Citations

AbstractBackground & AimsAntiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta‐analysis of clinical trials.MethodsWe conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair‐wise meta‐analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments.ResultsSeventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair‐wise meta‐analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04–0.37; I2 = 0%), and Lamivudine (HR 0.40, 95% CI 0.24–0.65; I2 = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)‐positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results.ConclusionsBased on a Bayesian network meta‐analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.

Multiple anomalies including micromelia, poor mineralization of the vertebrae, and a persistent notochord were identified on second trimester ultrasound in a fetus with aCOL2A1mutation. To our knowledge, this represents the first case of a persistent notochord associated with aCOL2A1mutation in humans. In this case report, we describe ultrasound and postmortem findings and review the pathogenesis associated with a persistent notochord.

ABSTRACT Bisphosphonates (BPs) are the most commonly used medications for osteoporosis. This ASBMR report provides guidance on BP therapy duration with a risk-benefit perspective. Two trials provided evidence for long-term BP use. In the Fracture Intervention Trial Long-term Extension (FLEX), postmenopausal women receiving alendronate for 10 years had fewer clinical vertebral fractures than those switched to placebo after 5 years. In the HORIZON extension, women who received 6 annual infusions of zoledronic acid had fewer morphometric vertebral fractures compared with those switched to placebo after 3 years. Low hip T-score, between –2 and –2.5 in FLEX and below –2.5 in HORIZON extension, predicted a beneficial response to continued therapy. Hence, the Task Force suggests that after 5 years of oral BP or 3 years of intravenous BP, reassessment of risk should be considered. In women at high risk, for example, older women, those with a low hip T-score or high fracture risk score, those with previous major osteoporotic fracture, or who fracture on therapy, continuation of treatment for up to 10 years (oral) or 6 years (intravenous), with periodic evaluation, should be considered. The risk of atypical femoral fracture, but not osteonecrosis of the jaw, clearly increases with BP therapy duration, but such rare events are outweighed by vertebral fracture risk reduction in high-risk patients. For women not at high fracture risk after 3 to 5 years of BP treatment, a drug holiday of 2 to 3 years can be considered. The suggested approach for long-term BP use is based on limited evidence, only for vertebral fracture reduction, in mostly white postmenopausal women, and does not replace the need for clinical judgment. It may be applicable to men and patients with glucocorticoid-induced osteoporosis, with some adaptations. It is unlikely that future trials will provide data for formulating definitive recommendations. © 2015 American Society for Bone and Mineral Research.

Purpose The appropriate duration of surveillance for renal cell carcinoma (RCC) after radical or partial nephrectomy remains unknown, and evidence to support current guidelines are lacking. Herein, we provide an approach to surveillance that balances the risk of recurrence versus the risk of non-RCC death. Patients and Methods We identified 2,511 patients who underwent surgery for M0 RCC between 1990 and 2008. Patients were stratified for analysis by pathologic stage (pT1Nx-0, pT2Nx-0, pT3/4Nx-0, and pTanyN1), relapse location (abdomen, chest, bone, and other), age (< 50, 50 to 59, 60 to 69, 70-79 and ≥ 80 years), and Charlson comorbidity index (CCI; ≤ 1 and ≥ 2). Risks of disease recurrence and non-RCC death were estimated by using parametric models for time-to-failure with Weibull distributions. Surveillance duration was estimated at the point when the risk of non-RCC death exceeded the risk of recurrence. Results At a median follow-up of 9.0 years (interquartile range, 6.4 to 12.7 years), a total of 676 patients developed recurrence. By using a competing-risk model, vastly different surveillance durations were appreciated. Specifically, among patients with pT1Nx-0 disease and a CCI ≤ 1, risk of non-RCC death exceeded that of abdominal recurrence risk at 6 months in patients age 80 years and older but failed to do so for greater than 20 years in patients younger than age 50 years. For patients with pT1Nx-0 disease but a CCI ≥ 2, the risk of non-RCC death exceeded that of abdominal recurrence risk already at 30 days after surgery, regardless of patient age. Conclusion We present an individualized approach to RCC surveillance that bases the duration of follow-up on the interplay between competing risk factors of recurrence and non-RCC death. This strategy may improve the balance between the derived benefit from surveillance and medical resource allocation.

There are clear epidemiological associations between circadian disruption, obesity, and pathogenesis of type 2 diabetes. The mechanisms driving these associations are unclear. In the current study, we hypothesized that continuous exposure to constant light (LL) compromises pancreatic β-cell functional and morphological adaption to diet-induced obesity leading to development of type 2 diabetes. To address this hypothesis, we studied wild type Sprague Dawley as well as Period-1 luciferase reporter transgenic rats (Per1-Luc) for 10 weeks under standard light-dark cycle (LD) or LL with concomitant ad libitum access to either standard chow or 60% high-fat diet (HFD). Exposure to HFD led to a comparable increase in food intake, body weight, and adiposity in both LD- and LL-treated rats. However, LL rats displayed profound loss of behavioral circadian rhythms as well as disrupted pancreatic islet clock function characterized by the impairment in the amplitude and the phase islet clock oscillations. Under LD cycle, HFD did not adversely alter diurnal glycemia, diurnal insulinemia, β-cell secretory function as well as β-cell survival, indicating successful adaptation to increased metabolic demand. In contrast, concomitant exposure to LL and HFD resulted in development of hyperglycemia characterized by loss of diurnal changes in insulin secretion, compromised β-cell function, and induction of β-cell apoptosis. This study suggests that circadian disruption and diet-induced obesity synergize to promote development of β-cell failure, likely mediated as a consequence of impaired islet clock function.

A mosaic pattern of lung attenuation on chest computed tomography (CT) may be due to various etiologies. There is limited published data on CT results when used to evaluate pulmonary hypertension (PH). We retrospectively studied the frequency of mosaic pattern in patients with PH and the cause of the PH by diagnostic group, as well as the correlation between the mosaic pattern and the following: demographics, severity of the PH, main pulmonary artery (PA) size, PA/aorta (PA/Ao) ratio, pulmonary function tests (PFT), and ventilation perfusion scan results. Overall, 18% of the cohort had CT mosaic pattern (34/189). Mosaic pattern was present in 17/113 (15%) in Group 1 pulmonary arterial hypertension, 5/13 (28%) in Group 2 pulmonary venous hypertension and 8/50 (16%) in Group 3 PH. Conversely, Group 4 chronic thromboembolic PH was more prevalent in 4/8 (50%). Main PA size, PA/Ao ratio, and segmental perfusion defect were positively associated with mosaic pattern. In contrast, factors such as age, gender, body mass index, functional class, hemodynamic data, and PFT values were not associated with mosaic pattern. Mosaic pattern is not specific as an isolated finding for distinguishing the subtype of PH.

SummaryBackgroundObesity is associated with increased oesophageal acid exposure time (AET) in patients with gastro‐oesophageal reflux (GER), and may decrease the effects of proton pump inhibitors (PPIs).AimTo evaluate the effects of increased body mass on the ability of PPI therapy to decrease AET in patients with reflux symptoms.MethodsAcid exposure time profiles collected from adult patients using wireless pH‐metry while on or off PPI therapy was retrospectively reviewed. Patients were separated into five body mass index (BMI) categories as defined by the World Health Organization. A multivariable logistic regression evaluated the association between abnormal AET and BMI groups while controlling for age, gender and pH capsule placement methods.ResultsThe study group comprised 968 patients with 336 (34.7%) studied on a PPI and 632 (65.3%) studied off PPI therapy. AET (total greater than 5.3%) was found more frequently in the overweight (67%) and obese classes (74–80%) compared to those who were normal weight (40%) while off acid‐suppressing medications (P < 0.001). No significant differences were found between these groups when studied on acid‐suppressing medications, and the proportion of patients with abnormal AET across BMI classes was similar regardless of taking a PPI either once or twice daily.ConclusionsThis is the largest study to report on the relationship between BMI and oesophageal acid exposure time in patients with GER on and off PPI therapy. We conclude that obesity is related to increased acid exposure time, but with no significant difference in acid exposure time among different weight‐based groups when taking a once or twice‐daily PPI.

Objective To evaluate whether elective off‐clamp laparoscopic partial nephrectomy ( LPN ) affords long‐term renal functional benefit compared with the on‐clamp approach. Patients and Methods This is a retrospective review of patients who underwent elective LPN between 2006 and 2011. Patients were followed longitudinally for up to 5 years. In all, 315 patients with radiographic evidence of a solitary renal mass and normal‐appearing contralateral kidney underwent elective LPN ; 209 were performed on‐clamp vs 106 off‐clamp. One patient who required conversion from LPN to open PN was excluded from the study. Additionally, four patients in the on‐clamp cohort who underwent subsequent radical nephrectomy for local‐regional recurrence were excluded from longitudinal functional evaluation after their procedure. The primary objective was to evaluate differences in postoperative estimated glomerular filtration rate ( eGFR ) between hilar clamping groups. Subgroup analyses were performed for patients with clamp times >30 min and those with baseline renal insufficiency ( eGFR <60 mL/min/1.73m 2 ). Risk of developing worsened or new‐onset renal insufficiency was also compared. Results The mean preoperative eGFR was similar between the on‐clamp and off‐clamp cohorts (80.7 vs 84.1 mL/min/1.73m 2 , P > 0.05). Univariable and multivariable analyses did not show significant differences in postoperative eGFR between both groups among all‐comers, those with clamp times >30 min, and patients with baseline renal insufficiency. Risk of chronic kidney disease was not diminished by the off‐clamp approach with up to 5 years of follow‐up. Conclusions Progressive recovery of renal function after hilar clamping in the elective setting eclipses short‐term functional benefit achieved with off‐clamp LPN by 6 months; there was no significant difference in eGFR or the percentage incidence of chronic kidney disease between the on‐clamp and off‐clamp cohorts with up to 5 years follow‐up. As such, eliminating transient ischaemia during elective LPN does not confer clinical benefit.

ObjectivesWe investigated the impact of neoadjuvant chemotherapy (NAC) on axillary disease burden in clinically node‐negative (cN0) HER‐2 positive breast cancer patients.MethodsWe studied 215 cN0 patients with HER‐2 positive tumors. Multivariable logistic regression was used to compare NAC versus primary surgery (PS) with respect to outcome of pathologic nodal disease.ResultsOf 215 patients, 42 (20%) received NAC. NAC use correlated with higher clinical T stage (P < 0.0001) and younger age (P = 0.03) with no difference in ER/PR status or tumor grade. Despite higher clinical T stage in the NAC group, rate of pathologic positive axillary nodes was non‐significantly lower (NAC 5/42 = 11.9%, PS 27/173 = 15.6%, P = 0.54). In multivariable analysis, after adjustment for confounders including clinical T stage, age, and multifocal/multicentric disease, NAC showed significant reduction in odds of pathologic nodal disease (OR 0.26, 95%CI:0.06–0.90, P = 0.03). Further, among those with pathologic nodal disease, the number of positive nodes was lower after NAC (adjusted P = 0.03). Extranodal extension was present in 8/27 (30%) PS patients vs. 1/5 (20%) of the NAC patients (adjusted P = 0.36).ConclusionNAC in cN0 HER‐2 positive breast cancers reduces the rate of pathologic node‐positive disease at operation and nodal disease burden and may decrease the need for axillary node dissection. J. Surg. Oncol. 2015; 112:453–457. © 2015 Wiley Periodicals, Inc.