Suchergebnisse

The HAART reduces the risk of HIV‐related renal disease but the incidence of end‐stage renal disease (ESRD). Therefore, efficacy and safety of renal transplantation (Tx) is an important resource in the HIV‐infected population. We reported the results of kidney Tx in HIV+patients from deceased donors from June 2007 to March 2012 at our institution. The patients had to have CD4+T‐cell counts≥200/mm3 and undetectable plasma HIV‐RNA if on HAART. The induction immunosuppressive therapy consisted of metilprednisolone and basilixmab; tacrolimus and/or mycofenolic acid were used for maintenance therapy. The therapeutic drug monitoring (TDM) has been performed for the adjusting of both their doses [1]. A total of 14 patients underwent kidney Tx. They were on dialysis (haemodialysis=13, 92.9%; peritoneal=1, 7.1%) for 5±3.1 years and they were included on the Tx waiting list for 10±8 months. The baseline characteristics are showed in Table 1.







Donor at baseline



Mean age
38±12.5 years


Deceased
14/14 (100%)


High/unclassified infectious risk
9 (64.29%)


Recipients



Mean age
44 years


Patients with previous AIDS‐defining events
3 (21.4%)


Median follow‐up months (IQR range)
42.75 (8.5–55.2)


Patient survival at last follow‐up
14/14 (100%)


Graft survival at last follow‐up
13/14 (92.9%)


Mean time of acute rejection since Tx
28±20 days


Patients not treated with steroid at last follow‐up
6 (43%)


Plasma creatinine at last follow‐up
1.87±1.93 mg/dl


Severe infectious complications (CMV pneumonia, malaria, Kaposi sarcoma)
3 (21.4%)


Diabetes
3 (21.4%)


CMV infection without localization
3 (21.4%)


Bacterial pneumonia
4 (28.6%)


Reactivation of HIV RNA
3 (21.4%)




At the last available point of follow‐up (median=42.8 months, IQR=8.5–55.2), 8 out of the 13 patients (61.6%) without steroid had at least one acute rejection episode, but only 1 patient lost the graft, after 43 months (7.1%) due to chronic rejection associated with infectious and vascular complications. After Tx the median CD4+T‐cell count increased from 382.5 (IQR range=233–415) to 434 (IQR range=282–605) cells/mm3 (p=0.055). In Figure 1 are reported the CD4+trends of 9 patients with a follow‐up of at least 6 months.HIV infection was well controlled, with only 2 (14.3%) cases of virological failure which were promptly resolved after HAART regimen modification. Table 1 shows the observed infectious complications. The skin Kaposi sarcoma has been resolved by switching to immunosuppressive therapy with sirolimus [2]. Kidney Tx appears to be safe in HIV‐positive patients undergoing HAART. The viro‐immunological parameters remained well controlled with no increases in infectious complications or neoplasm and a satisfactory control of HIV infection. However, the high rejection rate is a serious concern and suggests to consider a steroid‐containing immunosuppressive regimen also in these patients.
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BACKGROUND: We aimed to understand the relationship between serum biomarker concentration and lesion type and volume found on computed tomography (CT) following all severities of TBI. METHODS: Concentrations of six serum biomarkers (GFAP, NFL, NSE, S100B, t-tau and UCH-L1) were measured in samples obtained <24 hours post-injury from 2869 patients with all severities of TBI, enrolled in the CENTER-TBI prospective cohort study (NCT02210221). Imaging phenotypes were defined as intraparenchymal haemorrhage (IPH), oedema, subdural haematoma (SDH), extradural haematoma (EDH), traumatic subarachnoid haemorrhage (tSAH), diffuse axonal injury (DAI), and intraventricular haemorrhage (IVH). Multivariable polynomial regression was performed to examine the association between biomarker levels and both distinct lesion types and lesion volumes. Hierarchical clustering was used to explore imaging phenotypes; and principal component analysis and k-means clustering of acute biomarker concentrations to explore patterns of biomarker clustering. FINDINGS: 2869 patient were included, 68% (n=1946) male with a median age of 49 years (range 2-96). All severities of TBI (mild, moderate and severe) were included for analysis with majority (n=1946, 68%) having a mild injury (GCS 13-15). Patients with severe diffuse injury (Marshall III/IV) showed significantly higher levels of all measured biomarkers, with the exception of NFL, than patients with focal mass lesions (Marshall grades V/VI). Patients with either DAI+IVH or SDH+IPH+tSAH, had significantly higher biomarker concentrations than patients with EDH. Higher biomarker concentrations were associated with greater volume of IPH (GFAP, S100B, t-tau;adj r2 range:0·48-0·49; p<0·05), oedema (GFAP, NFL, NSE, t-tau, UCH-L1;adj r2 range:0·44-0·44; p<0·01), IVH (S100B;adj r2 range:0.48-0.49; p<0.05), Unsupervised k-means biomarker clustering revealed two clusters explaining 83·9% of variance, with phenotyping characteristics related to clinical injury severity. INTERPRETATION: Interpretation: Biomarker concentration within 24 hours of TBI is primarily related to severity of injury and intracranial disease burden, rather than pathoanatomical type of injury. FUNDING: CENTER-TBI is funded by the European Union 7th Framework programme (EC grant 602150).