bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver stiffness measurement using acoustic radiation force impulse elastography in hepatitis C virus‐infected patients with a sustained virological response
Authors: Tachi Y. , Hirai T. , Kojima Y. , Miyata A. , Ohara K. , Ishizu Y. , Honda T. , Kuzuya T. , Hayashi K. , Ishigami M. , Goto H. 
Published: June 2016

SummaryBackgroundAcoustic radiation force impulse (ARFI) elastography is a non‐invasive method for measuring liver stiffness. However, there are no reports evaluating the value of ARFI elastography for liver fibrosis in chronic hepatitis C patients with a sustained virological response (SVR).AimTo investigate the diagnostic performance of ARFI elastography for the assessment of liver fibrosis in hepatitis C virus (HCV) infected patients with an SVR.MethodsIn this prospective study, we enrolled 336 patients: 121 HCV patients with an SVR (44.6% women) and 215 patients with HCV (47.9% women). ARFI elastography measurements of all patients were performed on the same day of liver biopsy.ResultsThe diagnostic accuracies, expressed as areas under the receiver operating characteristic curves for ARFI elastography, in HCV patients with an SVR and those in patients with HCV were 0.818 and 0.875 for the diagnosis of significant fibrosis (≥F2), 0.909 and 0.888 for the diagnosis of severe fibrosis (≥F3), and 0.981 and 0.890 for the diagnosis of liver cirrhosis (F4), respectively. The optimum cut‐off values for ARFI elastography were 1.26 m/s for ≥F2, 1.31 m/s for ≥F3 and 1.49 m/s for F4 in HCV patients with an SVR. The liver stiffness values were lower in patients with SVR compared with those in patients with HCV at the same stage of fibrosis. The liver stiffness values were affected by the necroinflammatory activity and the time after SVR.ConclusionAcoustic radiation force impulse elastography is an acceptable method for predicting the severity of fibrosis in patients with hepatitis C virus and a sustained viral response.
Comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin vs. ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin in 6961 genotype 1 patients treated in routine medical practice
Authors: Backus L. I. , Belperio P. S. , Shahoumian T. A. , Loomis T. P. , Mole L. A. 
Published: June 2016

SummaryBackgroundReal‐world data are needed to inform hepatitis C virus (HCV) treatment decisions.AimTo assess the comparative effectiveness of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) vs. ombitasvir/paritaprevir/ritonavir + dasabuvir (OPrD) ± RBV in genotype 1 HCV patients treated in routine medical practice.MethodsObservational intent‐to‐treat cohort of genotype 1 patients initiating 8 or 12 weeks of LDV/SOF ± RBV or 12 weeks of OPrD ± RBV. Sustained virological response (SVR) required RNA below the limit of quantification at least 10 weeks after end of treatment.Results6961 patients initiated LDV/SOF (N = 4478), LDV/SOF + RBV (N = 1269), OPrD (N = 297), and OPrD + RBV (N = 917) at 126 facilities. Intention‐to‐treat SVR rates were 91.4% (3813/4170) for LDV/SOF, 90.0% (1098/1220) for LDV/SOF + RBV, 95.1% (269/283) for OPrD and 85.8% (746/869) for OPrD + RBV. SVR rates in those completing 8 weeks of LDV/SOF were 91.7% (1223/1333) and 12 weeks of LDV/SOF 94.6% (2475/2615), LDV/SOF + RBV 92.2% (1033/1120), OPrD 98.0% (248/253) and OPrD + RBV 95.5% (705/738). Significant predictors of SVR were African American race (OR 0.71, 95%CI 0.59–0.86, P < 0.001), body mass index (BMI) > 30 kg/m2 (OR 0.73, 95% CI 0.60–0.89, P = 0.002), FIB4 > 3.25 (OR 0.60, 95% CI 0.49–0.72, P < 0.001), OPrD + RBV compared to LDV/SOF (OR 0.60, 95% CI 0.48–0.76, P < 0.001) and subtype 1b (OR 1.38, 95% CI 1.11–1.71, P = 0.003). For those completing 12 weeks, FIB‐4 > 3.25 and high BMI remained significant predictors.ConclusionsIn this robust real‐world cohort, SVR rates were similar to clinical trials. FIB‐4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12‐week course.
Vegetation assessment of native tree species in Broussonetia papyrifera‐dominated degraded forest landscape in southern Ghana
Authors: Agyeman Victor K. , Addo‐Danso Shalom D. , Kyereh Boateng , Abebrese Isaac K. 
Published: June 2016

AbstractQuestionDoes the invasive tree species Broussonetia papyrifera facilitate the natural regeneration of native tree species in a degraded tropical forest landscape?LocationAfram Headwaters Forest Reserve, southern Ghana.MethodsWe established sampling areas and assessed seedlings and saplings <5 cm DBH in nine habitats. The habitats were logging road, skid trail, large canopy gaps dominated by B. papyrifera, large canopy gaps dominated by invasive Chromolaena odorata, Nauclea diderrichii plantation, Mansonia altissima plantation, Terminalia ivorensis plantation, abandoned farmland and unlogged forest.ResultsWe found that the abundance of pioneers declined with increasing abundance of B. papyrifera. This trend was more pronounced in the farmland and in the N. diderrichii plantation. By contrast, increased abundance of B. papyrifera did not lead to a decrease in the abundance of the shade‐tolerant species. B. papyrifera seedlings and saplings were absent in the forest understorey. We also found a lower abundance and richness of some vulnerable tree species and valuable timber species in the N. diderrichii plantation and in gaps dominated by B. papyrifera. However, we recorded both shade‐tolerant and shade‐intolerant species in the gaps dominated by B. papyrifera.ConclusionsWe found both shade‐tolerant and shade‐intolerant species in the B. papyrifera‐dominated gaps. This can provide a basis for future studies to explore the potential of such tree species in restoration programmes targeted at B. papyrifera‐invaded sites. Our results also suggest that the integrity of the undisturbed forest patches in the landscape must be protected to help prevent B. papyrifera from spreading further. We suggest further studies should be conducted at replicated sites with a similar habitat that represent varying levels of invasion by B. papyrifera to draw conclusions regarding the species’ potential to facilitate regeneration of native tree species.
Documents and Shifting Labor Environments Among Undocumented Migrant Workers in Northern California
Authors: Ordóñez Juan Thomas 
Published: June 2016

AbstractThis article explores the ways in which migrant workers establish particular relations to the state in shifting environments of criminalization and stigmatization that change the geography and nature of undocumented labor in the United States. Centering on Northern California, I address the results of the economic downturn between 2007 and 2009 for undocumented migrant men who had established jobs and paid taxes using fake Social Security cards, but whose labor conditions became unsustainable, leading many of them to turn to informal labor sites. I argue that work environments for many migrants shift to effectively ensure the marginalization of cheap labor, while maintaining their contributions to local economies and accommodating to the political constraints of the moment. I follow accounts of counterfeit identification, mainly fake Social Security cards, in labor practices that inscribe migrant laborers into the “system” they are supposed to be abusing, but to which they actually contribute a great deal through mimetic articulations of citizenship. I show how severing such ties becomes necessary in times of economic crisis and heighted criminalization, and I illustrate the ways in which real and imagined state repression make what Nicholas De Genova (2002) has called “deportability” an effective way to control and maintain an undocumented labor force within the boundaries of the country.
Mood stabilizers during breastfeeding: a systematic review of the recent literature
Authors: Uguz Faruk , Sharma Verinder 
Published: June 2016

AbstractObjectiveThis review examined the safety of mood stabilizers in exposed breastfed infants.MethodsPubMed was searched for English language reports between 1 January 1995 and 30 August 2015 by using combinations of key words breastfeeding, lactation, postpartum period, puerperium, mood stabilizers, lithium, lamotrigine, valproate, carbamazepine, and oxcarbazepine. Case reports, case series, and prospective or cross‐sectional studies including relevant data such as relative infant dose, milk‐to‐plasma ratio, infant drug plasma levels, and adverse events were identified.ResultsA total of 26 of 604 relevant reports in PubMed were included in the study. These reports included lamotrigine (122 cases in 12 reports), lithium (26 cases in five reports), carbamazepine (64 cases in five reports), valproate (nine cases in three reports), and oxcarbazepine (two cases in two reports). Of 26 reports, one report included both carbamazepine and valproate. The reports suggest that a considerable amount of lithium and lamotrigine are excreted into breast milk. There is a paucity of data on valproate and oxcarbazepine; however, the infant/maternal ratio of serum drug concentration seems to be lower in valproate exposure compared to other mood stabilizers. The incidence of adverse events in infants exposed to mood stabilizers is reported to be very low.ConclusionsThe current data suggest that mood stabilizers can be prescribed without any adverse events in most infants in lactating women. The available reports also suggest a low prevalence rate of laboratory abnormalities including hepatic, kidney, and thyroid functions in the infants. Additional studies examining short‐term and especially long‐term effects of mood stabilizers on breastfed infants are required.
Phase Ib trial of the PI3K/mTOR inhibitor voxtalisib (SAR245409) in combination with chemoimmunotherapy in patients with relapsed or refractory B‐cell malignancies
Authors: Awan Farrukh T. , Gore Lia , Gao Lei , Sharma Jyoti , Lager Joanne , Costa Luciano J. 
Published: June 2016

This phase Ib, dose‐escalation study investigated the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety, pharmacokinetics (PK) and preliminary efficacy of the pan‐class I phosphoinositide 3‐kinase (PI3K) and mechanistic target of rapamycin (mTOR) inhibitor voxtalisib [30 or 50 mg twice daily (BID)], in combination with rituximab (voxtalisib+rituximab) or rituximab plus bendamustine (voxtalisib+rituximab+bendamustine), in relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma (NHL), mantle cell lymphoma and chronic lymphocytic leukaemia (CLL). MTD and RP2D of voxtalisib were determined using a 3 + 3 dose‐escalation design. Adverse events (AEs), plasma PK and disease response were recorded. Thirty‐seven patients were enrolled. The RP2D of voxtalisib in combination with rituximab or rituximab+bendamustine was 50 mg BID. Four patients experienced a total of five dose‐limiting toxicities. The most frequent AEs were nausea (45·9%), fatigue (37·8%) headache (32·4%) and pyrexia (32·4%). The most frequent grade ≥3 AEs were neutropenia (27·0%), thrombocytopenia (24·3%), anaemia (16·2%) and febrile neutropenia (10·8%). Voxtalisib PK parameters were not affected by co‐administration with rituximab or rituximab+bendamustine. Of 35 efficacy‐evaluable patients, four (11·4%) achieved complete response and 13 (37·1%) achieved partial response. Voxtalisib, in combination with rituximab or rituximab+bendamustine, demonstrated an acceptable safety profile and encouraging anti‐tumour activity in relapsed or refractory B‐cell malignancies.
Recent advances in therapy of chronic lymphocytic leukaemia
Authors: Routledge David J. M. , Bloor Adrian J. C. 
Published: June 2016

SummaryThe last 5 to 10 years have been marked by considerable advances in both our understanding of the biology and treatment of chronic lymphocytic leukaemia (CLL). Fludarabine‐based immuno‐chemotherapy is the current standard of care for first line therapy in younger fit patients and although this can be highly effective its use in older co‐morbid patients is limited by toxicity, and the prognosis for patients with high risk or fludarabine‐refractory disease is poor. The introduction of new antibodies has however, facilitated the use of immuno‐chemotherapy in co‐morbid patients. Beyond this, the recognition that CLL cells are critically dependent on B‐cell receptor (BCR) signalling and interactions with the cellular micro‐environment for proliferation and survival has led to the investigation of BCR inhibitors in CLL treatment. These have been shown to be highly effective although a number of questions remain about how they should be optimally used in clinical practice.
Mortality and cancer incidence among patients treated with recombinant growth hormone during childhood in Israel
Authors: Libruder Carmit , Blumenfeld Orit , Dichtiar Rita , Laron Zvi , Zadik Zvi , Shohat Tamy , Afek Arnon 
Published: June 2016

SummaryContextThe inconclusive evidence regarding long‐term safety of recombinant human growth hormone (rhGH) therapy underlines the need for long‐term large‐scale cohorts.ObjectiveTo assess long‐term mortality and cancer incidence among patients treated with rhGH during childhood in Israel.DesignA population‐based cohort study.SettingData were retrieved from a national register established in 1988. Mortality data from the national population register were available through 31 December 2014. Data on cancer incidence from the national cancer registry were available through 31 December 2012.ParticipantsAll patients ≤19 years approved for rhGH treatment during 1988–2009 were included. Patients were assigned to three risk categories, according to the underlying condition leading to growth disorder.Main outcome measuresAll‐cause mortality and cancer incidence rates were calculated, based on person‐years at risk. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated, using the Israeli general population as a reference.ResultsIncluded were 1687 patients assigned to the low‐risk category and 440 patients assigned to the intermediate‐risk category. In the low‐risk category, all‐cause mortality and cancer incidence were not significantly different than expected (SMR 0·81, 95% CI 0·22–2·08 and SIR 0·76, 95% CI 0·09–2·73). In the intermediate‐risk category, all‐cause mortality and cancer incidence were significantly higher than expected (SMR 4·05, 95% CI 1·62–8·34 and SIR 4·52, 95% CI 1·22–11·57).ConclusionsNo increased risk of mortality or cancer incidence was found in low‐risk patients treated with rhGH during childhood. Patients with prior risk factors were at higher risk of both mortality and cancer.
Functional characterization of two novel germline mutations of the KCNJ5 gene in hypertensive patients without primary aldosteronism but with ACTH‐dependent aldosterone hypersecretion
Authors: Sertedaki Amalia , Markou Athina , Vlachakis Dimitrios , Kossida Sophia , Campanac Emilie , Hoffman Dax A. , Sierra Maria De La Luz , Xekouki Paraskevi , Stratakis Constantine A. , Kaltsas Gregory , Piaditis George P. , Chrousos George P. , Charmandari Evangelia 
Published: June 2016

SummaryBackgroundGermline mutations of the KCNJ5 gene encoding Kir3·4, a member of the inwardly rectifying K+ channel, have been identified in ‘normal’ adrenal glands, patients with familial hyperaldosteronism (FH) type III, aldosterone‐producing adenomas (APAs) and sporadic cases of primary aldosteronism (PA).ObjectiveTo present two novel KCNJ5 gene mutations in hypertensive patients without PA, but with Adrenocorticotropic hormone (ACTH)‐dependent aldosterone hypersecretion.Design and PatientsTwo hypertensive patients without PA, who exhibited enhanced ACTH‐dependent response of aldosterone secretion, underwent genetic testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. Genomic DNA was isolated from peripheral white blood cells, and the exons of the entire coding regions of the above genes were amplified and sequenced. Electrophysiological studies were performed to determine the effect of identified mutation(s) on the membrane reversal potentials. Structural biology studies were also carried out.ResultsTwo novel germline heterozygous KCNJ5 mutations, p.V259M and p.Y348N, were detected in the two subjects. Electrophysiological studies showed that the Y348N mutation resulted in significantly less negative reversal potentials, suggesting loss of ion selectivity, while the V259M mutation did not affect the Kir3.4 current. In the mutated structural biology model, the N348 mutant resulted in significant loss of the ability for hydrogen bonding, while the M259 mutant was capable of establishing weaker interactions. The CYP11B1/CYP11B2 chimeric gene was not detected.ConclusionsThese findings expand on the clinical spectrum of phenotypes associated with KCNJ5 mutations and implicate these mutations in the pathogenesis of hypertension associated with increased aldosterone response to ACTH stimulation.
Clinical characteristics of PRKACA mutations in Chinese patients with adrenal lesions: a single‐centre study
Authors: Li Xintao , Wang Baojun , Tang Lu , Lang Bin , Zhang Yu , Zhang Fan , Chen Luyao , Ouyang Jinzhi , Zhang Xu 
Published: June 2016

SummaryContextRecent studies have identified that the somatic PRKACA L206R mutation can cause cortisol‐producing adenomas (CPAs). This study investigated the prevalence and characteristics of PRKACA, GNAS and CTNNB1 mutations in adrenal lesions in patients from a single centre in China.Design, Patients and MeasurementsWe sequenced PRKACA, GNAS and CTNNB1 genes in 108 patients, including 60 patients with CPAs (57 with unilateral and three with bilateral adenomas), 13 with nonfunctional adenomas, 12 with adrenocortical carcinomas (ACCs), 15 with primary bilateral macronodular hyperplasia (PBMAH) and eight with aldosterone and cortisol cosecreting adenomas. Mutations in PRKACA, GNAS and CTNNB1 were examined, and clinical characteristics were compared.ResultsAmong the unilateral CPAs, we identified somatic mutations in PRKACA (L206R) in 23 cases (40·4%), GNAS (R201C and R201H) in six cases (10·5%), CTNNB1 (S45C, L46P and S45P) in six cases (10·5%) and CTNNB1 plus GNAS in two cases (3·5%). PRKACA and GNAS mutations were mutually exclusive. Among the patients with nonfunctional adenoma, two carried CTNNB1 mutations. Among the patients with ACC, two carried GNAS and CTNNB1 mutations but none carried PRKACA mutations. One patient showed bilateral CPA, and one PBMAH patient carried PRKACA mutations. No mutations in PRKACA, GNAS or CTNNB1 were identified in the eight patients with aldosterone and cortisol cosecreting adenomas. PRKACA‐mutant adenomas were associated with young age, overt Cushing's syndrome and high cortisol levels compared with non‐PRKACA‐mutant or CTNNB1‐mutant lesions.ConclusionsPRKACA mutations are present in CPAs and bilateral adrenal macronodular hyperplasia. PRKACA mutation is associated with more severe autonomous cortisol secretion.
Hepatitis E in post‐liver transplantation: is it time to routinely consider it?
Authors: Borg Brian B. , Feng Zongdi , Earl Truman M. , Anderson Christopher D. 
Published: June 2016

AbstractHepatitis E, although commonly recognized in the Eastern Hemisphere, is less well recognized in the West. Particularly owing to this disease's grave impact on outcomes after liver transplantation, greater consideration of hepatitis E is necessary in the context of abnormal liver tests. Here, we review the most recent data on detecting and managing hepatitis E, both pre‐ and post‐liver transplantation, discuss major detection assay limitations, consider future directions, and propose an algorithm for the diagnosis and management of pre‐and post‐transplantation hepatitis E.
Impact and persistence of cirrhotic cardiomyopathy after liver transplantation
Authors: Sonny Abraham , Ibrahim Ahmed , Schuster Andres , Jaber Wael A. , Cywinski Jacek B. 
Published: June 2016

AbstractCirrhotic cardiomyopathy causes variable degree of systolic and diastolic dysfunction (DD) and conduction abnormalities. The primary aim of our study was to determine whether pre‐transplant DD and prolonged corrected QT (QTc) predict a composite of mortality, graft failure, and major cardiovascular events after liver transplantation. We also evaluated the reversibility of cirrhotic cardiomyopathy after transplantation. Adult patients who underwent liver transplantation at our institution from January 2007 to March 2009 were included. Data were obtained from institutional registry, medical record review, and evaluation of echocardiographic images. Among 243 patients, 113 (46.5%) had grade 1 DD, 16 (6.6%) had grade 2 DD, and none had grade 3 DD. The mean pre‐transplant QTc was 453 milliseconds. After a mean post‐transplant follow‐up of 5.2 years, 75 (31%) patients satisfied the primary composite outcome. Cox regression analysis did not show any significant association between DD and the composite outcome (P=.17). However, longer QTc was independently associated with the composite outcome (HR: 1.01, 95% confidence interval: 1.00–1.02, P=.05). DD (P<.001) and left ventricular mass index (P=.001) worsened after transplantation. In conclusion, QTc prolongation appears to be associated with worse outcomes. Although DD did not impact outcomes, it significantly worsened after transplantation.
Upper midline incision for living donor right hepatectomy
Authors: Singh Manoj K. , Lubezky Nir , Facciuto Matias , Contreras‐Saldivar Alan , Wadhera Vikram , Arvelakis Antonios , LaPointe‐Rudow Dianne , Florman Sander , Facciuto Marcelo E. 
Published: June 2016

AbstractBackgroundLiving donor liver transplantation is a viable option to increase access to transplantation and techniques to limit the operative incision is one way to increase donation by decreasing donor morbidity. We describe our experience with a limited upper midline incision (UMI) for living donor right hepatectomy.Study DesignProspective data were collected on 58 consecutive living liver donors who underwent right hepatectomy via a UMI.ResultsDonor median age was 32 years, with median body mass index of 24.6. The mean incision length was 11.7 cm. Ten liver grafts included middle hepatic vein. The mean graft volume by preoperative imaging was 940 cc. The mean operative time was 407 minutes; cellsaver was utilized in 35 patients with median of 1 unit. Mean peak aspartate transaminase (AST) and alanine transaminase (ALT) were 492 and 469, and peak bilirubin and international normalized ratio (INR) were 3.3 and 1.8. The average length of stay was 6 days. There were 10 Clavien grade I and 11 Clavien grade II complications. Three patients developed an incisional hernia requiring surgical repair.ConclusionLiving liver donor hepatectomy can be safely performed through a UMI. This approach consolidates the steps of liver mobilization, hilar dissection, and parenchymal transection in a single‐exposure technique, with incision comparable to the laparoscopic‐assisted modality.