Mycophenolate mofetil and sirolimus as calcineurin inhibitor-free immunosuppression for late cardiac-transplant recipients with chronic renal failure

BACKGROUND: Calcineurin-inhibitor (CNI)-related renal failure is a common problem after cardiac transplantation (HTx). The aim of this study was to introduce a CNI-free immunosuppressive regimen to HTx recipients with late posttransplant renal impairment and to evaluate the impact of conversion to this new immunosuppression (mycophenolate mofetil [MMF] and sirolimus [Sir]) treatment on renal function. METHODS AND RESULTS: Thirty-one HTx patients (25 men, 6 women; 0.2-14.2 years after transplantation) with CNI-based immunosuppression and a serum creatinine greater than 1.9 mg/dL were included in the study. Creatinine and cystatin levels were monitored to detect renal function. Mean patient age was 50+/-14 (range 19-74) years. Conversion was started with 6 mg Sir, continued with 2 mg, and the dose was adjusted to achieve target trough levels between 8 and 14 ng/mL. MMF was continued with trough level adjusted (1.5-4 microg/mL). Subsequently, the CNIs were tapered down and stopped. Clinical follow-up (first and every 3 months after conversion) included endomyocardial biopsies, echocardiography, and laboratory studies. Survival was 90% after a mean follow-up of 13+/-95 months. No acute rejection episode was detected during the study period. Renal function improved significantly after conversion: creatinine preconversion vs. postconversion: 3.14+/-0.76 mg/dL vs. 2.14+/-0.83 mg/dL, P =0.001. Cystatin preconversion vs. postconversion: 2.95+/-1.06 mg/L vs. 2.02+/-1.1 mg/L, P =0.01. In three patients, hemodialysis therapy was stopped completely after conversion. Graft function remained stable. Fractional shortening preconversion vs. postconversion: 36.9+/-6% vs. 36.4+/-6%. There were no serious adverse events. One patient had to be excluded because of noncompliance. CONCLUSIONS: Conversion from CNI-based immunosuppression to MMF and Sir in HTx patients with chronic renal failure was safe, preserved graft function, and improved renal function.     

Spontaneity as predictive factor for well-being

The study discusses the construct of spontaneity and its causal relationship with psychological well-being. It develops a preview phase of validation of the SAI-R and its correlation with the Clinical Outcomes for Routine Evaluation-Outcome Measure (CORE-OM) and the Beck Depression Inventory (BDI-II) and assumes the hypothesis that a high level of spontaneity is correlated negatively with low level of well-being and positively with depression. The research involved Italian and Austrian participants, consisting of 166 Italian and 146 Austrian university students. The findings suggested a causal relationship between low spontaneity and psychological suffering. The results obtained confirm the hypothesized model, showing significant negative causal relationship. The verification of this theoretical model on non-clinical samples allows us to set the ground for future use in clinical samples. Furthermore, this result encourages the development of further research into the use of SAI-R.     

18F-FDG PET/CT as predictive and prognostic factor in esophageal cancer treated with combined modality treatment

Annals of Nuclear Medicine - [18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) is used for diagnosis, staging, response assessment and prognosis...     

Anesthetic and recovery profiles of lidocaine versus mepivacaine for spinal anesthesia in patients undergoing outpatient orthopedic arthroscopic procedures

Study ObjectiveTo compare isobaric lidocaine and mepivacaine in outpatient arthroscopic surgery.DesignProspective, randomized, double-blinded study.SettingAmbulatory surgery center affiliated with an academic tertiary-care hospital.Patients84 adult, ASA physical status 1, 2, and 3 ambulatory patients, age 18-70 years, undergoing arthroscopic knee surgery.InterventionPatients were randomized to receive a combination spinal-epidural anesthetic using 80 mg of either isobaric 2% mepivacaine or isobaric 2% lidocaine. Patients also received a femoral 3-in-1 block with 0.5% bupivacaine applied to the affected extremity.MeasurementsDemographic data and level and duration of the block were recorded. The use of supplemental epidural anesthesia was noted along with frequency of bradycardia, hypotension, and episodes of nausea and vomiting. Duration of block and times to ambulation and voiding were recorded. Delayed variables, including fatigue, difficulty urinating, back pain, and transient neurologic symptoms (TNS) were obtained.Main ResultsNo demographic differences were noted between groups, and surgical duration was similar. Satisfactory anesthesia was achieved in all cases, with no differences noted in hypotension, bradycardia, nausea, or vomiting. Onset of sensory and motor block was similar. Duration of block before epidural supplementation was 94 ± 21 minutes with lidocaine versus 122 ± 23 minutes for mepivacaine (P < 0.011). Times to ambulation and voiding were longer in patients receiving mepivacaine but did not affect PACU stay. Twenty-four and 48-hour recovery was similar with no TNS symptoms reported.ConclusionNo major differences were noted between lidocaine and mepivacaine spinal anesthesia. Time to ambulation and voiding were longer in patients who received mepivacaine as was time to first dose of epidural catheter. Neither group had TNS symptoms. Lidocaine and mepivacaine are both appropriate spinal anesthetics for ambulatory orthopedic lower extremity procedures.     

Evidence That Hyperglycemia After Recovery From Hypoglycemia Worsens Endothelial Function and Increases Oxidative Stress and Inflammation in Healthy Control Subjects and Subjects With Type 1 Diabetes

Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia–reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.Recent evidence suggests that hypoglycemia may play an important role in the vascular complications of diabetes (1). Hypoglycemia causes oxidative stress (2), inflammation (3), and endothelial dysfunction (4). Oxidative stress is considered the key player in the pathogenesis of diabetes complications (5). During hyperglycemia, oxidative stress is produced at the mitochondrial level (5), similarly as in hypoglycemia (2). Therefore, oxidative stress might be considered the common factor linking hyperglycemia, hypoglycemia, and the vascular complications of diabetes. Consistent with this hypothesis is the evidence that hyperglycemia (6) and hypoglycemia both produce endothelial dysfunction and inflammation through the generation of oxidative stress (4,7). Endothelial dysfunction and inflammation are well-recognized pathogenic factors for vascular disease, particularly in diabetes (8).There is, however, evidence that free radical production rises, not only during hypoglycemia but particularly during glucose reperfusion after hypoglycemia (9). In both mice and cultured neurons, hypoglycemia, followed by different concentrations of glucose reperfusion, has been linked to a degree of superoxide production and neuronal death that increased proportionally with glucose concentrations during the reperfusion period (9).Until now, little attention has been given to studying the effects of recovery from hypoglycemia. The aim of this study was to evaluate these effects and, in particular, to determine if the level of glycemia reached during recovery could have a different impact, in vivo, on oxidative stress generation, inflammation, and endothelial function.     

High dose fractionated ionizing radiation inhibits prostate cancer cell adhesion and beta(1) integrin expression

BACKGROUND: The effect of ionizing radiation on extracellular matrix (ECM)-mediated cellular functions is an important area of research for translational science. Mechanisms of tumor cell ability to proliferate, migrate, and survive appear dependent on integrin-mediated adhesion to the ECM; however, the exact role therapeutic radiation plays in altering signaling pathways and promoting cell death within remains less well established. METHODS: To examine these effects on prostate carcinoma cell lines, cells were irradiated at sub-lethal doses. We have studied two human prostate cancer cell lines (PC3 and DU-145) irradiated with different fractionated radiation schedules. Three groups were compared to non-irradiated controls. Group A was given a single dose of 5 Gy. Group B was given 5 Gy the first week and then 10 Gy the second week for a total of 15 Gy. Group C was given 5 Gy the first week, and then 10 Gy the second and third week for a total of 25 Gy. Cells were analyzed at their prescribed total dose. At 48 hr post irradiation, cells were detached from culture dishes and were subsequently used for adhesion assays and immunoblotting analysis. RESULTS: Our findings revealed that two prostate carcinoma cell lines, PC3 and DU-145, had a reduced cellular adhesion to fibronectin (FN) compared to the non-irradiated control groups. Both prostate cancer cell lines showed decreased adhesion to FN and reduced beta(1) integrin protein levels at a total dose of 25 Gy, but not at the doses of 15 and 5 Gy. In a parallel analysis, at the maximum total dose of 25 Gy, both PC3 and DU-145 demonstrated a significant decrease in cell proliferation. CONCLUSIONS: High dose radiation treatment of prostate cancer cell lines inhibits integrin expression. Our study suggests that promoting a synergistic decrease in adhesion could bring additional therapeutic benefit to patients treated with radiation therapy.     

VAC therapy for the treatment of complex wounds after cardio‐thoracic surgery

The aim of this study is to report our experience about the treatment of complex sternal and thoracic wounds following cardiothoracic surgery, using vacuum‐assisted closure (VAC therapy. Twelve patients presenting with sternal (five cases) and thoracic (seven cases) wounds that were difficult to heal were treated through VAC therapy after the first surgical debridement. The duration of VAC application ranged from 12 to 36 days with an average hospital stay of 24·6 ± 11·4 days. During a mean follow‐up of 12 months, we observed complete wound healing in seven cases (58·3%), in an average period of 25·5 ± 14·3 days; one patient died during follow‐up, two patients were lost to follow‐up and two patients required definitive surgical closure of the wound cavity. In conclusion, VAC therapy promotes faster wound healing, with shorter hospital stay and subsequent lesser in‐hospital cost, reducing the mortality rate in the long run. It also promotes early rehabilitation and alleviates the need for a second procedure, thus improving patient satisfaction, with minimal discomfort or inconvenience.     

Risk factors for decreased total body and regional bone mineral density in hemodialysis patients with severe secondary hyperparathyroidism.

Hyperparathyroidism contributes significantly to decreased bone mineral density (BMD) in end-stage renal disease patients, but this negative influence is not homogeneous throughout the skeleton. We studied the BMD by dual-energy X-ray absorptiometry on total body and on different regions of the skeleton in 42 patients with severe hyperparathyroidism on hemodialysis. We also evaluated the relationship between different risk factors and BMD found on the regions examined in these patients. The legs and other sites where cortical bone predominate were mostly affected, whereas trabecular bone was relatively preserved. This is probably the result of the different effects of hyperparathyroidism on cortical and trabecular bone, but we cannot rule out the interference of ectopic calcifications and sclerotic lesions of vertebral end-plates falsely increasing lumbar spine BMD. The main determinants of low total-body BMD were, in order of importance, immobility, high intact parathyroid hormone levels, low body mass index, and low albumin. Eleven patients presented with pathologic fractures, mainly in the legs, and BMD was lower in this group than in patients without fractures. In conclusion, our study makes clear that hyperparathyroidism is a great threat to bone density in hemodialysis patients, mainly in the legs, the site mostly affected by fragility fractures in our patients. Physicians must worry not only with high parathyroid hormone levels, but also with the nutritional state of these patients.     

Outcome and management of isolated moderate renal pelvis dilatation detected at postnatal screening

The aim of this study was to evaluate the incidence and outcome of isolated moderate renal pelvis dilatation (RPD) [anterior–posterior diameter (APD) 10–15 mm] in an unselected population of 2-month-old infants prospectively followed for up to 12–14 months of life. Isolated moderate renal pelvis dilatation was detected in 282 of the 11,801 (2.4%), infants screened; 240 infants with normal renal ultrasound were enrolled as the control group. Resolution of RPD was considered when an APD ≤ 5 mm was found on two consecutive sonograms. Urological investigations were initiated if the RPD persisted or if urinary tract infection (UTI) occurred during follow-up, and antibiotic therapy was administered only when UTI occurred. The events of interest were resolution of the RPD, presence of uropathy and UTI. At follow-up, RPD persisted only in 18 infants; of these, four infants were diagnosed with vesicoureteral reflux (grade 1–3) and 14 with ureteropelvic junction obstruction. Of the 223 infants with RPD and 230 control infants who completed follow-up, UTI occurred in 3.6 and 2.5%, respectively. The incidence rate of UTI per 1000 person-months was 5.98 episodes in the patient group and 5.22 episodes in the control group. The rate ratio was 1.146 (95% confidence interval 0.389–3.54, p = 0.8). Our data suggest that isolated moderate RPD is essentially a self-limiting condition and that antibiotic prophylaxis for the prevention of UTI should not be performed. A non-invasive ultrasound scan performed during the follow-up is sufficient to diagnose a potentially dangerous and persistent RPD.