Tacrolimus or cyclosporine: which is the better partner for mycophenolate mofetil in heart transplant recipients?

BACKGROUND: The aim of this single-center study was to investigate whether trough level adjusted mycophenolate mofetil (MMF) is more efficacious in combination with tacrolimus (TAC) or cyclosporine (CsA) and to evaluate the impact of either drug on MMF dosage. METHODS: Sixty patients (TAC, n = 30; CsA, n = 30) undergoing heart transplantation were randomized into a prospective, open-label, controlled trial. Immunosuppression consisted of TAC or CsA in combination with MMF and corticosteroids. Target blood trough levels of TAC, CsA, and mycophenolic acid (MPA) were in the range of 10 to 15 ng/mL, 100 to 300 ng/mL, and 1.5 to 4.0 microg/mL, respectively. Acute rejection episodes (ARE); survival data; and adverse events with a special emphasis on infections, diabetes, hypertension, hypercholesterolemia, and the development of graft vessel disease (GVD) were recorded. RESULTS: Baseline characteristics were well balanced. All patients were successfully withdrawn from corticosteroids within 6 months of transplant. Freedom from acute rejection was significantly higher (P = 0.0001) and the incidence of ARE per 100 patient days significantly lower in the TAC-MMF group than in the CsA-MMF group (0.03 vs. 0.15; P = 0.00007). Overall patient survival during follow-up was similar (93% vs. 90%). To achieve the targeted MPA blood levels, a significantly lower dose of MMF was required for TAC versus CsA patients. After a follow-up time of 2 years, the mean GVD score was 1.85 +/- 3.18 in the TAC-MMF group and 3.95 +/- 4.8 in the CsA-MMF group (P = 0.08). CONCLUSIONS: At the selected doses and target levels for TAC and CsA used in this study, trough level adjusted MMF was more efficacious in combination with TAC for prevention of ARE. Furthermore, CsA patients need significantly more MMF to achieve similar MPA levels.     

Use of diffusion-weighted magnetic resonance imaging in differentiating purulent brain processes from cystic brain tumors

OBJECT: Brain abscesses and other purulent brain processes represent potentially life-threatening conditions for which immediate correct diagnosis is necessary to administer treatment. Distinguishing between cystic brain tumors and abscesses is often difficult using conventional imaging methods. The authors' goal was to study the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to differentiate between these two pathologies in patients within the clinical setting. METHODS: Diffusion-weighted MR imaging studies and calculation of the apparent diffusion coefficient (ADC) values were completed in a consecutive series of 16 patients harboring surgically verified purulent brain processes. This study group included 11 patients with brain abscess (one patient had an additional subdural hematoma and another also had ventriculitis), two with subdural empyema, two with septic embolic disease, and one patient with ventriculitis. Data from these patients were compared with similar data obtained in 16 patients matched for age and sex, who harbored surgically verified neoplastic cystic brain tumors. In patients with brain abscess, subdural empyema, septic emboli, and ventriculitis, these lesions appeared hyperintense on DW MR images, whereas in patients with tumor, the lesion was visualized as a hypointense area. The ADC values calculated in patients with brain infections (mean 0.68 x 10(3) mm2/sec) were significantly lower than those measured in patients with neoplastic lesions (mean 1.63 x 10(3) mm2/sec; p < 0.05). CONCLUSIONS: Diffusion-weighted MR imaging can be used to identify infectious brain lesions and can help to differentiate between brain abscess and cystic brain tumor, thus making it a strong additional imaging modality in the early diagnosis of central nervous system purulent brain processes.     

Fkbp10 Deletion in Osteoblasts Leads to Qualitative Defects in Bone

Osteogenesis imperfecta (OI), also known as brittle bone disease, displays a spectrum of clinical severity from mild (OI type I) to severe early lethality (OI type II), with clinical features including low bone mass, fractures, and deformities. Mutations in the FK506 Binding Protein 10 (FKBP10), gene encoding the 65‐kDa protein FKBP65, cause a recessive form of OI and Bruck syndrome, the latter being characterized by joint contractures in addition to low bone mass. We previously showed that Fkbp10 expression is limited to bone, tendon, and ligaments in postnatal tissues. Furthermore, in both patients and Fkbp10 knockout mice, collagen telopeptide hydroxylysine crosslinking is dramatically reduced. To further characterize the bone specific contributions of Fkbp10, we conditionally ablated FKBP65 in Fkbp10^fl/fl mice (Mus musculus; C57BL/6) using the osteoblast‐specific Col1a1 2.3‐kb Cre recombinase. Using μCT, histomorphometry and quantitative backscattered electron imaging, we found minimal alterations in the quantity of bone and no differences in the degree of bone matrix mineralization in this model. However, mass spectroscopy (MS) of bone collagen demonstrated a decrease in mature, hydroxylysine‐aldehyde crosslinking. Furthermore, bone of mutant mice exhibits a reduction in mineral‐to‐matrix ratio and in crystal size as shown by Raman spectroscopy and small‐angle X‐ray scattering, respectively. Importantly, abnormalities in bone quality were associated with impaired bone biomechanical strength in mutant femurs compared with those of wild‐type littermates. Taken together, these data suggest that the altered collagen crosslinking through Fkbp10 ablation in osteoblasts primarily leads to a qualitative defect in the skeleton. © 2017 American Society for Bone and Mineral Research.     

Treatment of facial lipodystrophy syndromes. Lipofilling versus free flap surgery

Facial lipodystrophies are characterized by a progressive atrophy of the subcutaneous fat of the face. The aim of our study, which includes two types of facial lipodystrophy (Barraquer–Simons (BS) and Parry–Romberg (PR) syndromes), was to compare the results of treatment with lipofilling and with free flaps and to evaluate the long-term outcome. Eighteen patients (seven cases of BS and 11 cases of PR), issued from four different plastic surgery departments, underwent surgery from 1986 to 2004. The average follow-up period was 5.25 years. Of seven patients who had free flap surgery, four presented satisfying results and three bad results. Dissatisfaction in this group was mainly due to ptosis and a partial atrophy of the flaps. Three good and nine excellent results were seen in patients treated with lipofilling. The results in this group were technique-related, with the nine patients treated with lipostructure (Coleman’s technique) presenting the best outcome. Lipofilling, as an alternative of free flaps, seems to offer superior results. This technique is simple, not expensive, and minor compared to free tissue transfer. It allows the treatment of two areas in one-stage procedure without leaving scars. Lipostructure fills all the conditions to become the technique of choice in the treatment of facial lipodystrophies.     

Tuberculosis control in a border state. Treatment of the foreign-born

As the epidemiology of TB in the United States changes, with more foreign-born and fewer native-born residents developing the disease, treatment can be expected to become more complicated and expensive.     

Dielectric constant of atomic fluids with variable polarizability

The Clausius-Mossotti function for the dielectric constant is expanded in terms of single atom and pair polarizabilities, leading to contributions that depend on both the trace and the anisotropy of the pair-polarizability tensor. The short-range contribution of the anisotropic part to the pair polarizabilities has previously been obtained empirically from light scattering experiments, whereas the trace contribution is now empirically determined by comparison to dielectric experiments. For helium, the short-range trace part agrees well with electronic structure calculations, whereas for argon qualitative agreement is achieved.     

Perception of sexuality and fertility in women living with HIV: a questionnaire study from two Nordic countries

Introduction

As the human immunodeficiency virus (HIV)-positive population ages, issues concerning sexuality and fertility, among others, are becoming relevant. HIV is still surrounded by stigma and taboos, and there have been few studies conducted in industrialized settings concerning these questions. We therefore wanted to investigate the perception of sexuality and fertility in women living with HIV (WLWH) in an industrialized setting, using a questionnaire.

Methods

WLWH were recruited at their regular outpatient clinic visits, at the major Departments of Infectious Diseases in Denmark and Finland, from January 2012 to October 2013. A questionnaire was developed, study participants were informed of the nature of study and, if they agreed to participate and signed a consent form, they filled in the questionnaire. Demographic information on the participants was obtained from patient files (in Finland) or from a national HIV cohort (in Denmark). Statistical analysis was performed using STATA^®, version 11.

Results

In total, 560 women were included in the study. The median age was 44 years. The majority were of white European origin, with fully suppressed HIV viral load, CD4 cell count >350 µL and mild or no symptoms of their HIV infection. A total of 62% were sexually active, stating condom use as their sole form of contraception. Of the sexually inactive women, one-third were in steady relationships. Eighty percent reported prior pregnancies, of which the majority had one or more children. Most children were born prior to the women''s HIV diagnosis and the mode of conception was predominantly natural. One-quarter of the participating women desired pregnancy, while more than half did not. The remaining quarter either stated that they already had the desired number of children or chose not to answer the question. Fourteen percent stated that their HIV diagnosis ended their wish for children; of these women, the median time of diagnosis was between 1995 and 1996. Pregnancy had been attempted unsuccessfully in one-quarter of study participants. The final question inquired what the risk of mother-to-child transmission was, with all precautions taken. Fifteen percent estimated the risk to be above two percent.

Conclusions

In conclusion, the majority of WLWH in industrialized settings in Denmark and Finland have few HIV-related symptoms, are sexually active and have a strong desire for children.