Background & Aims Pancreatobiliary cancer is detected by fluorescence in situ hybridization (FISH) of pancreatobiliary brush samples with UroVysion probes, originally designed to detect bladder ...cancer. We designed a set of new probes to detect pancreatobiliary cancer and compared its performance with that of UroVysion and routine cytology analysis. Methods We tested a set of FISH probes on tumor tissues (cholangiocarcinoma or pancreatic carcinoma) and non-tumor tissues from 29 patients. We identified 4 probes that had high specificity for tumor vs non-tumor tissues; we called this set of probes pancreatobiliary FISH. We performed a retrospective analysis of brush samples from 272 patients who underwent endoscopic retrograde cholangiopancreatography for evaluation of malignancy at the Mayo Clinic; results were available from routine cytology and FISH with UroVysion probes. Archived residual specimens were retrieved and used to evaluate the pancreatobiliary FISH probes. Cutoff values for FISH with the pancreatobiliary probes were determined using 89 samples and validated in the remaining 183 samples. Clinical and pathologic evidence of malignancy in the pancreatobiliary tract within 2 years of brush sample collection was used as the standard; samples from patients without malignancies were used as negative controls. The validation cohort included 85 patients with malignancies (46.4%) and 114 patients with primary sclerosing cholangitis (62.3%). Samples containing cells above the cutoff for polysomy (copy number gain of ≥2 probes) were classified as positive in FISH with the UroVysion and pancreatobiliary probes. Multivariable logistic regression was used to estimate associations between clinical and pathology findings and results from FISH. Results The combination of FISH probes 1q21, 7p12, 8q24, and 9p21 identified cancer cells with 93% sensitivity and 100% specificity in pancreatobiliary tissue samples and were therefore included in the pancreatobiliary probe set. In the validation cohort of brush samples, pancreatobiliary FISH identified samples from patients with malignancy with a significantly higher level of sensitivity (64.7%) than the UroVysion probes (45.9%) ( P < .001) or routine cytology analysis (18.8%) ( P < .001), but similar specificity (92.9%, 90.8%, and 100.0% respectively). Factors significantly associated with detection of carcinoma, in adjusted analyses, included detection of polysomy by pancreatobiliary FISH ( P < .001), a mass by cross-sectional imaging ( P < .001), cancer cells by routine cytology (overall P = .003), as well as absence of primary sclerosing cholangitis ( P = .011). Conclusions We identified a set of FISH probes that detects cancer cells in pancreatobiliary brush samples from patients with and without primary sclerosing cholangitis with higher levels of sensitivity than UroVysion probes. Cytologic brushing test results and clinical features were independently associated with detection of cancer and might be used to identify patients with pancreatobiliary cancers.
Pulmonary exposure to Bacillus anthracis spores initiates inhalational anthrax, a life-threatening infection. It is known that dormant spores can be recovered from the lungs of infected animals ...months after the initial spore exposure. Consequently, a 60-day course antibiotic treatment is recommended for exposed individuals. However, there has been little information regarding details or mechanisms of spore persistence in vivo. In this study, we investigated spore persistence in a mouse model. The results indicated that weeks after intranasal inoculation with B. anthracis spores, substantial amounts of spores could be recovered from the mouse lung. Moreover, spores of B. anthracis were significantly better at persisting in the lung than spores of a non-pathogenic Bacillus subtilis strain. The majority of B. anthracis spores in the lung were tightly associated with the lung tissue, as they could not be readily removed by lavage. Immunofluorescence staining of lung sections showed that spores associated with the alveolar and airway epithelium. Confocal analysis indicated that some of the spores were inside epithelial cells. This was further confirmed by differential immunofluorescence staining of lung cells harvested from the infected lungs, suggesting that association with lung epithelial cells may provide an advantage to spore persistence in the lung. There was no or very mild inflammation in the infected lungs. Furthermore, spores were present in the lung tissue as single spores rather than in clusters. We also showed that the anthrax toxins did not play a role in persistence. Together, the results suggest that B. anthracis spores have special properties that promote their persistence in the lung, and that there may be multiple mechanisms contributing to spore persistence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Bisphenol A (BPA) is a synthetic compound used to produce plastics and epoxy resins. BPA can leach from these products in appreciable amounts, resulting in nearly ubiquitous daily ...exposure to humans. Whether BPA is harmful to humans, especially when administered orally in concentrations relevant to humans, is a topic of debate. Objectives: In this study, we investigated the role of chronic oral exposure to BPA during adulthood on mammary carcinogenesis by using a transgenic mouse model that spontaneously develops tumors through overexpression of wild-type erbB2 mouse mammary tumor virus (MMTV)-erbB2. Methods: MMTV-erbB2 mice were exposed to 0, 2.5, 25, 250, or 2,500 µg BPA/L drinking water from 56 until 112 days of age (for mechanism of action) or 252 days of age (for tumorigenesis). Cellular and molecular mechanisms of BPA action in the mammary gland were investigated via immunohistochemistry and immunoblotting. Results: Only low doses of BPA significantly decreased tumor latency and increased tumor multiplicity, tumor burden, and the incidence of metastasis. All BPA doses significantly increased the cell proliferation index, but only the higher doses also increased the apoptotic index in the mammary gland. At the molecular level, 25 µg BPA/L, but not 2,500 µg BPA/L, increased phosphorylation of erbB2, erbB3, insulin-like growth factor 1 receptor, and Akt in the mammary gland. Discussion: LOW, but not high, BPA doses significantly accelerated mammary tumorigenesis and metastasis in MMTV-erbB2 mice. The combined ratio of cell proliferation and apoptosis indices and alterations in protein expression best predicted the ability of each dose of BPA to alter tumorigenesis in this model.
Background
The objective of this randomized trial was to evaluate the short‐term effect of bilingual written and interpersonal education regarding mammographic breast density (MBD).
Methods
Latinas ...aged 40 to 74 years who were presenting for screening mammography were recruited and randomized 1:1:1 to receive a letter with their mammogram and MBD results (usual care UC), a letter plus a brochure (enhanced care ENH), or a letter plus a brochure and telephonic promotora education (interpersonal care INT). Surveys were administered at enrollment (T0) and 2 weeks to 6 months after intervention delivery (T1). Differences were assessed with χ2, Kruskal‐Wallis, and McNemar tests and pairwise comparisons as appropriate. INT metrics and audio recordings were analyzed with descriptive statistics and qualitative content analysis.
Results
Between October 2016 and October 2019, 943 of 1108 Latina participants (85%) completed both surveys. At T1, INT participants were more likely (P < .001) to report seeing their MBD results in the letter (70.2%) than UC (53.1%) or ENH participants (55.1%). The percentage of INT women who reported speaking with a provider about MBD (29.0%) was significantly greater (P < .001) than the percentage of UC (14.7%) or ENH participants (15.6%). All groups saw significant (P < .001) but nondifferential improvements in their knowledge of MBD as a masking and risk factor. In the INT group, the promotora delivered education to 77.1% of the 446 participants randomized to INT and answered questions at 28.3% of the encounters for an average of $4.70 per participant.
Conclusions
Among Latinas in a low‐resource setting, MBD knowledge may increase with written or interpersonal education, but with modest investment, interpersonal education may better improve MBD awareness and prompt patient‐provider discussions.
Bilingual educational interventions increase knowledge of mammographic breast density among Latinas at a Federally Qualified Health Center. Promotora intervention is especially effective at raising awareness and prompting conversations with health care providers.
Anaplastic thyroid cancer (ATC) is rare and a highly fatal malignancy. The role of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) as prognostic and/or predictive markers in ATC is ...unknown.
Multimodal therapy offers the best chance at tumor control. The objective of this study was to detect potential associations of PD-1/PD-L1 axis variables with outcome data in ATC.
Retrospective study of a uniformly treated cohort.
Single institution retrospective cohort study.
Sixteen patients who received intensity-modulated radiation therapy (15 had preceding surgery) were studied.
Patients treated with multimodal therapy were followed and assessed for overall survival (OS) and progression-free survival (PFS).
All samples demonstrated PD-1 expression in inflammatory cells whereas tumor cells were primarily negative. PD-L1 was expressed on ATC tumor cells in most samples and showed mainly membranous staining. High PD-1 expression (>40% staining) in inflammatory cells was associated with worse overall survival (OS; hazard ratio, 3.36; 95% confidence interval, 1.00 to 12.96; P < 0.05) and trended toward worse PFS, whereas high PD-L1 expression in tumor cells (>33% staining) trended toward worse PFS and OS.
PD-1/PD-L1 pathway proteins are highly expressed in ATC tumor samples and appear to represent predictive markers of PFS and OS in multimodality-treated ATC patients.
Legislation mandating disclosure of breast density (BD) information has passed in 21 states; however, actual awareness of BD and knowledge of its impact on breast cancer detection and risk are ...unknown.
We conducted a national cross-sectional survey administered in English and Spanish using a probability-based sample of screening-age women, with oversampling of Connecticut, the only state with BD legislation in effect for > 1 year before the survey.
Of 2,311 women surveyed, 65% responded. Overall, 58% of women had heard of BD, 49% knew that BD affects breast cancer detection, and 53% knew that BD affects cancer risk. After multivariable adjustment, increased BD awareness was associated with white non-Hispanic race/ethnicity (Hispanic v white non-Hispanic: odds ratio OR, 0.23; P < .001), household income (OR, 1.07 per category increase; P < .001), education (OR, 1.19 per category increase; P < .001), diagnostic evaluation after a mammogram (OR, 2.64; P < .001), and postmenopausal hormone therapy (OR, 1.69; P = .002). Knowledge of the masking effect of BD was associated with higher household income (OR, 1.10; P < .001), education (OR, 1.22; P = .01), prior breast biopsy (OR, 2.16; P < .001), and residing in Connecticut (Connecticut v other states: OR, 3.82; P = .003). Connecticut residents were also more likely to have discussed their BD with a health care provider (67% v 43% for residents of other US states; P = .001).
Disparities in BD awareness and knowledge exist by race/ethnicity, education, and income. BD legislation seems to be effective in increasing knowledge of BD impact on breast cancer detection. These findings support continued and targeted efforts to improve BD awareness and knowledge among women eligible for screening mammography.
Spores of Bacillus anthracis, the causative agent of anthrax, are known to persist in the host lungs for prolonged periods of time, however the underlying mechanism is poorly understood. In this ...study, we demonstrated that BclA, a major surface protein of B. anthracis spores, mediated direct binding of complement factor H (CFH) to spores. The surface bound CFH retained its regulatory cofactor activity resulting in C3 degradation and inhibition of downstream complement activation. By comparing results from wild type C57BL/6 mice and complement deficient mice, we further showed that BclA significantly contributed to spore persistence in the mouse lungs and dampened antibody responses to spores in a complement C3-dependent manner. In addition, prior exposure to BclA deletion spores (ΔbclA) provided significant protection against lethal challenges by B. anthracis, whereas the isogenic parent spores did not, indicating that BclA may also impair protective immunity. These results describe for the first time an immune inhibition mechanism of B. anthracis mediated by BclA and CFH that promotes spore persistence in vivo. The findings also suggested an important role of complement in persistent infections and thus have broad implications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Telemedicine in an ambulatory surgical population remains incompletely evaluated. Objective To investigate patient encounters in the outpatient setting using video visit (VV) ...technology compared to traditional office visits (OVs). Design, setting, and participants From June 2013 to March 2014, 55 prescreened men with a history of prostate cancer were prospectively randomized. VVs, with the patient at home or at work, were included in the outpatient clinic calendar of urologists. Intervention Remote VV versus traditional OV. Outcome measurements and statistical analysis An equivalence analysis was used to assess the primary outcome, visit efficiency as measured by time studies. Secondary outcomes were patient/provider satisfaction and costs. Results and limitations There were 28 VVs and 27 OVs. VVs were equivalent in efficiency to relative to OVs, as measured by patient–provider face time (mean 14.5 vs 14.3 min; p = 0.96), patient wait time (18.4 vs 13.0 min; p = 0.20), and total time devoted to care (17.9 vs 17.8 min; p = 0.97). There were no significant differences in patient perception of visit confidentiality, efficiency, education quality, or overall satisfaction. VVs incurred lower costs, including distance traveled (median 0 vs 95 miles), travel time (0 vs 95 min), missed work (0 vs 1 d), and money spent on travel ($0 vs $48; all p < 0.0001). There was a high level of urologist satisfaction for both VVs (88%) and OVs (90%). The major limitation was sample size. Conclusions VV in the ambulatory postprostatectomy setting may have a future role in health care delivery models. We found equivalent efficiency, similar satisfaction, but significantly reduced patient costs for VV compared to OV. Further prospective analyses are warranted. Patient summary Among men with surgically treated prostate cancer, we evaluated the utility of remote video visits compared to office visits for outpatient consultation with a urologist. Video visits were associated with equivalent efficiency, similar satisfaction, and significantly lower patient costs when compared to office visits. We conclude that video visits may have a future role in health care delivery models.
OBJECTIVE To describe management of patients with permanent pacemaker (PPM)- and implantable cardioverter-defibrillator (ICD)-related endocarditis. PATIENTS AND METHODS We retrospectively reviewed ...all cases of infection involving PPMs and ICDs among patients presenting to Mayo Clinic's site in Rochester, MN, between January 1, 1991, and December 31, 2003. Cardiac device-related infective endocarditis (CDIE) was defined as the presence of both vegetation on a device lead or valve and clinical or microbiological evidence of CDIE. Of 189 patients with PPM or ICD infection who were admitted during the study period, 44 met the case definition for CDIE (33 PPM, 11 ICD). RESULTS The mean ± SD age of patients was 67±14 years. Staphylococci (36 82%) were the most commonly isolated pathogens. Nearly all patients (43 98%) were treated with a combined approach of complete hardware removal and parenteral antibiotics. The median duration of antibiotic treatment after infected device explantation was 28 days (interquartile range, 19-42 days). Device leads were removed percutaneously in 34 cases (77%); only 7 cases (16%) required surgical lead extraction. Percutaneous extraction was uncomplicated in 15 patients with lead vegetation greater than 10 mm in diameter. Six patients (14%) died during hospitalization. Twenty-seven (96%) of 28 patients remained infection free at their last visit (median follow-up, 183 days; intraquartile range, 36-628 days). CONCLUSION Prompt hardware removal and prolonged parenteral antibiotic administration decrease mortality among patients with CDIE. The presence of a large (>10 mm in diameter) vegetation on a lead is not a contraindication for percutaneous lead extraction. This study found that prompt hardware removal and prolonged parenteral antibiotic administration decrease mortality among patients with cardiac device-related infective endocarditis.
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