Nabil Dagher - Academia.edu (original) (raw)

Papers by Nabil Dagher

Transplantation, Apr 15, 2012

La Revue de Médecine Interne, 2010

Abstracts / La Revue de médecine interne 31S (2010) S342-S403 S379 (intervalle de confiance à 95 ... more Abstracts / La Revue de médecine interne 31S (2010) S342-S403 S379 (intervalle de confiance à 95 % ; 0,74-0,75) de la population recevait à chaque instant une corticothérapie prolongée. Cette prévalence augmentait régulièrement au cours de la période d'étude et passait de 0,59 % (0,52-0,67) en 1989 à 0,79 % (0,78-0,80) en 2008. Cependant, durant cette période, la prévalence de prescription diminuait significativement dans la population de patients souffrant d'asthme (passant de 2,6 % [2,3-2,9] à 1,2 % [1,1-1,3]), de BPCO (5,5 % [4,3] → 3,6 % [3,4-3,7]) ou de maladie de Crohn (10,1 % [6,7-13,4] → 3,9 % [3,4-4,4]), restait stable chez les patients souffrant de RCH (5,0 % [4,2]] → 3,8 % [3,7-3,9]) et augmentait chez les patients souffrant de PR (10,3 % [8,7-11,9] → 13,6 % [12,9-14,2]) ou de PPR/MDH (57,6 % [53,3-62,0] → 66,5 % [65,2-67,7]), principalement en raison de durées de prescription plus longues. Il faut néanmoins noter qu'en ne prenant en compte que les cas incidents de ces pathologies, la prévalence des prescriptions prolongées de glucocorticoïdes diminuait chez les patients souffrant de PR (OR : 0,97 [0,97] par année calendaire) ou de RCH (OR : 0,94 [0,96]). Conclusion.-Entre 1989 et 2008, la prévalence des prescriptions prolongées de glucocorticoïdes a augmentée de 34 %. Cependant, concernant la PR, la maladie de Crohn et la RCH, les patients les plus récemment diagnostiqués se voyaient moins souvent prescrire une corticothérapie prolongée que les patients ayant une maladie évoluant depuis plusieurs années. Cette constatation peut suggérer des modifications des pratiques des médecins au cours du temps, modifications peut être liées à la disponibilité de nouvelles molécules telles que les biothérapies.

Current Surgical Therapy, 2011

Transplantation, 2014

Live donor kidney transplantation (LDKT) remains underutilized, partly resulting from the challen... more Live donor kidney transplantation (LDKT) remains underutilized, partly resulting from the challenges many patients face in asking someone to donate. Actual and perceived kidney transplantation (KT) knowledge are potentially modifiable factors that may influence this process. Therefore, we sought to explore the relationships between these constructs and the pursuit of LDKT. We conducted a cross-sectional survey of transplant candidates at our center to assess actual KT knowledge (5-point assessment) and perceived KT knowledge (5-point Likert scale, collapsed empirically to 4 points); we also asked candidates if they had previously asked someone to donate. Associations between participant characteristics and having asked someone to donate were quantified using modified Poisson regression. Of 307 participants, 45.4% were female, 56.4% were non-white race, and 44.6% had previously asked someone to donate. In an adjusted model that included both actual and perceived knowledge, each unit increase in perceived knowledge was associated with 1.21-fold (95% CI: 1.03-1.43, P=0.02) higher likelihood of having asked someone to donate, whereas there was no statistically significant association with actual knowledge (RR=1.08 per unit increase, 95% CI: 0.99-1.18, P=0.10). A conditional forest analysis confirmed the importance of perceived but not actual knowledge in predicting the outcome. Our results suggest that perceived KT knowledge is more important to a patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s pursuit of LDKT than actual knowledge. Educational interventions that seek to increase patient KT knowledge should also focus on increasing confidence about this knowledge.

Dialysis & Transplantation, 2000

American Journal of Transplantation, 2010

neys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data ... more neys, yet evidence remains inconclusive. We hypothesized that lack of good survival benefit data has led to wide practice variation. Our goal was to characterize national utilization of HCV(+) kidneys for HCV(+) recipients, and to quantify the risks/benefits of this practice. Of 93,825 deceased donors between 1995 and 2009, HCV(+) kidneys were 2.60-times more likely to be discarded (p < 0.001). However, of 6830 HCV(+) recipients, only 29% received HCV(+) kidneys. Patients over 60 relative rate (RR 0.86), women (RR 0.73) and highly sensitized patients (RR 0.42) were less likely to receive HCV(+) kidneys, while African Americans (RR 1.56), diabetics (RR 1.29) and those at centers with long waiting times (RR 1.19) were more likely to receive them. HCV(+) recipients of HCV(+) kidneys waited 310 days less than the average waiting time at their center, and 395 days less than their counterparts at the same center who waited for HCV(−) kidneys, likely offsetting the slightly higher patient (HR 1.29) and graft loss (HR 1.18) associated with HCV(+) kidneys. A better understanding of the risks and benefits of transplanting HCV(+) recipients with HCV(+) kidneys will hopefully improve utilization of these kidneys in an evidence-based manner.

Biochem Biophys Res Commun, 2004

Mutations in presenilin-1 and 2 (PS) lead to increased intracellular calcium stores and an attenu... more Mutations in presenilin-1 and 2 (PS) lead to increased intracellular calcium stores and an attenuation in the refilling mechanism known as capacitative calcium entry (CCE). Previous studies have shown that the mechanism by which PS modulates intracellular calcium signaling is dependent on c-secretase activity. Although the modulation of intracellular calcium signaling can lead to alterations in CCE, it is plausible that PS can also directly affect CCE independent of the effect it exerts on intracellular stores. To investigate this possibility, we studied the effects of the dominant negative variant of PS1 known as DTM1-2, which lacks the first two transmembrane domains of PS1 and in which c-secretase activity is abrogated. We demonstrate that, like other dominant negative isoforms of PS1, DTM1-2 expression leads to reduced intracellular calcium. However, unlike other dominant negative isoforms, DTM1-2 leads to a deficit rather than a potentiation of CCE. These data suggest that changes in the structural components of presenilin can modulate CCE independent of its function in c-secretase activity and intracellular calcium stores.

Annals of surgery, Jan 8, 2016

To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in... more To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for ...

Transplantation, 2016

Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal di... more Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnorma...

Annals of transplantation, 2016

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. One of the most important... more Hepatocellular carcinoma (HCC) is the most common primary liver cancer. One of the most important risk factors of HCC is cirrhosis. The optimal treatment of HCC is liver transplantation, since it treats both the underlying cirrhosis and the cancer. Patients that have risk factors should be included in surveillance programs since HCC can be cured only during the early stages. Surveillance can be performed by ultrasonography (US), which is an inexpensive, non-invasive, and widely available technique, but it is considered to have a low sensitivity. If a suspicious lesion is detected on US exam, computerized tomography (CT) or magnetic resonance imaging (MRI) can be used to further evaluate this lesion. MRI is considered to be superior to CT because it has greater contrast resolution and tissue characterization. In this article, we present a review of MRI for HCC in liver transplantation (LT) with a focus on characteristic MR features of this tumor and current guidelines.

Journal of Clinical and Translational Hepatology, 2016

A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome ... more A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal hypertension, intrapulmonary vascular dilatations, and increased alveolar-arterial oxygen gradient. Prevalence varies according to various study groups from 4%-47%. While the most common presenting symptom of HPS is dyspnea, it is usually asymptomatic, and thus all liver transplant candidates should be screened for its presence. Pulse oximetry is a useful screening method, but arterial blood gas examination is the gold standard. If there is an abnormal P (A-a)O2 gradient, microbubble transthoracic echocardiography should be done for diagnosis. Outcome is unpredictable, and there is currently no effective medical therapy. The only effective therapy is considered to be liver transplantation. Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.

Clinical Transplants, 2009

We present four cases of renal transplant recipients who were treated with bortezomib for four di... more We present four cases of renal transplant recipients who were treated with bortezomib for four different indications, each of whom had circulating anti-HLA antibodies that were followed serially throughout their courses of bortezomib therapy. It is important to note that each patient was administered bortezomib in conjunction with other agents and therapies traditionally used for desensitization or the treatment of AMR. The results have been mixed. In some cases substantial decreases in HLA-antibody were temporally related to bortezomib therapy. In the one case of recalcitrant AMR there has been no reduction in DSA after 2 cycles of the drug. Bortezomib has been well tolerated. One patient developed reversible peripheral neuropathic pain while another experienced line sepsis, a urinary tract infection, and an invasive fungal skin infection. Again, this patient had also received protracted courses of plasmapheresis combined with T-cell and B-cell depleting agents. The use of these other drugs precludes the ability to rigorously evaluate the efficacy of bortezomib in isolation and points towards a need for large-scale, controlled trials to determine whether the drug's promising mechanism of action is applicable in the setting of solid organ transplantation.

American Journal of Transplantation

Journal of neuroinflammation, 2015

Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their sur... more Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-complete elimination of all microglia brainwide. Here, we determined the dose-dependent effects of a specific CSF1R inhibitor (PLX5622) on microglia in both wild-type and the 3xTg-AD mouse model of Alzheimer's disease. Wild-type mice were treated with PLX5622 for up to 21 days, and the effects on microglial numbers were assessed. 3xTg-AD mice were treated with PLX5622 for 6 or 12 weeks and effects on microglial numbers and pathology subsequently assessed. High doses of CSF1R inhibitor eliminate most microglia from the brain, but a 75% lower-dose results in sustained elimination of ~30 of microglia in both wild-type and 3xTg-AD mice. No behavioral or cognitive deficits were found in mice either depleted of microglia or treated with lower CSF1R inhibitor concentrations. Aged 3xTg...

Clinical transplants, 2009

Journal of Gastrointestinal Surgery, 2014

Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an ... more Sarcopenia is a surrogate marker of patient frailty that estimates the physiologic reserve of an individual patient. We sought to investigate the impact of sarcopenia on short- and long-term outcomes in patients having undergone surgical intervention for primary hepatic malignancies. Ninety-six patients who underwent hepatic resection or liver transplantation for HCC or ICC at the John Hopkins Hospital between 2000 and 2013 met inclusion criteria. Sarcopenia was assessed by the measurement of total psoas major volume (TPV) and total psoas area (TPA). The impact of sarcopenia on perioperative complications and survival was assessed. Mean age was 61.9 years and most patients were men (61.4 %). Mean adjusted TPV was lower in women (23.3 cm(3)/m) versus men (34.9 cm(3)/m) (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01); 47 patients (48.9 %) had sarcopenia. The incidence of a postoperative complication was 40.4 % among patients with sarcopenia versus 18.4 % among patients who did not have sarcopenia (P = 0.01). Of note, all Clavien grade ≥3 complications (n = 11, 23.4 %) occurred in the sarcopenic group. On multivariable analysis, the presence of sarcopenia was an independent predictive factor of postoperative complications (OR = 3.06). Sarcopenia was not associated with long-term survival (HR = 1.23; P = 0.51). Sarcopenia, as assessed by TPV, was an independent factor predictive of postoperative complications following surgical intervention for primary hepatic malignancies.

Experimental and Clinical Transplantation, 2014

There has been a large gap between the number of patients awaiting liver transplants and those re... more There has been a large gap between the number of patients awaiting liver transplants and those receiving them. In the East, living-donor liver transplant has become the major source of grafts, whereas in the West, deceased-donor grafts have been the major source for liver transplants. Some newly developed or developing donor types are discussed.

Transplantation Journal, 2012

Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal... more Human leukocyte antigen (HLA) sensitization presents a major obstacle for patients awaiting renal transplantation. HLA antibody reduction and favorable transplantation rates have been reported after treatment with high-dose intravenous immunoglobulin (IVIg). We enrolled 27 patients whose median flow cytometric calculated panel reactive antibody (CPRA) was 100% and mean wait-list time exceeded 4 years in a protocol whereby high-dose IVIg was administered, HLA antibody profiles of sera obtained before and after treatment were characterized, and cross-match tests were performed with all blood group identical kidney offers. Whereas 12.8% of a similarly sensitized historic control cohort underwent transplantation in the course of a year, 41% of the IVIg-treated group underwent transplantation during the study period. Surprisingly, HLA antibody profiles, measured by CPRA, showed no significant change in response to IVIg treatment. In fact, retrospective cross-match testing using pretreatment sera of those receiving deceased-donor allografts showed that all patients would have been eligible for transplantation with their respective donors before IVIg infusions. This study does not corroborate previous reports of CPRA reduction leading to increased deceased-donor transplantation rates in broadly sensitized patients undergoing desensitization with high-dose IVIg. The increased rate of transplantation relative to historic controls is not related to improved cross-match eligibility and likely resulted from frequent crossmatching using a cytotoxic strength threshold, improved medical readiness for transplantation, and newly recognized options for live-donor transplantation, all of which could have been achieved without IVIg treatment.