The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall ...survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up.
In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18–76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0–2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed.
Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4–12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5–13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months 95% CI 9·6–12·0) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months 12·0–18·5; hazard ratio HR 0·63 95% CI 0·48–0·83, stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months 95% CI 29·0–39·1) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months 95% CI 38·6–55·1; HR 0·70 95% CI 0·53–0·92, stratified log-rank p=0·011).
These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery.
Dutch Cancer Foundation (KWF Kankerbestrijding).
The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to ...explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer.
CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of ≥5 CTCs per 7.5 ml blood.
No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to ≥1 and ≥5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as ≥80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of ≥5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease.
The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.
Intraplaque hemorrhage contributes to lipid core enlargement and plaque progression, leading to plaque destabilization and stroke. The mechanisms that contribute to the development of intraplaque ...hemorrhage are not completely understood. A higher incidence of intraplaque hemorrhage and thin/ruptured fibrous cap (upstream of the maximum stenosis in patients with severe ≥70% carotid stenosis) has been reported. We aimed to noninvasively study the distribution of intraplaque hemorrhage and a thin/ruptured fibrous cap in patients with mild-to-moderate carotid stenosis.
Eighty-eight symptomatic patients with stroke (<70% carotid stenosis included in the Plaque at Risk study) demonstrated intraplaque hemorrhage on MR imaging in the carotid artery plaque ipsilateral to the side of TIA/stroke. The intraplaque hemorrhage area percentage was calculated. A thin/ruptured fibrous cap was scored by comparing pre- and postcontrast black-blood TSE images. Differences in mean intraplaque hemorrhage percentages between the proximal and distal regions were compared using a paired-samples
test. The McNemar test was used to reveal differences in proportions of a thin/ruptured fibrous cap.
We found significantly larger areas of intraplaque hemorrhage in the proximal part of the plaque at 2, 4, and 6 mm from the maximal luminal narrowing, respectively: 14.4% versus 9.6% (
= .04), 14.7% versus 5.4% (
< .001), and 11.1% versus 2.2% (
= .001). Additionally, we found an increased proximal prevalence of a thin/ruptured fibrous cap on MR imaging at 2, 4, 6, and 8 mm from the MR imaging section with the maximal luminal narrowing, respectively: 33.7% versus 18.1%,
= .007; 36.1% versus 7.2%,
< .001; 33.7% versus 2.4%,
= .001; and 30.1% versus 3.6%,
= .022.
We demonstrated that intraplaque hemorrhage and a thin/ruptured fibrous cap are more prevalent on the proximal side of the plaque compared with the distal side in patients with mild-to-moderate carotid stenosis.
The European Society of Breast Cancer Specialists (EUSOMA) has fostered a voluntary certification process for breast centres to establish minimum standards and ensure specialist multidisciplinary ...care. Prospectively collected anonymous information on primary breast cancer cases diagnosed and treated in the units is transferred annually to a central EUSOMA data warehouse for continuous monitoring of quality indicators (QIs) to improve quality of care. Units have to comply with the EUSOMA Breast Centre guidelines and are audited by peers. The database was started in 2006 and includes over 110,000 cancers from breast centres located in Germany, Switzerland, Belgium, Austria, The Netherlands, Spain, Portugal and Italy. The aim of the present study is assessing time trends of QIs in EUSOMA-certified breast centres over the decade 2006–2015.
Previously defined QIs were calculated for 22 EUSOMA-certified breast centres (46122 patients) during 2006–2015.
On the average of all units, the minimum standard of care was achieved in 8 of 13 main EUSOMA QIs in 2006 and in all in 2015. All QIs, except removal of at least 10 lymph nodes at axillary clearance and oestrogen receptor–negative tumours (T > 1 cm or N+) receiving adjuvant chemotherapy, improved significantly in this period. The desirable target was reached for two QIs in 2006 and for 7 of 13 QIs in 2015.
The EUSOMA model of audit and monitoring QIs functions well in different European health systems and results in better performance of QIs over the last decade. QIs should be evaluated and adapted on a regular basis, as guidelines change over time.
•The time trends of quality indicators in EUSOMA-certified breast centres over the decade 2006–2015 are evaluated.•The EUSOMA model of audit and monitoring QIs functions well in different European health systems.•Audit and measuring quality indicators result in better performance.
A curated Web-based user-friendly sequence typing tool based on antimicrobial resistance determinants in
was developed and is publicly accessible (https://ngstar.canada.ca). The
Sequence Typing for ...Antimicrobial Resistance (NG-STAR) molecular typing scheme uses the DNA sequences of 7 genes (
,
,
,
,
,
, and 23S rRNA) associated with resistance to β-lactam antimicrobials, macrolides, or fluoroquinolones. NG-STAR uses the entire
sequence, combining the historical nomenclature for
types I to XXXVIII with novel nucleotide sequence designations; the full
sequence and a portion of its promoter region; portions of
,
,
, and
; and 23S rRNA sequences. NG-STAR grouped 768 isolates into 139 sequence types (STs) (
= 660) consisting of 29 clonal complexes (CCs) having a maximum of a single-locus variation, and 76 NG-STAR STs (
= 109) were identified as unrelated singletons. NG-STAR had a high Simpson's diversity index value of 96.5% (95% confidence interval CI = 0.959 to 0.969). The most common STs were NG-STAR ST-90 (
= 100; 13.0%), ST-42 and ST-91 (
= 45; 5.9%), ST-64 (
= 44; 5.72%), and ST-139 (
= 42; 5.5%). Decreased susceptibility to azithromycin was associated with NG-STAR ST-58, ST-61, ST-64, ST-79, ST-91, and ST-139 (
= 156; 92.3%); decreased susceptibility to cephalosporins was associated with NG-STAR ST-90, ST-91, and ST-97 (
= 162; 94.2%); and ciprofloxacin resistance was associated with NG-STAR ST-26, ST-90, ST-91, ST-97, ST-150, and ST-158 (
= 196; 98.0%). All isolates of NG-STAR ST-42, ST-43, ST-63, ST-81, and ST-160 (
= 106) were susceptible to all four antimicrobials. The standardization of nomenclature associated with antimicrobial resistance determinants through an internationally available database will facilitate the monitoring of the global dissemination of antimicrobial-resistant
strains.
Interpretation of serological assays in Lyme borreliosis requires an understanding of the clinical indications and the limitations of the currently available tests. We therefore systematically ...reviewed the accuracy of serological tests for the diagnosis of Lyme borreliosis in Europe.
We searched EMBASE en MEDLINE and contacted experts. Studies evaluating the diagnostic accuracy of serological assays for Lyme borreliosis in Europe were eligible. Study selection and data-extraction were done by two authors independently. We assessed study quality using the QUADAS-2 checklist. We used a hierarchical summary ROC meta-regression method for the meta-analyses. Potential sources of heterogeneity were test-type, commercial or in-house, Ig-type, antigen type and study quality. These were added as covariates to the model, to assess their effect on test accuracy.
Seventy-eight studies evaluating an Enzyme-Linked ImmunoSorbent assay (ELISA) or an immunoblot assay against a reference standard of clinical criteria were included. None of the studies had low risk of bias for all QUADAS-2 domains. Sensitivity was highly heterogeneous, with summary estimates: erythema migrans 50% (95% CI 40% to 61%); neuroborreliosis 77% (95% CI 67% to 85%); acrodermatitis chronica atrophicans 97% (95% CI 94% to 99%); unspecified Lyme borreliosis 73% (95% CI 53% to 87%). Specificity was around 95% in studies with healthy controls, but around 80% in cross-sectional studies. Two-tiered algorithms or antibody indices did not outperform single test approaches.
The observed heterogeneity and risk of bias complicate the extrapolation of our results to clinical practice. The usefulness of the serological tests for Lyme disease depends on the pre-test probability and subsequent predictive values in the setting where the tests are being used. Future diagnostic accuracy studies should be prospectively planned cross-sectional studies, done in settings where the test will be used in practice.
Superconducting nanowire single-photon detectors with peak efficiencies above 90% and unrivalled timing jitter (<30 ps) have emerged as a potent technology for quantum information and sensing ...applications. However, their high cost and cryogenic operation limit their widespread applicability. Here, we present an approach using tapered InP nanowire p-n junction arrays for high-efficiency, broadband and high-speed photodetection without the need for cryogenic cooling. The truncated conical nanowire shape enables a broadband, linear photoresponse in the ultraviolet to near-infrared range (~500 nm bandwidth) with external quantum efficiencies exceeding 85%. The devices exhibit a high gain beyond 10
, such that a single photon per pulse can be distinguished from the dark noise, while simultaneously showing a fast pulse rise time (<1 ns) and excellent timing jitter (<20 ps). Such detectors open up new possibilities for applications in remote sensing, dose monitoring for cancer treatment, three-dimensional imaging and quantum communication.
It is unclear which patients with multiple sclerosis (MS) are most susceptible for omicron breakthrough infections.
We assessed omicron breakthrough infections in vaccinated patients with MS with and ...without disease-modifying therapies enrolled in an ongoing large prospective study. We longitudinally studied humoral responses after primary and booster vaccinations and breakthrough infections.
Omicron breakthrough infections were reported in 110/312 (36%) patients with MS, and in 105/110 (96%) infections were mild. Omicron breakthrough infections occurred more frequently in patients treated with anti-CD20 therapies and sphingosine-1 phosphate receptor (S1PR) modulators, patients with impaired humoral responses after primary immunisation (regardless of treatment) and patients without prior SARS-CoV-2 infections. After infection, antibody titres increased in patients on S1PR modulator treatment while anti-CD20 treated patients did not show an increase.
SARS-COV-2 omicron breakthrough infections are more prevalent in patients with MS on anti-CD20 therapies and S1PR modulators compared with other patients with MS, which correlated with decreased humoral responses after vaccination. Humoral responses after infection were higher in S1PR modulator-treated patients in comparison to patients on anti-CD20 therapies, suggesting that immunological protection from contracting infection or repeated exposures may differ between these therapies.
Tunable Supercurrent Through Semiconductor Nanowires Doh, Yong-Joo; van Dam, Jorden A; Roest, Aarnoud L ...
Science (American Association for the Advancement of Science),
07/2005, Letnik:
309, Številka:
5732
Journal Article
Recenzirano
Odprti dostop
Nanoscale superconductor/semiconductor hybrid devices are assembled from indium arsenide semiconductor nanowires individually contacted by aluminum-based superconductor electrodes. Below 1 kelvin, ...the high transparency of the contacts gives rise to proximity-induced superconductivity. The nanowires form superconducting weak links operating as mesoscopic Josephson junctions with electrically tunable coupling. The supercurrent can be switched on/off by a gate voltage acting on the electron density in the nanowire. A variation in gate voltage induces universal fluctuations in the normal-state conductance, which are clearly correlated to critical current fluctuations. The alternating-current Josephson effect gives rise to Shapiro steps in the voltage-current characteristic under microwave irradiation.
Tuberculosis remains one of the deadliest diseases. Emergence of drug-resistant and multidrug-resistant
strains makes treating tuberculosis increasingly challenging. In order to develop novel ...intervention strategies, detailed understanding of the molecular mechanisms behind the success of this pathogen is required. Here, we review recent literature to provide a systems level overview of the molecular and cellular components involved in divalent metal homeostasis and their role in regulating the three main virulence strategies of
: immune modulation, dormancy and phagosomal rupture. We provide a visual and modular overview of these components and their regulation. Our analysis identified a single regulatory cascade for these three virulence strategies that respond to limited availability of divalent metals in the phagosome.
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