Treatment of acute antibody-mediated rejection: a single-center experience

Introduction

Acute antibody-mediated rejection (AMR) leads to graft loss. The combination of plasmapheresis (PP), intravenous immunoglobulin (IVIG), and rituximab (RTX) has been reported to be effective therapy.

Patients and methods

Between October 2005 and September 2009, 8 (4.7%) kidney transplant recipients developed AMR, diagnosed by severe acute rejection and extensive C4d staining in peritubular capillaries.

Results

All patients were treated with two to six sessions of PP with IVIG added after the last PP. In two patients, RTX was prescribed after PP and IVIG. Baseline immunosuppression was based on steroids, mycophenolate mofetil or azathioprine, and tacrolimus or cyclosporine or everolimus. The presence of subsequent significant decrease in anti-HLA class I antibodies was demonstrated in a highly sensitized patient before and after transplantation with PP treatment. An increase was observed before the diagnosis of AMR. After a mean follow-up of 10 months (range = 1-23), patient and graft survivals were 100% and 50%, respectively. Three patients lost their transplants to AMR refractory to treatment and one patient, due to interstitial fibrosis and tubular atrophy at 23 months after AMR. Finally, four patients recovered renal function, showing a mean serum creatinine of 2.2 ± 0.45 mg/dL.

Conclusions

Early diagnosis and treatment with PP, IVIG, and RTX may resolve AMR. PP before and after transplantation in high-risk patients may result in anti-HLA class I and class II antibody removal from plasma and prevention of AMR.     

Human ventral parietal cortex plays a functional role on visuospatial attention and primary consciousness. A repetitive transcranial magnetic stimulation study

In this paper, we used repetitive transcranial magnetic stimulation (rTMS) in 18 normal subjects to investigate whether the ventral posterior parietal cortex (PPC) plays a causal role on visuospatial attention and primary consciousness and whether these 2 functions are linearly correlated with each other. Two distinct experimental conditions involved a similar visual stimuli recognition paradigm. In "Consciousness" experiment, number of consciously perceived visual stimuli was lower by about 10% after rTMS (300 ms, 20 Hz, motor threshold intensity) on left or right PPC than after sham (pseudo) rTMS. In "Attentional" Posner's experiment, these stimuli were always consciously perceived. Compared with sham condition, parietal rTMS slowed of about 25 ms reaction time to go stimuli, thus disclosing effects on endogenous covert spatial attention. No linear correlation was observed between the rTMS-induced impairment on attention and conscious perception. Results suggest that PPC plays a slight but significant causal role in both visuospatial attention and primary consciousness. Furthermore, these high-level cognitive functions, as modulated by parietal rTMS, do not seem to share either linear or simple relationships.     

Timing of Resection of Liver Metastases Synchronous to Colorectal Tumor: Proposal of Prognosis-Based Decisional Model

Background Timing of hepatectomy for synchronous metastases of colorectal cancer is still debated. The aim of this retrospective study was to analyze prognostic factors after synchronous and delayed liver resections to define selection criteria for choosing timing of hepatectomy. Methods The study was performed on 127 patients with synchronous metastases undergoing radical hepatectomy. We divided patients according to the timing of hepatectomy: 70 synchronous (group A) and 57 delayed (group B). Results Overall survival was similar between the two groups (5-year survival 30.8% vs. 32.0% A vs. B, P = .406). The multivariate analysis evidenced four independent prognostic factors in group A: male sex (P = .04), T4 (P = .0035), more than three metastases (P = .0001), and metastatic infiltration of nearby structures (P < .0001). There were no statistically significant prognostic factors in group B. Patients with more than three metastases had a significantly worse survival in group A than in group B (3-year survival, 15.0% vs. 34.3%, P = .007); similarly, borderline significant difference was encountered in patients with T4 primary tumor (3-year survival, 16.7% vs. 60%, P = .064) Conclusions Patients with liver metastases synchronous with colorectal cancer with T4 primary tumor, metastasis infiltration of neighboring structures, and especially with more than three metastases should receive neoadjuvant chemotherapy before liver resection.     

Postoperative Liver Dysfunction and Future Remnant Liver: Where Is the Limit?

Background The future remnant liver (FRL) limit for safe major hepatectomy with low risk of postoperative liver failure has not yet been well defined. Methods Between April 2000 and September 2004, every patient scheduled for major hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE, associated vascular resection and liver cirrhosis. The FRL was correlated with short-term results in patients with normal liver (group A) and those with impaired liver function secondary to neoadjuvant chemotherapy or cholestasis (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50% and serum bilirubin level >5 mg/100 ml for three or more consecutive days. Results A total of 119 patients were analyzed, 72 in group A and 47 in group B. The FRL value was the only significant risk factor for postoperative liver dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did not correlate with postoperative mortality and morbidity. Bilirubin and prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in both groups. In group A, patients with postoperative liver dysfunction had a FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV. Conclusions Hepatectomy can be considered safe when FRL is >26.5% in patients with healthy liver and >31% in patients with impaired liver function.     

Visual proprioception in the timing of movements: evidence from deafferentation

The present study investigated the control of movements in two patients with severe somatosensory deafferentation by systematically manipulating the visual information about the produced movements. In a synchronization task requiring the production of finger taps in synchrony with a regular auditory signal, participants controlled their movements under full vision or when the sight of the effector was partially or completely occluded. Results demonstrated large effects of visual feedback on the synchronization performance in the deafferented patients. Although the patients' performance differed substantially from that of unimpaired controls under partial or no feedback, their performance was comparable under full vision, the latter suggesting a compensation of the somatosensory loss by visual monitoring.     

Phonemic fluency in Portuguese-speaking subjects in Brazil: ranking of letters

Phonological verbal fluency studies in English most commonly employ the letters F-A-S as stimuli. We assessed the production of words with these and 14 other letters in Portuguese-speaking healthy subjects (n = 74). The letters F-A-S were ranked among the easiest to produce words in one minute, which is consistent with the findings of studies with English-speaking subjects. There were differences in the overall ranking of letters depending on whether the total word number or the latency between words were considered. Our findings provide a databank of phonological verbal fluency performance using different stimuli in Portuguese, and demonstrate that the ranking of the letters F-A-S is comparable between the English and Portuguese languages in terms of the level of difficulty to produce words, when the task is used in its traditional format.     

Effects of N-acetylcysteine on renal hemodynamics in contrast media-induced nephropathy

Background: N-acetylcysteine (NAC) has been proposed to prevent radiocontrast nephropathy in high-risk patients. Methods: The effect of single-dose and prolonged administration of NAC before application of either the ionic, high-osmolar radiocontrast agent diatrizoate sodium (DTZ) or the nonionic, low-osmolar radiocontrast agent iohexol (IOH) in a rat model combining uninephrectomy, salt depletion, and administration of indomethacin was explored. Arterial blood pressure and total, cortical, and medullary blood flow were continuously recorded in anesthetized Sprague-Dawley rats. Results: NAC had no effect on renal hemodynamics in control rats. Both DTZ and IOH induced biphasic changes in renal blood flow and cortical renal blood flux and persistently reduced medullary blood flux. Neither single-dose nor prolonged administration of NAC prevented the hemodynamic changes following administration of DTZ or IOH, respectively. Acute prophylactic administration of NAC prevented increased urinary ET excretion after injection of IOH and, to a smaller degree, of DTZ. Both an ionic, high-osmolar (DTZ) and a nonionic, low-osmolar (IOH) radiocontrast agent induce marked changes in renal hemodynamics in salt-depleted rats treated with indomethacin. Conclusions: Renal perfusion is not affected by NAC application in a model of experimental contrast nephropathy in rats. Other effects of NAC might thus account for the presumed renoprotective properties.     

Long-term experience with early single Mitomycin C instillations in patients with low-risk non-muscle-invasive bladder cancer: prospective, single-centre randomised trial

Purpose  

To study the benefits of a single, early, intravesical instillation of mitomycin C(MMC) after transurethral bladder resection (TURB) in patients with low-risk non-muscle-invasive bladder cancer (NMIBC).