Renal transplantation outcomes in obese patients: a French cohort-based study.

BACKGROUND: Whilst there are a number of publications comparing the relationship between body mass index (BMI) of kidney transplant recipients and graft/patient survival, no study has assessed this for a French patient cohort. METHODS: In this study, cause-specific Cox models were used to study patient and graft survival and several other time-to-event measures. Logistic regressions were performed to study surgical complications at 30 days post-transplantation as well as delayed graft function. RESULTS: Among the 4691 included patients, 747 patients were considered obese with a BMI level greater than 30 kg/m2. We observed a higher mortality for obese recipients (HR = 1.37, p = 0.0086) and higher risks of serious bacterial infections (HR = 1.24, p = 0.0006) and cardiac complications (HR = 1.45, p < 0.0001). We observed a trend towards death censored graft survival (HR = 1.22, p = 0.0666) and no significant increased risk of early surgical complications. CONCLUSIONS: We showed that obesity increased the risk of death and serious bacterial infections and cardiac complications in obese French kidney transplant recipients. Further epidemiologic studies aiming to compare obese recipients versus obese candidates remaining on dialysis are needed to improve the guidelines for obese patient transplant allocation.

Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d'endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie - dialyse - transplantation (SFNDT).

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Propensity score-based comparison of the graft failure risk between kidney transplant recipients of standard and expanded criteria donor grafts: Toward increasing the pool of marginal donors.

From a prospective and multicentric French cohort, we proposed an external validation study for the expanded criteria donor (ECD), based on 4833 kidney recipients transplanted for the first time between 2000 and 2014. We estimated the subject-specific effect from a multivariable Cox model. We confirmed a 1.75-fold (95% confidence interval [CI] 1.53-2.00, P < .0001) increase in graft failure risk if a given patient received an ECD graft compared to a graft from a donor with standard criteria (standard criteria donor [SCD]). Complementarily, we estimated the population-average effect using propensity scores. We estimated a 1.34-fold (95% CI 1.09-1.64, P = .0049) increase in graft failure risk among ECD patients receiving an ECD graft compared to receiving a SCD graft. With a 10-year follow-up, it corresponded to a decrease of 8 months of the mean time to graft failure due to ECD transplantation (95% CI 2-14 months). The population-average relative risk due to ECD transplantation and the corresponding absolute effect seem finally not so high. Regarding the increase of quality of life in transplantation, our study constitutes an argument to extend the definition of marginality by considering more grafts at high risk and thereby enlarging the pool of kidney grafts.

EVALUATION OF ANTIOXIDANT ACTIVITY OF SOME IMINES DERIVATIVES OF L-ARGININE.

UNLABELLED: L-Arginine is an a-amino acid which plays important roles in different diseases or processes, such as Alzheimer disease, inflammatory process, healing and tissue regeneration and it also could be useful as an anti-atherosclerotic agent. AIM: Considering the large amount of studies on the beneficial effects of different antioxidants, this paper is focused on the evaluation of the antioxidant potential of some imine derivatives, synthesized by the authors and described in a previous article. MATERIAL AND METHODS: The evaluation of the antioxidant power was performed using phosphomolydenum-reducing antioxidant power (PRAP) and ferric reducing antioxidant power (FRAP) assays, tests described in the literature and which are used with some minor modifications. RESULTS: It was found that most of the imine derivatives are more active than the L-Arginine in the PPAP and FRAP assays. The most active derivative was the compound obtained by condensation of L-arginine with 2,3-dihydroxybenzaldehyde (2k) and 2-nitrobenzaldehyde (2g). CONCLUSIONS: Following the described protocol, some imine derivatives of L-arginine were evaluated in terms of antioxidant potential using in vitro methods. The most favorable influence was obtained by the aromatic substitution with nitro and hydroxyl, the corresponding derivatives being the most active derivatives compared to L-arginine.

Community-acquired Legionnaires' disease in a renal transplant recipient with unclear incubation period: the importance of molecular typing.

Transplant recipients are at risk of developing Legionnaires' disease (LD) because of impaired cellular immunity. Here, we describe a renal transplant recipient who developed LD at least 10 days after hospital admission and transplantation. The hospital water network was initially suspected, but further testing determined that the probable source was the patient's domestic water supply. Our report also suggests that the patient's immunosuppressed state may have switched potential colonization to pneumonia.

Recent advances in the chemistry and biology of pyridopyrimidines.

The interest in pyridopyrimidine cores for pharmaceutical products makes this scaffold a highly useful building block for organic chemistry. These derivatives have found applications in various areas of medicine such as anticancer, CNS, fungicidal, antiviral, anti-inflammatory, antimicrobial, and antibacterial therapies. This review mainly focuses on the progress achieved since 2004 in the chemistry and biological activity of pyridopyrimidines.

Synthesis, characterization and antioxidant activity of some new thiazolidin-4-one derivatives.

AIM: To design new thiazolidin-4-ones derivatives and to evaluate their potential antioxidant effects using in vitro methods. MATERIAL AND METHODS: New ethyl esters of the 2-(R-phenyl)-4-oxo-thiazolidin-3-yl propionic acid were synthesized using "one step reaction" between different aromatic aldehydes, thioglycolic acid and beta-alanine ethyl ester hydrochloride. The antioxidant potential of the synthesized compounds was evaluated using the DPPH radical scavenging assay and phosphomolybdenum method. RESULTS: Eight thiazolidine-4-one derivatives were obtained in good yields and high purity. The structure of the synthesized compounds was confirmed using IR spectroscopy. The evaluation of antioxidant activity showed that 2-[(4-NO2)-phenyl]-4-oxo-thiazolidin-3-yl propionic acid ethyl ester (compound 16) was the most active compound. For this derivative the DPPH radical scavenger activity (I% = 91.63% +/- 0.77) and the total antioxidant capacity (absorbance = 1.0691 +/- 0.0763) were similar with that of ascorbic acid used as standard antioxidant. CONCLUSIONS: The antioxidant activity of the thiazolidine-4-one derivatives depends on the nature of the phenyl ring substituents, the NO2 and OH radicals having the most significant influence.

Development and optimization of the synthesis of new thiazolidin-4-one derivatives of ibuprofen.

UNLABELLED: Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most prescribed drugs for the treatment of pain and inflammation from various rheumatic diseases, but some side effects can occur on long-term use. AIM: The method for synthesis optimization of new derivatives of Ibuprofen with thiazolidin-4-one moiety, with improved pharmacological and toxicological profile. MATERIAL AND METHODS: To optimize the derivatization method of free carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction conditions were varied (reagent ratio, catalyst, reaction medium). RESULTS: The most favorable method was proved to be the reaction between ibuprofen hydrazone and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96% conversion rate. CONCLUSIONS: The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)-2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying it as a general procedure for the synthesis of other derivatives with related structure. The chemical structure and molecular weight of the synthesized compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

Epstein-Barr virus-associated smooth muscle tumors in a composite tissue allograft and a pediatric liver transplant recipient.

Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes that can cause lymphoproliferative disorders particularly in immunocompromised patients. More recently, the development of rare EBV-associated smooth muscle tumors has been reported in transplant recipients. We herein describe 2 new cases of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the first in a facial composite tissue graft recipient. Among the striking features shared by these 2 patients were their young ages, the fact that they were naïve for EBV before the transplantation, that they developed a post-transplant lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they responded favorably to reduction of immunosuppression. Radiological and histologic features of EBV-PTSMT are shown. Finally, pathophysiology and therapeutic management of EBV-PTSMT are discussed based on a comprehensive review of the literature.

The first simultaneous kidney-adrenal gland-pancreas transplantation: outcome at 1 year.

Adrenal insufficiency is a rare but life-threatening disease. Replacement therapy sometimes fails to prevent an acute adrenal crisis and most often does not lead to restoration of well-being. We report here the 1-year outcome of the first simultaneous kidney-adrenal gland-pancreas transplantation in a 33-year-old patient with type 1 diabetes and concomitant autoimmune adrenal insufficiency. En bloc left adrenal gland and kidney grafts were anastomosed on the left iliac vessels in normal vascular conditions and the pancreas graft was anastomosed on the right iliac vessels. The immunosuppressive regimen was not modified by the addition of the adrenal gland. We observed no additional morbidity due to the adrenal gland transplantation, as there were no surgical complications. One-year kidney and pancreas graft functions were satisfactory (estimated glomerular filtration rate: 55 mL/min/1.73 m(2) and HbA1c: 4.8%). The adrenal graft functioned well at 12 months with a normalization of cortisol and aldosterone baseline levels. Functional imaging at 3 months showed good uptake of [(123) I]-metaiodobenzylguanidine by the adrenal graft. Transplantation of the adrenal gland en bloc with the left kidney appears to be a good therapeutic option in patients with adrenal insufficiency awaiting kidney or kidney-pancreas transplantation.

Kidney graft outcome and quality (after transplantation) from uncontrolled deceased donors after cardiac arrest.

The use of uncontrolled deceased donors after cardiac arrest (uDDCA) has been developed in France to compensate for organ shortage. The quality of these kidneys remains unclear. We analyzed kidney graft function and histology from 27 uDDCA and compared them with kidneys from 30 extended criteria donors (ECD) and from 24 simultaneous pancreas kidney (SPK) donors as a control group of optimal deceased donors. Kidneys from ECD and SPK donors were preserved by static cold storage while kidneys from uDDCA were preserved by pulsatile perfusion. The uDDCA graft function at 3 years posttransplantation (estimated with MDRD and measured with inulin clearance) did not differ from that of the ECD group (eGFR 44.1 vs. 37.4 mL/min/1.73 m(2) , p = 0.13; mGFR 44.6 vs. 36.1 mL/min/1.73 m(2) , p = 0.07 in the uDDCA and ECD groups, respectively). The histological assessment of 3-month and 1-year protocol biopsies did not show differences for interstitial lesions between the uDDCA and ECD grafts (IF score at M3 was 30 vs. 28% and at M12 36 vs. 33%, p = NS). In conclusion, the results at 3 years with carefully selected and machine-perfused uDDCA kidneys have been comparable to ECD kidneys and encourage continuation of this program and development of similar programs.

[Agreement between verbal numerical scale and visual analog scale assessments in monitoring acute postoperative pain]. / Concordancia entre la escala verbal numérica y la escala visual analógica en el seguimiento del dolor agudo postoperatorlo.

OBJECTIVE: To determine the agreement between verbal numerical and visual analog scale assessments of acute postoperative pain on 3 consecutive days. METHODS: Pain data were recorded for 2 months for sequentially enrolled patients receiving parenteral opioids or neuraxial blocks for analgesia after major surgery in a tertiary level hospital. Each patient was asked to assess pain on the visual analog and verbal numerical scales every 24 hours for 3 consecutive days. Agreement was estimated by the intraclass correlation coefficient and the Spearman correlation coefficient. The results were analyzed in 2 age strata: age 65 years or younger and older than 65 years. RESULTS: Data for 159 patients (105 < or =65 years; 54 >65 years) were analyzed. The visual analog scale could not be used with 12 patients; all patients were able to assess pain on the verbal numerical scale. The intraclass correlation coefficient was > 0.70 for all 3 days; the highest coefficients were for patients over 65 years of age. CONCLUSIONS: Agreement between pain assessments on the visual analog and verbal numerical scales can be considered good or very good on all 3 days, with stronger agreement when the scales are used in patients over the age of 65 years. Cooperation was better for the numerical scale than for the visual analog scale. Scores on the verbal numerical scale were consistently higher than scores on the visual analog scale.

Concordancia entre la escala verbal numérica y la escala visual analógica en el seguimiento del dolor agudo postoperatorio / Agreement between verbal numerical scale and visual analog scale assessments in monitoring acute postoperative pain

Objetivo: Evaluar la concordancia entre la escala verbal numérica y la escala visual analógica en la valoración del seguimiento del dolor agudo postoperatorio durante 3 días consecutivos. Métodos: Recogida secuencial de datos a los pacientes sometidos a cirugía mayor subsidiaria de pauta de analgesia postoperatoria con opiáceos parenterales o técnicas neuroaxiales en un hospital terciario durante 2 meses consecutivos. Se interrogó a los pacientes durante 3 días consecutivos con intervalos de 24 horas mediante las escalas visual numérica (EVN) y visual analógica (EVA). Para valorar la concordancia entre variables cuantitativas se utilizó el coeficiente de correlación intraclase, y coeficiente de correlación de Spearman, estratificándose los resultados por edad (menos o mayor de 65 años). Resultados: Se analizaron datos de 159 pacientes (105 <= 65 años y 54 > 65 años). La valoración de la EVA no fue posible realizarla en 12 pacientes, mientras que la valoración de la EVN fue posible en todos los pacientes. Los valores del coeficiente de correlación interclase fueron globalmente > 0,70 durante los tres días, siendo más altos los coeficientes en mayores de 65 años. Conclusiones: La concordancia entre las EVA y EVN de dolor se puede considerar como buena o muy buena durante los tres días de seguimiento, siendo mejor en pacientes con edad superior a 65 años. El grado de colaboración para recoger los datos fue mejor para la EVN que para la EVA. En la comparación de las valores numéricos del dolor la EVN mostró repetidamente valores más altos que la EVA(AU)

Objective: To determine the agreement between verbal numerical and visual analog scale assessments of acute postoperative pain on 3 consecutive days. Methods: Pain data were recorded for 2 months for sequentially enrolled patients receiving parenteral opioids or neuraxial blocks for analgesia after major surgery in a tertiary level hospital. Each patient was asked to assess pain on the visual analog and verbal numerical scales every 24 hours for 3 consecutive days. Agreement was estimated by the intraclass correlation coefficient and the Spearman correlation coefficient. The results were analyzed in 2 age strata: age 65 years or younger and older than 65 years. Results: Data for 159 patients (105 65 years; 54 > 65 years) were analyzed. The visual analog scale could not be used with 12 patients; all patients were able to assess pain on the verbal numerical scale. The intraclass correlation coefficient was > 0.70 for all 3 days; the highest coefficients were for patients over 65 years of age. Conclusions: Agreement between pain assessments on the visual analog and verbal numerical scales can be considered good or very good on all 3 days, with stronger agreement when the scales are used in patients over the age of 65 years. Cooperation was better for the numerical scale than for the visual analog scale. Scores on the verbal numerical scale were consistently higher than scores on the visual analog scale(AU)

[Evaluation of a protocol for predicting difficult airway in routine practice: interobserver agreement]. / Evaluación de un protocolo de predicción de vía aérea difícil en la práctica habitual: estudio de concordancia.

OBJECTIVES: To evaluate a protocol for routine assessment of potential risk factors for difficult airway intubation in an anesthesia department, by measuring interobserver agreement and the behavior of the factors in a predictive model. MATERIAL AND METHODS: A cross-sectional study group of 320 consecutive patients undergoing major surgery requiring orotracheal intubation was assessed for possible difficult airway. We calculated interrater agreement for recording of the Mallampati score, thyromental distance less than 6 cm, thick neck, kyphosis, small mouth, macroglossia, and dental prosthesis during the preanesthesia examination (by an anesthetist) and on the day of the operation (by an anesthetist and a resident). We constructed a model to predict difficult intubation (requiring 3 or more attempts). RESULTS: The kappa indices of agreement between the anesthetists at the preoperative examination and in the operating room or the resident were all less than 0.6. Factors like thyromental distance, small mouth, and kyphosis had kappa indices less than 0.21. The kappa index between the resident and the anesthetist in the operating room was over 0.55. The only factor that had a different level of agreement was the presence or not of a dental prosthesis. None of the studied individual factors, nor these factors in association with the Mallampati score, achieved significance in a bivariate regression model to predict difficult intubation. CONCLUSIONS: There is poor interobserver agreement on factors for predicting difficult airway in comparisons between preoperative and operating room assessment by an anesthetist or a resident. The individual predictive factors and their association with the Mallampati score did not prove useful for predicting difficult intubation.

Human mesenchymal stem cells and immunosuppressive drug interactions in allogeneic responses: an in vitro study using human cells.

OBJECTIVES: The use of mesenchymal stem cells (MSC), which display immunosuppressive activity, seems to be a promising therapeutic approach in solid organ transplantation. However, little is known about their interactions with immunosuppressive drugs. The objective of this study was to assess these interactions in allogeneic responses. METHODS: We studied the effects on alloimmune responses in mixed lymphocyte reactions of MSC plus five agents-cyclosporine, tacrolimus, rapamycin, mycophenolate acid (MPA), and dexamethasone (DEX). RESULTS: Human MSC isolated from bone marrow were characterized by their phenotype and their ability to differentiate into adipocytes or osteoblastes. MSC plus the agents inhibited allogeneic lymphocyte proliferation in a dose-dependent manner. Calcineurin inhibitors and rapamycin antagonized the inhibitory effect of MSC, whereas MPA promoted it and DXM did not modify it. CONCLUSION: MPA seems to be the best immunosuppressant to associated with MSC for transplanted patients.