Citations

Background: Cranial dural arteriovenous fistulas with cortical venous drainage are rare lesions that can present with hemorrhage. A high rate of rebleeding in the early period following hemorrhage has been reported, but published long-term rates are much lower. No study has examined how risk of rebleeding changes over time. Our objective was to quantify the relative incidence of rebleeding in the early and later periods following hemorrhage. Methods: Patients with dural arteriovenous fistula and cortical venous drainage presenting with hemorrhage were identified from the multinational CONDOR (Consortium for Dural Fistula Outcomes Research) database. Natural history follow-up was defined as time from hemorrhage to first treatment, rebleed, or last follow-up. Rebleeding in the first 2 weeks and first year were compared using incidence rate ratio and difference. Results: Of 1077 patients, 250 met the inclusion criteria and had 95 cumulative person-years natural history follow-up. The overall annualized rebleed rate was 7.3% (95% CI, 3.2–14.5). The incidence rate of rebleeding in the first 2 weeks was 0.0011 per person-day; an early rebleed risk of 1.6% in the first 14 days (95% CI, 0.3–5.1). For the remainder of the first year, the incidence rate was 0.00015 per person-day; a rebleed rate of 5.3% (CI, 1.7–12.4) over 1 year. The incidence rate ratio was 7.3 (95% CI, 1.4–37.7; P , 0.026). Conclusions: The risk of rebleeding of a dural arteriovenous fistula with cortical venous drainage presenting with hemorrhage is increased in the first 2 weeks justifying early treatment. However, the magnitude of this increase may be considerably lower than previously thought. Treatment within 5 days was associated with a low rate of rebleeding and appears an appropriate timeframe.

Open reading frame 8 (ORF8) shows one of the highest levels of variability among accessory proteins in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits the presentation of viral antigens by the major histocompatibility complex class I (MHC-I), which interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 in evading immunity and plays a role in SARS-CoV-2 replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein, defines the B.1.1.7 lineage of SARS-CoV-2, engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) with the Q27STOP mutations were identified among 49,055 available B.1.1.7 SARS-CoV-2 sequences. The results show that only one of the 47 T-ORF8 variants spread to over 57 geo-locations in North America, and other continents, which include Africa, Asia, Europe and South America. Based on various quantitative features, such as amino acid homology, polar/non-polar sequence homology, Shannon entropy conservation, and other physicochemical properties of all specific 47 T-ORF8 protein variants, nine possible T-ORF8 unique variants were defined. The question as to whether T-ORF8 variants function similarly to the wild type ORF8 is yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.

Abstract Background. DCIS consists of a molecularly heterogeneous group of premalignant lesions, with variable risk of invasive progression. Understanding biomarkers for invasive progression could help individualize treatment recommendations based upon tumor biology. As part of the NCI Human Tumor Atlas Network (HTAN), we conducted comprehensive genomic analyses on two large DCIS case-control cohorts. Methods. We performed smart3-seq and low-pass whole genome sequencing on two independent, retrospective, longitudinally sampled DCIS case-control cohorts. TBCRC 038 was a multicenter cohort diagnosed with DCIS between 1998 and 2016 at one of the Translational Breast Cancer Research sites; the RAHBT (Resource of Archival Human Breast Tissue) cohort included women identified through the St. Louis Breast Tissue Repository, and the Women’s Health Repository diagnosed between 1997 and 2001. We studied the spectrum of molecular changes present and sought genomic predictors of subsequent ipsilateral breast events (iBEs: DCIS recurrence or invasive progression) in both DCIS epithelium and stroma in formalin fixed paraffin embedded tissue. We generated de novo tumor and stroma-centric subtypes for DCIS that represents fundamental transcriptomic organization. Copy number analysis was performed using low-pass DNA sequencing. Non-negative matrix factorization (NMF) was applied to the RNA expression of all coding genes to identify clusters. A negative-binomial regression model was used to identify differentially expressed genes. Results. We analyzed 677 DCIS samples from 481 patients with 7.1 years median follow-up. In TBCRC samples, we identified three clusters via NMF in TBCRC referred to as ER low, quiescent, and ER high. The ER-low cluster had significantly higher levels of ERBB2 and lower levels of ESR1 compared to quiescent and ER-high clusters. Quiescent cluster lesions were less proliferative and less metabolically active than ER high and ER low subtypes. These findings were replicated in the RAHBT cohort. Focusing on the stromal component of DCIS from laser capture microdissection in RAHBT samples, we identified four distinct DCIS-associated stromal clusters. A “normal-like” stromal cluster with ECM organization and PI3K-AKT signaling; a “collagen-rich” stromal cluster; a “desmoplastic” stromal cluster with high fibroblast and total myeloid abundance, mostly associated with macrophages and myeloid dendritic cells (mDC); and an “immune-dense” stromal cluster. Further, we compared differentially expressed genes in patients with or without subsequent iBEs within 5 years of diagnosis. Hypothesizing that the resulting 812 DE genes (DESeq2) represent multiple routes to subsequent iBEs, we leveraged NMF to identify paths to progression. In both TBCRC and RAHBT cohorts, poor outcome groups exhibited increased ER, MYC signaling, and oxidative phosphorylation, supporting that these pathways are important for DCIS recurrence and progression. Conclusion. Comprehensive genomic profiling in two independent DCIS cohorts with longitudinal outcomes shows distinct DCIS stromal expression patterns and immune cell composition. RNA expression profiles reveal underlying tumor biology that is associated with later iBEs in both cohorts. These studies provide new insight into DCIS biology and will guide the design of diagnostic strategies to prevent invasive progression. Citation Format: Siri H Strand, Belén Rivero-Gutiérrez, Kathleen E Houlahan, Jose A Seoane, Lorraine M King, Tyler Risom, Lunden Simpson, Sujay Vennam, Aziz Khan, Timothy Hardman, Bryan E Harmon, Fergus J Couch, Kristalyn Gallagher, Mark Kilgore, Shi Wei, Angela DeMichele, Tari King, Priscilla F McAuliffe, Julie Nangia, Joanna Lee, Jennifer Tseng, Anna Maria Storniolo, Alastair Thompson, Gaorav Gupta, Robyn Burns, Deborah J Veis, Katherine DeSchryver, Chunfang Zhu, Magdalena Matusiak, Jason Wang, Shirley X Zhu, Jen Tappenden, Daisy Yi Ding, Dadong Zhang, Jingqin Luo, Shu Jiang, Sushama Varma, Cody Straub, Sucheta Srivastava, Christina Curtis, Rob Tibshirani, Robert Michael Angelo, Allison Hall, Kouros Owzar, Kornelia Polyak, Carlo Maley, Jeffrey R Marks, Graham A Colditz, E Shelley Hwang, Robert B West. The Breast PreCancer Atlas DCIS genomic signatures define biology and correlate with clinical outcomes: An analysis of TBCRC 038 and RAHBT cohorts [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-07.

The present large scale study aimed to assess the prevalence and consequences of malnutrition, based on clinical assessment (body mass index and preoperative weight loss) and severe hypoalbuminemia (<3.1 g/L), in a representative US cohort undergoing IBD surgery. The American College of Surgeons National Quality improvement program (ACS-NSQIP) Public User Files (PUF) between 2005 and 2018 were assessed. A total of 25,431 patients were identified. Of those, 6560 (25.8%) patients had severe hypoalbuminemia, 380 (1.5%) patients met ESPEN 2 criteria (≥10% weight loss over 6 months PLUS BMI < 20 kg/m2 in patients <70 years OR BMI < 22 kg/m2 in patients ≥70 years), and 671 (2.6%) patients met both criteria (severe hypoalbuminemia and ESPEN 2). Patients who presented with malnutrition according to any of the three definitions had higher rates of overall, minor, major, surgical, and medical complications, longer LOS, higher mortality and higher rates of readmission and reoperation. The simple clinical assessment of malnutrition based on BMI and weight loss only, considerably underestimates its true prevalence of up to 50% in surgical IBD patients and calls for dedicated nutritional assessment.

AbstractMagnetic resonance imaging (MRI) is routinely used for preoperative tumor staging and to assess response to therapy in rectal cancer patients. The aim of our study was to evaluate the accuracy of MRI based restaging after neoadjuvant chemoradiotherapy (CRT) in predicting pathologic response. This multicenter cohort study included adult patients with histologically confirmed locally advanced rectal adenocarcinoma treated with neoadjuvant CRT followed by curative intent elective surgery between January 2014 and December 2019 at four academic high‐volume institutions. Magnetic resonance tumor regression grade (mrTRG) and pathologic tumor regression grade (pTRG) were reviewed and compared for all the patients. The agreement between radiologist and pathologist was assessed with the weighted k test. Risk factors for poor agreement were investigated using logistic regression. A total of 309 patients were included. Modest agreement was found between mrTRG and pTRG when regression was classified according to standard five‐tier systems (k = 0.386). When only two categories were considered for each regression system, (pTRG 0‐3 vs pTRG 4; mrTRG 2‐5 vs mrTRG 1) an accuracy of 78% (95% confidence interval [CI] 0.73‐0.83) was found between radiologic and pathologic assessment with a k value of 0.185. The logistic regression model revealed that “T3 greater than 5 mm extent” was the only variable significantly impacting on disagreement (OR 0.33, 95% CI 0.15‐0.68, P = .0034). Modest agreement exists between mrTRG and pTRG. The chances of appropriate assessment of the regression grade after neoadjuvant CRT appear to be higher in case of a T3 tumor with at least 5 mm extension in the mesorectal fat at the pretreatment MRI.

Objective: We aimed to determine a safe zone of intraoperative fluid management associated with the lowest postoperative complication rates without increased acute kidney injury (AKi) risk for elective colorectal surgery patients. Background: To date, standard practice within institutions, let alone national expectations related to fluid administration, are limited. This fact has perpetuated a quality gap. Methods: Elective colorectal surgeries between 2018 and 2020 were included. Unadjusted odds ratios (ORs) for postoperative ileus, prolonged LOS, and AKi were plotted against the rate of intraoperative RL infusion (mL/ kg/h) and total intraoperative volume. Binary logistic regression analysis, including fluid volumes as a confounder, was used to identify risk factors for postoperative complications. Results: A total of 2900 patients were identified. Of them, 503 (17.3%) patients had ileus, 772 (26.6%) patients had prolonged LOS, and 240 (8.3%) patients had AKI. The intraoperative fluid resuscitation rate (mg/kg/h) was less impactful on postoperative ileus, LOS, and AKI than the total amount of intraoperative fluid. A total fluid administration range between 300 mL and 2.7 L was associated with the lowest complication rate. Total intraoperative RL ≥2.7 L was independently associated with a higher risk of ileus (adjusted OR 1.465; 95% confidence interval 1.154–1.858) and prolonged LOS (adjusted OR 1.300; 95% confidence interval 1.047–1.613), but not AKI. Intraoperative RL ≤300 mL was not associated with an increased risk of AKI. Conclusion: Total intraoperative RL ≥2.7 L was independently associated with postoperative ileus and prolonged LOS in elective colorectal surgery patients. A new potential standard for intraoperative fluids will require anesthesia case planning (complexity and duration) to ensure total fluid volume meets this new opportunity to improve care.

Abstract Background Minimally invasive surgery (MIS) is the first-line approach for ileocolic resection in patients with Crohn’s disease (CD) and it is safe and feasible even in complex cases. However, an open approach is still required, but indications to open ileocolic resection for CD are not well described. Methods All consecutive adult patients with CD who underwent elective ileocolic resection in the Departments of Colon and Rectal Surgery at Mayo Clinic Rochester, Minnesota and Jacksonville, Florida between September 2014 and March 2021 were included and divided into “open” and “MIS” groups. Open approach was defined as upfront laparotomy, MIS included laparoscopic and robotic approaches, and conversion was defined as incision made earlier than planned. Indications to open approach were retrospectively reviewed by two authors, and any incongruity was resolved. Analogous indications were also assessed in the MIS group, as appropriate. Indications, baseline, perioperative characteristics, and short-term postoperative outcomes were compared between open and MIS. Results Among 319 ileocolic resections for CD, 45 (14.1%) were open and 274 (85.9%) MIS. Indications for open approach were severe disease, adhesions at previous surgery, history of abdominal sepsis, multifocal and extensive disease, abdominal wall involvement, concomitant open procedures, small bowel dilatation, and anaesthesiologic contraindications (Table 1). In addition, two or more of the above indications were present in 40 patients (89%) in the open group, while only in 6 patients (2%) in the MIS group (p&lt;0.001). Compared to MIS patients, patients undergoing open ileocolic resection were older, with longer CD duration, more previous surgery and preoperative intra-abdominal abscess drainage (Table 2). Nine patients were converted in the MIS group (3.3%). Intraoperatively, open group had more adhesiolysis ≥45 min, more intraoperative complications, more blood loss, more primary stoma, less anastomosis, and longer operative time (Table 3). Postoperatively, they had more overall postoperative complications, ileus, surgical site infections, dehydration, vascular thromboembolism, higher severity by Clavien-Dindo classification, and longer length of stay (Table 4). Conclusion Overall rate of open approach ileocolic resection for CD was 14 % during a 7-years period in a referral centre. Open approach was the only operation performed in cases of abdominal wall involvement, concomitant open procedures, and anaesthesiologic contraindication. In addition, the presence of at least two indications,predicting high technical complexity, may be considered as a no-go for the MIS approach in ileocolic resections for CD.

Abstract Background There is controversy regarding the postoperative outcomes in Crohn’s disease [CD] patients exposed to vedolizumab [VDZ] or ustekinumab [UST]. We aimed to describe our surgical outcomes in patients who underwent minimally invasive ileocolonic resection [MIS-ICR] for CD who had preoperative biologic therapy. Methods All consecutive adult patients who had MIS-ICR for CD between 2014 and 2021 at our institution were included. Patients were divided into four groups: VDZ, UST, anti-tumour necrosis factor [anti-TNF], and no biologic group. Timing between the last dose of biologics and surgery was per surgeon’s discretion. The primary outcome was intra-abdominal septic complications. Secondary outcomes included all 30-day complications. Results A total of 274 patients were identified. Of these, 113 [41.2%] patients had received anti-TNF, 52 [19%] had received UST, and 19 [7%] had received VDZ. There was no difference between the four groups regarding baseline risk factors. There was no difference between the four groups regarding intra-abdominal septic complications [4.4% for no biologic, 5.3% for anti-TNF, 5.8% for UST, and 5.3% for VDZ; p = 0.987], surgical site infection rate, overall 30-day morbidity, overall 30-day readmission, overall surgical and medical complications, urinary tract infection, pulmonary infections, or length of stay. Those results were consistent after a subgroup analysis based on complexity of the disease. Conclusions This retrospective analysis demonstrates an equivalent postoperative safety profile for patients treated with preoperative anti-TNF, VDZ, or UST versus no biologic therapy within 3 months of MIS-ICR for Crohn’s disease. Preoperative biologic therapy may not increase complications after minimally invasive ileocolonic resection in Crohn’s disease. Further studies with larger sample sizes are needed to confirm results.