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Guidelines for the management of a brain death donor in the rhesus macaque: A translational transplant model.

Wed, 09/20/2017 - 12:45
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Guidelines for the management of a brain death donor in the rhesus macaque: A translational transplant model.

PLoS One. 2017;12(9):e0182552

Authors: Zens TJ, Danobeitia JS, Chlebeck PJ, Zitur LJ, Odorico S, Brunner K, Coonen J, Capuano S, D'Alessandro AM, Matkowskyj K, Zhong W, Torrealba J, Fernandez L

Abstract
INTRODUCTION: The development of a translatable brain death animal model has significant potential to advance not only transplant research, but also the understanding of the pathophysiologic changes that occur in brain death and severe traumatic brain injury. The aim of this paper is to describe a rhesus macaque model of brain death designed to simulate the average time and medical management described in the human literature.
METHODS: Following approval by the Institutional Animal Care and Use Committee, a brain death model was developed. Non-human primates were monitored and maintained for 20 hours after brain death induction. Vasoactive agents and fluid boluses were administered to maintain hemodynamic stability. Endocrine derangements, particularly diabetes insipidus, were aggressively managed.
RESULTS: A total of 9 rhesus macaque animals were included in the study. The expected hemodynamic instability of brain death in a rostral to caudal fashion was documented in terms of blood pressure and heart rate changes. During the maintenance phase of brain death, the animal's temperature and hemodynamics were maintained with goals of mean arterial pressure greater than 60mmHg and heart rate within 20 beats per minute of baseline. Resuscitation protocols are described so that future investigators may reproduce this model.
CONCLUSION: We have developed a reproducible large animal primate model of brain death which simulates clinical scenarios and treatment. Our model offers the opportunity for researchers to have translational model to test the efficacy of therapeutic strategies prior to human clinical trials.

PMID: 28926566 [PubMed - in process]

High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study.

Wed, 09/20/2017 - 12:45
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High Levels of Morbidity and Mortality Among Pediatric Hematopoietic Cell Transplant Recipients With Severe Sepsis: Insights From the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study.

Pediatr Crit Care Med. 2017 Sep 16;:

Authors: Lindell RB, Gertz SJ, Rowan CM, McArthur J, Beske F, Plunkett A, Weiss SL, Thomas NJ, Nadkarni VM, Fitzgerald JC, Sepsis PRevalence, OUtcomes, and Therapies Study Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network

Abstract
OBJECTIVES: Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant.
DESIGN: Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality.
SETTING: International; 128 PICUs in 26 countries.
PATIENTS: Pediatric patients with severe sepsis prospectively identified over a 1-year period.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27).
CONCLUSIONS: In an international study of pediatric severe sepsis, history of hematopoietic cell transplant is associated with a four-fold increased odds of hospital mortality after adjustment for potential measured confounders. Hematopoietic cell transplant patients more often originated from within the hospital compared to children with severe sepsis without hematopoietic cell transplant, possibly providing an earlier opportunity for sepsis recognition and intervention in this high-risk population.

PMID: 28926489 [PubMed - as supplied by publisher]

Clostridium difficile Infection in Intestinal Transplant Recipients.

Wed, 09/20/2017 - 12:45
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Clostridium difficile Infection in Intestinal Transplant Recipients.

Transpl Int. 2017 Sep 19;:

Authors: Goldenberg V, Berbel A, Camargo JF, Simkins J

Abstract
Clostridium difficile infection (CDI) is a common complication among solid organ transplant (SOT) recipients with an estimated incidence of 7-31% for lung recipients, 8-15% for heart, 3-19% for liver, 9% for intestinal, 4-16% for kidney and 2-8% for pancreas-kidney recipients (1) and it is associated with increased mortality (2). There is limited data on CDI in intestinal transplant (ITx) recipients. This is a retrospective study that was conducted at Jackson Memorial Hospital, a 1558-licensed bed tertiary care teaching hospital. Our study was approved by the Institutional Review Board of University of Miami. This article is protected by copyright. All rights reserved.

PMID: 28926130 [PubMed - as supplied by publisher]

Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia.

Wed, 09/20/2017 - 12:45
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Technical Advances in the Measurement of Residual Disease in Acute Myeloid Leukemia.

J Clin Med. 2017 Sep 19;6(9):

Authors: Roloff GW, Lai C, Hourigan CS, Dillon LW

Abstract
Outcomes for those diagnosed with acute myeloid leukemia (AML) remain poor. It has been widely established that persistent residual leukemic burden, often referred to as measurable or minimal residual disease (MRD), after induction therapy or at the time of hematopoietic stem cell transplant (HSCT) is highly predictive for adverse clinical outcomes and can be used to identify patients likely to experience clinically evident relapse. As a result of inherent genetic and molecular heterogeneity in AML, there is no uniform method or protocol for MRD measurement to encompass all cases. Several techniques focusing on identifying recurrent molecular and cytogenetic aberrations or leukemia-associated immunophenotypes have been described, each with their own strengths and weaknesses. Modern technologies enabling the digital quantification and tracking of individual DNA or RNA molecules, next-generation sequencing (NGS) platforms, and high-resolution imaging capabilities are among several new avenues under development to supplement or replace the current standard of flow cytometry. In this review, we outline emerging modalities positioned to enhance MRD detection and discuss factors surrounding their integration into clinical practice.

PMID: 28925935 [PubMed]

Laparoscopic-Assisted Resection for Advanced Colorectal Cancer in Solid Organ Transplant Recipients.

Wed, 09/20/2017 - 12:45
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Laparoscopic-Assisted Resection for Advanced Colorectal Cancer in Solid Organ Transplant Recipients.

J Invest Surg. 2017 Sep 19;:1-8

Authors: Xia ZN, Hou R, Zhu W, Yao R, Lu Z, Qiu HZ, Lin GL

Abstract
AIM: To evaluate the feasibility, short- and long-term outcomes, and safety of laparoscopic resection for advanced colorectal cancer (CRC) in solid organ transplant recipients.
METHODS: Between September 2001 and April 2016, five patients who underwent laparoscopic-assisted resection for CRC after solid organ transplantation were included in this study. Their clinical data were retrospectively analyzed with regard to patient demographics, immunosuppressive therapy, tumor characteristics, surgical outcomes, and follow-up data.
RESULTS: Four kidney and one heart transplant recipients were included. Laparoscopic-assisted low anterior resection was performed in four patients with rectal or rectosigmoid junction cancer, and sigmoidectomy was done in one with sigmoid colon cancer. One kidney transplant patient received a protective loop transverse colostomy. All resections achieved complete tumor removal with tumor-free margins and total mesorectal excision, with an average number of 14 lymph nodes harvested. Most tumors were in stage III (n = 3), one was in stage II, and one in stage IV. The mean duration of surgery, intraoperative blood loss, and postoperative hospital stay were 144 min, 105 mL, and 8.8 days, respectively. No major complications occurred and graft function stayed well. During a mean follow-up period of 62 months, two patients developed metastasis and died eventually.
CONCLUSION: Laparoscopic resection for advanced CRC in organ transplant recipients is technically feasible and therapeutically safe, and seems to have the advantages of few postoperative complications, short recovery time, and acceptable oncological outcomes.

PMID: 28925783 [PubMed - as supplied by publisher]

Role of cardiopulmonary exercise testing in clinical stratification in heart failure. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology.

Wed, 09/20/2017 - 12:45
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Role of cardiopulmonary exercise testing in clinical stratification in heart failure. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail. 2017 Sep 18;:

Authors: Corrà U, Agostoni PG, Anker SD, Coats AJS, Crespo Leiro MG, de Boer RA, Hairola VP, Hill L, Lainscak M, Lund LH, Metra M, Ponikowski P, Riley J, Seferović PM, Piepoli MF

Abstract
Traditionally, the main indication for cardiopulmonary exercise testing (CPET) in heart failure (HF) was for the selection of candidates to heart transplantation: CPET was mainly performed in middle-aged male patients with HF and reduced left ventricular ejection fraction. Today, CPET is used in broader patients' populations, including women, elderly, patients with co-morbidities, those with preserved ejection fraction, or left ventricular assistance device recipients, i.e. individuals with different responses to incremental exercise and markedly different prognosis. Moreover, the diagnostic and prognostic utility of symptom-limited CPET parameters derived from submaximal tests is more and more considered, since many patients are unable to achieve maximal aerobic power. Repeated tests are also being used for risk stratification and evaluation of intervention, so that these data are now available. Finally, patients, physicians and healthcare decision makers are increasingly considering how treatments might impact morbidity and quality of life rather than focusing more exclusively on hard endpoints (such as mortality) as was often the case in the past. Innovative prognostic flowcharts, with CPET at their core, that help optimize risk stratification and the selection of management options in HF patients, have been developed.

PMID: 28925073 [PubMed - as supplied by publisher]

Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation.

Wed, 09/20/2017 - 12:45
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Extracorporeal Membrane Oxygenation Can Save Lives in Children With Heart or Lung Failure After Liver Transplantation.

Artif Organs. 2017 Sep;41(9):862-865

Authors: Jean S, Chardot C, Oualha M, Capito C, Bustarret O, Pouard P, Renolleau S, Lacaille F, Dupic L

Abstract
The risk of cardiac or lung failure after liver transplantation (LT) is significant. In rare cases, the usual intensive care techniques fail to maintain organ oxygenation with a risk of multiorgan dysfunction. Although extracorporeal membrane oxygenation (ECMO) is a difficult and risky procedure, it can be proposed as life-saving. Four children with either acute pulmonary (three) or cardiac (one) failure after LT, and the criteria that decided the use of ECMO (level of ventilation and results, dosage of inotropic drugs, cardiac ultrasound, blood lactate) were retrospectively reported. These patients, 1-11 years old, were treated with either veno-arterial (three) or veno-venous (one) ECMO. Two experienced a full recovery, with 3 and 6 years of follow-up. Two died of systemic inflammatory response syndrome (SIRS) due to ECMO, and relapse of heart failure due to the underlying disease. Although our patients' survival was only 50%, we showed that ECMO can be useful in children after LT. It should be considered before the development of irreversible multiorgan failure.

PMID: 28925053 [PubMed - in process]

Quantification of Etoposide Hypersensitivity: A Sensitive, Functional Method for Assessing Pluripotent Stem Cell Quality.

Wed, 09/20/2017 - 12:45
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Quantification of Etoposide Hypersensitivity: A Sensitive, Functional Method for Assessing Pluripotent Stem Cell Quality.

Stem Cells Transl Med. 2017 Sep 19;:

Authors: Secreto FJ, Li X, Smith AJ, Bruinsma ES, Perales-Clemente E, Oommen S, Hawse G, Hrstka SCL, Arendt BK, Brandt EB, Wigle DA, Nelson TJ

Abstract
Human induced pluripotent stem cells (hiPSC) hold great promise in diagnostic and therapeutic applications. However, translation of hiPSC technology depends upon a means of assessing hiPSC quality that is quantitative, high-throughput, and can decipher malignant teratocarcinoma clones from normal cell lines. These attributes are lacking in current approaches such as detection of cell surface makers, RNA profiling, and/or teratoma formation assays. The latter remains the gold standard for assessing clone quality in hiPSCs, but is expensive, time-consuming, and incompatible with high-throughput platforms. Herein, we describe a novel method for determining hiPSC quality that exploits pluripotent cells' documented hypersensitivity to the topoisomerase inhibitor etoposide (CAS No. 33419-42-0). Based on a study of 115 unique hiPSC clones, we established that a half maximal effective concentration (EC50) value of <300 nM following 24 hours of exposure to etoposide demonstrated a positive correlation with RNA profiles and colony morphology metrics associated with high quality hiPSC clones. Moreover, our etoposide sensitivity assay (ESA) detected differences associated with culture maintenance, and successfully distinguished malignant from normal pluripotent clones independent of cellular morphology. Overall, the ESA provides a simple, straightforward method to establish hiPSC quality in a quantitative and functional assay capable of being incorporated into a generalized method for establishing a quality control standard for all types of Pluripotent Stem Cells. Stem Cells Translational Medicine 2017.

PMID: 28924979 [PubMed - as supplied by publisher]

The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.

Wed, 09/20/2017 - 12:45
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The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.

J Nucl Cardiol. 2017 Sep 18;:

Authors: AlJaroudi W, Anokwute C, Fughhi I, Campagnoli T, Wassouf M, Vij A, Kharouta M, Appis A, Ali A, Doukky R

Abstract
BACKGROUND: In asymptomatic end-stage renal disease (ESRD) patients undergoing vasodilator stress myocardial perfusion imaging (MPI) prior to renal transplantation (RT), the impact of pre-transplant heart rate response (HRR) to vasodilator stress on post-RT outcomes is unknown.
METHODS: We analyzed a retrospective cohort of asymptomatic patients with ESRD who underwent a vasodilator stress SPECT-MPI and subsequently received RT. Blunted HRR was defined as HRR <28% for regadenoson stress and <20% for adenosine stress. The primary endpoint was major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. Clinical risk was assessed using the sum of risk factors set forth by the AHA/ACCF consensus statement on the assessment of RT candidates.
RESULTS: Among 352 subjects, 140 had an abnormal pre-transplant HRR. During a mean follow-up of 3.2 ± 2.0 years, 85 (24%) MACEs were observed. Blunted HRR was associated with increased MACE risk (hazard ratio 1.72; 95% confidence interval 1.12-2.63, P = 0.013), and remained significant after adjustment for gender, sum of AHA/ACCF risk factors, summed stress score, baseline heart rate, and β-blocker use. HRR was predictive of MACE in patients with normal MPI and irrespective of clinical risk. Blunted HRR was associated with a significant increase in post-operative (30-day) MACE risk (17.9% vs 8.5%; P = 0.009).
CONCLUSION: In asymptomatic ESRD patients being evaluated for RT, a blunted pre-transplant HRR was predictive of post-RT MACE. HRR may be a valuable tool in the risk assessment of RT candidates.

PMID: 28924814 [PubMed - as supplied by publisher]

Primary Cutaneous CD4-Positive Small/Medium-Sized Pleomorphic T-Cell Lymphoma Following Heart Transplantation.

Wed, 09/20/2017 - 12:45
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Primary Cutaneous CD4-Positive Small/Medium-Sized Pleomorphic T-Cell Lymphoma Following Heart Transplantation.

Int J Organ Transplant Med. 2017;8(3):168-169

Authors: Shakerian B, Razavi N, Mandegar MH

Abstract
Post-transplantation cutaneous lymphoproliferative diseases (PTCLD) are rare, with 29 cases have so far been reported in the literature-only 4 cases underwent cardiac transplantation. Herein, we report on, to the best of our knowledge, the first case in the English literature of primary cutaneous CD4-positive small/medium-sized pleomorphic T-cell lymphoma in a cardiac transplant recipient.

PMID: 28924466 [PubMed]

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy for the Metabolic Assessment of Acute Rejection After Cardiac Transplantation in Rats.

Wed, 09/20/2017 - 12:45
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High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy for the Metabolic Assessment of Acute Rejection After Cardiac Transplantation in Rats.

Transplant Proc. 2017 Oct;49(8):1935-1941

Authors: Lee CW, Lee JS, Woo CW, Kim S

Abstract
PURPOSE: To evaluate the potential of high-resolution magic angle spinning (HR-MAS) (1)H nuclear magnetic resonance (NMR) spectroscopy for metabolite characterization and the differentiation of acute rejection after heart transplantation in rat models.
METHODS: We transplanted syngeneic heart grafts from Lewis rats (n = 4) and allogeneic heart grafts from F344 rats (n = 4) heterotopically into Lewis recipients. On day 7 postoperatively, the transplanted hearts were harvested for ex vivo (1)H NMR spectroscopy and HR-MAS (1)H NMR spectroscopy. (1)H NMR spectroscopy and HR-MAS (1)H NMR spectroscopy were performed at 4.7 T and 11.7 T, respectively. Metabolomic profiles contributing to the differentiation of allogeneic and syngeneic graft groups were statistically assessed by orthogonal partial least squares discriminant analysis (OPLS/O2PLS-DA). Metabolite concentrations were normalized by total spectral intensities and were compared using Mann-Whitney U tests.
RESULTS: One allogeneic graft that showed extensive necrotic change suggesting graft failure was excluded from the statistical analysis of the NMR spectroscopy. In the 4.7-T (1)H NMR spectroscopy, the creatine peak was decreased in the allogeneic group. The PLS-DA and OPLS/O2PLS-DA score plot demonstrated good discrimination of the allogeneic graft group from syngeneic graft group. The concentrations of creatine, myo-inositol, glucose, niacinamide, hypoxanthine, inosine, and glutamine were significantly decreased in the allogeneic graft group, whereas the concentrations of glycine, phosphoethanolamine, xanthine, sn-glycero-3-phosphocholine, leucine, valine, and tyrosine were significantly increased (P < .05).
CONCLUSIONS: HR-MAS (1)H NMR spectroscopy can metabolically characterize the acute rejection of heart transplantation.

PMID: 28923651 [PubMed - in process]

Comparison of Segmental Versus Longitudinal Intravascular Ultrasound Analysis for Pediatric Cardiac Allograft Vasculopathy.

Wed, 09/20/2017 - 12:45
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Comparison of Segmental Versus Longitudinal Intravascular Ultrasound Analysis for Pediatric Cardiac Allograft Vasculopathy.

Transplant Proc. 2017 Oct;49(8):1899-1902

Authors: Kuhn MA, Burch M, Chinnock RE, Fenton MJ

Abstract
Intravascular ultrasound (IVUS) has been routinely used in some centers to investigate cardiac allograft vasculopathy in pediatric heart transplant recipients. We present an alternative method using more sophisticated imaging software. This study presents a comparison of this method with an established standard method. All patients who had IVUS performed in 2014 were retrospectively evaluated. The standard technique consisted of analysis of 10 operator-selected segments along the vessel. Each study was re-evaluated using a longitudinal technique, taken at every third cardiac cycle, along the entire vessel. Semiautomatic edge detection software was used to detect vessel imaging planes. Measurements included outer and inner diameter, total and luminal area, maximal intimal thickness (MIT), and intimal index. Each IVUS was graded for severity using the Stanford classification. All results were given as mean ± standard deviation (SD). Groups were compared using Student t test. A P value <.05 was considered significant. There were 59 IVUS studies performed on 58 patients. There was no statistically significant difference between outer diameter, inner diameter, or total area. In the longitudinal group, there was a significantly smaller luminal area, higher MIT, and higher intimal index. Using the longitudinal technique, there was an increase in Stanford classification in 20 patients. The longitudinal technique appeared more sensitive in assessing the degree of cardiac allograft vasculopathy and may play a role in the increase in the degree of thickening seen. It may offer an alternative way of grading severity of cardiac allograft vasculopathy in pediatric heart transplant recipients.

PMID: 28923645 [PubMed - in process]

Combination of Echinocandins and Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jiroveci Pneumonia After Heart Transplantation.

Wed, 09/20/2017 - 12:45
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Combination of Echinocandins and Trimethoprim/Sulfamethoxazole for the Treatment of Pneumocystis jiroveci Pneumonia After Heart Transplantation.

Transplant Proc. 2017 Oct;49(8):1893-1898

Authors: Lu YM, Lee YT, Chang HC, Yang HS, Chang CY, Huang CM, Wei J

Abstract
BACKGROUND: The echinocandins have shown anti-Pneumocystis jiroveci activity in nonhuman animal models; however, the corresponding human clinical experience has been rarely reported. We report a clinical picture of P jiroveci pneumonia (PJP) and determine the effects of concomitant therapy with echinocandins and trimethoprim (TMP)-sulfamethoxazole (SMZ).
METHODS: We investigated a retrospective case series of heart transplantation (HT) recipients with PJP from July 1988 to December 2015. Recipient charts were reviewed for their demographic characteristics, underlying conditions, concomitant infections, PJP prophylaxis, TMP-SMZ dosages, adverse events, echinocandin use, oxygenation, and outcomes.
RESULTS: Eleven of 451 HT recipients developed PJP after a median duration of 2.8 years after transplantation. All 11 were treated with TMP-SMZ; 5 of them were treated with echinocandins added to the standard TMP-SMZ regimen. The longest interval between transplantation and PJP development was 16.3 years. The mortality rate was 33.3% in recipients receiving TMP-SMZ alone, whereas it was 20% in those receiving echinocandins as well. The most common side effects of TMP-SMZ include nausea and vomiting, metabolic acidosis, and hyperkalemia. Five recipients developed acute psychosis after a median duration of 6 days of TMP-SMZ therapy. The incidence of psychosis increased from 25% in recipients receiving TMP at ≤15 mg/kg/d to 100% in those receiving TMP at >15 mg/kg/d.
CONCLUSIONS: Echinocandins along with the standard TMP-SMZ regimen may effectively alleviate PJP developed after HT. The ideal prophylaxis duration is lifelong owing to the late onset of PJP. The typically intolerable adverse effects of TMP-SMZ therapy for PJP may necessitate dosage adjustments in some cases.

PMID: 28923644 [PubMed - in process]

Feasibility of Lung Transplantation From Donation After Circulatory Death Donors Following Portable Ex Vivo Lung Perfusion: A Pilot Study.

Wed, 09/20/2017 - 12:45
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Feasibility of Lung Transplantation From Donation After Circulatory Death Donors Following Portable Ex Vivo Lung Perfusion: A Pilot Study.

Transplant Proc. 2017 Oct;49(8):1885-1892

Authors: Luc JGY, Jackson K, Weinkauf JG, Freed DH, Nagendran J

Abstract
BACKGROUND: Donation after circulatory death (DCD) has the potential to significantly alleviate the shortage of transplantable lungs. We report our initial experience with the use of portable ex vivo lung perfusion (EVLP) with the Organ Care System Lung device for evaluation of DCD lungs.
METHODS: We performed a retrospective review of the DCD lung transplantation (LTx) experience at a single institution through the use of a prospective database.
RESULTS: From 2011 to 2015, 208 LTx were performed at the University of Alberta, of which 11 were DCD LTx with 7 (64%) that underwent portable EVLP. DCD lungs preserved with portable EVLP had a significantly shorter cold ischemic time (161 ± 44 vs 234 ± 60 minutes, P = .045), lower grade of primary graft dysfunction at 72 hours after LTx (0.4 ± 0.5 vs 2.1 ± 0.7, P = .003), similar mechanical ventilation time (55 ± 44 vs 103 ± 97 hours, P = .281), and hospital length of stay (29 ± 11 vs 33 ± 10 days, P = .610). All patients were alive at 1-year follow-up after LTx with improved functional outcomes and acceptable quality of life compared with before LTx, although there were no intergroup differences.
CONCLUSIONS: In our pilot cohort, portable EVLP was a feasible modality to increase confidence in the use of DCD lungs with validated objective evidence of lung function during EVLP that translates to acceptable clinical outcomes and quality of life after LTx. Further studies are needed to validate these initial findings in a larger cohort.

PMID: 28923643 [PubMed - in process]

Role of Coronary Angiography in Pre-Liver Transplantation Cardiac Evaluation: Experience From an Asian Transplant Institution.

Wed, 09/20/2017 - 12:45
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Role of Coronary Angiography in Pre-Liver Transplantation Cardiac Evaluation: Experience From an Asian Transplant Institution.

Transplant Proc. 2017 Oct;49(8):1797-1805

Authors: Pang NQ, Kow WCA, Law JH, Pan LTT, Lim BLK, Wong CCR, Chang KYS, Ganpathi IS, Madhavan K

Abstract
BACKGROUND: Liver transplant (LT) patients with significant coronary artery disease (CAD) have poorer outcomes. Pre-LT coronary angiography (CA) is associated with significant complications in cirrhotic patients.
METHODS: This study aimed to identify predictors of abnormal CA in pre-LT cardiac assessment and to develop a predictive model to reduce unnecessary CA. From January 2006 to June 2013, 122 patients underwent CA based on the current institutional protocol.
RESULTS: Forty-one (33.6%) patients had abnormal CA. Univariate analysis showed age ≥65 years (P = .001), cryptogenic cirrhosis (P = .046), cardiac comorbidities (P = .027), ischemic heart disease (IHD; P = .002), left ventricular hypertrophy (LVH; P = .004), hypertension (P = .002), diabetes mellitus (P = .017), dyslipidemia (P < .001), metabolic syndrome (P = .003), ≥2 CAD risk factors (P = .001), and high Framingham risk score (hard CAD risk, P = .018; cardiovascular disease: lipids, P = .002; body mass index, P < .001) to be significant predictors of abnormal CA. A predictive model was developed with the use of multivariable logistic regression and included diabetes, dyslipidemia, IHD, age ≥65 years, and LVH, achieving a specificity of 55.1% and sensitivity of 90.0%. This would reduce unnecessary CA by up to one-half in our study population (from 81 to 35) while maintaining a false negative rate of only 8.5%.
CONCLUSIONS: Diabetes, dyslipidemia, IHD, age ≥65 years, and LVH appear to be predictors of abnormal CA in pre-LT patients. Our predictive model may help to better select patients for CA, although further validation is required.

PMID: 28923628 [PubMed - in process]

Subcutaneous infection by Graphium basitruncatum in a heart transplant patient.

Wed, 09/20/2017 - 12:45
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Subcutaneous infection by Graphium basitruncatum in a heart transplant patient.

Braz J Infect Dis. 2017 Sep 15;:

Authors: Fernández AL, Andres PO, Veciño CH, Nagel CB, Mujica MT

Abstract
Graphium basitruncatum, a synanamorph of Pseudoallescheria has been rarely reported in human infections. We report a case of subcutaneous phaeohyphomycosis caused by this fungus in a heart transplant recipient. We also describe the phenotypic, molecular methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) used to achieve isolate identification.

PMID: 28923505 [PubMed - as supplied by publisher]

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial.

Wed, 09/20/2017 - 12:45
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A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial.

Lancet Respir Med. 2017 Sep 08;:

Authors: Birring SS, Wijsenbeek MS, Agrawal S, van den Berg JWK, Stone H, Maher TM, Tutuncu A, Morice AH

Abstract
BACKGROUND: Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied.
METHODS: This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants.
FINDINGS: Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48-0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78-2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported.
INTERPRETATION: This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation.
FUNDING: Patara Pharma.

PMID: 28923239 [PubMed - as supplied by publisher]

A randomized comparison of flow characteristics of semiskeletonized and pedicled internal thoracic artery preparations in coronary artery bypass.

Wed, 09/20/2017 - 12:45
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A randomized comparison of flow characteristics of semiskeletonized and pedicled internal thoracic artery preparations in coronary artery bypass.

J Cardiothorac Surg. 2017 May 16;12(1):28

Authors: Satdhabudha O, Noppawinyoowong N

Abstract
BACKGROUND: Harvesting the internal thoracic artery (ITA) with semiskeletonization is an alternative technique between conventional wide pedicle and skeletonization. It is almost as simple as pedicle harvesting; however, it is supposed to provide the advantage of graft flow and length. Since the heart is unique being the only organ which is perfused during diastole, for comparing the intraoperative graft flow characteristics of semiskeletonization and pedicle technique, we used diastolic filling (DF) using transit-time flow measurement as a primary result. The objective of this study is to compare if semiskeletonized ITA has a greater effect on the intraoperative DF of graft flow versus conventional pedicled ITA in coronary artery bypass.
METHODS: Between July 2015 and May 2016, a prospective evaluation of 60 consecutive patients undergoing coronary artery bypass grafting for left anterior descending artery revascularization were randomized to having semiskeletonized (n = 30) or conventional pedicled (n = 30) ITA graft harvested by the same surgeon. Intraoperative transit-time flows were obtained. The DF of the ITA graft at the end of operation was evaluated in two groups.
RESULTS: The intraoperative DF was significantly greater in the semiskeletonized grafts than in the pedicled grafts (70.50 ± 14.15 versus 57.6 ± 19.39%; p = 0.005). No statistical difference was observed comparing quantitative pulsatile flow and pulsatile index at the end of the operation in the two groups. However, the free flow of the conduit during the cardiopulmonary bypass before the anastomosis performed was greater in semiskeletonized group than in pedicled group (94 ± 48.37 versus 56.35 ± 34.90 ml/min; p = 0.003). The total operative time was comparable between two groups (p = 0.092).
CONCLUSIONS: Semiskeletonized ITA resulted in superior DF of left anterior descending bypass graft flow as compared with pedicled ITA. It is also provide a greater free flow and length of the graft without the long-delayed operative time.
TRIAL REGISTRATION: Trial registration number (Study ID): TCTR20160913002 Date of registration: September 10, 2016.

PMID: 28511656 [PubMed - indexed for MEDLINE]

Redo coronary bypass grafting for congenital left main coronary atresia: a case report.

Wed, 09/20/2017 - 12:45
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Redo coronary bypass grafting for congenital left main coronary atresia: a case report.

J Cardiothorac Surg. 2017 May 15;12(1):26

Authors: Yajima S, Toda K, Nishi H, Yoshioka D, Nakamura T, Miyagawa S, Yoshikawa Y, Fukushima S, Sawa Y

Abstract
BACKGROUND: Congenital left main coronary atresia is an extremely rare coronary anomaly. Long-term surgical outcomes and the optimal management strategies for recurrence of ischemia remain uncertain. Herein, we present a case involving successful redo coronary artery bypass grafting for unstable angina 27 years after the initial coronary artery bypass grafting for congenital left main coronary atresia.
CASE PRESENTATION: A 33-year-old woman was referred to our department with unstable angina. At the age of 6, she had undergone coronary artery bypass grafting of the second diagonal branch using the left internal thoracic artery and the obtuse marginal branch using saphenous vein grafting for left main coronary atresia. Although a coronary angiogram showed a patent left internal thoracic artery graft to the second diagonal branch and a patent saphenous vein graft to the obtuse marginal branch, the left anterior descending artery was not being perfused by the grafts because of a disruption of blood flow to the left anterior descending artery from the left internal thoracic artery. Therefore, we performed a redo coronary artery bypass grafting using the in situ right internal thoracic artery to the first diagonal branch, which was to be connected to the left anterior descending artery, resulting in amelioration of the ischemia of the left anterior wall. The patient was discharged 10 days after the operation and has been in good health for over 3 years without recurrence of chest symptoms.
CONCLUSIONS: Coronary revascularization using a saphenous vein and left internal thoracic artery grafts is effective in achieving an adequate blood supply to the distal coronary arteries, and this effect can last for decades. However, careful follow-up is necessary because recurrent myocardial ischemia due to the development of a coronary artery occlusion may occur in adulthood.

PMID: 28506276 [PubMed - indexed for MEDLINE]

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report.

Wed, 09/20/2017 - 12:45
Related Articles

Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report.

Cancer Immunol Immunother. 2017 Jan;66(1):45-50

Authors: Owonikoko TK, Kumar M, Yang S, Kamphorst AO, Pillai RN, Akondy R, Nautiyal V, Chatwal MS, Book WM, Sahu A, Sica GL, Ahmed R, Ramalingam SS

Abstract
INTRODUCTION: The increased availability of immunotherapeutic agents for the treatment of a wide array of cancer in the general oncology practice setting will reveal rare and unique toxicities.
MATERIALS AND METHODS: The mechanism of cardiac allograft rejection in the context of PD-1 antibody therapy was explored in a patient with cutaneous squamous cell cancer complicating long-standing cardiac allograft. Immune cell infiltrate in the myocardium and peripheral blood lymphocyte repertoire were assessed using myocardial biopsy and temporal analysis of peripheral blood samples. The efficacy of high-intensity immunosuppression to reverse graft rejection was explored.
RESULTS: Endomyocardial biopsy showed acute moderate diffuse cellular rejection with a predominant population of CD3+, CD8+ and CD4+ infiltrating lymphocytes; peripheral blood circulating lymphocytes showed a high frequency of proliferating and activated CD8+ T cells expressing PD-1 compared to a normal control. There was no difference in the activation and proliferation of CD4+ T cells compared to a normal control. Cardiac function improved following high-intensity immunosuppression and patient survived for up to 7 months after discontinuation of nivolumab.
CONCLUSIONS: Immune checkpoint inhibitors should be avoided in allograft recipients but high-intensity immunosuppression is effective to salvage allograft rejection induced by these agents.

PMID: 27771741 [PubMed - indexed for MEDLINE]

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