Sialyltransferase ST6GAL-1 mediates resistance to chemoradiation in rectal cancer.

Locally advanced rectal cancer is typically treated with chemoradiotherapy followed by surgery. Most patients do not display a complete response to chemoradiotherapy, but resistance mechanisms are poorly understood. ST6GAL-1 is a sialyltransferase that adds the negatively charged sugar, sialic acid (Sia), to cell surface proteins in the Golgi, altering their function. We therefore hypothesized that ST6GAL-1 could mediate resistance to chemoradiation in rectal cancer by inhibiting apoptosis. Patient-derived xenograft and organoid models of rectal cancer and rectal cancer cell lines were assessed for ST6GAL-1 protein with and without chemoradiation treatment. ST6GAL-1 mRNA was assessed in untreated human rectal adenocarcinoma by PCR assays. Samples were further assessed by Western blotting, Caspase-Glo apoptosis assays, and colony formation assays. The presence of functional ST6GAL-1 was assessed via flow cytometry using the Sambucus nigra lectin, which specifically binds cell surface α2,6-linked Sia, and via lectin precipitation. In patient-derived xenograft models of rectal cancer, we found that ST6GAL-1 protein was increased after chemoradiation in a subset of samples. Rectal cancer cell lines demonstrated increased ST6GAL-1 protein and cell surface Sia after chemoradiation. ST6GAL-1 was also increased in rectal cancer organoids after treatment. ST6GAL-1 knockdown in rectal cancer cell lines resulted in increased apoptosis and decreased survival after treatment. We concluded that ST6GAL-1 promotes resistance to chemoradiotherapy by inhibiting apoptosis in rectal cancer cell lines. More research will be needed to further elucidate the importance and mechanism of ST6GAL-1-mediated resistance.

Seroconversion and fever are dose-dependent in a nonhuman primate model of inhalational COVID-19.

While evidence exists supporting the potential for aerosol transmission of SARS-CoV-2, the infectious dose by inhalation remains unknown. In the present study, the probability of infection following inhalation of SARS-CoV-2 was dose-dependent in a nonhuman primate model of inhalational COVID-19. The median infectious dose, assessed by seroconversion, was 52 TCID50 (95% CI: 23-363 TCID50), and was significantly lower than the median dose for fever (256 TCID50, 95% CI: 102-603 TCID50), resulting in a group of animals that developed an immune response post-exposure but did not develop fever or other clinical signs of infection. In a subset of these animals, virus was detected in nasopharyngeal and/or oropharyngeal swabs, suggesting that infected animals without signs of disease are able to shed virus and may be infectious, which is consistent with reports of asymptomatic spread in human cases of COVID-19. These results suggest that differences in exposure dose may be a factor influencing disease presentation in humans, and reinforce the importance of public health measures that limit exposure dose, such as social distancing, masking, and increased ventilation. The dose-response data provided by this study are important to inform disease transmission and hazard modeling, and, ultimately, mitigation strategies. Additionally, these data will be useful to inform dose selection in future studies examining the efficacy of therapeutics and vaccines against inhalational COVID-19, and as a baseline in healthy, young adult animals for assessment of the importance of other factors, such as age, comorbidities, and viral variant, on the infectious dose and disease presentation.

Video Interviews and Surgical Applicants' Ability to Assess Fit to Residency Programs.

INTRODUCTION: Due to the COVID-19 pandemic, the recruitment cycle for the 2021 Match was performed virtually. This Association for Surgical Education (ASE)-sponsored survey set out to study applicants' ability to assess the factors contributing to fit through video interviews. METHODS: An IRB-approved, online, anonymous survey was distributed to surgical applicants at a single academic institution and through the ASE clerkship director distribution list between the rank order list certification deadline and Match Day. Applicants used 5-point Likert-type scales to rate factors for importance to fit and their ease of assessment through video interviewing. A variety of recruitment activities were also rated by applicants for their perceived helpfulness in assessment of fit. RESULTS: One hundred and eighty-three applicants responded to the survey. The three most important factors for applicant fit were how much the program cared, how satisfied residents seem with their program, and how well residents get along. Resident rapport, diversity of the patient population, and quality of the facilities were hardest to assess through video interviews. In general, diversity-related factors were more important to female and non-White applicants, but not more difficult to assess. Interview day and resident-only virtual panels were the most helpful recruitment activities, while virtual campus tours, faculty-only panels, and a program's social media were the least helpful. CONCLUSIONS: This study provides valuable insight into the limitations of virtual recruitment for surgical applicants' perception of fit. These findings and the recommendations herein should be taken into consideration by residency program leadership to ensure successful recruitment of diverse residency classes.

Insect biomass density: measurement of seasonal and daily variations using an entomological optical sensor.

Insects are major actors in Earth's ecosystems and their recent decline in abundance and diversity is alarming. The monitoring of insects is paramount to understand the cause of this decline and guide conservation policies. In this contribution, an infrared laser-based system is used to remotely monitor the biomass density of flying insects in the wild. By measuring the optical extinction caused by insects crossing the 36-m long laser beam, the Entomological Bistatic Optical Sensor System used in this study can evaluate the mass of each specimen. At the field location, between July and December 2021, the instrument made a total of 262,870 observations of insects for which the average dry mass was 17.1 mg and the median 3.4 mg. The daily average mass of flying insects per meter cube of air at the field location has been retrieved throughout the season and ranged between near 0 to 1.2 mg/m3. Thanks to its temporal resolution in the minute range, daily variations of biomass density have been observed as well. These measurements show daily activity patterns changing with the season, as large increases in biomass density were evident around sunset and sunrise during Summer but not during Fall.

HDAC3 deacetylates the DNA mismatch repair factor MutSß to stimulate triplet repeat expansions.

Trinucleotide repeat (TNR) expansions cause nearly 20 severe human neurological diseases which are currently untreatable. For some of these diseases, ongoing somatic expansions accelerate disease progression and may influence age of onset. This new knowledge emphasizes the importance of understanding the protein factors that drive expansions. Recent genetic evidence indicates that the mismatch repair factor MutSß (Msh2-Msh3 complex) and the histone deacetylase HDAC3 function in the same pathway to drive triplet repeat expansions. Here we tested the hypothesis that HDAC3 deacetylates MutSß and thereby activates it to drive expansions. The HDAC3-selective inhibitor RGFP966 was used to examine its biological and biochemical consequences in human tissue culture cells. HDAC3 inhibition efficiently suppresses repeat expansion without impeding canonical mismatch repair activity. Five key lysine residues in Msh3 are direct targets of HDAC3 deacetylation. In cells expressing Msh3 in which these lysine residues are mutated to arginine, the inhibitory effect of RGFP966 on expansions is largely bypassed, consistent with the direct deacetylation hypothesis. RGFP966 treatment does not alter MutSß subunit abundance or complex formation but does partially control its subcellular localization. Deacetylation sites in Msh3 overlap a nuclear localization signal, and we show that localization of MutSß is partially dependent on HDAC3 activity. Together, these results indicate that MutSß is a key target of HDAC3 deacetylation and provide insights into an innovative regulatory mechanism for triplet repeat expansions. The results suggest expansion activity may be druggable and support HDAC3-selective inhibition as an attractive therapy in some triplet repeat expansion diseases.

Postoperative Proton Pump Inhibitors are associated with a significantly higher rate of delayed gastric emptying after pancreatoduodenectomy.

BACKGROUND: Proton pump inhibitors (PPIs) are effective in reducing marginal ulcers after pancreatoduodenectomy. However, their impact on perioperative complications has not been defined. METHODS: We retrospectively analyzed the effect of postoperative PPIs on 90-day perioperative outcomes in all patients who underwent pancreatoduodenectomy at our institution from April 2017 to December 2020. RESULTS: 284 patients were included; 206 (72.5%) received perioperative PPIs, 78 (27.5%) did not. The two cohorts were similar in demographics and operative variables. Postoperatively, the PPI cohort had significantly higher rates of overall complications (74.3% vs. 53.8%) and delayed gastric emptying (28.6% vs. 11.5%), p < 0.05. However, no differences in infectious complications, postoperative pancreatic fistula, or anastomotic leaks were seen. On multivariate analysis, PPI was independently associated with a higher risk of overall complications (OR 2.46, CI 1.33-4.54) and delayed gastric emptying (OR 2.73, CI 1.26-5.91), p = 0.011. Four patients developed marginal ulcers within 90-days postoperatively; all were in the group who received PPIs. CONCLUSION: Postoperative proton pump inhibitor use was associated with a significantly higher rate of overall complications and delayed gastric emptying after pancreatoduodenectomy.

4,300 steps per day prior to surgery are associated with improved outcomes after pancreatectomy.

BACKGROUND: Decreased preoperative physical fitness and low physical activity have been associated with preoperative functional reserve and surgical complications. We sought to evaluate daily step count as a measure of physical activity and its relationship with post-pancreatectomy outcomes. METHODS: Patients undergoing pancreatectomy were given a remote telemonitoring device to measure their preoperative levels of physical activity. Patient activity, demographics, and perioperative outcomes were collected and compared in univariate and multivariate logistic regression analysis. RESULTS: 73 patients were included. 45 (61.6%) patients developed complications, with 17 (23.3%) of those patients developing severe complications. These patients walked 3437.8 (SD 1976.7) average daily steps, compared to 5918.8 (SD 2851.1) in patients without severe complications (p < 0.001). In logistic regression analysis, patients who walked less than 4274.5 steps had significantly higher odds of severe complications (OR = 7.5 (CI 2.1, 26.8), p = 0.002). CONCLUSION: Average daily steps below 4274.5 before surgery are associated with severe complications after pancreatectomy. Preoperative physical activity levels may represent a modifiable target for prehabilitation protocols.

Profiling Human Cytomegalovirus-Specific T Cell Responses Reveals Novel Immunogenic Open Reading Frames.

Despite the prevalence and medical significance of human cytomegalovirus (HCMV) infections, a systematic analysis of the targets of T cell recognition in humans that spans the entire genome and includes recently described potential novel open reading frames (ORFs) is not available. Here, we screened a library of epitopes predicted to bind HLA class II that spans over 350 different HCMV ORFs and includes ∼150 previously described and ∼200 recently described potential novel ORFs by using an ex vivo gamma interferon (IFN-γ) FluoroSpot assay. We identified 235 unique HCMV-specific epitopes derived from 100 ORFs, some previously described as immunodominant and others that were not previously described to be immunogenic. Of those, 41 belong to the set of recently reported novel ORFs, thus providing evidence that at least some of these are actually expressed in vivo in humans. These data reveal that the breadth of the human T cell response to HCMV is much greater than previously thought. The ORFs and epitopes identified will help elucidate how T cell immunity relates to HCMV pathogenesis and instruct ongoing HCMV vaccine research. IMPORTANCE To understand the crucial role of adaptive immunity in controlling cytomegalovirus infection and disease, we systematically analyzed the CMV "ORFeome" to identify new CMV epitopes targeted primarily by CD4 T cells in humans. Our study identified >200 new T cell epitopes derived from both canonical and novel ORFs, highlighting the substantial breadth of the anti-CMV T cell response and providing new targets for vaccine design.

Increased Morbidity and Mortality After Hepatectomy for Colorectal Liver Metastases in Frail Patients is Largely Driven by Worse Outcomes After Minor Hepatectomy: It's Not "Just a Wedge".

BACKGROUND: Frailty is associated with postoperative mortality, but its significance after hepatectomy for colorectal liver metastases (CRLM) is poorly defined. This study evaluated the impact of frailty after hepatectomy for CRLM. METHODS: The study identified 8477 patients in National Surgical Quality Improvement Program databases from 2014 to 2019 and stratified them by frailty score using the risk analysis index as very frail (>90th percentile), frail (75th-90th percentile), or non-frail (< 75th percentile). Multivariate regression models determined the impact of frailty on perioperative outcomes, including by the extent of hepatectomy. RESULTS: The procedures performed were 2752 major hepatectomies (left hepatectomy, right hepatectomy, trisectionectomy) and 5725 minor hepatectomies (≤2 segments) for 870 (10.3%) very frail, 1680 (19.8%) frail, and 5927 (69.9%) non-frail patients. Postoperatively, the very frail and frail patients experienced more complications (very frail [41.8%], frail [35.1%], non-frail [31.0%]), which resulted in a longer hospital stay (very-frail [5.7 days], frail [5.8 days], non-frail [5.1 days]), a higher 30-day mortality (very-frail [2.2%], frail [1.3%], non-frail [0.5%]), and more discharges to a facility (very frail [6.8%], frail [3.7%], non-frail [2.6%]) (p < 0.05) although they underwent similarly extensive (major vs. minor) hepatectomies. In the multivariate analysis, frailty was independently associated with complications (very-frail [odds ratio {OR}, 1.70], frail [OR, 1.25]) and 30-day mortality (very-frail [OR, 4.24], frail [OR, 2.41]) (p < 0.05). After minor hepatectomy, the very frail and frail patients had significantly higher rates of complications and 30-day mortality than the non-frail patients, and in the multivariate analysis, frailty was independently associated with complications (very frail [OR, 1.97], frail [OR, 1.27]) and 30-day mortality (very frail [OR, 6.76], frail [OR, 3.47]) (p < 0.05) after minor hepatectomy. CONCLUSIONS: Frailty predicted significantly poorer outcomes after hepatectomy for CRLM, even after only a minor hepatectomy.

18 F-FDG positron emission tomography-computed tomography has a low positive predictive value for detecting occult recurrence in asymptomatic patients with high-risk Stages IIB, IIC, and IIIA melanoma.

BACKGROUND AND OBJECTIVES: High recurrence rates of Stages II and IIIA melanoma make close follow-up essential, especially with new adjuvant therapies for metastatic disease. However, there are currently no consensus guidelines for routine imaging for Stages IIB, IIC, and IIIA melanoma. The study's aim is to determine the utility of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography/computed tomography (PET/CT) for detecting asymptomatic recurrence of melanoma after primary surgical resection. METHODS: This retrospective cohort study included 158 patients with the American Joint Committee on Cancer 8th edition Stages IIB, IIC, or IIIA cutaneous melanoma who underwent an 18 F-FDG PET/CT from 2010 to 2020. We retrospectively analyzed clinical data after a median follow-up time of 39 months. RESULTS: We calculated a positive predictive value (PPV) of 32% (95% confidence interval: 11%-53%) for 154 routine PET/CTs, including six true positives and 13 false positives (FPs). PPV was 33% for Stage IIB, 50% for Stage IIC, and 14% for Stage IIIA. FPs were mostly benign or inflammatory foci (75%), and some other malignancies were found (21%). CONCLUSIONS: This cohort of patients imaged for high-risk melanoma demonstrated a high FP rate and low PPV. These findings suggest that routine surveillance with 18 F-FDG PET/CT may not be indicated for monitoring recurrence in this population.

CD4 T cells mediate brain inflammation and neurodegeneration in a mouse model of Parkinson's disease.

α-Synuclein, a key pathological component of Parkinson's disease, has been implicated in the activation of the innate and adaptive immune system. This immune activation includes microgliosis, increased inflammatory cytokines, and the infiltration of T cells into the CNS. More recently, peripherally circulating CD4 and CD8 T cells derived from individuals with Parkinson's disease have been shown to produce Th1/Th2 cytokines in response to α-synuclein, suggesting there may be a chronic memory T cell response present in Parkinson's disease. To understand the potential effects of these α-syn associated T cell responses we used an α-synuclein overexpression mouse model, T cell-deficient mice, and a combination of immunohistochemistry and flow cytometry. In this study, we found that α-synuclein overexpression in the midbrain of mice leads to the upregulation of the major histocompatibility complex II (MHCII) protein on CNS myeloid cells as well as the infiltration of IFNγ producing CD4 and CD8 T cells into the CNS. Interestingly, genetic deletion of TCRß or CD4, as well as the use of the immunosuppressive drug fingolimod, were able to reduce the CNS myeloid MHCII response to α-synuclein. Furthermore, we observed that CD4-deficient mice were protected from the dopaminergic cell loss observed due to α-syn overexpression. These results suggest that T cell responses associated with α-synuclein pathology may be damaging to key areas of the CNS in Parkinson's disease and that targeting these T cell responses could be an avenue for disease modifying treatments.

Yield of Surveillance Colonoscopy in Older Adults with a History of Polyps: A Systematic Review and Meta-Analysis.

BACKGROUND: The benefit of surveillance colonoscopy in older adults is not well described. AIMS: To quantify the detection of colorectal cancer (CRC) and advanced polyps during surveillance colonoscopy in older adults with a history of colon polyps. METHODS: We conducted a systematic review (MEDLINE, Cochrane Library, Web of Science, and Embase) for all published studies through May 2020 in adults age > 70 undergoing surveillance colonoscopy. The main outcome was CRC and advanced polyps detection. We performed meta-analysis to pool results by age (>70 vs. 50-70). RESULTS: The search identified 6239 studies, of which 569 underwent full-text review and 64 data abstraction, of which 19 were included. The risk of detecting CRC (N = 11) was higher in those >70 compared to 50-70 (risk ratio 1.5 (95% CI 1.1-2.2); risk difference 0.8% (95% CI -0.2%-1.8%)). Similarly, the risk of detecting advanced polyps (N = 8) was higher in those >70 compared to 50-70 (risk ratio 1.3 (95% CI 1.2-1.3), risk difference 2.7% (95% CI 1.3%-4.0%)). Most studies did not stratify results by baseline polyp risk. CONCLUSIONS: The detection of CRC and advanced polyps during surveillance colonoscopy in older individuals was higher than in younger controls; however, the absolute risk increase for both was small. These differences must be weighed against competing medical problems and limited life expectancy in older adults when making decisions about surveillance colonoscopy. More primary data on the risks of CRC and advanced polyps accounting for number of past colonoscopies, prior polyp risk, and duration of time since last polyp are needed.

Cause and outcome of aborting a difficult laparoscopic cholecystectomy due to severe inflammation: a study of operative notes.

BACKGROUND: Upon encountering a difficult cholecystectomy in which, after a reasonable trial of dissection, anatomical identification has not been attained due to severe inflammation, and the risk of additional dissection is deemed to be hazardous, "bail-out" strategies are encouraged safety valves. One strategy is to abort the cholecystectomy and refer the patient to a HPB center for further management. METHODS: A retrospective review was conducted of cholecystectomies performed by HPB surgeons at our center between 2005 and 2019. We identified 63 patients who had an aborted cholecystectomy because of acute or chronic cholecystitis and were referred for additional care. Of these, operative notes and other clinical records were available for 43 patients who were included in this study. RESULTS: 42 cholecystectomies (98%) were started laparoscopically. 25 patients (58%) had chronic cholecystitis, and 18 (42%) had acute cholecystitis. 40 cases (93%) fell into the highest level of difficulty on the Nassar scale (Grade 4). Procedures were aborted at the following stages of dissection: in 10 patients (23%), none of the gallbladder was identified; in another 11 (26%), only the dome of gallbladder was identified; the body of the gallbladder was exposed in 13 (30%); and dissection of the hepatocystic triangle was attempted unsuccessfully in 9 (21%). Following referral to our center, 30 patients (70%) were managed with total cholecystectomy while in 13 cases (30%), subtotal cholecystectomy was performed. CONCLUSION: Aborting cholecystectomy and referring the patient to an HPB center is rarely needed but is an effective bail-out strategy for general surgeons encountering highly difficult operative conditions due to inflammation.

Improved outcomes with minimally invasive pancreaticoduodenectomy in patients with dilated pancreatic ducts: a prospective study.

BACKGROUND: Little is known about what factors predict better outcomes for patients who undergo minimally invasive pancreaticoduodenectomy (MIPD) versus open pancreaticoduodenectomy (OPD). We hypothesized that patients with dilated pancreatic ducts have improved postoperative outcomes with MIPD compared to OPD. METHODS: All patients undergoing pancreaticoduodenectomy were prospectively followed over a time period of 47 months, and perioperative and pathologic covariates and outcomes were compared. Ideal outcome after PD was defined as follows: (1) no complications, (2) postoperative length of stay < 7 days, and (3) negative (R0) margins on pathology. Patients with dilated pancreatic ducts (≥ 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with dilated ducts who underwent OPD and outcomes compared. Likewise, patients with non-dilated pancreatic ducts (< 3 mm) who underwent MIPD were 1:3 propensity score-matched to patients with non-dilated ducts who underwent OPD and outcomes were compared. RESULTS: 371 patients underwent PD-74 (19.9%) MIPD and 297 (80.1%) underwent OPD. Overall, patients who underwent MIPD had significantly less intraoperative blood loss. After 1:3 propensity score matching, patients with dilated pancreatic ducts who underwent MIPD (n = 45) had significantly lower overall complication and 90-day readmission rates compared to matched OPD patients (n = 135) with dilated ducts. Patients with dilated duct who underwent MIPD were more likely to have an ideal outcome than patients with OPD (29 vs 15%, p = 0.035). There were no significant differences in postoperative outcomes among propensity score-matched patients with non-dilated pancreatic ducts who underwent MIPD (n = 29) compared to matched patients undergoing OPD (n = 87) with non-dilated ducts. CONCLUSIONS: MIPD is safe with comparable perioperative outcomes to OPD. Patients with pancreatic ducts ≥ 3 mm appear to derive the most benefit from MIPD in terms of fewer complications, lower readmission rates, and higher likelihood of ideal outcome.

Applicants' perception of fit to residency programmes in the video-interview era: A large multidisciplinary survey.

INTRODUCTION: 'Fit' refers to an applicants' perceived compatibility to a residency programme. A variety of structural, identity-related and relational factors contribute to self-assessments of fit. The 2021 residency recruitment cycle in the USA was performed virtually due to the COVID-19 pandemic. Little is known about how video-interviewing may affect residency applicants' ability to gauge fit. METHODS: A multidisciplinary, anonymous survey was distributed to applicants at a large academic institution between rank order list (ROL) certification deadline and Match Day 2021. Using Likert-type scales, applicants rated factors for importance to 'fit' and their ease of assessment through video-interviewing. Applicants also self-assigned fit scores to the top-ranked programme in their ROL using Likert-type scales with pairs of anchoring statements. RESULTS: Four hundred seventy-three applicants responded to the survey (25.7% response rate). The three most important factors to applicants for assessment of fit (how much the programme seemed to care, how satisfied residents seem with their programme and how well the residents get along) were also the factors with the greatest discrepancy between importance and ease of assessment through video-interviewing. Diversity-related factors were more important to female applicants compared with males and to non-White applicants compared with White applicants. Furthermore, White male applicants self-assigned higher fit scores compared with other demographic groups. CONCLUSION: There is a marked discrepancy between the most important factors to applicants for fit and their ability to assess those factors virtually. Minoritised trainees self-assigned lower fit scores to their top-ranked programme, which should raise concern amongst medical educators and highlights the importance of expanding current diversity, equity and inclusion efforts in academic medicine.

Equivocal associations between small-scale shoreline restoration and subtidal fishes in an urban estuary.

Restoration of degraded coastal and estuarine habitats owing to human activities is a major global concern. In Puget Sound, Washington, U.S.A., removal of hard armor from beaches and intertidal zones has become a priority for state and local agencies. However, the effectiveness of these shoreline restoration programs for subtidal habitats and fish is unknown. We surveyed six restoration sites in Puget Sound over 2 years to evaluate associations between shoreline restoration and subtidal fish abundance. We measured the abundance of juvenile salmonids and forage fishes along armored, restored, and reference shorelines. Bayesian generalized linear models showed limited support for associations between shoreline restoration and these fishes in the 3-7 years since armor removal. Pacific herring were more abundant at reference shorelines; the shoreline effect for surf smelt varied by survey site. Shoreline restoration was not an important predictor of salmonid abundance; the best models for Chinook and chum salmon included predictors for survey site and eelgrass, respectively. The retention of survey site in several species' top models reveals the influence of the broader landscape context. We also found seasonal variation in abundance for chum salmon and surf smelt. Our results suggest that juvenile forage fish and salmonids in estuaries likely have unique responses to shoreline features, and that the positive effects of armor removal either do not extend into subtidal areas or are not detectable at local scales. To be most effective, coastal restoration programs should consider broader landscape patterns as well as species-specific habitat needs when prioritizing investments.

Enhanced recovery pathway after open pancreaticoduodenectomy reduces postoperative length of hospital stay without reducing composite length of stay.

BACKGROUND/PURPOSE: There is no data regarding the impact of enhanced recovery pathways (ERP) on composite length of stay (CLOS) after procedures with increased risk of morbidity and mortality, such as pancreaticoduodenectomy. METHODS: Patients undergoing open pancreaticoduodenectomy before and after implementation of ERP were prospectively followed for 90 days after surgery and complications were severity graded using the Modified Accordion Grading System. A retrospective analysis of patient outcomes were compared before and after instituting ERP. 1:1 propensity score matching was used to compare ERP patient outcomes to those of matched pre-ERP patients. CLOS is defined as postoperative length of hospital stay (PLOS) plus readmission length of hospital stay within 90 days after surgery. RESULTS: 494 patients underwent open pancreaticoduodenectomy - 359 pre-ERP and 135 ERP. In a 1:1 propensity-score-matched analysis of 110 matched pairs, ERP patients had significantly decreased superficial surgical site infections (5.5% vs 15.5% p = 0.015) and significantly increased rates of urinary retention (29.1% vs 7.3% p < 0.0001) compared to matched pre-ERP patients. However, overall complication rate and 90-day readmission rate were not significantly different between matched groups. Propensity score-matched ERP patients had significantly decreased PLOS (7 days vs 8 days p = 0.046) compared to matched pre-ERP patients, but CLOS was not significantly different (9 days vs 9.5 days p = 0.615). CONCLUSION: ERP may reduce PLOS but might not impact the total postoperative time spent in the hospital (i.e. CLOS) within 90 days after pancreaticoduodenectomy.

The Stability of an Isolate of the SARS-CoV-2 B.1.1.7 Lineage in Aerosols Is Similar to 3 Earlier Isolates.

BACKGROUND: Our laboratory previously examined the influence of environmental conditions on the stability of an early isolate of SARS-CoV-2 (hCoV-19/USA/WA-1/2020) in aerosols generated from culture medium or simulated saliva. However, genetic differences have emerged among SARS-CoV-2 lineages, and it is possible that these differences may affect environmental stability and the potential for aerosol transmission. METHODS: The influence of temperature, relative humidity, and simulated sunlight on the decay of 4 SARS-CoV-2 isolates in aerosols, including 1 belonging to the recently emerged B.1.1.7 lineage, were compared in a rotating drum chamber. Aerosols were generated from simulated respiratory tract lining fluid to represent aerosols originating from the deep lung. RESULTS: No differences in the stability of the isolates were observed in the absence of simulated sunlight at either 20°C or 40°C. However, a small but statistically significant difference in the stability was observed between some isolates in simulated sunlight at 20°C and 20% relative humidity. CONCLUSIONS: The stability of SARS-CoV-2 in aerosols does not vary greatly among currently circulating lineages, including B.1.1.7, suggesting that the increased transmissibility associated with recent SARS-CoV-2 lineages is not due to enhanced survival in the environment.

Safety and feasibility of initiating a hepatic artery infusion pump chemotherapy program for unresectable colorectal liver metastases: A multicenter, retrospective cohort study.

INTRODUCTION: Hepatic artery infusion pump (HAIP) chemotherapy is a specialized therapy for patients with unresectable colorectal liver metastases (uCRLM). Its effectiveness was demonstrated from a high volume center, with uncertainty regarding the feasibility and safety at other centers. Therefore, we sought to assess the safety and feasibility of HAIP for the management of uCRLM at other centers. METHODS: We conducted a multicenter retrospective cohort study of patients with uCRLM treated with HAIP from January 2003 to December 2017 at six North American centers initiating the HAIP program. Outcomes included the safety and feasibility of HAIP chemotherapy. RESULTS: We identified 154 patients with HAIP insertion and the median age of 54 (48-61) years. The burden of disease was >10 intra-hepatic metastatic foci in 59 (38.3%) patients. Patients received at least one cycle of systemic chemotherapy before HAIP insertion. Major complications occurred in 7 (4.6%) patients during their hospitalization and 13 (8.4%) patients developed biliary sclerosis during follow-up. A total of 148 patients (96.1%) received at least one-dose of HAIP chemotherapy with a median of 5 (4-7) cycles. 78 patients (56.5%) had a complete or partial response and 12 (7.8%) received a curative liver resection. CONCLUSION: HAIP programs can be safely and effectively initiated in previously inexperienced centers with good response.

Predicting Outcomes in Patients Undergoing Pancreatectomy Using Wearable Technology and Machine Learning: Prospective Cohort Study.

BACKGROUND: Pancreatic cancer is the third leading cause of cancer-related deaths, and although pancreatectomy is currently the only curative treatment, it is associated with significant morbidity. OBJECTIVE: The objective of this study was to evaluate the utility of wearable telemonitoring technologies to predict treatment outcomes using patient activity metrics and machine learning. METHODS: In this prospective, single-center, single-cohort study, patients scheduled for pancreatectomy were provided with a wearable telemonitoring device to be worn prior to surgery. Patient clinical data were collected and all patients were evaluated using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator (ACS-NSQIP SRC). Machine learning models were developed to predict whether patients would have a textbook outcome and compared with the ACS-NSQIP SRC using area under the receiver operating characteristic (AUROC) curves. RESULTS: Between February 2019 and February 2020, 48 patients completed the study. Patient activity metrics were collected over an average of 27.8 days before surgery. Patients took an average of 4162.1 (SD 4052.6) steps per day and had an average heart rate of 75.6 (SD 14.8) beats per minute. Twenty-eight (58%) patients had a textbook outcome after pancreatectomy. The group of 20 (42%) patients who did not have a textbook outcome included 14 patients with severe complications and 11 patients requiring readmission. The ACS-NSQIP SRC had an AUROC curve of 0.6333 to predict failure to achieve a textbook outcome, while our model combining patient clinical characteristics and patient activity data achieved the highest performance with an AUROC curve of 0.7875. CONCLUSIONS: Machine learning models outperformed ACS-NSQIP SRC estimates in predicting textbook outcomes after pancreatectomy. The highest performance was observed when machine learning models incorporated patient clinical characteristics and activity metrics.