Citations

Abstract Objective Intracranial complications of pediatric sinusitis are uncommon but are often associated with significant morbidity, especially when appropriate care is delayed. The present study aimed to identify commonalities for the development and progression of these complications in the pediatric population. Data Sources CENTRAL, CINAHL, Citation searching, ClinicalTrials.gov , Embase, Google Scholar, MEDLINE, PsycINFO, PubMed, Scopus, Web of Science, and World Health Organization. Review Methods A comprehensive literature search was performed using Preferred Reporting Items for Systematic Reviews and Meta‐analyses scoping review guidelines. Studies describing intracranial infections secondary to sinusitis in the pediatric population (age <18 years) were included. Studies in which adult and pediatric data were not separated and studies in which the pediatric cohort was fewer than 10 cases were excluded. Ultimately, 33 studies describing 1149 unique patient cases were included for data collection and analysis. Results Our analysis revealed intracranial complications were more common in adolescent males. Most children presented with over 1 week of vague symptoms, such as headache and fever. The majority of complications were diagnosed radiographically with computed tomography. Subdural empyema and epidural abscess were the most common intracranial complications reported. On average, patients were admitted for over 2 weeks. Most children were treated with a combination of antibiotics and surgical intervention. Complications were rare, but when present, were often associated with significant morbidity. Conclusion This scoping review of the available literature has provided insight into commonalities among pediatric patients who develop intracranial complications of sinusitis, providing a foundation for further study to inform medical and surgical decision‐making in this population.

Abstract Isolation of neuron‐derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)‐specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single‐EV techniques to establish the neuronal origin and determine the abundance of L1CAM‐positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co‐expressed on single‐EVs with the neuronal proteins β‐III‐tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM‐positive EVs. Levels of L1CAM‐positive EVs carrying the neuronal proteins VAMP2 and β‐III‐tubulin range from 30% to 63%, in contrast to 0.8%–3.9% of L1CAM‐negative EVs. Plasma fluid‐phase L1CAM does not bind to single‐EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.

7510 Background: The randomized Phase 3 CANOVA study’s (NCT03539744) primary analysis showed multiple numerically improved efficacy endpoints with VenDex v PomDex, but the primary endpoint of mPFS by IRC was not statistically significant. Here, we report correlative biomarker analyses from CANOVA. Methods: CANOVA is a randomized, global, open-label Phase 3 study of VenDex v PomDex in pts with t(11;14)+ RRMM and ≥2 prior lines of therapy (LOTs). The primary endpoint was mPFS by IRC. Key secondary endpoints included ORR, ≥VGPR, mOS, and MRD negativity (<10-5). In post hoc mPFS sensitivity analysis, disease progression, death, and start of next LOT were defined as events. BCL2 gene expression by RNAseq (3.7 log2 FPKM prespecified median cutoff for BCL2high v BCL2low) and chr1q abnormalities by whole-exome sequencing (normal, gain, or amp) were assessed centrally from pretreatment, CD138-enriched BM aspirates. Results: mPFS, post hoc mPFS, and mOS in the VenDex arm were similar by BCL2 status, with numerically higher ORR, ≥VGPR, and MRD negativity rates in the BCL2highsubgroup. In contrast, mPFS and mOS within the PomDex arm were numerically longer in the BCL2lowsubgroup, despite equal ORR in both subgroups (Table). Presence of 1q abnormalities was evenly distributed across BCL2high v BCL2low subgroups in the VenDex arm (51% v 45%) but not in the PomDex arm (59% v 31%). Normal 1q and gain(1q) subgroups had numerically improved mPFS, mOS, ORR, ≥VGPR, and MRD negativity with VenDex; pts with amp(1q) had poor outcomes regardless of treatment, albeit the sample size was small. Conclusions: Pts with BCL2high or gain(1q) had numerically improved clinical efficacy with VenDex v PomDex. Clinical benefit was consistent across BCL2 subgroups ( BCL2high or BCL2low) with VenDex but not PomDex. Pts with amp(1q) fared poorly irrespective of treatment arm. Clinical trial information: NCT03539744 . [Table: see text]

Abstract Purpose: The purpose of this study was to evaluate RB1 expression and survival across ovarian carcinoma histotypes and how co-occurrence of BRCA1 or BRCA2 (BRCA) alterations and RB1 loss influences survival in tubo-ovarian high-grade serous carcinoma (HGSC). Experimental Design: RB1 protein expression was classified by immunohistochemistry in ovarian carcinomas of 7,436 patients from the Ovarian Tumor Tissue Analysis consortium. We examined RB1 expression and germline BRCA status in a subset of 1,134 HGSC, and related genotype to overall survival (OS), tumor-infiltrating CD8+ lymphocytes, and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cells with and without BRCA1 alterations to model co-loss with treatment response. We performed whole-genome and transcriptome data analyses on 126 patients with primary HGSC to characterize tumors with concurrent BRCA deficiency and RB1 loss. Results: RB1 loss was associated with longer OS in HGSC but with poorer prognosis in endometrioid ovarian carcinoma. Patients with HGSC harboring both RB1 loss and pathogenic germline BRCA variants had superior OS compared with patients with either alteration alone, and their median OS was three times longer than those without pathogenic BRCA variants and retained RB1 expression (9.3 vs. 3.1 years). Enhanced sensitivity to cisplatin and paclitaxel was seen in BRCA1-altered cells with RB1 knockout. Combined RB1 loss and BRCA deficiency correlated with transcriptional markers of enhanced IFN response, cell-cycle deregulation, and reduced epithelial–mesenchymal transition. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. Conclusions: Co-occurrence of RB1 loss and BRCA deficiency was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Abstract Background Surgical drains are a key component for recovery in breast reconstruction procedures. However, they are often cumbersome and carry a risk of infection with prolonged use. We aimed to develop a more thorough understanding of patient and health care provider perspectives on surgical drains, to inform future efforts in improving the breast reconstruction patient experience. Methods Twenty-nine breast reconstruction patients and eight plastic surgery providers were recruited to complete surveys focused on surgical drains. Likert scales ranging from 1 to 5 were developed to gauge how bothersome drains felt, as well as concern for infection. Ordinal variable and categorical multiple-choice analyses were applied as appropriate. Results Fifteen (51.7%) patients underwent implant-based breast reconstruction, and 14 (48.3%) patients underwent autologous breast reconstruction. The most common duration of drain placement was 2 weeks (N = 13). The surgical site infection (SSI) rate requiring antibiotics was 28% (N = 8). On a scale of 1 to 5, both patients (median = 3) and providers (median = 2.5) viewed drains as bothersome. Patients were “frequently” concerned about infection risk (median = 3). Other high-frequency patient concerns included general pain and discomfort. Conclusion Surgical drains are a common component of breast reconstruction procedures and are viewed as cumbersome by both patients and providers. Patients expressed concerns about drain site pain, discomfort, and tugging on clothing. Patients and providers both believed that drains could contribute to SSI. Overall, these data provide insight to drive future improvements in the patient drain experience.

Abstract Background Perioperative morbidity and mortality remain a point of concern for the Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS) procedure. Post-hepatectomy liver failure (PHLF) after the second step poses the most significant risk factor for futile outcome. Recovery of liver function after the first step of ALPPS is critically important to allow for sufficient liver function after this surgery. The APRI+ALBI score has been proposed as an easily assessable score to monitor liver function and its dynamic recovery. Aims We explored if the APRI+ALBI score was able to assess liver function recovery after the first step of ALPPS and allow for optimal timing of the 2nd step. Methods Based on the ALPPS registry, patients from 2012 to 2020 with available APRI+ALBI score were included. Postoperative outcomes (PHLF A – C, PHLF B + C, 90-day mortality and severe morbidity) were defined as per standard definitions. The APRI/ALBI score was monitored perioperatively. Results Overall, 464 patients from 16 international participating centers in the ALPPS registry were included. Clinically relevant PHLF (B + C) was observed in 7.5 % and of these 63 % of patients ultimately died due to liver failure. The APRI+ALBI score immediately increased after each surgical intervention and continuously decrease thereafter. Failure of the APRI+ALBI score to decrease until the 2nd step of ALPPS predicted PHLF B+C (p = 0.001; AUC 0.78). Particularly patients with high APRI+ALBI scores and short interstage intervals were at risk to develop PHLF B+C. Conclusion The APRI+ALBI score objectifies liver function recovery after the 1st step of ALPPS and failure to sufficiently decreased is associated with a higher risk for PHLF B+C. This might allow for optimized planning of the 2nd step of ALPPS to allow for sufficient liver function recovery to minimize the risk for PHLF B+C and associated futile outcome.