Valentín Cuervas-Mons - Academia.edu (original) (raw)
Papers by Valentín Cuervas-Mons
Liver Transplantation
Long-term humoral immunity and its protective role in liver transplant patients has not been eluc... more Long-term humoral immunity and its protective role in liver transplant patients has not been elucidated. We performed a prospective multicenter study to assess the persistence of IgG antibodies in liver transplant recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 liver transplant recipients were matched with 65 non-transplanted patients by a propensity score including variables with recognized impact on COVID-19. Liver transplant recipients showed a lower prevalence of anti-nucleocapsid (27.7% vs. 49.2%, P = 0.02) and anti-spike IgG antibodies (88.2% vs. 100.0%, P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplant patients one year after COVID-19 (0.49 [IQR 0.15-1.40] vs. 1.36 [IQR 0.53-2.91], P < 0.001). Vaccinated liver transplant recipients showed higher antibody levels compared to unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in non-transplanted individuals (P = 0.70). In liver transplant patients, a longer interval since transplantation (OR=1.10, 95% CI 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies one-year postinfection. In conclusion, compared with non-transplanted patients, liver transplant recipients show a lower long-term persistence of anti-SARS-CoV-2 antibodies. However, SARS-CoV-2 vaccination after COVID-19 in liver transplant patients achieves a significant increase in antibody levels, comparable to that of non-transplanted patients.
Revista Española de Enfermedades Digestivas
BACKGROUND AND AIM Reduction in calcineurin inhibitor levels is considered crucial to decrease th... more BACKGROUND AND AIM Reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and the impact on kidney function of everolimus plus reduced tacrolimus (EVR+rTAC) vs mycophenolate mofetil plus tacrolimus (MMF+TAC) in LT recipients from Spain. METHODS REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post transplantation to receive EVR+rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF+TAC (TAC levels 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS In the EVR+rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF+TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2) with significant (p < 0.05) differences in eGFR changes throughout the study. However, both groups had a similar clinical benefit in renal function (improvement in 18.6% vs 19.1% and stabilization in 81.4% vs 80.9% of patients in EVR+rTAC vs MMF+TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7% vs 3.8%), deaths (5.7% vs 2.8%), and serious adverse events (51.9% vs 44.0%) between the 2 groups. CONCLUSION EVR+rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.
The Lancet Gastroenterology & Hepatology, 2020
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Transplantation Proceedings, 2016
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR)... more New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015. Regimens were as follows: sofosbuvir+simeprevir (8), SOF+ledipasvir (6), sofosbuvir+daclatasvir (5) and sofosbuvir+ribavirin (5). Overall, treatment was very well tolerated with only mild adverse events in 42% of patients. However, a 52-year-old woman developed severe respiratory failure within 10 days after beginning sofosbuvir+daclatasvir. High-resolution computerized tomography showed areas of diffused ground-glass opacities in both lungs, suggesting drug-induced lung injury. The bronchoalveolar lavage showed marked signs of acute inflammation without recovering any infectious agent. The patient was treated with high-dose corticosteroids and steadily recovered. DAA therapy was not discontinued, but sofosbuvir was replaced by simeprevir. She reached sustained virologic response after completing 24 weeks of DAA therapy. Given the close temporal association, radiologic and bronchoalveolar lavage findings, and negative work-up for infectious agents, we postulated that sofosbuvir was the most likely explanation for drug-induced lung injury in our patient.
Gastroenterología y Hepatología, 2004
Transplantation reviews (Orlando, Fla.), Jan 26, 2017
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multid... more Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contac...
The Journal of heart transplantation
A 13-year-old boy underwent orthotopic heart transplantation for end-stage idiopathic dilated car... more A 13-year-old boy underwent orthotopic heart transplantation for end-stage idiopathic dilated cardiomyopathy. Immunosuppressive therapy consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Endomyocardial biopsies revealed persistent moderate rejection, which was treated aggressively. In the sixth week, septic arthritis by Salmonella enteritidis developed. We discuss our management of this exceptional complication and the poor results obtained because of superimposed cytomegalovirus infection.
International Journal of Infectious Diseases, 2021
Journal of Hepatology, 1990
European Journal of Cancer, 1999
s141 1 gmlm' on days l-4 and days 29-32 and a bolus dose of mitomycin C IO mg/m2 on day I. Result... more s141 1 gmlm' on days l-4 and days 29-32 and a bolus dose of mitomycin C IO mg/m2 on day I. Results: A total of 96 patients satisfied the inclusion criteria, 70% female. The median age was 62 years (range 33-86). T stages at presentation were: TX 2%, Tl 18%, T2 50%, T3 9%, T4 21%. Thirteen patients (14%) had involved inguinal nodes. Disease persisted after chemoradiation in 10%. At 10 years following commencement of radiotherapy a further 19% were estimated to have suffered locoregional relapse, 6% distant metastases and 19% death without known progression, leaving 46% surviving failure-free at 10 years. Estimated overall survival was 91% at 2 years, 72% at 5 years and 59% at 10 years. There were no significant differences in failure-free survival between T stages-Tl, T2, T3, T4, between NO and NI-3, between Tl-2N0 and T3m4/N1-3. Patients with tumours ~4 cm survived significantly longer without failure than patients with larger tumours (P = 0.006). In terms of overall survival, there were no significant differences between T stages, between NO and N1-3, between Tl-2N0 and T3/r4/Nl-3, or between ~4 cm and >4 cm tumours. Conclusion: In our experience, TNM stage for carcinoma of anus does not predict failure-free survival or overall survival in patients treated with chemoradiation. 514 POSTER A phase II study of hypofractionated radiotherapy in combination with Gemcitabin in the palliative treatment of advanced pancreatic carcinoma
Transplantation Proceedings
Internal and Emergency Medicine
Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of b... more Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of bacterial infections were examined in patients consecutively admitted with COVID-19 at one tertiary hospital in Madrid between March 1st and April 30th, 2020. Among 1594 hospitalized patients with COVID-19, 135 (8.5%) experienced bacterial infectious events, distributed as follows: urinary tract infections (32.6%), bacteremia (31.9%), pneumonia (31.8%), intra-abdominal infections (6.7%) and skin and soft tissue infections (6.7%). Independent predictors of bacterial infections were older age, neurological disease, prior immunosuppression and ICU admission (p
Gastroenterología y Hepatología, 2003
OBJECTIVES To conduct a descriptive study with an analysis of risk factors for early infection in... more OBJECTIVES To conduct a descriptive study with an analysis of risk factors for early infection in liver transplant patients, and to determine the resistance of the bacteria involved. PATIENTS AND METHODS The study included 149 liver transplant recipients. All cases of infection occurring 0-90 days after transplantation were considered early infection. Pre-, intra- and postoperative variables were analyzed, and isolated microorganisms were studied. Selective bowel decontamination with quinolones, and perioperative and antifungal prophylaxis were carried out in all patients. RESULTS The incidence of infection was 73.1%: bacterial (49.7%), viral (35.5%), fungal (10.1%) and mixed (4.5%). In the first postoperative month the most frequent infections were bacterial and in the second and third months, viral (p = 0.001). Multivariate analysis of risk factors identified the following: days of parenteral nutrition, duration of surgery > 5 hours, rejection and CMV seronegative status. Among...
Ascites is one of the most severe complications of cirrhosis with portal hypertension. Since mast... more Ascites is one of the most severe complications of cirrhosis with portal hypertension. Since mast cells by type 2 immunity could be involved in the production of portal hypertensive ascites, we are studying the effectiveness of Ketotifen administration, a mast cell stabilizer, to modulate the production of interleukin-13, a type-2 associated cytokine, as well as calcitonin gene-related peptide (CGRP), one important regulator of its production, in the ascitic fluid of microsurgical extrahepatic cholestatic rats. The increased IL-13 and CGRP release in the ascitic fluid of the rats with obstructive cholestasis and its significant reduction after both, prophylactic plus therapeutic and delayed therapeutic oral administration of Ketotifen, allows for proposing that mast cells could play an important role in the etiopathogeny of portal hypertensive ascites.
Transplantation Proceedings
Liver Transplantation
Long-term humoral immunity and its protective role in liver transplant patients has not been eluc... more Long-term humoral immunity and its protective role in liver transplant patients has not been elucidated. We performed a prospective multicenter study to assess the persistence of IgG antibodies in liver transplant recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 liver transplant recipients were matched with 65 non-transplanted patients by a propensity score including variables with recognized impact on COVID-19. Liver transplant recipients showed a lower prevalence of anti-nucleocapsid (27.7% vs. 49.2%, P = 0.02) and anti-spike IgG antibodies (88.2% vs. 100.0%, P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplant patients one year after COVID-19 (0.49 [IQR 0.15-1.40] vs. 1.36 [IQR 0.53-2.91], P < 0.001). Vaccinated liver transplant recipients showed higher antibody levels compared to unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in non-transplanted individuals (P = 0.70). In liver transplant patients, a longer interval since transplantation (OR=1.10, 95% CI 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies one-year postinfection. In conclusion, compared with non-transplanted patients, liver transplant recipients show a lower long-term persistence of anti-SARS-CoV-2 antibodies. However, SARS-CoV-2 vaccination after COVID-19 in liver transplant patients achieves a significant increase in antibody levels, comparable to that of non-transplanted patients.
Revista Española de Enfermedades Digestivas
BACKGROUND AND AIM Reduction in calcineurin inhibitor levels is considered crucial to decrease th... more BACKGROUND AND AIM Reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and the impact on kidney function of everolimus plus reduced tacrolimus (EVR+rTAC) vs mycophenolate mofetil plus tacrolimus (MMF+TAC) in LT recipients from Spain. METHODS REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post transplantation to receive EVR+rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF+TAC (TAC levels 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS In the EVR+rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF+TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2) with significant (p < 0.05) differences in eGFR changes throughout the study. However, both groups had a similar clinical benefit in renal function (improvement in 18.6% vs 19.1% and stabilization in 81.4% vs 80.9% of patients in EVR+rTAC vs MMF+TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7% vs 3.8%), deaths (5.7% vs 2.8%), and serious adverse events (51.9% vs 44.0%) between the 2 groups. CONCLUSION EVR+rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.
The Lancet Gastroenterology & Hepatology, 2020
Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on ... more Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
Transplantation Proceedings, 2016
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR)... more New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015. Regimens were as follows: sofosbuvir+simeprevir (8), SOF+ledipasvir (6), sofosbuvir+daclatasvir (5) and sofosbuvir+ribavirin (5). Overall, treatment was very well tolerated with only mild adverse events in 42% of patients. However, a 52-year-old woman developed severe respiratory failure within 10 days after beginning sofosbuvir+daclatasvir. High-resolution computerized tomography showed areas of diffused ground-glass opacities in both lungs, suggesting drug-induced lung injury. The bronchoalveolar lavage showed marked signs of acute inflammation without recovering any infectious agent. The patient was treated with high-dose corticosteroids and steadily recovered. DAA therapy was not discontinued, but sofosbuvir was replaced by simeprevir. She reached sustained virologic response after completing 24 weeks of DAA therapy. Given the close temporal association, radiologic and bronchoalveolar lavage findings, and negative work-up for infectious agents, we postulated that sofosbuvir was the most likely explanation for drug-induced lung injury in our patient.
Gastroenterología y Hepatología, 2004
Transplantation reviews (Orlando, Fla.), Jan 26, 2017
Solid organ transplant (SOT) recipients are especially at risk of developing infections by multid... more Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contac...
The Journal of heart transplantation
A 13-year-old boy underwent orthotopic heart transplantation for end-stage idiopathic dilated car... more A 13-year-old boy underwent orthotopic heart transplantation for end-stage idiopathic dilated cardiomyopathy. Immunosuppressive therapy consisted of cyclosporine, azathioprine, prednisone, and antithymocyte globulin. Endomyocardial biopsies revealed persistent moderate rejection, which was treated aggressively. In the sixth week, septic arthritis by Salmonella enteritidis developed. We discuss our management of this exceptional complication and the poor results obtained because of superimposed cytomegalovirus infection.
International Journal of Infectious Diseases, 2021
Journal of Hepatology, 1990
European Journal of Cancer, 1999
s141 1 gmlm' on days l-4 and days 29-32 and a bolus dose of mitomycin C IO mg/m2 on day I. Result... more s141 1 gmlm' on days l-4 and days 29-32 and a bolus dose of mitomycin C IO mg/m2 on day I. Results: A total of 96 patients satisfied the inclusion criteria, 70% female. The median age was 62 years (range 33-86). T stages at presentation were: TX 2%, Tl 18%, T2 50%, T3 9%, T4 21%. Thirteen patients (14%) had involved inguinal nodes. Disease persisted after chemoradiation in 10%. At 10 years following commencement of radiotherapy a further 19% were estimated to have suffered locoregional relapse, 6% distant metastases and 19% death without known progression, leaving 46% surviving failure-free at 10 years. Estimated overall survival was 91% at 2 years, 72% at 5 years and 59% at 10 years. There were no significant differences in failure-free survival between T stages-Tl, T2, T3, T4, between NO and NI-3, between Tl-2N0 and T3m4/N1-3. Patients with tumours ~4 cm survived significantly longer without failure than patients with larger tumours (P = 0.006). In terms of overall survival, there were no significant differences between T stages, between NO and N1-3, between Tl-2N0 and T3/r4/Nl-3, or between ~4 cm and >4 cm tumours. Conclusion: In our experience, TNM stage for carcinoma of anus does not predict failure-free survival or overall survival in patients treated with chemoradiation. 514 POSTER A phase II study of hypofractionated radiotherapy in combination with Gemcitabin in the palliative treatment of advanced pancreatic carcinoma
Transplantation Proceedings
Internal and Emergency Medicine
Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of b... more Bacterial infections may complicate the course of COVID-19 patients. The rate and predictors of bacterial infections were examined in patients consecutively admitted with COVID-19 at one tertiary hospital in Madrid between March 1st and April 30th, 2020. Among 1594 hospitalized patients with COVID-19, 135 (8.5%) experienced bacterial infectious events, distributed as follows: urinary tract infections (32.6%), bacteremia (31.9%), pneumonia (31.8%), intra-abdominal infections (6.7%) and skin and soft tissue infections (6.7%). Independent predictors of bacterial infections were older age, neurological disease, prior immunosuppression and ICU admission (p
Gastroenterología y Hepatología, 2003
OBJECTIVES To conduct a descriptive study with an analysis of risk factors for early infection in... more OBJECTIVES To conduct a descriptive study with an analysis of risk factors for early infection in liver transplant patients, and to determine the resistance of the bacteria involved. PATIENTS AND METHODS The study included 149 liver transplant recipients. All cases of infection occurring 0-90 days after transplantation were considered early infection. Pre-, intra- and postoperative variables were analyzed, and isolated microorganisms were studied. Selective bowel decontamination with quinolones, and perioperative and antifungal prophylaxis were carried out in all patients. RESULTS The incidence of infection was 73.1%: bacterial (49.7%), viral (35.5%), fungal (10.1%) and mixed (4.5%). In the first postoperative month the most frequent infections were bacterial and in the second and third months, viral (p = 0.001). Multivariate analysis of risk factors identified the following: days of parenteral nutrition, duration of surgery > 5 hours, rejection and CMV seronegative status. Among...
Ascites is one of the most severe complications of cirrhosis with portal hypertension. Since mast... more Ascites is one of the most severe complications of cirrhosis with portal hypertension. Since mast cells by type 2 immunity could be involved in the production of portal hypertensive ascites, we are studying the effectiveness of Ketotifen administration, a mast cell stabilizer, to modulate the production of interleukin-13, a type-2 associated cytokine, as well as calcitonin gene-related peptide (CGRP), one important regulator of its production, in the ascitic fluid of microsurgical extrahepatic cholestatic rats. The increased IL-13 and CGRP release in the ascitic fluid of the rats with obstructive cholestasis and its significant reduction after both, prophylactic plus therapeutic and delayed therapeutic oral administration of Ketotifen, allows for proposing that mast cells could play an important role in the etiopathogeny of portal hypertensive ascites.
Transplantation Proceedings