Kidney Intragraft Homing of De Novo Donor-Specific HLA Antibodies Is an Essential Step of Antibody-Mediated Damage but Not Per Se Predictive of Graft Loss.

Donor-specific HLA antibody (DSA)-mediated graft injury is the major cause of kidney loss. Among DSA characteristics, graft homing has been suggested as an indicator of severe tissue damage. We analyzed the role of de novo DSA (dnDSA) graft homing on kidney transplantation outcome. Graft biopsy specimens and parallel sera from 48 nonsensitized pediatric kidney recipients were analyzed. Serum samples and eluates from graft biopsy specimens were tested for the presence of dnDSAs with flow bead technology. Intragraft dnDSAs (gDSAs) were never detected in the absence of serum dnDSAs (sDSAs), whereas in the presence of sDSAs, gDSAs were demonstrated in 72% of biopsy specimens. A significantly higher homing capability was expressed by class II sDSAs endowed with high mean fluorescence intensity and C3d- and/or C1q-fixing properties. In patients with available sequential biopsy specimens, we detected gDSAs before the appearance of antibody-mediated rejection. In sDSA-positive patients, gDSA positivity did not allow stratification for antibody-mediated graft lesions and graft loss. However, a consistent detection of skewed unique DSA specificities was observed over time within the graft, likely responsible for the damage. Our results indicate that gDSAs could represent an instrumental tool to identify, among sDSAs, clinically relevant antibody specificities requiring monitoring and possibly guiding patient management.

Impact of galactooligosaccharides delivered in ovo on mitigating negative effects of heat stress on performance and welfare of broilers.

Galactooligosaccharides (GOS) delivered in ovo improve intestinal health of broiler chickens. This study aimed to demonstrate the impact of in ovo stimulation with GOS prebiotic on day 12 of egg incubation on performance and welfare traits in broiler chickens. The incubating eggs were divided into 3 groups, based on the substance injected in ovo: 3.5 mg of GOS dissolved in 0.2 mL physiological saline (GOS), 0.2 mL physiological saline (S), or uninjected controls (C). Constant heat stress (HS) was induced on days 32 to 42 post-hatch by increasing environmental temperature to 30°C. Thermoneutral (TN) animals were kept at 25°C. The performance (body weight [BW], daily feed intake [DFI], daily weight gain [DWG], and feed conversion rate [FCR]) were measured and mortality was scored for starter (days 0 to 13), grower (days 14 to 27), and finisher (days 28 to 42) feeding phases. Rectal temperature was scored on days 32 to 42. Food-pad dermatitis (FPD) was scored post-mortem (day 42). GOS increased (P < 0.01) BW on day 42 (2.892 kg in GOS vs. 2.758 kg in C). Heat stress significantly reduced (P < 0.01) final BW (2.516 kg in TN vs. 3.110 kg in HS). During finisher phase, DFI was significantly higher in GOS vs. C (173.2 g vs. 165.7 g; P < 0.05). FCR calculated for the entire rearing period (days 0 to 42) ranged from 1.701 in C to 1.653 in GOS (P < 0.05). GOS improved FCR in HS animals during finisher phase (P < 0.05). Rectal temperature of GOS chickens under HS reached 42.5°C 1 day earlier than C and S (P < 0.05), which suggests that those birds recovered earlier from the high environmental temperature. Heat stress increased (P < 0.05) mortality about 5 times compared to TN during finisher phase (from 1.59% in TN to 7.69% in HS). GOS decreased FPD in TN conditions by 20% (no lesions in 81% in GOS vs. 60% in C). GOS delivered in ovo mitigated negative effects of HS on performance and welfare in broiler chickens.

Effect of galactooligosaccharides delivered in ovo on meat quality traits of broiler chickens exposed to heat stress.

A study was carried out to evaluate meat quality traits in fast-growing chickens stimulated in ovo with trans-galactoolighosaccarides (GOS) and exposed to heat stress. On day 12 of egg incubation, 3,000 fertilized eggs (Ross 308) were divided into prebiotic group (GOS) injected with 3.5 mg GOS/egg, saline group (S) injected with physiological saline, and control group (C) uninjected. After hatching, 900 male chicks (300 chicks/treatment) were reared in floor pens in either thermoneutral (TN; 6 pens/group, 25 birds/pen) or heat stress conditions (HS, 30°C from 32 to 42 D; 6 pens/group, 25 birds/pen). At 42 D of age, 15 randomly chosen birds/treatment/temperature were slaughtered and the pectoral muscle (PM) was removed for analyses. Data were analyzed by GLM in a 3 × 2 factorial design. In ovo treatment had no effect on PM weight, pH, water-holding capacity, and shear force. GOS and S birds had lighter (L*, P < 0.01) PM than C group, whereas the latter showed a higher (P < 0.05) yellowness index (b*) compared to S group. Proximate composition, cholesterol, and intramuscular collagen properties were not affected by treatment. As for fatty acid composition, only total polyunsaturated fatty acids (PUFA) content and n-6 PUFA were slightly lower in GOS group compared to S. Heat stress had a detrimental effect on PM weight (P < 0.01) and increased meat pH (P < 0.01). PM from HS chickens was darker with a higher b* index (P < 0.05) and had a higher (P < 0.01) lipid content and a lower (P < 0.05) total collagen amount. Total saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and PUFA were similar among groups. Significant interactions between factors were found for fatty acid composition: GOS decreased (P < 0.01) SFA and increased (P < 0.05) MUFA contents in HS birds. In conclusion, in ovo injection of GOS could mitigate the detrimental effect of heat stress on some meat quality traits.

[Bronchial carcinoma and tobacco: An update]. / Cancer bronchique et tabac : mise à jour.

Lung cancer remains the most lethal cancer. The most common cause is smoking, which is also preventable, unlike the causes of other types of cancer. A genetic characteristic has emerged over several years, which explains particular profiles of smokers, or highly dependent smokers. The emergence of new therapies for the treatment of lung cancer, and the impact of tobacco on reducing the effectiveness of these therapies must challenge practitioners to obtain a complete cessation of smoking regardless of the stage of the disease.

Renal transplant compartment syndrome: a case report.

An unusual case of early double kidney transplant dysfunction due to abdominal compartment syndrome is herein reported. A 62-year-old woman on peritoneal dialysis underwent dual kidney transplantation. The grafts were positioned extraperitoneally in both iliac possae using standard techniques. Surgical procedures and immediate postoperative period were uneventful. The urine output was immediate and the creatinine decreased, but in a few days she developed severe ascites with reduced urine output, increased creatinine, and progressive changes on Doppler ultrasound. The patient underwent paracentesis: the kidney function recovered as well as the Doppler ultrasound. Kidney biopsy was negative for rejection or renal pathology. Graft dysfunction was related to the presence of ascites. A catheter inserted in the abdomen measured intra-abdominal pressure (IAP) of 14 mm Hg. IAP correlated with renal function showing that IAP probably explained renal flow modifications.

Radical radiotherapy for bladder cancer: retrospective analysis of a series of 459 patients treated in an Italian institution.

AIMS: To contribute to the available evidence about the efficacy of exclusive radiotherapy for bladder cancer through a retrospective analysis of a large series of patients consecutively treated in a single institution. MATERIALS AND METHODS: A total of 459 patients with UICC categories T1-T4, N0-Nx and M0 bladder cancer consecutively treated with radiotherapy alone with radical intent formed the clinical basis for this study. Many of them (and particularly the T1 cases) had poor medical conditions or were unfit for surgery. About half of the cases (54%) had a T2 tumour, and about 18% had T3-T4 disease. Eighty per cent of the cases received minimal doses in the target volume in the range 60-70 Gy; pelvic lymph nodes were treated in 34%. Simple radiotherapy techniques were used in most cases. Average follow-up for living patients was 4.4 years. Results were analysed according to number and type of relapses: overall survival, disease-specific survival, failure-free survival probability, acute and late toxicity (RTOG scale). RESULTS: Actuarial 5-year overall survival, disease-specific survival and failure-free survival rates at 5 years for the entire series were 36%, 56%, 33%, respectively. Age, T category (for all the end points) and tumour dose (only for failure-free survival) were significantly related to prognosis at multivariate survival analysis. Late enteric toxicity (6.1% of the cases) was significantly linked with the treated volumes (univariate analysis). Urinary late toxicity (23% of cases) was linked with age and T category (multivariate analysis). In both cases, toxicity was mostly Grade 1 or 2. CONCLUSIONS: The results of radiotherapy in this negatively selected series, accrued over a long period of time in patients treated with unsophisticated techniques, are reasonably good; they add to the evidence available to support the use of modern bladder-sparing programmes, including the association of chemo- and radiotherapy.

Dopamine "renal dose" versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation.

Low dose of dopamine is commonly used after kidney transplantation as a reno-protective agent, although its benefits are controversial. Dopamine may increase renal blood flow, decrease resistive index (RI), and induce urine output in normal kidneys. Many authors hypothesized that the vasculature of a denervated renal transplant may not respond to dopamine in the same fashion as healthy native kidneys, which led us to find other drugs to attenuate the ischemia-reperfusion (I/R) injury. Fenoldopam is a selective dopamine1 (DA1) receptor agonist, most of the activity of which resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activities. Fenoldopam produces a vasidilatory effect in vascular beds that are rich in vascular DA1 receptors, producing increased renal blood flow at doses that do not affect blood pressure. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function. The aim of this study was to investigate the possible effects of fenoldopan mesylate in recent kidney transplants. Creatinine, blood urea nitrogen, urine output, and renal vascular resistive index (IR) were measured using Doppler ultrasound. Two groups of patients with no statistical differences in demographic data were treated with dopamine or fenoldopan, showing no significant difference but a trend favoring the fenoldopan group.

SCORTEN: a severity-of-illness score for toxic epidermal necrolysis.

The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate.

HLA class-I-soluble antigen serum levels in liver transplantation. A predictor marker of acute rejection.

The serum levels of sHLA-I have been determined in 16 patients following liver transplantation. sHLA-I levels did not show remarkable variations in six patients without evidence of transplant-related complications. sHLA-I levels strongly increased in 10 patients undergoing acute rejection episodes. In these patients, an average 20% daily increase of sHLA-I levels was detected on the 6 days preceding and on the 2 days following the rejection episode. A fast decrease of sHLA-I levels was observed in seven patients following treatment of acute rejection with anti-CD3 mAb. The serum level of sHLA-I antigens positively correlated with ALT serum level and inversely correlated with PT. The determination of sHLA-I in serum may therefore be proposed as a useful marker in the monitoring of patients following liver transplantation. The increase of sHLA-I antigens may predict the onset of acute rejection whereas their decrease may be related to a good response of acute rejection to immunosuppressive treatment.

Parvovirus B19 infection in thoracic organ transplant recipients.

BACKGROUND: Clinical manifestations of parvovirus B19 infection in immunocompromised patients are mostly reported as acute or chronic hematologic disorders. More recently, respiratory or renal involvement has been described. OBJECTIVE: We started in 1994 a prospective study of parvovirus B19 infection in a group of lung (LTP) and heart-lung (HLTP) transplanted patients, including occasionally heart transplanted (HTP) patients. STUDY DESIGN: 62 patients (49 LTP, 11 HLTP, 2 HTP) were included in a serological survey and DNA detection by PCR was performed on each serum sample of the first 29 patients; later we performed it only when serology could suggest an acute episode, or when parvovirus infection could be suspected on clinical or biological observations. A total of 1655 sera were examined by serological tests and DNA detection was done in 500 samples. Specific IgM, seroconversion, significant increase of specific IgG levels, and/or parvovirus B19 DNA detection, were considered as markers of viral infection. RESULTS: We observed the presence of both markers of infection in 24 patients (39%), with an individual combination of positive antibody and PCR results. Acute or chronic anaemia, neutropenia were associated to these laboratory findings in 19 patients, but in five cases, an asymptomatic clinical infection suggested viral persistence. CONCLUSIONS: We report parvovirus associated acute or chronic anaemia and pancytopenia in a group of LTP, HLTP and HTP patients, as well as asymptomatic cases of infection. In the hypothesis of a parvoviral persistent or latent infection, current diagnosis methods may be unreliable to identify any other clinical manifestations.

Lung perfusion demonstrated by contrast-enhanced dynamic magnetic resonance imaging. Application to unilateral lung transplantation.

RATIONALE AND OBJECTIVES: The authors evaluate the use of magnetic resonance (MR) to image pulmonary perfusion in healthy controls and to detect pulmonary defects in patients with unilateral lung transplantation, using dynamic images after contrast administration. METHODS: Five patients with right lung transplantation and nine healthy volunteers underwent MR imaging. Twenty-five subsecond contrast-enhanced MR images (turbo-fast low-angle shot [FLASH]) were obtained at the level of the pulmonary arteries after a single injection of gadopentetate dimeglumine (0.1 mmol/kg) in an antecubital vein. Perfusion lung scintigraphy was done within 24 hours after the MR imaging examination in the transplanted patients. RESULTS: Before administration of contrast material, MR images showed both lungs to be homogeneous and of low signal intensity in healthy controls and in patients with lung transplantation. After contrast administration in controls, the mean signal intensity of the dependent lung increased markedly to 171 +/- 24% above baseline, whereas the nondependent signal intensity lung increased by only 105 +/- 17%; these changes were significantly different. In all patients with lung transplantation, a clear perfusion defect was demonstrated in the native lung. This defect was confirmed in all cases by perfusion nuclear scintigraphy, which showed that the majority of lung perfusion is directed to the transplanted allograft, compared with the native contralateral lung. CONCLUSIONS: Our results suggest that dynamic contrast-enhanced MR imaging is a potential method for detecting pulmonary perfusion defects in patients with lung transplantation.

Self-expanding metal stents for the management of bronchial stenosis and bronchomalacia after lung transplantation.

BACKGROUND: Airway stenosis or malacia after lung transplantation, usually as a result of anastomotic ischemia, remains a major problem. METHODS: The authors report their experience with the Gianturco expandable stent for the management of 23 bronchial stenoses in 18 patients following lung transplantation. Stent placement occurred an average of 5.6 months after transplantation. RESULTS: Stents were well tolerated and produced immediate symptomatic and functional improvement. The mean follow-up after implantation was 21 months (range, 4 to 48 mo). The authors removed five stents by endoscopy and replaced them, and removed one stent entirely. Laser resection was used to control granulomas or partial fibrosis stenosis that occurred in four stents (14.3%) after an average of 4 months. One stent broke but was still in place and effective 32 months later. One patient died of hemorrhage 4 months after stenting. CONCLUSION: Although it can still be improved, this expandable metal stent is suitable for the treatment of posttransplantation proximal bronchial stenosis.

Preliminary report on impact of pretransplant dialysis on early graft function: peritoneal versus hemodialysis.

Delayed graft function and acute renal failure after kidney transplant negatively influence graft outcome. It has been reported that pretransplantation peritoneal dialysis (PD) instead of hemodialysis (HD) correlated with better short-term graft outcome in adult kidney recipients. In this study the impact of PD versus HD was evaluated among pediatric kidney recipients. This study suggested that different forms of dialysis pretransplantation did not affect early graft function among pediatric kidney recipients.

Severe rhabdomyolysis and acute renal failure in a kidney transplant patient treated with tacrolimus and chimaeric CD25 monoclonal antibody.

Recently observations of rhabdomyolysis in patients treated with tacrolimus have been reported. The authors present a kidney transplant patient who had an epileptic seizures, severe rhabdomyolysis, and acute renal failure. The patient was initially immunosuppressed with tacrolimus and chimeric CD25 monoclonal antibody. After intensive therapy with plasmapheresis, CVVH, and dialysis, the patient completely recovered at 11/2 year his serum creatinine is 1.2 mg/dL.

Simultaneous liver-kidney transplantation for glycogen storage disease type IA (von Gierke's disease).

INTRODUCTION: Glycogen storage disease type Ia (GSDIa) is due to the deficiency of glucose-6-phosphatase activity in the liver, kidney, and intestine. Although significant progress has been achieved in the management of patients with GSDIa, complications still emerge. The potential for development of liver adenomatosis and kidney failure makes these patients candidates for simultaneous liver-kidney transplantation (SLKT). Herein, we describe such a transplantation in a patient affected by this rare storage disease. METHODS: A 25-year-old female patient with GSDIa developed hepatic adenoma and kidney failure despite dietary therapy. The patient underwent an SLKT from a cadaveric donor. RESULTS: The operative time was 8 hours without hemotransfusion. Only a transitory lactic acidosis was observed. Laboratory results normalized on postoperative day 7. The patient was discharged on postoperative day 9. After 4 months, the patient is in good condition with well-functioning kidney and liver allografts. CONCLUSION: Patients with end-stage renal disease secondary to GSDIa should be considered for SLKT, especially when the disease is in an early stage.

[Intensive care in lung and heart-lung transplantation]. / Réanimation en transplantation pulmonaire et cardiopulmonaire.

Intensive care after lung, and heart-lung transplantation may have simple post operative course specially after preventive procedures of reperfusion injury, nosocomial infections during mechanical ventilation and immunosuppression risks. Nevertheless a severe mediastinal shift may occurred after single lung transplantation in emphysema. Rapid changes in ventilation/perfusion ratio during lung infection or rejection specially in pulmonary hypertension are responsible of dramatic respiratory failure. Knowledge of multiorgan dysfunction and multidisciplinary experience encourage to future development.

[Delayed detection of cystic fibrosis in a patient with Mycobacterium avium complex infection]. / Infections à mycobacterium avium complex révélant tardivement une mucoviscidose.

We report a case of pulmonary infection by Mycobacterium avium complex revealing in a 21 years old patient a cystic fibrosis heterozygous for the delta F 508 deletion. The role of this bacteria in the lung infection is suggested by repeated isolation. This infection caused bronchitis, hypoxemia and pulmonary nodules at CT scan. The clinical and radiological signs improved after treatment with four antibiotics whereas only clarithromycin showed in vitro activity. An obstructive disease due to allergic bronchopulmonary aspergillosis developed and was controlled by steroid therapy.

[Lung transplantation in cystic fibrosis in adults. Patient selection criteria]. / Transplantation pulmonaire dans la mucoviscidose de l'adulte. Recommandations pour la sélection des candidats.

Lung transplantation (LT) became during the ten past years an important therapeutic option for cystic fibrosis adult patients with end-stage chronic lung disease. LT clearly improves both survival and long term quality of life. A rigorous selection of the candidates is of paramount importance to improve the results of LT because of the lack of shortage of organs. This selection requires a multidisciplinary assessment to refuse patients with absolute exclusion criteria or general medical conditions that impact negatively on short- and long-term outcome. One of the major difficulties is to determine the best time to refer patients to transplantation, arguing the comparison between the predicted survival time of the candidate, under optimal medical therapy, with or without LT. The selection period is also an active process to prepare the patients to the postoperative follow-up and includes a nutritional and rehabilitation program with an educational and psychological preparation. The aim of the present work is to gather the worldwide principles of the selection of the CF patients for LT, commonly used by the LT centers. These recommendations should provide the CF center practitioners with the main elements to prepare their patients to an LT project before a relentless end-stage clinical condition.

[Outcome of adult patients with cystic fibrosis admitted to intensive care with respiratory failure: the role of non-invasive ventilation]. / Devenir des adultes mucoviscidosiques admis en réanimation pour décompensation respiratoire.

Recourse to mechanical ventilation may prove necessary in adult patients with cystic fibrosis who have reached the stage of severe respiratory insufficiency. We report the experience of an intensive care service using non-invasive ventilation (NIV) as the first step in the management of acute respiratory failure in these patients. The records of 16 patients with cystic fibrosis presenting with acute respiratory failure and treated with NIV were analysed retrospectively. The characteristics of the group were: mean age 26.9 +/- 9.5 years; mean FEV1 21.5 +/- 10.4% predicted; mean body mass index 16.8 +/- 2.1; mean Pa CO(2) on admission 66 +/- 15 mm Hg. The mean duration of NIV in the ICU was 10 +/- 7 days. Eight patients (50%) died after having been intubated on account of failure of NIV. The eight survivors were discharged home with long-term NIV (mean duration 235 +/- 158 days). Six of them have received a lung transplant. The mode of onset of respiratory failure was an important prognostic factor: a rapid onset (<7 days) was invariably associated with death, on the other hand a gradual deterioration (> 7 days) was noted in the eight patients able to leave the ICU. In conclusion NIV may be regarded as the treatment of choice in patients with cystic fibrosis admitted to ICU with respiratory failure. In the case of persistent hypercapnia after the acute episode long-term NIV may keep them stable while awaiting lung transplantation.

[Type AA renal amyloidosis in sarcoidosis]. / Amyloïdose rénale AA au cours d'une sarcoïdose.

Sarcoidosis is an uncommon cause of secondary amyloidosis. We describe in this paper the case of a 39 years old patient, with a pulmonary and hepatosplenic sarcoidosis. A nephrotic syndrome led to a renal biopsy which showed AA type amyloidosis. As no other cause of amyloidosis has been found we admitted that it was a result of sarcoidosis which was associated with the unusual inflammatory syndrome.