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Cancer-associated mucins: role in immune modulation and metastasis
Mucins (MUC) protect epithelial barriers from environmental insult to maintain homeostasis. However, their aberrant overexpression and glycosylation in various malignancies facilitate oncogenic events from inception to metastasis. Mucin-associated sialyl-Tn (sTn) antigens bind to various receptors present on the dendritic cells (DCs), macrophages, and natural killer (NK) cells, resulting in overall immunosuppression by either receptor masking or inhibition of cytolytic activity. MUC1-mediated interaction of tumor cells with innate immune cells hampers cross-presentation of processed antigens on MHC class I molecules. MUC1 and MUC16 bind siglecs and mask Toll-like receptors (TLRs), respectively, on DCs promoting an immature DC phenotype that in turn reduces T cell effector functions. Mucins, such as MUC1, MUC2, MUC4, and MUC16, interact with or form aggregates with neutrophils, macrophages, and platelets, conferring protection to cancer cells during hematological dissemination and facilitate their spread and colonization to the metastatic sites. On the contrary, poor glycosylation of MUC1 and MUC4 at the tandem repeat region (TR) generates cancer-specific immunodominant epitopes. The presence of MUC16 neo-antigen-specific T cell clones and anti-MUC1 antibodies in cancer patients suggests that mucins can serve as potential targets for developing cancer therapeutics. The present review summarizes the molecular events involved in mucin-mediated immunomodulation, and metastasis, as well as the utility of mucins as targets for cancer immunotherapy and radioimmunotherapy.
Journal Article
Revision of the World Meteorological Organization Global Atmosphere Watch (WMO/GAW) CO2 calibration scale
The NOAA Global Monitoring Laboratory serves as the World Meteorological Organization Global Atmosphere Watch (WMO/GAW) Central Calibration Laboratory (CCL) for CO2 and is responsible for maintaining the WMO/GAW mole fraction scale used as a reference within the WMO/GAW program. The current WMO-CO2-X2007 scale is embodied by 15 aluminum cylinders containing modified natural air, with CO2 mole fractions determined using the NOAA manometer from 1995 to 2006. We have made two minor corrections to historical manometric records: fixing an error in the applied second virial coefficient of CO2 and accounting for loss of a small amount of CO2 to materials in the manometer during the measurement process. By incorporating these corrections, extending the measurement records of the original 15 primary standards through 2015, and adding four new primary standards to the suite, we define a new scale, identified as WMO-CO2-X2019. The new scale is 0.18 µmol mol-1 (ppm) greater than the previous scale at 400 ppm CO2. While this difference is small in relative terms (0.045 %), it is significant in terms of atmospheric monitoring. All measurements of tertiary-level standards will be reprocessed to WMO-CO2-X2019. The new scale is more internally consistent than WMO-CO2-X2007 owing to revisions in propagation and should result in an overall improvement in atmospheric data records traceable to the CCL.
Journal Article
A decline in global CFC-11 emissions during 2018−2019
The atmospheric concentration of trichlorofluoromethane (CFC-11) has been in decline since the production of ozone-depleting substances was phased out under the Montreal Protocol
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. Since 2013, the concentration decline of CFC-11 slowed unexpectedly owing to increasing emissions, probably from unreported production, which, if sustained, would delay the recovery of the stratospheric ozone layer
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. Here we report an accelerated decline in the global mean CFC-11 concentration during 2019 and 2020, derived from atmospheric concentration measurements at remote sites around the world. We find that global CFC-11 emissions decreased by 18 ± 6 gigagrams per year (26 ± 9 per cent; one standard deviation) from 2018 to 2019, to a 2019 value (52 ± 10 gigagrams per year) that is similar to the 2008−2012 mean. The decline in global emissions suggests a substantial decrease in unreported CFC-11 production. If the sharp decline in unexpected global emissions and unreported production is sustained, any associated future ozone depletion is likely to be limited, despite an increase in the CFC-11 bank (the amount of CFC-11 produced, but not yet emitted) by 90 to 725 gigagrams by the beginning of 2020.
Atmospheric concentration measurements at remote sites around the world reveal an accelerated decline in the global mean CFC-11 concentration during 2018 and 2019, reversing recent trends and building confidence in the timely recovery of the stratospheric ozone layer.
Journal Article
Emergent cholecystectomy is superior to percutaneous cholecystostomy tube placement in critically ill patients with emergent calculous cholecystitis
The role of percutaneous cholecystostomy (PC) is undefined in patients with multiple comorbidities presenting with emergent calculous cholecystitis (CC). This study compared outcomes between PC, laparoscopic (LC), and open cholecystectomy (OC).
The Vizient UHC database was queried for high-risk patients with CC who underwent PC, LC, OC, or laparoscopic converted to open cholecystectomy (CONV). Demographics, outcomes, mortality, length of stay (LOS), and direct cost were compared between the groups.
LC was the most common approach with the lowest risk of death, complications, LOS, and cost. Complication risk was highest in OC. Nearly 20% of patients underwent PC. Complication rate, LOS, infection, aspiration pneumonia, and mortality were higher in PC. Direct cost was lowest in LC, followed by CONV, PC, and OC.
Emergent cholecystectomy for CC in high-risk patients is safer and more cost effective than PC and this study supports the use of cholecystectomy as the primary treatment approach in these patients.
•Percutaneous (PC), laparoscopic (LC), and open cholecystectomy (OC) outcomes.•LC has improved overall peri- and post-operative outcomes compared to other groups.•Outcomes, cost, and LOS in PC are worse compared to LC and converted cases.•LC may be superior to PC for high-risk patients with calculous cholecystitis (CC).•Recommend attempted LC for CC unless an absolute surgical contraindication exists.
Journal Article
Hydrocarbon emissions characterization in the Colorado Front Range: A pilot study
The multispecies analysis of daily air samples collected at the NOAA Boulder Atmospheric Observatory (BAO) in Weld County in northeastern Colorado since 2007 shows highly correlated alkane enhancements caused by a regionally distributed mix of sources in the Denver‐Julesburg Basin. To further characterize the emissions of methane and non‐methane hydrocarbons (propane, n‐butane, i‐pentane, n‐pentane and benzene) around BAO, a pilot study involving automobile‐based surveys was carried out during the summer of 2008. A mix of venting emissions (leaks) of raw natural gas and flashing emissions from condensate storage tanks can explain the alkane ratios we observe in air masses impacted by oil and gas operations in northeastern Colorado. Using the WRAP Phase III inventory of total volatile organic compound (VOC) emissions from oil and gas exploration, production and processing, together with flashing and venting emission speciation profiles provided by State agencies or the oil and gas industry, we derive a range of bottom‐up speciated emissions for Weld County in 2008. We use the observed ambient molar ratios and flashing and venting emissions data to calculate top‐down scenarios for the amount of natural gas leaked to the atmosphere and the associated methane and non‐methane emissions. Our analysis suggests that the emissions of the species we measured are most likely underestimated in current inventories and that the uncertainties attached to these estimates can be as high as a factor of two. Key Points Emissions from oil and gas operations in the Denver Julesburg Basin Multispecies observations are used to interpret CH4 variability in NE Colorado Atmospheric observations are used to evaluate bottom‐up inventories
Journal Article
Association of gravity drainage and complications following Whipple: an analysis of the ACS-NSQIP targeted database
Background
The optimal type of operative drainage following pancreaticoduodenectomy (PD) remains unclear. Our objective is to investigate risk associated with closed drainage techniques (passive [gravity] vs. suction) after PD.
Methods
We assessed operative drainage techniques utilized in patients undergoing PD in the ACS-NSQIP pancreas-targeted database from 2016 to 2018. Using multivariable logistic regression to adjust for characteristics of the patient, procedure, and pancreas, we examined the association between use of gravity drainage and postoperative outcomes.
Results
We identified 9665 patients with drains following PD from 2016 to 2018, of which 12.7% received gravity drainage. 61.0% had a diagnosis of adenocarcinoma or pancreatitis, 26.5% had a duct <3 mm, and 43.5% had a soft or intermediate gland. After multivariable adjustment, gravity drainage was associated with decreased rates of postoperative pancreatic fistula (odds ratio [OR] 0.779, 95% confidence interval [CI] 0.653–0.930,
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=0.006), delayed gastric emptying (OR 0.830, 95% CI 0.693–0.988,
p
=0.036), superficial SSI (OR 0.741, 95% CI 0.572–0.959,
p
=0.023), organ space SSI (OR 0.791, 95% CI 0.658–0.951,
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=0.012), and readmission (OR 0.807, 95% CI 0.679–0.958,
p
=0.014) following PD.
Conclusions
Gravity drainage is independently associated with decreased rates of CR-POPF, DGE, SSI, and readmission following PD. Additional prospective research is necessary to better understand the preferred drainage technique following PD.
Journal Article
Age of air from in situ trace gas measurements: insights from a new technique
The age of air is an important transport diagnostic that can be derived from trace gas measurements and compared to global chemistry climate model output. We describe a new technique to calculate the age of air, measuring transport times from the Earth's surface to any location in the atmosphere based on simultaneous in situ measurements of multiple key long-lived trace gases. The primary benefits of this new technique include (1) optimized ages of air consistent with simultaneously measured SF6 and CO2; (2) age of air from the upper troposphere through the stratosphere; (3) estimates of the second moment of age spectra that have not been well constrained from measurements; and (4) flexibility to be used with measurements across multiple instruments, platforms, and decades. We demonstrate the technique on aircraft and balloon measurements from the 1990s, the last period of extensive stratospheric in situ sampling, and several recent missions from the 2020s, and compare the results with previously published and modeled values.
Journal Article
No survival advantage exists for patients undergoing loop ileostomy for clostridium difficile colitis
We aim to compare outcomes between loop ileostomy (LI) and total abdominal colectomy (TAC) for clostridium difficile infection (CDI) and hypothesize that LI is associated with fewer complications.
The 2011–2016 ACS-NSQIP database was queried for patients undergoing LI or TAC for CDI. Patients with high outlying age, LOS, and operative time were excluded. Statistics were performed using IBM-SPSS and NCSS PASS-11.
Of 457 patients identified, 47 underwent LI. Predicted morbidity was higher in the TAC cohort (62% vs. 37%, p < 0.001). Patients in the LI cohort experienced fewer complications (72% vs. 87%, p = 0.021); however, mortality did not differ between LI (36%) and TAC (31%). Blood transfusions were more than twice as frequent in the TAC cohort (54% vs. 19%, p < 0.001). Four patients in the LI cohort required reoperation; however, none required colectomy.
No mortality difference was observed between LI and TAC. Prospective studies are required to determine the utility of LI.
An analysis of the ACS-NSQIP database was performed and demonstrates that no survival benefit exists for patients who undergo loop ileostomy for C difficile infection compared to those who undergo total colectomy; however, patients who undergo loop ileostomy are likely to retain their colon with low risk of requiring subsequent colectomy.
•Loop ileostomy offers no survival benefit over total colectomy for C. difficile.•Loop ileostomy for C. difficile permits high rates of colonic preservation.•Transfusions are more common after TAC compared to LI for C. difficile infection.
Journal Article
Prolonged non-operative management of clostridium difficile colitis is associated with increased mortality, complications, and cost
We aim to investigate the effects of delaying surgery on outcomes and cost in patients admitted with severe clostridium difficile infection (CDI).
The Vizient database was queried for patients with CDI who underwent open total abdominal colectomy (TAC). Patients operated on the day of admission were excluded. Chi-square, Fisher's exact, student T-test, and logistic regression were performed with α = 0.05.
Logistic regression analyses using days from admission to surgery (DATO), age, race, and gender demonstrated that increased DATO was associated with higher 30-day mortality (OR 1.022, 95% CI 1.001–1.044, p = 0.040), overall complications (OR 1.034, 95% CI 1.014–1.054, p = 0.001), and infectious complications (OR 1.040, 95% CI 1.018–1.062, p < 0.001) compared to age for all three outcomes. Total length of stay (LOS), intensive care unit LOS, and direct cost increased in conjunction with DATO (p < 0.001).
Early surgical intervention in appropriately selected patients should be considered when there is a high suspicion for prolonged non-operative treatment.
•In surgical patients, prolonged non-operative care increases morbidity, mortality, and cost.•Younger patients are more likely to undergo prolonged non-operative management.•Patient gender and race are not associated with poor surgical outcomes for C difficile colitis.
Journal Article