Fluoroquinolone Use Preceding Visceral Artery Dissection: A Case Series.

Fluoroquinolones (FQ), commonly prescribed antibiotics, may trigger aortic and carotid dissections. We report three successive cases of visceral artery dissection: one patient with celiac trunk dissection and two with dissection of the superior mesenteric artery. These events occurred up to 4 months after 7 to 14 days of FQ treatment (2 cases of ofloxacin, 1 of norfloxacin). There was no other apparent cause of dissection. These dissections were isolated, apart from a minimal aortic dissection separate from the visceral arterial dissection in one case. A case series cannot certify the relationship between dissection and FQ, but it can be hypothesized. The association between fluoroquinolone use and higher occurrence of aneurysm and dissection remains discussed in aortic syndrome. The potential link between FQ and visceral artery dissection is even less described but should be reported in the absence of previous cases in the literature. The pathophysiological theory is the induction of overexpression of some matrix metalloproteinases and a decrease of their inhibitors, provoking a dysregulation in collagen synthesis and degradation of the extracellular matrix.

Novel Association of the NOTCH Pathway Regulator MIB1 Gene With the Development of Bicuspid Aortic Valve.

Importance: Nonsyndromic bicuspid aortic valve (nsBAV) is the most common congenital heart valve malformation. BAV has a heritable component, yet only a few causative genes have been identified; understanding BAV genetics is a key point in developing personalized medicine. Objective: To identify a new gene for nsBAV. Design, Setting, and Participants: This was a comprehensive, multicenter, genetic association study based on candidate gene prioritization in a familial cohort followed by rare and common association studies in replication cohorts. Further validation was done using in vivo mice models. Study data were analyzed from October 2019 to October 2022. Three cohorts of patients with BAV were included in the study: (1) the discovery cohort was a large cohort of inherited cases from 29 pedigrees of French and Israeli origin; (2) the replication cohort 1 for rare variants included unrelated sporadic cases from various European ancestries; and (3) replication cohort 2 was a second validation cohort for common variants in unrelated sporadic cases from Europe and the US. Main Outcomes and Measures: To identify a candidate gene for nsBAV through analysis of familial cases exome sequencing and gene prioritization tools. Replication cohort 1 was searched for rare and predicted deleterious variants and genetic association. Replication cohort 2 was used to investigate the association of common variants with BAV. Results: A total of 938 patients with BAV were included in this study: 69 (7.4%) in the discovery cohort, 417 (44.5%) in replication cohort 1, and 452 (48.2%) in replication cohort 2. A novel human nsBAV gene, MINDBOMB1 homologue MIB1, was identified. MINDBOMB1 homologue (MIB1) is an E3-ubiquitin ligase essential for NOTCH-signal activation during heart development. In approximately 2% of nsBAV index cases from the discovery and replication 1 cohorts, rare MIB1 variants were detected, predicted to be damaging, and were significantly enriched compared with population-based controls (2% cases vs 0.9% controls; P = .03). In replication cohort 2, MIB1 risk haplotypes significantly associated with nsBAV were identified (permutation test, 1000 repeats; P = .02). Two genetically modified mice models carrying Mib1 variants identified in our cohort showed BAV on a NOTCH1-sensitized genetic background. Conclusions and Relevance: This genetic association study identified the MIB1 gene as associated with nsBAV. This underscores the crucial role of the NOTCH pathway in the pathophysiology of BAV and its potential as a target for future diagnostic and therapeutic intervention.

Methods: Aortic wall deformation assessment by ultrafast ultrasound imaging: Application to bicuspid aortic valve associated aortopathy.

Purpose: Aortic maximal rate of systolic distention (MRSD) is a prognosis factor of ascending aorta dilatation with magnetic resonance imaging. Its calculation requires precise continuous tracking of the aortic diameter over the cardiac cycle, which is not feasible by focused ultrasound. We aimed to develop an automatic aortic acquisition using ultrafast ultrasound imaging (UUI) to provide access to the aortic MRSD. Methods: A phased array probe and developed sequences at 2000 frames/s were used. A created interface automatically tracked the anterior and posterior aortic walls over the cardiac cycle. Tissue Doppler allowed a precise estimation of the walls' movements. MRSD was the maximum derivative of the aortic diameter curve over time. To assess its feasibility, 34 patients with bicuspid aortic valve (BAV) and 31 controls were consecutively included to evaluate the BAV-associated aortopathy at the sinus of Valsalva, the tubular ascending aorta, and the aortic arch. Results: UUI acquisitions and the dedicated interface allow tracking of the aortic diameter and calculating the MRSD for the BAV patients and controls (mean age of 34 vs. 43 years, p = 0.120). A trend toward lower deformation in the different aortic segments was observed, as expected. Still, only the MRSD with UUI was significantly different at the sinus of Valsalva in this small series: (0.61 .103.s-1 [0.37-0.72] for BAV patients vs. 0.92 .103.s-1 [0.72-1.02] for controls, p = 0.025). Conclusion: Aortic deformation evaluated with UUI deserves attention with a simple and automated measurement technique that could assess the segmental aortic injury associated with BAV.

Women Specific Characteristics and 1-Year Outcome Among Patients Hospitalized for Peripheral Artery Disease: A Monocentric Cohort Analysis in a Tertiary Center.

Although women have lower age-standardized cardiovascular disease incidence, prevalence, and death-related rates than men, there are also reports indicating that women with cardiovascular disease receive less care, fewer investigations, and have poorer outcomes after a coronary event. The aims of this study were to compare the characteristics of men and women hospitalized for peripheral artery disease (PAD), their cardiovascular and limb outcomes, and their 1-year mortality. The study is a prospective registry collecting data about all consecutive patients hospitalized for PAD within the vascular department of the tertiary center Georges-Pompidou European Hospital (Paris, France). Patients were required to have one of three inclusion criteria: previous revascularization of the lower limb or any lower limb artery occlusion due to an atherosclerotic vascular disease or hemodynamic evidence of PAD. Exclusion criteria were patients with lower extremity arterial occlusion due to another cause. All patients were followed-up for at least 12 months after the initial hospitalization. Among the 235 patients included, there were 61 women (26%), older than men with a median age of 75.6 and 68.3 years, respectively. Main cardiovascular risk factors and comorbidities were similar for men and women except more former or current smokers [145 (83.4%) vs. 33 (54.1%)] and more history of coronary heart disease [42 (24.1%) vs. 7 (11.5%)] in men. Most patients [138 (58.8%)] had critical limb ischemia and 97 (41.3%) had claudication, with no difference for sex. After discharge, 218 patients received an antithrombotic therapy (93.2%), 195 a lipid-lowering drug (83.3%), 185 an angiotensin converting enzyme inhibitor or angiotensin-receptor blocker (78.9%), similarly between sex. At 1-year, overall mortality, major adverse cardiovascular events, major adverse limb events did not differ with 23 (13.2%), 11 (6.3%) and 32 (18.4%) in men, and 8 (13.1%), 3 (4.9%), 15 (24.6%) in women, respectively, despite the difference in age. Overall mortality, cardiovascular outcomes, limb revascularization or amputation did not differ between men and women, 1-year after hospitalization for PAD although the latter were older, less smoker and had less coronary artery disease. Due to the small size of this cohort, larger studies and future research are needed to better understand sex-specific mechanisms in the pathophysiology and natural history of PAD.

Is Bicuspid Aortic Valve Morphology Genetically Determined? A Family-Based Study.

Bicuspid aortic valve (BAV) is a common congenital heart disease, with a 10-fold higher prevalence in first-degree relatives. BAV has different phenotypes based on the morphology of cusp fusion. These phenotypes are associated with different clinical courses and prognoses. Currently, the determinants of the valve phenotype are unknown. In this study we evaluated the role of genetics using familial cohorts. Patients with BAV and their first-degree relatives were evaluated by echocardiography. The concordance in BAV phenotype between pairs of family members was calculated and compared with the concordance expected by chance. We then performed a systematic literature review to identify additional reports and calculated the overall concordance rate. During the study period, 70 cases from 31 families and 327 sporadic cases were identified. BAV was diagnosed in 14% of the screened relatives. The proportions of the morphologies identified was: 12.3% for type 0, 66.2% for type 1-LR, 15.4% for type 1-RN, 4.6% for type 1-NL, and 1.5% for type 2. For the assessment of morphologic concordance, we included 120 pairs of first-degree relatives with BAV from our original cohort and the literature review. Concordance was found only in 62% of the pairs which was not significantly higher than expected by chance. In conclusion, our finding demonstrates intrafamilial variability in BAV morphology, suggesting that morphology is determined by factors other than Mendelian genetics. As prognosis differs by morphology, our findings may suggest that clinical outcomes may vary even between first-degree relatives.

Clinical Outcomes of Adults With Bicuspid Aortic Valve: A European Perspective.

OBJECTIVE: To describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery. PATIENTS AND METHODS: Between 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months. RESULTS: In the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed. CONCLUSION: This regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference.

Intranasal Fentanyl for Procedural Analgesia in Preterm Infants.

Background: Despite the availability of evidence-based analgesic strategies, neonatal pain management continues to be suboptimal. Intranasal (IN) fentanyl is an alternative pharmacotherapy for procedural pain in neonatal units. The objective was to evaluate the effectiveness and safety of IN fentanyl for procedural pain in preterm infants. Methods: A retrospective cohort study was conducted in infants who received IN fentanyl between May 2019 and December 2020 at an academic neonatal intensive care unit. Main outcome measures were pain responses, physiological parameters before and up to 60 min after IN fentanyl administration, and adverse events. Paired t-test and analysis of variance were used to compare pain scores and physiological parameters, respectively. Results: Thirteen infants received IN fentanyl on 22 occasions. Median (interquartile range [IQR]) gestational age and birthweight were 27 (25, 27.6) weeks and 850 (530, 1,030) grams, while median (IQR) post-menstrual age and weight were 30.9 (28.9, 32.9) weeks and 1,280 (945, 1,623) grams at the time of IN fentanyl administration. IN fentanyl was most used for lumbar puncture (55%) followed by insertion of epicutaneo-caval catheters (27%). There was a difference between the mean pre- and post-procedure Premature Infant Pain Profile scores of 1.3 (95% CI = 0.07, 2.5; p = 0.04). Physiological parameters did not differ before and up to 60 min post IN fentanyl administration (p > 0.05). Two adverse events (one apnea and one desaturation) were noted. Conclusion: In our limited experience, IN fentanyl appears to be an alternative pharmacotherapy for procedural pain management in the absence of intravenous access in preterm infants.

Predictive Factor for COVID-19 Worsening: Insights for High-Sensitivity Troponin and D-Dimer and Correlation With Right Ventricular Afterload.

Background: Coronavirus disease 2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. Objectives: To explore clinical and biological parameters of COVID-19 patients with hospitalization criteria that could predict referral to intensive care unit (ICU). Methods: Analyzing the clinical and biological profiles of COVID-19 patients at admission. Results: Among 99 consecutive patients that fulfilled criteria for hospitalization, 48 were hospitalized in the medicine department, 21 were first admitted to the medicine ward department and referred later to ICU, and 30 were directly admitted to ICU from the emergency department. At admission, patients requiring ICU were more likely to have lymphopenia, decreased SpO2, a D-dimer level above 1,000 ng/mL, and a higher high-sensitivity cardiac troponin (Hs-cTnI) level. A receiver operating characteristic curve analysis identified Hs-cTnI above 9.75 pg/mL as the best predictive criteria for ICU referral [area under the curve (AUC), 86.4; 95% CI, 76.6-96.2]. This cutoff for Hs-cTnI was confirmed in univariate [odds ratio (OR), 22.8; 95% CI, 6.0-116.2] and multivariate analysis after adjustment for D-dimer level (adjusted OR, 20.85; 95% CI, 4.76-128.4). Transthoracic echocardiography parameters subsequently measured in 72 patients showed an increased right ventricular (RV) afterload correlated with Hs-cTnI (r = 0.42, p = 0.010) and D-dimer (r = 0.18, p = 0.047). Conclusion: Hs-cTnI appears to be the best relevant predictive factor for referring COVID-19 patients to ICU. This result associated with the correlation of D-dimer with RV dilatation probably reflects a myocardial injury due to an increased RV wall tension. This reinforces the hypothesis of a COVID-19-associated microvascular thrombosis inducing a higher RV afterload.

Curative anticoagulation prevents endothelial lesion in COVID-19 patients.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with cardiovascular complications and coagulation disorders. OBJECTIVES: To explore the coagulopathy and endothelial dysfunction in COVID-19 patients. METHODS: The study analyzed clinical and biological profiles of patients with suspected COVID-19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). RESULTS: Among 96 consecutive COVID-19-suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS-CoV-2. COVID-19-positive patients were more likely to present with fever (P = .02), cough (P = .03), and pneumonia at computed tomography (CT) scan (P = .002) at admission. Prevalence of D-dimer >500 ng/mL was higher in COVID-19-positive patients (74.2% versus 43.3%; P = .007). No sign of disseminated intravascular coagulation were identified. Adding D-dimers >500 ng/mL to gender and pneumonia at CT scan in receiver operating characteristic curve analysis significantly increased area under the curve for COVID-19 diagnosis. COVID-19-positive patients had significantly more CECs at admission (P = .008) than COVID-19-negative ones. COVID-19-positive patients treated with curative anticoagulant prior to admission had fewer CECs (P = .02) than those without. Interestingly, patients treated with curative anticoagulation and angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers had even fewer CECs (P = .007). CONCLUSION: Curative anticoagulation could prevent COVID-19-associated coagulopathy and endothelial lesion.

Carotid Stiffness Assessment With Ultrafast Ultrasound Imaging in Case of Bicuspid Aortic Valve.

AIMS: To compare the carotid stiffness and flow parameters by ultrafast ultrasound imaging (UF), in bicuspid aortic valve (BAV) patients to first-degree relatives (controls). METHODS: BAV patients (n = 92) and controls (n = 48) were consecutively included at a reference center for BAV. Aortic valve and ascending aorta were evaluated by echocardiography. Common carotid arteries were evaluated by UF with a linear probe. A high frame rate (2,000 frames/s) was used to measure the pulse wave velocity (PWV). The arterial diameter change over the cardiac cycle was obtained by UF-Doppler imaging. This allowed us to measure the distensibility and the maximal rate of systolic distension (MRSD). The wall shear stress (WSS) was measured based on the same acquisitions, by analyzing blood flow velocities close to the carotid walls. RESULTS: BAV patients had significantly larger aortic diameters (p < 0.001) at the Valsalva sinus and at the tubular ascending aorta but no larger carotid diameters. No significant differences were found in carotid stiffness parameters (distensibility, MRSD, and PWV), even though these patients had a higher aortic stiffness. Carotid stiffness correlated linearly with age and similar slopes were obtained for BAV patients and controls. No difference in carotid WSS was found between BAV patients and controls. CONCLUSION: Our results clearly show that the carotid stiffness and flow parameters are not altered in case of BAV compared with controls.

An In Vitro Model Assessing the Penetration of Hyaluronidase through Optic Nerve Dura for Management of Hyaluronic Acid Facial Filler Embolism.

BACKGROUND: Blindness from ophthalmic or central retinal artery embolism is one of the most devastating complications of cosmetic filler facial injections. A proposed therapy to mitigate visual loss is prompt retrobulbar injection of hyaluronidase into the retrobulbar space. Despite Zhu et al. showing a lack of evidence and very limited published literature for reversing visual loss with this intervention, it is still widely accepted as a treatment for filler-related emboli. The purpose of this study was to evaluate the penetration of hyaluronidase through optic nerve dura using an in vitro model. METHODS: At study conclusion, five 1-cm-long segments of fresh optic nerve were obtained and injected with highly crosslinked hyaluronic acid filler, then ligated on both ends in a watertight fashion. The sections were immersed in three concentrations of hyaluronidase solution for 24 hours. Histopathologic examination of the specimen was performed to assess the presence of filler. RESULTS: The optic nerve sections were 1.1 cm (range, 0.8 to 1.2 cm). Three were immersed in 20 ml of 1500 IU/ml hyaluronidase solution and two were immersed in saline as control. After 24 hours, there was a persistence of hyaluronic acid within the optic nerves. CONCLUSIONS: There is a lack of evidence for penetration of optic nerve sheath by hyaluronidase. This raises question about the effectiveness of retrobulbar injection of hyaluronidase in reversing filler-related blindness. Further studies are needed before this can be adopted as the treatment of choice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

International trade of environmental goods in gravity models.

Environmental goods are goods used or produced by industry that reduce air and water pollution and optimize the use of resources in production. Despite several Sustainable Development Goals explicitly calling for resilient and sustainable development, the diffusion of such goods is still low, especially in developing countries. Only sporadic research on the determinants of international trade of environmental goods is available. Based on the OECD classification of environmental goods, this gap is filled by adopting a gravity model, using trade data over a time span of 15 years from 1999 to 2014 across 71 countries. The central message of this paper is that environmental regulatory stringency is a key determinant of environmental goods trade. It is specifically provided evidence that a substitution effect exists between environmental regulation stringency and trade of environmental goods. In line with empirical literature on traditional gravity models, increased capacity to innovate, cultural ties, geographical proximity and financial uncertainty also play a role.

Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA), a mini-chromosome essential for HBV replication, is supposed to be resistant to nucleos(t)ide analogue treatment. We investigated the effect of long-term nucleos(t)ide analogue treatment on cccDNA. METHODS: Among 129 patients who had been enrolled in previous international nucleos(t)ide analogue clinical trials and had liver biopsies at baseline and one year after treatment, we recruited 43 patients on long-term continuous treatment for 72 to 145months for a third liver biopsy. Serum HBV DNA, hepatitis B surface antigen (HBsAg) levels, total intrahepatic HBV DNA (ihHBV DNA), cccDNA, HBV pregenomic RNA (pgRNA) as well as histologic changes were examined. RESULTS: At the time of the third biopsy, serum HBV DNA levels were undetectable in all but one patient. The median levels of HBsAg, ihHBV DNA, and cccDNA were 2.88logIU/ml, 0.03copies/cell, and 0.01copies/cell, respectively. Compared to baseline levels, there was reduction of HBsAg levels by 0.54log (71.46%), ihHBV DNA levels by 2.81log (99.84%), and cccDNA levels by 2.94log (99.89%), with 49% having cccDNA levels below the detection limit. One patient had undetectable HBsAg. The median pgRNA level, measured only in the third biopsy, was 0.021copies/cell, with 40% of patients having undetectable pgRNA. CONCLUSIONS: Long-term nucleos(t)ide analogue treatment induced marked depletion of cccDNA in the majority of patients while serum HBsAg levels, though reduced, were detectable in all but one patient. Whether cccDNA depletion is sustained and associated with better patient outcome requires further study. LAY SUMMARY: It is generally presumed that a form of hepatitis B virus DNA, called covalently closed circular DNA (cccDNA), which hides inside the nuclei of liver cells of patients with chronic hepatitis B, cannot be reduced by antiviral treatment. The present study showed that with prolonged treatment (median period 126months), cccDNA can be markedly reduced, with 49% of liver biopsies having undetectable cccDNA. This suggests that viral replication capacity would be very low after prolonged antiviral treatment.

Approach to improve compound recovery in a high-throughput Caco-2 permeability assay supported by liquid chromatography-tandem mass spectrometry.

The Caco-2 cell culture system is widely employed as an in vitro model for prediction of intestinal absorption of test compounds in early drug discovery. Poor recovery is a commonly encountered issue in Caco-2 assay, which can lead to difficulty in data interpretation and underestimation of the apparent permeability of affected compounds. In this study, we systematically investigated the potential sources of compound loss in our automated, high-throughput Caco-2 assay, sample storage, and analysis processes, and as a result found the nonspecific binding to various plastic surfaces to be the major cause of poor compound recovery. To minimize the nonspecific binding, we implemented a simple and practical approach in our assay automation by preloading collection plates with organic solvent containing internal standard prior to transferring incubations samples. The implementation of this new method has been shown to significantly increase recovery in many compounds previously identified as having poor recovery in the Caco-2 permeability assay. With improved recovery, permeability results were obtained for many compounds that were previously not detected in the basolateral samples. In addition to recovery improvement, this new approach also simplified sample preparation for liquid chromatography-tandem mass spectrometric analysis and therefore achieved time and cost savings for the bioanalyst.

Evaluation and validation of multiple cell lines and primary mouse macrophages to predict phospholipidosis potential.

Phospholipidosis (PLD) in preclinical species can lead to regulatory delays thereby creating incentives to screen for PLD during drug discovery. The objective of this work was to compare, optimize, and validate in vitro PLD assays in primary mouse macrophages and hepatocyte- (HepG2, HuH7) or macrophage-derived cells lines (I.13.35, RAW264.7) and to evaluate whether primary cells were better at predicting PLD. Assay precision, determined by a measure of signal to noise window (Z'), within assay variability, and day-to-day variability, using amiodarone, was generally acceptable for all cell types; however, precision limits for HepG2 and HuH7 were slightly below assay acceptance criteria. Up to 66 known PLD inducers and non-inducers were subsequently tested to validate the assays. The concordance for predicting PLD in primary macrophages, I-13.35, RAW264.7, HuH7, and HepG2 cells was 91%, 74%, 73%, 62%, and 62% respectively using a decision limit of EC50≤125 µM as a positive finding. Increasing the number of negative controls tested in RAW264.7 cells and changing the decision limit to ≥4-fold increase in PLD, improved the specificity and overall concordance to 88%. RAW264.7 cells were selected as the primary screen for predicting PLD, and together with the primary macrophages, were integrated into an overall testing paradigm proposed for use in PLD risk identification.

Randomized trial of lamivudine versus entecavir in entecavir-treated patients with undetectable hepatitis B virus DNA: outcome at 2 Years.

UNLABELLED: We aimed to determine the 2-year outcomes of entecavir followed by lamivudine in patients with undetectable viral load (<12 IU/mL) and normal alanine aminotransferase (ALT) after initial entecavir treatment for at least 6 months. Patients were randomly assigned 1:1 to continue with entecavir or switch to lamivudine. Liver biochemistry and hepatitis B virus (HBV) DNA were determined at weeks 0, 4, 12, 24, 48, 72, and 96. Mutational analysis using line-probe assay were performed at weeks 0, 24, 48, and 96 and at the time of HBV DNA relapse. There was no elevation of ALT observed in any patients up to 96 weeks. At 96 weeks of follow-up, 19/25 (76%) patients in the lamivudine arm had persistently undetectable HBV DNA, compared with 25/25 (100%) patients in the entecavir arm. Six patients in the lamivudine arm had HBV DNA >20 IU/mL, occurring at a range of 12 to 96 weeks. Of these, four patients had HBV DNA of less than 100 IU/mL during rebound (three had undetectable HBV DNA after switching back to entecavir), and the remaining two patients had HBV DNA levels of 7,973 and 699 IU/mL. Three patients (12%) had evidence of drug-resistant mutations, of which two patients had rtM204I mutation and one patient had rtM204V mutation. One of these three patients had previous lamivudine exposure before entecavir treatment and one patient had questionable drug compliance. CONCLUSION: Sequential therapy using entecavir followed by lamivudine resulted in virological rebound in 24% of patients after 96 weeks. Prior optimal viral suppression with entecavir did not confer any significant advantage in patients who switched to lamivudine.

Mild-to-moderate elevation of alanine aminotransferase increases liver stiffness measurement by transient elastography in patients with chronic hepatitis B.

OBJECTIVES: Liver stiffness measurement has been shown to be increased in severe acute flares of hepatitis. Whether lesser degree of hepatitis can also increase liver stiffness is not known. The present study aimed to investigate the effect of mild-to-moderate elevations of alanine aminotransferase (ALT) on liver stiffness in chronic hepatitis B. METHODS: Fifty-eight patients with chronic hepatitis B with ALT levels from 1 to 10 × upper limit of normal were recruited. Liver stiffness measurements were performed at the time of ALT elevation, and liver stiffness measurement was repeated once normalization of ALT occurred after antiviral therapy. Liver biopsies were performed in 38 patients. RESULTS: All 58 patients achieved normalization of ALT after antiviral therapy, with a median time of 3 months between the first and second liver stiffness measurement. There was a significantly lower median liver stiffness measurement after commencement of antiviral therapy, with the normalization of ALT levels compared with pre-treatment levels (6.4 vs. 7.9 kPa, respectively; P<0.001). The area under the receiver operator characteristic curve for diagnosing F2 fibrosis in elevated ALT was 0.68, compared with 0.73 after ALT normalization. Twelve (32%) patients would have been misclassified as having cirrhosis using liver stiffness measurements taken at the time of ALT elevation, compared with 16% after normalization of ALT. CONCLUSIONS: Even mild-to-moderate elevation in ALT levels may increase liver stiffness independent of underlying liver fibrosis. Higher levels of ALT were associated with higher discrepancies in liver stiffness. Therefore, the timing of liver stiffness measurement is important.

Can pancreaticoduodenectomy performed at a comprehensive community cancer center have comparable results as major tertiary center?

BACKGROUND: Pancreatic resection is a definitive treatment modality for pancreatic neoplasm. Pancreaticoduodenectomy (PD) is the primary procedure for tumor arising from head of pancreas. Prognosis is overwhelmingly poor despite adequate resection. We maintained a prospective database covering years 2001 to 2010. Outcome data is analyzed and compared with those from tertiary centers. METHODS: Sixty-two patients with various histology were included. Pylorus preserving pancreatico-duodenectomy (PPPD), classic pancreaticoduodenectomy, and subtotal pancreatectomy were procedures performed. Three patients had portal venorrhaphy performed to obtain clinically negative margin. Forty six patients had malignancy on final pathologic analysis. RESULTS: The average age of patients was 63. Mean preoperative CA19-9 for exocrine pancreatic malignancies was higher than for more benign lesions. There was a decrease in operative time during this period. Blood transfusion was uncommon. There was very few pancreatic leak among the patients. Two bile leaks were identified, one controlled with the drainage tube and the other one required repeat surgery. The primary reason for the prolonged hospitalization was gastric ileus. For patients without a gastrostomy tube, nasogastric tube was kept in until gastric ileus resolved. 30 days mortality rate was calculated at 4.8. Mean survival time during our follow up was 30.6 months. Comparing to published literature, present series' mortality, morbidity, and survival are similar. Five year survival was 39%. CONCLUSION: Despite overall poor outcome for patients with pancreatic and biliary malignancies, we conclude that surgery can be performed in community hospitals with special interest in treating pancreatic disorder, offering patients equivalent survival and quality of life as those operated in tertiary centers.