The efficacy and safety of cyclosporine reduction in de novo renal allograft patients receiving sirolimus and corticosteroids: results from an open‐label comparative study

This study evaluated the safety and efficacy of a sirolimus, corticosteroid, and cyclosporine reduction regimen in an open‐label, 12‐month trial of 420 de novo renal allograft recipients at 49 European transplant centers. One month post‐transplantation, 357 patients were randomized to receive standard‐dose cyclosporine (sCsA, n = 179) or reduced‐dose cyclosporine (rCsA, n = 178). All patients also received sirolimus and corticosteroids. The primary end points were the rate of biopsy‐confirmed acute rejection (BCAR) and renal function, as measured by serum creatinine. Baseline demographic and donor characteristics were similar between groups. BCAR rates at 12 months were not significantly different: 11.2% for rCsA patients and 16.2% for sCsA patients. Mean serum creatinine (±SEM) was significantly lower (1.75 ± 0.10 vs. 1.97 ± 0.07 mg/dl, P < 0.001), and creatinine clearance (±SEM; Nankivell method) was significantly higher (57.8 ± 1.78 vs. 49.5 ± 2.46 ml/min, P < 0.001) in patients receiving rCsA versus sCsA at 1 year, respectively. Patient and graft survival exceeded 98% in both groups. No significant differences in infection or malignancy were noted between groups. The rCsA with sirolimus and corticosteroid regimen resulted in excellent 12‐month patient and graft survival, a low incidence of BCAR, and improved renal function in renal allograft recipients. Sirolimus administered with rCsA and corticosteroids provided adequate immunosuppression while reducing the potential for the nephrotoxic effects of cyclosporine. These findings may help to improve long‐term renal allograft outcomes.     

The impact of the prevention strategies on the indirect effects of CMV infection in solid organ transplant recipients

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.     

Synthesis and anion recognition studies of new oligomethylene bis(nitrophenylureylbenzamide) receptors

A new series of oligomethylene bis(nitrophenylureylbenzamide) receptors were synthesized varying the relative position of the urea and amide groups (ortho4 and meta8) and the length of the oligomethylene chain (C₂ to C₈). An anion recognition study was performed with TBAX salts (X = AcO⁻, BzO⁻, F⁻, H₂PO₄⁻, and HP₂O₇³⁻) by UV-vis and ¹H NMR. The flexibility of these receptors allows a cooperative effect of both ureylbenzamide units in the receptors. Noteworthy, the ortho position favored the 1 : 1 stoichiometry in the complexes with the carboxylates. The formation of 2 : 1 receptor–anion complexes with both types of receptors 4 and 8 and with hydrogen pyrophosphate and high log K values obtained were very significant in this work. The NMR studies evidenced the formation of supramolecular complexes, even in a competitive solvent, such as DMSO.

Synthesis and supramolecular interaction of new oligomethylene bis(4-nitrophenylureylbenzamide) receptors with different anions.     

Platysma Flap: An Alternative to Free Flaps

Objective

The objective of this paper is to show that platysma flaps have good results and should be an alternative in reconstructive surgery for oral tumors when microsurgery is not possible. It is a versatile, portable, and thin flap, is easy to perform, and can be obtained during neck dissection, with a primary closure of the donor site.

Methods

Five cases are presented, three men and two women, 51 and 71 years old, with medium size (2–4 cm) defects of oral cavity after the excision of squamous cell carcinomas. All of them were reconstructed with a platysma flap after neck dissection. This reconstruction technique was chosen because of the poor conditions of these patients to allow a microsurgical reconstruction.

Results

Non-local complications occurred with this technique. Overall aesthetic results were acceptable in all the patients. There were no cases of total necrosis flap, dehiscence, fistula or fibrosis. Only one case of partial necrosis occurred in one end of the flap, which was resolved with excision of necrotic tissue and closure by secondary intention.

Conclusion

The platysma flap is a good method to reconstruct small and medium sized defects of oral cavity, especially in patients where a microsurgery reconstruction is not possible.     

Exploration of clients living with HIV needs for reporting on experiences with sex

Talking about sex with people living with HIV receives insufficient attention in health care. A cross‐sectional and exploratory study describes the preferences of people living with HIV to talk about sex with specialized HIV physicians and nurses in a clinic in Barcelona (Spain). A 27‐item self‐administered questionnaire was used between June 2017 and May 2018. One hundred fourteen people agreed to participate. Data were analyzed using multivariate logistic regression. Most of the participants reported “never or almost never” having been asked about sex practices in visits with the HIV specialist physician (n = 65 [57.0%]) or nurse (n = 74 [64.9%]). Older participants stated that neither physicians nor nurses talked about sex during visits. Women felt that physicians hardly ever asked about their sexual practices. Men who had sex with other men indicated that their physicians always asked about their sex practices compared with heterosexuals living with HIV. Health professionals should reformulate how to talk about sex with people living with HIV to facilitate communication and provide adequate care.     

Validation of a differential PCR and an ELISA procedure in studying HER-2/neu status in breast cancer

HER-2/neu oncogene status and total cellular p185^HER-2 content were simultaneously analyzed in 415 invasive breast-cancer specimens by differential PCR and ELISA respectively. Mathematical analysis of the data led us to establish a cut-off value of 1.7 for the ratio between the intensity of the HER-2/neu gene band and the reference gene band, to consider the HER-2/neu gene amplified, and of 260 fmol/mg protein, to consider p185^HER-2 over-expressed. Of the 415 tumors studied, 15% showed a diverse degree of HER-2/neu gene amplification. Of these tumors, 87% showed over-expression of the p185^HER-2. Of the remaining 352 specimens that did not display HER-2/neu gene amplification, 97% showed no p185^HER-2 over-expression (p < 0.0001). In 40 selected samples with a p185^HER-2 level lower than 260 fmol/mg protein, the degree of p185^HER-2 phosphorylation was very low or undetectable. Conversely, 38 of 46 selected tumors with a p185^HER-2 level higher than 260 fmol/mg protein exhibited a considerable degree of p185^HER-2 phosphorylation (p < 0.0001). Our data suggest that: (i) differential PCR and ELISA, which are relatively simple procedures, give similar information on HER-2/neu status in breast cancer; and (ii) given the large series analyzed, the cutoff values established can be considered as safe values for determining whether, in a given tumor, the HER-2/neu oncogene is amplified or p185^HER-2 is over-expressed. © 1996 Wiley-Liss, Inc.     

Comparative metabolomics analysis of bronchial epithelium during barrier establishment after allergen exposure

BackgroundSeveral studies have shown a correlation between an altered metabolome and respiratory allergies. The epithelial barrier hypothesis proposes that an epithelial barrier dysfunction can result in allergic diseases development. Der p 1 allergen from house dust mite is a renowned epithelial barrier disruptor and allergy initiator due to its cysteine‐protease activity. Here, we compared the metabolic profile of the bronchial epithelium exposed or not to Der p 1 during barrier establishment to understand its active role in allergy development.MethodsCalu‐3 cells were cultivated in air‐liquid interface cultures and exposed to either Der p 1 or Ole e 1 allergens during barrier establishment. The comparative metabolomics analysis of apical and basolateral media were performed using liquid chromatography and capillary electrophoresis both coupled to mass spectrometry.ResultsWe showed that epithelial barrier disruption by Der p 1 was associated with a specific metabolic profile, which was highly dependent on the state of the epithelium at the time of contact. Moreover, an apical‐basolateral distribution of the metabolites was also observed, indicating a compartmentalization of the response with differential metabolic patterns. A number of metabolites were changed by Der p 1, mainly related to amino acids metabolism, such as L‐arginine, L‐kynurenine and L‐methionine.ConclusionThis work is the first report on the metabolic response in human bronchial epithelial cells associated with cysteine‐protease Der p 1 activity, which could contribute to allergy development. Moreover, it supports a reformulated epithelial barrier hypothesis that might help to explain allergies and their increasing prevalence.     

Multiple meningiomas: does quantity matter? a population-based survival analysis with underlined age and sex differences

Journal of Neuro-Oncology - Intracranial meningiomas rarely present with multiple lesions. To the best of our knowledge, current literature regarding meningiomatosis (MM) is mostly comprised of...