Pediatric-Inspired Regimens in the Treatment of Acute Lymphoblastic Leukemia in Adolescents and Young Adults: A Systematic Review

Adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) have significantly worse outcomes than their younger counterparts. Current treatment guidelines rely mostly on non-randomized retrospective studies. We performed a systematic review of studies published within the last 15 years comparing pediatric-inspired regimens (PIR) versus adult-type regimens or performing an age-stratified analysis of outcomes in the AYA population. Due to the heterogeneity of data, a meta-analysis was not possible. However, the gathered data show a trend toward improvement in outcomes and an acceptable toxicity profile in patients treated with PIRs compared to conventional adult-type regimens. There is still room for further improvement, as older patients within the AYA population tend to perform poorly with PIR or conventional adult-type chemotherapy. Further randomized studies are needed to develop an optimal treatment strategy for AYA with ALL

Sleep, Experimental Pain and Clinical Pain in Patients with Chronic Musculoskeletal Pain and Healthy Controls

Purpose: Everyday variations in night sleep in healthy pain-free subjects are at most weakly associated with pain, whereas strong alterations (eg, sleep deprivation, insomnia) lead to hyperalgesic pain changes. Since it remains unclear how substantial sleep alterations need to be in order to affect the pain system and lead to a coupling of both functions, the present study aimed at providing sufficient variance for co-variance analyses by examining a sample consisting of both healthy subjects and chronic pain patients. Methods: A sample of 20 chronic musculoskeletal pain patients and 20 healthy controls was examined. This sample was assumed to show high inter-individual variability in sleep and pain, as pain patients frequently report sleep disturbances, whereas healthy subjects were required to be pain-free and normal sleepers. Sleep of two non-consecutive nights was measured using portable polysomnography and questionnaires. Experimental pain parameters (pressure pain thresholds (PPT), temporal summation of pain (TSP), conditioned pain modulation (CPM)) and situational pain catastrophizing (SCQ) were assessed in laboratory sessions before and after sleep. Pain patients’ clinical pain was assessed via questionnaire. Results: As expected, both groups differed in several sleep parameters (reduced total sleep time and sleep efficiency, more time awake after sleep onset, lower subjective sleep quality in the patients) and in a few pain parameters (lower PPTs in the patients). In contrast, no differences were found in TSP, CPM, and SCQ. Contrary to our expectations, regression analyses indicated no prediction of overnight pain changes by sleep parameters. Conclusion: Since sleep parameters were hardly apt to predict overnight pain changes, this leaves the association of both systems mainly unproven when using between-subject variance for verification

Definition of the Surgical Case Complexity in the Treatment of Soft Tissue Tumors of the Extremities and Trunk

BACKGROUND: We intend to establish a complexity score for soft tissue tumor surgeries to compare the complexities of different soft tissue tumor surgeries and to ultimately assign affected patients to appropriate treatments. METHODS: We developed a soft tissue tumor complexity score (STS-SCS) based on three pillars: in addition to patient-related factors, tumor biology and surgery-associated parameters were taken into account. The STS-SCS was applied to our sampling group of 711 patients. RESULTS: The minimum STS-SCS was 4, the maximum score was 34 and the average score 11.4 ± 5.9. The scores of patients with malignant diagnoses were notably higher and more widely scattered than those of patients with benign or intermediate malignant tumors. To better categorize the complexities of individual surgeries, we established four categories using the collected data as a reference dataset. Each of the categories contained approximately one-quarter of the registered patients. DISCUSSION: The STS-SCS allows soft tissue tumor surgeries to be retrospectively evaluated for their complexity and forms the basis for the creation of a prospective concept to provide patients with the right intervention in the right geographic location, which can lead to better results and provision of the most cost-effective overall treatment

Attentional processing of pain faces and other emotional faces in chronic pain–an eye-tracking study

Altered attentional processing of pain-associated stimuli–which might take the form of either avoidance or enhanced vigilance–is thought to be implicated in the development and maintenance of chronic pain. In contrast to reaction time tasks like the dot probe, eye tracking allows for tracking the time course of visual attention and thus differentiating early and late attentional processes. Our study aimed at investigating visual attention to emotional faces in patients with chronic musculoskeletal pain (N = 20) and matched pain-free controls (N = 20). Emotional faces (pain, angry, happy) were presented in pairs with a neutral face for 2000 ms each. Three parameters were determined: First fixation probabilities, fixation durations (overall and divided in four 500 ms intervals) and a fixation bias score as the relative fixation duration of emotional faces compared to neutral faces. There were no group differences in any of the parameters. First fixation probabilities were lower for pain faces than for angry faces. Overall, we found longer fixation duration on emotional compared to neutral faces (‘emotionality bias’), which is in accord with previous research. However, significant longer fixation duration compared to the neutral face was detected only for happy and angry but not for pain faces. In addition, fixation durations as well as bias scores yielded evidence for vigilant-avoidant processing of pain faces in both groups. These results suggest that attentional bias towards pain-associated stimuli might not generally differentiate between healthy individuals and chronic pain patients. Exaggerated attentional bias in patients might occur only under specific circumstances, e.g., towards stimulus material specifically relating to the specific pain of the patients under study or under high emotional distress

Intraoperative pain during caesarean delivery: Incidence, risk factors and physician perception

Background: Intraoperative pain is a possible complication of neuraxial anaesthesia for caesarean delivery. There is little information available about its incidence, risk factors and physician perception. Methods: Parturients undergoing spinal anaesthesia for elective caesarean delivery were enrolled. Before surgery, parturients were asked about preoperative anxiety on a verbal numerical scale (VNS), anticipated analgesic requirement, postoperative pain levels, Spielberger STATE-TRAIT inventory index, Pain Catastrophizing Scale. After surgery, parturients were asked to answer questions (intraoperative VNS pain). The anaesthesiologist and obstetrician were asked to fill out a questionnaire asking about perceived intraoperative pain. Influence of preoperative anxiety on intraoperative pain (yes/no) was assessed using logistic regression. Mc Fadden's R2 was calculated. The agreement in physician perception of intraoperative pain with reported pain by the parturient was examined by calculating Cohen's kappa and 95% Confidence Intervals (CI). Results: We included 193 parturients in our analysis. Incidence of intraoperative pain was 11.9%. Median intraoperative VNS pain of parturients with pain was 4.0 (1st quartile 4.0; 3rd quartile 9.0). Preoperative anxiety was not a good predictor of intraoperative pain (p-value of β-coefficient = 0.43, Mc Fadden's R2 = 0.01). Including further preoperative variables did not result in a good prediction model. Cohen's kappa between reported pain by parturient and by the obstetrician was 0.21 (95% CI: 0.01, 0.41) and by the anaesthesiologist was 0.3 (95% CI: 0.12, 0.48). Conclusions: We found a substantial incidence (11.9%) of intraoperative pain during caesarean delivery. Preoperative anxiety did not predict intraoperative pain. Physicians did not accurately identify parturients' intraoperative pain. Significance: Intraoperative pain occurred in 11.9% and severe intraoperative pain occurred in 1.11% of parturients undergoing elective caesarean delivery under spinal anaesthesia. We did not find any preoperative variables that could reliably predict intraoperative pain. Obstetricians and anaesthesiologists underestimated the incidence of intraoperative pain in our cohort and thus, more attention must be put to parturients' pain

Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes

Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector$^{®}$, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector$^{®}$, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector$^{®}$ can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs

Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards

BACKGROUND AND INTRODUCTION Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis. MATERIALS AND METHODS For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care. RESULTS A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p < 0.05), whereas the number of oligometastases was not (p = 0.202). CONCLUSION More than half of oligometastatic cases were discussed in MDTs, of which more than every second received a recommendation including the addition of local therapy. This frequency of MDT use underscores the importance of multidisciplinary decision-making, yet efforts should be increased to standardize reporting and use standard nomenclature on oligometastasis in MDTs to better frame multidisciplinary discussion

Patterns of metastatic spread and tumor burden in unselected cancer patients using PET imaging: Implications for the oligometastatic spectrum theory

INTRODUCTION AND BACKGROUND: Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging. MATERIALS AND METHODS: All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed. RESULTS: For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs. CONCLUSION: The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease

FR II radio galaxies at low frequencies I : morphology, magnetic field strength and energetics

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2016 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Due to their steep spectra, low-frequency observations of FR II radio galaxies potentially provide key insights in to the morphology, energetics and spectrum of these powerful radio sources. However, limitations imposed by the previous generation of radio interferometers at metre wavelengths has meant that this region of parameter space remains largely unexplored. In this paper, the first in a series examining FR IIs at low frequencies, we use LOFAR observations between 50 and 160 MHz, along with complementary archival radio and X-ray data, to explore the properties of two FR II sources, 3C452 and 3C223. We find that the morphology of 3C452 is that of a standard FR II rather than of a double-double radio galaxy as had previously been suggested, with no remnant emission being observed beyond the active lobes. We find that the low-frequency integrated spectra of both sources are much steeper than expected based on traditional assumptions and, using synchrotron/inverse-Compton model fitting, show that the total energy content of the lobes is greater than previous estimates by a factor of around 5 for 3C452 and 2 for 3C223. We go on to discuss possible causes of these steeper than expected spectra and provide revised estimates of the internal pressures and magnetic field strengths for the intrinsically steep case. We find that the ratio between the equipartition magnetic field strengths and those derived through synchrotron/inverse-Compton model fitting remains consistent with previous findings and show that the observed departure from equipartition may in some cases provide a solution to the spectral versus dynamical age disparity.Peer reviewe

Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Multiple sclerosis is a complex neurological disease, with 3c20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFN\u3b3 biology, and NF\u3baB signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS. In a large multi-cohort study, unexplained heritability for multiple sclerosis is detected in low-frequency coding variants that are missed by GWAS analyses, further underscoring the role of immune genes in MS pathology