José Antonio Herrero

Clinical Presentation And Outcome Of Tuberculosis In Kidney, Liver, And Heart Transplant Recipients In Spain1

BACKGROUNDnTuberculosis is unusual in transplant recipients. The incidence, clinical manifestations, and optimal treatment of this disease in this population has not been adequately defined. The present study was undertaken to assess the incidence, clinical features, and response to therapy of Mycobacterium tuberculosis infection in solid-organ transplant recipients.nnnMETHODSnWe evaluated retrospectively the incidence, clinical characteristics, diagnostic procedures, antituberculous treatment, clinical course, and factors influencing mortality in 51 solid-organ transplant recipients who developed tuberculosis after transplantation. We also reviewed the world literature on tuberculosis in solid-organ transplantation.nnnRESULTSnThe overall incidence of tuberculosis was 0.8%. The localization was pulmonary in 63% of the cases, disseminated in 25%, and extrapulmonary in 12%. Tuberculosis developed from 15 days to 13 years after surgery (mean, 23 months). In one third of the cases, diagnosis was not suspected initially, and in three cases, diagnosis was made at necropsy. Fever was the most frequent symptom, followed by constitutional symptoms, cough, respiratory insufficiency, and pleuritic pain. Fifteen patients (33%) developed hepatotoxicity during treatment; hepatotoxicity was severe in seven cases. Hepatotoxicity was higher in patients receiving four or more antituberculous drugs (50%) than in patients receiving three drugs (21%; P=0.03). Serum levels of cyclosporine decreased in the 26 patients under the simultaneous use of rifampin. Nine of them (35%) developed acute rejection, and five (56%) died, in comparison with 3 of 17 patients (18%) who did not develop rejection after the use of cyclosporine and rifampin (P=0.03). Although microbiological response was favorable in 94% of the 35 patients who completed 6 or more months of treatment, 16 other patients (31%) died before diagnosis or in the course of treatment. None of the patients treated for more than 9 months died as a consequence of tuberculosis, whereas the mortality rate was 33% among those treated for 6 to 9 months (P=0.03). Use of antilymphocyte antibodies or high doses of steroids for acute rejection before tuberculosis was associated with a higher mortality rate.nnnCONCLUSIONSnM tuberculosis causes serious and potentially life-threatening disease in solid-organ transplant recipients. Treatment with at least three drugs during 9 months or more, avoiding the use of rifampin, appears to be appropriate.

Cardiovascular effects of recombinant human erythropoietin in predialysis patients

Treatment with recombinant human erythropoietin (rHuEPO) has solved the problem of anemia in patients on dialysis. However, its application to predialysis patients has raised some doubts about its effects on the progression of renal disease and on blood pressure (BP) and hemodynamic regulation. We have prospectively studied over at least 6 months a group of 11 predialysis patients receiving rHuEPO treatment (initial dose, 1,000 U subcutaneously three times a week). Clinical assessment and biochemical and hematologic measurements were made once every 2 weeks. Twenty-four-hour ambulatory BP monitoring, echocardiography, and determination of neurohumoral mediators of hemodynamics were performed once every 3 months. An adequate hematologic response was found (hemoglobin, 11.7 +/- 0.4 g/dL v 9 +/- 0.3 g/dL) without changes in the progression of renal disease. A decrease in cardiac output and an increase in total peripheral resistance was seen as anemia improved. A trend toward decreased left ventricular (LV) thickness and a significant decrease in LV mass index (from 178.2 +/- 20.6 g/m2 to 147.3 +/- 20.6 g/m2) were observed. Blood pressure control did not improve; moreover, in some patients an increase in systolic values was detected by ambulatory BP. Casual BP remained seemingly stable. Sequential determinations of neurohumoral mediators of hemodynamic substances (endothelin, renin, norepinephrine, epinephrine, dopamine) failed to explain these results. Ambulatory BP reveals a worse control in some patients who were previously hypertensive and confirms the utility of this technique in the assessment of patients under erythropoietin treatment. The trend toward LV hypertrophy regression without improved BP control confirms the role of anemia among the multiple factors leading to LV hypertrophy in end-stage renal disease (ESRD), and opens therapeutic possibilities. Better control of BP may avoid a potential offsetting of beneficial effects that correcting anemia would have on the cardiovascular system.

Functional glomerular reserve in recipients of en bloc pediatric transplant kidneys

BACKGROUNDnThe transplantation of an adequate renal mass is increasingly recognized to be of importance. The improved graft survival is probably due to a lesser risk of developing hyperfiltration-associated lesions.nnnMETHODSnWe have reviewed the glomerular reserve in our recipients of en bloc pediatric transplant kidneys after an intravenous amino acid overload and compared them to single adult kidney transplant recipients.nnnRESULTSnEn bloc transplants evidenced increased glomerular filtration rate as compared with baseline as from the second hour of amino acid infusion (from 71+/-14 to 84.9+/-17 ml/min, 1.73 m2, P<0.05) and increased renal plasma flow as from the third hour (from 335+/-116 to 402+/-155 ml/min, 1.73 m2, P<0.05). In the single adult kidney recipient group, no change was seen either in the glomerular filtration rate (from 62.5+/-13 to 58.1+/-13 ml/min, 1.73 m2, P=NS) nor in renal plasma flow (from 354+/-125 to 304+/-98 ml/min, 1.73 m2, P=NS).nnnCONCLUSIONSnThese results show that patients receiving en bloc pediatric kidney transplantations have a greater renal functional reserve and show a lesser risk of hyperfiltration.

Usefulness of tissue Doppler on early detection of cardiac disease in Fabry patients and potential role of enzyme replacement therapy (ERT) for avoiding progression of disease

AIMSnCardiac involvement, including progressive cardiomyopathy, is common in Fabry disease and is a leading cause of premature mortality. We sought to determine if tissue Doppler imaging (TDI) could identify Fabry disease patients at risk for the development of cardiomyopathy and if enzyme replacement therapy (ERT) with agalsidase alfa might slow or prevent the progression of cardiac involvement.nnnMETHODS AND RESULTSnFabry disease patients were enrolled in this prospective, observational study. Echocardiography was performed at baseline and periodically throughout the study. A single investigator, blinded to both the type of assessment (baseline or follow-up) and enzyme replacement status of the patient, evaluated all echocardiograms. Seventy-six patients (26 male, 50 females) were enrolled in the study. Twenty men and 13 women were treated with agalsidase alfa during the study. At baseline, increasing interventricular septum thickness was significantly associated with decreasing TDI velocities. Twenty-nine patients >18 years old (23 females) had no evidence of cardiac involvement at baseline (normal LVM and normal TDI velocities). In this cohort, 80% (16 of 20) of patients not on ERT progressed to demonstrating an abnormal TDI velocity during follow-up, whereas only 33% (3 of 9) of patients on ERT progressed to TDI abnormalities (P= 0.031).nnnCONCLUSIONnIn Fabry disease, reduced TDI velocity seems to be the initial sign of cardiac involvement that occurs before the development of cardiac hypertrophy. ERT with agalsidase alfa delays the onset of cardiac involvement and should be considered at an earlier stage of the disease, even in the absence of left ventricular hypertrophy.

Double renal transplant from infant donors : a good alternative for adult recipients

Several groups have reported technical complications and poor graft survival rates in kidney transplants from pediatric donors to adult recipients. Increased incidences of acute rejections, vascular thrombosis, and early glomerulosclerotic lesions have led many groups to abandon this graft combination. Over the last 4 years, we have set up a program of two-kidney transplantation from cadaveric infant donors under age 3 years, which to date includes 15 adult recipients. Thirteen of these grafts are currently functioning at least as well as those from adult donors, after a mean follow-up of 1.5 years. Our surgical and therapeutic procedures have led to a minimization of the early complications reported by other groups. With this transplantation procedure, the patients receive double the number of nephrons, which will probably give them better long-term function. The encouraging results achieved by our group may help change the current consideration of pediatric donors as suboptimal ones.

Nosocomial candidemia at a general hospital: The change of epidemiological and clinical characteristics. A comparative study of 2 cohorts (1993–1998 versus 2002–2005)

BACKGROUNDnNosocomial candidemia (NC) is associated with high mortality, increased hospital stay and greater economical cost.nnnAIMSnTo evaluate epidemiological and clinical aspects of 2 different cohorts of non-paediatric patients with NC.nnnMETHODSnA retrospective observational and comparative study of patients with NC. Patients were identified by review of results of blood cultures from the hospital microbiology laboratory. We analysed epidemiological, clinical, microbiological and laboratory data and changes in the 2 cohorts: 1993-1998 (P1) and from 2002 to 2005 (P2).nnnRESULTSnEighty patients were studied during P1 and 107 during P2; incidence was 9/10,000 in P1 and 15.8/10,000 admitted patients in P2 (p<0.05). Mean age was 52 years in P1 and 61 years in P2 (p<0.05); 66% and 49% NC were due to Candida albicans in P1 and P2, respectively (p<0.05); diabetes was present in 12% in P1 and in 25% in P2 (p<0.05). All of the patients had previously received at least one course of broad-spectrum antibiotics. A statistically significant difference (p<0.05) in predisposing conditions was identified in central intravenous line rate (100% in P1 and 91% in P2) and previous surgery (43% in P1 and 78% in P2). Acute severity of illness at onset and complications were more frequent in P2 (p<0.05). Mortality rate was similar in P1 and P2 (51% and 49.5%, respectively).nnnCONCLUSIONSnFrequency of NC has increased and non-albicans Candida is now more frequent than C. albicans. Although acute severity of illness at onset and complications are now more frequent, mortality remains the same.

Incidence of renal artery stenosis in pediatric en bloc and adult single kidney transplants.

Background. The incidence, time of onset, and outcome of transplant renal artery stenosis (TRAS) in pediatric en bloc (PT) and adult single-kidney (AT) transplants were reviewed. Methods. Forty-three cases (7 PT and 36 AT) of suspected TRAS were selected out of 367 functioning grafts (35 of them PT). Diagnosis was performed by digital subtraction arteriography. Percutaneous transluminal angioplasty (PTA) was performed when needed. Results. Seven (20%) PT and 24 (7.1%) AT presented TRAS. Time of onset was 7±1 months in PT and 18±17 months in AT (P <0.05). PTA was performed in all cases of TRAS in PT and in 19 AT. One PT and 7 AT had re-stenosis. There was no significant difference in renal function after treatment. Control of blood pressure improved in both groups. Conclusions. Recipients of PT grafts showed a higher incidence and earlier onset of TRAS. Re-stenosis was more frequent in AT.

Early initiation of peritoneal dialysis in diabetic patients

Objective. Starting dialysis earlier in diabetic patients than in other patients with chronic kidney disease slows the progression of some diabetic complications, and could affect the survival outcome. The aim of this study is to assess the effect of starting dialysis early in diabetic patients on survival and hospitalization outcome. Material and methods. One-hundred diabetic patients on peritoneal dialysis (PD), 54 with type 1 and 46 with type 2 diabetes, were reviewed. Renal function was estimated by Modification of Diet in Renal Disease-7 (MDRD-7). The patients comprised two groups according to average MDRD-7 (7.7 ml/min/1.73 m2): group I > 7.7 (56 patients) and group II ≤ 7.7 (44 patients). Survival was analysed by Kaplan–Meier plots and Cox hazard regression for the different variables. Results. MDRD-7 values (mean±SD) at the start of PD were 10.6±2.1 in group I and 5.4±1.2 in group II (p<0.001). Serum albumin (p<0.001) and haematocrit values (p=0.013) were higher in group I, while glycosylated haemoglobin was higher in group II. Kaplan–Meier plots showed higher survival, at 3 years, in group I than in group II (61% vs 39%, p=0.007). In patients with type 2 diabetes there was also greater survival in patients who began PD early compared with later PD initiation. In univariate analysis cerebrovascular pathology had a major influence on survival (odds ratio 2.94, 95% confidence interval 1.3–6.3, p=0.006). Multivariate analysis showed that age and initial serum albumin, and comorbidities such as cerebrovascular disease and cardiac failure, were the factors with the greatest impact on survival. Conclusions. Early initiation of peritoneal dialysis in diabetic patients seems to improve patient survival. Initial serum albumin and age, and the presence of cerebrovascular pathology and cardiac failure are critical factors affecting survival outcome.

Nosocomial candidemia at a general hospital: prognostic factors and impact of early empiric treatment on outcome (2002–2005)

OBJECTIVESnTo evaluate epidemiological and clinical prognosis factors related to mortality and impact of early empiric treatment on patients with nosocomial candidemia (NC).nnnPATIENTS AND METHODSnObservational study of a cohort of 107 adult patients with NC admitted at a tertiary hospital (2002-5).nnnRESULTSnIn bivariate analysis, risk factors significantly associated with mortality rate (49.5%) were: age >65 years, previous steroid treatment, solid organ transplant, acute severity of illness, shock, renal failure and respiratory distress at onset, delayed or inadequate antifungal treatment, non-removal of central venous catheter and associated post-surgical bacterial sepsis or respiratory infection. In multivariate analysis, risk factor associated with mortality was acute severity of illness at onset (OR 76.9; CI 12.5-500) being early and adequate treatment (OR 11.8; CI 1.7-81.2) and early (<48h) removing of central venous catheter (OR 12.2; CI 1.9-74.9) factors associated with cure; there was no statistically significant difference between fungistatic (azoles) or fungicidal (amphotericin or caspofungin) treatment.nnnCONCLUSIONSnAcute severity of illness at onset is associated with mortality in patients with NC whereas early and adequate treatment and early removing of central venous catheter are associated with cure.

Sweet's Syndrome Associated with Multiple Myeloma

Case Report A 69-year-old woman developed groin lesions diagnosed as bullous pemphigoid by biopsy. She developed oral erosions and nasal bleeding 6 months later, and when these problems persisted for many months, she was referred to our institution for evaluation. Examination of the oropharynx revealed an exuberant ulcerated lesion of the mandibular-labial sulcus and ulceration of the left lateral soft palate. The left anterior nasal septum showed crusting and ulceration. Routine histologic examination of biopsies revealed nonspecific ulceration and granulation tissue at the anterior mandibular labial sulcus, and ulceration and chronic inflammation with squamous metaplasia at the right nasal septal mucosa. Serum pemphigus and pemphigoid antibody titers were negative. Direct immunofluorescence of submucosal connective tissue from the mandibular labial sulcus and the left anterior soft palate revealed nonspecific findings. Biopsy of the right nasal septal mucosa revealed diffuse deposition of fibrinogen-related products on the surface of the specimen and an absence of surface epithelium. A sharp linear pattern of IgC (3+) and C3c (1+) was noted in the basement membrane zone of the numerous mucous glands (Eig. 1). This finding was considered to be diagnostic of CP.