Palliative systemic therapy alternated with electrostatic precipitation oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (ePIPAC) has never been prospectively investigated in ...patients with unresectable colorectal peritoneal metastases (CPM). The CRC-PIPAC-II study aimed to assess safety, feasibility and efficacy of such bidirectional therapy.
This two-center, single-arm, phase II trial enrolled chemotherapy-naïve patients to undergo three treatment cycles, consisting of systemic therapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI, all with bevacizumab) and oxaliplatin-based ePIPAC (92 mg/m2) with intravenous leucovorin (20 mg/m2) and 5-fluorouracil (400 mg/m2). Primary outcome were major treatment-related adverse events. Secondary outcomes included minor events, tumor response, progression-free survival (PFS) and overall survival (OS).
Twenty patients completed 52 treatment cycles. Fifteen major events occurred in 7 patients (35 %): 5 events (33 %) related to systemic therapy; 5 (33 %) related to ePIPAC; and 5 (33 %) were biochemical events. No treatment-related deaths occurred. All patients experienced minor events, mostly abdominal pain, nausea and peripheral sensory neuropathy. After treatment, radiological, pathological, cytological, and biochemical response was observed in 0 %, 88 %, 38 %, and 31 % of patients respectively. Curative surgery was achieved in one patient. Median PFS was 10.0 months (95 % confidence interval CI 8.0–13.0) and median OS was 17.5 months (95 % CI 13.0–not reached).
Combining palliative systemic therapy with oxaliplatin-based ePIPAC in patients with unresectable CPM was feasible and showed an acceptable safety profile. Treatment-induced response and survival are promising, yet further research is required to determine the additional value of ePIPAC to systemic therapy.
Background
Everolimus is a mTOR inhibitor used for the treatment of different solid malignancies. Many patients treated with the registered fixed 10 mg dose once daily are in need of dose ...interruptions, reductions or treatment discontinuation due to severe adverse events. This study determined the correlation between systemic everolimus exposure and toxicity. Additionally, the effect of different covariates on everolimus pharmacokinetics (PK) was explored.
Methods
Forty-two patients with advanced thyroid carcinoma were treated with 10 mg everolimus once daily. Serial pharmacokinetic sampling was performed on days 1 and 15. Subsequently, a population PK model was developed using NONMEM to estimate individual PK values used for analysis of an exposure–toxicity relationship. Furthermore, this model was used to investigate the influence of patient characteristics and genetic polymorphisms in genes coding for enzymes relevant in everolimus PK.
Results
Patients who required a dose reduction (
n
= 18) due to toxicity at any time during treatment had significant higher everolimus exposures mean AUC
0–24
(SD) 600 (274) vs. 395 (129) µg h/L,
P
= 0.008 than patients without a dose reduction (
n
= 22). A significant association between everolimus exposure and stomatitis was found in the four-level ordered logistic regression analysis (
P
= 0.047). The presence of at least one TTT haplotype in the
ABCB1
gene was associated with a 21 % decrease in everolimus exposure.
Conclusion
The current study showed that dose reductions and everolimus-induced stomatitis were strongly associated with systemic everolimus drug exposure in patients with cancer. Our findings confirm observations from another study in patients with cancer and show us that everolimus is a good candidate for individualized dosing in patients with cancer.
ClinicalTrial.gov number
NCT01118065.
Purpose
Bronchoscopy is an indispensable tool for invasive pulmonary evaluation with high diagnostic yield and low incidence of major complications. However, hypoxemia increases the risk of ...complications, in particular after bronchoalveolar lavage. Non-invasive positive pressure ventilation may prevent hypoxemia associated with bronchoalveolar lavage. The purpose of this study is to present a modified total face mask to aid bronchoscopy during non-invasive positive pressure ventilation.
Methods
A commercially available full face mask was modified to allow introduction of the bronchoscope without interfering with the ventilator circuit. Bronchoscopy with bronchoalveolar lavage was performed in 12 hypoxemic non-ICU patients during non-invasive positive pressure ventilation in the ICU.
Results
Patients had severely impaired oxygen uptake as indicated by PaO
2
/FiO
2
ratio 192 ± 23 mmHg before bronchoscopy. Oxygenation improved after initiation of non-invasive positive pressure ventilation. In all patients the procedure could be completed without subsequent complications, although in one patient SpO
2
decreased until 86% during bronchoscopy. A microbiological diagnosis could be established in 8 of 12 patients with suspected for infection.
Conclusions
Our modified face mask for non-invasive positive pressure ventilation is a valuable tool to aid diagnostic bronchoscopy in hypoxemic patients.
ABSTRACT
BACKGROUND AND PURPOSE
The posterior circulation Acute Stroke Prognosis Early CT Score (pc‐APECTS) applied to CT angiography source images (CTA‐SI) predicts the functional outcome of ...patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc‐ASPECTS applied to perfusion CT (CTP) in the BASICS registry population.
METHODS
We applied pc‐ASPECTS to CTA‐SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA‐SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal.
RESULTS
CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval CI, 76%‐99%), compared with 78% (58%‐91%) for CTA‐SI and CBF, and 46% (27%‐67%) for CBV (P < .001). All 3 patients with a CBV pc‐ASPECTS < 8 compared to 6/23 patients with a CBV pc‐ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9‐7.6).
CONCLUSION
CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc‐ASPECTS < 8 may indicate patients with high case fatality.
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
There is much debate on the use of angiotensin receptor blockers (ARBs) in severe acute respiratory syndrome–coronavirus-2 (SARS-CoV-2)–infected patients. Although it has been suggested that ARBs ...might lead to a higher susceptibility and severity of SARS-CoV-2 infection, experimental data suggest that ARBs may reduce acute lung injury via blocking angiotensin-II–mediated pulmonary permeability, inflammation, and fibrosis. However, despite these hypotheses, specific studies on ARBs in SARS-CoV-2 patients are lacking.
The PRAETORIAN-COVID trial is a multicenter, double-blind, placebo-controlled 1:1 randomized clinical trial in adult hospitalized SARS-CoV-2–infected patients (n = 651). The primary aim is to investigate the effect of the ARB valsartan compared to placebo on the composite end point of admission to an intensive care unit, mechanical ventilation, or death within 14 days of randomization. The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160 mg bid, and the placebo arm will receive matching placebo. Treatment duration will be 14 days, or until the occurrence of the primary end point or until hospital discharge, if either of these occurs within 14 days. The trial is registered at clinicaltrials.gov (NCT04335786, 2020).
The PRAETORIAN-COVID trial is a double-blind, placebo-controlled 1:1 randomized trial to assess the effect of valsartan compared to placebo on the occurrence of ICU admission, mechanical ventilation, and death in hospitalized SARS-CoV-2–infected patients. The results of this study might impact the treatment of SARS-CoV-2 patients globally.
Objectives To develop and validate a delirium prediction model for adult intensive care patients and determine its additional value compared with prediction by caregivers.Design Observational ...multicentre study.Setting Five intensive care units in the Netherlands (two university hospitals and three university affiliated teaching hospitals).Participants 3056 intensive care patients aged 18 years or over.Main outcome measure Development of delirium (defined as at least one positive delirium screening) during patients’ stay in intensive care.Results The model was developed using 1613 consecutive intensive care patients in one hospital and temporally validated using 549 patients from the same hospital. For external validation, data were collected from 894 patients in four other hospitals. The prediction (PRE-DELIRIC) model contains 10 risk factors—age, APACHE-II score, admission group, coma, infection, metabolic acidosis, use of sedatives and morphine, urea concentration, and urgent admission. The model had an area under the receiver operating characteristics curve of 0.87 (95% confidence interval 0.85 to 0.89) and 0.86 after bootstrapping. Temporal validation and external validation resulted in areas under the curve of 0.89 (0.86 to 0.92) and 0.84 (0.82 to 0.87). The pooled area under the receiver operating characteristics curve (n=3056) was 0.85 (0.84 to 0.87). The area under the curve for nurses’ and physicians’ predictions (n=124) was significantly lower at 0.59 (0.49 to 0.70) for both.Conclusion The PRE-DELIRIC model for intensive care patients consists of 10 risk factors that are readily available within 24 hours after intensive care admission and has a high predictive value. Clinical prediction by nurses and physicians performed significantly worse. The model allows for early prediction of delirium and initiation of preventive measures.Trial registration Clinical trials NCT00604773 (development study) and NCT00961389 (validation study).
Samenvatting
De MRI-scan van de prostaat heeft de bioptstrategie sterk beïnvloed. Toch kunnen bij een normale MRI biopten geïndiceerd blijven: zowel gerichte als systematische. In deze studie werd ...geanalyseerd welke prostaattumoren gemist zouden worden in de hypothetische situatie dat er geen systematische biopten genomen waren in ons cohort, en dat de MRI volledig leidend zou zijn geweest in het diagnostisch pad. Als referentie dienden de uitkomsten van het standaardprotocol, waarin alle verwezen patiënten (
n
= 496) een MRI krijgen, er bij een verhoogde kans op prostaatkanker volgens de ERSPC-prostaatwijzer óf afwijkende MRI biopten worden genomen, en er altijd systematische, plusgerichte biopten worden verricht, indien mogelijk. Uit de analyse bleek dat 16 % van de tumoren met een ISUP-graad ≥2 (≥3 + 4 = 7) gemist zou zijn, maar ook dat slechts 66 % van de patiënten gebiopteerd zou hoeven worden, met 50–75 % minder cores, en dat 52 % van de ISUP-gr 1 (3 + 3 = 6)-tumoren ongedetecteerd zouden blijven.
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