Time-varying prognostic value of primary tumor sidedness in metastatic colorectal cancer: A population-based study and meta-analysis

We studied the prognostic value of primary tumor sidedness in metastatic colorectal cancer over time and across treatment lines. Population data on synchronous metastatic colorectal cancer patients were extracted from the Netherlands Cancer Registry and SEER database. Pubmed, EMBASE and Cochrane library were searched for prospective studies on metastatic colorectal cancer to conduct a meta-analysis. Inclusion criteria consisted of metastatic disease, systemic treatment with palliative intent and specification of primary tumor location. Data were pooled using a random-effects model. For the population-based data, multivariable Cox models were constructed. The Grambsch-Therneau test was conducted to evaluate the potential time-varying nature of sidedness. Meta-regression incorporating treatment-line as variable was conducted to test the pre-specified hypothesis that the prognostic value of sidedness varies over time. Analysis of 12 885 and 16 160 synchronous metastatic colorectal cancer patients registered in the Netherlands Cancer Registry and SEER database, respectively, indicated a time-varying prognostic value of sidedness (P < .01). Thirty-one studies were selected for the meta-analysis (9558 patients for overall survival analysis). Pooled univariable hazard ratio_{left-sided/right-sided} for overall survival was 0.71 (95% CI: 0.65-0.76) in 1st-line, 0.76 (0.54-1.06) in 2nd-line and 1.01 (0.86-1.19) in 3rd-line studies. Hazard ratios were significantly influenced by treatment line (P = .035). The prognostic value of sidedness of the primary tumor in metastatic colorectal cancer patients treated with palliative systemic therapy decreases over time since diagnosis, suggesting that sidedness may not be a useful stratification factor in late-line trials. This decrease in prognostic value should be taken into account when providing prognostic information to patients.     

Patients’ and Psychologists’ Preferences for Feedback Reports on Expected Mental Health Treatment Outcomes: A Discrete-Choice Experiment

In recent years, there has been an increasing focus on routine outcome monitoring (ROM) to provide feedback on patient progress during mental health treatment, with some systems also predicting the expected treatment outcome. The aim of this study was to elicit patients’ and psychologists’ preferences regarding how ROM system-generated feedback reports should display predicted treatment outcomes. In a discrete-choice experiment, participants were asked 12–13 times to choose between two ways of displaying an expected treatment outcome. The choices varied in four different attributes: representation, outcome, predictors, and advice. A conditional logistic regression was used to estimate participants’ preferences. A total of 104 participants (68 patients and 36 psychologists) completed the questionnaire. Participants preferred feedback reports on expected treatment outcome that included: (a) both text and images, (b) a continuous outcome or an outcome that is expressed in terms of a probability, (c) specific predictors, and (d) specific advice. For both patients and psychologists, specific predictors appeared to be most important, specific advice was second most important, a continuous outcome or a probability was third most important, and feedback that includes both text and images was fourth in importance. The ranking in importance of both the attributes and the attribute levels was identical for patients and psychologists. This suggests that, as long as the report is understandable to the patient, psychologists and patients can use the same ROM feedback report, eliminating the need for ROM administrators to develop different versions.

     

Genetic factors explain a significant part of associations between adolescent well-being and the social environment

European Child & Adolescent Psychiatry - Socio-environmental factors play an important role in adolescent well-being, but potential genetic contributions to these associations are rarely...     

Rethinking the uncertainty of African swine fever virus contamination in feed ingredients and risk of introduction into the United States

Economically relevant pathogens, such as African swine fever virus (ASFV), have been shown to survive when experimentally inoculated in some feed ingredients under the environmental conditions in transoceanic transport models. However, these models did not characterize the likelihood of virus survival under various time and temperature processes that feed ingredients undergo before they are added to swine diets. Here, we developed a quantitative risk assessment model to estimate the probability that one or more corn or soybean meal ocean vessels (25,000 tonnes) contaminated with ASFV would be imported into the United States annually. This final probability estimate was conditionally based on five likelihoods: the probability of initial ASFV contamination (p0), ASFV inactivation during processing (p1) and transport (p2), recontamination (pR), and ASFV inactivation while awaiting customs clearance at United States entry (p3). The probability of ASFV inactivation was modelled using corn and soybean (extruded or solvent extracted) processing conditions (times and temperatures), D-values (time to reduce 90% or 1-log) estimated from studies of ASFV thermal inactivation in pork serum (p1), and survival in feed ingredients during transoceanic transport (p2 and p3). ‘What-if’ scenarios using deterministic values for p0 and pR (1%, 10%, 25%, 50%, 75%, and 100%) were used to explore their impact on risk. The model estimated complete inactivation of ASFV after extrusion or solvent extraction processes regardless of the initial ASFV contamination probability assumed. The value of recontamination (ranging from 1% to 75%) was highly influential on the risk of one ASFV-contaminated soybean meal vessel entering the United States. Median risk estimates ranged from 0.064% [0.006%–0.60%; 95% probability interval (PI)], assuming a pR of 1.0%, up to 4.67% (0.45%–36.50% 95% PI) assuming a pR of 75.0%. This means that at least one vessel with ASFV-contaminated soybean meal would be imported once every 1563–21 years, respectively. When all raw corn was assumed to be contaminated (p0 = 100%), and no recontamination was assumed to occur (pR = 0%), the median probability of one vessel with ASFV-contaminated corn entering the United States was 2.02% (0.28%–9.43% 95% PI) or once every 50 years. Values of recontamination between 1% and 75% did not substantially change the risk of corn. Days of transport, virus survival during transport (D-value), and number of vessels shipped were the parameters most influential for increased likelihood of a vessel with ASFV-contaminated soybean meal or corn entering the United States. The model helped to identify knowledge gaps that are most influential on output values and serves as a framework that could be updated and parameterized as new scientific information becomes available. We propose that the quantitative risk assessment model developed in this study can be used as a framework for estimating the risk of ASFV entry into the United States and other ASFV-free countries through other types of imported feed ingredients that may potentially become contaminated. Ultimately, this model can be used to develop risk mitigation strategies and critical control points for inactivating ASFV during feed ingredient processing, storage, and transport, and contribute to the design and implementation of biosecurity measures to prevent the introduction of ASFV into the United States and other ASFV-free countries.     

Oral health-related quality of life before,during, and after orthodontic-orthognathic treatment: a systematic review and meta-analysis

Clinical Oral Investigations - The effect of combined orthodontic-orthognathic treatment was estimated, specifically the impact of pre-surgical orthodontic treatment, on oral health-related quality...     

The feasibility of quantitative MRI of extra‐ocular muscles in myasthenia gravis and Graves' orbitopathy

Although quantitative MRI can be instrumental in the diagnosis and assessment of disease progression in orbital diseases involving the extra‐ocular muscles (EOM), acquisition can be challenging as EOM are small and prone to eye‐motion artefacts. We explored the feasibility of assessing fat fractions (FF), muscle volumes and water T2 (T2_water) of EOM in healthy controls (HC), myasthenia gravis (MG) and Graves' orbitopathy (GO) patients. FF, EOM volumes and T2_water values were determined in 12 HC (aged 22‐65 years), 11 MG (aged 28‐71 years) and six GO (aged 28‐64 years) patients at 7 T using Dixon and multi‐echo spin‐echo sequences. The EOM were semi‐automatically 3D‐segmented by two independent observers. MANOVA and t‐tests were used to assess differences in FF, T2_water and volume of EOM between groups (P < .05). Bland–Altman limits of agreement (LoA) were used to assess the reproducibility of segmentations and Dixon scans. The scans were well tolerated by all subjects. The bias in FF between the repeated Dixon scans was ?0.7% (LoA: ±2.1%) for the different observers; the bias in FF was ?0.3% (LoA: ±2.8%) and 0.03 cm³ (LoA: ± 0.36 cm³) for volume. Mean FF of EOM in MG (14.1% ± 1.6%) was higher than in HC (10.4% ± 2.5%). Mean muscle volume was higher in both GO (1.2 ± 0.4 cm³) and MG (0.8 ± 0.2 cm³) compared with HC (0.6 ± 0.2 cm³). The average T2_water for all EOM was 24.6 ± 4.0 ms for HC, 24.0 ± 4.7 ms for MG patients and 27.4 ± 4.2 ms for the GO patient. Quantitative MRI at 7 T is feasible for measuring FF and muscle volumes of EOM in HC, MG and GO patients. The measured T2_water was on average comparable with skeletal muscle, although with higher variation between subjects. The increased FF in the EOM in MG patients suggests that EOM involvement in MG is accompanied by fat replacement. The unexpected EOM volume increase in MG may provide novel insights into underlying pathophysiological processes.     

Compressed sensing with signal averaging for improved sensitivity and motion artifact reduction in fluorine‐19 MRI

Fluorine‐19 (¹⁹F) MRI of injected perfluorocarbon emulsions (PFCs) allows for the non‐invasive quantification of inflammation and cell tracking, but suffers from a low signal‐to‐noise ratio and extended scan time. To address this limitation, we tested the hypotheses that a ¹⁹F MRI pulse sequence that combines a specific undersampling regime with signal averaging has both increased sensitivity and robustness against motion artifacts compared with a non‐averaged fully sampled pulse sequence, when both datasets are reconstructed with compressed sensing. As a proof of principle, numerical simulations and phantom experiments were performed on selected variable ranges to characterize the point spread function of undersampling patterns, as well as the vulnerability to noise of undersampling and reconstruction parameters with paired numbers of x signal averages and acceleration factor x (NAx ‐AFx ). The numerical simulations demonstrated that a probability density function that uses 25% of the samples to fully sample the k‐space central area allowed for an optimal balance between limited blurring and artifact incoherence. At all investigated noise levels, the Dice similarity coefficient (DSC) strongly depended on the regularization parameters and acceleration factor. In phantoms, the motion robustness of an NA8‐AF8 undersampling pattern versus NA1‐AF1 was evaluated with simulated and real motion patterns. Differences were assessed with the DSC, which was consistently higher for the NA8‐AF8 compared with the NA1‐AF1 strategy, for both simulated and real cyclic motion patterns (P < 0.001). Both strategies were validated in vivo in mice (n = 2) injected with perfluoropolyether. Here, the images displayed a sharper delineation of the liver with the NA8‐AF8 strategy than with the NA1‐AF1 strategy. In conclusion, we validated the hypotheses that in ¹⁹F MRI the combination of undersampling and averaging improves both the sensitivity and the robustness against motion artifacts.     

Radiotherapy is not indicated in patients with vulvar squamous cell carcinoma and only one occult intracapsular groin node metastasis

ObjectiveMost guidelines advise no adjuvant radiotherapy in vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis. However, several recent studies have questioned the validity of this recommendation. The aim of this study was to analyze the groin recurrence rate in patients with a single intracapsular positive lymph node treated without adjuvant radiotherapy.MethodsPatients with a single clinically occult intracapsular lymph node metastasis, treated without adjuvant radiotherapy, formed the basis for this study. Groin recurrences, and the risk of death, were analyzed in relation to the size of the metastasis in the lymph node and the lymph node ratio. Data were analyzed using SPSS, version 26.0 for Windows.ResultsAfter a median follow-up of 64 months, one of 96 patients (1%) was diagnosed with an isolated groin recurrence and another two (2.1%) were diagnosed with a combination of a local and a groin recurrence. The only isolated groin recurrence occurred in a contralateral lymph node negative groin. Size of the metastasis and lymph node ratio had no impact on the groin recurrence risk, nor on survival. The 5-year actuarial disease-specific and overall survivals were 79% and 62.5% respectively. The 5-year actuarial groin recurrence-free survival was 97%.ConclusionBecause of the low risk of groin recurrence and the excellent groin recurrence-free survival, we recommend that adjuvant radiotherapy to the groin in patients with vulvar squamous cell carcinoma and a single occult intracapsular lymph node metastasis can be safely omitted to prevent unnecessary toxicity and morbidity.