Genetic Clustering of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Patients of Colorectal Origin: KRAS and Not TP53 Cluster Alterations are Associated with Poor Outcomes.

BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.

Non-tobacco nicotine E-cigarette use and flavored E-cigarette use among young adults in the United States.

BACKGROUND: E-cigarette flavors can create sensations of sweetness and coolness while masking the aversiveness of nicotine. Recently, non-tobacco nicotine (NTN) products were introduced to the market, but little is known about flavors in NTN e-cigarette use. We examined associations between flavors (i.e., sweet, mint/menthol) and susceptibility to and use of NTN e-cigarettes. METHODS: 1239 US young adults (18-25 years) completed an anonymous, online survey in Fall 2021. The analytic sample included 520 participants who had used e-cigarettes and heard of NTN. Multinomial logistic regression models analyzed associations of flavored e-cigarette use (sweet and mint/menthol) with NTN e-cigarette use status (i.e., current [past-month] use, past [ever but not current] use, susceptible to use, and non-susceptible to use [reference]). RESULTS: Overall, 46.2% of participants reported current NTN use, 14.8% reported past use, 16.7% were susceptible to use, and 22.3% reported no susceptibility. Participants reported dual-use of sweet and mint/menthol NTN e-cigarette flavors (56.5%), sweet flavors use (24.8%), and mint/menthol flavor use (1.7%). Ever dual use of sweet and mint/menthol flavors was associated with current (OR = 9.64, 95%CI: 3.21-28.98) and past NTN e-cigarette use (8.30, [2.10-32.80]). Ever sweet flavor use was associated with current NTN use (3.80, 95%CI: 1.44-10.03) and susceptibility to future use (4.25, [1.53-11.81]). Similar findings were observed for mint/menthol flavors (current: 5.03, [1.41-17.99]; susceptible: 5.65, [1.64-19.51]). CONCLUSION: The use of sweet and mint/menthol flavors was significantly associated with NTN e-cigarette use among US young adults, highlighting the need for ongoing surveillance of flavored NTN e-cigarettes and appropriate regulations to discourage use.

Biliary Disorders, Anomalies, and Malignancies in Children.

Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Genital Pain and the Spectrum of Bladder-Related Symptoms: Findings from the Prevention of Lower Urinary Tract Symptoms Research Consortium RISE FOR HEALTH Study, USA.

INTRODUCTION AND HYPOTHESIS: Women with vulvovaginal or genital pain more commonly experience interstitial cystitis/bladder pain syndrome (IC/BPS) and urinary tract infections. However, the relationship between genital pain and bladder health is lacking. METHODS: Women in the Prevention of Lower Urinary Tract Symptoms Consortium's RISE FOR HEALTH population-based study answered questions about bladder health globally, and across nine bladder health domains of holding, efficacy, social-occupation, physical activity, intimacy, travel, emotion, perception, and freedom. Bladder function was assessed across six indices including urinary frequency, sensation, continence, comfort, emptying, and dysbiosis (e.g., urinary tract infections). Participants were grouped by no pain beyond transitory events (i.e., minor headaches, toothaches, or sprains), nongenital-related pain only, and any genital pain using a validated pain diagram. Mean adjusted scores and indices were compared using general linear modelling. RESULTS: Of 1,973 eligible women, 250 (12.7%) reported genital pain, 609 (30.9%) reported nongenital pain only, and 1,114 (56.5%) reported no pain. Women with any genital pain had lower (worse) adjusted mean scores across all bladder health scales (BHS; BHS global adjusted mean 47.5; 95% CI 40.8-54.1), compared with those with nongenital pain only (53.7; 95% CI 47.6-59.8), and no pain (59.3; 95% CI 53.3-65.4). Similarly, adjusted mean total Bladder Functional Index scores were lower for those with genital pain (63.1; 95% CI 58.4-67.9) compared with nongenital pain (72.1; 95% CI 67.7-76.5) and no pain (77.4; 95% CI 73.0-81.8). CONCLUSIONS: Heightened awareness of the relationship between genital pain and bladder health should prompt clinicians caring for women with genital pain to assess bladder health and function.

Association Between Maternal Depression and Lower Urinary Tract Symptoms in Their Primary School-Age Daughters: A Birth Cohort Study.

PURPOSE: Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters. DESIGN: Observational cohort study. SUBJECTS AND SETTING: The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children. METHOD: Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks' gestation and 21 months postpartum and their children's LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters. RESULTS: Compared to daughters of mothers without depression, those born to mothers with prenatal and postpartum depression had higher odds of LUTS, including urinary urgency (adjusted odds ratio [aOR] range = 1.99-2.50) and nocturia (aOR range = 1.67-1.97) at 6, 7, and 9 years of age. Additionally, daughters born to mothers with prenatal and postpartum depression had higher odds of daytime wetting (aOR range = 1.81-1.99) and nighttime wetting (aOR range = 1.63-1.95) at 6 and 7 years of age. Less consistent associations were observed for depression limited to the prenatal or postpartum periods only. CONCLUSIONS: Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS.

Evolution of Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disease characterized by thrombosis and/or pregnancy complications caused by antiphospholipid antibodies (aPL). The history of APS can be traced back to observations made during screening programs for syphilis conducted in the mid-20th century, with identification of patients with the so-called biological false-positive serological reactions for syphilis. Initial observation linking aPL with recurrent miscarriages was first reported more than 40 years ago. Since then, our understanding of the pathogenesis and management of APS has evolved markedly. Although APS is an autoimmune disease, anticoagulation mainly with vitamin K antagonists (VKAs) rather than immunomodulation, is the treatment of choice for thrombotic APS. Direct acting oral anticoagulants are inferior to VKAs, especially those with triple-positive APS and arterial thrombosis. Inflammation, complement activation, and thrombosis in the placenta may contribute to pathogenesis of obstetric APS. Heparin, mainly low-molecular-weight heparin, and low-dose aspirin represent the treatments of choice for women with obstetric complications. Increasingly, immunomodulatory agents such as hydroxychloroquine for thrombotic and obstetric APS are being used, especially in patients who are refractory to present standard treatment.

The first nicotine product tried is associated with current multiple nicotine product use and nicotine dependence among a nationally representative sample of U.S. youths.

This study examines the demographic factors associated with youths' first product tried (i.e., cigarettes, e-cigarettes, cigars, hookah, or smokeless tobacco). This study also evaluates whether the first product tried is associated with future nicotine product use (i.e., no use, single product use, and multiple product use) and nicotine dependence. Participants were 1999 youths (ages 12-17 years) who had ever tried a nicotine product and completed the Population Assessment of Tobacco Health study's Wave 1 (2013-2014) and Wave 4 (2016-2018) assessments. Two separate multinomial logistic regression models examined the association between 1) demographic factors and the first product tried at Wave 1 and 2) the first product tried at Wave 1 and past-30-day product use status at Wave 4. A two-part multivariable model examined the association between the first product tried and nicotine dependence, with part 1 modeling the presence (or absence) of any symptom of dependence and part 2 modeling the degree of dependence among those with any symptom of dependence. The first product tried was associated with sex, race, urbanicity, and parent education. First trying smokeless tobacco (vs. e-cigarettes) was associated with a greater likelihood of multiple product use (vs. no use and vs. single product use). Regarding the degree of nicotine dependence (n = 713), first trying smokeless tobacco (vs. e-cigarettes) was associated with higher nicotine dependence scores among those with any symptom of dependence. Youths who first try smokeless tobacco (vs. e-cigarettes) may be at higher risk for future multiple product use and more symptoms nicotine dependence. Research should explore tailored interventions for smokeless tobacco users.

"Tobacco-free" Nicotine Pouches: Risk Perceptions, Awareness, Susceptibility, and Use Among Young Adults in the United States.

BACKGROUND: Nicotine pouches containing synthetic nicotine or tobacco-derived nicotine (TDN) are available in the United States. Synthetic nicotine pouches are often marketed as "tobacco-free nicotine" (TFN), which may alter risk perceptions and product appeal. This study examined young adults' perceptions of TFN versus TDN pouches and the associations between product perceptions and TFN pouch awareness, susceptibility, and use, respectively. AIMS AND METHODS: In total 630 young adults (18-25 years) completed an online Qualtrics panels survey in 2021. Participants were informed that TFN pouches contain synthetic nicotine as opposed to TDN. Participants reported on comparative risk perceptions for TFN versus TDN pouches and on TFN pouch awareness, susceptibility, and use. Unadjusted between-group comparisons and adjusted binary logistic regressions were run to examine relationships between product perceptions and TFN pouch awareness, susceptibility, and use. RESULTS: Participants were aware of (37.3%), susceptible to (29.2%), or had used TFN pouches (3.8%). In unadjusted comparisons, TFN pouch awareness, susceptibility, and use were associated with disproportionately perceiving TFN pouches as less harmful or otherwise better than TDN pouches. In adjusted models, relationships between favorable perceptions and both TFN pouch awareness and susceptibility remained significant. CONCLUSIONS: The descriptor "tobacco-free" may impact risk perceptions and the appeal of nicotine pouches among young adults. While no direct relationship was observed between TFN perceptions and TFN pouch use in the adjusted model, perceptions remained related to product awareness and susceptibility, which may be linked to future use. Continued surveillance is needed to fully determine how the term "tobacco-free" on product packaging and advertising impacts longitudinal public health outcomes. IMPLICATIONS: Nicotine pouches originally contained TDN. Today, numerous brands of synthetic nicotine pouches, which are often marketed as "tobacco-free," are available on the market. We informed participants that "tobacco-free nicotine" pouches contain synthetic nicotine and examined comparative risk perceptions (i.e. tobacco-free vs. TDN pouches) and TFN pouch awareness, susceptibility, and use. Perceiving tobacco-free nicotine pouches as less harmful than tobacco-derived pouches was associated with product awareness, susceptibility, and use in unadjusted models and with awareness and susceptibility in adjusted models. Restricting the term "tobacco-free" may become necessary if the term inaccurately reduces product risk perceptions or increases product appeal.

Synovial sarcoma with intra-abdominal metastasis causing hemoperitoneum: a case-report.

Synovial sarcoma is a rare soft tissue sarcoma which frequently involves the upper or lower extremities. Soft tissue sarcomas including synovial sarcoma have a propensity to metastasize to the lungs, and there are very few reports of metastatic lesions in other locations.Here, we report a case of a 49-year-old patient who underwent neoadjuvant chemoradiation for an upper extremity synovial sarcoma and presented approximately 4 years later with abdominal pain and hemoperitoneum and was ultimately found to have metastatic synovial sarcoma involving the greater curvature of the stomach and surrounding peri-gastric soft tissue. We describe the multidisciplinary management of this complex patient presentation and propose that expanded surveillance imaging beyond that of the local tumor resection bed and the chest may be beneficial especially in tumors with high-risk features.

Thoracic surgery in patients on veno-venous extracorporeal membrane oxygenation for COVID-19 associated acute respiratory distress syndrome.

OBJECTIVES: The COVID-19 pandemic has generated a new type of acute respiratory distress syndrome (ARDS) arising as a complication of COVID-19 pneumonia. Extreme cases require the support of extracorporeal membrane oxygenation (ECMO). Here we present the outcomes of patients that underwent surgical tracheostomy or thoracic surgery at a single tertiary centre whilst on ECMO support for COVID-19 related ARDS. METHODS: 18 patients requiring thoracic input whilst on ECMO support during the first wave of COVID-19 (March-June 2020) were included. Thoracic surgery was required both for performing surgical tracheostomies in the operating theatre and for treating emergencies arising under the ECMO treatment such as bleeding complications. RESULTS: Thirteen patients underwent a surgical tracheostomy, whilst five patients had an invasive thoracic procedure. Anticoagulation was withheld for at least 12 h in the perioperative setting regardless of the indication. One patient was re-operated for haemothorax immediately after the end of the primary operation. 94.5% of the patients were successfully decannulated from ECMO support. Overall 30-day mortality in the cohort was 5.5% (1/18). CONCLUSIONS: Thoracic surgeons can play a valuable role in supporting an ECMO unit during the COVID pandemic, by treating ECMO related complications and by safely performing surgical tracheostomies. Withholding anticoagulation in the perioperative window was not associated with increased thromboembolic events and is desirable when interventions or surgery is indicated in this patient cohort to avoid excessive bleeding.

Pigmented Microbial Extract (PMB) from Exiguobacterium Species MB2 Strain (PMB1) and Bacillus subtilis Strain MB1 (PMB2) Inhibited Breast Cancer Cells Growth In Vivo and In Vitro.

Breast cancer (BC) continues to be one of the major causes of cancer deaths in women. Progress has been made in targeting hormone and growth factor receptor-positive BCs with clinical efficacy and success. However, little progress has been made to develop a clinically viable treatment for the triple-negative BC cases (TNBCs). The current study aims to identify potent agents that can target TNBCs. Extracts from microbial sources have been reported to contain pharmacological agents that can selectively inhibit cancer cell growth. We have screened and identified pigmented microbial extracts (PMBs) that can inhibit BC cell proliferation by targeting legumain (LGMN). LGMN is an oncogenic protein expressed not only in malignant cells but also in tumor microenvironment cells, including tumor-associated macrophages. An LGMN inhibition assay was performed, and microbial extracts were evaluated for in vitro anticancer activity in BC cell lines, angiogenesis assay with chick chorioallantoic membrane (CAM), and tumor xenograft models in Swiss albino mice. We have identified that PMB from the Exiguobacterium (PMB1), inhibits BC growth more potently than PMB2, from the Bacillus subtilis strain. The analysis of PMB1 by GC-MS showed the presence of a variety of fatty acids and fatty-acid derivatives, small molecule phenolics, and aldehydes. PMB1 inhibited the activity of oncogenic legumain in BC cells and induced cell cycle arrest and apoptosis. PMB1 reduced the angiogenesis and inhibited BC cell migration. In mice, intraperitoneal administration of PMB1 retarded the growth of xenografted Ehrlich ascites mammary tumors and mitigated the proliferation of tumor cells in the peritoneal cavity in vivo. In summary, our findings demonstrate the high antitumor potential of PMB1.

Gallbladder Cancer: A Single-Institution 10-Year Experience-Analysis of Adenocarcinoma Subtypes and Tumors Arising from Intracholecystic Papillary Neoplasms.

BACKGROUND: Gallbladder cancer accounts for 1.2% of global cancer diagnoses. Literature on biliary-type adenocarcinoma (BTA), and specifically carcinoma arising from intracholecystic papillary-tubular neoplasms (ICPNs), is limited. This study describes a retrospective, single-institution experience with gallbladder cancer, focusing on histological subtypes and prognosis. METHODS: A retrospective review was performed of patients who underwent cholecystectomy for a malignant neoplasm of the gallbladder between 2007 and 2017. Demographic, clinicopathologic, and operative variables, as well as survival outcomes, were analyzed. RESULTS: From a total of 145 patients, BTAs were most common (93, 64%). Compared with non-BTAs, BTAs were diagnosed at a lower American Joint Committee on Cancer stage (p = 0.045) and demonstrated longer median recurrence-free survival (38 vs. 16 months, p = 0.014; median follow-up 36 months). Tumors arising from ICPNs (18, 12%) were more commonly associated with BTA (14 cases). Compared with BTAs not associated with ICPNs (29 patients), associated cases demonstrated lower pathologic stage (p = 0.006) and lower rates of liver and perineural invasion (0% vs. 49% and 14% vs. 48%, respectively; p < 0.05). Cumulative 5-year survival probability was higher for patients with gallbladder neoplasm of any subtype associated with ICPNs compared with those that were not associated with ICPNs (54% vs. 41%, p = 0.019; median follow-up 23 months). This difference was also significant when comparing BTAs associated with ICPNs and non-associated cases (63% vs. 52%, p = 0.005). CONCLUSIONS: This study demonstrated unique pathological and prognostic features of BTAs and of carcinomas arising from ICPNs. Histopathological variance may implicate prognosis and may be used to better guide clinical decision making in the treatment of these patients.

Hypophosphatemia Is Associated With Postoperative Morbidity After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy: A Retrospective Study.

INTRODUCTION: Hypophosphatemia following surgery is associated with a higher rate of postoperative complications; however, the significance of postoperative hypophosphatemia after cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. METHODS: A prospectively maintained database was queried for all patients who underwent CRS/HIPEC for any histology at the Mount Sinai Health System. The perioperative serum phosphate levels, postoperative complications, and comorbidities were compared between patients with or without major complications. RESULTS: From 2007 to 2018, 327 patients underwent CRS/HIPEC. Most of the patients had low phosphate levels on postoperative day (POD) 2, reaching a median nadir of 2.3 mg/dL on POD 3. Patients with major complications had significantly lower levels of serum phosphate on POD 5-7 compared with patients without complications, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.4) versus 2.7 mg/dL, (IQR 2.3-3), P < 0.01. Hypophosphatemia on POD 5-7 was also more frequent in patients who developed an anastomotic leak, with median serum phosphate 2.2 mg/dL (IQR 1.9-2.6) versus 2.8 mg/dL (IQR 2.2-3.2), P = 0.001. On multivariate analysis, the number of organs resected at surgery, diaphragm resection, postoperative intensive care unit stay, and serum phosphate level <2.4 mg/dL on POD 5-7 were independently associated with a major complication after CRS/HIPEC. CONCLUSIONS: Following CRS/HIPEC, POD 5-7 hypophosphatemia is associated with severe postoperative complications and anastomotic leak.

Curiosity, use, and perceptions of "tobacco-free nicotine" E-cigarettes among U.S. young adults.

This study determined whether young adults perceptions of how tobacco free nicotine (TFN) compared to tobacco-derived nicotine (TDN) were associated with curiosity to try or use TFN e-cigarettes. U.S. young adults aged 18-25 years (n = 1176) completed an online survey in October 2021. Survey questions assessed TFN awareness, curiosity, use, and perceptions of how flavor, taste, ease of access, cost, and harm compared between TFN and TDN. Participants were categorized into 3 groups: not curious to try TFN (n = 511, 43.5%), curious to try TFN (n = 348, 29.6%), and ever used TFN (n = 317, 27%). Multinomial logistic regression measured associations between perceptions and TFN curiosity and use (vs. not curious to try), with total number tobacco products used and demographics as covariates. Compared to young adults who were not curious to try TFN e-cigarettes, those who were curious perceived TFN as less addictive than TDN (aOR = 2.27; 95% CI =1.34-3.86). Those who had used TFN e-cigarettes perceived TFN as having flavors that tasted better (aOR = 1.80; 95% CI = 1.63-1.99), "smoother" (aOR = 1.88; 95% CI =1.18-2.99), and less like tobacco (aOR 1.94; 95% CI 1.23-3.05). Adjusted models did not show differences in perceptions between those who had tried TFN and those who were curious to try TFN. Young adults who were curious to try or had used TFN had more positive perceptions of TFN. As it is currently unclear whether synthetic nicotine carries the same health risks as TDN, ongoing surveillance of TFN uptake among young adults is warranted.

Laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is associated with improved perioperative outcomes: a single-center early experience propensity-matched analysis.

INTRODUCTION: The role of laparoscopy in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is not well established. Herein, we describe our early experience of laparoscopic CRS/HIPEC in patients with low-volume peritoneal disease compared to patients who underwent open CRS/HIPEC during the same time period. METHODS: Using a prospectively maintained database, patients who underwent laparoscopic CRS/HIPEC were compared to a control cohort of patients who underwent open CRS/HIPEC, matched for peritoneal carcinomatosis index (PCI), completeness of cytoreduction, and tumor histology. RESULTS: Between 2008 and 2017, 16 patients underwent laparoscopic CRS/HIPEC and were compared to a matched control cohort of 32 patients who underwent open CRS/HIPEC. Clinical and demographic data were similar between the groups. PCI, number of resected organs, and optimal cytoreduction rates were comparable. Patients who underwent laparoscopic experienced a lower estimated blood loss, (median, [IQR 1-3]); 150 mL, [50-300] vs. 100 mL, [50-125], p = 0.04, shorter length of stay (median [IQR 1-3]; 4 days [3-6] vs. 6 days [5-8], p < 0.01, and a lower 30-day complication rate (6.3% vs. 56.3%, p < 0.01). There was no difference in progression-free survival (p = 0.577) and overall survival (p = 0.472) between the groups. CONCLUSIONS: This preliminary study demonstrates that laparoscopic CRS/HIPEC is feasible and safe for curative treatment in selected patients with low tumor volume. Minimally invasive CRS/HIPEC is associated with fewer postoperative complications and shorter length of stay. There was no difference in long-term oncological outcomes between the groups.

Hepatitis C-positive Black patients develop hepatocellular carcinoma at earlier stages of liver disease and present with a more aggressive phenotype.

BACKGROUND: In the United States, mortality after a diagnosis of hepatocellular carcinoma (HCC) is higher in patients who are Black than in patients of other racial groups. The objective of this study was to clarify factors contributing to this disparity by analyzing liver and tumor characteristics in patients with HCC who have a history of hepatitis C virus (HCV) infection. METHODS: Records of patients with HCV and HCC at the authors' institution from 2003 to 2018 were retrospectively reviewed. Race and ethnicity were self-identified. Imaging, laboratory, and pathologic features were compared between Black and non-Black cohorts. RESULTS: Among 1195 individuals with HCC, 390 identified as Black. At the time of HCC diagnosis, Black patients had better liver function, as measured by Child-Pugh score, Model of End-Stage Liver Disease score, histology of nontumor tissue, and fibrosis-4 (FIB-4) score (all P < .05). FIB-4 scores were <3.25 in 31% of Black patients. In addition, Black patients had less early stage HCC (20.2% vs 32.3%; P < .05), larger tumors (median [interquartile range]: 3.5 cm [2.2-6.2 cm] vs 3.1 cm [2.1-5.1 cm]; P < .01), more multiple tumors (median, [interquartile range]: 1 tumor [1-3 tumors] vs 1 tumor [1-2 tumors]; P = .03), more poorly differentiated tumors (30.3% vs 20.5%; P < .05), and more microvascular invasion (67.2% vs 56.5%; P < .05). CONCLUSIONS: Black patients with HCV exposure develop HCC at earlier stages of liver disease than members of other racial groups. Nearly one-third would not qualify for HCC screening using the common FIB-4 cirrhosis threshold. Practice guidelines that stress HCC surveillance for cirrhotic patients with HCV may need to be revised to be more inclusive for Black patients. In addition, tumors in Black patients carry worse prognostic features, and molecular studies are needed to characterize their biologic properties.

The heparin-von Willebrand factor interaction and conventional tests of haemostasis - the challenges in predicting bleeding in cardiopulmonary bypass.

Bleeding is a significant complication of cardiopulmonary bypass (CPB), despite routine anticoagulation monitoring. This is likely to be multifactorial. In this prospective, single-centre cohort study of 30 patients undergoing CPB surgery, our aim was to characterise the changes in von Willebrand factor (VWF) function, platelet interaction and the global coagulation changes during and after CPB surgery and to determine whether bleeding can be predicted. Samples were taken at six time points before, during and after CPB surgery. We observed a significant rise in VWF antigen (VWF:Ag) throughout surgery, which continued postoperatively. The absolute VWF collagen-binding assays (VWF:CB) and VWF ristocetin cofactor (VWF:RCo) rose significantly but the VWF:CB/VWF:Ag and VWF:Ag/VWF:RCo fell significantly (P = 0·0015 and P = 0·0143), suggesting loss of large multimers. We detected a non-significant trend to loss of VWF:RCo after heparinisation and a significant recovery after protamine reversal which could reflect a direct heparin effect. There was a significant increase in the R and K times with a fall in alpha angle and maximum amplitude after heparin administration, using heparinase-thromboelastography (TEG). The parameters both significantly improved following protamine (P = 0·007 and P = 0·0054). The activated clotting time (ACT) and heparin anti-Xa level correlated poorly; neither predicted clinically significant bleeding. None of these parameters had a relationship with intraoperative blood loss or requirement for blood product replacement.

The clinical course of COVID-19 in pregnant versus non-pregnant women requiring hospitalisation: results from the multicentre UK CA-COVID-19 study.

The impact of COVID-19 infection on pregnant women remains relatively unknown but the physiological changes of pregnancy and hypercoagulability of COVID-19 may further increase thrombotic risk. In this retrospective multicentre observational study, we report clinical characteristics and outcomes in 36 pregnant women requiring hospitalisation for COVID-19 compared to a propensity-matched cohort of non-pregnant women. Pregnant women had a lower haemoglobin and higher lymphocyte counts but no differences in other haematological or biochemical parameters on admission compared to non-pregnant women. There was no significant difference in the duration of hospitalisation; median two days (1-77) for pregnant versus eight days (1-49) for non-pregnant women. A higher proportion of non-pregnant women required mechanical ventilation [11/36 (31%) vs 3/36 (8%), P = 0·03] and received thromboprophylaxis with low-molecular-weight heparin (LMWH) within 24 h of admission [25/36 (69%) vs 15 /36(42%), P = 0·03] compared to pregnant women. One pregnant woman required extracorporeal membrane oxygenation. The rate of thrombosis was similar in both groups (one in each group). No women developed major bleeding or died. Data suggest that although non-pregnant women had a severe clinical course, overall outcomes were not different between women with or without pregnancy. The use of thromboprophylaxis was inconsistent, demonstrating a need for establishing evidence-based guidance for COVID-19 during pregnancy.

Intestinal Epithelial Expression of MHCII Determines Severity of Chemical, T-Cell-Induced, and Infectious Colitis in Mice.

BACKGROUND & AIMS: Intestinal epithelial cells (IECs) provide a barrier that separates the mucosal immune system from the luminal microbiota. IECs constitutively express low levels of major histocompatibility complex (MHC) class II proteins, which are upregulated upon exposure to interferon gamma. We investigated the effects of deleting MHCII proteins specifically in mice with infectious, dextran sodium sulfate (DSS)-, and T-cell-induced colitis. METHODS: We disrupted the histocompatibility 2, class II antigen A, beta 1 gene (H2-Ab1) in IECs of C57BL/6 mice (I-AbΔIEC) or Rag1-/- mice (Rag1-/-I-AbΔIEC); we used I-AbWT mice as controls. Colitis was induced by administration of DSS, transfer of CD4+CD45RBhi T cells, or infection with Citrobacter rodentium. Colon tissues were collected and analyzed by histology, immunofluorescence, xMAP, and reverse-transcription polymerase chain reaction and organoids were generated. Microbiota (total and immunoglobulin [Ig]A-coated) in intestinal samples were analyzed by16S amplicon profiling. IgA+CD138+ plasma cells from Peyer's patches and lamina propria were analyzed by flow cytometry and IgA repertoire was determined by next-generation sequencing. RESULTS: Mice with IEC-specific loss of MHCII (I-AbΔIEC mice) developed less severe DSS- or T-cell transfer-induced colitis than control mice. Intestinal tissues from I-AbΔIEC mice had a lower proportion of IgA-coated bacteria compared with control mice, and a reduced luminal concentration of secretory IgA (SIgA) following infection with C rodentium. There was no significant difference in the mucosal IgA repertoire of I-AbΔIEC vs control mice, but opsonization of cultured C rodentium by SIgA isolated from I-AbΔIEC mice was 50% lower than that of SIgA from mAbWT mice. Fifty percent of I-AbΔIEC mice died after infection with C rodentium, compared with none of the control mice. We observed a transient but significant expansion of the pathogen in the feces of I-AbΔIEC mice compared with I-AbWT mice. CONCLUSIONS: In mice with DSS or T-cell-induced colitis, loss of MHCII from IECs reduces but does not eliminate mucosal inflammation. However, in mice with C rodentium-induced colitis, loss of MHCII reduces bacterial clearance by decreasing binding of IgA to commensal and pathogenic bacteria.

Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning.

OBJECTIVES: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated. SETTING: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center. PATIENTS: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., d-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022). CONCLUSIONS: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU.