Assessing user perspectives on clinical pharmacogenomics consultation documentation: a user-centered evaluation.

The University of Florida Health Precision Medicine Program plays a crucial role in delivering pharmacogenomics (PGx) result notes to providers who request PGx testing. Despite this, there is currently a lack of a formal assessment of provider needs and established best practice design principles to guide the ongoing development of PGx result notes. This study aims to enhance the content and format of the PGx consult note at UF Health by incorporating valuable feedback from healthcare providers. Through in-depth user sessions involving 11 participants, we evaluated the usability of our consult note template. While overall satisfaction with the content was noted, specific sections, including those addressing phenoconversion and the medication list, were identified for revision to enhance clarity based on insightful provider feedback.

Multisite Verification of a Targeted CFTR Polymerase Chain Reaction/Capillary Electrophoresis Assay That Evaluates Pathogenic Variants Across Diverse Ethnic and Ancestral Groups.

CONTEXT.­: Existing targeted cystic fibrosis screening assays miss important pathogenic CFTR variants in the ethnically diverse US population. OBJECTIVE.­: To evaluate the analytic performance of a multiplex polymerase chain reaction (PCR)/capillary electrophoresis (CE) CFTR assay panel that simultaneously interrogates primary pathogenic variants of different ethnic/ancestral groups. DESIGN.­: Performance characteristic assessment and variant coverage comparison of the panel with a focus on ethnicity-specific CFTR variants were performed. Sample DNA was primarily from whole blood or cell lines. Detection of CFTR carriers was compared across several commercially available CFTR kits and recommended variant sets based on panel content. RESULTS.­: The panel interrogated 65 pathogenic CFTR variants representing 92% coverage from a recent genomic sequencing survey of the US population, including 4 variants with top 5 frequency in African or Asian populations not reflected in other targeted panels. In simulation studies, the panel represented 95% of carriers across the global population, resulting in 6.9% to 19.0% higher carrier detection rate compared with 10 targeted panels or variant sets. Precision and sensitivity/specificity were 100% concordant. Multisite sample-level genotyping accuracy was 99.2%. Across PCR and CE instruments, sample-level genotyping accuracy was 97.1%, with greater than 99% agreement for all variant-level metrics. CONCLUSIONS.­: The CFTR assay achieves 92% or higher coverage of CFTR variants in diverse populations and provides improved pan-ethnic coverage of minority subgroups of the US populace. The assay can be completed within 5 hours from DNA sample to genotype, and performance data exceed acceptance criteria for analytic metrics. This assay panel content may help address gaps in ancestry-specific CFTR genotypes while providing a streamlined procedure with rapidly generated results.

A systematic review and thematic synthesis of qualitative literature on personal recovery and voice hearing.

BACKGROUND: Personal recovery literature has been influential in the conceptualization of emotional distress and service provision. While personal recovery in psychosis has been well-studied, voice hearing literature has not been reviewed to elucidate recovery processes. METHOD: Five databases were systematically searched to identify relevant qualitative recovery literature. Twelve eligible studies were included in this review, and an appraisal tool was applied to assess quality. Thematic synthesis was used to examine the results. RESULTS: Three superordinate themes were found relating to 'Recovery Phases', 'Recovery Facilitators' and 'Barriers to Recovery'. Papers included descriptions of finding voices distressing initially yet moving towards integrating and accepting voices. Searching for meaning versus seeking distance from voices were pivotal processes to recovery pathways. Enabling and disrupting recovery experiences are discussed within a proposed model. CONCLUSIONS: Recovery in voice hearing is an individual and potentially ongoing process. Future research should seek to examine recovery factors in voice hearing longitudinally and add further evidence to the supportive role services can play in recovery and voice hearing.

Utilizing a Human-Computer Interaction Approach to Evaluate the Design of Current Pharmacogenomics Clinical Decision Support.

A formal assessment of pharmacogenomics clinical decision support (PGx-CDS) by providers is lacking in the literature. The objective of this study was to evaluate the usability of PGx-CDS tools that have been implemented in a healthcare setting. We enrolled ten prescribing healthcare providers and had them complete a 60-min usability session, which included interacting with two PGx-CDS scenarios using the "Think Aloud" technique, as well as completing the Computer System Usability Questionnaire (CSUQ). Providers reported positive comments, negative comments, and suggestions for the two PGx-CDS during the usability testing. Most provider comments were in favor of the current PGx-CDS design, with the exception of how the genotype and phenotype information is displayed. The mean CSUQ score for the PGx-CDS overall satisfaction was 6.3 ± 0.95, with seven strongly agreeing and one strongly disagreeing for overall satisfaction. The implemented PGx-CDS at our institution was well received by prescribing healthcare providers. The feedback collected from the session will guide future PGx-CDS designs for our healthcare system and provide a framework for other institutions implementing PGx-CDS.

COS-derived GPP relationships with temperature and light help explain high-latitude atmospheric CO2 seasonal cycle amplification.

In the Arctic and Boreal region (ABR) where warming is especially pronounced, the increase of gross primary production (GPP) has been suggested as an important driver for the increase of the atmospheric CO2 seasonal cycle amplitude (SCA). However, the role of GPP relative to changes in ecosystem respiration (ER) remains unclear, largely due to our inability to quantify these gross fluxes on regional scales. Here, we use atmospheric carbonyl sulfide (COS) measurements to provide observation-based estimates of GPP over the North American ABR. Our annual GPP estimate is 3.6 (2.4 to 5.5) PgC · y-1 between 2009 and 2013, the uncertainty of which is smaller than the range of GPP estimated from terrestrial ecosystem models (1.5 to 9.8 PgC · y-1). Our COS-derived monthly GPP shows significant correlations in space and time with satellite-based GPP proxies, solar-induced chlorophyll fluorescence, and near-infrared reflectance of vegetation. Furthermore, the derived monthly GPP displays two different linear relationships with soil temperature in spring versus autumn, whereas the relationship between monthly ER and soil temperature is best described by a single quadratic relationship throughout the year. In spring to midsummer, when GPP is most strongly correlated with soil temperature, our results suggest the warming-induced increases of GPP likely exceeded the increases of ER over the past four decades. In autumn, however, increases of ER were likely greater than GPP due to light limitations on GPP, thereby enhancing autumn net carbon emissions. Both effects have likely contributed to the atmospheric CO2 SCA amplification observed in the ABR.

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, p=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, p=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.

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 Protocol1,2. 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 layer1-12. 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.

A comprehensive quantification of global nitrous oxide sources and sinks.

Nitrous oxide (N2O), like carbon dioxide, is a long-lived greenhouse gas that accumulates in the atmosphere. Over the past 150 years, increasing atmospheric N2O concentrations have contributed to stratospheric ozone depletion1 and climate change2, with the current rate of increase estimated at 2 per cent per decade. Existing national inventories do not provide a full picture of N2O emissions, owing to their omission of natural sources and limitations in methodology for attributing anthropogenic sources. Here we present a global N2O inventory that incorporates both natural and anthropogenic sources and accounts for the interaction between nitrogen additions and the biochemical processes that control N2O emissions. We use bottom-up (inventory, statistical extrapolation of flux measurements, process-based land and ocean modelling) and top-down (atmospheric inversion) approaches to provide a comprehensive quantification of global N2O sources and sinks resulting from 21 natural and human sectors between 1980 and 2016. Global N2O emissions were 17.0 (minimum-maximum estimates: 12.2-23.5) teragrams of nitrogen per year (bottom-up) and 16.9 (15.9-17.7) teragrams of nitrogen per year (top-down) between 2007 and 2016. Global human-induced emissions, which are dominated by nitrogen additions to croplands, increased by 30% over the past four decades to 7.3 (4.2-11.4) teragrams of nitrogen per year. This increase was mainly responsible for the growth in the atmospheric burden. Our findings point to growing N2O emissions in emerging economies-particularly Brazil, China and India. Analysis of process-based model estimates reveals an emerging N2O-climate feedback resulting from interactions between nitrogen additions and climate change. The recent growth in N2O emissions exceeds some of the highest projected emission scenarios3,4, underscoring the urgency to mitigate N2O emissions.

No Opioids after Septorhinoplasty: A Multimodal Analgesic Protocol.

From a public health perspective, nasal surgery accounts for many unused opioids. Patients undergoing septorhinoplasty require few opioids, and efforts to eliminate this need may benefit both patients and the public. METHODS: A multimodal analgesic protocol consisting of 15 components encompassing all phases of care was implemented for 42 patients. RESULTS: Median age and BMI were 34 years and 23, respectively. Most were women (79%), White (79%), primary surgeries (62%), and self-pay (52%). Comorbid conditions were present in 74% of the patients, with anxiety (33%) and depression (21%) being the most common. Septoplasties (67%) and osteotomies (45%) were common. The median operative time was 70 minutes. No patients required opioids in recovery, and median time in recovery was 63 minutes. Ten (24%) patients required an opioid prescription after discharge. In those patients, median time to requirement was 27 hours (range 3-81), and median total requirement was 20 mg morphine equivalents (range 7.5-85). Protocol compliance inversely correlated to opioid use (P = 0.007). Compliance with local and regional anesthetic (20% versus 63%, P = 0.030) as well as ketorolac (70% versus 100%, P = 0.011) was lower in patients who required opioids. Patients who required opioids were less likely to be administered a beta blocker (0% versus 34%, P = 0.041). Pain scores were higher in opioid users on postoperative days 1-5 (P < 0.05). No complications occurred in those requiring opioids, and satisfaction rates were equivalent between groups. CONCLUSION: This protocol allowed us to safely omit opioid prescriptions in 76% of patients following septorhinoplasty, without adverse effects on outcomes or patient satisfaction.

A Comparative Analysis of Survival and Funding Discrepancies in Cancers With High Mortality.

OBJECTIVE: Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. BACKGROUND: Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). METHODS: The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. RESULTS: Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. CONCLUSIONS: Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

Perioperative Management and Factors Associated With Transfusion in Cranial Vault Reconstruction.

BACKGROUND: Bleeding is the most common adverse event in patients undergoing cranial vault reconstruction. The authors compare the transfusion rates against a national sample to determine whether the patients experience lower transfusion rates. METHODS: The authors queried the Pediatric National Surgical Quality Improvement Program (Peds-NSQIP) for patients who underwent cranial vault reconstruction (CPT 61559) and compared them to patients who underwent cranial vault reconstruction for sagittal craniosynostosis at Children's Hospital and Medical Center (CHMC) in Omaha, Nebraska. Patients over the age of 24 months were excluded. Binary logistic regression analysis was performed using IBM-SPSS v24.0 to determine factors associated with transfusion at CHMC. RESULTS: Patient demographics, preoperative hematocrit and platelet counts, readmission rates, and reoperation rates did not differ between CHMC (N = 54) and Peds-NSQIP (N = 1320) cohorts. Patients in the CHMC cohort had shorter preincision anesthesia times (47 versus 80 minutes, P < 0.001), shorter operative times (108 versus 175 minutes, P < 0.001), lower transfusion rates (50% versus 73%, P < 0.001), and smaller mean transfusion volumes (16 versus 33 mL/kg, P < 0.001); however mean length of stay was longer (4.1 versus 3.6 days, P < 0.001). Factors independently associated with transfusion at CHMC included preoperative hematocrit (odds ratio [OR] 0.423, P = 0.002), administration of an antifibrinolytic agent (OR 0.004, P = 0.001) and temperature at the time of incision (OR 0.020, P = 0.043). CONCLUSION: Patients at CHMC require less transfused blood and experience low transfusion rates. Preoperative hematocrit, administration of antifibrinolytic agents, and temperature at the time of incision are all modifiable factors associated with perioperative transfusion.

Risk factors for anastomotic leak after esophagectomy for cancer: A NSQIP procedure-targeted analysis.

BACKGROUND: Anastomotic leak is the most common major complication after esophagectomy. We investigated the 2016 American College of Surgeons National Surgical Quality Improvement Program esophagectomy targeted database to identify risk factors for anastomotic leak. METHODS: Patients who underwent esophagectomy for cancer were included. Patients experiencing an anstomotic leak were identified, and univariate and multivariable logistic regression was performed to identify variables independently associated with anastomotic leak. RESULTS: Of 915 patients included, 83% were male and the median age was 64 years. Patients with anastomotic leak more frequently had additional complications (87% vs 36%, P < .001). Rates of reoperation (64% vs 11%, P < .001) and mortality (8% vs 2%, P = .001) were higher in patients with anastomotic leak. After adjusting for patient and procedure characteristics, prolonged operative time (for each additional 30-minutes; adjusted odds ratios (AOR) 1.068, 95% CI, 1.022-1.115, P = .003), increased preoperative WBC count (for each 3000/µL increase; AOR 1.323, 95% CI, 1.048-1.670, P = .019), pre-existing diabetes (AOR 1.601, 95% CI, 1.012-2.534, P = .045), and perioperative transfusion (AOR 1.777, 95% CI, 1.064-2.965, P = .028) were independently associated with anastomotic leak. CONCLUSION: Both patient and procedure-related factors are associated with anastomotic leak. Though frequently non-modifiable, these findings could facilitate risk stratification and early detection of anastomotic leak to reduce associated morbidity.

Factors Predictive of Reoperation After Pancreaticoduodenectomy for Pancreatic Cancer.

While mortality is low, morbidity remains high for patients undergoing pancreas resections, especially for those who return to the operating room (RTOR). The aim of this study is to identify risk factors for RTOR following pancreaticoduodenectomy (PD) for ductal adenocarcinoma. Logistic regression models were constructed using the 2014 and 2015 National Surgical Quality Improvement Program (NSQIP) Pancreas Targeted database. Preoperative and procedure-related risk factors predictive of RTOR for patients undergoing either classic or pylorus-preserving pancreaticoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) were identified. A total of 1736 patients were included. Multivariable analysis of patients undergoing classic PD demonstrated that an abnormally low preoperative WBC count was significantly associated with RTOR (OR 2.78, 95% CI 1.27-6.06, p = 0.010). For patients who underwent pylorus-preserving PD, the wound classification (OR 3.99, 95% CI 1.75-9.11, p = 0.001) and arterial resection (OR 26.3, 95% CI 7.96-87.20, p < 0.001) were associated with a higher rate of RTOR. When analyzing both approaches (classic and pylorus-preserving PD) together, only isolated arterial (OR 9.98, 95% CI 3.81-26.18, p < 0.001) and isolated venous (OR 1.79, 95% CI 1.05-3.05, p = 0.032) resections were independently associated with RTOR. The results of our study demonstrate that few factors are predictive of RTOR. Knowledge of these few variables in combination with a focus on the components of medical care in the immediate postoperative period may help identify individuals at risk for RTOR and improve patient care.

Utilizing cell line-derived organoids to evaluate the efficacy of a novel LIFR-inhibitor, EC359 in targeting pancreatic tumor stroma.

Survival of pancreatic cancer (PC) patient is poor due to lack of effective treatment modalities, which is partly due to the presence of dense desmoplasia that impedes the delivery of chemotherapeutics. Therefore, PC stroma-targeting therapies are expected to improve the efficacy of chemotherapeutics. However, in vitro evaluation of stromal-targeted therapies requires a culture system which includes components of both tumor stroma and parenchyma. We aim to generate a cell line-derived 3D organoids to test the efficacy of stromal-targeted, LIFR-inhibitor EC359. Murine PC (FC1245) and stellate (ImPaSC) cells were cultured to generate organoids that recapitulated the histological organization of PC with the formation of ducts by epithelial cells surrounded by activated fibroblasts, as indicated by CK19 and α-SMA staining, respectively. Analysis by qRT-PCR demonstrated a significant downregulation of markers of activated stroma, POSTN, FN1, MMP9, and SPARC (p<0.0001), when treated with gemcitabine in combination with EC359. Concurrently, collagen proteins including COL1A1, COL1A2, COL3A1, and COL5A1 were significantly downregulated (p <0.0001) after treatment with gemcitabine in combination with EC359. Overall, our study demonstrates the utility of cell lines-derived 3D organoids to evaluate the efficacy of stroma-targeted therapies as well as the potential of EC359 to target activated stroma in PC.

Prolonged non-operative management of clostridium difficile colitis is associated with increased mortality, complications, and cost.

BACKGROUND: We aim to investigate the effects of delaying surgery on outcomes and cost in patients admitted with severe clostridium difficile infection (CDI). METHODS: 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. RESULTS: 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). CONCLUSIONS: Early surgical intervention in appropriately selected patients should be considered when there is a high suspicion for prolonged non-operative treatment.

Morbidity and Mortality Rates Following Cytoreductive Surgery Combined With Hyperthermic Intraperitoneal Chemotherapy Compared With Other High-Risk Surgical Oncology Procedures.

Importance: Currently, rates of referral of patients with peritoneal metastasis in the United States who qualify for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) are low, in part because of the misperception of high morbidity and mortality rates. However, patients requiring major gastrointestinal surgical procedures with similar complication rates are routinely referred. Objective: To evaluate the relative safety of CRS/HIPEC. Design, Setting, and Participants: Retrospective cohort study of 34 114 patients who underwent CRS/HIPEC, right lobe hepatectomy, trisegmental hepatectomy, pancreaticoduodenectomy, and esophagectomy between January 1, 2005, and December 31, 2015, included in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database. Data analysis was performed in 2018. Main Outcomes and Measures: Data from the NSQIP database were used to compare perioperative and 30-day postoperative morbidity and mortality rates of CRS/HIPEC (1822 patients) with other, well-accepted, high-risk surgical oncology procedures: right lobe hepatectomy (5109 patients), trisegmental hepatectomy (2449 patients), pancreaticoduodenectomy (Whipple) (16 793 patients), and esophagectomy (7941 patients). Results: For 34 114 patients, median (interquartile range [IQR]) age was 63 (55-71) years and 42% were female. Patients undergoing CRS/HIPEC tended to be younger, with a median age of 57 years, and esophagectomy had the highest median (IQR) American Society of Anesthesiologists classification (3 [3-3]). When compared with CRS/HIPEC, higher complication rates were reported in the following categories: (1) superficial incisional infection in Whipple and esophagectomy (5.4% [95% CI, 4.4%-6.4%] vs 9.7% [95% CI, 9.3%-10.1%] and 7.2% [95% CI, 6.6%-7.8%], respectively; P < .001); (2) deep incisional infection in Whipple (1.7% [95% CI, 1.1%-2.3%] vs 2.7% [95% CI, 2.5%-2.9%]; P < .01); (3) organ space infection in right lobe hepatectomy (7.2% [95% CI, 6.0%-8.4%] vs 9.0% [95% CI, 8.2%-9.8%]; P = .02), trisegmental hepatectomy (12.4% [95% CI, 11.1%-13.7%]; P < .001), and Whipple (12.9% [95% CI, 12.4%-13.4%]; P < .001); and (4) return to the operating room for esophagectomy (6.8% [95% CI, 5.6%-8.0%] vs 14.4% [95% CI, 13.6%-15.2%]; P < .001). Median (IQR) length of hospital stay was lower in CRS/HIPEC (8 [5-11] days) than Whipple (10 [7-15] days) and esophagectomy (10 [8-16] days) (P < .001). Overall 30-day mortality was lower in CRS/HIPEC (1.1%; 95% CI, 0.6%-1.6%) compared with Whipple (2.5%; 95% CI, 2.3%-2.7%), right lobe hepatectomy (2.9%; 95% CI, 2.4%-3.4%), esophagectomy (3.0%; 95% CI, 2.6%-3.4%), and trisegmental hepatectomy (3.9%; 95% CI, 3.1%-4.7%) (P < .001). Conclusions and Relevance: Comparative analysis revealed CRS/HIPEC to be safe, often safer across the spectrum of NSQIP safety metrics when compared with similar-risk oncologic procedures. Patient selection was important in achieving observed outcomes. High complication rates are a misperception from early CRS/HIPEC experience and should no longer deter referral of patients to experienced centers or impede clinical trial development in the United States.

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.

No survival advantage exists for patients undergoing loop ileostomy for clostridium difficile colitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: No mortality difference was observed between LI and TAC. Prospective studies are required to determine the utility of LI. SUMMARY: 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.

Pneumoperitoneum.

Pneumoperitoneum has a wide differential diagnosis and presents with varying degrees of severity; however, not all etiologies require operative intervention. It is imperative that all patients with this diagnosis are evaluated by a surgeon. A thorough history, physical examination, and workup, aimed at localization of the source of pneumoperitoneum will ultimately determine the necessary treatments, including the need for operative intervention. We aim to provide the reader with a working knowledge regarding the evaluation and treatment of patients with pneumoperitoneum.