BACKGROUND: Damage to the endothelium has been established as a key pathological process in lung transplantation and ex vivo lung perfusion (EVLP), a new technology that provides a platform for the assessment of injured...BACKGROUND: Damage to the endothelium has been established as a key pathological process in lung transplantation and ex vivo lung perfusion (EVLP), a new technology that provides a platform for the assessment of injured donor lungs. Damage to the lung endothelial glycocalyx, a structure that lines the endothelium and is integral to vascular barrier function, has been associated with lung dysfunction. We hypothesised that endothelial glycocalyx shedding occurs during EVLP and aimed to establish a porcine model to investigate the mechanism underlying glycocalyx breakdown during EVLP. METHODS: Concentrations of endothelial glycocalyx breakdown products, syndecan-1, hyaluronan, heparan sulphate, and CD44, were measured using the ELISA and matrix metalloproteinase (MMP) activity by zymography in the perfusate of both human ( = 9) and porcine ( = 4) lungs undergoing EVLP. Porcine lungs underwent prolonged EVLP (up to 12 hours) with perfusion and ventilation parameters recorded hourly. RESULTS: During human EVLP, endothelial glycocalyx breakdown products in the perfusate increased over time. Increasing MMP-2 activity over time was positively correlated with levels of syndecan-1 ( = 0.886; =0.03) and hyaluronan ( = 0.943; =0.02). In the porcine EVLP model, hyaluronan was the only glycocalyx product detectable during EVLP (1 hr: 19 (13-84) vs 12 hr: 143 (109-264) ng/ml; =0.13). Porcine hyaluronan was associated with MMP-9 activity ( = 0.83; =0.02) and also with dynamic compliance ( = 0.57; =0.03). CONCLUSION: Endothelial glycocalyx products accumulate during both porcine and human EVLP, and this accumulation parallels an accumulation of matrix-degrading enzyme activity. Preliminary evidence in our porcine EVLP model suggests that shedding may be related to organ function, thus warranting additional study.
BACKGROUND: The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests...BACKGROUND: The role of protocol renal allograft biopsy in kidney transplantation is controversial due to the concern with procedural-related complications; however, its role is slowly evolving. Recent evidence suggests that protocol biopsy is useful in detecting subclinical renal pathology. Early recognition and treatment of renal pathologies can improve long-term outcomes of renal allografts. METHODOLOGY: A total of 362 renal allograft protocol biopsies were performed in adult recipients of kidney transplantation between 2012 and 2017. After excluding those with poor quality or those performed with a baseline serum creatinine level >200 umol/L, we analyzed 334 (92.3%) biopsies. Histology reports were reviewed and categorized into histoimmunological and nonimmunological changes. The immunological changes were subcategorized into the following: (1) no acute rejection (NR), (2) borderline changes (BC), and (3) subclinical rejection (SCR). Nonimmunological changes were subcategorized into the following: (1) chronicity including interstitial fibrosis/tubular atrophy (IFTA), chronic T-cell-mediated rejection (TCMR), unspecified chronic lesions, and arterionephrosclerosis, (2) de novo glomerulopathy/recurrence of primary disease (RP), and (3) other clinically unsuspected lesions (acute pyelonephritis, calcineurin inhibitors toxicity, postinfective glomerulonephritis, and BK virus nephropathy). Risk factors associated with SCR were assessed. RESULTS: For the histoimmunological changes, 161 (48.2%) showed NR, 145 (43.4%) were BC, and 28 (8.4%) were SCR. These clinical events were more pronounced for the first 5 years; our data showed BC accounted for 59 (36.4%), 64 (54.2%), and 22 (40.7%) biopsies within <1 year, 1-5 years, and > 5 years, respectively (p = 0.011). Meanwhile, the incidence for SCR was 6 (3.7%) biopsies in <1 year, 18 (15.3%) in 1-5 years, and 4 (7.4%) in >5 years after transplantation (p=0.003). For the nonimmunological changes, chronicity, de novo glomerulopathy/RP, and other clinically unsuspected lesions were seen in 40 (12%), 10 (3%), and 12 (3.6%) biopsies, respectively. Living-related donor recipients were associated with decreased SCR (p=0.007). CONCLUSIONS: Despite having a stable renal function, our transplant recipients had a significant number of subclinical rejection on renal allograft biopsies.
Identification of patients at risk of kidney graft loss relies on early individual prediction of graft failure. Data from 616 kidney transplant recipients with a follow-up of at least one year were retrospectively studie...Identification of patients at risk of kidney graft loss relies on early individual prediction of graft failure. Data from 616 kidney transplant recipients with a follow-up of at least one year were retrospectively studied. A joint latent class model investigating the impact of serum creatinine (Scr) time-trajectories and onset of donor-specific anti-HLA antibody (DSA) on graft survival was developed. The capacity of the model to calculate individual predicted probabilities of graft failure over time was evaluated in 80 independent patients. The model classified the patients in three latent classes with significantly different Scr time profiles and different graft survivals. Donor age contributed to explaining latent class membership. In addition to the SCr classes, the other variables retained in the survival model were proteinuria measured one-year after transplantation (HR=2.4, p=0.01), pretransplant non-donor-specific antibodies (HR=3.3, p<0.001), and DSA in patient who experienced acute rejection (HR=15.9, p=0.02). In the validation dataset, individual predictions of graft failure risk provided good predictive performances (sensitivity, specificity, and overall accuracy of graft failure prediction at ten years were 77.7%, 95.8%, and 85%, resp.) for the 60 patients who had not developed DSA. For patients with DSA individual risk of graft failure was not predicted with a so good performance.
The possible risk factors for chronic kidney disease in transplant recipients have not been thoroughly investigated after living-donor liver transplantation. A retrospective cohort study of consecutive adults who underw...The possible risk factors for chronic kidney disease in transplant recipients have not been thoroughly investigated after living-donor liver transplantation. A retrospective cohort study of consecutive adults who underwent living-donor liver transplantation between May 2004 and October 2016, in a single center, was conducted. Kidney function was investigated successively for all the patients throughout the study period, with 12 months being the shortest follow-up. Postoperative renal dysfunction was defined in accordance with the Chronic Kidney Disease Epidemiology Collaboration criteria. The patients' demographic data, preoperative and intraoperative parameters, and outcomes were recorded. A calcineurin inhibitor-based immunosuppressive regimen, either tacrolimus or cyclosporine, was used in all the patients. Of the 413 patients included in the study, 33 (8%) who survived for ≥1 year experienced chronic kidney disease 1 year after living-donor liver transplantation. Twenty-seven variables were studied to compare between the patients with normal kidney functions and those who developed chronic kidney disease 1 year after living-donor liver transplantation. Univariate regression analysis for predicting the likelihood of chronic kidney disease at 1 year revealed that the following 4 variables were significant: operative time, < 0.0005; intraoperative blood loss, < 0.0005; preoperative renal impairment, = 0.001; and graft-to-recipient weight ratio (as a negative predictor), < 0.0005. In the multivariate regression analysis, only 2 variables remained as independent predictors of chronic kidney disease at 1 year, namely, operative time with a cutoff value of ≥714 minutes and graft-to-recipient weight ratio as a negative predictor with a cutoff value of <0.91. In this study, prolonged operative time and small graft-to-recipient weight ratio were independent predictors of chronic kidney disease at 1 year after living-donor liver transplantation.
BACKGROUND: Recent changes in the demographic of cardiac donors and recipients have modulated the rate and risk, associated with posttransplant diabetes mellitus (PTDM). We investigated the secular trends of the risk of...BACKGROUND: Recent changes in the demographic of cardiac donors and recipients have modulated the rate and risk, associated with posttransplant diabetes mellitus (PTDM). We investigated the secular trends of the risk of PTDM at 1 year and 3 years after transplantation over 30 years and explored its effect on major outcomes. METHODS: Three hundred and three nondiabetic patients were followed for a minimum of 36 months, after a first cardiac transplantation performed between 1983 and 2011. Based on the year of their transplantation, the patients were divided into 3 eras: (1983-1992 [era 1], 1993-2002 [era 2], and 2003-2011 [era 3]). RESULTS: In eras 1, 2, and 3, the proportions of patients with PTDM at 1 versus 3 years were 23% versus 39%, 21% versus 26%, and 33% versus 38%, respectively. Independent risk factors predicting PTDM at one year were recipient's age, duration of cold ischemic time, treatment with furosemide, and tacrolimus. There was a trend for overall survival being worse for patients with PTDM in comparison to patients without PTDM ( = 0.08). Patients with PTDM exhibited a significantly higher rate of renal failure over a median follow-up of 10 years ( = 0.03). CONCLUSION: The development of PTDM following cardiac transplantation approaches 40% at 3 years and has not significantly changed over thirty years. The presence of PTDM is weakly associated with an increased mortality and is significantly associated with a worsening in renal function long-term following cardiac transplantation.
Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in on...Survivin, an antiapoptotic molecule from inhibitor of apoptosis protein (IAP) family, is most known for its implication in cancer as there are some efforts to apply it for diagnostic as well as therapeutic purposes in oncology. On the other hand, it could be a useful molecule to be positively targeted when trying to save tissue and promote cells viability. Since protecting the allograft from ischemia reperfusion injury and inflammation-induced damage is a considerable objective in transplantation, it is reasonable to take advantage from antiapoptotic agents like survivin in order to achieve this goal. However, survivin's potential ability to induce malignancies makes some concerns about its use in clinic. The other barrier is this molecule's involvement in lymphocytes development and proliferation which might increase the risk of graft rejection due to adaptive immune system overactivation. In this review we summarize the few studies carried out about survivin's effect on graft survival and probable advantages and disadvantages of its overexpression in transplantation.
OBJECTIVE: Organ transplant recipients receive immunosuppressive regimens to prevent transplant rejection, which put them at increased risk for opportunistic infections like cytomegalovirus (CMV). Ganciclovir and Valganc...OBJECTIVE: Organ transplant recipients receive immunosuppressive regimens to prevent transplant rejection, which put them at increased risk for opportunistic infections like cytomegalovirus (CMV). Ganciclovir and Valganciclovir are mostly used to prevent or treat CMV. Any incorrect use of the drug may have serious consequences for patients. In this study, the outcome of transplant recipients was assessed in relation to the optimal or suboptimal use of Ganciclovir or Valganciclovir. METHODS: This study was performed on 148 hospitalized patients who received Ganciclovir or Valganciclovir in the nephrology and kidney transplantation departments of our university hospitals, from March 2012 to December 2016. Patients' demographic and clinical data including dose and duration of treatment were collected and then analyzed in comparison with the standard CMV treatment protocols. FINDINGS: About 94.6% of patients received Ganciclovir or Valganciclovir therapy consistent with the standard defined indications. The mean ratio of prescribed daily dose to the optimal dose was 2.9 in the first dose, 2.0 in the second dose, 1.3 in the third dose, and 1.5 in the fourth dose. From 148 included patients, 26.5% experienced CMV infection once, 7.2% experienced CMV infection twice, and 1.2% had CMV infection for 3 times, within six-month follow-up after first episode of antiviral therapy during hospitalization. CONCLUSION: In this study, empiric anti-CMV therapy was initially given. The doses used were generally higher than recommended but we could not find more adverse events in the patients receiving high initial doses. In any case, it seems necessary to advocate use of standard treatment guidelines to avoid adverse outcomes.
BACKGROUND: Near infrared light (NIR) fluorescence imaging with indocyanine green (ICG) has been used in various aspects of surgery, such as in the assessment of vascular anastomosis, tissue perfusion, and the identifica...BACKGROUND: Near infrared light (NIR) fluorescence imaging with indocyanine green (ICG) has been used in various aspects of surgery, such as in the assessment of vascular anastomosis, tissue perfusion, and the identification of lymph nodes. In this study we evaluated the utility of NIR/ICG fluorescence imaging in kidney transplantation. MATERIALS AND METHODS: NIR/ICG imaging was used to assess allograft perfusion in n=1 living donor (LDRT) and n=2 deceased donor (DDRT) renal transplantations, performed in February 2017. The allograft arterial and venous anastomoses were done end-to-side to the corresponding recipient external iliacs, and ureteroneocystostomies were performed for urinary reconstructions. After completion of vascular anastomosis, ICG was given as intravenous bolus at 0.3mg/kg, followed by visual assessment of tissue perfusion and vascular anastomoses at 1-minute interval using fluorescence imaging (KARL STORZ NIR/ICG System). RESULTS: Homogenous global fluorescence of the allograft and vascular anastomosis was observed in all 3 cases. Immediate postoperative perfusion studies showed patent inflow and outflow vessels and well perfused transplanted kidneys. Immediate graft function was observed in 2 recipients (1 LDRT and 1 DDRT). One session of haemodialysis was performed in 1 DDRT recipient, for high serum potassium in the immediate postoperative setting, who otherwise had good urine output and serially declining serum creatinine. CONCLUSIONS: NIR/ICG fluorescence imaging can be useful in renal transplantation for the intraoperative assessment of allograft perfusion, especially in complex cases with multiple renal arteries and vascular reconstructions.
The scope and application of hematopoietic stem cell transplantation are increasing. With advancement in science and close cooperation of health centers, HSCT units are coming up in new developing and underdeveloped coun...The scope and application of hematopoietic stem cell transplantation are increasing. With advancement in science and close cooperation of health centers, HSCT units are coming up in new developing and underdeveloped countries. India hosts many HSCT units and often provides financially viable option for HSCT to foreign patients as well. Recently Indian Council of Medical Research (ICMR) issued a guideline about HSCT unit in India. This review article discusses establishment of new HSCT unit in resource limited setting. Subsequent implication of ICMR guideline has been done.
Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe le...Drug-induced hematological cytopenia is common in kidney transplantation. Various cytopenia including leucopenia (neutropenia), thrombocytopenia, and anemia can occur in kidney transplant recipients. Persistent severe leucopenia or neutropenia can lead to opportunistic infections of various etiologies. On the contrary, reducing or stopping immunosuppressive medications in these events can provoke a rejection. Transplant clinicians are often faced with the delicate dilemma of balancing cytopenia and rejection from adjustments of immunosuppressive regimen. Differentials of drug-induced cytopenia are wide. Identification of culprit medication and subsequent modification is also challenging. In this review, we will discuss individual drug implicated in causing cytopenia and correlate it with corresponding literature evidence.
Delayed graft function (DGF) increases the risk of graft loss by up to 40%, and recent developments in kidney donation have increased the risk of its occurrence. Lowering the risk of DGF, however, is challenging due to a...Delayed graft function (DGF) increases the risk of graft loss by up to 40%, and recent developments in kidney donation have increased the risk of its occurrence. Lowering the risk of DGF, however, is challenging due to a complicated etiology in which ischemia-reperfusion injury (IRI) leads to acute tubular necrosis. Among various strategies explored, the choice of induction therapy is one consideration. Rabbit antithymocyte globulin (rATG [Thymoglobuline]) has complex immunomodulatory effects that are relevant to DGF. In addition to a rapid and profound T-cell depletion, rATG inhibits leukocyte migration and adhesion. Experimental studies of rATG have demonstrated attenuated IRI-related tissue damage in reperfused tissues, consistent with histological evidence from transplant recipients. Starting rATG intraoperatively instead of postoperatively can improve kidney graft function and reduce the incidence of DGF. rATG is effective in preventing acute rejection in kidney transplant recipients at high immunological risk, supporting delayed calcineurin inhibitor (CNI) introduction which protects the graft from early insults. A reduced rate of DGF has been reported with rATG (started intraoperatively) and delayed CNI therapy compared to IL-2RA induction with immediate CNI in patients at high immunological risk, but not in lower-risk patients. Overall, induction with rATG induction is the preferred choice for supporting delayed introduction of CNI therapy to avoid DGF in high-risk patients but shows no benefit versus IL-2RA in lower-risk individuals. Evidence is growing that intraoperative rATG ameliorates IRI, and it seems reasonable to routinely start rATG before reperfusion.
Ibrahim IA, Hassan EA, Alkhan AM
… +10 more, Hussein MA, Alhabashi AF, Ali TZ, Shah YZ, Alahmadi IS, Abdelsalam MS, Rashwan ME, Abdulbaki A, Broering DC, Aleid HA
BACKGROUND: Fasting during the lunar month of Ramadan is mandatory to all healthy adult Muslims. Renal transplant recipients are often worried about the impact of fluid and electrolyte deprivation during fasting on the f...BACKGROUND: Fasting during the lunar month of Ramadan is mandatory to all healthy adult Muslims. Renal transplant recipients are often worried about the impact of fluid and electrolyte deprivation during fasting on the function of their allograft. We aimed to examine the effect of fasting Ramadan on the graft function in renal transplant recipients. METHODS: This retrospective cohort study included patients who underwent kidney transplantation in our tertiary referral center. Baseline pre-Ramadan estimated glomerular filtration rate (eGFR), mean arterial pressure (MAP), and urinary protein excretion were compared to those during and after Ramadan within and between the fasting and non-fasting groups. RESULTS: The study population included 280 kidney transplant recipients who chose to fast during the Ramadan month (June-July 2014) and 285 recipients who did not fast. In the fasting group, baseline eGFR did not change from that during or post-Ramadan (72.6 ± 23.7 versus 72.3 ± 24.5 mL/min/1.73 m2, = 0.53; and 72.6 ± 23.7 versus 72 ± 23.2 mL/min/1.73 m2, = 0.14, respectively). Compared to baseline, there were no significant differences between the fasting and the non-fasting groups in terms of mean percent changes in eGFR, MAP, and urinary protein excretion. CONCLUSION: Fasting during the month of Ramadan did not have significant adverse effects on renal allograft function.
BACKGROUND: Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreemen...BACKGROUND: Grafts from elderly donors (ECD) are increasingly allocated to single (SKT) or dual (DKT) kidney transplantation according to biopsy score. Indications and benefits of either procedure lack universal agreement. METHODS: A total of 302 ECD-transplants in period from Jan 1, 2000, to Dec 31, 2015, were allocated to SKT (SKT) on clinical grounds alone (before Dec 2010, pre-DKT era, = 170) or according to a clinical-histological protocol (after Dec 2010, DKT era, = 132) to DKT ( = 48), SKT biopsy-based protocol ("high-risk", SKT, = 51), or SKT clinically based protocol ("low-risk", SKT, = 33). Graft and patient survival were compared between the two periods and between different transplant categories. RESULTS: Graft and overall survival in recipients from ECD in pre-DKT and DKT era did not differ (5-year graft survival 87.7% and 84.2%, resp.); equal survival in the 2 ECD periods was shown in both donor age ranges of 60-69 and >70-years, and in low-risk or high-risk ECD categories. Within the DKT protocol SKT showed worst graft and overall survival in the 60-69 donor age range; DKT did not result in significantly better outcome than SKT from ECD in either era. One-year posttransplant creatinine clearance in recipients did not differ between any ECD transplant category. At 3 and 5 years after transplantation there were significantly higher total dialysis-free recipient life years from an equal donor number in the pre-DKT era than in the DKT protocol. CONCLUSIONS: Use of a biopsy-based protocol to allocate grafts from aged donors to SKT or DKT did not result in better short term graft survival than a clinically based protocol with allocation only to SKT and reduced overall recipient dialysis-free life years in time.
BACKGROUND: Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one s...BACKGROUND: Calcineurin inhibitors are associated with chronic nephrotoxicity, manifesting as interstitial fibrosis/tubular atrophy (IF/TA) and arteriolar hyalinosis. Conversion from tacrolimus to belatacept may be one strategy to preserve renal function. METHODS: We conducted a retrospective review of renal transplant patients followed at our institution who were converted to belatacept and found to have chronic tacrolimus toxicity on biopsy. The primary outcome was eGFR at conversion as compared to eGFR at 3, 6, 12, and 24 months after conversion. We also assessed incidence of infection and rates of allograft survival at 1 year. RESULTS: The average time between transplant and conversion was 11.9 years. There was no decrease in eGFR at any postconversion time point as compared with preconversion. The mean eGFR at time of preconversion was 32.9 mL/min, as compared with 35.6 mL/min at 3 months ( = 0.09), 34.1 mL/min at 6 months ( = 0.63), 34.9 mL/min at 12 months ( = 0.57), and 39.6 mL/min at 24 months after conversion ( = 0.92). Four of 7 patients had increases in their eGFR after conversion. All grafts were functioning at 1 year after conversion. CONCLUSION: While this study was limited by a small number of patients, belatacept conversion stabilized eGFR at all time points in patients with late allograft function due to chronic tacrolimus toxicity, with a trend towards increased eGFR at 3 months.
The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospect...The impact of the kinetics of the anti-HLA antibodies after KTx on the occurrence of acute rejection as well as the better time-point to monitor anti-HLA Abs after transplantation is not completely defined. This prospective study followed 150 patients over 12 months after transplantation. Serum IgG anti-HLA Abs were detected by single antigen beads after typing donors and recipients for loci A, B, C, DR, and DQ. Before KTx, 89 patients did not present anti-HLA Abs and 2% developed "de novo" Abs during the 1st year, 39 patients were sensitized without DSAs, and 13% developed DSA after surgery; all of them presented ABMR. Sensitized patients presented higher acute rejection rates (36.4% versus 13.5%, < 0.001), although 60% of the patients did not present ABMR. Patients, in whom DSA-MFI decreased during the first two weeks after surgery, did not develop ABMR. Those who sustained their levels presented a rate of 22% of ABMR. 85% of patients developed ABMR when MFIs increased early after transplantation (which occurred in 30% of the DSA positive patients). In the ABMR group, we observed an iDSA-MFI sharp drop on the fourth day and then an increase between the 7th and 14th POD, which suggests DSA should be monitored at this moment in sensitized patients for better ABMR prediction.
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20-50%. We performed low-density lipoprot...BACKGROUND: Focal segmental glomerulosclerosis (FSGS) often develops rapidly and frequently progresses to renal failure, while the recurrence rate after kidney transplantation is 20-50%. We performed low-density lipoprotein (LDL) apheresis before kidney transplantation in FSGS patients to prevent recurrence. METHODS: Five adult patients with chronic renal failure due to FSGS undergoing living related donor kidney transplantation were investigated retrospectively. LDL apheresis was done 1-2 times before transplantation. Postoperative renal function and recurrence of FSGS were assessed. RESULTS: The patients were two men and three women aged 24 to 41 years. The observation period ranged from 60 days to 22 months. Preoperative LDL apheresis was performed once in one patient and twice in four patients. Blood LDL cholesterol levels were normal before LDL apheresis and remained normal both after LDL apheresis and after kidney transplantation. Additional LDL apheresis was performed once in one patient with mild proteinuria after transplantation. The renal graft survived in all patients and there was no evidence of recurrent FSGS. CONCLUSIONS: Although the observation period was short, FSGS did not recur in all 5 patients receiving preoperative LDL apheresis. These results suggest that LDL apheresis can be effective in preventing recurrence of FSGS after kidney transplantation.
BACKGROUND: Since the introduction of direct antiviral agents (DAAs), morbidity of HCV has considerably decreased but still no guidelines have been formulated in renal transplant recipients (RTRs). We studied efficacy an...BACKGROUND: Since the introduction of direct antiviral agents (DAAs), morbidity of HCV has considerably decreased but still no guidelines have been formulated in renal transplant recipients (RTRs). We studied efficacy and tolerability of direct antiviral agents in RTRs. METHODS: This prospective observational study was conducted at Army Hospital Research & Referral, Delhi, from June 2016 to May 2017. Forty-five HCV infected RTRs with stable graft function were included. RESULTS: Median time between renal transplantation and the start of anti-HCV therapy was 36 months (1-120 months). The majority (66.7%) were infected with genotype 3. Baseline median HCV RNA level was 542648 IU/ml (1189-55028534 IU/ml). Sofosbuvir-Ribavirin combination (24 weeks) was given to 30 patients including 3 cirrhotics, Ledipasvir-Sofosbuvir combination to 8 patients, and Daclatasvir-Sofosbuvir combination to 7 patients, including 2 cirrhotics. Rapid virological response was observed in 29 patients treated with Sofosbuvir/Ribavirin, all 8 patients on Sofosbuvir/Ledipasvir, and all 7 patients on Sofosbuvir/Daclatasvir. End treatment response and sustained virological response (12 weeks) were achieved in all patients irrespective of genotype or treatment regimen. Decrease in mean HCV RNA level and transaminase level was statistically significant ( < 0.01). Ribavirin was significantly associated with anaemia ( = 0.032). CONCLUSIONS: DAA regimens are well tolerated and highly efficacious. Response to DAA is good irrespective of genotype, drug combination, initial HCV RNA level, age or sex of patient, or graft age. However, Sofosbuvir/Ledipasvir and Sofosbuvir/Daclatasvir combination is preferable.
Stress-induced heart failure, also known as Broken Heart Syndrome or Takotsubo Syndrome, is a phenomenon characterized as rare but well described in the literature, with increasing incidence. While more commonly associat...Stress-induced heart failure, also known as Broken Heart Syndrome or Takotsubo Syndrome, is a phenomenon characterized as rare but well described in the literature, with increasing incidence. While more commonly associated with postmenopausal women with psychiatric disorders, this entity is found in the postoperative patient. The nonischemic cardiogenic shock manifests as biventricular failure with significant decreases in ejection fraction and cardiac function. In a review of over 3000 kidney and liver transplantations over the course of 17 years within two transplant centers, we describe a series of 7 patients with Takotsubo Syndrome after solid organ transplantation. Furthermore, we describe a novel approach of successfully treating the transient, though potentially fatal, cardiogenic shock with a percutaneous ventricular assistance device in two liver transplant patients, while treating one kidney transplant patient medically and the remaining four liver transplant patients with an intra-aortic balloon pump. We describe our experience with Takotsubo's Syndrome and compare the three modalities of treatment and cardiac augmentation. Our series is novel in introducing the percutaneous ventricular assist device as a more minimally invasive intervention in treating nonischemic heart failure in the solid organ transplant patient, while serving as a comprehensive overview of treatment modalities for stress-induced heart failure.
BACKGROUND: Despite earlier studies describing the feasibility of steroid weaning in heart transplant patients, the majority of patients are maintained on steroid therapy for life. We examined a strategy based on a singl...BACKGROUND: Despite earlier studies describing the feasibility of steroid weaning in heart transplant patients, the majority of patients are maintained on steroid therapy for life. We examined a strategy based on a single morning serum cortisol measurement. METHODS: We assigned stable posttransplant patients, who were maintained on tacrolimus, mycophenolate mofetil, and corticosteroids, into one of two groups based on a screening morning cortisol level. Patients with a cortisol < 8 micrograms/deciliter were assigned to a "maintenance" group and the others were assigned to the weaning group and steroids were tapered off over 4-6 weeks. Patients were monitored on subsequent office visits for adrenal insufficiency and allograft rejection. RESULTS: Thirty-one patients were enrolled (6 patients in the maintenance group and 25 in the steroid-weaning group). Mean follow-up was 10.2 ± 4 years for the weaning group and 9.0 ± 4.9 years in the maintenance group ( = 0.6). No cases of rejection were noted, nor did any patient resume steroid treatment following discontinuation. CONCLUSION: Steroids can be safely discontinued in stable heart transplant patients with an AM serum cortisol ≥ 8 micrograms/deciliter with appropriate outpatient follow-up. In this study, no patient suffered late rejection or clinically noted adrenal insufficiency.