%) by day 4, defining our fast-track group. Thirty-day-readmission rate (34.9%) was significantly lower (28.6% vs. 44.7% p=0.015) in the fast-track group. Patient survival was 86.8% at 1 year and 78.6% at five years. Conclusion Fast-Tracking of Liver Transplant patients is feasible and can be applied as the standard of care

Background: HIV-2 is a neglected virus despite estimates of 1–2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with inte- grase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modal- ities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126cells/mm3, respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individ- uals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor-recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain.

Consortia on behalf of the Spanish HTLV Network: C. Rodríguez, M. Vera, J. del Romero, G. Marcaida, M. D. Ocete, E. Caballero, I. Molina, A. Aguilera, J. J. Rodríguez-Calviño, D. Navarro, C. Rivero, M. D. Vilariño, R. Benito, S. Algarate, J. Gil, R. Ortiz de Lejarazu, S. Rojo, J. M. Eirós, A. San Miguel, C. Manzardo, J. M. Miró, J. García, I. Paz, E. Poveda, E. Calderón, D. Escudero, M. Trigo, J. Diz, M. García-Campello, M. Rodríguez Iglesias, A. Hernández Betancor, A. M. Martín, J. M. Ramos, A. Gimeno, F. Gutiérrez, J. C. Rodríguez, V. Sánchez, C. Gómez Hernando, G. Cilla, E. Pérez Trallero, J. López Aldeguer, L. Fernández Pereira, J. Niubó, M. Hernández, A. M. López Lirola, J. L. Gómez Sirvent, L. Force, C. Cifuentes, S. Pérez, L. Morano, C. Raya, A. González Praetorius, J. L. Pérez, M. Peñaranda, S. Hernáez Crespo, J. M. Montejo, L. Roc, A. Martínez Sapiña, I. Viciana, T. Cabezas, A. Lozano, J. M. Fernández, I. García-Bermejo, G. Gaspar, R. García, M. Górgolas, C. Vegas, J. Blas, P. Miralles, M. Valeiro, T. Aldamiz, N. Margall, C. Guardia, E. do Pico, I. Polo, A. Aguinaga, C. Ezpeleta, S. Sauleda, M. Pirón, R. González, L. Barea, A. Jiménez, L. Blanco, A. Suárez, I. Rodríguez Avial, A. Pérez Rivilla, P. Parra, M. Fernández, M. Fernández Alonso, A. Treviño, S. Requena, L. Benítez Gutiérrez, V. Cuervas Mons, C. de Mendoza, P. Barreiro, V. Soriano, O. Corral & F. Gómez-Gallego, [Background]: HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain., [Methods]: All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008., [Results]: A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic., [Conclusion]: The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Two kidney transplant recipients from a single donor became infected with HTLV-1 (human T-lymphotropic virus type 1) in Spain. One developed myelopathy 8 months following surgery despite early prescription of antiretroviral therapy. The allograft was removed from the second recipient at month 8 due to rejection and immunosuppressors discontinued. To date, 3 years later, this patient remains infected but asymptomatic. HTLV-1 infection was recognized retrospectively in the donor, a native Spaniard who had sex partners from endemic regions. Our findings call for a reappraisal of screening policies on donor–recipient organ transplantation. Based on the high risk of disease development and the large flux of persons from HTLV-1 endemic regions, pre-transplant HTLV-1 testing should be mandatory in Spain.

Background. Although only 8%-10% of persons infected with human T-cell leukemia virus type 1 (HTLV-1) may develop virus-associated diseases lifelong, misdiagnosis of asymptomatic infected carriers frequently leads to late diagnoses. Methods. A nationwide HTLV-1 register was created in Spain in 1989. A total of 351 infected persons had been reported by the end of 2017. We examined all new HTLV-1 diagnoses during the last decade and compared their clinical presentation. Results. A total of 247 individuals with HTLV-1 infection had been reported in Spain since year 2008. The incidence has remained stable with 20-25 new diagnoses yearly. Women represented 62%. Only 12% were native Spaniards, most of whom were foreigners from Latin America (72.5%). Up to 57 (23%) individuals presented clinically with HTLV-1-associated conditions, including subacute myelopathy (n = 24; 42.1%), T-cell lymphoma (n = 19; 33.3%), or Strongyloides stercoralis infestation (n = 8; 14%). Human T-cell leukemia virus type 1 diagnosis had been made either at blood banks (n = 109; 44%) or at clinics (n = 138; 56%). It is interesting to note that Spaniards and especially Africans were overrepresented among patients presenting with HTLV-1-associated illnesses, suggesting that misdiagnosis and late presentation are more frequent in these populations compared to Latin Americans. Conclusions. Given that 23% of new HTLV-1 diagnoses in Spain are symptomatic, underdiagnosis must be common. Although screening in blood banks mostly identifies asymptomatic Latin American carriers, a disproportionately high number of Spaniards and Africans are unveiled too late, that is, they already suffer from classic HTLV-1 illnesses.

Background: Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. Methods: A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. Results: Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. Conclusion: HIV coinfection is infrequent (< 5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population.

Background: Whereas HIV-1 has spread globally, HIV-2 is mainly found in West Africa where dual HIV-1/HIV-2 coinfection is nowadays uncommon. Herein, we report the rate, main characteristics, and treatment outcomes of all dually infected patients living in Spain. Methods: We identified retrospectively all persons coinfected with HIV-1 recorded at the Spanish HIV-2 registry. Dual infection had been confirmed using PCR in plasma and/or cells, and/or using discriminatory serological tests. Results: From a total of 373 individuals with HIV-2 recorded at the Spanish registry, 34 (9.1%) were coinfected with HIV-1. Compared with HIV-2 monoinfected persons, dually infected patients were more often male (67.6%), presented with lower median CD4(+) cell counts (204 cells/mu l), and had developed more frequently AIDS events (26.5%). Although 61.7% came from West Africa, 6 (17.6%) were native Spaniards. HIV-1 non-B subtypes were recognized in 75% of coinfected patients, being the most prevalent CRF02_AG. At baseline, 45% of dually infected patients had undetectable plasma HIV-2 RNA. After a median follow-up of 32 (13-48) months on antiretroviral therapy, dually infected patients achieved undetectable viremia in 85% for HIV-1, in 80% for HIV-2; and in 70% for both viruses. Median CD4(+) cell counts reached up to 418 cells/mu l. Conclusion: Roughly 9% of individuals with HIV-2 infection living in Spain are coinfected with HIV-1. Overall, 70% of dually infected patients achieved viral suppression for both viruses under antiretroviral therapy. Given the relatively large population of West Africans living in Spain and the continuous migration flow from HIV-2 endemic areas, HIV-1/HIV-2 coinfection should always be excluded at first diagnosis in all HIV-seroreactive persons. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

Background: HIV-2 is a neglected virus despite estimates of 1-2 million people being infected worldwide. The virus is naturally resistant to some antiretrovirals used to treat HIV-1 and therapeutic options are limited for patients with HIV-2. Methods: In this retrospective observational study, we analysed all HIV-2-infected individuals treated with integrase strand transfer inhibitors (INSTIs) recorded in the Spanish HIV-2 cohort. Demographics, treatment modalities, laboratory values, quantitative HIV-2 RNA and CD4 counts as well as drug resistance were analysed. Results: From a total of 354 HIV-2-infected patients recruited by the Spanish HIV-2 cohort as of December 2017, INSTIs had been given to 44, in 18 as first-line therapy and in 26 after failing other antiretroviral regimens. After a median follow-up of 13 months of INSTI-based therapy, undetectable viraemia for HIV-2 was achieved in 89% of treatment-naive and in 65.4% of treatment-experienced patients. In parallel, CD4 gains were 82 and 126 cells/mm(3), respectively. Treatment failure occurred in 15 patients, 2 being treatment-naive and 13 treatment-experienced. INSTI resistance changes were recognized in 12 patients: N155H (5), Q148H/R (3), Y143C/G (3) and R263K (1). Conclusions: Combinations based on INSTIs are effective and safe treatment options for HIV-2-infected individuals. However, resistance mutations to INSTIs are selected frequently in failing patients, reducing the already limited treatment options.

International audience

International audience

We develop a model in which investment risk drives the demand for CDS insurance. We show that CDS overinsurance (insurance in excess of renegotiation proceeds) is procyclical and allows for greater financing of firms with positive NPV projects. In bad times, CDS overinsurance triggers the early liquidation of firms with low continuation values. Our analysis explains the benefits of CDS contracting over economic cycles and reconciles evidence showing that CDSs are most beneficial for firms that are safer and have higher continuation values. The model generates a number of empirical predictions and provides insights on the regulation of CDS markets.

A recent change to the U.S. tax code (IRS Regulation TD9599) lowered the costs certain creditors incur when restructuring debt out of court. We use this setting to show how CDS spreads gauge the cost wedge between in- versus out-of-court distress resolution. CDS spreads declined by record figures on the regulation's announcement, with declines concentrated among distressed firms with higher ratios of syndicated loans -- the credit category treated by TD9599. Critically, distressed firm's loan renegotiation rates more than doubled, reducing their exposure to financial distress costs, which we estimate are up to 36% of firm value. Those firms' access to syndicated loans increased while associated interest markups declined.

HIV-2 and HTLV-1 infections are globally less frequent than those produced by HIV-1, the classical AIDS agent. In Spain and up to the end of 2014, a total of 310 cases of HIV-2, 274 of HTLV-1, and 776 of HTLV-2 infections had been reported. No cases of HTLV-3 or HTLV-4 infections have been identified so far in Spain. Most persons infected with HIV-2 or HTLV-1 acknowledge epidemiological risk factors for contagion, such as originating from or living in endemic regions and/or having had sexual partners from those areas. However, risk factors could not be recognized in up to 20-25% of carriers in Spain. Thus, it seems worth keeping a high level of clinical suspicion in order to identify earlier these neglected human retroviral infections, since diagnostic procedures and antiviral treatment are specific for each of these agents. In this article we summarize the major contributions reported at the meeting of the Spanish Group for HIV-2/HTLV held in Madrid in December 2014

Producción Científica, Background:HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in compari-son with HIV-1 infection. However, antiretroviral therapy in patients with HIV-2 is less effective and often fails toprovide optimal CD4 recovery.Methods:We examined viral tropism in persons with HIV-2 infection enrolled in the HIV-2 Spanish cohort. Viraltropism was estimated based on V3 sequences obtained from plasma RNA and/or proviral DNA.Results:From a total of 279 individuals with HIV-2 infection recorded in the Spanish national register, 58 V3sequences belonging to 42 individuals were evaluated. X4 viruses were recognized in 14 patients (33%).Patients with X4 viruses had lower median CD4+cell counts than patients with R5 viruses [130 (17 – 210) versus359 (180 – 470) cells/mm3;P¼0.007]. This was true even considering only the subset of 19 patients on antiretro-viral therapy [94 (16 – 147) versus 184 (43 – 368) cells/mm3;P¼0.041]. In multivariate analysis, significant differ-ences in CD4+cell counts between patients with X4 and R5 viruses remained after adjusting for age, gender,antiretroviral therapy and viral load.Conclusions:The presence of X4-tropic viruses in HIV-2 infection is associated with low CD4+cell counts, regard-less of antiretroviral treatment. Along with CD4+cell counts, viral tropism testing may assist decisions aboutwhen to initiate antiretroviral therapy in HIV-2-infected individuals., Fundación Investigación y Educación en Sida. (RIS, ISCIII-RETICRD/12/0017/0031), Fondo de Investigación Sanitaria (FIS, PI10/00520), Ministerio de Salud Consumo y Bienestar Social (EC10/277), Ministerio de Ciencia e Innovación (MICINN, SAF2010/22232), El proyecto Europeo CHAIN (FP7-223131)

This paper develops a model of CDS demand when investment is subject to economic fluctuations and verification is imperfect. We show that CDS overinsurance (insurance in excess of renegotiation proceeds) is procyclical and allows for greater financing of firms with positive NPV projects. In bad times, CDS overinsurance triggers the early liquidation of firms with low continuation values. Our analysis explains the optimality of CDS contracting and reconciles evidence showing that CDSs are most beneficial for firms that are safer and have higher continuation values. The model generates a number of empirical predictions and provides insights on the regulation of CDS markets.