Segmental ureterectomy does not compromise the oncologic outcome compared with nephroureterectomy for pure ureter cancer

Purpose

Pure ureter cancers are rare and account for only 1–3 % of urothelial carcinomas with limited data. Nowadays, nephron-sparing methods are reserved mainly for imperative cases. This study intends to assess the oncologic outcome between segmental ureterectomy (SU) and radical nephroureterectomy (RNU) for pure ureteral urothelial carcinoma.

Methods

From July 2004 to August 2010, 112 patients at a single tertiary referral center were included. Perioperative data were obtained from our institutional database. Postoperative CT scan, cystoscopy, and contralateral renal echo were performed regularly for survey of disease recurrence.

Results

The mean length of follow-up was 43.8 and 48.3 months for the RNU and SU group, respectively. The bladder recurrences, local recurrences, distant metastasis, and cancer-specific survival rates showed no significant differences between RNU and SU (36.4 vs. 34.2 %, p = 0.83; 23.4 vs. 14.3 %, p = 0.27; and 16.9 vs. 8.6 %, p = 0.244, and 13.0 vs. 5.7 %, p = 0.249, respectively).

Conclusion

The study suggested that SU is not inferior to RNU for ureter cancer in oncologic outcomes and is less invasive and better nephron preservation.     

Chylothorax Complicating Video-Assisted Thoracoscopic Surgery for Non-small Cell Lung Cancer

Background

Chylothorax is an infrequent but well-known complication in lung cancer surgery. Previous published studies on this topic are limited, and thoracotomy has been the main surgical approach for treatment. However, chylothorax after lung cancer surgery performed solely by video-assisted thoracoscopic surgery (VATS) has rarely been investigated. The purpose of this study is to evaluate chylothorax after VATS for lung cancer.

Methods

The records of 776 patients with primary non-small-cell lung cancer (NSCLC) who underwent VATS for pulmonary resection and mediastinal lymph node dissection (MLND) at our hospital from January 2010 to August 2013 were retrospectively reviewed. Twenty patients with chylothorax (2.58 %) were included in the analysis.

Results

The 20 patients with chylothorax were all treated conservatively, but five patients (25 %) subsequently required reoperation for chylothorax. In patients with pleural drainage of less than 400 ml the first postoperative day, the chylothorax resolved with conservative treatment. Chylothorax also resolved in patients with pleural drainage of more than 400 ml the first or second postoperative day if drainage was less than 400 ml on postoperative day 4 and thereafter. Reoperations were required in cases with an increasing amount of pleural drainage on postoperative day 4 and thereafter.

Conclusions

Most of the chylothorax following VATS for lung cancer can be treated conservatively. However, the timing of surgical intervention for chylothorax following VATS for lung cancer can be earlier if pleural drainage does not show a trend toward decreasing with conservative treatment.     

Anaemia management in patients with chronic kidney disease: Taiwan practice guidelines

The introduction of erythropoiesis‐stimulating agents (ESAs) markedly improved the lives of many anaemic patients with chronic kidney disease (CKD). In Taiwan, the strategy of management of anaemia in patients with CKD was different from many other parts of the world. In 1996, the National Health Insurance Administration of Taiwan applied a more restrictive reimbursement criteria for ESA use in patients with CKD. ESA is to be initiated when non‐dialysis CKD patients have a serum creatinine >6 mg/dL and a hematocrit <28% to maintain a hematocrit level not exceeding 30%. The maximal dose of epoetin‐α or β was 20 000 U per month. The target haemoglobin range and dose limitation for ESAs were the same for dialysis CKD patients. Thus, long before randomized controlled trials showing an increased risk for cardiovascular events at nearly normal haemoglobin concentrations and higher ESA doses in CKD, nephrologists in Taiwan had avoided the use of disproportionately high dosages of ESAs to achieve a haemoglobin level of 10–11 g/dL. Moreover, intravenous iron supplementation was encouraged earlier in Taiwan in 1996, when we reached consensus on the diagnostic criteria for iron deficiency (serum ferritin <300 ng/mL and/or transferrin saturation <30%). The experience of CKD anaemia management in Taiwan demonstrated that a reasonable haemoglobin target can be achieved by using the lowest possible ESA dose and intravenous iron supplementation.     

The Role of Integrin αv in Proliferation and Differentiation of Human Dental Pulp Cell Response to Calcium Silicate Cement

Introduction

It has been proved that integrin αv activity is related to cell proliferation, differentiation, migration, and organ development. However, the biological functions of integrin αv in human dental pulp cells (hDPCs) cultured on silicate-based materials have not been explored. The aim of this study was to investigate the role of integrin αv in the proliferation and odontogenic differentiation of hDPCs cultured with the effect of calcium silicate (CS) cement and β-tricalcium phosphate (TCP) cement.

Methods

In this study, hDPCs were cultured on CS and TCP materials, and we evaluated fibronectin (FN) secretion and integrin αv expression during the cell attachment stage. After small interfering RNA transfection targeting integrin αv, the proliferation and odontogenesis differentiation behavior of hDPCs were analyzed.

Results

The results indicate that CS releases Si ion–increased FN secretion and adsorption, which promote cell attachment more effectively than TCP. The CS cement facilitates FN and αv subintegrin expression. However, the FN adsorption and integrin expression of TCP are similar to that observed in the control dish. Integrin αv small interfering RNA inhibited odontogenic differentiation of hDPCs with the decreased formation of mineralized nodules on CS. It also down-regulated the protein expression of multiple markers of odontogenesis and the expression of dentin sialophosphoprotein protein.

Conclusions

These results establish composition-dependent differences in integrin binding and its effectiveness as a mechanism regulating cellular responses to biomaterial surface.     

New horizontal v-shaped osteotomy for correction of protrusion of the zygoma and the zygomatic arch in East Asians: indication and results

Protrusion of the zygoma is commonly considered undesirable and unattractive among East-Asians, and many try to achieve a harmonious oval midface by having various cosmetic operations. However, effective contouring for a severe protruding zygoma has rarely been reported .The objectives of this study therefore were to investigate the feasibility and effectiveness of a horizontal V-shaped ostectomy for correction of protrusion of the zygoma and zygomatic arch, and to discuss its indications. From January 2008 to December 2011 we treated 27 patients by contouring of the zygoma with a horizontal V-shaped ostectomy through intraoral and preauricular incisions. The effectiveness was then evaluated with cephalometric radiographs, 3-dimensional computed tomography, and standard facial photographs taken before and after operation. The postoperative appearance of all 27 patients showed that the protrusion had been effectively reduced with no serious complications, and the facial contour had improved. The ?nal aesthetic outcomes were satisfactory for both surgeons and patients. The horizontal V-shaped osteotomy is a good technique for the reduction of protrusion of the zygoma and zygomatic arch, and it has the advantages of more convenient multishifting, better results, and fewer complications. It also ensures the integrity of the structure of the malar complex.     

Biomechanical effects of the implant material and implant–abutment interface in immediately loaded small-diameter implants

Objective

Small-diameter implants have been available since the 1990s, but few studies have analyzed their mechanical properties. This study evaluated the effects of the implant material and the implant–abutment connection designs on the primary stability and the marginal bone strain of small-diameter implant subject to immediate loading.

Materials and methods

Insertion torque value (ITV), implant stability quotient (ISQ), and Periotest value (PTV) of three implant systems with four parameters (titanium, titanium alloy, internal and external hexagon connections) were measured after placing implants into artificial type 2 jaw-bone models. Specimens were tested under both vertical and oblique static loads at 190 N. Peak values of the principal bone strain were recorded and analyzed statistically by the Kruskal–Wallis test and multiple-comparisons Bonferroni test.

Results

PTV and ISQ were higher for the NIOSM311 (internal-hex and Ti alloy) and FOSM311 (external-hex and pure Ti) implants, respectively, than for the NOSM311 (external-hex and Ti alloy) implant. Under vertical loading the peak value of peri-implant bone strains did not differ significantly among these three implant systems. However, the peak bone strains were at least 32 % lower for the NIOSM311 and FOSM311 implants than for the NOSM311 implant under lateral loading.

Conclusions

The implant material and the implant–abutment connection design significantly influence the peri-implant bone strain of immediately loaded small-diameter implants, but barely affect their primary stability.

Clinical Relevance

A commercially pure titanium implant with an internal connection has the potential to reduce the risk of implant failure of small-diameter implant related to biomechanical complications.     

Assessing short and long‐term educational impact of visits to hospice via a combination of qualitative methods

While qualitative methods have gained considerable recognition in medical education research, employing multiple qualitative data sources in assessing long‐term educational impact is rare. Utilising in‐depth data analysis method to six cross‐sectional cohorts (2004–2009) of students’ reflection papers (n = 213), this article demonstrates how students experienced subtle but important shifts in their attitudes (including personal, professional and spiritual domains) after making field visits to a hospice centre as part of the Special Needs Dentistry module. For retrospective assessment of learning retention, a pilot focus group was conducted with three junior faculty members who participated in the field visits to a hospice during their own undergraduate training. A subsequent focus group was conducted with graduates of the 2008 (n = 8) cohort using a refined discussion guide arising from the analysis of pilot group results. Graduates were unanimous in stating that the visits had sown ‘seeds’ in their minds and hearts, seeds which started to grow after they completed dental school and began to practice. This is demonstrative of the long‐term positive educational impact of the pedagogical design that entailed a special site visit coupled with post‐visit debrief and written reflection.     

Functional traits explain variation in plant life history strategies

Ecologists seek general explanations for the dramatic variation in species abundances in space and time. An increasingly popular solution is to predict species distributions, dynamics, and responses to environmental change based on easily measured anatomical and morphological traits. Trait-based approaches assume that simple functional traits influence fitness and life history evolution, but rigorous tests of this assumption are lacking, because they require quantitative information about the full lifecycles of many species representing different life histories. Here, we link a global traits database with empirical matrix population models for 222 species and report strong relationships between functional traits and plant life histories. Species with large seeds, long-lived leaves, or dense wood have slow life histories, with mean fitness (i.e., population growth rates) more strongly influenced by survival than by growth or fecundity, compared with fast life history species with small seeds, short-lived leaves, or soft wood. In contrast to measures of demographic contributions to fitness based on whole lifecycles, analyses focused on raw demographic rates may underestimate the strength of association between traits and mean fitness. Our results help establish the physiological basis for plant life history evolution and show the potential for trait-based approaches in population dynamics.Recent evidence for global patterns of functional variation in plants, such as the leaf economics spectrum (1, 2), the wood economics spectrum (3), and the seed size–seed number tradeoff (4, 5), has convinced many ecologists that functional traits offer the best available approach for achieving a general predictive understanding of communities and ecosystems (6, 7). Trait-based approaches are now being used to predict the outcome of community assembly (8–10), global vegetation dynamics (11), and the rate of ecosystem processes (6, 12–14). A central assumption of trait-based ecology is that morphological traits determine physiological performance, which influences vital rates and determines individual fitness and life history evolution (15, 16). However, because of the challenge of quantifying the contribution of traits to fitness, the assumed links between functional traits and life history have not been fully tested.Research in tropical and Mediterranean forests has revealed cross-species relationships between functional traits and the survival and growth rates of individuals (3, 17–24). Although these relationships provide evidence that functional traits influence vital rates, they offer only limited insight into associations between those traits and individual fitness and life history. Vital rates (e.g., survival and fecundity) represent fitness components, but their influence on mean fitness, defined as the population growth rate (λ), is best understood in the context of the full lifecycle of a species (25, 26). A significant negative correlation between wood density and individual growth (18) might not translate into a significant effect on mean fitness if individual growth has little influence on λ. Conversely, a weak relationship between a functional trait and another vital rate could have a significant effect on mean fitness if that vital rate has a strong influence on λ. Perturbation analyses, such as the sensitivities and elasticities frequently applied to matrix projection models (27), address this problem by quantifying the contribution of vital rates to λ (28), making it possible to characterize a species'' overall life history in terms of the relative importance of survival, individual growth, and fecundity to mean fitness. Species with slow life histories have population growth rates with high elasticities to survival, whereas species with fast life histories have relatively higher elasticities to individual growth or fecundity (29, 30).Armed with vital rate elasticities, we can test quantitative hypotheses about whether functional tradeoffs scale up to generate life history tradeoffs. For example, plants can allocate their reproductive effort to provision a few large seeds, which tolerate low light and resource availability and have a high survival probability, or they can spread their reproductive effort among many small seeds, maximizing fitness under high resource availability (31, 32). If this functional tradeoff at the seedling stage translates into a life history tradeoff, seed mass should be positively related to the elasticity of the population growth rate to survival and negatively related to elasticities to individual growth and fecundity. The leaf economics spectrum represents another allocation tradeoff. Species can construct long-lived, well-defended leaves that are often favored in low resource environments or build leaves that assimilate carbon quickly under conditions of high resource availability but are prone to rapid tissue loss (1, 33). Species with slow leaf economics traits, such as long leaf lifespans, low specific leaf area (SLA), and low leaf N, might also lead slow lives, characterized by high elasticities to survival and low elasticities to individual growth and recruitment. A wood economics spectrum also exists: species with dense wood tend to have higher survival but lower relative growth rates than species with soft wood (3, 34). Elasticities to survival should increase with wood density, whereas elasticities to individual growth and fecundity should decrease.The main obstacle in testing these hypotheses is availability of the detailed demographic data necessary to describe a species’ full lifecycle and estimate vital rate elasticities. We overcame this limitation by crossing the TRY Global Plant Traits Database (35) with the COMPADRE Plant Matrix Database (www.compadre-db.org/), a collection of published matrix population models. This approach produced a dataset of 222 plant species spanning a global range of biomes and perennial growth forms (Table S1), for which we have at least one functional trait measurement as well as a matrix population model that we used to calculate the elasticity of the population growth rate to each of the three vital rates: survival, growth, and fecundity (30).Our primary objective was to evaluate the ability of functional traits to explain variation across species in life history, which we quantified with vital rate elasticities. Our secondary objective was to evaluate whether inferences about life history can be drawn directly from the raw vital rates, which would save researchers the considerable time and effort required to parameterize population models and calculate elasticities. We used two statistical approaches to quantify relationships between vital rate elasticities and seed mass, wood density, and leaf economics traits (leaf lifespan, SLA, and leaf N). Dirichlet regression is a multivariate approach that accounts for the fact that the survival, growth, and fecundity elasticities for each species sum to one but does not account for phylogenetic relationships. Phylogenetic generalized least squares (PGLS) regression ignores the nonindependence of the elasticities but accounts for phylogenetic relationships. We repeated both types of regressions with plant growth form and then biome included as covariates to confirm that trait effects did not simply represent differences between trees and herbaceous species or plants adapted to different environments.     

The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase

Complex hereditary spastic paraplegia (HSP) is a genetic disorder that causes lower limb spasticity and weakness and intellectual disability. Deleterious mutations in the poorly characterized serine hydrolase DDHD2 are a causative basis for recessive complex HSP. DDHD2 exhibits phospholipase activity in vitro, but its endogenous substrates and biochemical functions remain unknown. Here, we report the development of DDHD2^−/− mice and a selective, in vivo-active DDHD2 inhibitor and their use in combination with mass spectrometry-based lipidomics to discover that DDHD2 regulates brain triglycerides (triacylglycerols, or TAGs). DDHD2^−/− mice show age-dependent TAG elevations in the central nervous system, but not in several peripheral tissues. Large lipid droplets accumulated in DDHD2^−/− brains and were localized primarily to the intracellular compartments of neurons. These metabolic changes were accompanied by impairments in motor and cognitive function. Recombinant DDHD2 displays TAG hydrolase activity, and TAGs accumulated in the brains of wild-type mice treated subchronically with a selective DDHD2 inhibitor. These findings, taken together, indicate that the central nervous system possesses a specialized pathway for metabolizing TAGs, disruption of which leads to massive lipid accumulation in neurons and complex HSP syndrome.Determining the genetic basis for rare hereditary human diseases has benefited from advances in DNA sequencing technologies (1). As a greater number of disease-causing mutations are mapped, however, it is also becoming apparent that many of the affected genes code for poorly characterized proteins. Assigning biochemical and cellular functions to these proteins is critical to achieve a deeper mechanistic understanding of human genetic disorders and for identifying potential treatment strategies.Hereditary spastic paraplegia (HSP) is a genetically heterogeneous neurologic syndrome marked by spasticity and lower extremity weakness (2). Many genetic types of HSP have been identified and are numbered according to their order of discovery [spastic paraplegia (SPG) 1-72] (2, 3). Of these genetic variants, more than 40 have been mapped to causative mutations in protein-coding genes. HSP genes code for a wide range of proteins that do not conform to a single sequence- or function-related class. A subset of HSP genes, including PNPLA6 (or neuropathy-target esterase) (SPG39) (4), DDHD1 (SPG28) (5), and DDHD2 (SPG54) (3, 6–8), code for serine hydrolases. These enzymes have been designated as (lyso)phospholipases based on in vitro substrate assays (9–11), but their endogenous substrates and physiological functions remain poorly understood. The mutational landscape that affects these lipid hydrolases to cause recessive HSP is complex but collectively represents a mix of null and putatively null and/or functional mutations. Moreover, the type of HSP appears to differ in each case, with DDHD1 mutations causing uncomplicated HSP, whereas PNPLA6 and DDHD2 mutations lead to complex forms of the disease that exhibit additional phenotypes including, in the case of DDHD2, intellectual disability. Human subjects with DDHD2 mutations also displayed evidence of brain lipid accumulation as detected by cerebral magnetic resonance spectroscopy (6). Both rodent and human DDHD2 enzymes are highly expressed in the brain compared with most peripheral tissues (6, 9); however, the specific lipids regulated by DDHD2 in the central nervous system (CNS) have not yet been identified.Determining the metabolic function of DDHD2 in the brain is an important step toward understanding how mutations in this enzyme promote complex HSP and for identifying possible therapeutic strategies for the disease. Toward this end, we report herein the generation and characterization of DDHD2^−/− mice and a selective DDHD2 inhibitor. DDHD2^−/− mice exhibit defects in movement and cognitive function. Mass spectrometry (MS)-based lipidomics (12, 13) revealed a striking and selective elevation in triglycerides (triacylglycerols, or TAGs) throughout the CNS, but not in peripheral tissues, of DDHD2^−/− mice. This metabolic change correlated with pervasive lipid droplet (LD) accumulation in neuronal cell bodies of DDHD2^−/− mice. Biochemical assays confirmed that DDHD2 possesses TAG hydrolase activity. Finally, wild-type mice treated subchronically with a DDHD2 inhibitor also exhibited significant elevations in CNS TAGs. These data, taken together, indicate that DDHD2 is a principal TAG hydrolase of the mammalian brain and point to deregulation of this pathway as a major contributory factor to complex HSP.