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Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.

Wed, 10/11/2017 - 12:45

Routine C4d immunohistochemistry in cardiac allografts: Long-term outcomes.

J Heart Lung Transplant. 2017 Sep 14;:

Authors: Husain AN, Mirza KM, Fedson SE

Abstract
BACKGROUND: In the past decade, C4d has emerged as a potential marker for antibody-mediated rejection (AMR); however, evidence on its use as a prognostic tool has been controversial. Although the International Society for Heart and Lung Transplantation guideline recommends early routine surveillance of C4d in heart transplantation, there is no consensus on its value in the pathologic assessment of AMR. Herein we present a correlation analysis of C4d immunoreactivity in endomyocardial biopsies with clinical cardiac dysfunction, cellular rejection, human leukocyte antigen (HLA) status, cardiac allograft vasculopathy (CAV) and death.
METHODS: A total of 5,840 endomyocardial biopsies from 296 heart transplant recipients (January 2004 to December 2014) were stained prospectively for C4d. Strong, diffuse endothelial staining was considered positive. All patients had at least 1 year of follow-up. Positive C4d staining was present in 53 biopsies from 28 patients. Sixteen of 28 patients had clinically significant cardiac dysfunction at the time of positive biopsy. In C4d-positive patients, the mean panel-reactive antibody (PRA) level was 33%. Ten patients demonstrated a first C4d positivity within the first year post-transplant, whereas 18 patients had C4d positivity after 1 year post-transplant. At autopsy, all 11 C4d-positive patients examined demonstrated cardiac allograft vasculopathy (CAV) as the underlying cause of death. In contrast, only 2 of 8 (25%) C4d-negative patients had CAV at autopsy. In the surviving cohort, there was an angiographic diagnosis of higher-than-moderate CAV in 10 patients (3.8%).
RESULTS: C4d-positive patients contributed to 67% of the overall institutional mortality in heart transplant recipients. Late C4d positivity (>1 year post-transplant) demonstrated an even higher risk for developing CAV and poor prognosis than early C4d positivity (within 1 year). In the C4d-negative group with postmortem examination, 75% (6 of 8) deaths were due to non-cardiac causes.
CONCLUSIONS: Our findings show a positive association of C4d with CAV and death. We identified a prognostic role for C4d in heart transplantation warranting routine long-term detection of this marker in the pathologic evaluation of cardiac AMR.

PMID: 28988608 [PubMed - as supplied by publisher]

Clinical impact of intrapulmonary vascular dilatation in liver transplant candidates.

Wed, 10/11/2017 - 12:45

Clinical impact of intrapulmonary vascular dilatation in liver transplant candidates.

Chest. 2017 Oct 05;:

Authors: DuBrock HM, Krowka MJ, Forde KA, Krok K, Patel M, Sharkoski T, Sprys M, Lin G, Oh JK, Mottram CD, Scanlon PD, Fallon MB, Kawut SM

Abstract
BACKGROUND: Intrapulmonary vascular dilatations (IPVD) are frequently detected in patients with liver disease by the delayed appearance of microbubbles on contrast-enhanced echocardiography. IPVD with an elevated alveolar-arterial (A-a) gradient define hepatopulmonary syndrome, however the importance of IPVD in the absence of abnormal gas exchange is unknown. We aimed to determine the clinical impact of IPVD in patients with liver disease.
METHODS: We performed a cross-sectional study within the Pulmonary Vascular Complications of Liver Disease (PVCLD2) Study, a multicenter prospective cohort study of patients being evaluated for liver transplantation. We excluded patients with obstructive or restrictive lung disease, hepatopulmonary syndrome (HPS), or intracardiac shunting. Patients with and without IPVD were compared.
RESULTS: Forty-six patients with IPVD and 81 patients without IPVD were included. Patients with IPVD were more likely to have autoimmune hepatitis and less likely to have cryptogenic cirrhosis and hepatocellular carcinoma. Patients with IPVD had higher Child-Pugh scores (6 [IQR 5-7] vs 5 [IQR 4-7], P=0.04), possibly higher MELD scores (14.5 [IQR 11.6-15.8] vs 12.1 [IQR 9.4-15.0], P=0.06), a higher partial pressure of oxygen in arterial blood (PaO2) (97.9 [IQR 92.0-103.0] mmHg vs 89.0 [IQR 82.0-96.9] mmHg, P<0.001) and lower A-a gradient (9.9 [IQR 6.2-13.5] mmHg vs 14.9 [IQR 9.0-21.8] mmHg, P<0.001). Symptoms and quality of life were similar between the groups.
CONCLUSIONS: Autoimmune hepatitis and increased liver disease severity are associated with the presence of IPVD, which is characterized by higher PaO2. Future studies to better characterize IPVD pathogenesis and the relationship of IPVD to HPS are warranted.

PMID: 28987478 [PubMed - as supplied by publisher]

PPARGC1A is upregulated and facilitates lung cancer metastasis.

Wed, 10/11/2017 - 12:45
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PPARGC1A is upregulated and facilitates lung cancer metastasis.

Exp Cell Res. 2017 Oct 15;359(2):356-360

Authors: Li JD, Feng QC, Qi Y, Cui G, Zhao S

Abstract
Lung cancer remains a leading cause of cancer-related mortality, with metastatic progression remaining the single largest cause of lung cancer mortality. Hence it is imperative to determine reliable biomarkers for lung cancer prognosis. We performed quantitative real-time PCR (qRT-PCR) analysis to explore epithelial-mesenchymal transition (EMT) inducers that regulate EMT process in three patients with advanced lung cancer disease. Peroxisome proliferator-activated receptor gamma (PPARGC1A) was uniformly the topmost overexpressed gene in all three human non-small cell lung cancer (NSCLC) patient samples. Further evaluation in human normal lung and metastatic lung cancer cell lines revealed that the expression of PPARGC1A was upregulated in metastatic lung cancer cell lines. Metagenomic analysis revealed direct correlation among PPARGC1A, zinc-finger transcription factor snail homolog 1 (SNAI1), and metastatic lung disease. Upregulation of PPARGC1A transcript expression was independent of a differential upregulation of the upstream AMP-dependent protein kinase (AMPK) activation or steady state expression of the silent mating type information regulation 2 homolog 1 (SIRT1). Xenograft tail vein colonization assays proved that the high expression of PPARGC1A was a prerequisite for metastatic progression of lung cancer to brain. Our results indicate that PPARGC1A might be a potential biomarker for lung cancer prognosis.

PMID: 28803067 [PubMed - indexed for MEDLINE]

Molecular, cellular and pharmacological effects of platinum(II) diiodido complexes containing 9-deazahypoxanthine derivatives: A group of broad-spectrum anticancer active agents.

Wed, 10/11/2017 - 12:45
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Molecular, cellular and pharmacological effects of platinum(II) diiodido complexes containing 9-deazahypoxanthine derivatives: A group of broad-spectrum anticancer active agents.

J Photochem Photobiol B. 2017 Aug;173:423-433

Authors: Vančo J, Trávníček Z, Křikavová R, Gáliková J, Dvořák Z, Chalupová M

Abstract
The platinum(II) iodido complexes 1-5 of the general formula cis-[PtI2(Ln)2], where Ln stands for O-substituted 9-deazahypoxanthine derivatives, were prepared and thoroughly characterized by various techniques, including multinuclear 1D and 2D NMR spectroscopy. The complexes were screened for their anticancer potential in vitro on ten human cancer cell lines, concretely breast adenocarcinoma (MCF7), osteosarcoma (HOS), lung carcinoma (A549), cervix epithelioid carcinoma (HeLa), malignant melanoma (G-361), prostate carcinoma (22Rv1, PC-3), hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780) and cisplatin-resistant ovarian carcinoma (A2780R). The complexes exhibited significant wide-spectrum anticancer activity in vitro against all the employed cell lines, with IC50≈0.5-24.0μM. Very good correlation between the lipophilicity parameter log P and IC50 values of anticancer activity in vitro were obtained by simple QSAR analysis. The most lipophilic complexes 2, 4 and 5 showed the best results, as they reached the sub-micromolar IC50 values against the A2780 and A2780R sub-lines, with the best result equal 0.5±0.1μM on A2780 for complex 5. The in vivo testing of the representative complexes 1, 4 and 5 (applied at the same dose of Pt as 2mg/kg dose of cisplatin) on a L1210 leukaemia model revealed their positive effect on the prolongation of the mean survival time, even if it was lower than that of cisplatin. The (1)H NMR interaction study revealed the ability of complexes to interact with glutathione (GSH) and 5'-guanosine monophosphate (GMP) and overall higher stability of the complexes 1-5 as compared to cisplatin. The electrospray-ionization mass spectrometry experiments with complex 1 identified the formation of a rich collection of hydrolytic species in water-containing media after 24h and the interaction intermediates with sulfur-containing biomolecule l-cysteine, but not with the reduced glutathione at physiologically relevant concentration levels.

PMID: 28662469 [PubMed - indexed for MEDLINE]

American Society of Anesthesiologists Classification Versus ARISCAT Risk Index: Predicting Pulmonary Complications Following Renal Transplant.

Wed, 10/11/2017 - 12:45
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American Society of Anesthesiologists Classification Versus ARISCAT Risk Index: Predicting Pulmonary Complications Following Renal Transplant.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):208-213

Authors: Kupeli E, Er Dedekarginoglu B, Ulubay G, Oner Eyuboglu F, Haberal M

Abstract
OBJECTIVES: Patients with chronic renal failure are prone to pulmonary complications. Renal transplant recipients should undergo complete preoperative evaluation to determine risk of postoperative pulmonary complications. The American Society of Anesthesiologists classification and the Assess Respiratory Risk in Surgical Patients in Catalonia risk index correlate well with incidence of postoperative pulmonary complications. Here, we compared their accuracy in predicting pulmonary complications following renal transplant.
MATERIALS AND METHODS: We retrospectively reviewed medical records of renal transplant recipients between years 2004 and 2015. We collected patient data on Assess Respiratory Risk in Surgical Patients in Catalonia risk index, including demographics, smoking history, comorbidities, preoperative pulmonary risk score, laboratory results, surgery information, history of lower respiratory tract infection 1 month pretransplant, urgency of surgery, American Society of Anesthesiologists classification, and pulmonary complications within 1 month posttransplant.
RESULTS: Of 172 patients (123 males; mean age 38.82 y), 22 (12.8%) developed pulmonary complication during the first month posttransplant, including effusion (9 patients), pneumonia (10 patients), respiratory inefficiency (2 patients), and pulmonary embolism (1 patient). Atelectasis was observed in 95.4% of patients with complications. A positive correlation was observed between age and development of complications (r = 0.171; P = .025). Regarding risk score, 75% of patients at high risk and 19.5% at intermediate risk developed pulmonary complications. Patients with low-risk scores had significantly lower complications than intermediate- and high-risk groups (P < .001). A positive correlation was observed between preoperative risk score and complications (r = 0.34; P < .001). There was no association between the American Society of Anesthesiologists scores and postoperative complications (P = .7).
CONCLUSIONS: The American Society of Anesthesiologists classification was found to be a weaker modality to predict pulmonary complications after renal transplant; as it relates to the general health status, than the Assess Respiratory Risk in Surgical Patients in Catalonia risk index.

PMID: 28260470 [PubMed - indexed for MEDLINE]

Sirolimus-Induced Combined Posterior Reversible Encephalopathy Syndrome and Lymphocytic Pneumonitis in a Renal Transplant Recipient: Case Report and Review of the Literature.

Wed, 10/11/2017 - 12:45
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Sirolimus-Induced Combined Posterior Reversible Encephalopathy Syndrome and Lymphocytic Pneumonitis in a Renal Transplant Recipient: Case Report and Review of the Literature.

Exp Clin Transplant. 2017 Feb;15(Suppl 1):170-174

Authors: Gheith O, Cerna M, Halim MA, Nampoory N, Al-Otaibi T, Nair P, Said T, Atteya HA, Katchy K

Abstract
The mammalian target of rapamycin inhibitor sirolimus was introduced into clinical transplant practice in 1999. Dose-related myelosuppression and hyper lipidemia are the most common adverse effects. Pulmonary toxicity has been reported since 2004 and can cause interstitial pneumonitis, organizing pneumonia, and alveolar hemorrhage. Moreover, it can occasionally induce posterior reversible encephalopathy syndrome, as documented in scarce reports. To our knowledge; this is the 1st report of combined posterior reversible encephalopathy syndrome and lymphocytic pneumonitis to be induced by sirolimus. Here, we present a renal transplant recipient with reversible sirolimus-induced brain lesions who was diagnosed after exclusion of infections (viral, bacterial, and fungal), tumors, sarcoidosis, and autoimmune disorders. Both brain lesions and pneumonitis resolved completely after sirolimus discontinuation with excellent patient and graft outcome. Early and gradual sirolimus withdrawal can reverse posterior reversible encephalopathy syndrome and lymphocytic pneumonitis with preservation of stable graft function.

PMID: 28260460 [PubMed - indexed for MEDLINE]

Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics.

Wed, 10/11/2017 - 12:45
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Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics.

BMC Cancer. 2016 Aug 08;16:614

Authors: Chen W, Allen SG, Reka AK, Qian W, Han S, Zhao J, Bao L, Keshamouni VG, Merajver SD, Fu J

Abstract
BACKGROUND: Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the majority of current CTC capture methods rely on positive selection techniques that require a priori knowledge about the surface protein expression of disseminated CTCs, which are known to be a dynamic population.
METHODS: We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for capturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer cells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on the physical size or surface protein expression of CTCs.
RESULTS: The microfluidic CTC capture chip was able to achieve a superior capture yield for both epithelial cell adhesion molecule positive (EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic CTC chip captured CTCs undergoing transforming growth factor beta-induced epithelial-to-mesenchymal transition (TGF-β-induced EMT) with dynamically down-regulated EpCAM expression. In a mouse model of human breast cancer using EpCAM positive and negative cell lines, the number of CTCs captured correlated positively with the size of the primary tumor and was independent of their EpCAM expression. Furthermore, in a syngeneic mouse model of lung cancer using cell lines with differential metastasis capability, CTCs were captured from all mice with detectable primary tumors independent of the cell lines' metastatic ability.
CONCLUSIONS: The microfluidic CTC capture chip using a novel nanoroughened glass substrate is broadly applicable to capturing heterogeneous CTC populations of clinical interest independent of their surface marker expression and metastatic propensity. We were able to capture CTCs from a non-metastatic lung cancer model, demonstrating the potential of the chip to collect the entirety of CTC populations including subgroups of distinct biological and phenotypical properties. Further exploration of the biological potential of metastatic and presumably non-metastatic CTCs captured using the microfluidic chip will yield insights into their relevant differences and their effects on tumor progression and cancer outcomes.

PMID: 27501846 [PubMed - indexed for MEDLINE]

A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study.

Sun, 10/08/2017 - 12:45

A bioprosthetic total artificial heart for end-stage heart failure: Results from a pilot study.

J Heart Lung Transplant. 2017 Sep 14;:

Authors: Latrémouille C, Carpentier A, Leprince P, Roussel JC, Cholley B, Boissier E, Epailly E, Capel A, Jansen P, Smadja DM

Abstract
BACKGROUND: The electro-hydraulically actuated Carmat total artificial heart (C-TAH) is designed to replace the heart in patients with end-stage heart failure, either as bridge to transplant or destination therapy. It provides pulsatile flow and contains bio-prosthetic blood contacting materials. A clinical feasibility study was conducted to evaluate the C-TAH safety and performance.
METHODS: Hospitalized patients, at imminent risk of death from irreversible biventricular failure despite optimal medical management, and not eligible for transplant or eligible but on extracorporeal life support, were enrolled. The primary endpoint was 30-days survival.
RESULTS: Four patients were implanted with the C-TAH, three as destination therapy (ages 76, 68, 74) and one as bridge to transplant (age 58). They had implant times of 74, 270, 254 and 20 days respectively. All patients were free from hemolysis, clinical neurologic events, clinical evidence of thrombus and device-related infections. Hemodynamic and physical recovery allowed two patients to be discharged home for a cumulative duration of 7 months. The anticoagulation management strategy comprised initial unfractionated heparin, from postoperative day 2, followed by low molecular weight heparin and aspirin. An increased D-dimer level was observed in all patients during months 1 to 4. Temporary suspension of heparin anticoagulation resulted in thrombocytopenia and increased fibrin monomer, reversed by resuming anticoagulation with heparin. Causes of death were device-related (2 cases), respiratory failure and multi-organ failure.
CONCLUSIONS: Preliminary clinical results with the C-TAH demonstrated good safety and performance profiles in patients suffering from biventricular failure, which need to be confirmed in a pivotal study.

PMID: 28986001 [PubMed - as supplied by publisher]

Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation.

Sun, 10/08/2017 - 12:45

Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation.

J Surg Res. 2017 Oct;218:341-347

Authors: Yamada Y, Iskender I, Arni S, Hillinger S, Cosgun T, Yu K, Jungraithmayr W, Cesarovic N, Weder W, Inci I

Abstract
BACKGROUND: We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation.
METHODS: Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed.
RESULTS: There was a trend toward better oxygenation throughout reperfusion period in the treatment group, which was accompanied by inhibited inflammatory response related to reduction in myeloperoxidase activity during EVLP and nuclear factor-κB activation at the end of reperfusion.
CONCLUSIONS: Ex vivo treatment of donor lungs with inhaled NAC reduced inflammatory response via its antioxidant activity in experimental porcine lung transplantation.

PMID: 28985871 [PubMed - in process]

Early declaration of death by neurologic criteria results in greater organ donor potential.

Sun, 10/08/2017 - 12:45

Early declaration of death by neurologic criteria results in greater organ donor potential.

J Surg Res. 2017 Oct;218:29-34

Authors: Resnick S, Seamon MJ, Holena D, Pascual J, Reilly PM, Martin ND

Abstract
BACKGROUND: Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation.
METHODS: Using data over a 5-year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs [2], kidneys [2], liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t-test.
RESULTS: Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (±16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates.
CONCLUSIONS: A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed.

PMID: 28985863 [PubMed - in process]

Escalation of extracorporeal life support as a bridge to lung transplantation in end-stage lung disease.

Sun, 10/08/2017 - 12:45

Escalation of extracorporeal life support as a bridge to lung transplantation in end-stage lung disease.

Perfusion. 2017 Oct;32(7):606-608

Authors: Mohite PN, Rosenberg A, Caballero CH, Soresi S, Fatullayev J, Reed A, Popov AF, Sabashnikov A, Simon AR

Abstract
Extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplant (LTx) is not uncommon, but it is not commonplace yet. We present a case of a 45-year-old man with cystic fibrosis with recent deterioration in lung function who was initially supported with veno-venous (VV) ECMO. However, he subsequently required conversion to veno-veno-arterial (VVA) ECMO. After 21 days of support, he underwent double lung transplantation, with an uneventful postoperative course. This case shows that, in patients with end-stage respiratory failure awaiting lung transplantation, extracorporeal life support may require escalation to improve gas exchange and address circulatory requirements.

PMID: 28985703 [PubMed - in process]

Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient.

Sat, 10/07/2017 - 12:45

Hepatic Sinusoidal-obstruction Syndrome and Busulfan-induced Lung Injury in a Post-autologous Stem Cell Transplant Recipient.

Indian Pediatr. 2017 Sep 15;54(9):765-770

Authors: Jain R, Gupta K, Bhatia A, Bansal A, Bansal D

Abstract
Veno-occlusive disease of the liver is mostly encountered as a complication of hematopoietic stem cell transplantation with myeloablative regimens with an incidence estimated to be 13.7%. It is clinically characterized by tender hepatomegaly, jaundice, weight gain and ascites. Strong clinical suspicion and an early recognition of clinical signs are essential to establish the diagnosis and institute effective regimen. Another complication of cytotoxic drugs given for cancers, is development of busulfan-induced lung injury. A strong index of suspicion is needed for its diagnosis, especially in setting where opportunistic fungal and viral infections manifest similarly. We illustrate the clinical and autopsy finings in a 2½-year-old boy who received autologous stem-cell transplantation following resection of stage IV neuroblastoma. He subsequently developed both hepatic veno-occlusive disease and busulfan-induced lung injury. The autopsy findings are remarkable for their rarity.

PMID: 28984258 [PubMed - in process]

Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study.

Sat, 10/07/2017 - 12:45

Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study.

Hepatol Int. 2017 Oct 05;:

Authors: Heo J, Noh OK, Oh YT, Chun M, Kim L

Abstract
PURPOSE: The aim of this study is to evaluate prevalence of second primary cancer (SPC) among hepatocellular carcinoma (HCC) patients after liver transplantation (LT) by using nationwide claims data from South Korea.
MATERIALS AND METHODS: The nationwide cohort included patients who were diagnosed with HCC and received LT from 1 January 2010 to 31 December 2014. We analyzed frequency and standardized incidence ratios (SIRs) to estimate the risk of SPC in HCC patients after LT.
RESULTS: A total of 2462 patients who were diagnosed with HCC and received LT were confirmed. Of these patients, 103 (4.2%) developed SPC after LT; the most common cancer site was lung (16.5%). Patients with HCC receiving LT had high risk of SPC [SIR 2.79, 95% confidence interval (CI) 2.27-3.38], particularly lymphoma (SIR 9.26), myeloma (SIR 10.60), and bladder cancer (SIR 7.19). The 12-, 24-, 36-, and 48-month overall survival for patients with HCC after LT was 92.7, 87.8, 84.6, and 82.1%, respectively.
CONCLUSIONS: HCC patients with LT had longer life expectancy and higher risk for SPC compared with the general population. Therefore, close surveillance for SPC is important in patients with HCC receiving LT.

PMID: 28983776 [PubMed - as supplied by publisher]

Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome.

Sat, 10/07/2017 - 12:45

Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome.

Mol Genet Metab Rep. 2017 Dec;13:64-68

Authors: Eisengart JB, Jarnes J, Ahmed A, Nestrasil I, Ziegler R, Delaney K, Shapiro E, Whitley C

Abstract
Mucopolysaccharidosis type I (MPS I) was added to the Recommended Uniform Screening Panel for newborn screening in 2016, highlighting recognition that early treatment of MPS I is critical to stem progressive, irreversible disease manifestations. Enzyme replacement therapy (ERT) is an approved treatment for all MPS I phenotypes, but because the severe form (MPS IH, Hurler syndrome) involves rapid neurocognitive decline, the impermeable blood-brain-barrier is considered an obstacle for ERT. Instead, hematopoietic cell transplantation (HCT) has long been recommended, as it is believed to be the only therapy that arrests neurocognitive decline. Yet ERT monotherapy has never been compared to HCT, because it is unethically unacceptable to evaluate a therapeutic alternative to one shown to treat Central Nervous System (CNS) disease. An unusual opportunity to address this question is presented with this clinical report of a 16-year-old female with MPS IH treated only with ERT since her diagnosis at age 2. Neurological functioning was stable until cervical spinal cord compression at age 8, hydrocephalus at age 11, and neurocognitive declines beginning at age 10. Somatic disease burden is significant for first degree AV block, restrictive lung disease, bilateral hearing loss, severe corneal clouding, joint pain/limitations requiring mobility assistance, and short stature. This patient's extended survival and prolonged intact neurocognitive functioning depart from the untreated natural history of MPS IH. Disease burden typically controlled by HCT emerged. Although not anticipated to provide benefit for CNS disease, ERT may have provided some amelioration or slowing of neurocognitive deterioration.

PMID: 28983455 [PubMed]

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome.

Fri, 10/06/2017 - 12:45

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome.

Atherosclerosis. 2017 Sep 21;266:58-63

Authors: Tolva J, Paakkanen R, Jarva H, Pussinen P, Havulinna AS, Salomaa V, Sinisalo J, Lokki ML

Abstract
BACKGROUND & AIMS: Elevated soluble HLA-DR (sHLA-DR) serum levels have been reported in HLA class II-associated inflammatory disorders. We have previously shown that the HLA class II allele HLA-DRB1*01 may predispose to acute coronary syndromes (ACS). To our knowledge, sHLA-DR serum levels have not been studied in ACS.
METHODS: sHLA-DR serum levels were measured in 477 ACS patients as cases and 475 area- and sex-matched controls by sandwich enzyme-linked immunosorbent assay. Binary logistic regression and ordinal logistic regression analyses adjusted for clinical parameters were conducted to evaluate the associations of sHLA-DR levels.
RESULTS: ACS patients had lower sHLA-DR serum levels compared to controls (OR = 0.837; 95% CI = 0.704-0.994; p = 0.043). After adjustment for smoking status, this association was no longer significant. This was explained by the notion that current smoking was inversely associated with sHLA-DR levels both in cases (OR = 0.592; 95% CI = 0.553-0.908; p = 0.016) and in controls (OR = 0.356; 95% CI = 0.226-0.563; p = 0.000010). A similar effect was not seen with other cardiovascular risk factors.
CONCLUSIONS: The results indicate, for the first time, that lower sHLA-DR levels are associated with smoking, but not with ACS. This is an important finding because previous studies of sHLA-DR have not accounted for the possible associations between smoking and sHLA-DR levels. Further studies are required to confirm these novel results and explore the mechanisms behind the observed associations.

PMID: 28982023 [PubMed - as supplied by publisher]

Initial treatment strategy for patients newly diagnosed with multiple myeloma.

Fri, 10/06/2017 - 12:45

Initial treatment strategy for patients newly diagnosed with multiple myeloma.

Rinsho Ketsueki. 2017;58(10):2050-2057

Authors: Yagi H

Abstract
In Japan, the latest trends in induction therapy for patients newly diagnosed with multiple myeloma are multi-drug combinations, including bortezomib, lenalidomide, and thalidomide. Patients <65 years old and those <70 years old who have normal cardiac and lung functions without any serious complications are good candidates for high-dose L-PAM with autologous stem cell transplantation. For successful stem cell collection, anti-cancer drugs that have a negative impact on stem cell mobilization are usually excluded from induction therapies. It has been reported that bortezomib and thalidomide do not affect mobilization of stem cells; however, extended exposure to lenalidomide may have a potential risk of poor mobilization. Under these circumstances, PAD, VTD, VCD, and RVD are recommended as first induction therapies for transplant-eligible patients. On the other hand, two- or three-drug combinations are effective as induction therapies for transplant-ineligible patients >65-70 years old and <65 years old with serious complications or insufficiencies of cardiac or lung functions as well as for any patients who refuse transplantation strategy. For these patients, VMP, MPT, and Rd are usually recommended. For elderly patients >75 years old, it is important that the dosage of each drug be properly reduced according to the frailty of the patient.

PMID: 28978848 [PubMed - in process]

Treatment strategy for patients with Hodgkin lymphoma.

Fri, 10/06/2017 - 12:45

Treatment strategy for patients with Hodgkin lymphoma.

Rinsho Ketsueki. 2017;58(10):1973-1982

Authors: Yoshida I

Abstract
Although Hodgkin lymphoma is a disease with a low incidence rate, there is a significant social resources perspective associated with this disease to ensure that adolescents and young adults are adequately treated and receive social reintegration. Consequently, Hodgkin lymphoma is considered an important disease in the field of oncology. Combined modality therapy, which combines chemotherapy and radiotherapy, has resulted in cure rates of more than 80% in patients with early stages of this disease, although long-term sequelae remain a problem. Response-adapted therapy using FDG-PET is being studied as a treatment strategy in an attempt to attenuate treatment to reduce toxicity in interim-PET negative cases and to enhance therapeutic intensity for interim-PET positive cases. In addition, brentuximab vedotin, which targets CD30 and anti-PD-1 antibodies, which represent immune checkpoint inhibitors, is effective even when treatment resistance develops after autologous transplantation. Both high cure rates and toxicity control are essential targets for treatment modalities of Hodgkin lymphoma. Long-term follow-up of secondary malignancy and heart and lung failure should be incorporated into such treatment strategies. In this review, I explore comprehensive treatment strategies for Hodgkin lymphoma in the early stage with both favorable and unfavorable prognosis, in the advanced stage, and relapsed or refractory disease.

PMID: 28978839 [PubMed - in process]

Strategies to manage costs in idiopathic pulmonary fibrosis.

Fri, 10/06/2017 - 12:45

Strategies to manage costs in idiopathic pulmonary fibrosis.

Am J Manag Care. 2017 Jul;23(11 Suppl):S191-S196

Authors: Owens GM

Abstract
Idiopathic pulmonary fibrosis (IPF) is a diagnostically challenging disease. Clinicians are faced with the need to exclude alternative diagnoses, limited treatment and management guidelines, and few treatment options. Patients with IPF have significantly increased healthcare usage compared with similar patients without the disease. Medicare estimates for this disease are as high as $3 billion, not including cost of treatment. The disease, characterized by worsening dyspnea, declining lung function, nonspecific respiratory symptoms, and a varied clinical course randomly punctuated by episodes of acute exacerbations, is also accompanied by a host of comorbid conditions that contribute significantly to increased healthcare usage and cost. The comorbidities, which increase impairment and disability, and compromise patient quality of life and survival, include pulmonary and cardiac conditions, sleep apnea, gastroesophageal reflux disease, depression and anxiety, and lung cancer. Until recently, palliative care and lung transplant were the only options for management of IPF. Without a lung transplant, the median survival was estimated at 3 to 5 years from the initial diagnosis. Newer treatments, pirfenidone and nintedanib, demonstrate a modest effect on slowing decline in lung function in patients with IPF. Both were approved for the treatment of IPF in 2014. As potentially effective therapies emerge, attention should be given to healthcare resource usage and healthcare processes that ensure patient-centered management with sustainable, cost-effective, and quality care. As such, it is imperative that a structured, comprehensive, multidisciplinary management approach is used in the treatment and management of IPF and its associated comorbidities to limit costs and provide effective and quality healthcare.

PMID: 28978214 [PubMed - in process]

Evaluating new treatment options.

Fri, 10/06/2017 - 12:45

Evaluating new treatment options.

Am J Manag Care. 2017 Jul;23(11 Suppl):S183-S190

Authors: Nathan SD

Abstract
Idiopathic pulmonary fibrosis (IPF) is the most prevalent type of idiopathic interstitial pneumonia, accounting for at least half of all diagnosed cases. Because it lacks a cure, the goal of treatment for IPF is to stabilize or reduce the rate of disease progression. Nonpharmacologic treatment options for IPF consist of long-term oxygen treatment, lung transplantation, and pulmonary rehabilitation. In the past, pharmacologic therapies for IPF included anticoagulants and anti-inflammatory or immunosuppressive agents. However, in late 2014, 2 therapies were approved by the US FDA for use in IPF: nintedanib and pirfenidone. While treatment of IPF was previously significantly impeded by a lack of effective agents and a paucity of clinical trial data on which to base guideline recommendations, these new agents provide notable breakthroughs in management of IPF, and continued research may break further, new fertile ground for management.

PMID: 28978213 [PubMed - in process]

Overview of idiopathic pulmonary fibrosis (IPF) and evidence-based guidelines.

Fri, 10/06/2017 - 12:45

Overview of idiopathic pulmonary fibrosis (IPF) and evidence-based guidelines.

Am J Manag Care. 2017 Jul;23(11 Suppl):S176-S182

Authors: Sharif R

Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of interstitial lung disease (ILD), characterized by fibrosis and worsening lung function, that primarily occurs in those 50 years and older. Various causes including genetic susceptibility, environmental risk factors, and exposures have been suggested in the literature. All of these cause repetitive micro-injury to the lung tissue and vasculature, which triggers a cascade of inflammatory response and fibrosis. Symptoms are nonspecific and most patients present several years after the initial radiographic changes occur. Diagnosis requires a high index of clinical suspicion supported by distinct radiographic and/or histopathologic findings. Median survival is estimated at between 2 and 3 years after diagnosis. Other than lung transplantation, no treatment has shown survival benefit. Two most recently approved medications for IPF, pirfenidone and nintedanib, can slow disease progression. Most patients have several comorbid conditions that can affect the course of their disease, including gastroesophageal reflux disease, obstructive sleep apnea, cardiomyopathy, and pulmonary hypertension. Observational studies suggested possible benefits in transplant-free survival and patients' outcomes with these medications. In addition to the new treatment options and optimal management of the comorbidities in patients with IPF, pulmonary rehabilitation remains a critical part of management and has been shown to improve quality of life and functional level. Considering the complexity of the diagnosis and management, the American Thoracic Society and European Respiratory Society published a joint statement on diagnosis and treatment of IPF. This article provides an overview of the epidemiology, pathophysiology, and guideline-recommended approaches for the diagnosis and management of IPF.

PMID: 28978212 [PubMed - in process]

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