D-dimer >5000 ng/ml at incident VTE is associated with a higher risk of subsequent cancer within one and two years. High D-dimer levels are also associated with more aggressive tumor biology and poor ...prognosis in these patients. As D-dimer is routinely measured in the assessment of suspected VTE, it may be a useful surrogate marker for the presence of an underlying malignancy. Our findings may suggest that high plasma D-dimer at incident VTE diagnosis should be taken into consideration when the decision to screen for underlying cancer is made.
We report the discovery and characterization of four transiting exoplanets by the HATNet survey. The planet HAT-P-50b has a mass of 1.35 M sub(J) and radius of 1.29 R sub(J), and orbits a bright (V = ...11.8 mag) M = 1.27 M sub(middot in circle), R = 1.70 R sub(middot in circle) star every P = 3.1220 days. The planet HAT-P-51b has a mass of 0.31 M sub(J) and radius of 1.29 R sub(J) and orbits a V = 13.4 mag, M = 0.98 M sub(middot in circle), R = 1.04 R sub(middot in circle) star with a period of P = 4.2180 days. The planet HAT-P-52b has a mass of 0.82M sub(J) and radius of 1.01 R sub(J), and orbits a V = 14.1 mag, M = 0.89 M sub(middot in circle), R = 0.89 R sub(middot in circle) star with a period of P = 2.7536 days. The planet HAT-P-53b has a mass of 1.48 M sub(J) and radius of 1.32 R sub(J), and orbits a V = 13.7 mag, M = 1.09 M sub(middot in circle), R = 1.21 R sub(middot in circle) star with a period of P = 1.9616 days. All four planets are consistent with having circular orbits and have masses and radii measured to better than 10% precision. The low stellar jitter and favorable Rp/Rlow * ratio for HAT-P-51 make it a promising target for measuring the Rossiter-McLaughlin effect for a Saturn-mass planet.
Osimertinib is effective for relapsed T790M-positive patients with brain metastases. The high brain permeability suggests that also such patients without T790M could benefit. Therefore, we evaluated ...the effect of osimertinib on brain metastases in both T790M-positive and -negative patients.
The TREM-study was an investigator-initiated phase II, single-arm, multi-institutional clinical trial conducted in Northern Europe. Patients with resistance to prior EGFR-TKIs received osimertinib until radiological progression, unacceptable toxicity or death. Baseline brain scans were performed in patients with known or suspected brain metastases and repeated every 8-12 weeks. We assessed intracranial efficacy in patients with baseline brain metastases.
Brain metastases were detected in 48/199 patients at baseline. Of these, 63% were T790M-positive, 27% -negative and 10% had unknown T790M-status. The majority (73%) of the patients had received prior whole brain radiotherapy and additionally 8% had received stereotactic radiosurgery (SRS). Brain scans were available for review for 42 patients. The intracranial progression free survival was 39.7 versus 3.5 months for T790M + and T790M- patients, respectively (p < 0.001). The overall intracranial disease control rate (iDCR) was 81%, and for T790M + and T790M- patients the DCR was 89% versus 55%, respectively. The estimated risk of CNS progression was 0.8% at 6 months and 6% at 12 months for T790M-positive patients, and 14% and 17% at 6 and 12 months, respectively, for the T790M-negative.
This subgroup analysis confirms CNS efficacy of osimertinib in patients with the T790M resistance mutation, while other treatment options should be considered for EGFR-TKI relapsed T790M-negative patients with brain metastases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. ...Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI.
In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI.
The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy.
The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Both brodalumab and guselkumab improve skin clearance in patients with moderate-to-severe plaque psoriasis after inadequate response to ustekinumab. In the absence of a direct head-to-head ...comparison, the relative efficacy of brodalumab and guselkumab in non-responders to ustekinumab were compared using a matching-adjusted indirect comparison (MAIC).
Individual patient data for brodalumab (n = 121) were pooled from the AMAGINE-2 and -3 trials and adjusted using a propensity score reweighting method, so that baseline and week 16 characteristics matched the aggregate published data of patients with an inadequate response to ustekinumab who switched to guselkumab (n = 135) in the NAVIGATE trial.
After inadequate response to ustekinumab, brodalumab resulted in significantly higher psoriasis area and severity index (PASI) 90 rates versus guselkumab at post-treatment switch week 12 (62.7% vs 48.1%, relative difference 14.6% 95% confidence interval CI 5.3-23.9, p = 0.002 number needed to treat NNT = 6.8) and week 36 (63.7% vs 51.1%; relative difference 12.6% 95% CI 4.1-21.0; p = 0.004 NNT = 7.9) and PASI 100 rate at week 36 (40.3% vs 20.0%; relative difference 20.3% 95% CI 11.8-28.7; p < 0.001 NNT = 4.9).
In this MAIC, brodalumab was associated with greater improvements than guselkumab in inadequate responders to ustekinumab. Switching to brodalumab in such patients may be a more effective strategy than switching to guselkumab.
A consecutive group of 259 patients with inoperable adenocarcinoma of the lung (ACL) were observed to define risk groups for and frequency of brain metastases together with prognosis. All patients ...received chemotherapy in a three-armed randomized trial. Brain metastases were diagnosed in 25 patients before protocol entry and in 37 during treatment. Brain autopsy was performed in 87 patients and was positive in 38 (44%). Eleven of these (29%) were not diagnosed clinically. Patients younger than 60 years had a somewhat higher overall frequency of brain metastases than older patients. Patients with initial performance status above 60% and patients responding to chemotherapy had higher risk for developing brain metastasis during treatment than other patients, probably because of the increasing cumulated risk for this complication with prolonged survival. Median survival after onset of brain metastases was 73 days and survival was significantly shorter for these patients than for patients without this complication at days 0, 90, 180, and 365 after protocol entry. Thus, brain metastases is a frequent complication in ACL and the frequency increases with prolonged survival. Survival after development of brain metastases is short and it is questionable whether the inclusion of this subgroup of ACL patients into experimental cytostatic treatments is justified.
The objective of the present experiment was to test the hypothesis that supplemental feeding of roughages (maize silage, rucola salad, or wheat sprouts) would reduce behavioral and physiological ...signs of stress and increase egg production. A total of 160 adult partridge breeder birds were housed in pairs of 1 male and 1 female/cage during the egg-laying period from April to June. Birds fed on maize silage spent more time laying and less time foraging than birds in the wheat sprout treatment (P < 0.05). Birds fed wheat sprouts were more active than control birds (active 57 vs. 43% of the time, P < 0.05). Birds on the western side of the shed spent more time eating (3.9 vs. 1.24%, P < 0.01). Aggression and dustbathing were rarely seen, and feather pecking was never observed. The basal level of corticosterone (SD) was, on average, 11.4 (6.0) ng/mL of plasma and was not affected by treatments. After 15 min of crating, the average level of corticosterone was 50.0 (20.5) ng/mL of plasma, and strongly tended (P = 0.066) to be higher in the birds on the wheat sprout treatment compared with those on the control or other treatments. Fewer eggs (P < 0.05) were produced by birds on the wheat sprout treatment compared with those on the control treatment (on average, 45.9 vs. 52.1 eggs in total and 40.9 vs. 47.3 eggs for setting). Treatments did not affect egg fertility, egg hatchability, or the number of hatched chicks. In conclusion, we cannot recommend supplementing partridge diets with wheat sprouts during the egg-laying period because this seems to cause behavioral and physiological stress responses and impaired egg production. In general, partridge breeders in the production system investigated here did not show overt signs of maladaptive behavior or physiological stress when fed pelleted concentrate only or concentrate with supplements of maize silage or fresh rucola salad.
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