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1.
Hernia ; 27(3): 677-685, 2023 06.
Article in English | MEDLINE | ID: mdl-37138139

ABSTRACT

Abdominal compartment syndrome is a potentially life-threatening condition seen in critically ill patients, and most often caused by acute pancreatitis, postoperative abdominal vascular thrombosis or mesenteric ischemia. A decompressive laparotomy is sometimes required, often resulting in hernias, and subsequent definitive wall closure is challenging. AIM: This study aims to describe short term results after a modified Chevrel technique for midline laparotomies in patients witch abdominal hypertension. MATERIALS AND METHODS: We performed a modified Chevrel as an abdominal closure technique in 9 patients between January 2016 and January 2022. All patients presented varying degrees of abdominal hypertension. RESULTS: Nine patients were treated with new technique (6 male and 3 female), all of whom had conditions that precluded unfolding the contralateral side as a means for closure. The reasons for this were diverse, including presence of ileostomies, intraabdominal drainages, Kher tubes or an inverted T scar from previous transplant. The use of mesh was initially dismissed in 8 of the patients (88,9%) because they required subsequent abdominal surgeries or active infection. None of the patients developed a hernia, although two died 6 months after the procedure. Only one patient developed bulging. A decrease in intrabdominal pressure was achieved in all patients. CONCLUSION: The modified Chevrel technique can be used as a closure option for midline laparotomies in cases where the entire abdominal wall cannot be used.


Subject(s)
Abdominal Wall , Abdominal Wound Closure Techniques , Pancreatitis , Humans , Male , Female , Critical Illness , Acute Disease , Herniorrhaphy , Pancreatitis/etiology , Pancreatitis/surgery , Abdominal Wall/surgery , Laparotomy/adverse effects , Surgical Mesh
2.
ESMO Open ; 6(4): 100215, 2021 08.
Article in English | MEDLINE | ID: mdl-34325108

ABSTRACT

BACKGROUND: Young oncologists are at particular risk of professional burnout, and this could have a significant impact on their health and care of their patients. The coronavirus disease 2019 (COVID-19) pandemic has forced rapid changes in professionals' jobs and training, with the consequent physical and psychological effects. We aimed to characterize burnout levels and determinants in young oncologists, and the effects of the pandemic on their training and health. METHODS: Two online surveys were conducted among oncology residents and young oncology specialists in Spain. The first addressed professional burnout and its determinants before the COVID-19 pandemic, while the second analyzed the impact of the pandemic on health care organization, training, and physical and psychological health in the same population. RESULTS: In total, 243 respondents completed the first survey, and 263 the second; 25.1% reported significant levels of professional burnout. Burnout was more common among medical oncology residents (28.2%), mainly in their second year of training. It was significantly associated with a poor work-life balance, inadequate vacation time, and the burnout score. Nearly three-quarters of respondents (72%) were reassigned to COVID-19 care and 84.3% of residents missed part of their training rotations. Overall, 17.2% of this population reported that they had contracted COVID-19, 37.3% had scores indicating anxiety, and 30.4% moderate to severe depression. Almost a quarter of young oncologists (23.3%) had doubts about their medical vocation. CONCLUSIONS: Burnout affects a considerable number of young oncologists. The COVID-19 pandemic has had a profound impact on causes of burnout, making it even more necessary to periodically monitor it to define appropriate detection and prevention strategies.


Subject(s)
Burnout, Professional , COVID-19 , Oncologists , Burnout, Professional/epidemiology , Burnout, Psychological/epidemiology , Burnout, Psychological/prevention & control , Humans , Medical Oncology , Pandemics , SARS-CoV-2
3.
Ann Vasc Surg ; 73: 86-96, 2021 May.
Article in English | MEDLINE | ID: mdl-33493590

ABSTRACT

OBJECTIVES: To analyze the outcome of vascular procedures performed in patients with COVID-19 infection during the 2020 pandemic. METHODS: This is a multicenter, prospective observational cohort study. We analyzed data from 75 patients with COVID-19 infection undergoing vascular surgery procedures in 17 hospitals across Spain and Andorra between March and May 2020. The primary end point was 30-day mortality. Clinical Trials registry number NCT04333693. RESULTS: The mean age was 70.9 (45-94) and 58 (77.0%) patients were male. Around 70.7% had postoperative complications, 36.0% of patients experienced respiratory failure, 22.7% acute renal failure, and 22.7% acute respiratory distress syndrome (ARDS). All-cause 30-days mortality rate was 37.3%. Multivariate analysis identified age >65 years (P = 0.009), American Society of Anesthesiologists (ASA) classification IV (P = 0.004), preoperative lymphocyte count <0.6 (×109/L) (P = 0.001) and lactate dehydrogenase (LDH) >500 (UI/L) (P = 0.004), need for invasive ventilation (P = 0.043), postoperative acute renal failure (P = 0.001), ARDS (P = 0.003) and major amputation (P = 0.009) as independent variables associated with mortality. Preoperative coma (P = 0.001), quick Sepsis Related Organ Failure Assessment (qSOFA) score ≥2 (P = 0.043), lymphocytes <0.6 (×109/L) (P = 0.019) leucocytes >11.5 (×109/L) (P = 0.007) and serum ferritin >1800 mg/dL (P = 0.004), bilateral lung infiltrates on thorax computed tomography (P = 0.025), and postoperative acute renal failure (P = 0.009) increased the risk of postoperative ARDS. qSOFA score ≥2 was the only risk factor associated with postoperative sepsis (P = 0.041). CONCLUSIONS: Patients with COVID-19 infection undergoing vascular surgery procedures showed poor 30-days survival. Age >65 years, preoperative lymphocytes <0.6 (x109/L) and LDH >500 (UI/L), and postoperative acute renal failure, ARDS and need for major amputation were identified as prognostic factors of 30-days mortality.


Subject(s)
COVID-19/complications , Postoperative Complications/epidemiology , Vascular Surgical Procedures/adverse effects , Acute Kidney Injury/etiology , Age Factors , Aged , Aged, 80 and over , Analysis of Variance , Andorra/epidemiology , COVID-19/mortality , Cohort Studies , Female , Humans , L-Lactate Dehydrogenase/blood , Lymphocyte Count , Male , Middle Aged , Postoperative Complications/mortality , Prognosis , Respiratory Distress Syndrome/etiology , Risk Factors , Spain/epidemiology , Treatment Outcome
4.
PLoS Pathog ; 16(10): e1008999, 2020 10.
Article in English | MEDLINE | ID: mdl-33057424

ABSTRACT

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus known to cause epidemics resulting in predominantly symptomatic infections, which in rare cases cause long term debilitating arthritis and arthralgia. Significant progress has been made in understanding the roles of canonical RNA sensing pathways in the host recognition of CHIKV; however, less is known regarding antagonism of CHIKV by cytosolic DNA sensing pathways like that of cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING). With the use of cGAS or STING null cells we demonstrate that the pathway restricts CHIKV replication in fibroblasts and immune cells. We show that DNA accumulates in the cytoplasm of infected cells and that CHIKV blocks DNA dependent IFN-ß transcription. This antagonism of DNA sensing is via an early autophagy-mediated degradation of cGAS and expression of the CHIKV capsid protein is sufficient to induce cGAS degradation. Furthermore, we identify an interaction of CHIKV nsP1 with STING and map the interaction to 23 residues in the cytosolic loop of the adaptor protein. This interaction stabilizes the viral protein and increases the level of palmitoylated nsP1 in cells. Together, this work supports previous publications highlighting the relevance of the cGAS-STING pathway in the early detection of (+)ssRNA viruses and provides direct evidence that CHIKV interacts with and antagonizes cGAS-STING signaling.


Subject(s)
Chikungunya virus/immunology , Interferon Type I/immunology , Membrane Proteins/immunology , Nucleotidyltransferases/immunology , Aedes , Animals , Autophagy/immunology , Cell Culture Techniques , Chikungunya virus/physiology , HEK293 Cells , Humans , Immunity, Innate , Interferon Type I/metabolism , Interferon-beta/immunology , Interferon-beta/metabolism , Membrane Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Transcription, Genetic , Viral Proteins/metabolism , Virus Replication
5.
Transplant Proc ; 52(5): 1468-1471, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32204902

ABSTRACT

Abdominal wall transplant is developed in the context of intestinal and multivisceral transplant, in which it is often impossible to perform a primary wall closure. Despite the fact that abdominal wall closure is not as consequential in liver transplant, there are circumstances in which it might determine the success of the liver graft, especially in situations that compromise the abdominal cavity and facilitate an abdominal compartment syndrome. CASE 1: A 14-year-old girl suffering from cryptogenic cirrhosis with severe portal hypertension that causes ascites and severe malnutrition. Uneventful liver transplant, with a graft procured from a 14-year-old donor. At the time of wall closure it was decided to implant a nonvascularized fascia graft to supplement the right side of the transverse incision, with a 17 x 7 cm defect. This required reintervention after 4 months for biliary stricture. At that point, the wall graft was almost completely integrated into the native tissue. CASE 2: A 63-year-old man, transplanted for hepatitis C virus+ hepatocellular carcinoma+ nonocclusive portal thrombosis. Thirty-six hours after transplant the patient developed portal thrombosis. Thrombectomy and closure with biological mesh were performed. After 24 hours he was reoperated on for abdominal compartment syndrome and temporary closure with a Bogotá bag. Six days later he underwent omentectomy, intestinal decompression, and left components separation, identifying a 25 x 20 cm defect. For definitive closure, a nonvascularized fascia graft procured from a different donor was used, accomplishing a reduction in intra-abdominal pressure. Nonvascularized fascia transplantation is an interesting alternative in liver transplant recipients with abdominal wall closure difficulties.


Subject(s)
Abdominal Wall , Abdominal Wound Closure Techniques , Fascia/transplantation , Liver Transplantation/methods , Plastic Surgery Procedures/methods , Abdominal Wall/surgery , Adolescent , Female , Humans , Male , Middle Aged , Retrospective Studies
6.
Transplant Proc ; 51(1): 33-37, 2019.
Article in English | MEDLINE | ID: mdl-30598229

ABSTRACT

BACKGROUND: The prevalence of obesity has increased dramatically, even in the population awaiting a liver transplantation. Despite their associated complications, we cannot consider morbid obesity any longer as an absolute contraindication to liver transplantation. Dietary approaches alone are usually completely ineffective. Bariatric surgery is the gold-standard treatment for morbid obesity and can be performed before, during, or after transplantation. MATERIALS AND METHODS: At our Liver Transplantation Unit, a single surgeon performed a sleeve gastrectomy in 8 patients with liver cirrhosis due to nonalcoholic steatohepatitis, alcohol, or HCV. The Child score was A in 6 patients and B in the remaining 2 patients. Two of our patients had portal hypertension with mild esophageal varices. The procedure was performed laparoscopically in 7 cases (87.5%); in the other case, it was performed by open approach due to portal hypertension and according to patient preferences. RESULTS: Patients showed no postoperative morbidity or mortality. The mean postoperative body mass index of our patients was 37.4, 33.3, and 30.3 kg/m2 at 3, 6, and 12 months after surgery, respectively. The mean percentage excess weight loss of our patients was 42.9%, 62.2%, and 76.3% at 3, 6, and 12 months. Two of the patients have already undergone a successful liver transplant. CONCLUSION: Bariatric surgery in selected patients with compensated cirrhosis and without significative portal hypertension is reasonable. There are not clear guidelines on the use of bariatric surgery in patients with cirrhosis. In our experience, the sleeve gastrectomy is safe and effective in the treatment of patients with compensated cirrhosis; in a short time, the sleeve gastrectomy can improve candidacy in morbidly obese patients awaiting transplantation.


Subject(s)
Bariatric Surgery/methods , Liver Cirrhosis/complications , Liver Transplantation , Obesity, Morbid/complications , Obesity, Morbid/surgery , Adult , Female , Gastrectomy/methods , Humans , Liver Cirrhosis/surgery , Male , Middle Aged
7.
Transplant Proc ; 48(2): 539-42, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27109996

ABSTRACT

BACKGROUND: Surgical complications in multivisceral transplantation (MVT) are frequent and always severe. Those related to technical issues are relevant as they have implications not only on the graft but also on patient survival. The aim of this study was to review our case-based data and experience with 5 MVT performed since December 2004. CASE REPORT: A 38 year-old woman presented with ultra-short bowel syndrome due to massive ischemia also affecting the celiac trunk. She also had moderate to severe hepatitis/steatosis with some degree of fibrosis on liver biopsy, due to long-term home parenteral nutrition (HPN). An MVT was carried out in September 2010 including the liver, stomach, pancreatoduodenal complex with the spleen, and small bowel. The postoperative course was complicated by a leak from the pyloromiotomy, requiring reoperation on postoperative day 13. She also had central line catheter infection and renal impairment, requiring renal replacement therapy, and was discharged on postoperative day 150. Fifteen days later she was hospitalized because of severe abdominal pain associated with an abdominal mass. Computed tomography showed an aortic donor graft pseudoaneurysm, so we decided to operate on the patient. A complete resection of the pseudoaneurysm using an interposed polytetrafluoroethylene graft was performed. Six months after the MVT, the patient died due to sepsis, despite a functional graft and complete digestive autonomy. CONCLUSIONS: Although this complication is rare, surgical complications in MVT are severe and may seriously impair graft and patient survival.


Subject(s)
Aneurysm, False/surgery , Aneurysm, Infected/etiology , Aortic Aneurysm, Thoracic/etiology , Blood Vessel Prosthesis/adverse effects , Intestine, Small/transplantation , Liver Transplantation/adverse effects , Short Bowel Syndrome/surgery , Adult , Aneurysm, False/etiology , Aneurysm, False/microbiology , Aneurysm, Infected/diagnosis , Aneurysm, Infected/microbiology , Aortic Aneurysm, Thoracic/diagnosis , Aortic Aneurysm, Thoracic/microbiology , Blood Vessel Prosthesis/microbiology , Female , Humans , Reoperation
8.
Springerplus ; 5: 276, 2016.
Article in English | MEDLINE | ID: mdl-27006884

ABSTRACT

This article proposes the application of Laplace Transform-Homotopy Perturbation Method and some of its modifications in order to find analytical approximate solutions for the linear and nonlinear differential equations which arise from some variational problems. As case study we will solve four ordinary differential equations, and we will show that the proposed solutions have good accuracy, even we will obtain an exact solution. In the sequel, we will see that the square residual error for the approximate solutions, belongs to the interval [0.001918936920, 0.06334882582], which confirms the accuracy of the proposed methods, taking into account the complexity and difficulty of variational problems.

9.
Am J Transplant ; 16(1): 72-82, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26317573

ABSTRACT

We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids. Compared with controls, more CD3(-) IELs of the grafts expressed CD56, NKp44, interleukin (IL)-23 receptor, retinoid-related orphan receptor gamma t (RORγt), and CCR6. No difference was observed in granzyme B, and CD3(-) CD127(+) cells were more abundant in native intestines. Ex vivo, and after in vitro activation, CD3(-) IELs in grafts produced significantly more interferon (IFN)-γ and IL-22, and a double IFNγ(+) IL-22(+) population was observed. Epithelial cell-depleted grafts IELs were cytotoxic, whereas this was not observed in controls. In conclusion, different from native intestines, a CD3(-) IEL subset predominates in grafts, showing features of natural killer cells and intraepithelial ILC1 (CD56(+) , NKp44(+) , CCR6(+) , CD127(-) , cytotoxicity, and IFNγ secretion), ILC3 (CD56(+) , NKp44(+) , IL-23R(+) , CCR6(+) , RORγt(+) , and IL-22 secretion), and intermediate ILC1-ILC3 phenotypes (IFNγ(+) IL-22(+) ). Viability of intestinal grafts may depend on the balance among proinflammatory and homeostatic roles of ILC subsets.


Subject(s)
Antigens, CD/metabolism , CD3 Complex/metabolism , Epithelial Cells/immunology , Integrin alpha Chains/metabolism , Intestinal Diseases/surgery , Intestines/transplantation , T-Lymphocyte Subsets/immunology , Adult , Aged , Allografts , Case-Control Studies , Cytokines/metabolism , Female , Humans , Intestinal Diseases/immunology , Killer Cells, Natural/immunology , Lymphocyte Activation , Male , Middle Aged , Young Adult
10.
Nucleic Acids Res ; 43(1): 179-95, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25514925

ABSTRACT

Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs.


Subject(s)
Fungal Proteins/metabolism , Gene Expression Regulation, Fungal , Polyadenylation , mRNA Cleavage and Polyadenylation Factors/metabolism , 5' Untranslated Regions , Fungal Proteins/chemistry , Fungal Proteins/genetics , Magnaporthe/genetics , Magnaporthe/growth & development , Magnaporthe/metabolism , Open Reading Frames , Plant Diseases/microbiology , Protein Structure, Tertiary , Proteolysis , TOR Serine-Threonine Kinases/metabolism , mRNA Cleavage and Polyadenylation Factors/chemistry , mRNA Cleavage and Polyadenylation Factors/genetics
11.
Transplant Proc ; 46(6): 2140-2, 2014.
Article in English | MEDLINE | ID: mdl-25131125

ABSTRACT

BACKGROUND: Renal failure (RF) is a frequent complication in non-renal solid organ transplants. In the present study, we analyze our experience with intestinal transplants (ITx). METHODS: Between 2004 and 2012, we performed 21 ITx in 19 adult patients. Alemtuzumab was used as an induction agent followed by tacrolimus. Renal function was assessed before ITx and during the perioperative period. RESULTS: The main cause for transplants was non-resectable desmoids tumors (33.3%), followed by vascular thrombosis (19%) and others. Medical complications were frequent, especially infectious diseases, which were the most common (51%). Surgical complications were also frequent, but most of them (>50%) were mild but leading to a great number of re-operations and prolonged stays in hospital. Acute rejection is very frequent (66.6%) but mild in more than 70% of the cases. Finally, RF was very frequent (68.4%; 13/19 patients) and accounted for 15.6% of all medical complications. Causes were multiple. One patient is awaiting a kidney transplant, but no other patients need renal replacement therapy at the moment. Ileostomy closure was performed in 5 of 12 patients alive, showing improved renal function in 3 of them. CONCLUSIONS: RF is a problem in ITx and is always multifactorial. Increases in hospital stay, higher morbidity and is a cause for hospital readmission. Almost all patients had an impaired renal function when discharged. Immunosuppressants and ileostomy closure as soon as possible might prevent RF.


Subject(s)
Intestinal Diseases/surgery , Intestine, Small/transplantation , Organ Transplantation/adverse effects , Renal Insufficiency/etiology , Adult , Female , Humans , Incidence , Male , Middle Aged , Renal Insufficiency/epidemiology , Retrospective Studies , Spain/epidemiology , Young Adult
12.
Pediatr Transplant ; 18(6): 594-8, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25039398

ABSTRACT

Children are one of the groups with the highest mortality rate on the waiting list for LT. Primary closure of the abdominal wall is often impossible in the pediatric population, due to a size mismatch between a large graft and a small recipient. We present a retrospective cohort study of six pediatric patients, who underwent delayed abdominal wall closure with a biological mesh after LT, and in whom early closure was impossible. A non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) Reconstructive Tissue Matrix; LifeCell Corp, Bridgewater, NJ, USA) was used in all of the cases of the series. After a mean follow-up of 26 months (21-32 months), all patients were asymptomatic, with a functional abdominal wall after physical examination. Non-cross-linked porcine-derived acellular dermal matrix (Strattice(™) ) is a good alternative for delayed abdominal wall closure after pediatric LT. Randomized controlled trials are necessary to determine the best moment and the best technique for abdominal wall closure.


Subject(s)
Abdominal Wall/surgery , Acellular Dermis , Liver Transplantation , Animals , Child, Preschool , Humans , Infant , Male , Retrospective Studies , Surgical Mesh , Swine , Treatment Outcome
13.
Int Sch Res Notices ; 2014: 747098, 2014.
Article in English | MEDLINE | ID: mdl-27433526

ABSTRACT

The homotopy perturbation method (HPM) is coupled with versions of Laplace-Padé and Padé methods to provide an approximate solution to the nonlinear differential equation that describes the behaviour of a flow with a stretching flat boundary due to partial slip. Comparing results between approximate and numerical solutions, we concluded that our results are capable of providing an accurate solution and are extremely efficient.

14.
Transplant Proc ; 45(5): 1966-8, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769084

ABSTRACT

BACKGROUND: Sexual and reproductive abnormalities affect up to 50% patients with terminal liver failure. However, these functions recover quickly after orthotopic liver transplantation (OLT). Thus, 80%-90% of OLT women of childbearing age recover menstruation within a few months after transplantation. The aim of our study was to analyze the impact of pregnancy among liver transplant recipients at our center, as well as to analyze the effects of immunosuppression on the fetus. METHODS: From April 1986 to April 2011, we performed 1500 OLT in 1341 recipients. Among these recipients, 18 patients (1.2%) become pregnant during the follow-up. RESULTS: The most frequent causes of terminal liver failure were as follows: chronic parenchymal disease (n = 9; 50%), cholestatic disease (n = 3; 16.6%), acute liver failure (n = 5; 27.7%), and metabolic disease (n = 1; 5.5%) The average recipient age at the beginning of pregnancy was 21.2 (±7.3) years. Sixteen patients (88%) became pregnant beyond a year after OLT. The 30 pregnancies in our study resulted in the following: newborns alive (NBA; n = 20; 66.6%) abortions (n = 8; 26.6%) or fetal deaths (n = 2; 6%). The most common immunosuppressant used during pregnancy was tacrolimus (75%) followed by cyclosporine (25%). There were no maternal deaths during pregnancy or the postpartum period. DISCUSSION: We did not observe significant differences between immunosuppression type and maternal complications, pregnancy duration, and childbirth type. Although pregnancy is potential risk, the literature and our results suggest that at a year or more after OLT it usually is safe and successful.


Subject(s)
Liver Transplantation , Adolescent , Adult , Female , Humans , Immunosuppressive Agents/administration & dosage , Infant, Newborn , Pregnancy , Pregnancy Outcome , Retrospective Studies , Young Adult
15.
Transplant Proc ; 45(5): 1971-4, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23769086

ABSTRACT

INTRODUCTION: Everolimus is a potent immunosuppressant with several advantages over calcineurin inhibitors, such as good tolerance, preventive effects on cardiovascular morbidity, and mortality and cancer prevention as it inhibits cell proliferation. PATIENTS AND METHODS: Between April 1986 and December 2010, we performed 1500 liver transplants (OLT) in 1341 recipients, including 57 patients who were prescribed everolimus 24 (42.1%) as monotherapy and 33 (57.9%) as treatments combined with other immunosuppressants. We performed a retrospective analysis of our experience with conversion to everolimus in OLT recipients. RESULTS: The 43 men and 14 women had a mean overall age at transplantation of 59.1 ± 10 years. The most frequent indication for OLT was hepatocellular carcinoma (HCC; 53.8%). Everolimus was introduced to prevent HCC recurrence (53%), development of de novo tumors (33%), address renal dysfunction (7%), or overcome side effects of other immunosuppressants (7%). We observed a significant improvement in renal function using the estimated glomerular filtration rate (Crockcroft-Gault formula) from 68.5 mL/min before to 74.5 mL/min after switching to everolimus. The 72% of recipients who developed ≥1 adverse event, most frequently showed hyperlipidemia (34.4%). CONCLUSION: Both monotherapy and combined everolimus regimens were well-tolerated immunosuppressive regimens in liver transplant recipients with recurrent or de novo malignancies. Everolimus improved renal function. The most common side effects were hyperlipidemia, edema, and mouth ulcerations, which were well controlled with anti-lipidemic agents or decreased everolimus dosages.


Subject(s)
Immunosuppressive Agents/administration & dosage , Liver Transplantation , Sirolimus/analogs & derivatives , Aged , Carcinoma, Hepatocellular/surgery , Drug Therapy, Combination , Everolimus , Female , Humans , Liver Neoplasms/surgery , Male , Middle Aged , Sirolimus/administration & dosage
16.
Transplant Proc ; 44(6): 1475-8, 2012.
Article in English | MEDLINE | ID: mdl-22841188

ABSTRACT

BACKGROUND: Hepatitis C (HCV) is among the most common causes of end-stage liver disease worldwide. The donor shortage leads us to consider alternative organ sources such as HCV-positive donors. The outcomes of these transplants must be evaluated thoroughly since there is universal recurrence of disease among HCV-positive liver transplant recipients. METHODS: From January 2005 to April 2011, we performed 143 liver transplants (OLT) to treat end-stage liver disease secondary to HCV infection. Thirteen patients (9,1%) received livers from HCV-positive donors. A control group consisted of 130 HCV-positive patients who underwent OLT during the same period with organs from HCV-negative donors. Donor HCV status was assessed by 2 tests: HCV antibodies and viral load. Not only recipient and graft survivals were analyzed, but also frequency, timing and severity of hepatitis recurrence. RESULTS: Among 143 transplants performed in HCV-positive recipients during a 6-year period from January 1, 2005, to April 30, 2011, 9.1% of patients received an organ from an anti-HCV-positive donor, 72.7% of whom showed a negative viral load. The vast majority (80%) of our patients suffered hepatitis during their follow-up, 22.4% of which were severe cases. CONCLUSIONS: No significant difference in patient or graft survival was observed between the 2 groups. A high percentage of grafts with initial positive serology for HCV showed no viral replication. Grafts from HCV-positive donors can be considered to be a safe, effective source for liver donation.


Subject(s)
Donor Selection , End Stage Liver Disease/surgery , Hepacivirus/immunology , Hepatitis C Antibodies/blood , Hepatitis C/complications , Liver Transplantation , Tissue Donors/supply & distribution , Biomarkers/blood , Chi-Square Distribution , End Stage Liver Disease/mortality , End Stage Liver Disease/virology , Female , Graft Survival , Hepacivirus/genetics , Hepacivirus/growth & development , Hepatitis C/blood , Hepatitis C/diagnosis , Hepatitis C/mortality , Humans , Kaplan-Meier Estimate , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , RNA, Viral/blood , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Spain , Time Factors , Treatment Outcome , Viral Load , Virus Replication
17.
Transplant Proc ; 41(6): 2469-71, 2009.
Article in English | MEDLINE | ID: mdl-19715954

ABSTRACT

OBJECTIVE: Bladder drainage (BD) of exocrine secretions is associated with urological and pancreatitis complications. Herein we have analyzed our experience with conversion from BD to enteric drainage (ED). PATIENTS AND METHODS: From March 1995 to September 2008, 118 patients underwent pancreas transplantation. There were 68 men and 50 women of a overall mean age at transplantation of 37.8 years. There were 66 patients with bladder drainage (BD) and 52 with enteric drainage (ED). RESULTS: Eight of 66 BD pancreas recipients (12.1%) underwent ED conversion. The mean time from pancreas transplantation to ED conversion was 29.3 +/- 30.6 months (range, 1-91 months). The major indications for conversion were recurrent reflux pancreatitis and chronic urinary tract infections in 7 patients; metabolic acidosis in 8; urethritis with severe perineoscrotal swelling in 1; and duodenocystostomy leak in 1. A comparative analysis of converted ED and not converted BD showed only a significantly prolonged period in the intensive care unit for patients who needed ED conversion (89 vs 47 hours; P < .01). Only 1 patient showed a duodenoenteric leak and peritonitis after conversion that required removal of the pancreas graft. The remaining 7 patients did not develop any postoperative complications and are currently well, showing normal pancreas graft function at a mean follow-up of 51.7 months after ED conversion. Patient and graft survivals were 100% and 87.5%, respectively. After ED conversion all urological complications disappeared; patients discontinued the use of oral bicarbonate. CONCLUSION: ED conversion in pancreas transplant recipients with urological and reflux pancreatitis complications was a safe, effective procedure.


Subject(s)
Drainage/methods , Intestine, Small/surgery , Pancreas Transplantation/methods , Urinary Bladder/surgery , Adult , Aged , Diabetes Mellitus, Type 1/surgery , Diabetes Mellitus, Type 2/surgery , Diabetic Nephropathies/surgery , Drainage/adverse effects , Female , Graft Survival , Humans , Male , Middle Aged , Pancreas Transplantation/adverse effects , Pancreas Transplantation/physiology , Renal Replacement Therapy/statistics & numerical data , Retrospective Studies
18.
Transplant Proc ; 41(6): 2472-4, 2009.
Article in English | MEDLINE | ID: mdl-19715955

ABSTRACT

INTRODUCTION: Surgical complications after pancreas transplantation, and subsequently relaparotomies, are frequently associated with graft loss, important morbidities, and occasionally patient death. PATIENTS AND METHODS: From March 1995 to September 2008, 118 diabetic patients underwent pancreas transplantation: 109 simultaneous pancreas-kidney and nine pancreas after kidney. There were 68 men and 50 women. Mean age at transplantation was 37.8 +/- 7.8 years (range = 25-66). We analyzed donor and recipient characteristics, rate of relaparotomies, risk factors, as well as patient and graft survivals. RESULTS: Forty patients (33.9%) underwent one or more relaparotomies. The causes for relaparotomy were: graft thrombosis in 15 patients (12.7%), bleeding in 14 (11.9%), duodenal stump leak in 7 (5.9%), severe pancreatitis and/or abscess in 5 (4.2%), and small bowel obstruction in 3 (2.5%). Graft pancreatectomy was performed in 52.5% (21 patients). The causes of graft loss were: graft thrombosis in 15 patients (12.7%), bleeding in 14 (11.9%), and duodenal stump leaks in 7 (5.9%). Mortality rate after relaparotomy was 3.38% (four patients). Relaparotomy rate for thrombosis was higher among the portoiliac than the portocaval vein anastomosis group (20.0% vs 10.2%; P = NS), and significantly higher for the bladder drainage than the enteric drainage technique (18.2% vs 5.8%; P < .05). Patients without relaparotomy experienced a significantly higher 5-year graft survival rate than those who underwent relaparotomy (87.2% vs 37.9%; P < .001), but 5-year patient survivals were similar (96.8% without relaparotomy vs 89.6% with relaparotomy). CONCLUSIONS: Abdominal complications and the necessity for relaparotomy were associated with important morbidity and significantly reduced pancreas graft survival.


Subject(s)
Laparotomy/statistics & numerical data , Pancreas Transplantation/adverse effects , Reoperation/statistics & numerical data , Abscess/mortality , Adult , Aged , Diabetes Mellitus/surgery , Diabetic Nephropathies/surgery , Duodenum/pathology , Female , Graft Survival , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Kidney Transplantation/statistics & numerical data , Male , Middle Aged , Pancreas Transplantation/mortality , Pancreas Transplantation/statistics & numerical data , Postoperative Complications/classification , Postoperative Complications/epidemiology , Postoperative Complications/mortality , Retrospective Studies , Survival Rate
19.
Infect Disord Drug Targets ; 7(4): 336-43, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18220965

ABSTRACT

The influenza virus NS1 protein has been shown to be a multifunctional immune modulator and a virulence factor for this virus. Among its multiple functions are the inhibition of the type I interferon (IFN) system in infected cells, the binding and sequestration of dsRNA, the interference with the host mRNA processing, the facilitation of preferential viral mRNA translation, and the inhibition of dendritic cell (DC) activation. The combination of all these functions makes the NS1 protein a very potent inhibitor of immunity and allows influenza virus to efficiently escape the immune surveillance and to establish infection in the host. There are different domains in the NS1 protein that are required for specific functions, which provides several potential targets for the action of antiviral drugs. Additionally, the crystal structure of both the N-terminal RNA binding domain and the C-terminal effector domain of the NS1 protein have been resolved, potentially allowing for better antiviral drug design. Recent advances in the understanding how viruses are detected by infected cells are unveiling the mechanisms by which the NS1 protein can perform some of its multiple immune modulating activities. In this review the multiple functions of the NS1 protein are discussed and several possible options for drug targets within the influenza virus NS1 protein will be explored. Such drugs could make influenza viruses less efficient at evading the immune system in the host.


Subject(s)
Immunity, Innate , Interferon Type I/antagonists & inhibitors , Viral Nonstructural Proteins/immunology , Humans , Immune Tolerance/immunology , Influenza A virus/chemistry , Influenza A virus/immunology , Influenza B virus/chemistry , Influenza B virus/immunology , Influenza, Human/immunology , Influenza, Human/prevention & control , Interferon Type I/immunology , RNA, Viral/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/physiology
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