•Methodological differences between RHI studies have frequently been overlooked.•Differences relate to the experimental set-up, the induction method, the quantification of effects, and the study ...design.•Accounting for these differences can explain many inconsistent results.•Our categorization of differences between RHI studies provides a solid basis for the comparison of associated results.
The rubber hand illusion (RHI) is a widely applied paradigm to investigate changes in body representations. Extensive scientific interest has produced a great variability in the observed results and many contradictory findings have been reported. Taking into account the numerous variations in the experimental implementation of the RHI, many of these contradictive findings can be reconciled, but to date a thorough analysis of the methodological differences between RHI studies is lacking.
Here we summarize and analyse methodological differences between RHI studies. In distinction from other reviews focusing on the integration of findings from various studies, the present paper is devoted to the differences in (i) the experimental setup, (ii) the method used to induce the RHI, (iii) the quantification of its effects, and (iv) aspects of the experimental design and data analysis. This approach will provide a reference frame for the interpretation of previous studies as well as for the design of future studies.
Background
Patients with colorectal carcinoma and high‐grade microsatellite instability (MSI‐H) or deficiency in mismatch repair (dMMR) exceptionally respond to immune checkpoint inhibitors (ICIs). ...ICIs are more active in treatment‐naïve patients than in patients with refractory MSI‐H/dMMR metastatic colorectal cancer and even more active in patients with locally advanced tumors.
Material and Methods
A 33‐year‐old male patient with Lynch syndrome was diagnosed with a locally advanced rectal cancer and refused standard neoadjuvant chemoradiation because of the potential harm of sexual dysfunction. MMR and microsatellite instability status were analyzed by immunohistochemistry and fragment length polymerase chain reaction followed by capillary electrophoresis.
Results
After MSI‐H/dMMR was confirmed, the patient was treated with ICIs (1 mg/kg ipilimumab at day 1 and 3 mg/kg nivolumab at day 1 and 15). A complete clinical response was documented at day 21 after start of treatment. The patient underwent a total mesorectal excision at day 30. In the extirpated tissue, a complete pathological response was confirmed.
Conclusion
In MSI‐H/dMMR locally advanced rectal cancer short‐course ICI treatment is highly effective and may be discussed in patients with dMMR locally advanced rectal cancer.
Key Points
Immune checkpoint inhibitors are more active in treatment‐naïve patients than in patients with refractory high‐grade microsatellite instability (MSI‐H)/deficiency in mismatch repair (dMMR) colorectal cancer.
Standard neoadjuvant chemoradiation is less effective in MSI‐H/dMMR rectal cancer patients than in patients with proficient mismatch repair.
A young patient with Lynch syndrome and MSI‐H/dMMR locally advanced rectal cancer refused chemoradiation in order to preserve his fertility.
After neoadjuvant treatment with one dose of ipilimumab and two doses of nivolumab a complete clinical and pathological response was documented.
Clinical trials are needed to first establish neoadjuvant treatment with immune checkpoint inhibitors in patients with locally advanced MSI‐H/dMMR rectal cancer and thereafter to evaluate organ‐preservation strategies.
This report describes the case of a 33‐year‐old male patient with Lynch syndrome who was diagnosed with locally advanced rectal cancer. Instead of chemoradiation, neoadjuvant treatment with immune checkpoint inhibitors was given.
Stress poses a major issue in our modern society, making restoration an important research focus. Restoration likelihood has mostly been observed in nature, which was compared with urban environments ...that have little restorative potential, eg, industrial areas. However, many people reside in and need to find restoration in cities. The main aim of this review is to summarize research that has focused on investigating restoration possibilities in urban environments and the environmental elements interacting with the restoration likelihood of an urban environment. This review focuses on studies addressing the topic of restoration possibilities in urban settings in built and human-made natural urban environments. The studies were searched via Google Scholar, PsycINFO, PsycARTICLES, and PSYNDEX. All studies concerned with restoration in urban environments were included. However, studies concerned with nonoriginal data, solely investigating effects of natural environments or treating urban environments as a control for restoration in nature, were excluded from the review. Overall, 39 studies corresponded to the criteria and were included. Natural elements in urban environments have a restorative potential and can increase the restorativeness of urban settings. Furthermore, built urban environments vary in their restorative potential, but promising results have been uncovered as well. Architectural elements, cultural, and leisure areas had a restorative value, whereas the findings on streets and residential areas differ. In sum, many urban locations can have restorative effects, but these effects may be influenced by factors such as cultural background, age, social components, and individual dispositions. Certain urban environments hold a restorative potential. However, the literature on restoration in urban environments is still quite scarce and therefore has been of little practical use. Even though applying the findings to real-life environments is desirable, it might prove difficult, considering the overall sparse evidence. More research on the predictors of restoration likelihood (eg, social factors), generational and cultural differences, and comparisons between natural and urban environments is recommended.
The body schema is a much discussed aspect of body awareness. Although there is still no single definition, there is widespread consensus that the body schema is responsible for movement and ...interaction with the environment. It usually remains outside of active consciousness. There are only few investigations on influences on the body schema and none of them investigated feeling of satiety or hunger. Thirty-two healthy women were investigated twice, one time sat and the other time hungry. To measure the body schema, we used a door-like-aperture and compared the critical aperture-to-shoulder-ratio (cA/S). A cover story was used to ensure that the unconscious body schema has been measured. We found a significantly higher cA/S for satiety compared to hungry, which indicates that during satiety participants rotate their shoulders for relatively larger door compared to hunger, unconsciously estimating their body size to be larger. We showed that even a moderate rated feeling of hunger or satiety leads to an adjustment in body-scaled action and consequently also an adaptation of body schema. It suggests that, in addition to the visual-spatial and the proprioceptive representation, somatic information can also be relevant for the body schema.
Tivantinib (ARQ 197), a selective, oral MET inhibitor, improved overall survival and progression-free survival compared with placebo in a randomised phase 2 study in patients with high MET expression ...(MET-high) hepatocellular carcinoma previously treated with sorafenib. The aim of this phase 3 study was to confirm the results of the phase 2 trial.
We did a phase 3, randomised, double-blind, placebo-controlled study in 90 centres in Australia, the Americas, Europe, and New Zealand. Eligible patients were 18 years or older and had unresectable, histologically confirmed, hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0–1, high MET expression (MET-high; staining intensity score ≥2 in ≥50% of tumour cells), Child-Pugh A cirrhosis, and radiographically-confirmed disease progression after receiving sorafenib-containing systemic therapy. We randomly assigned patients (2:1) in block sizes of three using a computer-generated randomisation sequence to receive oral tivantinib (120 mg twice daily) or placebo (twice daily); patients were stratified by vascular invasion, extrahepatic spread, and α-fetoprotein concentrations (≤200 ng/mL or >200 ng/mL). The primary endpoint was overall survival in the intention-to-treat population. Efficacy analyses were by intention to treat and safety analyses were done in all patients who received any amount of study drug. This study is registered with ClinicalTrials.gov, number NCT01755767.
Between Dec 27, 2012, and Dec 10, 2015, 340 patients were randomly assigned to receive tivantinib (n=226) or placebo (n=114). At a median follow-up of 18·1 months (IQR 14·1–23·1), median overall survival was 8·4 months (95% CI 6·8–10·0) in the tivantinib group and 9·1 months (7·3–10·4) in the placebo group (hazard ratio 0·97; 95% CI 0·75–1·25; p=0·81). Grade 3 or worse treatment-emergent adverse events occurred in 125 (56%) of 225 patients in the tivantinib group and in 63 (55%) of 114 patients in the placebo group, with the most common being ascites (16 7% patients), anaemia (11 5% patients), abdominal pain (nine 4% patients), and neutropenia (nine 4% patients) in the tivantinib group. 50 (22%) of 226 patients in the tivantinib group and 18 (16%) of 114 patients in the placebo group died within 30 days of the last dose of study medication, and general deterioration (eight 4% patients) and hepatic failure (four 2% patients) were the most common causes of death in the tivantinib group. Three (1%) of 225 patients in the tivantinib group died from a treatment-related adverse event (one sepsis, one anaemia and acute renal failure, and one acute coronary syndrome).
Tivantinib did not improve overall survival compared with placebo in patients with MET-high advanced hepatocellular carcinoma previously treated with sorafenib. Although this METIV-HCC trial was negative, the study shows the feasibility of doing integral tissue biomarker studies in patients with advanced hepatocellular carcinoma. Additional randomised studies are needed to establish whether MET inhibition could be a potential therapy for some subsets of patients with advanced hepatocellular carcinoma.
ArQule Inc and Daiichi Sankyo (Daiichi Sankyo Group).
The use of immune checkpoint inhibitors constitutes an emerging therapeutic field for the therapy of gastrointestinal (GI) malignancies following the recent FDA approvals of PD-1 inhibitors for ...esophago-gastric adenocarcinoma, hepatocellular carcinoma and for microsatellite-instable tumors, which are mainly colorectal cancers. This paper reviews the clinical evidence end of 2017 and discusses the clinical development programs of atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab in GI-tract cancers. Since 2014, these antagonists of the PD-1/PD-L1 axis have gained approval for use in numerous other tumors. Phase II trials and phase I expansion cohorts demonstrate clinical activity in patients with oesophageal, gastric, colorectal, anal and hepatic cancer. Signals of outstanding efficacy are particularly observed in biomarker selected populations and for certain combination regimen. Comprehensive phase III development programs have been initiated in oesophageal and gastric cancer, with randomized trials ongoing in hepatocellular and colorectal cancer as well.
Patients with gastric cancer often show signs of malnutrition. We sought to evaluate the influence of sarcopenia in patients with locally advanced, not metastasized, gastric or gastro-esophageal ...junction (GEJ) cancer undergoing curative treatment (perioperative chemotherapy and surgery) on morbidity and mortality in order to identify patients in need for nutritional intervention.
Two-centre study, conducted in the Frankfurt University Clinic and Krankenhaus Nordwest (Frankfurt) as part of the University Cancer Center Frankfurt (UCT). 47/83 patients were treated in the FLOT trial (NCT01216644). Patients´ charts were reviewed for clinical data. Two consecutive CT scans were retrospectively analyzed to determine the degree of sarcopenia. Survival was calculated using the Kaplan-Meier method, multivariate analysis was performed using the Cox regression.
60 patients (72.3%) were male and 23 (27.7%) female. 45 patients (54.2%) had GEJ type 1-3 and 38 (45.8%) gastric tumors, respectively. Sarcopenic patients were significantly older than non-sarcopenic patients (mean age 65.1 years vs. 59.5 years, p = 0.042), terminated the chemotherapy significantly earlier (50% vs. 22.6%, p = 0.037) and showed higher Clavien-Dindo scores, indicating more severe perioperative complications (score ≥3 43.3 vs. 17.0%, p = 0.019). Sarcopenic patients had a significantly shorter survival than non-sarcopenic patients (139.6 ± 19.5 95% CI, 101.3-177.9 vs. 206.7 ± 13.8 95% CI, 179.5-233.8 weeks, p = 0.004). Multivariate Cox regression analysis showed that, besides UICC stage, sarcopenia significantly influenced survival.
Sarcopenia is present in a large proportion of patients with locally advanced gastric or GEJ cancer and significantly influences tolerability of chemotherapy, surgical complications and survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or ...plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.
62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = -0.494, P = 0.00002), alanine aminotransferase (ALT) (r = -0.309, P = 0.007), aspartate aminotransferase (r = -0.495, P = 0.000007), bilirubin (r = -0.362, P = 0.002), international normalized ratio (r = -0.338, P = 0.034) and γ-glutamyltransferase (r = -0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dC(T) of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.
The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Voluntary motor control over artificial hands has been shown to provoke a subjective incorporation of the artificial limb into body representations. However, in most studies projected or mirrored ...images of own hands were presented as ‘artificial’ body parts. Using the paradigm of the rubber hand illusion (RHI), we assessed the impact of tactile sensations and voluntary movements with respect to an unambiguously body-extraneous, artificial hand. In addition to phenomenal self-reports and pointing movements towards the own hand, we introduced a new procedure for perceptual judgements enabling the assessment of proprioceptive drift and judgement reliability regarding perceived hand location. RHI effects were comparable for tactile sensations and voluntary movements, but characteristic discrepancies were found for pointing movements. They were differently affected by the induction methods, and RHI effects were uncorrelated between both methods. These observations shed new light on inconsistent results concerning RHI effects on motor responses.
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