Clearance of Neutrophils From ICH-Affected Brain by Macrophages Is Beneficial and Is Assisted by Lactoferrin and CD91.

BACKGROUND: Within hours after intracerebral hemorrhage (ICH) onset, masses of polymorphonuclear neutrophils (PMNs) infiltrate the ICH-affected brain. After degranulation involving controlled release of many toxic antimicrobial molecules, the PMNs undergo rapid apoptosis and then are removed by phagocytic microglia/macrophages (MΦ) through a process called efferocytosis. Effective removal of PMNs may limit secondary brain damage and inflammation; however, the molecular mechanisms governing these cleanup activities are not well understood. We propose that scavenger receptor CD91 on myeloid phagocytes especially in presence of CD91 ligand, LTF (lactoferrin, protein abundant in PMNs), plays an important role in clearance of dead apoptotic PMNs (ANs). METHODS: Mice/rats were subjected to an autologous blood injection model of ICH. Primary cultured microglia were used to assess phagocytosis of ANs. Immunohistochemistry was employed to assess CD91 expression and PMN infiltration. CD91 knockout mice selectively in myeloid phagocytes (Mac-CD91-KO) were used to establish the CD91/LTF function in phagocytosis and in reducing ICH-induced injury, as assessed using behavioral tests, hematoma resolution, and oxidative stress. RESULTS: Masses of PMNs are found in ICH-affected brain, and they contain LTF. MΦ at the outer border of hematoma are densely packed, expressing CD91 and phagocytosing ANs. Microglia deficient in CD91 demonstrate defective phagocytosis of ANs, and mice deficient in CD91 (Mac-CD91-KO) subjected to ICH injury have increased neurological dysfunction that is associated with impaired hematoma resolution (hemoglobin and iron clearance) and elevated oxidative stress. LTF that normally ameliorates ICH injury in CD91-proficient control mice shows reduced therapeutic effects in Mac-CD91-KO mice. CONCLUSIONS: Our study suggests that CD91 plays a beneficial role in improving ANs phagocytosis and ultimately post-ICH outcome and that the beneficial effect of LTF in ICH is in part dependent on presence of CD91 on MΦ.

How Variable Is the Volar Subcutaneous Tissue of the Digits on B-Mode and Color Doppler Ultrasound in Non-Psoriatic Individuals and Could It Be Included in a Dactylitis Score?

BACKGROUND: Digital subcutaneous tissue (SCT) changes are involved in dactylitis, a hallmark feature of psoriatic arthritis (PsA). There are no studies on the ultrasound (US) characteristics of the digital SCT in the general population. OBJECTIVES: To investigate the variability in US-measured thickness (TH) and color Doppler (CD)-detected blood flow of the SCT of the volar aspects of the fingers in a non-psoriatic population and to investigate the impact of the scanning method and demographics and clinical features on these measurements. METHODS: SCT TH and semiquantitative (SQD) and quantitative (QD) Doppler signals were measured in the bilateral second finger at the proximal and middle phalanges in 81 non-psoriatic volunteers [49 female, 32 men; 18-78 years]. Two scanning methods with and without (thick gel layer interposition) probe-skin contact were used. Demographics and clinical features were collected. RESULTS: There was high variability of SCT TH and Doppler measurements between individuals. All US measurements obtained without probe-skin contact were significantly greater than their corresponding measurements obtained with the probe contacting the skin (p < 0.001). SCT TH was positively related to dominant hand, age, masculine gender, weight, height, body mass index, and alcohol consumption while Doppler measurements were positively related to age and non-dominant hand. CONCLUSIONS: US-measured SCT thickness and Doppler-detected SCT blood flow of the volar aspect of the fingers seem to be highly variable in the non-psoriatic population as well as highly dependent on the US scanning method. This variability is of utmost importance for assessing dactylitis in PsA.

Can ultrasound-detected subclinical synovitis be an indicator of flare recurrence in juvenile idiopathic arthritis remission patients on tapered TNFi?

OBJECTIVES: Subclinical synovitis is often detected by musculoskeletal ultrasound (MSUS) in juvenile idiopathic arthritis (JIA) patients in clinical remission. The main objective of this prospective, observational, longitudinal, multicentre study was to evaluate the predictive value of MSUS-detected subclinical synovitis in relation to flares at 12 months following TNFi tapering in a JIA population in stable clinical remission. METHODS: We included 56 JIA patients in stable remission undergoing TNFi therapy tapered at baseline and in some cases at 6 months. We performed baseline and 6-month MSUS assessment on B-mode (BM) and power Doppler (PD) mode of 22 joints and 8 tendons. RESULTS: Eighteen patients (32.1%) experienced a flare during the 12-month study period. BM synovitis was frequent (83.9%) but PD synovitis was scarcely found (8.9%). There were no significant differences in MSUS findings between patients who experienced a flare and those who remained in remission. Only 5 patients had positive for PD synovitis, in joints with BM synovitis grades 2 or 3, and none experienced a flare. Concomitant methotrexate (MTX) was more frequent in patients who were successfully tapered (71.1% vs. 27.8%; p=0.002) and patients older than 12 experienced a greater number of flares and earlier onset. CONCLUSIONS: Subclinical synovitis, as detected by MSUS, proved not to be a predictor of flares. Those patients on a TNFi-tapered concomitant methotrexate regimen experienced the fewest flares although flare risk increased with age.

To what extend is nail ultrasound discriminative between psoriasis, psoriatic arthritis and healthy subjects?

To assess the discriminative utility of nail features detected by B-mode (BM) and color Doppler (CD) ultrasound (US) between patients with psoriasis (PsO) and psoriatic arthritis (PsA) and healthy controls. Sixty patients with PsA, 21 patients with PsO, and 20 healthy controls were prospectively included. All patients underwent a dermatologic assessment and PsA patients also a rheumatologic assessment. All patients and controls underwent a US assessment of the finger nails that included a BM score for nail plate integrity and four different CD scores based on the amount and location of CD signals in the nail bed/matrix. In addition, we measured the thickness of the nail bed (TNB) and nail plate (TNP). The BM score and the CD score based on the amount of signals in the nail bed in contact with the ventral plate discriminated between the control group (median, range 0.0, 0-4 and 2.0, 0-9, respectively) and the PsO/PsA group (median, range: 7.0, 0-31 and 5.14, 0-13, respectively) (p < 0.05) with or without clinical nail involvement. The CD scores based on the percentage of the nail bed/matrix occupied by Doppler signals did not discriminate between controls and PsO/PsA patients. TNB and TNP were significantly higher in psoriatic nails with or without clinical involvement than in control nails. In PsO/PsA patients, the BM score, TNB and TNP were significantly higher in clinically involved nail than in clinically non-involved nails. Our results showed discriminative utility of BM US and some CD US features for PsO/PsA nails.

Identifying markers of sustained remission in rheumatoid arthritis patients on long-term tapered biological disease-modifying antirheumatic drugs.

To identify features associated with long-term persistent remission in rheumatoid arthritis (RA) patients on tapered biological disease-modifying antirheumatic drugs (bDMARD) (tap-bDMARD) therapy. We carried out a 40-month (m) extension follow-up study of 77 RA patients from a previous 12 m tap-bDMARD study. Disease activity was assessed at baseline and every 3 months. Doppler US investigation of 42 joints for the presence and grade (0-3) of B-mode synovial hypertrophy (SH) and synovial power Doppler signal (i.e., Doppler synovitis) was performed before starting the tap-bDMARD strategy by a rheumatologist blinded to clinical and laboratory data. At the 40 m mark, 44 (57.1%) patients failed the tap-bDMARD strategy, while 33 (42.9%) succeeded. Patients who presented a failed tap-bDMARD had significantly longer disease duration, a longer time from symptom onset to synthetic (s) DMARD start, longer duration of sDMARD treatment, a greater number of sDMARDs, and a higher baseline DAS28 and SDAI than patients with successful tap-bDMARD at 40 months. In logistic regression analysis, the presence of baseline Doppler synovitis, a DAS28 ≥ 2.2, and the presence of rheumatoid factor were identified as predictors of tap-bDMARD failure at 40 m. In those patients who succeed tap-bDMARD at 12 m, a smoking habit was significantly more frequently found in tap-bDMARD failures at 40 m. Our results showed that DAS28 and the presence of Doppler synovitis, RF and a smoking habit predicted long-term tap-bDMARD failure.

Ratio of Circulating Estrogen Receptors Beta and Alpha (ERß/ERα) Indicates Endoscopic Activity in Patients with Crohn's Disease.

BACKGROUND: Data supporting a role of female hormones and/or their receptors in inflammatory bowel disease (IBD) are increasing, but most of them are derived from animal models. Estrogen receptors alpha (ERα) and beta (ERß) participate in immune and inflammatory response, among a variety of biological processes. Their effects are antagonistic, and the net action of estrogens may depend on their relative proportions. AIM: To determine the possible association between the balance of circulating ERß and ERα (ERß/ERα) and IBD risk and activity. METHODS: Serum samples from 145 patients with IBD (79 Crohn's disease [CD] and 66 ulcerative colitis [UC]) and 39 controls were retrospectively studied. Circulating ERα and ERß were measured by ELISA. Disease activities were assessed by clinical and endoscopic indices specific for CD and UC. RESULTS: Low values of ERß/ERα ratio were directly associated with clinical (p = 0.019) and endoscopic (p = 0.002) disease activity. Further analyses by type of IBD confirmed a strong association between low ERß/ERα ratio and CD clinical (p = 0.011) and endoscopic activity (p = 0.002). The receiver operating curve (ROC) analysis showed that an ERß/ERα ratio under 0.85 was a good marker of CD endoscopic activity (area under the curve [AUC]: 0.84; p = 0.002; sensitivity: 70%; specificity: 91%). ERß/ERα ratio was not useful to predict UC activity. CONCLUSIONS: An ERß/ERα ratio under 0.85 indicated CD endoscopic activity. The determination of serum ERß/ERα might be a useful noninvasive screening tool for CD endoscopic activity.

Event- and Time-Driven Techniques Using Parallel CPU-GPU Co-processing for Spiking Neural Networks.

Modeling and simulating the neural structures which make up our central neural system is instrumental for deciphering the computational neural cues beneath. Higher levels of biological plausibility usually impose higher levels of complexity in mathematical modeling, from neural to behavioral levels. This paper focuses on overcoming the simulation problems (accuracy and performance) derived from using higher levels of mathematical complexity at a neural level. This study proposes different techniques for simulating neural models that hold incremental levels of mathematical complexity: leaky integrate-and-fire (LIF), adaptive exponential integrate-and-fire (AdEx), and Hodgkin-Huxley (HH) neural models (ranged from low to high neural complexity). The studied techniques are classified into two main families depending on how the neural-model dynamic evaluation is computed: the event-driven or the time-driven families. Whilst event-driven techniques pre-compile and store the neural dynamics within look-up tables, time-driven techniques compute the neural dynamics iteratively during the simulation time. We propose two modifications for the event-driven family: a look-up table recombination to better cope with the incremental neural complexity together with a better handling of the synchronous input activity. Regarding the time-driven family, we propose a modification in computing the neural dynamics: the bi-fixed-step integration method. This method automatically adjusts the simulation step size to better cope with the stiffness of the neural model dynamics running in CPU platforms. One version of this method is also implemented for hybrid CPU-GPU platforms. Finally, we analyze how the performance and accuracy of these modifications evolve with increasing levels of neural complexity. We also demonstrate how the proposed modifications which constitute the main contribution of this study systematically outperform the traditional event- and time-driven techniques under increasing levels of neural complexity.

Investigating the link between disease activity and infliximab serum levels in rheumatoid arthritis patients.

OBJECTIVES: The aim of this study was to examine the extent to which infliximab (IFX) serum levels impact disease activity in rheumatoid arthritis (RA) patients. METHODS: In this cross sectional study, serum samples were taken prior to drug infusion from 60 RA patients who had been undergoing IFX therapy > 12 months as a first line of biological treatment. Patient IFX levels were tested and then associated with clinical disease activity. Three DAS28 cut-off points, <2.6, <3.2 and <5.1 were used to determine whether detectable IFX levels were any predictor of clinical disease activity. Logistic regression analysis was run to check other possible factors associated with RA clinical outcomes such as MTX concomitant use, CRP and ESR. RESULTS: Sixteen (27%) out of the 60 patients tested negative; 28 (46%) presented subtherapeutic and 16 (27%) therapeutic IFX levels. Median IFX levels were higher in patients either in remission or showing low disease activity than in those with moderate and high disease activity (p=0.014). Significant association was found between IFX levels and clinical disease activity (p=0.001). Detectable levels of IFX shows better sensitivity and specificity to identify patients with DAS28<3.2 than to identify patients with DAS28<2.6 or DAS28<5.1. Conversely, the best DAS28 cut-off to identify detectable/undetectable IFX was 3.19, with AUC under ROC curve 0.804 (Sd.E 0.070), 76% specificity and 83% sensitivity (p<0.001). MTX use, CRP and ESR did not interfere with this association. Seven out of the 8 patients with anti-IFX antibodies presented DAS28>3.2 (p=0.005). CONCLUSIONS: DAS28 and IFX serum levels were shown to have an inverse correlation. Undetectable IFX serum levels were associated to RA patients presenting DAS28>3.2 meaning that DAS28 <3.2 may be useful to clinicians to evaluate patient response to drug therapy.

Comparison of Mycobacterium lentiflavum and Mycobacterium avium-intracellulare complex lymphadenitis.

BACKGROUND: Mycobacterium lentiflavum is considered a rare pathogen causing nontuberculous mycobacterial (NTM) lymphadenitis. METHODS: A multicenter, retrospective study was performed in immunocompetent children <14 years of age with microbiologically confirmed NTM lymphadenitis treated at 6 hospitals in Madrid, Spain, during 2000-2010. We compared children with M. lentiflavum and Mycobacterium avium-intracellulare complex infection. RESULTS: Forty-five microbiologically confirmed NTM lymphadenitis patients were identified: 19 (45.2%) caused by M. avium-intracellulare complex, 17 (40.5%) by M. lentiflavum, 1 by both and 5 by other mycobacteria. Out of 17 M. lentiflavum cases, 14 were diagnosed in the past 5 years. Regarding M. lentiflavum cases, median age was 23 months. Submandibular nodes were the most frequently involved (76.5%), with multiple locations seen in 41% of the children and spontaneous drainage in 41% of them. Drug susceptibility tests were performed in 14 isolates and showed a complete susceptibility to clarithromycin and cycloserine, whereas 93% were resistant to rifampin, 33% to quinolones and full resistance to other tested antimycobacterial drugs was detected. All but 1 child required surgery and 11 were treated additionally with various drug combinations. Total resolution was achieved in 50% of children within 6 months.Compared with M. avium-intracellulare complex cases, children were younger and laterocervical nodes were significantly less frequently involved. No statistically significant differences were found related to clinical characteristics, treatment and outcome. CONCLUSIONS: M. lentiflavum is an emerging pathogen producing NTM lymphadenitis in Madrid.

Three-dimensional volumetric ultrasound: a valid method for blinded assessment of response to therapy in rheumatoid arthritis.

OBJECTIVE: To assess the responsiveness and repeatability of volumetric power Doppler ultrasound (PDUS) evaluation of synovitis and bone erosions in rheumatoid arthritis (RA). METHODS: Twenty-three patients with RA (19 women, mean age 52.7 ± 12.6 yrs, mean disease duration 10.1 ± 8.6 yrs) were prospectively enrolled. All patients were beginning therapy with rituximab because of disease activity despite therapy with synthetic disease-modifying antirheumatic drugs and tumor necrosis factor-blocking agents. Patients underwent clinical, laboratory, and volumetric PDUS examination at baseline, 6 months, and 12 months. Ten centers participated in the study. Four centers recruited the patients and performed the volumetric acquisitions of PDUS images, while the remaining 6 centers assessed the PDUS volumes, blinded to the identity of patients and date of the visits. The most symptomatic hand and foot were scored for B-mode synovitis, synovial PD signal, and bone erosions. The repeatability of the volumetric PDUS assessment was investigated. RESULTS: An overall improvement in clinical and PDUS measurements was found at the followup assessments. The mean indexes for synovial PD signal and bone erosions and the number of sites with abnormalities decreased significantly throughout the followup (p < 0.05). The intraacquisition, intrareader reliability was excellent for all PDUS measurements (intraclass correlation coefficients > 0.9). CONCLUSION: The results of our pilot study suggest that volumetric PDUS can be responsive and repeatable in multicenter cohort studies of RA. This technique may minimize assessment biases and reduce acquisition variability in open-label and observational studies.

A multicentre study on high-frequency ultrasound evaluation of the skin and joints in patients with psoriatic arthritis treated with infliximab.

OBJECTIVES: Our objective was to describe the ultrasound features of patients with PsA in joints and skin and their changes after treatment with infliximab. METHODS: Eight hospitals recruited PsA active patients. Clinical (joint count for pain, TJC, and swelling, SJC, pain VAS, ESR, C-reactive protein and PASI) and US variables (plaque thickness, PD signal of dermal lesions, synovitis, erosions, and PD signal, assessed by 4-category ordinal scales) were independently recorded at baseline and 4, 12 and 24-week after starting treatment with infliximab. The results were analysed with paired T, Wilcoxon test, ANOVA and marginal homogeneity test. RESULTS: Changes in 24 patients from baseline to last available data were significant for clinical variables, pain VAS, TJC and SJC as well as for ESR, CRP (all p<0.0005). Dermatological PASI changed from 14.6±14.9 to 2.1±4.1 and plaque thickness from 3.34±1.75 mm to 1.74±0.96 mm (both p<0.0005); synovitis and PD signal improved (both p<0.0005). Psoriatic plaque PD improved across the study (p<0.0005) with no signal increasing from 36.4% to 88.9% and positive PD signal decreasing from 63.6% to 11.1% of the plaques. CONCLUSIONS: Treatment with anti-TNF-α infliximab improves the symptoms of patients with PsA at joint and psoriatic skin levels from a clinical and ultrasonographic perspective.

[Description of a new mutation in a female patient with Fabry disease]. / Mutação de novo causadora de doença de Fabry em paciente do sexo feminino.

Fabry disease is caused by intracellular accumulation of glycosphingolipids in various tissues, secondary to mutations in the GLA gene (Xq22). Classically described as affecting hemizygous males with no residual alpha-galactosidase A activity, it is now known to affect both sexes, with later and less severe manifestations in females. The manifestations of this disease are systemic: neurological, cutaneous (angiokeratomas), renal, cardiovascular (left ventricular hypertrophy, valve thickening or rhythm disturbances), cochlear-vestibular, and cerebrovascular. In the absence of treatment there is progressive damage to vital organs with renal failure, stroke, heart failure or rhythm perturbations, leading to severe impairment of quality of life as well as reduced life expectancy. We describe the case of a female patient with a history of cryptogenic ischemic stroke at the age of 38 years and chronic renal failure with proteinuria, who presented to the emergency room with atrial fibrillation. The echocardiogram revealed concentric left ventricular hypertrophy, diastolic dysfunction and decreased longitudinal strain in the basal septum. In the context of a screening protocol, she was diagnosed with Fabry disease and a previously undescribed mutation was identified.

Multi-examiner reliability of automated radio frequency-based ultrasound measurements of common carotid intima-media thickness in rheumatoid arthritis.

OBJECTIVES: To assess the reliability of the automated radio frequency (RF)-based US measurement of carotid intima-media thickness (IMT) performed by rheumatologists and to evaluate the variability between this method and the conventional B-mode US measurement of carotid IMT in RA patients. METHODS: Twelve rheumatologists measured in two blinded rounds the IMT of both common carotid arteries (CCAs) of seven RA patients with an automated RF-based method. At each round, a cardiologist measured both CCA-IMTs of the patients using an automated B-mode method. Inter-observer reliability for RF-based IMT measurements was evaluated by the intra-class correlation coefficient (ICC). Intra-observer reliability for RF-based IMT measurements was assessed using the root mean square coefficient of variation (RMS-CV), Bland-Altman method and ICC. Agreement between the two US methods was evaluated by the Bland-Altman method, ICC and RMS-CV. RESULTS: Inter-observer ICCs for the RF-based CCA-IMT measurements were 0.85 (95% CI 0.69, 0.94) for the first round, and 0.77 (95% CI 0.55, 0.91) for the second round. RMS-CVs for the RF-based CCA-IMT measurements varied from 5.6 to 11.7%. The mean intra-observer ICC for the RF-based CCA-IMT measurements was 0.61 (95% CI 0.46, 0.71). In the Bland-Altman analysis for agreement between RF-based and B-mode CCA-IMT measurements, the mean difference varied from -0.6 to -19.7 µm. Inter-method ICCs varied from 0.57 to 0.83 for 11 rheumatologists. Inter-method RMS-CVs varied from 11.3 to 13.7%. CONCLUSIONS: Our results suggest that automated RF-based CCA-IMT measurement performed by rheumatologists can be a reliable method for assessing cardiovascular risk in RA patients.

[Evidence on the role of HLA and MICA antibodies in renal graft loss]. / Evidencia del impacto de los anticuerpos anti-HLA y anti-MICA en la pérdida del injerto renal.

BACKGROUND: HLA and MICA antibodies are increasingly associated with poorer graft survival. The aim of this study is to report the frequency of graft loss 2 years after the detection of HLA abs and MICA abs among a group of kidney transplant recipients. METHODS: We tested 196 patients with a functioning graft. Sera were screened for HLA and MICA IgG abs by Luminex, using the LABScreen Mixed, and LABScreen PRA. The sera were screened for MICA abs by Luminex. RESULTS: Of 196 kidney transplant recipients (mean age 36.7 years, 42% female), one hundred twenty four (63.3%) were negative to all tested abs, and 72 (36.7%) were positive for: HLA abs alone = 34, MICA abs alone = 29, and HLA+MICA abs = 9. At a median followup of 20.5 (1.2-25.2) months, 8 patients lost their grafts due to biopsy-confirmed chronic allograft injury: 2/124 (1.6%) ab-negative, and 6/72 (8.3%) ab-positive, with a significantly lower survival for the Ab-positive group (p = 0.046, log-rank test). CONCLUSIONS: The presence of circulating abs was associated with an increased risk of graft loss, and the coexistence of HLA and MICA abs increases the risk of graft loss.

Power Doppler ultrasonographic monitoring of response to anti-tumor necrosis factor therapy in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the validity, responsiveness, and predictive value of power Doppler ultrasonography (PDUS) monitoring of response to tumor necrosis factor (TNF) blocking agents in rheumatoid arthritis (RA). METHODS: Three hundred sixty-seven RA patients were prospectively recruited at 25 Spanish centers; complete clinical, laboratory, and PDUS data were obtained on 278 patients. The patients underwent clinical, laboratory, and PDUS assessment at baseline and after 1, 3, 6, and 12 months of anti-TNF treatment, and radiographic assessment of the hands and feet at baseline and 12 months. The Disease Activity Score in 28 joints (DAS28) was recorded at each visit. PDUS examination included 86 intraarticular and periarticular sites in 28 joints. US synovial fluid (SF), synovial hypertrophy (SH), and PD signal were scored in all synovial sites. US count and index for SF, SH, and PD signal were obtained. Sensitivity to change of the PDUS variables was assessed by estimating the smallest detectable difference (SDD) from the intraobserver variability. RESULTS: A significant parallel improvement in DAS28 and PDUS parameters was found at followup assessment (P < 0.0005 for within-subject between-visit changes). The SDD for PDUS parameters was lower than the mean changes throughout followup. Time-integrated values of US joint count for PD signal and rheumatoid factor (RF) showed predictive value in relation to progression of radiographic erosion (R = 0.64), and time-integrated values of US joint count for PD signal, RF, and erythrocyte sedimentation rate were predictors of progression of the total radiographic score (R = 0.59). CONCLUSION: These findings indicate that PDUS is a valid method for monitoring response to anti-TNF therapy in RA; results obtained by PDUS are reproducible and sensitive to change. PDUS findings may have predictive value in relation to radiologic outcome.

Evidencia del impacto de los anticuerpos anti-HLA y anti-MICA en la pérdida del injerto renal / Evidence on the role of HLA and MICA antibodies in renal graft loss

Antecedentes: Los anticuerpos anti-HLA y anti-MICA se han asociado cada vez con mayor frecuencia a menor supervivencia del injerto renal. El objetivo de este estudio es comunicar la frecuencia de pérdida del injerto dos años después de la detección de anticuerpos anti-HLA, anti-MICA, o ambos, en un grupo de receptores de trasplante renal (RTR). Métodos: Estudiamos a 196 RTR con injerto funcional. El suero de los pacientes fue analizado para la presencia de anticuerpos IgG anti-HLA clase I y clase II con Luminex utilizando LABScreen®Mixed y LABScreen® PRA. La presencia de anticuerpos anti-MICA en el mismo suero se analizó por Luminex. Resultados: De 196 RTR (edad promedio 36.7 años, 42% sexo femenino), 124 (63.3%) fueron negativos a todos los anticuerpos estudiados y 72 (36.7%) fueron positivos: 34 para anticuerpos anti-HLA solo, 29 para anticuerpos anti-MICA solo y nueve para anticuerpos anti-HLA+anti-MICA. A una mediana de seguimiento de 20.5 meses (1.2-25.2), ocho pacientes perdieron el injerto por daño crónico del mismo, confirmado por biopsia: 2/124 (1.6%) del grupo de anticuerpos negativos y 6/72 (8.3%) del grupo de anticuerpos positivos, con una supervivencia del injerto significativamente inferior para el grupo de anticuerpos positivos (p=0.046, log-rank test). Conclusiones: La presencia de anticuerpos circulantes estuvo asociados con riesgo incrementado para pérdida del injerto; la coexistencia de anticuerpos anti-HLA y anti-MICA produjo el riesgo más alto para pérdida del injerto en la población analizada.

BACKGROUND: HLA and MICA antibodies are increasingly associated with poorer graft survival. The aim of this study is to report the frequency of graft loss 2 years after the detection of HLA abs and MICA abs among a group of kidney transplant recipients. METHODS: We tested 196 patients with a functioning graft. Sera were screened for HLA and MICA IgG abs by Luminex, using the LABScreen Mixed, and LABScreen PRA. The sera were screened for MICA abs by Luminex. RESULTS: Of 196 kidney transplant recipients (mean age 36.7 years, 42% female), one hundred twenty four (63.3%) were negative to all tested abs, and 72 (36.7%) were positive for: HLA abs alone = 34, MICA abs alone = 29, and HLA+MICA abs = 9. At a median followup of 20.5 (1.2-25.2) months, 8 patients lost their grafts due to biopsy-confirmed chronic allograft injury: 2/124 (1.6%) ab-negative, and 6/72 (8.3%) ab-positive, with a significantly lower survival for the Ab-positive group (p = 0.046, log-rank test). CONCLUSIONS: The presence of circulating abs was associated with an increased risk of graft loss, and the coexistence of HLA and MICA abs increases the risk of graft loss.

Cyclophosphamide-intolerant Wegener's granulomatosis successfully treated with mycophenolate mofetil.

Cyclophosphamide (CYC) is a classical drug for the treatment of severe Wegener's granulomatosis (WG). However as it causes substantial toxicity alternative agents should be considered if optimal therapeutic CYC dose is not tolerated by an individual patient. We report the successful use of mycophenolate mofetil (MMF) in a 35-year-old patient with renal biopsy-proven pANCA WG and lung involvement. Despite a good clinical and biological response to the standard induction of remission therapy the patient developed persistent severe CYC-related leucopoenia after two months of treatment. Thus CYC was replaced by MMF; and during the three and a half years of follow-up the patient never required haemodialysis. He has remained in complete clinical remission for the last two years without MMF-related adverse effects.

Pseudoaneurysm of the iliac artery secondary to Aspergillus infection in two recipients of kidney transplants from the same donor.

The authors report 2 cases of patients who underwent cadaveric renal transplantation from the same donor in a multiorgan extraction procedure. Both cases showed, during the first 6 months posttransplantation, a worsening in renal graft function and signs of ischemia in the homolateral lower limb. One of the cases was preceded by pain in the sciatic region. In imaging tests, a pseudoaneurysm was detected in the iliac artery in both patients. Grafts had to be removed, and the iliac arteries were ligated with posterior isolation of Aspergillus spp from the arterial vessels but not from the renal tissue. Besides surgery, medical treatment with liposomal amphotericin B was initiated with a different outcome in each patient: patient A died, whereas patient B recovered. The absence of Aspergillus spp infection in liver and heart recipients ruled out a donor-transmitted infection. The graft placements were carried out in different operating rooms, which rules out contamination during the transplantation process. All of this leads us to conclude that the infection must have occurred during the preservation phase of the kidney.

Evaluation of intestinal iron absorption by indirect methods in patients on hemodialysis receiving oral iron and recombinant human erythropoietin.

Intestinal iron absorption was evaluated in 40 patients on hemodialysis therapy treated over 4 months with 105 mg/d of oral iron and recombinant human erythropoietin (rHuEPO). The effect of iron stores, erythropoietic activity (EA), and route of rHuEPO administration on absorption was evaluated. Iron was administered after basal determinations had been made and was stopped 15 days before obtaining the final determinations. Intestinal iron absorption was calculated by summing the increase in hemoglobin (Hb) iron (iron used for the synthesis of new Hb) and variations in estimated tissue iron reserves (reserves at the end of the study minus basal reserves). Markers of EA included soluble transferrin receptors (sTfRs) and erythron transferrin uptake (ETU). Iron losses caused by dialysis or normal obligatory iron losses were not measured. Hb levels increased from 8.38 +/- 1.4 to 10.75 +/- 1.5 g/dL (P < 0.05). sTfR levels reached their maximum value at 45 days (3.22 +/- 0.84 mg/mL; P < 0.05), and ETU increased from 40 +/- 26 to 61 +/- 39 micromol/L whole blood/d (P = 0.007). Intestinal iron absorption was 238 mg (interquartile range [Q75 to Q25], 255) at 2 months and 348 mg (Q75 to Q25, 475) at 4 months (P =0.02) and correlated positively with hematocrit at the end of the study (r = 0.826; P = 0.0001). No relationship between iron absorption and basal serum ferritin level or EA markers was observed. Intestinal iron absorption was similar regardless of the route of rHuEPO administration. In conclusion, intestinal iron absorption from medicinal iron covers erythropoietic requirements and allows Hb levels to increase significantly. It is proportional to the degree of efficient erythropoiesis reached and independent of tissue iron stores present before treatment, markers of EA, and rHuEPO administration route.