Salvage radiation therapy is often necessary in men who have undergone radical prostatectomy and have evidence of prostate-cancer recurrence signaled by a persistently or recurrently elevated ...prostate-specific antigen (PSA) level. Whether antiandrogen therapy with radiation therapy will further improve cancer control and prolong overall survival is unknown.
In a double-blind, placebo-controlled trial conducted from 1998 through 2003, we assigned 760 eligible patients who had undergone prostatectomy with a lymphadenectomy and had disease, as assessed on pathological testing, with a tumor stage of T2 (confined to the prostate but with a positive surgical margin) or T3 (with histologic extension beyond the prostatic capsule), no nodal involvement, and a detectable PSA level of 0.2 to 4.0 ng per milliliter to undergo radiation therapy and receive either antiandrogen therapy (24 months of bicalutamide at a dose of 150 mg daily) or daily placebo tablets during and after radiation therapy. The primary end point was the rate of overall survival.
The median follow-up among the surviving patients was 13 years. The actuarial rate of overall survival at 12 years was 76.3% in the bicalutamide group, as compared with 71.3% in the placebo group (hazard ratio for death, 0.77; 95% confidence interval, 0.59 to 0.99; P=0.04). The 12-year incidence of death from prostate cancer, as assessed by means of central review, was 5.8% in the bicalutamide group, as compared with 13.4% in the placebo group (P<0.001). The cumulative incidence of metastatic prostate cancer at 12 years was 14.5% in the bicalutamide group, as compared with 23.0% in the placebo group (P=0.005). The incidence of late adverse events associated with radiation therapy was similar in the two groups. Gynecomastia was recorded in 69.7% of the patients in the bicalutamide group, as compared with 10.9% of those in the placebo group (P<0.001).
The addition of 24 months of antiandrogen therapy with daily bicalutamide to salvage radiation therapy resulted in significantly higher rates of long-term overall survival and lower incidences of metastatic prostate cancer and death from prostate cancer than radiation therapy plus placebo. (Funded by the National Cancer Institute and AstraZeneca; RTOG 9601 ClinicalTrials.gov number, NCT00002874 .).
The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene ...reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD
, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.
Bone is the most common organ for tumor metastasis, especially in patients with cancers of the breast or prostate. Bone metastases disrupt skeletal metabolism and result in considerable skeletal ...morbidity, including intractable, chronic bone pain, hypercalcemia of malignancy, pathologic fracture and spinal-cord compression. In addition to the chronic pain caused by bone metastases, skeletal-related events (SREs) such as pathologic fractures and spinal-cord compression can result in acute increases in pain. These effects can severely impair mobility and contribute to a general decrease in quality of life. Palliative options to treat bone metastases include radiotherapy, analgesics, surgery and bisphosphonates. These drugs bind to the surface of the bone and impair osteoclast-mediated bone resorption, and reduce the tumor-associated osteolysis that is initiated by the development of skeletal metastases. In addition to preventing SREs, bisphosphonates can palliate bone pain caused by a variety of solid tumors. This Review summarizes the clinical trial data of bisphosphonates for the prevention of SREs and the palliation of bone pain. Among these agents, nitrogen-containing bisphosphonates are recognized as the most effective, and zoledronic acid has demonstrated the broadest clinical utility.
The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of ...patients with tuberous sclerosis complex (TSC).
A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients' records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden.
Of the 103 patients with TSC, 40%were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers.
The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed.
The objectives of this study were to systematically review the literature for studies that used cone beam CT (CBCT) to automatically or semi-automatically model the upper airway (including the ...pharyngeal, nasal and paranasal airways), and to assess their validity and reliability. Several electronic databases (MEDLINE®, MEDLINE In-Process & Other Non-Indexed Citations, all evidence-based medicine reviews including the Cochrane database, and Scopus) were searched. Abstracts that appeared to meet the initial selection criteria were selected by consensus. The original articles were then retrieved and their references were searched manually for potentially suitable articles that were missed during the electronic search. Final articles that met all the selection criteria were evaluated using a customized evaluation checklist. 16 articles were finally selected. From these, five scored more than 50% based on their methodology. Although eight articles reported the reliability of the airway model generated, only three used intraclass correlation (ICC). Two articles tested the accuracy/validity of airway models against the gold standard, manual segmentation, using volumetric measurements; however, neither used ICC. Only three articles properly tested the reliability of the three-dimensional (3D) upper airway model generated from CBCT and only one article had sufficiently sound methodology to test the airway model's accuracy/validity. The literature lacks proper scientific justification of a solid and optimized CBCT protocol for airway imaging. Owing to the limited number of adequate studies, it is difficult to generate a strong conclusion regarding the current validity and reliability of CBCT-generated 3D models.
The authors conducted a systematic review to consolidate the current knowledge regarding craniofacial morphological characteristics associated with obstructive sleep apnea syndrome (OSAS) in ...nonsyndromic pediatric patients.
The authors included clinical studies in which participants were younger than 18 years, polysomnography was performed to determine the presence and severity of OSAS and the study group was compared with a control group or normative growth center data. The authors excluded studies with syndromic participants or participants who had received orthodontic treatment, orthognathic treatment or both previously.
The authors identified nine articles. They conducted a meta-analyses of the data from all but one of the studies to evaluate the eight most common cephalometric variables in children with OSAS. The I(2) values were 79.53 percent for the angle from the basion point to the sella nasion (SN) line, 89.54 percent for the angle between the SN and palatal plane lines and 96.82 percent for the angle between the mandibular plane and SN lines (MP-SN). Therefore, for these three variables, the authors conducted a random-effect model meta-analysis. For the remaining five variables (MP-SN, the angle from SN to Apoint, the angle from SN to B point SNB, the angle from A point to nasion point to B point ANB and the angle from articulare point to gonion point to gnathion point), I(2) values were all less than 40 percent, and therefore the authors conducted a fixed-effects model meta-analysis. Three of the evaluated cephalometric variables (MP-SN, SNB and ANB) had statistically significant differences in comparison with those in a control group. Although the values of these variables were increased in children with OSAS, results of the meta-analysis should be considered cautiously owing to the limited number of cephalometric variables included.
Dentists who identify patients with a craniofacial morphology consistent with pediatric OSAS (retrusive chin, steep mandibular plane, vertical direction of growth and a tendency toward Class II malocclusion) should inquire further into their patients' medical histories. When the craniofacial morphology is accompanied by a history of snoring, inability to breathe through the nose, significant allergies, asthma or obesity, the dentist should refer the patient to an otolaryngologist for assessment.
The periodontal ligament (PDL) provides support, proprioception, nutrition, and protection within the tooth–PDL–bone complex (TPBC). While understanding the mechanical behavior of the PDL is ...critical, current research has inferred PDL mechanics from finite element models, from experimental measures on complete TPBCs, or through direct measurement of isolated PDL sections. Here, transducers are used in an attempt to quantify ex vivo PDL strain. In-fiber Bragg grating (FBG) sensors are small flexible sensors that can be placed within an intact TPBC and yield repeatable strain measurements from within the PDL space. The objective of this study was to determine: 1) if the FBG strain measured from the PDL space of intact swine premolars ex vivo was equivalent to physical PDL strains estimated through finite element analysis and 2) if a change in FBG strain could be linearly related to a change in finite element strain under variable tooth displacement, applied to an intact swine TPBC. Experimentally, individual TPBCs were subjected to 2 displacements (n = 14). The location of the FBG was determined from representative micro–computed tomography images. From a linear elastic finite element model of a TPBC, the strain magnitudes at the sensor locations were recorded. An experimental ratio (i.e., FBG strain at the first displacement divided by the FBG strain at the second displacement) and a finite element ratio (i.e., finite element strain at the first displacement divided by the finite element strain at the second displacement) were calculated. A linear regression model indicated a statistically significant relationship between the experimental and finite element ratio (P = 0.017) with a correlation coefficient (R2) of 0.448. It was concluded that the FBG sensor could be used as a measure for a change in strain and thus could be implemented in applications where the mechanical properties of an intact PDL are monitored over time.
Many dental procedures are considered aerosol-generating procedures that may put the dental operator and patients at risk for cross-infection due to contamination from nasal secretions and saliva. ...This aerosol, depending on the size of the particles, may stay suspended in the air for hours. The primary objective of the study was to characterize the size and concentrations of particles emitted from 7 different dental procedures, as well as estimate the contribution of the nasal and salivary fluids of the patient to the microbiota in the emitted bioaerosol. This cross-sectional study was conducted in an open-concept dental clinic with multiple operators at the same time. Particle size characterization and mass and particle concentrations were done by using 2 direct reading instruments: Dust-Trak DRX (Model 8534) and optical particle sizer (Model 3330). Active bioaerosol sampling was done before and during procedures. Bayesian modeling (SourceTracker2) of long-reads of the 16S ribosomal DNA was used to estimate the contribution of the patients’ nasal and salivary fluids to the bioaerosol. Aerosols in most dental procedures were sub-PM1 dominant. Orthodontic debonding and denture adjustment consistently demonstrated more particles in the PM1, PM2.5, PM4, and PM10 ranges. The microbiota in bioaerosol samples were significantly different from saliva and nasal samples in both membership and abundance (P < 0.05) but not different from preoperative ambient air samples. A median of 80.15% of operator exposure was attributable to sources other than the patients’ salivary or nasal fluids. Median operator’s exposure from patients’ fluids ranged from 1.45% to 2.75%. Corridor microbiota showed more patients’ nasal bioaerosols than oral bioaerosols. High-volume saliva ejector and saliva ejector were effective in reducing bioaerosol escape. Patient nasal and salivary fluids are minor contributors to the operator’s bioaerosol exposure, which has important implications for COVID-19. Control of bioaerosolization of nasal fluids warrants further investigation.
Summary
Mild traumatic brain injury (mTBI) and sports concussion are a growing public health concern, with increasing demands for more rigorous methods to quantify changes in the brain post‐injury. ...Electrophysiology, and in particular, transcranial magnetic stimulation (TMS), have been demonstrated to provide prognostic value in a range of neurological conditions; however, no review has quantified the efficacy of TMS in mTBI/concussion. In the present study, we present a systematic review and critical evaluation of the scientific literature from 1990 to 2014 that has used TMS to investigate corticomotor excitability responses at short‐term (< 12 months), medium‐term (1–5 years), and long‐term (> 5 years) post‐mTBI/concussion. Thirteen studies met the selection criteria, with six studies presenting short‐term changes, five studies presenting medium‐term changes, and two studies presenting long‐term changes. Irrespective of time post‐concussion, change in intracortical inhibition was the most reported observation. Other findings included increased stimulation threshold, and slowed neurological conduction time. Although currently limited, the data suggest that TMS has prognostic value in detecting neurophysiological changes post‐mTBI/concussion.
Background
Until recently there has been little data available about long-term outcomes of laparoscopic rectal cancer surgery. But new randomized controlled trials regarding laparoscopic colorectal ...surgery have been published. The aim of this study was to compare the short- and long-term oncologic outcomes of laparoscopy and open surgery for rectal cancer through a systematic review of the literature and a meta-analysis of relevant RCTs.
Methods
A systematic review of Medline, Embase and the Cochrane library from January 1966 to October 2016 with a subsequent meta-analysis was performed. Only randomized controlled trials with data on circumferential resection margins were included. The primary outcome was the status of circumferential resection margins. Secondary outcomes included lymph node yield, distal resection margins, disease-free and overall survival rates for 3 and 5 years and local recurrence rates.
Results
Eleven studies were evaluated, involving a total of 2018 patients in the laparoscopic group and 1526 patients in the open group. The presence of involved circumferential margins was reported in all studies. There were no statistically significant differences in the number of positive circumferential margins between the laparoscopic group and open group, RR 1.16, 95% CI 0.89–1.50 and no significant differences in involvement of distal margins (RR 1.13 95% CI 0.35–3.66), completeness of mesorectal excision (RR 1.22, 95% CI 0.82–1.82) or number of harvested lymph nodes (mean difference = −0.01, 95% CI −0.89 to 0.87). Disease-free survival rates at 3 and 5 years were not different (
p
= 0.26 and
p
= 0.71 respectively), and neither were overall survival rates (
p
= 0.19 and
p
= 0.64 respectively), nor local recurrence rates (RR 0.88, 95% CI 0.63–1.23).
Conclusions
Laparoscopic surgery for rectal cancer is associated with similar short-term and long-term oncologic outcomes compared to open surgery. The oncologic quality of extracted specimens seems comparable regardless of the approach used.
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