Convection-Enhanced Delivery for Targeted Delivery of Antiglioma Agents: The Translational Experience

Recent improvements in the understanding of glioblastoma (GBM) have allowed for increased ability to develop specific, targeted therapies. In parallel, however, there is a need for effective methods of delivery to circumvent the therapeutic obstacles presented by the blood-brain barrier and systemic side effects. The ideal delivery system should allow for adequate targeting of the tumor while minimizing systemic exposure, applicability across a wide range of potential therapies, and have existing safe and efficacious systems that allow for widespread application. Though many alternatives to systemic delivery have been developed, this paper will focus on our experience with convection-enhanced delivery (CED) and our focus on translating this technology from pre-clinical studies to the treatment of human GBM

Results of the 2016 Indianapolis Biodiversity Survey, Marion County, Indiana

Surprising biodiversity can be found in cities, but urban habitats are understudied. We report on a bioblitz conducted primarily within a 24-hr period on September 16 and 17, 2016 in Indianapolis, Indiana, USA. The event focused on stretches of three waterways and their associated riparian habitat: Fall Creek (20.6 ha; 51 acres), Pleasant Run (23.5 ha; 58 acres), and Pogue’s Run (27.1 ha; 67 acres). Over 75 scientists, naturalists, students, and citizen volunteers comprised 14 different taxonomic teams. Five hundred ninety taxa were documented despite the rainy conditions. A brief summary of the methods and findings are presented here. Detailed maps of survey locations and inventory results are available on the Indiana Academy of Science website (https://www.indianaacademyofscience.org/)

Leveraging pediatric PROMIS item banks to assess physical functioning in children at risk for severe functional loss

Background: Pediatric neuromuscular illnesses often result in decreased health-related quality of life (HRQL), notably in physical functioning. Generic HRQL measures have been developed for use in general populations, but may not adequately assess patients with severe functional loss. To address this measurement gap, we created two custom parent-proxy physical functioning short forms for use among children at risk for low levels of functioning, using pediatric Patient Reported Outcomes Measurement Information System (PROMIS) item banks for Upper Extremity and Mobility. Methods: Two custom short forms from PROMIS Upper Extremity (13 items) and Mobility (13 items) parent-proxy item banks were created and administered to parents of children (ages 5 – 22 years) enrolled in an integrated care program for management of chronic respiratory insufficiency, largely due to neuromuscular illnesses. Standardized PROMIS T-scores have a mean of 50 (SD = 10); higher scores indicate better functioning. Physicians rated clinical severity. Single proxy-rated items on mental and physical health from the Child Health Rating Inventories (CHRIs) global health scale were completed by parents. Psychometric properties, including known groups comparisons, were explored. Results: Fifty-seven parents completed the parent-proxy custom PROMIS short forms. The mean Upper Extremity T-score was 21 (SD = 13); the mean Mobility T-score was 22 (SD = 11). Some participants scored at the measurement floor; two items on assistive devices did not perform well in this sample and were excluded from the Mobility T-score. Known groups comparisons showed that those with lower clinical severity had better median Upper Extremity (22 vs. 14, p < 0.001) and Mobility (28 vs. 16, p = 0.004) function than those with worse clinical severity. Both Upper Extremity and Mobility T-scores were higher in the subgroups defined by better physical and mental health, as measured by the CHRIs. Conclusions: Upper Extremity and Mobility T-scores were nearly three standard deviations below the PROMIS pediatric calibration population mean. Preliminary psychometrics demonstrated the potential to more accurately measure lower physical functioning using items from PROMIS item banks. However, some participants scored at the measurement floor despite targeting items at the lower end of the scale. Further short form refinement, enrichment of the item banks, and larger-scale field testing are needed

Virchow: A Million-Slide Digital Pathology Foundation Model

Computational pathology uses artificial intelligence to enable precision medicine and decision support systems through the analysis of whole slide images. It has the potential to revolutionize the diagnosis and treatment of cancer. However, a major challenge to this objective is that for many specific computational pathology tasks the amount of data is inadequate for development. To address this challenge, we created Virchow, a 632 million parameter deep neural network foundation model for computational pathology. Using self-supervised learning, Virchow is trained on 1.5 million hematoxylin and eosin stained whole slide images from diverse tissue groups, which is orders of magnitude more data than previous works. When evaluated on downstream tasks including tile-level pan-cancer detection and subtyping and slide-level biomarker prediction, Virchow outperforms state-of-the-art systems both on internal datasets drawn from the same population as the pretraining data as well as external public datasets. Virchow achieves 93% balanced accuracy for pancancer tile classification, and AUCs of 0.983 for colon microsatellite instability status prediction and 0.967 for breast CDH1 status prediction. The gains in performance highlight the importance of pretraining on massive pathology image datasets, suggesting pretraining on even larger datasets could continue improving performance for many high-impact applications where limited amounts of training data are available, such as drug outcome prediction

Bedside breath tests in children with abdominal pain: a prospective pilot feasibility study

Background: There is no definitive method of accurately diagnosing appendicitis before surgery. We evaluated the feasibility of collecting breath samples in children with abdominal pain and gathered preliminary data on the accuracy of breath tests. Methods: We conducted a prospective pilot study at a large tertiary referral paediatric hospital in the UK. We recruited 50 participants with suspected appendicitis, aged between 5 and 15 years. Five had primary diagnosis of appendicitis. The primary outcome was the number of breath samples collected. We also measured the number of samples processed within 2 h and had CO2 ≥ 3.5%. Usability was assessed by patient-reported pain pre- and post-sampling and user-reported sampling difficulty. Logistic regression analysis was used to predict appendicitis and evaluated using the area under the receiver operator characteristic curve (AUROC). Results: Samples were collected from all participants. Of the 45 samples, 36 were processed within 2 h. Of the 49 samples, 19 had %CO2 ≥ 3.5%. No difference in patient-reported pain was observed (p = 0.24). Sampling difficulty was associated with patient age (p = 0.004). The logistic regression model had AUROC = 0.86. Conclusions: Breath tests are feasible and acceptable to patients presenting with abdominal pain in clinical settings. We demonstrated adequate data collection with no evidence of harm to patients. The AUROC was better than a random classifier; more specific sensors are likely to improve diagnostic performance. Trial registration: ClinicalTrials.gov, NCT03248102. Registered 14 Aug 2017

Neurosurgical Mimics

The goal of the following article is to help the practicing physician learn to recognize conditions that mimic conditions requiring neurosurgical intervention. Each case vignette is presented with relevant clinical history and examination, imaging studies and findings, as well as other testing results. The management for the corresponding diagnosis is presented. Finally, the relevant mimics and differentiating features are discussed

Syrinx shunts for syringomyelia: a systematic review and meta-analysis of syringosubarachnoid, syringoperitoneal, and syringopleural shunting

OBJECTIVE Syringomyelia is a debilitating, progressive disease process that can lead to loss of neurological function in patients already experiencing significant compromise. Syringosubarachnoid, syringoperitoneal, and syringopleural shunts are accepted treatment options for patients with persistent syringomyelia, but direct comparisons have been lacking to date. The authors conducted a systematic review of the literature and meta-analysis to compare clinical outcomes between these three syrinx shunt modalities. METHODS Utilizing PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews, Ovid Embase, PubMed, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, American College of Physicians Journal Club, and Database of Abstracts of Review of Effectiveness were searched to identify all potentially relevant studies published from inception until July 2020. Data were extracted and analyzed using meta-analysis of proportions. The primary study outcome was the rate of reoperation based on the initial shunt modality. Secondary outcomes included clinical improvement, clinical deterioration, and complications following shunt placement. RESULTS A total of 22 articles describing 27 distinct treatment cohorts published between 1984 and 2019 satisfied the inclusion criteria. This captured 473 syrinx shunt procedures, 193 (41%) by syringosubarachnoid shunt, 153 (32%) by syringoperitoneal shunt, and 127 (27%) by syringopleural shunt, with an overall median clinical follow-up of 44 months. The pooled incidences of revision surgery were estimated as 13% for syringosubarachnoid, 28% for syringoperitoneal, and 10% for syringopleural shunts, respectively (p-interaction = 0.27). The rate of clinical improvement was estimated as 61% for syringosubarachnoid, 64% for syringoperitoneal, and 71% for syringopleural shunts. The rate of clinical deterioration following placement was estimated as 13% for syringosubarachnoid, 13% for syringoperitoneal, and 10% for syringopleural shunts. CONCLUSIONS The preferred modality of syrinx shunting remains a controversial topic for symptomatic syringomyelia. This study suggests that while all three modalities offer similar rates of clinical improvement and deterioration after placement, syringoperitoneal shunts have a greater rate of malfunction requiring surgical revision. These data also suggest that syringopleural shunts may offer the best rate of clinical improvement with the lowest rate of reoperation

The essentials of algebra : for secondary schools /

Answers (31 p.) at end.Mode of access: Internet

Challenges in Diagnosis and Management of Previously Embolized Spinal Dural Arteriovenous Fistulae

Given the growing prevalence of initial endovascular treatment for type 1 spinal dural arteriovenous fistulae (dAVF), there are an increasing number of patients presenting with progressive symptoms related to recurrent previously embolized spinal dAVF. This study's goal was to identify demographic, clinical, and radiographic variables among patients who have failed embolization of type I spinal dAVF.A retrospective review of 24 consecutive surgeries for type I spinal dAVF performed by the senior author (A.D.L.) identified 5 patients who underwent open surgery for failed embolization. These 5 cases were reviewed for location of fistula, time from embolization to recurrence, preoperative functional status, fistulous point encountered at surgery, and clinical outcome of the patient at 3-month follow-up. A representative example case is reviewed in detail.The median age at time of recurrence was 63 years (range 51–73 years). The median timing of embolization to recurrence of neurologic symptoms was 5 months (range 1–54) and to surgery 7 months (range 2–60 months). The level of the spinal dAVF was most frequently at T12–L1 (n = 3). Spinal magnetic resonance arteriography led to localization of the spinal dAVF in 2 patients and spinal catheter angiogram in 3 cases. All patients had definitive radiographic cure of the dAVF at last clinical follow-up.The increased use of endovascular treatment of spinal dAVF has led to the treatment of refractory cases with a greater degree of surgical complexity. Open surgical ligation continues to provide the most definitive treatment outcomes for this complex spinal vascular entity