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Gliomas are the most common malignant primary brain tumor in adults. Despite advances in multimodality therapy, incorporating surgery, radiotherapy, systemic therapy, tumor treating fields and supportive care, patient outcomes remain poor, especially in glioblastoma where median survival has remained static at around 15 months, for decades. Low-grade gliomas typically harbor isocitrate dehydrogenase (IDH) mutations, grow more slowly and confer a better prognosis than glioblastoma. However, nearly all gliomas eventually recur and progress in a way similar to glioblastoma. One of the novel therapies being developed in this area are poly(ADP-Ribose) polymerase (PARP) inhibitors. PARP inhibitors belong to a class of drugs that target DNA damage repair pathways. This leads to synthetic lethality of cancer cells with coexisting homologous recombination deficiency. PARP inhibitors may also potentiate the cytotoxic effects of radiotherapy and chemotherapy, and prime the tumor microenvironment for immunotherapy. In this review, we examine the rationale and clinical evidence for PARP inhibitors in glioma and suggest therapeutic opportunities.

OBJECTIVE Suprasellar meningioma resection via either the transcranial approach (TCA) or the endoscopic endonasal approach (EEA) is an area of controversy and active evaluation. Skull base surgeons increasingly consider patient-reported outcomes (PROs) when choosing an approach. No PRO measure currently exists to assess quality of life for suprasellar meningiomas. METHODS Adult patients undergoing suprasellar meningioma resection between 2013 and 2019 via EEA (n = 14) or TCA (n = 14) underwent semistructured interviews. Transcripts were coded using a grounded theory approach to identify themes as the basis for a PRO measure that includes all uniquely reported symptoms. To assess content validity, 32 patients and 15 surgeons used a Likert scale to rate the relevance of items on the resulting questionnaire and the general Patient-Reported Outcomes Measurement Information System–29 (PROMIS29). The mean scores were calculated for all items and compared for TCA versus EEA patient cohorts by using unpaired t-tests. Items on either questionnaire with mean scores ≥ 2.0 from patients were considered meaningful and were aggregated to form the novel Suprasellar Meningioma Patient-Reported Outcome Survey (SMPRO) instrument. RESULTS Qualitative analyses resulted in 55 candidate items. Relative to patients who underwent the EEA, those who underwent the TCA reported significantly worse future outlook before surgery (p = 0.01), tiredness from medications 2 weeks after surgery (p = 0.001), and word-finding and memory difficulties 3 months after surgery (p = 0.05 and < 0.001, respectively). The items that patients who received a TCA were most concerned about included medication-induced lethargy after surgery (2.9 ± 1.3), blurry vision before surgery (2.7 ± 1.5), and difficulty reading due to blurry vision before surgery (2.7 ± 2.7). Items that patients who received an EEA were most concerned about included blurry vision before surgery (3.5 ± 1.3), difficulty reading due to blurry vision before surgery (2.4 ± 1.3), and problems with smell postsurgery (2.9 ± 1.3). Although surgeons overall overestimated how concerned patients were about questionnaire items (p < 0.0005), the greatest discrepancies between patient and surgeon relevance scores were for blurry vision pre- and postoperatively (p < 0.001 and < 0.001, respectively) and problems with taste postoperatively (p < 0.001). Seventeen meningioma-specific items were considered meaningful, supplementing 8 significant PROMIS29 items to create the novel 25-item SMPRO. CONCLUSIONS The authors developed a disease- and approach-specific measure for suprasellar meningiomas to compare quality of life by operative approach. If demonstrated to be reliable and valid in future studies, this instrument may assist patients and providers in choosing a personalized surgical approach.

125 Background: Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) is being evaluated as a novel minimally invasive palliative treatment of peritoneal metastases (PM). Prior studies have established the feasibility and safety of repeated PIPAC treatments in gastrointestinal and gynecologic cancers. The goal of the present phase 1 trial was to establish the safety and feasibility of PIPAC oxaliplatin in a highly chemotherapy refractory colorectal and appendiceal cancer patient population. Methods: Patients with biopsy-proven peritoneal metastases from colorectal or appendiceal cancer underwent up to three PIPAC treatments using oxaliplatin (92 mg/m2) with a six-week interval at two academic centers. Patients with bowel obstruction, extra-peritoneal metastases, or poor performance status (ECOG>2) were excluded. PIPAC was nebulized over 5 min with a 30 min aerosol dwell time. Apart from the first PIPAC cycle, the patients also received a sensitizing dose of 5FU/LV (400mg/m2) within 24 hours of the procedure. Primary end point was safety as assessed by dose limiting toxicities within 6 weeks of the first PIPAC. Secondary endpoints included safety with the addition of 5FU/LV, efficacy, surgical morbidity, technical failure rate, progression-free and overall survival, pharmacokinetics (PK), and quality of life assessment. Results: A total of 8 patients were included: 5 colorectal; and 3 appendiceal. Median number of prior chemotherapy cycles was 2 (Interquartile range – IQR; 1.5-3.5). All patients were refractory to systemic oxaliplatin-based chemotherapy. Median time from diagnosis to PIPAC was 16 months (IQR; 5.6, 17.5) and Peritoneal Carcinomatosis Index was 29 (IQR; 20.5, 31.5). Five (62.5%) patients completed 3 PIPAC cycles while in 3 (37.5%) patients PIPAC was discontinued due to disease progression within the peritoneal cavity. No surgical complication or dose limiting toxicity was observed. Only one patient developed grade 3 treatment-related toxicity after first PIPAC (anemia), and another patient after second PIPAC (abdominal pain and anemia). At the completion of PIPAC treatment 5 patients had stable disease and 3 had disease progression. Pharmacokinetic, histologic response and preliminary survival data will be presented at the meeting. Conclusions: PIPAC with oxaliplatin is safe and feasible in a highly chemotherapy refractory cohort of appendiceal and colorectal carcinomatosis patients with or without sensitizing 5-FU/ LV. Clinical trial information: NCT04329494.

Abstract Background We aimed to determine if patient symptoms and computed tomography enterography (CTE) and magnetic resonance enterography (MRE) imaging findings can be used to predict near-term risk of surgery in patients with small bowel Crohn’s disease (CD). Methods CD patients with small bowel strictures undergoing serial CTE or MRE were retrospectively identified. Strictures were defined by luminal narrowing, bowel wall thickening, and unequivocal proximal small bowel dilation. Harvey-Bradshaw index (HBI) was recorded. Stricture observations and measurements were performed on baseline CTE or MRE and compared to with prior and subsequent scans. Patients were divided into those who underwent surgery within 2 years and those who did not. LASSO (least absolute shrinkage and selection operator) regression models were trained and validated using 5-fold cross-validation. Results Eighty-five patients (43.7 ± 15.3 years of age at baseline scan, majority male [57.6%]) had 137 small bowel strictures. Surgery was performed in 26 patients within 2 years from baseline CTE or MRE. In univariate analysis of patients with prior exams, development of stricture on the baseline exam was associated with near-term surgery (P = .006). A mathematical model using baseline features predicting surgery within 2 years included an HBI of 5 to 7 (odds ratio [OR], 1.7 × 105; P = .057), an HBI of 8 to 16 (OR, 3.1 × 105; P = .054), anastomotic stricture (OR, 0.002; P = .091), bowel wall thickness (OR, 4.7; P = .064), penetrating behavior (OR, 3.1 × 103; P = .096), and newly developed stricture (OR: 7.2 × 107; P = .062). This model demonstrated sensitivity of 67% and specificity of 73% (area under the curve, 0.62). Conclusions CTE or MRE imaging findings in combination with HBI can potentially predict which patients will require surgery within 2 years.

(1) Background: COVID-19 computed tomography (CT) lung segmentation is critical for COVID lung severity diagnosis. Earlier proposed approaches during 2020–2021 were semiautomated or automated but not accurate, user-friendly, and industry-standard benchmarked. The proposed study compared the COVID Lung Image Analysis System, COVLIAS 1.0 (GBTI, Inc., and AtheroPointTM, Roseville, CA, USA, referred to as COVLIAS), against MedSeg, a web-based Artificial Intelligence (AI) segmentation tool, where COVLIAS uses hybrid deep learning (HDL) models for CT lung segmentation. (2) Materials and Methods: The proposed study used 5000 ITALIAN COVID-19 positive CT lung images collected from 72 patients (experimental data) that confirmed the reverse transcription-polymerase chain reaction (RT-PCR) test. Two hybrid AI models from the COVLIAS system, namely, VGG-SegNet (HDL 1) and ResNet-SegNet (HDL 2), were used to segment the CT lungs. As part of the results, we compared both COVLIAS and MedSeg against two manual delineations (MD 1 and MD 2) using (i) Bland–Altman plots, (ii) Correlation coefficient (CC) plots, (iii) Receiver operating characteristic curve, and (iv) Figure of Merit and (v) visual overlays. A cohort of 500 CROATIA COVID-19 positive CT lung images (validation data) was used. A previously trained COVLIAS model was directly applied to the validation data (as part of Unseen-AI) to segment the CT lungs and compare them against MedSeg. (3) Result: For the experimental data, the four CCs between COVLIAS (HDL 1) vs. MD 1, COVLIAS (HDL 1) vs. MD 2, COVLIAS (HDL 2) vs. MD 1, and COVLIAS (HDL 2) vs. MD 2 were 0.96, 0.96, 0.96, and 0.96, respectively. The mean value of the COVLIAS system for the above four readings was 0.96. CC between MedSeg vs. MD 1 and MedSeg vs. MD 2 was 0.98 and 0.98, respectively. Both had a mean value of 0.98. On the validation data, the CC between COVLIAS (HDL 1) vs. MedSeg and COVLIAS (HDL 2) vs. MedSeg was 0.98 and 0.99, respectively. For the experimental data, the difference between the mean values for COVLIAS and MedSeg showed a difference of <2.5%, meeting the standard of equivalence. The average running times for COVLIAS and MedSeg on a single lung CT slice were ~4 s and ~10 s, respectively. (4) Conclusions: The performances of COVLIAS and MedSeg were similar. However, COVLIAS showed improved computing time over MedSeg.

AbstractBackgroundMedical trainees’ work schedule is designed to cover duties without consideration of differences in circadian rhythms during a 24-hour period (chronotype).ObjectiveTo explore chronotype variation among medical trainees and understand its association with burn-out and schedule satisfaction.MethodsIn a multicentre observational study, we conducted two surveys between 1 October 2018 and 1 April 2019. Trainees from nine centres across the USA participated. We measured burn-out using Maslach Burnout Inventory (MBI), and trainee chronotype using the Morningness-Eveningness Questionnaire (MEQ).Results324 (32%) out of 1012 responded to our survey. Participants were 51% female and had a mean age of 30.8 years. Most participants had an intermediate MEQ type (65%). A large proportion of participants had burn-out on at least one of three tested MBI scales (62%); 5% of participants had burn-out on all three MBI scales. More participants with evening MEQ type had burn-out (66%) compared with morning MEQ type (55%), however, the results were not statically significant (p=0.294). Overall satisfaction with work shifts was 6.5 (95% CI 6.3 to 6.7), with higher satisfaction with day shift 7.7 (95% CI 7.5 to 7.9) and lowest satisfaction with overnight 24-hour call 3.5 (95% CI 3.2 to 3.9). Satisfaction was lower in trainees with burn-out 6.0 (95% CI 5.7 to 6.4), (p&lt;0.001). In the follow-up survey, burn-out was present in at least one scale in 64% compared with 60% of respondents in the initial survey.ConclusionBurn-out is prevalent among medical trainees. Improving alignment between trainee preferences may improve performance, reduce human errors and burn-out.

In the last few decades, carcinogenesis has been extensively explored and substantial research has identified immunogenic involvement in various types of cancers. As a result, immune checkpoint blockers and other immune-based therapies were developed as novel immunotherapeutic strategies. However, despite being a promising therapeutic option, immunotherapy has significant constraints such as a high cost of treatment, unpredictable toxicity, and clinical outcomes. miRNAs are non-coding, small RNAs actively involved in modulating the immune system’s multiple signalling pathways by binding to the 3′-UTR of target genes. miRNAs possess a unique advantage in modulating multiple targets of either the same or different signalling pathways. Therefore, miRNA follows a ‘one drug multiple target’ hypothesis. Attempts are made to explore the therapeutic promise of miRNAs in cancer so that it can be transported from bench to bedside for successful immunotherapeutic results. Therefore, in the current manuscript, we discussed, in detail, the mechanism and role of miRNAs in different types of cancers relating to the immune system, its diagnostic and therapeutic aspect, the effect on immune escape, immune-checkpoint molecules, and the tumour microenvironment. We have also discussed the existing limitations, clinical success and the prospective use of miRNAs in cancer.

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced with the help of proper nutrition. Layout: The review presents a pathophysiological link between nutrition and atherosclerosis by gaining a deep insight into the processes involved at each stage of plaque development. After targeting the causes and finding out results by low-cost, user-friendly, ultrasound-based arterial imaging, it is important to (i) stratify the risks and (ii) monitor them by measuring plaque burden and computing risk score as part of the preventive framework. Artificial intelligence (AI)-based strategies are used to provide efficient CVD risk assessments. Finally, the review presents the role of AI for CVD risk assessment during COVID-19. Conclusions: By studying the mechanism of low-density lipoprotein formation, saturated and trans fat, and other dietary components that lead to plaque formation, we demonstrate the use of CVD risk assessment due to nutrition and atherosclerosis disease formation during normal and COVID times. Further, nutrition if included, as a part of the associated risk factors can benefit from atherosclerotic disease progression and its management using AI-based CVD risk assessment.