Polycystic liver disease presenting with an exudative pleural effusion: a case report

<p>Abstract</p> <p>Introduction</p> <p>Polycystic liver disease is asymptomatic in 95% of patients. In the remaining 5% it causes symptoms due to the local mass effect of the polycystic liver. We describe the case of a patient who presented with symptoms of a pleural effusion and was also found to have polycystic liver disease. The effusion recurred despite repeated efforts at drainage and only resolved following surgical debridement of the cystic liver.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian woman presented with a two-week history of increasing dyspnoea. An examination revealed a large right pleural effusion and gross hepatomegaly. An ultrasound confirmed a large polycystic liver and diagnostic thoracocentesis revealed an exudate, which was sterile to culture. The pleural effusion proved refractory to drainage and our patient underwent surgery to deroof the main hepatic cysts in an attempt to reduce the pressure on her right diaphragm. The histology was compatible with that of polycystic liver disease. No evidence of malignancy was found. After surgery, our patient had no recurrence of her effusion and, to date, has remained asymptomatic from her polycystic liver disease.</p> <p>Conclusion</p> <p>The case in this report illustrates that an exudative pleural effusion is a rare complication of polycystic liver disease. We feel that the mechanical effects of a large polycystic liver, and subsequent disruption of sub-diaphragmatic capillaries, resulted in a persistent exudative pleural effusion. Thus, surgical debulking of the hepatic cysts is required to manage these effusions.</p

Combined exome and transcriptome sequencing of non-muscle-invasive bladder cancer: associations between genomic changes, expression subtypes, and clinical outcomes.

BACKGROUND: Three-quarters of bladder cancer patients present with early-stage disease (non-muscle-invasive bladder cancer, NMIBC, UICC TNM stages Ta, T1 and Tis); however, most next-generation sequencing studies to date have concentrated on later-stage disease (muscle-invasive BC, stages T2+). We used exome and transcriptome sequencing to comprehensively characterise NMIBCs of all grades and stages to identify prognostic genes and pathways that could facilitate treatment decisions. Tumour grading is based upon microscopy and cellular appearances (grade 1 BCs are less aggressive, and grade 3 BCs are most aggressive), and we chose to also focus on the most clinically complex NMIBC subgroup, those patients with grade 3 pathological stage T1 (G3 pT1) disease. METHODS: Whole-exome and RNA sequencing were performed in total on 96 primary NMIBCs including 22 G1 pTa, 14 G3 pTa and 53 G3 pT1s, with both exome and RNA sequencing data generated from 75 of these individual samples. Associations between genomic alterations, expression profiles and progression-free survival (PFS) were investigated. RESULTS: NMIBCs clustered into 3 expression subtypes with different somatic alteration characteristics. Amplifications of ARNT and ERBB2 were significant indicators of worse PFS across all NMIBCs. High APOBEC mutagenesis and high tumour mutation burden were both potential indicators of better PFS in G3pT1 NMIBCs. The expression of individual genes was not prognostic in BCG-treated G3pT1 NMIBCs; however, downregulated interferon-alpha and gamma response pathways were significantly associated with worse PFS (adjusted p-value < 0.005). CONCLUSIONS: Multi-omic data may facilitate better prognostication and selection of therapeutic interventions in patients with G3pT1 NMIBC. These findings demonstrate the potential for improving the management of high-risk NMIBC patients and warrant further prospective validation

Variation in hepatitis B immunization coverage rates associated with provider practices after the temporary suspension of the birth dose

BACKGROUND: In 1999, the American Academy of Pediatrics and U.S. Public Health Service recommended suspending the birth dose of hepatitis B vaccine due to concerns about potential mercury exposure. A previous report found that overall national hepatitis B vaccination coverage rates decreased in association with the suspension. It is unknown whether this underimmunization occurred uniformly or was associated with how providers changed their practices for the timing of hepatitis B vaccine doses. We evaluate the impact of the birth dose suspension on underimmunization for the hepatitis B vaccine series among 24-month-olds in five large provider groups and describe provider practices potentially associated with underimmunization following the suspension. METHODS: Retrospective cohort study of children enrolled in five large provider groups in the United States (A-E). Logistic regression was used to evaluate the association between the birth dose suspension and a child's probability of being underimmunized at 24 months for the hepatitis B vaccine series. RESULTS: Prior to July 1999, the percent of children who received a hepatitis B vaccination at birth varied widely (3% to 90%) across the five provider groups. After the national recommendation to suspend the hepatitis B birth dose, the percent of children who received a hepatitis B vaccination at birth decreased in all provider groups, and this trend persisted after the policy was reversed. The most substantial decreases were observed in the two provider groups that shifted the first hepatitis B dose from birth to 5–6 months of age. Accounting for temporal trend, children in these two provider groups were significantly more likely to be underimmunized for the hepatitis B series at 24 months of age if they were in the birth dose suspension cohort compared with baseline (Group D OR 2.7, 95% CI 1.7 – 4.4; Group E OR 3.1, 95% CI 2.3 – 4.2). This represented 6% more children in Group D and 9% more children in Group E who were underimmunized in the suspension cohort compared with baseline. Children in the reversal cohort in these groups remained significantly more likely to be underimmunized compared with baseline. In contrast, in a third provider group where the typical timing of the third dose was unchanged and in two other provider groups whose hepatitis B vaccination schedules were unaffected by the birth dose suspension, hepatitis B vaccination coverage either was maintained or improved. CONCLUSION: When the hepatitis B birth dose was suspended, provider groups that moved the first dose of vaccination to 5–6 months of age or later had decreases in hepatitis B vaccine coverage at 24 months. These findings suggest that as vaccine policy changes occur, providers could attempt to minimize underimmunization by adopting vaccination schedules that minimize delays in the recommended timing of vaccine doses

Diet-Independent Remodeling of Cellular Membranes Precedes Seasonally Changing Body Temperature in a Hibernator

Polyunsaturated fatty acids (PUFA) have a multitude of health effects. Their incorporation into membrane phospholipids (PL) is generally believed to depend directly on dietary influx. PL influence transmembrane protein activity and thus can compensate temperature effects; e.g. PL n-6 PUFA are thought to stabilize heart function at low body temperature (Tb), whereas long chain (>C18) n-3 PUFA may boost oxidative capacity. We found substantial remodeling of membranes in free-living alpine marmots which was largely independent of direct dietary supply. Organ PL n-6 PUFA and n-6 to n-3 ratios were highest at onset and end of hibernation after rapid increases during a brief transitional period prior to hibernation. In contrast, longer chain PL n-3 PUFA content was low at end of summer but maximal at end of hibernation. After termination of hibernation in spring, these changes in PL composition were rapidly reversed. Our results demonstrate selective trafficking of PUFA within the body, probably governed by a circannual endogenous rhythm, as hibernating marmots were in winter burrows isolated for seven months from food and external cues signaling the approaching spring. High concentrations of PL n-6 PUFA throughout hibernation are in line with their hypothesized function of boosting SERCA 2a activity at low Tb. Furthermore, we found increasing rate of rewarming from torpor during winter indicating increasing oxidative capacity that could be explained by the accumulation of long-chain PL n-3 PUFA. It may serve to minimize the time necessary for rewarming despite the increasing temperature range to be covered, because rewarming is a period of highest metabolic rate and hence production of reactive oxygen species. Considering the importance of PUFA for health our results may have important biomedical implications, as seasonal changes of Tb and associated remodeling of membranes are not restricted to hibernators but presumably common among endothermic organisms

Environment Orientation : a structured simulation approach for agent-based complex systems

Complex systems are collections of independent agents interacting with each other and with their environment to produce emergent behaviour. Agent-based computer simulation is one of the main ways of studying complex systems. A naive approach to such simulation can fare poorly, due to large communication overhead, and due to the scope for deadlock between the interacting agents sharing a computational platform. Agent interaction can instead be considered entirely from the point of view of the environment(s) within which the agents interact. Structuring a simulation using such Environment Orientation leads to a simulation that reduces communication overhead, that is effectively deadlock-free, and yet still behaves in the manner required. Additionally the Environment Orientation architecture eases the development of more sophisticated large-scale simulations, with multiple kinds of complex agents, situated in and interacting with multiple kinds of environments. We describe the Environment Orientation simulation architecture. We report on a number of experiments that demonstrate the effectiveness of the Environment Orientation approach: a simple flocking system, a flocking system with multiple sensory environments, and a flocking system in an external environment

Life Cycle Replacement by Gene Introduction under an Allee Effect in Periodical Cicadas

Periodical cicadas (Magicicada spp.) in the USA are divided into three species groups (-decim, -cassini, -decula) of similar but distinct morphology and behavior. Each group contains at least one species with a 17-year life cycle and one with a 13-year cycle; each species is most closely related to one with the other cycle. One explanation for the apparent polyphyly of 13- and 17-year life cycles is that populations switch between the two cycles. Using a numerical model, we test the general feasibility of life cycle switching by the introduction of alleles for one cycle into populations of the other cycle. Our results suggest that fitness reductions at low population densities of mating individuals (the Allee effect) could play a role in life cycle switching. In our model, if the 13-year cycle is genetically dominant, a 17-year cycle population will switch to a 13-year cycle given the introduction of a few 13-year cycle alleles under a moderate Allee effect. We also show that under a weak Allee effect, different year-classes (“broods”) with 17-year life cycles can be generated. Remarkably, the outcomes of our models depend only on the dominance relationships of the cycle alleles, irrespective of any fitness advantages

Major depression, fibromyalgia and labour force participation: A population-based cross-sectional study

BACKGROUND: Previous studies have documented an elevated frequency of depressive symptoms and disorders in fibromyalgia, but have not examined the association between this comorbidity and occupational status. The purpose of this study was to describe these epidemiological associations using a national probability sample. METHODS: Data from iteration 1.1 of the Canadian Community Health Survey (CCHS) were used. The CCHS 1.1 was a large-scale national general health survey. The prevalence of major depression in subjects reporting that they had been diagnosed with fibromyalgia by a health professional was estimated, and then stratified by demographic variables. Logistic regression models predicting labour force participation were also examined. RESULTS: The annual prevalence of major depression was three times higher in subjects with fibromyalgia: 22.2% (95% CI 19.4 – 24.9), than in those without this condition: 7.2% (95% CI 7.0 – 7.4). The association persisted despite stratification for demographic variables. Logistic regression models predicting labour force participation indicated that both conditions had an independent (negative) effect on labour force participation. CONCLUSION: Fibromyalgia and major depression commonly co-occur and may be related to each other at a pathophysiological level. However, each syndrome is independently and negatively associated with labour force participation. A strength of this study is that it was conducted in a large probability sample from the general population. The main limitations are its cross-sectional nature, and its reliance on self-reported diagnoses of fibromyalgia

Risk management of biosimilars in oncology: each medicine is a work in progress

Drug licensing and drug safety monitoring for standard chemical entities have been established and are routinely used. These have resulted in a solid foundation of knowledge from which confident therapeutic decisions can be made. For many chemical entities, this advanced level of experience is also present for the generic products. The expertise surrounding the development of biosimilar competitor versions is increasing and progress is encouraging. To address the re-engineering and comparability complexities of biosimilars, the European Union imposed a requirement that risk management plans be included in the medications’ marketing applications. This paper summarizes and discusses the circumstances complicating the public’s view of drug safety, historical incidents during the transition from innovative to competitor products, as well as retrospective assessments of the development and post-marketing experiences thus far with two biosimilars. Through assessing the market entries and post-marketing experiences of biosimilars used in oncology, the healthcare field can better prepare for the next wave of comparator-products: biosimilar monoclonal antibodies

A case of familial isolated hemihyperplasia

BACKGROUND: Hemihyperplasia (hemihypertrophy) is defined as asymmetric body overgrowth of one or more body parts. Hemihyperplasia can be isolated or be part of well-defined syndromes such as in the case of Beckwith-Wiedemann syndrome (BWS). Isolated hemihyperplasia is usually sporadic, but a number of familial occurrences have been described. CASE PRESENTATION: We describe a Tunisian family in which three maternal cousins and their maternal grandfather present with isolated hemihyperplasia. CONCLUSIONS: The etiology of isolated hemihyperplasia is unknown although in BWS, genomic imprinting has been shown to play a role in the asymmetric overgrowth. Given the similarity between these two conditions, it is possible that both may share a common pathogenesis. We also discuss the possible genetic mechanisms leading to the production of hemihyperplasia in this family

Theorems on existence and global dynamics for the Einstein equations

This article is a guide to theorems on existence and global dynamics of solutions of the Einstein equations. It draws attention to open questions in the field. The local-in-time Cauchy problem, which is relatively well understood, is surveyed. Global results for solutions with various types of symmetry are discussed. A selection of results from Newtonian theory and special relativity that offer useful comparisons is presented. Treatments of global results in the case of small data and results on constructing spacetimes with prescribed singularity structure or late-time asymptotics are given. A conjectural picture of the asymptotic behaviour of general cosmological solutions of the Einstein equations is built up. Some miscellaneous topics connected with the main theme are collected in a separate section.Comment: Submitted to Living Reviews in Relativity, major update of Living Rev. Rel. 5 (2002)