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Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis.

Thu, 08/10/2017 - 12:45
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Combination of sofosbuvir and daclatasvir in the treatment of genotype 3 chronic hepatitis C virus infection in patients on maintenance hemodialysis.

Ther Clin Risk Manag. 2017;13:733-738

Authors: Sperl J, Frankova S, Kreidlova M, Merta D, Tothova M, Spicak J

Abstract
Chronic hepatitis C virus infection (HCV) has a negative impact on the long-term survival of recipients of kidney transplants. HCV should be treated in hemodialyzed patients before their enlistment for kidney transplantation in order to avoid the reactivation of virus after transplantation. Direct-acting antivirals represent the current standard of care in hemodialyzed patients with HCV genotypes 1 and 4; in patients with genotypes 2 or 3, the optimal regimen is yet to be established. Sofosbuvir (SOF) and daclatasvir (DCV) represent an antiviral pangenotypic regimen with favorable pharmacokinetics in hemodialyzed patients. We retrospectively evaluated safety and efficacy of the combination of SOF and DCV in the treatment of genotype 3a chronic HCV in six male patients (mean age of 39 years, range 25-53 years) with end-stage renal disease on maintenance hemodialysis; these patients were treated with a reduced dose of SOF (one half of a 400 mg tablet) and 60 mg of DCV once daily. The anticipated treatment duration was 12 weeks. Initial HCV RNA ranged from 120,000 to 11,000,000 IU/mL. Two of the six patients had compensated liver cirrhosis based on shear-wave elastography result. All of the patients completed a 12-week treatment. Viremia became negative on treatment and remained negative 12 weeks after the end of therapy in all the patients. All of them (6/6, 100%) achieved sustained virological response, including two with cirrhosis and two with HCV RNA >6,000,000 IU/mL. The treatment was well tolerated: none of the patients presented with a serious adverse event requiring hospital admission and none had anemia or any significant changes in blood count. One patient had a short period of diarrhea, which was resolved with antibiotic treatment. The combination of reduced-dose SOF and full-dose DCV, daily, was a safe and effective treatment in our group of hemodialyzed patients infected with HCV genotype 3.

PMID: 28790832 [PubMed]

[Critical Care Managements after Lung Transplantation].

Thu, 08/10/2017 - 12:45
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[Critical Care Managements after Lung Transplantation].

Kyobu Geka. 2017 Jul;70(8):701-707

Authors: Anraku M

Abstract
Lung transplantation is a viable treatment option for patients with end-stage lung diseases such as interstitial pneumonia/pulmonary fibrosis, emphysema, pulmonary hypertension, and so on. Collecting available clinical, physiological, serological, and surgical information of both donor and recipient is vital when planning relevant postoperative managements. The goal of the managements is to keep the transplanted lung (s) functional while preventing/treating infection, rejection, and ischemiareperfusion lung injury. Immunosuppressive therapy, anti-mycobacterial/viral therapy, and cardio-pulmonary supports should be optimized without causing unfavorable side-effects that can lead to kidney, liver, digestive and neurological malfunction. During the post-transplant intensive care period, satisfying the endorgan oxygen requirement is the key to maintain vital organ stability. Aggressive rehabilitation should be utilized as soon as the hemodynamic status allows it. Deep venous thrombosis and subsequent pulmonary embolism should be prevented by giving anti-coagulants and active mobilization, because the incidence could be underrecognized. Avoiding multifactorial allograft injuries can improve not only short-term graft function, but also long-term patients' outcome after lung transplantation.

PMID: 28790293 [PubMed - in process]

Detecting circulating tumor DNA in renal cancer: An open challenge.

Thu, 08/10/2017 - 12:45
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Detecting circulating tumor DNA in renal cancer: An open challenge.

Exp Mol Pathol. 2017 Apr;102(2):255-261

Authors: Corrò C, Hejhal T, Poyet C, Sulser T, Hermanns T, Winder T, Prager G, Wild PJ, Frew I, Moch H, Rechsteiner M

Abstract
BACKGROUND: Detection of circulating tumor DNA (ctDNA) in blood of cancer patients is regarded as an important step towards personalized medicine and treatment monitoring. In the present study, we investigated the clinical applicability of ctDNA as liquid biopsy in renal cancer.
METHODS: ctDNA in serum and plasma samples derived from ccRCC and colon cancer patients as well as ctDNA isolated from RCC xenografts with known VHL mutation status was investigated using next generation sequencing (NGS). Additionally, a Taqman mutation specific assay was used for specific VHL mutation detection in blood.
RESULTS: In our study, we successfully identified KRAS mutation in colon cancer patients. We also confirmed the presence of specific VHL mutations in ctDNA derived from RCC xenografts indicating the capability of renal tumors to release DNA into the blood circulation. However, we could not detect any VHL mutation in plasma or serum samples derived from nine ccRCC patients. To increase the sensitivity, a VHL mutation specific Taqman assay was tested. With this approach, the pVHL mutation p.Val130Leu in exon 2 in one patient was successfully detected.
CONCLUSION: These data suggest a reduced tumor DNA shedding and an increased clearance of the tumor DNA from the circulation in renal cancer patients independently of tumor size, metastases, and necrosis. This implies that highly sensitive detection methods for mutation calling and prior knowledge of the mutation are required for liquid biopsies in ccRCC.

PMID: 28214514 [PubMed - indexed for MEDLINE]

Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques.

Thu, 08/10/2017 - 12:45
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Development of high resolution 3D hyperpolarized carbon-13 MR molecular imaging techniques.

Magn Reson Imaging. 2017 May;38:152-162

Authors: Milshteyn E, von Morze C, Reed GD, Shang H, Shin PJ, Zhu Z, Chen HY, Bok R, Goga A, Kurhanewicz J, Larson PE, Vigneron DB

Abstract
The goal of this project was to develop and apply techniques for T2 mapping and 3D high resolution (1.5mm isotropic; 0.003cm(3)) (13)C imaging of hyperpolarized (HP) probes [1-(13)C]lactate, [1-(13)C]pyruvate, [2-(13)C]pyruvate, and [(13)C,(15)N2]urea in vivo. A specialized 2D bSSFP sequence was implemented on a clinical 3T scanner and used to obtain the first high resolution T2 maps of these different hyperpolarized compounds in both rats and tumor-bearing mice. These maps were first used to optimize timings for highest SNR for single time-point 3D bSSFP acquisitions with a 1.5mm isotropic spatial resolution of normal rats. This 3D acquisition approach was extended to serial dynamic imaging with 2-fold compressed sensing acceleration without changing spatial resolution. The T2 mapping experiments yielded measurements of T2 values of >1s for all compounds within rat kidneys/vasculature and TRAMP tumors, except for [2-(13)C]pyruvate which was ~730ms and ~320ms, respectively. The high resolution 3D imaging enabled visualization the biodistribution of [1-(13)C]lactate, [1-(13)C]pyruvate, and [2-(13)C]pyruvate within different kidney compartments as well as in the vasculature. While the mouse anatomy is smaller, the resolution was also sufficient to image the distribution of all compounds within kidney, vasculature, and tumor. The development of the specialized 3D sequence with compressed sensing provided improved structural and functional assessments at a high (0.003cm(3)) spatial and 2s temporal resolution in vivo utilizing HP (13)C substrates by exploiting their long T2 values. This 1.5mm isotropic resolution is comparable to (1)H imaging and application of this approach could be extended to future studies of uptake, metabolism, and perfusion in cancer and other disease models and may ultimately be of value for clinical imaging.

PMID: 28077268 [PubMed - indexed for MEDLINE]

The Kidney Allocation System Claims Equity;It Is Time to Review Utility and Fairness.

Wed, 08/09/2017 - 12:45

The Kidney Allocation System Claims Equity;It Is Time to Review Utility and Fairness.

Am J Transplant. 2017 Aug 08;:

Authors: Klintmalm GB, Kaplan B

Abstract
The current kidney allocation system (KAS) implemented by the United Network for Organ Sharing in December 2014 was intended to balance inequities in kidney allocation while increasing utility by transplanting kidneys expected to last the longest in patients expected to live the longest. In its first iteration, termed Life Years from Transplant (LYFT), a fairly simple system of allocation was proposed to allocate kidneys based on this principle. LYFT, as opposed to our current process, also addressed the need to have a codified system to allocate kidneys unsuitable for younger patients to older recipients, such that utility could be maximized across the spectrum of potential recipients. Due to political pressures, LYFT was not instituted and our current KAS was implemented as a compromise solution (1).

PMID: 28787775 [PubMed - as supplied by publisher]

Dosing of indocyanine-green for intraoperative laser fluorescence angiography in kidney transplantation.

Wed, 08/09/2017 - 12:45

Dosing of indocyanine-green for intraoperative laser fluorescence angiography in kidney transplantation.

Microcirculation. 2017 Aug 08;:

Authors: Rother U, Gerken ALH, Karampinis I, Klumpp M, Regus S, Meyer A, Apel H, Krämer BK, Hilgers K, Lang W, Nowak K

Abstract
OBJECTIVE: Sufficient blood supply is a crucial factor determining postoperative allograft function in kidney transplantation. Therefore, besides the surgeon's individual impression a method for evaluating the quality of the organ's microperfusion is required. Laser fluorescence angiography with indocyanine-green (ICG) is an emerging tool for this purpose. However, no reproducible quantification of ICG fluorescence has been performed in transplantation so far.
METHODS: This retrospective two-center study was designed to evaluate the dosing of ICG for intraoperative laser fluorescence angiography in kidney transplantation. The Spy Elite(®) system (NOVADAQ, Canada) was employed for quantitative assessment of allograft microperfusion. ICG was administered systemically 5 min after reperfusion applying doses between 0.25 and 0.01 mg ICG per kg body weight. Quantitative assessment was performed with the implemented SPY-Q Software.
RESULTS: 57 kidney recipients were included in two centers. The generated curves showing ICG ingress and egress rates were not evaluable due to oversensing when doses exceeded 0.02 mg per kg body weight.
CONCLUSIONS: Fluorescence angiography with ICG is an emerging tool for the intraoperative quality control and evaluation of microperfusion in kidney transplantation. A dose of 0.02 mg ICG per kg body weight is recommended in order to ensure the quantitative assessment with SPY-Q. This article is protected by copyright. All rights reserved.

PMID: 28787770 [PubMed - as supplied by publisher]

Current State and Future Trends to Optimize the Care of African Americans with End-Stage Renal Disease.

Wed, 08/09/2017 - 12:45

Current State and Future Trends to Optimize the Care of African Americans with End-Stage Renal Disease.

Am J Nephrol. 2017 Aug 05;46(2):156-164

Authors: Harding K, Mersha TB, Webb FA, Vassalotti JA, Nicholas SB

Abstract
BACKGROUND: Chronic kidney disease is a progressive disease, which terminates in end-stage renal diseases (ESRD) that requires either dialysis or kidney transplantation for the patient to survive. There is an alarming trend in the disparities of ESRD in African Americans (AAs). Currently, AAs represent more than 30% of incident ESRD cases, yet they constitute 15% of the overall US population. Despite the reductions in mortality, increases in access to patient-centered home dialysis and preemptive kidney transplantation for the overall US ESRD population over the last decade, disparities in the care of AAs with ESRD remain largely unaffected.
SUMMARY: This review discusses patient-, community-, and practitioner-related factors that contribute to disparities in ESRD care for AAs. In particular, the review addresses issues related to end-of-life support, the importance of Apolipoprotein-1 gene variants, and the advent of pharmacogenomics toward achieving precision care. The need for accessible clinical intelligence for the ESRD population is discussed. Several interventions and a call to action to address the disparities are presented. Key Messages: Significant disparities in ESRD care exist for AAs. Strategies to enhance patient engagement, education, accountable partnerships, and clinical intelligence may reduce these disparities.

PMID: 28787724 [PubMed - as supplied by publisher]

Health Disparities in Kidney Transplantation for African Americans.

Wed, 08/09/2017 - 12:45

Health Disparities in Kidney Transplantation for African Americans.

Am J Nephrol. 2017 Aug 05;46(2):165-175

Authors: Harding K, Mersha TB, Pham PT, Waterman AD, Webb FA, Vassalotti JA, Nicholas SB

Abstract
BACKGROUND: The persistent challenges of bridging healthcare disparities for African Americans (AAs) in need of kidney transplantation continue to be unresolved at the national level. This healthcare disparity is multifactorial: stemming from limited kidney donors suitable for AAs; inconsistent care coordination and suboptimal risk factor control; social determinants, low socioeconomic status, reduced access to care; and mistrust of clinicians and the healthcare system.
SUMMARY: There are numerous opportunities to significantly lessen the disparities in kidney transplantation for AAs through the following measures: the adoption of new care and patient engagement models that include education, enhanced practice-level cultural sensitivity, and timely referral as well as increased research on the impact of the environment on genetic risk, and implementation of new transplantation-related policies. Key Messages: This systematic review describes pretransplant concerns related to access to kidney transplantation, posttransplant complications, and policy interventions to address the challenging issues associated with kidney transplantation in AAs.

PMID: 28787713 [PubMed - as supplied by publisher]

Living Kidney Donor Phenotype and Likelihood of Postdonation Follow-up.

Wed, 08/09/2017 - 12:45

Living Kidney Donor Phenotype and Likelihood of Postdonation Follow-up.

Transplantation. 2017 Aug 03;:

Authors: Reed RD, Shelton BA, MacLennan PA, Sawinski D, Locke JE

Abstract
BACKGROUND: The Organ Procurement and Transplantation Network requires that United States transplant centers maintain follow-up with living donors for 2 years postdonation, but lack of donor follow-up is pervasive. Donor characteristics, including younger age, minority race, and lower education, have been associated with incomplete follow-up, but it is unknown whether altruistic donors, having no prior connection to their recipient, differ from traditional donors in their likelihood of follow-up.
METHODS: Utilizing Scientific Registry of Transplant Recipients data, we examined all adult living kidney donors from 2005-2015 (n=63 592) classified as altruistic or traditional, and compared likelihood of 6-month medical follow-up using modified Poisson regression.
RESULTS: Altruistic donors did not differ from traditional donors in likelihood of follow-up (aRR: 1.02, 95% CI: 0.99-1.06). Among previously identified at-risk subgroups, however, altruistic donors were more likely to have follow-up than their traditional counterparts, including those who were younger (aRR: 1.04, 95% CI: 1.00-1.09), had less than college education (aRR: 1.05, 95% CI: 1.00-1.11), and were unmarried (aRR: 1.08, 95% CI: 1.04-1.12). Having medical follow-up at 6 months was significantly associated with having follow-up at 1 (aRR: 1.84, 95% CI: 1.75-1.93) and 2 years (aRR: 1.63, 95% CI: 1.56-1.70) postdonation.
CONCLUSIONS: These data provide additional granularity on living donor phenotypes associated with short-term (6 month) postdonation follow-up, which is important given its association with future likelihood of follow-up. These findings offer the opportunity to tailor and direct educational efforts to increase living donor follow-up, particularly among groups at higher risk of loss to follow-up.

PMID: 28787311 [PubMed - as supplied by publisher]

External Validation of Kidney Donor Risk Index (KDRI) Does not Mitigate its Basic Limitations.

Wed, 08/09/2017 - 12:45

External Validation of Kidney Donor Risk Index (KDRI) Does not Mitigate its Basic Limitations.

Transplantation. 2017 Aug 05;:

Authors: Budhiraja P, Kaplan B

PMID: 28787309 [PubMed - as supplied by publisher]

Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant.

Wed, 08/09/2017 - 12:45

Serum Aberrant N-Glycan Profile as a Marker Associated with Early Antibody-Mediated Rejection in Patients Receiving a Living Donor Kidney Transplant.

Int J Mol Sci. 2017 Aug 08;18(8):

Authors: Noro D, Yoneyama T, Hatakeyama S, Tobisawa Y, Mori K, Hashimoto Y, Koie T, Tanaka M, Nishimura SI, Sasaki H, Saito M, Harada H, Chikaraishi T, Ishida H, Tanabe K, Satoh S, Ohyama C

Abstract
We determined if the serum N-glycan profile can be used as a diagnostic marker of antibody-mediated rejection (ABMR) in living donor kidney transplant (LKTx) recipients. Glycoblotting, combined with mass spectrometry, was used to retrospectively examine N-glycan levels in the postoperative sera of 197 LKTx recipients of whom 16 recipients had ABMR with or without T-cell-mediated rejection (TCMR), 40 recipients had TCMR, and 141 recipients had no adverse events. Multivariate discriminant analysis for prediction of ABMR was performed by inputting an ABMR event as an explanatory variable and sex, age, and serum N-glycan level as objective variables. The N-glycan score was calculated by multiplying the level of candidate objective variables by objective function values. The ABMR predictive performance of the N-glycan score was assessed by receiver operator characteristic curve and Kaplan-Meier curve analyses. The N-glycan score discriminated ABMR with 81.25% sensitivity, 87.85% specificity, and an area under the curve (AUC) of 0.892 that was far superior to that of preformed donor-specific antibody status (AUC, 0.761). Recipients with N-glycan-positive scores >0.8770 had significantly shorter ABMR survival than that of recipients with N-glycan-negative scores. Although the limitations of our study includ its small sample size and retrospective nature, the serum N-glycan score may contribute to prediction of ABMR.

PMID: 28786963 [PubMed - in process]

Should all dialysis patients with hepatitis C be treated? If so, before or after kidney transplantation?

Wed, 08/09/2017 - 12:45
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Should all dialysis patients with hepatitis C be treated? If so, before or after kidney transplantation?

Semin Dial. 2017 Aug 07;:

Authors: Jadoul M, Martin P

Abstract
HCV infection by genotype 1 and 4 can now be cured in close to 100% of patients with stage 4 or 5 CKD, including dialysis patients. Several regimens are available, all interferon-free and given for only 12 weeks. Thus unless life expectancy is short, HCV infection should be treated. The optimal timing of antiviral treatment will be dependent on several parameters: the possibility of being transplanted rapidly (either with a HCV+ graft or from a living donor) calls for treatment after transplantation. On the contrary, severe liver fibrosis, especially with portal hypertension calls for immediate treatment of HCV. Finally specific HCV genotype also impacts the treatment decision as genotypes 2,3,5 and 6 currently can be treated more easily after restoration of kidney function rather than in the presence of severe CKD, although this is anticipated to change soon once newer pangenotypic regimens are licensed.

PMID: 28786139 [PubMed - as supplied by publisher]

Serum Iron Protects from Renal Postischemic Injury.

Wed, 08/09/2017 - 12:45
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Serum Iron Protects from Renal Postischemic Injury.

J Am Soc Nephrol. 2017 Aug 07;:

Authors: Vaugier C, Amano MT, Chemouny JM, Dussiot M, Berrou C, Matignon M, Ben Mkaddem S, Wang PHM, Fricot A, Maciel TT, Grapton D, Mathieu JRR, Beaumont C, Peraldi MN, Peyssonnaux C, Mesnard L, Daugas E, Vrtovsnik F, Monteiro RC, Hermine O, Ginzburg YZ, Benhamou M, Camara NOS, Flamant M, Moura IC

Abstract
Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-κB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants.

PMID: 28784700 [PubMed - as supplied by publisher]

Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy.

Wed, 08/09/2017 - 12:45
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Kidney Disease in HIV: Moving beyond HIV-Associated Nephropathy.

J Am Soc Nephrol. 2017 Aug 07;:

Authors: Jotwani V, Atta MG, Estrella MM

Abstract
In developed countries, remarkable advances in antiretroviral therapy have transformed HIV infection into a chronic condition. As a result, HIV-associated nephropathy, the classic HIV-driven kidney lesion among individuals of African descent, has largely disappeared in these regions. However, HIV-positive blacks continue to have much higher rates of ESRD than HIV-positive whites, which could be attributed to the APOL1 renal risk variants. Additionally, HIV-positive individuals face adverse consequences beyond HIV itself, including traditional risk factors for CKD and nephrotoxic effects of antiretroviral therapy. Concerns for nephrotoxicity also extend to HIV-negative individuals using tenofovir disoproxil fumarate-based pre-exposure prophylaxis for the prevention of HIV infection. Therefore, CKD remains an important comorbid condition in the HIV-positive population and an emerging concern among HIV-negative persons receiving pre-exposure prophylaxis. With the improved longevity of HIV-positive individuals, a kidney transplant has become a viable option for many who have progressed to ESRD. Herein, we review the growing knowledge regarding the APOL1 renal risk variants in the context of HIV infection, antiretroviral therapy-related nephrotoxicity, and developments in kidney transplantation among HIV-positive individuals.

PMID: 28784698 [PubMed - as supplied by publisher]

Piperacillin-induced Thrombocytopenia in a Dual Heart and Kidney Transplant Patient: A Case Report.

Wed, 08/09/2017 - 12:45
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Piperacillin-induced Thrombocytopenia in a Dual Heart and Kidney Transplant Patient: A Case Report.

Transplant Proc. 2017 Aug 04;:

Authors: Patel S, Levin-Epstein R, Kobashigawa J

Abstract
BACKGROUND: The present study reports a case of piperacillin-induced thrombocytopenia in a dual heart and kidney transplant patient on January 28, 2016 (taking mycophenolate mofetil and tacrolimus). Before the transplant, the patient was treated with Zosyn twice, with no reports of thrombocytopenia or allergy. However, he was diagnosed with heparin-induced thrombocytopenia and vancomycin allergy during each of those hospitalizations, respectively. Eight months after the transplant, the patient presented with infectious symptoms and was started on Zosyn.
RESULTS: One day after starting Zosyn, the patient experienced a drop in platelet count from 6,000/μL from 216,000/μL. Platelets decreased as low as 1 on day 3 of hospitalization. Administration of mycophenolate mofetil, tacrolimus, Bactrim, vancomycin, Zosyn, ranitidine, and Rivaroxaban were discontinued. Platelet counts stabilized the day after Zosyn was discontinued and slowly increased after the patient was treated with 2 doses of intravenous immunoglobulin, 4 units of platelets, and a tapered dose of prednisone.
CONCLUSIONS: The patient was initially diagnosed with vancomycin-induced thrombocytopenia but then tested positive for antibodies to piperacillin and negative for antibodies to vancomycin and tazobactam. The patient was discharged with a diagnosis of piperacillin-induced thrombocytopenia. This case report presents a case of piperacillin-induced thrombocytopenia, previously misdiagnosed as vancomycin-induced thrombocytopenia and heparin-induced thrombocytopenia.

PMID: 28784558 [PubMed - as supplied by publisher]

Anesthesia for Kidney and Pancreas Transplantation.

Wed, 08/09/2017 - 12:45
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Anesthesia for Kidney and Pancreas Transplantation.

Anesthesiol Clin. 2017 Sep;35(3):439-452

Authors: Mittel AM, Wagener G

Abstract
Kidney transplants are the most common solid organ abdominal transplant and are occasionally performed simultaneously with pancreas transplants in diabetic patients. Preoperative evaluation of potential transplant recipients should focus on the potential for occult cardiovascular disease while also screening for other signs of end-organ dysfunction. Intraoperatively, it is of utmost importance to ensure adequate graft perfusion to limit the risk of postoperative graft dysfunction or rejection. Postoperative care of the kidney or pancreas transplant patient should focus on ensuring normalization of volume status, electrolyte concentrations, and glycemic control.

PMID: 28784219 [PubMed - in process]

Anesthetic Management of Pediatric Liver and Kidney Transplantation.

Wed, 08/09/2017 - 12:45
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Anesthetic Management of Pediatric Liver and Kidney Transplantation.

Anesthesiol Clin. 2017 Sep;35(3):421-438

Authors: Wasson NR, Deer JD, Suresh S

Abstract
Pediatric patients with liver dysfunction and renal failure may exhibit many comorbidities. There are often associated congenital syndromes to be taken into account. Liver and renal transplantation offer a solution and substantial improvement in quality of life. Anesthetic management of pediatric liver and renal transplantation has not been well described. There are key differences between adults and children undergoing these procedures, and acknowledgment of some key principles provide a solid foundation to optimize perioperative outcomes. This article provides an overview of the perioperative management and considerations in pediatric patients undergoing liver and renal transplantation.

PMID: 28784218 [PubMed - in process]

Development of fresh and vitrified agouti ovarian tissue after xenografting to ovariectomised severe combined immunodeficiency (SCID) mice.

Wed, 08/09/2017 - 12:45
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Development of fresh and vitrified agouti ovarian tissue after xenografting to ovariectomised severe combined immunodeficiency (SCID) mice.

Reprod Fertil Dev. 2017 Aug 08;:

Authors: Praxedes ÉCG, Lima GL, Bezerra LGP, Santos FA, Bezerra MB, Guerreiro DD, Rodrigues APR, Domingues SFS, Silva AR

Abstract
The aim of the present study was to evaluate the development of fresh and vitrified agouti ovarian tissue after xenografting to C57Bl/6 severe combined immunodeficiency (SCID) female mice. Ovaries were obtained from five female agoutis and divided into 16 fragments. Five fragments were transplanted immediately to ovariectomised SCID mice and the others were vitrified, stored for 2 weeks and transplanted only after rewarming. Tissue fragments were transplanted under the kidney capsule in recipients. The return of ovarian activity in recipients was monitored by the observation of external signs of oestrus and vaginal cytology over a period of 40 days after transplantation, after which the grafts were removed and evaluated for morphology, cell proliferation and the occurrence of DNA fragmentation. Ovarian activity returned in four of five mice that received fresh ovarian tissue from agoutis and in one of six mice that had received vitrified tissue a mean (±s.e.m.) 20.6±8.6 days after xenotransplantation. After graft removal, a predominance of primordial and primary follicles was observed in all grafts. Vitrification reduced cell proliferation and increased the occurrence of DNA fragmentation in grafted agouti ovarian tissue. In conclusion, the present study demonstrates that xenografted agouti ovarian tissue, fresh or vitrified, is able to promote the return of ovarian activity in ovariectomised SCID C57B1/6 mice. However, improvements to vitrification protocols for agouti ovarian tissue are necessary.

PMID: 28784201 [PubMed - as supplied by publisher]

Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.

Wed, 08/09/2017 - 12:45
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Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.

Nephrol Dial Transplant. 2016 Dec;31(12):1982-1988

Authors: Gargani L, Sicari R, Raciti M, Serasini L, Passera M, Torino C, Letachowicz K, Ekart R, Fliser D, Covic A, Balafa O, Stavroulopoulos A, Massy ZA, Fiaccadori E, Caiazza A, Bachelet T, Slotki I, Shavit L, Martinez-Castelao A, Coudert-Krier MJ, Rossignol P, Kraemer TD, Hannedouche T, Panichi V, Wiecek A, Pontoriero G, Sarafidis P, Klinger M, Hojs R, Seiler-Mußler S, Lizzi F, Onofriescu M, Zarzoulas F, Tripepi R, Mallamaci F, Tripepi G, Picano E, London GM, Zoccali C

Abstract
Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

PMID: 27672089 [PubMed - indexed for MEDLINE]

Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway.

Wed, 08/09/2017 - 12:45
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Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway.

J Immunol. 2016 Sep 15;197(6):2045-50

Authors: Adams AB, Ford ML, Larsen CP

Abstract
T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4-Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology. Abatacept and belatacept are clinically approved agents for the treatment of rheumatoid arthritis and renal transplantation, respectively. Future interventions may include selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4.

PMID: 27591335 [PubMed - indexed for MEDLINE]

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