Pharmacokinetic Model for Cefuroxime Dosing during Cardiac Surgery under Cardiopulmonary Bypass.

Cefuroxime (CXM) is an antibiotic recommended for surgical site infection prevention in cardiac surgery. However, the dosing regimens commonly used do not sustain therapeutic concentrations throughout surgery. The aim of this study was to conduct a population analysis of CXM pharmacokinetics (PK), and to propose an optimized dosing regimen. Adult patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) received a 1,500 mg CXM intravenous bolus followed by a 750 mg bolus at CPB priming, then every 2 h thereafter. Model-based PK simulations were used to develop an optimized dosing regimen and evaluate its efficacy in attaining various concentration thresholds, including those recommended in US and European guidelines. In total, 447 CXM measurements were acquired in 50 patients. A two-compartment model best fit the data, with total body weight and creatinine clearance determining interpatient variability in the central and peripheral volumes of distribution, and in elimination clearance, respectively. Using our optimized dosing regimen, different dosing schemes adapted to body weight and renal function were calculated to attain total concentration thresholds ranging from 12 to 96 mg/liter. Our simulations showed that the dosing regimens recommended in US and European guidelines failed to maintain concentrations above 48 mg/liter. Our individualized dosing strategy was capable of ensuring therapeutic CXM concentrations conforming to each target threshold. Our model yielded an optimized CXM dosing regimen adapted to body weight and renal function, and sustaining therapeutic concentrations consistent with each desired threshold. The optimal target concentration and necessary duration of its maintenance in cardiac surgery still remain unclear.

High prevalence of central hypothyroidism in adult patients with ß-thalassemia major.

The commonest form of thyroid dysfunction seen in subjects with TM is primary hypothyroidism due to abnormalities of the thyroid gland. Central hypothyroidism (CH) has been reported as an uncommon clinical entity in TM patients although the anterior pituitary gland is particularly sensitive to free radical oxidative stresses. Diagnosis is usually made on a biochemical basis showing low circulating concentrations of thyroid hormone associated with an inappropriately low TSH levels. The diagnosis is not clinically obvious and a basal normal TSH level does not exclude the diagnosis of CH. Therefore, it is important that clinicians accurately interpret thyroid function tests. In TM patients, CH prevalence differs at different ages is unknown and it is not easy to diagnose because most of the symptoms of symptoms of CH are non specific and are frequently attributed to anaemia or other associated complications . We performed a cross-sectional analysis on a large database using the clinical records of our TM patients to explore the prevalence of CH in prepubertal (<11 years: 25 patients; 13 males) peripubertal (between 11 and 16 years: 9 patients; 3 males), and pubertal TM subjects (>16 years: 305 patients; 164 males). Central hypothyroidism was present in 26 (7,6%) TM patients. Their mean age was 29.9 ± 8.4 years, 14 (53.8%) were males and 12 (46.1%) were females. The prevalence of CH was 6% in patients with a chronological age below 21 years and 7.9% in those above 21 years. Clinicians should be alert for the diagnosis of CH through accurate interpretation of thyroid function tests. We recommend L-thyroxine therapy if the level of FT4 is consistently low provided that the patient has normal cortisol levels.

Amenorrhea in eating disorders: poor stability of symptom after a one-year treatment.

OBJECTIVE: To examine whether patients with Eating Disorders (ED) who restore menses differ from those who remain amenorrheic after treatment and to provide longitudinal data about this debated criterion of Anorexia Nervosa (AN). METHODS: 184 outpatients were recruited: 50 patients with AN Restrictive type, 75 amenorrheic Eating Disorder Not Otherwise Specified (EDNOS) patients, 24 patients who recovered from AN with persistent amenorrhea, and 35 amenorrheic patients without ED. All participants were clinically assessed by psychiatrists and gynaecologists at the beginning of treatment and at the one-year follow-up. They also completed several psychometric tests: Eating Disorder Inventory-2, Temperament and Character Inventory, and Beck Depression Inventory. RESULTS: After treatment, a large portion of the sample resumed menses but very few recovered completely from the ED. No psychopathological variables could clearly predict the recovery of menses in the different groups. However, Body Mass Index and some biological variables were associated with restoration of menses in ED patients. CONCLUSION: Resumption of menses was not associated with a less severe eating symptomatology at the beginning of treatment nor with unequivocal psychopathological changes after treatment. It is important that clinicians consider not only the presence or absence of regular menses but also that they improve both ED screening and assessment in amenorrheic patients. Amenorrhea does not seem to represent a specific predictor of severity of illness or to show prognostic value.

Papillary thyroid microcarcinoma in thalassaemia: an emerging concern for physicians?

The occurrence of malignancies in thalassaemic patients is an emerging concern for physicians. In the last five years, in a single Thalassaemia Unit following 195 thalassaemic patients, eleven cases of carcinoma were diagnosed: 4 cases of liver, 1 of lung, 1 of adrenal gland and 5 cases of papillary thyroid carcinoma (patient mean age 42.6 years).Therefore, we decided to perform a thyroid ultrasonography (US) in addition to the periodic (6-12 months) assessment of FT4 and TSH in all adult patients with thalassaemia followed at the Thalassaemia Unit of Siracusa and at the Outpatient Clinic of Quisisana Hospital of Ferrara. Thyroid nodules were found in 8.6% of 58 examined thalassaemia major or intermedia patients. To exclude thyroid malignancy, fine needle biopsy (FNAC) under US guidance was performed. A diagnosis of incidental papillary thyroid microcarcinoma (PTMC) was made in 3 female patients with iron overload. According to the World Health Organization, PTMC is defined as papillary thyroid carcinoma measuring < or = 10 mm in the greatest dimension. Two patients were HCV positive. All underwent a total or subtotal thyroidectomy with histological confirmation of the FNAC cytology diagnosis. In conclusion, it seems that patients with thalassaemia have a substantial risk for malignancies. Further studies are needed in these patients to clarify the possible link between cellular iron content, hepatitis C virus infection and cancer development. A thyroid ultrasonography is recommended for all adult thalassaemic patients in addition to the annual FT4 and TSH assessment.

Fluid- and Biomechanical Analysis of Ascending Thoracic Aorta Aneurysm with Concomitant Aortic Insufficiency.

We present a comprehensive and original framework for the biomechanical analysis of patients affected by ascending thoracic aorta aneurysm and aortic insufficiency. Our aim is to obtain crucial indications about the role played by deranged hemodynamics on the ATAAs risk of rupture. Computational fluid dynamics analysis was performed using patient-specific geometries and boundary conditions derived from 4D MRI. Blood flow helicity and wall shear stress descriptors were assessed. A bulge inflation test was carried out in vitro on the 4 ATAAs after surgical repair. The healthy volunteers showed no eccentric blood flow, a mean TAWSS of 1.5 ± 0.3 Pa and mean OSI of 0.325 ± 0.025. In 3 aneurismal patients, jet flow impingement on the aortic wall resulted in large TAWSS values and low OSI which were amplified by the AI degree. However, the tissue strength did not appear to be significantly reduced. The fourth patient, which showed the lowest TAWSS due to the absence of jet flow, had the smallest strength in vitro. Interestingly this patient presented a bovine arch abnormality. Jet flow impingement with high WSS values is frequent in ATAAs and our methodology seems to be appropriate for determining whether it may increase the risk of rupture or not.

Serum lactate dehydrogenase isoenzyme pattern in non-Hodgkin's lymphomas.

Serum lactate dehydrogenase (S-LDH) and its isoenzyme pattern were assayed in 63 non-Hodgkin's lymphoma (NHL) patients, 37 at diagnosis, 15 at relapse and 11 in complete remission (CR). S-LDH in NHL patients with active disease was higher than in normal subjects and CR patients (p less than 0.001). Among the isoenzymes, LDH-2 and LDH-5 showed no remarked differences; LDH-1 was reduced and LDH-3 and LDH-4 raised in comparison to the normal group (p less than 0.001). S-LDH levels and isoenzymes 1 and 4 were influenced by the stage, the histological subgroup and by the presence of general symptoms. In fact, cases in stage IV, with "high-grade malignancy" and with general symptoms, had higher S-LDH levels and more evident LDH-1 and LDH-4 changes than the other stages, the other histopathological subgroups and the cases classified as "A". S-LDH was the same as in normal subjects in the "low-grade" and "intermediate-grade" malignancies as was LDH-1 in stage II and LDH-4 in stages II and III, in "low-grade" malignancy and in the A cases. In contrast, LDH-3 was always high, with no significant difference in relation to the variables considered. Thus, in NHL, LDH-3 seems to be a reliable marker of the presence of the disease in any case, whereas S-LDH is more related to the spread of the lymphoma.

A case of deep vein thrombosis in idiopathic nephrotic syndrome with resistance to activated protein C.

We report a case of deep vein thrombosis in a young man with idiopathic nephrotic syndrome and resistance to activated protein C. We postulate that patients with concurrent nephrotic syndrome and factor V may have an increased risk of thrombosis. Screening for factor V Leiden may be indicated in patients with idiopathic nephrotic syndrome.

Treatment with deferiprone (L1) in a thalassemic patient with bone lesions due to desferrioxamine.

A male thalassemia major patient who developed bone and cartilage abnormalities with a standard dose of desferrioxamine (DFX) given subcutaneously from the age of 4 years was treated with the oral iron chelator deferiprone (L1). During L1 treatment an improvement of genu valgum, evidence of healing and filling in of bone at the periphery of knee metaphysis and improvement in growth velocity were observed. However, the sitting height had decreased further, confirming the irreversibility of platyspondylosis, so affecting the near final standing height (156.8 cm) which was below the mid-parental height (168 cm). Prospective studies are warranted to determine the effect of different iron chelators on the bone metabolism of patients with thalassemia.

Subclavian vein stenosis: a potentially serious complication in chronic hemodialysis patients with permanent cardiac pacemakers.

We report on two hemodialyzed patients in whom subclavian and brachiocephalic vein stenosis secondary to permanent cardiac pacemakers led to massive congestive edema of the same arm after arteriovenous fistula/grafts were created. Therapeutic solutions regarding hemodialysis access are discussed in these patients with permanent pacemakers requiring hemodialysis.

Internal jugular vein catheterization under echographic guidance.

Having examined the various disadvantages of the catheterization of the central veins performed using the Seldinger technique, we report our results of internal jugular vein catheterization under echographic guidance in 38 uremic patients. The echographic guidance technique allows an easier and safer utilization of the internal jugular vein as vascular access in emergency situations.

[Subclavian vein stenosis in hemodialysis patients]. / La stenosi della vena succlavia nei pazienti in emodialisi.

Six haemodialyzed patient are reported in whom subclavian and brachiocephalic vein stenosis secondary to subclavian vein catheterization and to permanent cardiac pacemakers led to massive congestive edema of the same arm after an arteriovenous fistula/grafts were created. In view of the fact that subclavian vein stenosis or occlusion is not associated with any clinical findings and it is not possible to identify any predisposing factors associated with the use of the catheters, all patients who have had previous subclavian vein catheters or with permanent pacemakers should be evaluated to determine the patency of the subclavian vein before creation of a permanent access in that arm. Therapeutic answers as to haemodialysis access are discussed in these patients with permanent pacemakers who need haemodialysis. Because of all of these problems, the practice of subclavian cannulation in patients with end-stage renal failure has been discontinued in our centre. Good and reliable technology is now available for repeated short-term or long-term cannulation of the jugular veins for hemodialysis.

Standardization of progenitor cell assay for cord blood banking.

Cord blood has proved itself, if correctly stored with rational criteria, an excellent source of stem cells for related and unrelated transplants. It has been recently proven that the factor which predicts the best the speed of engraftment in cord blood transplants in the dose of progenitor cells injected per kg of body weight of the recipient. This result has been obtained thanks to a careful standardization of the neonatal progenitor cell assay. This manuscript describes such a standardization realized as a joined effort by the Istituto Superiore di Sanità, Rome, and the pivotal cord blood bank founded as a feasibility study by the National Institutes of Health, Bethesda at the New York Blood Center.

[Horizontal transmission of hepatitis C virus to family members of infected polytransfused pediatric patients]. / Transmissione orizzontale del virus dell'epatite C tra i familiari di pazienti pediatrici politrasfusi infetti.

The aim of this study is to evaluate the prevalence of the HCV antibodies in the relatives of polytransfused patients with different haemoglobinopathies. Our results have shown that 4.7% of relatives are aHCV positive. This incidence is much higher than that one reported in scientific publications with regard to non-haemoglobinopathis aHCV positive patients. Therefore a careful prevention and surveillance is needed in order to avoid the risk of infection in these subjects.

[Celiac disease associated with major thalassemia. A case report]. / Malattia celiaca in una paziente affetta da talassemia maior. Descrizione di un caso.

The spectrum of clinical manifestations of coeliac disease, the most common chronic intestinal disorder in children, has widened considerably over the past years and new associations with other diseases, both immunological and non-immunological, have been described. AGA and EMA have proved to be an efficient screening method both in populations with gastrointestinal pathologies and in groups of pauci- or even asymptomatic subjects. The clinical picture of beta-thalassemia has gradually altered over the years owing to improved treatment. However, growth is still affected in a considerable proportion of thalassemic patients. A number of hormonal and other causes, combined in varying ways, contribute to determining this clinical condition. The authors report a case of coeliac disease in an adolescent with thalassemia major characterised by anorexia, arrest of weight gain and low stature. The identification of a new association between coeliac disease and thalassemia major highlights the need to search for this pathology in all thalassemic patients who present scarce growth in stature and weight.