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Biomedical subjects

M Navasa

Publications and source records attributed to M Navasa.

At least 19 recordsLinked to original sources

Multifocal avascular necrosis after liver transplantation: an unusual presentation of the antiphospholipid syndrome.

We describe the case of a 31-year-old man who presented with an antiphospholipid syndrome (APS), which manifested as multifocal avascular necrosis (AVN) one year after orthotopic liver transplantation. The patient developed multiple AVN affecting hips, left knee, humerus and tarsal bones just after withdrawal of corticosteroid therapy. Three years later when lupus anticoagulant was detected, he began anticoagulant treatment and no further AVN episodes were observed. It is important to be aware of this clinical manifestation of APS, especially in these cases where it can be easily overlooked because of corticosteroid therapy.

Acenocoumarol↗

One thousand liver transplants: the hospital clinic experience.

OBJECTIVES: Our goal was to study a consecutive series of 1000 liver transplants performed in our institution to evaluate the changes over time in donors, recipients, and results. PATIENTS AND METHODS: With the aim to evaluate differences between transplantation in the first period and the present period, the first consecutive 100 liver transplants performed from June 1988 to June 1990 (first period) were compared with the last consecutive 200 liver transplants performed from January 2001 to June 2003 (second period). RESULTS: Increased donor age, change in donor cerebral death etiology, and increasing numbers of grafts from alternative methods using cadaveric donors were observed in the second period. Piggy-back technique and the biliary anastomosis without a t-tube was also started in the second period. One-year actuarial patient survival was higher in the second period (84% vs 91.3%). The need for retransplantation in the overall series was 95%. One-, 5-, and 10-year actuarial retransplant survival was 67.7%, 51.3%, and 39.4%, respectively. CONCLUSIONS: Technical innovations, better understanding of donor and recipient aspects, and global improvements were the reasons for time-related improved results of liver transplantation.

Adult↗

Bacteremia and septic shock after solid-organ transplantation.

BACKGROUND: Bacteremia and septic shock remain important causes of morbidity and mortality after solid-organ transplantation. The aim of this study was to assess the characteristics and risk factors for mortality among patients with bloodstream infections and shock. METHODS: From January 1991 to December 2000, all episodes of bloodstream infection were prospectively examined, considering bacteremia or fungemia as significant according to the CDC criteria. Septic shock was diagnosed in a patient with systemic inflammatory response syndrome and persistent dysfunction of at least one organ caused by hypoperfusion despite hemodynamic support. RESULTS: There were 466 episodes of bacteremia in 382 patients, with 66 of them developing septic shock. Risk factors for developing shock were age >50 (P = .006), liver transplant (P = .029), nosocomial infection (P = .034), pulmonary focus (P = .0001), P. aeruginosa infection (P = .001), and polymicrobial etiology (P = .039). On multivariate analysis, only age, nosocomial infection, and pulmonary source were significant. Among 66 shock patients, bacteremia was due to gram-negative bacteria in 53%, gram-positive bacteria in 24%, fungal in 7.5%, and polymicrobial in 12% of patients. The most frequent source was the lung (26%). Empiric antimicrobial therapy was correctly chosen in 79%; however, 36 patients died (54%), including 27 despite correct therapy. Urinary tract infections had less mortality than other foci. CONCLUSIONS: Risk factors for developing septic shock in bacteremia were age more than 50 years, nosocomial acquisition, and pulmonary focus. Despite adequate empiric antibiotic therapy, the mortality remained high.

Bacteremia↗

Invasive pulmonary aspergillosis in solid organ and bone marrow transplant recipients.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed. METHODS: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed. RESULTS: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05). CONCLUSIONS: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.

Amphotericin B↗

Steroids and living liver donation increase tacrolimus blood levels in living donor liver transplantation.

The aim of this study was to determine the tacrolimus blood levels in recipients of living donor liver transplants (LDLT) compared with recipients who undergo whole cadaveric liver grafts and to correlate the tacrolimus trough levels with the 12-hour area under the concentration (AUC) curve. From June 2002 to June 2003, the 10 LDLT were prospectively compared with 11 cadaveric transplants. The main immunosuppression was tacrolimus plus steroids. Intraoperative methylprednisolone was administered to all cadaveric organ recipients and only 6 of the 10 LDLT. Median tacrolimus trough levels at day 10 were 14.1 ng/mL for the LDLT group and 9.1 ng/mL for the CLT group (P = NS). The median tacrolimus AUC at day 10 were 185.2 ngxh/mL and 148.1 ngxh/mL for the LDLT group and the cadaveric group, respectively (P = NS). Median tacrolimus trough levels at day 2 were 24.3 ng/mL versus 9.9 ng/mL in the LDLT recipients with and without steroids, respectively (P < .05). Also, median tacrolimus AUC at day 2 were 239 ngxh/mL and 179.7 ngxh/mL when we compared LDLT recipients with and without steroids (P = NS). A significant correlation was observed between tacrolimus trough levels and AUC in the LDLT group (C.C. = 0.936; P < .0001). In conclusion, LDLT recipients display higher tacrolimus blood levels in comparison with cadaveric liver recipients, with a good correlation between tacrolimus trough levels and AUC. Intraoperative steroid administration induces higher tacrolimus levels in LDLT recipients.

Adrenal Cortex Hormones↗

Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.

Antibiotic Prophylaxis↗

[Adult living donor liver transplantation. Analysis of the first 30 cases].

INTRODUCTION: In the last 2-3 years, adult living donor liver transplantation (ALDLT) has been developed on an international scale, multiplying the number of procedures performed. Despite this, analysis of the results is still incomplete. The aim of the present study was to perform a descriptive analysis of the results after the first 3 years of the initiation of the program. MATERIAL AND METHODS: During this period, 30 ALDLT were performed. In all procedures, right lobe grafts were used. The mean age of donors and recipients was 31.8 and 52.7 years, respectively. The main indication for liver transplantation was liver cirrhosis due to hepatitis C virus (70%) and 38% of recipients were stage C in the Child-Pugh classification. A total of 46.7% of recipients had hepatocellular carcinoma. RESULTS: Donors: The mean volume of the remnant liver was 632 cc (40.5% of the previous hepatic mass). Ten donors (33%) presented complications. The most frequent complication was biliary fistula (20%) and three patients required reintervention. The mean length of hospital stay among donors was 11.7 days. Recipients: The mean weight of the graft was 775 g, with a mean difference between graft weight and that of the recipient of 1.11. Fifteen recipients (50%) presented biliary leaks and nine of these (30%) required reintervention. There were no graft losses for technical reasons. Four patients died. With a median follow-up of 14 months, actuarial survival at 18 months was 92.9%. CONCLUSION: ALDLT is an effective method for reducing the number of patients on the waiting list. The probability of survival is similar to that of cadaveric transplantation. Biliary complications in the recipient constitute a problem, the long-term repercussions of which remain to be resolved.

Adolescent↗

Cost effectiveness of adjuvant therapy for hepatocellular carcinoma during the waiting list for liver transplantation.

BACKGROUND: Survival after liver transplantation for early hepatocellular carcinoma (HCC) is worsened by the increasing dropout rate while waiting for a donor. AIMS: To assess the cost effectiveness of adjuvant therapy while waiting for liver transplantation in HCC patients. METHOD: Using a Markov model, a hypothetical cohort of cirrhotic patients with early HCC was considered for: (1) adjuvant treatment-resection was limited to Child-Pugh's A patients with single tumours, and percutaneous treatment was considered for Child-Pugh's A and B patients with single tumours unsuitable for resection or with up to three nodules < 3 cm; and (2) standard management. Length of waiting time ranged from six to 24 months. RESULTS: Surgical resection increased the transplantation rate (>10%) and provided gains in life expectancy of 4.8-6.1 months with an acceptable cost ($40,000/ year of life gained) for waiting lists > or = 1 year whereas it was not cost effective ($74,000/life of year gained) for shorter waiting times or high dropout rate scenarios. Percutaneous treatment increased life expectancy by 5.2-6.7 months with a marginal cost of approximately $20,000/year of life gained in all cases, remaining cost effective for all waiting times. CONCLUSIONS: Adjuvant therapies for HCC while waiting for liver transplantation provide moderate gains in life expectancy and are cost effective for waiting lists of one year or more. For shorter waiting times, only percutaneous treatment confers a relevant survival advantage.

Carcinoma, Hepatocellular↗

Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A.

The purpose of this study was to compare the effects of Cyclosporine A (CyA) and FK506 on bone mass and mineral metabolism in liver transplantation (LT) patients. A prospective study was performed on 18 male patients who underwent LT treated with CyA, and 7 LT patients who received FK506. Bone mineral density (BMD) of the lumbar spine and proximal femur (DPX-L) was measured before and at 6, 12, and 24 months after transplantation. Moreover, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) levels were determined at the same time. The cumulative dose of glucocorticoids was calculated in all patients. At 6 months, lumbar BMD decreased 5.2 +/- 1.2% (P = 0.0005) and 2.9 +/- 2.1% (p = ns) in CyA and FK506 groups, respectively. Lumbar BMD reached baseline values at 1 year in the FK506 group and 2 years after LT in the CyA group. Moreover, significant intergroup differences in femoral neck BMD changes after 2 years of transplant were observed (CyA: -5.2 +/- 1.97 versus FK506: +1.55 +/- 2.2%; P = 0.039). In the first year posttransplant both groups showed a marked increase in PTH and 25OHD levels. The mean cumulative dose of glucocorticoids was higher in the CyA group (CyA group 11.06 +/- 0.46 g versus FK 506 group 6.71 +/- 0.42 g; P < 0.001), and multiple linear regression analysis showed a negative correlation between BMD changes at the lumbar spine and mean cumulative dose of glucocorticoids (P = 0.022). In conclusion, our data suggest that after liver transplantation treatment with FK506 shows a more favorable long-term effect on bone mass evolution than CyA therapy. These differences seem to be associated with the lower dose of glucocorticoids used in the FK506 group.

Absorptiometry, Photon↗

Intrahepatic biliary lesions after orthotopic liver transplantation.

Intrahepatic biliary lesions (IBL) are rare (2-9%) after orthotopic liver transplantation (OLT). The aim was to evaluate the incidence, etiology and outcome. In nine years, a total 532 OLTs were performed in 481 patients. Twenty-four patients developed IBL. Eight were due to HAT, seven to ABOI, three to CDR and six to PI. The time until diagnosis of HAT is longest in patients (14+/-6) with IBL. ABOI is another cause of IBL. CDR is a rare cause of IBL, however when it takes place, patients must undergo Rtx. Finally, PI is a relevant cause of IBL. In order to suppress the incidence of IBL we should consider 1) the systematic use of Doppler-Ultrasound; 2) emergency reoperation of patients with HAT, 3) avoid ABOI in OLT; 4) Rtx in cases of CDR, and 5) OLT should still be performed as an emergency procedure.

ABO Blood-Group System↗

Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics.

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

Adult↗

Bacterial translocation of enteric organisms in patients with cirrhosis.

BACKGROUND/AIMS: The aim of the study was to investigate the prevalence and associated risk factors for bacterial translocation in patients with cirrhosis, a mechanism involved in the pathogenesis of bacterial infections in experimental cirrhosis. METHODS: Mesenteric lymph nodes were obtained for microbiological culture from 101 patients with cirrhosis and from 35 non-cirrhotic patients. RESULTS: Enteric organisms were grown from mesenteric lymph nodes in 8.6% of non-cirrhotic patients. In the 79 cirrhotic patients without selective intestinal decontamination, the prevalence of bacterial translocation significantly increased according to the Child-Pugh classification: 3.4% in Child A, 8.1% in Child B and 30.8% in Child C patients (chi2 = 6.106, P < 0.05). However, translocation by Enterobacteriaceae, the organisms commonly responsible for spontaneous bacteremia and peritonitis in cirrhosis, was only observed in 25% of the cases. The prevalence of bacterial translocation in the 22 cirrhotic patients undergoing selective intestinal decontamination, all Child-Pugh class B and C, was 4.5%. The Child-Pugh score was the only independent predictive factor for bacterial translocation (odds ratio 2.22, P = 0.02). CONCLUSIONS: Translocation of enteric organisms to mesenteric lymph nodes is increased in patients with advanced cirrhosis and is reduced to the level found in non-cirrhotic patients by selective intestinal decontamination.

Adolescent↗