Recent technological and analytical progress in brain imaging has enabled the examination of brain organization and connectivity at unprecedented levels of detail. The Human Connectome Project in ...Development (HCP-D) is exploiting these tools to chart developmental changes in brain connectivity. When complete, the HCP-D will comprise approximately ∼1750 open access datasets from 1300 + healthy human participants, ages 5–21 years, acquired at four sites across the USA. The participants are from diverse geographical, ethnic, and socioeconomic backgrounds. While most participants are tested once, others take part in a three-wave longitudinal component focused on the pubertal period (ages 9–17 years). Brain imaging sessions are acquired on a 3 T Siemens Prisma platform and include structural, functional (resting state and task-based), diffusion, and perfusion imaging, physiological monitoring, and a battery of cognitive tasks and self-reports. For minors, parents additionally complete a battery of instruments to characterize cognitive and emotional development, and environmental variables relevant to development. Participants provide biological samples of blood, saliva, and hair, enabling assays of pubertal hormones, health markers, and banked DNA samples. This paper outlines the overarching aims of the project, the approach taken to acquire maximally informative data while minimizing participant burden, preliminary analyses, and discussion of the intended uses and limitations of the dataset.
•The HCP-D aims to chart the development of human brain connectivity.•N = 1300+ 5–21 year olds complete multimodal brain imaging and behavioral assessments.•This paper describes the primary aims and scientific approach of the project.•Data can address a wide range of questions concerning healthy neurodevelopment.•These data will be publicly released to the scientific community in a timely manner.
Periarticular hardware placement can be challenging and a source of angst for orthopaedic surgeons due to fear of penetrating the articular surface and causing undue harm to the joint. In recent ...years, many surgeons have turned to computed tomography (CT) and other intraoperative or postoperative modalities to determine whether hardware is truly extraarticular in areas of complex anatomy. Yet, these adjuncts are expensive, time consuming, and often unnecessary given the advancement in understanding of intraoperative fluoroscopy. We present a review article with the goal of empowering surgeons to leave the operating room, with fluoroscopy alone, assured that all hardware is beneath the articular surface that is being worked on. By understanding a simple concept, surgeons can extrapolate the information in this article to any joint and bony surface in the body. While targeted at both residents and surgeons who may not have completed a trauma fellowship, this review can benefit all orthopaedic surgeons alike.
Purpose Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. Although radical cystectomy (RC) ...currently is viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) that combines transurethral resection of bladder tumor, chemotherapy for radiation sensitization, and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, this study compared the oncologic outcomes between patients treated with RC or TMT by using a propensity score matched-cohort analysis. Methods Data from patients treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were reviewed retrospectively. Those who received TMT for MIBC were identified and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status, Charlson comorbidity score, treatment date, age, carcinoma in situ status, and hydronephrosis) with propensity scores to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox proportional hazards modeling and a competing risk analysis, respectively. Results A total of 112 patients with MIBC were included after matching (56 who had been treated with TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths (35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6 (10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC, TMT yielded survival outcomes similar to those of matched patients who underwent RC. Appropriately selected patients with MIBC should be offered the opportunity to discuss various treatment options, including organ-sparing TMT.
Purpose
Skin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually ...fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient‐specific skin collimation (in‐house 3D printed and vendor‐provided machined brass) using clinically relevant metrics.
Methods
Attenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials.
Results
Clinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation.
Conclusion
Both skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in‐house or outsource the fabrication to a vendor.
We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer.
...In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated.
pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08).
Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.
Background
Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma (mUC) in Study 1108 (NCT01693562). An important focus in treatment is health‐related ...quality of life (HRQOL). Here, patient‐reported outcomes (PROs) from Study 1108 and their relationship with inflammatory biomarkers are explored.
Methods
Disease‐related symptoms, functioning, and HRQOL were assessed with the Functional Assessment of Cancer Therapy–Bladder (FACT‐Bl) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ‐C30). Relationships between PRO improvements and the best changes in the tumor size, albumin level, and neutrophil‐lymphocyte ratio (NLR) were assessed with Spearman correlation analysis.
Results
The mean FACT‐Bl total score improved from 107.5 (standard deviation SD, 23.0) at the baseline to 115.4 (SD, 22.6) on day 113, with similar increases found for the Trial Outcome Index (TOI) and Bladder Cancer Subscale (BLCS) scores. The mean FACT‐Bl total scores improved over time, and the FACT‐Bl TOI scores significantly improved by day 113 (P < .05). The mean EORTC QLQ‐C30 Global Health Status/Quality of Life score improved from 57.1 (SD, 24.8) at the baseline to 69.0 (SD, 21.4) on day 113; the functional scale and symptom scores (day 113) were higher than the baseline scores (P < .05) for EORTC Social Functioning. The FACT‐Bl total, BLCS, and TOI scores improved in 32.6%, 34.9%, and 32.6% of the patients by day 113; 26.3% to 37.8% of the patients exhibited improvements in EORTC QLQ‐C30 functional scores. The best tumor shrinkage and posttreatment improvements in serum albumin and NLR correlated with increases in FACT‐Bl total, TOI, and BLCS scores and in EORTC Physical Functioning and Role Functioning scores (P < .05).
Conclusions
Durvalumab was associated with improvements in disease‐related symptoms, functioning, and HRQOL in patients with mUC. Improvements in systemic inflammation may contribute to PRO improvements in these patients.
In patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab, improvements in patient‐reported outcomes correlate not only with objective tumor responses but also with reductions in markers of systemic inflammation. These findings provide insight into potential links between attenuation of inflammation in cancer and patient‐reported outcomes.
Although there have been many lower limb robotic exoskeletons that have been tested for human walking, few devices have been tested for assisting running. It is possible that a pseudo-passive elastic ...exoskeleton could benefit human running without the addition of electrical motors due to the spring-like behavior of the human leg. We developed an elastic lower limb exoskeleton that added stiffness in parallel with the entire lower limb. Six healthy, young subjects ran on a treadmill at 2.3 m/s with and without the exoskeleton. Although the exoskeleton was designed to provide ~50% of normal leg stiffness during running, it only provided 24% of leg stiffness during testing. The difference in added leg stiffness was primarily due to soft tissue compression and harness compliance decreasing exoskeleton displacement during stance. As a result, the exoskeleton only supported about 7% of the peak vertical ground reaction force. There was a significant increase in metabolic cost when running with the exoskeleton compared with running without the exoskeleton (ANOVA, P < .01). We conclude that 2 major roadblocks to designing successful lower limb robotic exoskeletons for human running are human-machine interface compliance and the extra lower limb inertia from the exoskeleton.
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