Is the diagnostic yield of prostate needle biopsies affected by prostate volume?

ObjectivesTo determine the effect of prostate volume on the diagnostic yield of prostate biopsies.Materials and methods155 consecutive patients underwent 12-core transrectal ultrasound guided needle biopsies. Data were collected prospectively on age, serum PSA, digital rectal examination (DRE), previous prostate biopsies, prostate volume and pathologic result. Univariate and multivariate logistic regressions were undertaken to determine the effect of prostate volume on the risk for a positive biopsy.Results45 patients (29%) were diagnosed with cancer. The median patient age was 63 (range 48–82) years, the median PSA level was 6.7 ng/ml (0.5–156 ng/ml), and the median prostate volume was 57 ml (16–273 ml). 42 patients (27%) had an abnormal DRE and 51 (33%) had undergone previous prostate biopsies. Positive biopsy rates were 39%, 33%, and 14% for prostate volume below 46 ml, between 45 and 73 ml, and above 72 ml, respectively. Univariate analysis showed that age, serum PSA, DRE and prostate volume were all associated with a positive biopsy. Multivariate analysis adjusted for age, PSA and DRE showed a significant risk increase for a positive biopsy in smaller prostates. (OR = 5.6 95% CI 1.75–17.89; and 8.86 95% CI 2.72–28.82, for prostate volume between 45 and 72 ml and below 45 ml, respectively).ConclusionThe diagnostic yield of prostate biopsies is significantly lower in large prostates. As the result the standard 12-core biopsy may be insufficient for the diagnosis of cancer in large prostates.     

Total hip arthroplasty in patients with fibrous dysplasia: a modern update

BackgroundFibrous dysplasia (FD) results from an abnormality in lamellar bone formation and most frequently involves the proximal femur. This can lead to the development of osteoarthritis requiring total hip arthroplasty (THA). Such cases are challenging, and there is a lack of information guiding best management. As such, we devised a study assessing the outcomes and complications in patients with FD undergoing THA with modern implant technology, and we outlined our preferred surgical technique.MethodsA search of our institutional arthroplasty database was performed to identify patients who underwent THA for FD between January 2001 and July 2018 at Mount Sinai Hospital in Toronto, Canada. Data regarding implants used and the use of allograft material or metal augments or both were obtained. Complications and revision requirements were noted. Radiographic and clinical leg length discrepancies were assessed.ResultsA total of 10 hips in 9 patients who underwent THA for FD were identified. Mean follow-up time was 6.0 years (range 0.5 to 10.3 yr). The majority of patients underwent THA using uncemented femoral and acetabular components with large femoral heads on highly cross-linked polyethylene liners. Most cases (80% of hips) required allograft to the proximal femur. A single complication requiring revision was noted. In 90% of hip surgeries, the patient required transfusion of packed red blood cells. Mean radiographic and clinical leg length discrepancies were 0.9 cm (range −2.4 to 2.4 cm) and 0.9 cm (range −4 to 0 cm), respectively.ConclusionContrary to previous reports, low complication and revision rates were observed with cementless components and routine use of allograft material. The challenging nature of such cases warrants use of an experienced arthroplasty treatment team.     

Factors influencing outcome and incidence of long-term complications in children who underwent autologous stem cell transplantation for acute myeloid leukemia in first complete remission

To evaluate factors influencing outcome and incidence of long-term complications, we analyzed, in a retrospective, multicenter study, 387 children who underwent autologous hematopoietic stem cell transplantation (HSCT) for acute myeloid leukemia (AML) in first complete remission (CR). Median follow-up time from transplantation was 60 months. Transplantation of bone marrow cells was performed in 318 children, whereas in 60 patients peripheral blood progenitor cells (PBPCs) were used. In multivariate analysis, we investigated the variables influencing probability of hematopoietic recovery, transplantation-related mortality (TRM), relapse, and leukemia-free survival (LFS). We found that use of PBPCs as stem cell sources and use of BCNU (N,N-bis[2-chloroethyl]-N-nitrosourea), amsacrine, VP-16, and cytosine arabinoside (BAVC) as a preparative regimen were associated with faster neutrophil recovery. Infusion of PBPCs, young age of patients, use of BAVCs, and absence of marrow purging predicted an accelerated platelet reconstitution. The 5-year Kaplan-Meier estimates of TRM, relapse, and LFS were 3% +/- 1%, 39% +/- 3% and 60% +/- 3%, respectively. Relapse probability was increased in children given the BAVC regimen, and it was decreased after in vitro purging of hematopoietic progenitors and in children with a French-American-British classification of M3 and a time interval of 170 days or more between CR and HSCT. These 2 latter variables favorably influenced the probability of LFS, which was, by contrast, reduced with the BAVC regimen. Thirty-three percent of patients surviving more than 18 months experienced at least one late sequela; use of total body irradiation was the only predictive factor. The results obtained in this analysis can be of help in designing prospective studies of autologous HSCT in children with AML in first CR.     

Rapid turnover of acetyl groups in the four core histones of simian virus 40 minichromosomes.

The four core histones (H2a, H2b, H3, and H4) bound to simian virus 40 minichromosomes isolated from infected cells contain rapidly labeled acetyl groups in internal positions of the histone polypeptide chain. Upon chase, these acetyl residues decay with a half-life of less than 15 min. The acetyl groups are incorporated in histones bound to mature chromosomes and not in newly synthesized histones bound to replicating viral chromosomes. The rate of acetate incorporation is not related to the degree of steady state acetylation of the individual viral or cellular histones. This rate is 4-fold higher for the viral chromatin than for its cellular counterpart isolated from the same nuclei. The possible role for histone acetylation in viral genome expression is discussed.     

Mapping the diatom redox-sensitive proteome provides insight into response to nitrogen stress in the marine environment

Diatoms are ubiquitous marine photosynthetic eukaryotes responsible for approximately 20% of global photosynthesis. Little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a quantitative mass spectrometry-based approach to elucidate the redox-sensitive signaling network (redoxome) mediating the response of diatoms to oxidative stress. We quantified the degree of oxidation of 3,845 cysteines in the Phaeodactylum tricornutum proteome and identified approximately 300 redox-sensitive proteins. Intriguingly, we found redox-sensitive thiols in numerous enzymes composing the nitrogen assimilation pathway and the recently discovered diatom urea cycle. In agreement with this finding, the flux from nitrate into glutamine and glutamate, measured by the incorporation of ¹⁵N, was strongly inhibited under oxidative stress conditions. Furthermore, by targeting the redox-sensitive GFP sensor to various subcellular localizations, we mapped organelle-specific oxidation patterns in response to variations in nitrogen quota and quality. We propose that redox regulation of nitrogen metabolism allows rapid metabolic plasticity to ensure cellular homeostasis, and thus is essential for the ecological success of diatoms in the marine ecosystem.Aerobic organisms produce reactive oxygen species (ROS) as a byproduct of oxygen-based metabolic pathways, such as photosynthesis, photorespiration, and oxidative phosphorylation (1). Perturbations in oxygenic metabolism under various stress conditions can induce oxidative stress from overproduction of ROS (2, 3). Because ROS are highly reactive forms of oxygenic metabolites, critical mechanisms for ROS detoxification have evolved consisting of ROS-scavenging enzymes and small molecules, including glutathione (GSH) (4). As the most abundant low molecular weight thiol antioxidant, GSH has critical roles in maintaining a proper cellular thiol–disulfide balance and in detoxifying H₂O₂ via the ascorbate–GSH cycle (5).Although classically ROS were considered toxic metabolic byproducts that ultimately lead to cell death, it is now recognized that ROS act as central secondary messengers involved in compartmentalized signaling networks (1, 6–8). Modulation of various cell processes by ROS signaling is mediated largely by posttranslational thiol oxidation, whereby their physical structure and biochemical activity are modified upon oxidation (9). Thus, the redox states of these proteins possess crucial information needed for cell acclimation to stress conditions (10, 11). The emergence of advanced redox proteomic approaches, such as the OxICAT method (12), has created new opportunities to identify redox-sensitive proteins (e.g., redoxome) on the system level and to quantify their precise level of oxidation on exposure to environmental stress conditions.Marine photosynthetic microorganisms (phytoplankton) are the basis of marine food webs. Despite the fact that their biomass represents only approximately 0.2% of the photosynthetic biomass on earth, they are responsible for nearly 50% of the annual global carbon-based photosynthesis and greatly influence the global biogeochemical carbon cycle (13). This high ratio of productivity to biomass, reflected in high turnover rates, makes phytoplankton highly responsive to climate change. Phytoplankton can grow rapidly and form massive blooms that stretch over hundreds of kilometers in the oceans and are regulated by such environmental factors as nutrient availability and biotic interactions with grazers and viruses.Diatoms are a highly diverse clade of phytoplankton, responsible for roughly 20% of global primary productivity (14). Consequently, diatoms play a central role in the biogeochemical cycling of important nutrients, including carbon, nitrogen, and silica, which constitute part of their ornate cell wall. As members of the eukaryotic group known as stramenopiles (or heterokonts), diatoms are derived from a secondary endosymbiotic event involving red and green algae engulfed within an ancestral protest (15).The unique multilineage content of diatom genomes reveals a melting pot of biochemical characteristics that resemble bacterial, plant, and animal traits, including the integration of a complete urea cycle, fatty acid oxidation in the mitochondria, and plant C4-like related pathways (16, 17). During bloom succession, phytoplankton cells are subjected to diverse environmental stress conditions that lead to ROS production, such as allelopathic interactions (18), CO₂ availability (19, 20), UV exposure (21), iron limitation (22), and viral infection (23). Recently reported evidence suggests that diatoms possess a surveillance system based on the induction of ROS that have been implicated in response to various environmental stresses (22, 24). Nevertheless, very little is known about cell signaling processes in marine phytoplankton and their potential role in acclimation to rapid fluctuations in the chemophysical gradients in the marine environment (25).Using a mass spectrometry-based approach, we examined the diatom redoxome and quantified its degree of oxidation under oxidative stress conditions. The wealth of recently identified redox-sensitive proteins participating in various cellular functions suggests a fundamental role of redox regulation in diatom biology. We mapped the redox-sensitive enzymes into a metabolic network and evaluated their role in the adjustment of metabolic flux under variable environmental conditions. We further explored the redox sensitivity of the primary nitrogen-assimilating pathway and demonstrated the role of compartmentalized redox regulation in cells under nitrogen stress conditions using a redox-sensitive GFP sensor targeted to specific subcellular localizations.