To evaluate technical outcome and safety of computed tomographic (CT) fluoroscopy-guided percutaneous fiducial marker placement before CyberKnife stereotactic radiosurgery.
Retrospective analysis was ...performed of 196 patients (106 men) undergoing CT fluoroscopy-guided fiducial marker placement in 222 consecutive procedures under local anesthesia from March 2006 to February 2012. Technical success was defined as fiducial marker location in the tumor or vicinity suitable for CyberKnife radiosurgery evaluated on postinterventional planning CT. Complications were classified per Society of Interventional Radiology (SIR).
One hundred ninety-six patients (age, 61.5 y ± 13.1) underwent percutaneous placement of 321 fiducial markers (mean per tumor, 1.2 ± 0.5; range, 1-4) in 37 primary tumors and 227 metastases in the thorax (n = 121), abdomen (n = 122), and bone (n = 21). Fiducial marker placement was technically successful in all procedures: intratumoral localization in 193 (60.1%), at tumor margin in 50 (15.6%), and outside of tumor in 78 cases (24.3%; mean distance to marker, 0.4 cm ± 0.6; range, 0-2.9 cm). Complications were observed in 63 placement procedures (28.4%), including minor self-limiting pneumothorax (n = 21; SIR class B) and self-limiting pulmonary hemorrhage (n = 35; SIR class A), and major pneumothorax requiring thoracostomy/drainage insertion (n = 14; SIR class D) and systemic toxicity of local anesthetic drug (n = 1; SIR class D).
CT fluoroscopy-guided percutaneous fiducial marker placement can be performed with high technical success under local anesthesia in various anatomic regions. Although self-limiting in most cases, pneumothorax and pulmonary hemorrhage are frequently observed during fiducial marker implantation into lung tumors.
We have derived a secondary structure model for 16S ribosomal RNA on the basis of comparative sequence analysis, chemical modification studies and nuclease susceptibility data. Nucleotide sequences ...of the E. coli and B. brevis 16S rRNA chains, and of RNAse T1 oligomer catalogs from 16S rRNAs of over 100 species of eubacteria were used for phylogenetic comparison. Chemical modification of G by glyoxal, A by m-chloroperbenzoic acid and C by bisulfite In naked 16S rRNA, and G by kethoxal in active and inactive 30S ribosomal subunits was taken as an indication of single stranded structure. Further support for the structure was obtained from susceptibility to RNases A and T1. These three approaches are in excellent agreement. The structure contains fifty helical elements organized into four major domains, in which 46 percent of the nucleotides of 16S rRNA are involved in base pairing. Phylogenetic comparison shows that highly conserved sequences are found principally in unpaired regions of the molecule. No knots are created by the structure.
Abstract Background Experience of bullying victimisation in childhood and heightened interpersonal sensitivity have been independently linked to the clinical high risk for psychosis. Aim To examine ...the potential mediating effect of interpersonal sensitivity in explaining the link between childhood bullying victimisation and real-time paranoid ideation in adult participants at clinical high risk for psychosis. Method In a cross-sectional study data were collected for 64 individuals at clinical high risk for psychosis. Measures included history of bullying victimisation, interpersonal sensitivity and state paranoid ideation following exposure to a social virtual reality environment. The virtual reality scenario was a London Underground journey. Results Path analysis indicated that interpersonal sensitivity fully explained the significant association between severe bullying victimisation in childhood and paranoid ideation in the clinical-high risk group. Based on AIC criteria the best model selected was the full mediation model: severe bullying → interpersonal sensitivity → state paranoid ideation. The results suggest that severity of bullying is more important than frequency of bullying in explaining state paranoid ideation. Conclusions The significant role played by interpersonal sensitivity in the association between being bullied in childhood and paranoid ideation in the clinical high risk group suggests that this could become a target for intervention.
•Vaccinoscopie is an annual French web-based survey targeting mothers, which monitors vaccine coverage rates (VCRs) in children as well as the opinion of mothers regarding vaccination.•This ...publication focused on evolution of VCRs in infants during the period 2008–2018.•This study shows for the first time in 2018 an increased proportion of mothers in favour of vaccination.•During this period, the VCRs were stable and high for diphtheria, tetanus, poliomyelitis, pertussis and pneumococcus components and highly progressed for measles, mumps rubella, hepatitis B and meningococcus C components.•Extension of mandatory vaccination for all infants born from first of January 2018 in France further increased MenC and HepB VCRs.
Monitoring of vaccination coverage rates (VCRs) is essential to assess the implementation of a country's vaccine policy and its effectiveness. Through the French Vaccinoscopy study, we measured the evolution of VCRs as well as mothers’ opinion towards vaccination between 2008 and 2018, before and after implementation of infant mandatory vaccination extension.
This is a study based on an internet-standardised questionnaire. In 2018, a representative sample of 3000 mothers of infants 0 to 35 months of age answered on their opinion on vaccination and reported all vaccinations recorded in their child's health record.
On the period considered, infant VCRs were stable and high for diphtheria, tetanus, poliomyelitis, pertussis and pneumococcus components and progressed for measles, mumps rubella, 2 doses at 24 months of age from 45.3% in 2008 to 81.0% in 2018, hepatitis B (HepB) complete primovaccination at 6 months of age from 45.9% in 2008 to 86.3% in 2017 and 95.5% in 2018, and meningococcus C (MenC) 1 dose at 6 months of age from 43.0% in 2017 to 74.2% in 2018. In 2018, 69.0% of mothers were in favour of vaccination while this rate dropped from 80.2% in 2012 to 64.0% in 2017, and 80.8 to 89.6% perceived HepB, MenC measles and pertussis vaccinations as useful/essential, percentages in progress versus 2017.
Following the implementation of infant mandatory vaccination in 2018, proportion of mothers in favour of vaccination increased significantly. HepB and MenC VCRs significantly progressed between 2017 and 2018.
The MinION sequencer has made in situ sequencing feasible in remote locations. Following our initial demonstration of its high performance off planet with Earth-prepared samples, we developed and ...tested an end-to-end, sample-to-sequencer process that could be conducted entirely aboard the International Space Station (ISS). Initial experiments demonstrated the process with a microbial mock community standard. The DNA was successfully amplified, primers were degraded, and libraries prepared and sequenced. The median percent identities for both datasets were 84%, as assessed from alignment of the mock community. The ability to correctly identify the organisms in the mock community standard was comparable for the sequencing data obtained in flight and on the ground. To validate the process on microbes collected from and cultured aboard the ISS, bacterial cells were selected from a NASA Environmental Health Systems Surface Sample Kit contact slide. The locations of bacterial colonies chosen for identification were labeled, and a small number of cells were directly added as input into the sequencing workflow. Prepared DNA was sequenced, and the data were downlinked to Earth. Return of the contact slide to the ground allowed for standard laboratory processing for bacterial identification. The identifications obtained aboard the ISS,
and
, matched those determined on the ground down to the species level. This marks the first ever identification of microbes entirely off Earth, and this validated process could be used for in-flight microbial identification, diagnosis of infectious disease in a crewmember, and as a research platform for investigators around the world.
No study has contextualized the excess mortality attributable to racial and ethnic disparities in surgical outcomes. Further, not much effort has been made to quantify the effort needed to eliminate ...these disparities.
We examined the current trends in mortality attributable to racial or ethnic disparities in the US postsurgical population. We then identified the target for mortality reduction that would be necessary to eliminate these disparities by 2030.
We performed a population-based study of 1,512,974 high-risk surgical procedures among adults (18-64 years) performed across US hospitals between 2000 and 2020.
Between 2000 and 2020, the risk-adjusted mortality rates declined for all groups. Nonetheless, Black patients were more likely to die following surgery (adjusted relative risk 1.42; 95% CI, 1.39-1.46) driven by higher Black mortality in the northeast (1.60; 95% CI, 1.52-1.68), as well as the West (1.53; 95% CI, 1.43-1.62). Similarly, mortality risk remained consistently higher for Hispanics compared with White patients (1.21; 95% CI, 1.19-1.24), driven by higher mortality in the West (1.26; 95% CI, 1.21-1.31). Overall, 8364 fewer deaths are required for Black patients to experience mortality on the same scale as White patients. Similar figures for Hispanic patients are 4388. To eliminate the disparity between Black and White patients by 2030, we need a 2.7% annualized reduction in the projected mortality among Black patients. For Hispanics, the annualized reduction needed is 0.8%.
Our data provides a framework for incorporating population and health systems measures for eliminating disparity in surgical mortality within the next decade.
CONTEXT In the United States, 192 000 men were diagnosed as having prostate cancer in 2009, the majority with low-risk, clinically localized disease. Treatment of these cancers is associated with ...substantial morbidity. Active surveillance is an alternative to initial treatment, but long-term outcomes and effect on quality of life have not been well characterized. OBJECTIVE To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. DESIGN AND SETTING Decision analysis using a simulation model was performed: men were treated at diagnosis with brachytherapy, intensity-modulated radiation therapy (IMRT), or radical prostatectomy or followed up by active surveillance (a strategy of close monitoring of newly diagnosed patients with serial prostate-specific antigen measurements, digital rectal examinations, and biopsies, with treatment at disease progression or patient choice). Probabilities and utilities were derived from previous studies and literature review. In the base case, the relative risk of prostate cancer–specific death for initial treatment vs active surveillance was assumed to be 0.83. Men incurred short- and long-term adverse effects of treatment. PATIENTS Hypothetical cohorts of 65-year-old men newly diagnosed as having clinically localized, low-risk prostate cancer (prostate-specific antigen level <10 ng/mL, stage ≤T2a disease, and Gleason score ≤6). MAIN OUTCOME MEASURE Quality-adjusted life expectancy (QALE). RESULTS Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years QALYs), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer–specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. CONCLUSIONS Under a wide range of assumptions, for a 65-year-old man, active surveillance is a reasonable approach to low-risk prostate cancer based on QALE compared with initial treatment. However, individual preferences play a central role in the decision whether to treat or to pursue active surveillance.
The complement system plays an important role in mediating tissue injury after oxidative stress. The role of mannose-binding lectin (MBL) and the lectin complement pathway (LCP) in mediating ...complement activation after endothelial oxidative stress was investigated. iC3b deposition on hypoxic (24 hours; 1% O(2))/reoxygenated (3 hours; 21% O(2)) human endothelial cells was attenuated by N-acetyl-D-glucosamine or D-mannose, but not L-mannose, in a dose-dependent manner. Endothelial iC3b deposition after oxidative stress was also attenuated in MBL-deficient serum. Novel, functionally inhibitory, anti-human MBL monoclonal antibodies attenuated MBL-dependent C3 deposition on mannan-coated plates in a dose-dependent manner. Treatment of human serum with anti-MBL monoclonal antibodies inhibited MBL and C3 deposition after endothelial oxidative stress. Consistent with our in vitro findings, C3 and MBL immunostaining throughout the ischemic area at risk increased during rat myocardial reperfusion in vivo. These data suggest that the LCP mediates complement activation after tissue oxidative stress. Inhibition of MBL may represent a novel therapeutic strategy for ischemia/reperfusion injury and other complement-mediated disease states.
Real-life clinical outcomes of patients treated with anti-VEGF drugs for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or macular edema secondary to branch ...retinal vein occlusion (BRVO) are often inferior to results from randomized clinical trials. This observational cohort study investigates treatment adherence and real-life clinical outcomes within the first year of treatment.
A total of 708 treatment-naïve patients (466 nAMD, 134 DME, and 108 BRVO) were included. Patients were followed with a PRN treatment protocol with three intravitreal injections (IVIs) and a series of 3 monthly injections in case of persistent or recurrent disease activity, as determined by monthly follow-up exams including optical coherence tomographies. Occurrence of gaps of >56 days between treatments or follow-up (nonadherence NA) and the reasons for NA (patient- or center-associated) as well as disease activity within the first 12 months of treatment were analyzed. Visual acuity (VA) as well as numbers and dates of optical coherence tomography and IVI were extracted from medical records.
NA occurred significantly more often in patients with DME (44%) than nAMD (32%) or BRVO (25%,
<0.01 between groups). NA was mainly patient-associated (nAMD: 80.0%, DME: 83.1%, BRVO: 70.4%,
=0.38 between groups). Patients with nAMD and DME and appropriate treatment/follow-up adherence had a better chance of significantly gaining or maintaining VA, respectively (19.9% vs 12.0% with 3-line-gain in nAMD and 1.3% vs 15.3% 3-line loss in DME; each
<0.05). NA did not correlate with VA outcomes in BRVO (3-line gain 30.9% vs 48.1% and 3-line loss 8.6% vs 7.4%;
>0.05).
NA to treatment and follow-up regimens is a common problem in the management of patients with AMD and DME and limits clinical treatment outcomes under real-life conditions. Patients with DME have the highest risk of patient-associated NA, associated with a higher risk for significant VA loss.
Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular ...basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%–90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment.
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