Evaluating the incidence, risk factors and postoperative complications associated with leaks following duodenal switch procedures: an analysis of the MBSAQIP.

BACKGROUND: Metabolic and Bariatric Surgery (MBS) is the most effective management for patients with obesity and weight-related medical conditions. Duodenal switch (DS) is a recent MBS procedure with increasing attention in recent years, however the risk of anastomotic or staple line leaks and the lack of efficient surgical expertise hinders the procedure from becoming fully adopted. OBJECTIVES: To determine the 30-day predictors of leaks following DS and explore their association with other 30-day postoperative complications. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. METHODS: Patients who underwent a primary biliopancreatic diversion with DS or single-anastomosis duodenoileostomy with sleeve procedure, categorized as DS, were assessed for 30-day leaks. A multivariable logistic regression was constructed to identify the predictors of leaks. The assessment of postoperative complications arising from leaks was also performed. RESULTS: A total of 21,839 DS patients were included, of which 177 (.8%) experienced leaks within 30 postoperative days. The most significant predictor of leaks was steroid immunosuppressive use (adjusted odds ratio [aOR] = 3.01, 95% confidence interval [CI] [1.56-5.13], P < .001) and age, with each decade of life associated with a 26% increase in risk (aOR = 1.26, 95% CI [1.09-1.45], P = .001). Operative length was also associated with leaks, with every additional 30 minutes increasing the odds of a leak by 23% (aOR = 1.23, 95% CI [1.18-1.29], P < .001). The occurrence of leaks was correlated with postoperative septic shock (Crude Odds Ratio [COR] = 280.99 [152.60-517.39]) and unplanned intensive care unit (ICU) admissions (COR = 79.04 [56.99-109.59]). Additionally, mortality rates increased 17-fold with the incidence of leaks (COR = 17.64 [7.41-41.99]). CONCLUSIONS: Leaks following DS are a serious postoperative complication with significant risk factors of steroid use, prolonged operative time and advanced age. Leaks are also associated with other severe complications, highlighting the need for early diagnosis and intervention along with additional studies to further validate our results.

ß-Cell-selective regulation of gene expression by nitric oxide.

Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It is through the inhibition of mitochondrial oxidative metabolism, specifically aconitase and complex 4 of the electron transport chain, that nitric oxide inhibits insulin secretion. Nitric oxide also attenuates protein synthesis, induces DNA damage, activates DNA repair pathways, and stimulates stress responses (unfolded protein and heat shock) in ß-cells. In this report, the time- and concentration-dependent effects of nitric oxide on the expression of six genes known to participate in the response of ß-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and Ppargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates ß-cell gene expression in a narrow concentration range of ∼0.5-1 µM or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in ß-cells, and this is associated with the inhibition of mitochondrial oxidative metabolism. This narrow concentration range of responses is ß-cell selective, as the actions of nitric oxide in non-ß-cells (α-cells, mouse embryonic fibroblasts, and macrophages) are concentration dependent. Our findings suggest that ß-cells respond to a narrow concentration range of nitric oxide that is consistent with the levels produced following iNOS induction, and that these concentration-dependent actions are selective for insulin-containing cells.

American Society for Metabolic and Bariatric Surgery 2022 estimate of metabolic and bariatric procedures performed in the United States.

BACKGROUND: Metabolic and bariatric surgery (MBS), despite being the most effective durable treatment for obesity, remains underused as approximately 1% of all qualified patients undergo surgery. The American Society for Metabolic and Bariatric Surgery established a Numbers Taskforce to specify the annual rate of obesity treatment interventions utilization and to determine if patients in need are receiving appropriate treatment. OBJECTIVE: To provide the best estimated number of metabolic and bariatric procedures being performed in the United States in 2022. SETTING: United States. METHODS: We reviewed data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and National Surgical Quality Improvement Program. In addition, data from industry and state databases were used to estimate activity at non-accredited centers. Data from 2022 were compared mainly with data from the previous 2 years. RESULTS: Compared with 2021, the total number of MBS performed in 2022 increased from approximately 262,893 to 280,000. The sleeve gastrectomy (SG) continues to be the most commonly performed procedure. The gastric bypass procedure trend remained relatively stable. The percentage of revision procedures and biliopancreatic diversion with duodenal switch procedures increased slightly. Intragastric balloon placement increased from the previous year. Endoscopic sleeve gastroplasty increased in numbers. CONCLUSIONS: There was a 6.5% increase in MBS volume from 2021 to 2022 and a 41% increase from 2020, which demonstrates a recovery from the COVID-19 pandemic. SG continues to be the most dominant MBS procedure.

Tourniquet Use in Extremity-Based Microsurgery.

BACKGROUND: The use of tourniquets and their role in extremity-based microsurgery has not been thoroughly investigated. The purpose of this study was to investigate tourniquet use and its associated outcomes and complications. The authors hypothesize that tourniquets enhance visualization, bloodless approaches to vessel harvest, flap elevation, and anastomosis without added complications. METHODS: A retrospective chart review was completed for patients who had undergone extremity-based microsurgery with the use of a tourniquet between January 2018 and February 2022 at two large academic institutions. Demographic characteristics, initial reasons for surgery, complications, and outcomes were recorded. Patients were separated into groups based on tourniquet use during three operative segments: (1) flap elevation, (2) vessel harvest, and (3) microvascular anastomosis. An internal comparison of complication rate was performed between cases for which a tourniquet was used for one operative segment to all cases in which it was not used for the same operative segment. Univariate and multivariate statistical analyses were performed to identify statistically significant results. RESULTS: A total of 99 patients (106 surgeries) were included in this study across sites. The mean age was 41.2 years and 67.7% of the patients were male. The most common reason for microsurgical reconstruction was trauma (50.5%). The need for an additional unplanned surgery was the most common surgical complication (16%). A total of 70, 61, and 32% of procedures used a tourniquet for flap elevation, vessel harvest, and for anastomosis, respectively. Statistical analyses identified no difference in complication rates for procedures for which a tourniquet was or was not used for interventions. CONCLUSION: Based on these results, the authors state that tourniquets can be utilized for extremity-based microsurgery to enable bloodless dissection without the concern of increased complication rates.

Third time's a charm: band to sleeve to bypass.

BACKGROUND: Adjustable gastric bands (AGB) are frequently converted to sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) due to weight recurrence or band complications. Such conversions carry a higher-risk than primary procedures. Some patients undergo two conversions-from AGB to SG, and subsequently from SG to RYGB. This presents a unique situation with limited literature on indications and complication rates associated with these double conversions. METHODS: We examined the 2020-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use File to evaluate conversions from AGB to SG and then to RYGB. Patient and operative characteristics, along with outcomes, were evaluated. Descriptive statistics were applied. RESULTS: We identified 276 patients who underwent a conversion from AGB to SG and then to RYGB. The primary reason for the second conversion (SG to RYGB) was gastroesophageal reflux disease (GERD) at 55.1%, followed by inadequate weight loss or weight regain (IWL/WR) at 36.9%. The remaining reasons included dysphagia, nausea, vomiting, or others. Patients converted for IWL/WR demonstrated a higher baseline body mass index and prevalence of sleep apnea compared to other cohorts (both p < 0.001). Meanwhile, patients in the "other reasons" group had the highest rate of open surgical approaches (9.1%) and concurrent lysis of adhesions (p = 0.001 and p = 0.022), with correspondingly higher rates of anastomotic leak, reoperations, serious complications, and mortality. CONCLUSIONS: Patients undergoing double conversions (AGB to SG to RYGB) do so primarily for GERD or IWL/WR. Further research is required to better define the optimal primary operation for each patient, aiming to reduce the necessity for multiple conversions.

MBSAQIP database: are the data reliable?

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database collects data from all accredited centers in the US. A prior study showed data quality issues limiting use of up to 20% of the 2015 database. OBJECTIVES: To evaluate the completeness and data quality (internal validity, accuracy, and consistency) of the MBSAQIP database between 2015 and 2019. SETTING: United States. METHODS: All subsets of data from the MBSAQIP Participant User Data File (PUDF) were compiled into one main file. Completeness, internal validity, accuracy, and consistency were evaluated. Completeness was determined via missing values. Internal validity was assessed using the percentage of patients with a body mass index (BMI) < 30 kg/m2 who underwent primary bariatric surgery. Accuracy was evaluated using reported versus calculated BMI. Consistency was assessed using the percentage of patients with a gain of >5 or a loss of >20 units of BMI change in 30 days. Effects across years were assessed using a chi-squared test. RESULTS: Missing data for age, BMI, and ASA was consistently low (<2.5%) with no significant difference across years. Only .02% of patients who underwent a primary bariatric procedure had a reported BMI <30 kg/m2. The mean difference between reported versus calculated BMI was -.02 units. A maximum of .33% of patients gained >5 units of BMI, and a maximum of .85% of patients lost > 20 units of BMI in early follow-up. CONCLUSIONS: While the MBSAQIP is a database with acceptable data quality and minimal changes from 2015-2019, ongoing efforts are needed to improve data.

Early Bowel Obstruction after Bariatric Surgery: An Analysis of the 2020-2021 MBSAQIP Database.

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program evaluates 30-day outcomes of bariatric cases performed in the United States. The Participant Use File in 2020 introduced bowel obstruction (BO). We compared the rates of BO, risk factors, and postoperative outcomes after laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and duodenal switch (DS). METHODS: Retrospective analysis of patients who underwent laparoscopic RYGB, SG, or DS obtained from the 2020-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. Patients who underwent either as a primary procedure with a body mass index >35 kg/m 2 were selected. Baseline characteristics, operative details, and postoperative complications were collected. The outcome of interest was BO occurring within 30 days. RESULTS: A total of 205,533 cases of which 148,944 were SG (72.4%), 54,606 were RYGB (26.5%), and 1983 were DS (1%). BO occurred in 0.74%, 0.4%, and 0.03% of patients who underwent an RYGB, DS, or SG, respectively. Patients with a BO in the RYGB group were more likely to be on immunosuppressive therapy (5.4% vs. 1.9%, P <0.001) with longer operative time (136.2 min±58.0 min vs. 117.4 min±53.6 min, P <0.001). SG patients with a BO were older (47.5±13.6 vs. 41.9±11.6, P =0.011) with longer operating times (98.6±63.8 vs. 68.9±33.4, P =0.002). Patients in the RYGB group with a BO had the highest rates of readmissions (71.9%) and reoperations (58.4%). CONCLUSIONS: Early bowel obstruction is rare after bariatric surgery. It is more common after RYGB and least common after SG. Readmission and reoperation rates were highest in patients with BO in the RYGB group.

When do leaks occur? An analysis of the metabolic and bariatric surgery accreditation and quality improvement program.

BACKGROUND: Leak is a feared complication of bariatric surgeries. Time to presentation is important in their management. We used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to evaluate the rate and timing of leaks. OBJECTIVES: To determine when leaks present after bariatric surgery. SETTING: MBSAQIP database. METHODS: The MBSAQIP Participant Use Files (PUF) for the years 2015-2020 were evaluated. Outcomes of interest were "organ space infection" and "leak." We evaluated the time to presentation for these variables as well as patient characteristics, operative time, complication rates and 30-day outcomes. RESULTS: There were 370,369 sleeve gastrectomies (SG) and 159,280 Roux-en-Y gastric bypasses (RYGB). We identified 598 (.16%) SG leaks with an average time to presentation of 13.2 ± 7.8 days. For RYGB, there were 520 leaks (.32%) with an average time to presentation of 9.5 ± 7.4 days. Both procedures had longer operative times for the patients with leak; RYGB was 115 minutes versus 131 minutes and SG was 67 minutes versus 77 minutes (both P < .01). SG and RYGB patients with a leak had a higher relative risk (RR) of grade 4 and 5 Clavien-Dindo complication rates. RR of mortality rates in SG patients with leak was 35.2 (confidence interval (CI): 20-61) and in RYGB with leak was 31.4 (CI: 19-50). CONCLUSIONS: The length of time for SG leak presentation was more delayed than RYGB leak presentation. Surgeons should be vigilant for leaks for at least 3 weeks after surgery. Leaks increase the mortality rate and overall serious complications.

ß-cell-selective inhibition of DNA damage response signaling by nitric oxide is associated with an attenuation in glucose uptake.

Nitric oxide (NO) plays a dual role in regulating DNA damage response (DDR) signaling in pancreatic ß-cells. As a genotoxic agent, NO activates two types of DDR signaling; however, when produced at micromolar levels by the inducible isoform of NO synthase, NO inhibits DDR signaling and DDR-induced apoptosis in a ß-cell-selective manner. DDR signaling inhibition by NO correlates with mitochondrial oxidative metabolism inhibition and decreases in ATP and NAD+. Unlike most cell types, ß-cells do not compensate for impaired mitochondrial oxidation by increasing glycolytic flux, and this metabolic inflexibility leads to a decrease in ATP and NAD+. Here, we used multiple analytical approaches to determine changes in intermediary metabolites in ß-cells and non-ß-cells treated with NO or complex I inhibitor rotenone. In addition to ATP and NAD+, glycolytic and tricarboxylic acid cycle intermediates as well as NADPH are significantly decreased in ß-cells treated with NO or rotenone. Consistent with glucose-6-phosphate residing at the metabolic branchpoint for glycolysis and the pentose phosphate pathway (NADPH), we show that mitochondrial oxidation inhibitors limit glucose uptake in a ß-cell-selective manner. Our findings indicate that the ß-cell-selective inhibition of DDR signaling by NO is associated with a decrease in ATP to levels that fall significantly below the KM for ATP of glucokinase (glucose uptake) and suggest that this action places the ß-cell in a state of suspended animation where it is metabolically inert until NO is removed, and metabolic function can be restored.

Effect of operative times in bariatric surgery on outcomes: a matched analysis of the MBSAQIP database.

BACKGROUND: The implications of operative time (OT) have been studied in different surgical specialties, showing a correlation with higher incidence rates of postoperative complications. However, the impact of OT on bariatric surgery complications is not well elucidated. METHODS: A retrospective review of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2015 and 2019 was performed. A total of 358,382 SG patients and 123,357 RYGB patients were included. The median OT was 68 min (10-720) and 113 min (10-640) for the sleeve gastrectomy (SG) group and the Roux-en-Y gastric bypass group, respectively. The groups were subdivided into two subgroups based on OT in comparison to the median time of each group. The subgroups were compared for surgical complications and outcomes. To reduce selection bias and risk of confounders, we performed a propensity score matching (PSM) for 22 variables. RESULTS: In the PSM-matched cohort, 18,915 SG and 6,495 RYGB patients were included in each subgroup. The SG cohort showed higher rates of Clavien-Dindo Class 1, 2, 3a, 4, and 5 complications as well as higher rates of readmission, reoperation, and reintervention in the longer OT group before matching. After PSM, the subgroup with longer times continued to have higher rates of Clavien-Dindo Class 2 complications and higher rates of readmission and reoperation. Similarly, there were higher rates of all Clavien-Dindo class complications as well as readmission, reoperation, and reintervention in the RYGB group with higher OT. After PSM, there were still higher rates of Clavien-Dindo Class 3a complications as well as readmission and reintervention in the RYGB subgroup with prolonged OT. CONCLUSION: In both SG and RYGB, longer OT was associated with increased rates of complications as well as readmission, reoperation, and reintervention. Surgeons should be cognizant of the increased rates of complications when operative times are longer.

One Anastomosis Gastric Bypass Versus Single Anastomosis Duodenoileostomy with Sleeve: Comparative Analysis of 30-Day Outcomes Using the MBSAQIP.

INTRODUCTION/PURPOSE: One anastomosis gastric bypass (OAGB) and single anastomosis duodenoileostomy with sleeve (SADI-S) are two highly effective bariatric procedures that have been recently endorsed by the American Society of Metabolic and Bariatric Surgery (ASMBS). We compared the outcomes and safety profiles of SADI-S and OAGB using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. MATERIALS AND METHODS: Retrospective analysis on patients who underwent SADI-S or OAGB obtained from the MBSAQIP database 2020-2021. Patients who underwent concurrent procedures (besides EGD) or had missing data were removed. Variables included age, sex, body mass index, American Society of Anesthesiologists (ASA) class, and pertinent medical comorbidities. Data were analyzed for 30-day postoperative morbidity, mortality, reoperation, reintervention, and readmissions. p values were calculated using Student's t-test or Fisher analysis. RESULTS: A total of 694 and 1068 patients respectively underwent SADI-S or OAGB. Statistically significant comorbidities included age (42.2 ± 10.8 vs. 43.7 ± 12.2), BMI (50.6 ± 9.1 vs. 45.3 ± 7.1), ASA 2 (66 (9.5%) vs. 165 (15.4%)), ASA 4 [69 (9.9%) vs. 20 (1.9%)], and immunosuppressive therapy [24 (3.5%) vs. 17 (1.6%)]. Clavien-Dindo-based analysis highlighted that SADI-S had higher grade 2 (p = 0.005) and grade 4b (p = 0.001) complications. Patients who underwent SADI-S were twice as likely to be readmitted within 30 days (3.7% vs. 1.9%; p = 0.021). CONCLUSION: SADI-S had higher readmission rates and higher Clavien-Dindo grade 2 and 4b complications. To note, SADI-S patients had higher BMIs. Further studies are needed to determine the long-term complications and efficacy of both operations.

Single-anastomosis duodenoileal bypass with sleeve in the United States: a first comparative safety analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database.

BACKGROUND: The single-anastomosis duodenoileal bypass with sleeve (SADI-S) is a relatively new bariatric procedure. In 2020, the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) started reporting outcomes for SADI-S. OBJECTIVES: We aimed to study the perioperative safety of SADI-S and compare it with other established bariatric procedures utilizing the MBSAQIP database. SETTING: Academic hospital, United States. METHODS: The 2020 MBSAQIP Participant Use File was used to evaluate SADI-S outcomes. We included SADI-S primary cases and excluded revisions and concurrent operations. A 5:1 propensity matched analysis (PMA) for 20 variables was performed to compare the outcomes of the SADI-S with the Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) and a 2:1 PMA to the biliopancreatic diversion with duodenal switch (BPD/DS). RESULTS: There were 255 primary SADI-S reported in 2020. After PMA, the only significant complications between the RYGB and SADI-S cohorts were Clavien-Dindo grade IVa and IVb (.1% and 1.4% versus 1.6% and 7.1%, respectively). SADI-S had more Clavien-Dindo grade II, IVa, and IVb complications than the SG cohort (1.3% versus 3.5%, P = .03; .2% versus 1.6%, P = 0; 1.% versus 7.1%, P = 0). When compared with BPD/DS, outcomes including readmission, reoperation, and intervention were not statistically significant. CONCLUSION: SADI-S, in its early adoption stage, has a higher incidence of perioperative complications than RYGB and SG. It has comparable 30-day outcomes to BPD/DS.

Duodenal switch without versus with laparoscopic cholecystectomy: a perioperative risk comparative analysis of the MBSAQIP database (2015-2019).

BACKGROUND: The results of concurrent cholecystectomy with Roux-en Y gastric bypass and sleeve gastrectomy have been well elucidated. Large-scale data on the outcomes of concomitant cholecystectomy during biliopancreatic diversion with duodenal switch (BPD-DS) are still lacking. Our study aimed to explore whether simultaneous cholecystectomy with BPD-DS alters the 30-day postoperative outcomes. METHODS: We conducted a retrospective analysis of the MBSAQIP database between 2015 and 2019. Propensity-score matching (PSM) in BPD-DS with cholecystectomy (Group 1) and BPD-DS without cholecystectomy (Group 2) cohorts was performed (PSM ratio 1:2). The two groups were matched for a total of 21 baseline variables including age, gender, BMI, ASA class, and other medical comorbidities and conditions. The 30-day postoperative morbidity, mortality, reoperation, reintervention, and readmissions were obtained. RESULTS: Initially, 568 patients in Group 1 and 5079 in Group 2 were identified. After performing PSM, 564 and 1128 patients respectively were compared. The BPD-DS with cholecystectomy group reported a higher rate of reoperation and reintervention compared to BPD-DS alone (3.9% versus 2.4% and 3.2% versus 2%, respectively), even though it did not reach statistical significance. The intervention time was significantly higher in Group 1 compared to Group 2 (192.4 ± 77.6 versus 126.4 ± 61.4 min). Clavien-Dindo complications (1-5) were similar between these two PSM cohorts. CONCLUSION: Concomitant cholecystectomy during BPD-DS increases operative times but does not affect the other outcomes. Based on our results, the decision of cholecystectomy at the time of BPD-DS should be left to the surgeon's judgment.

Duodenal switch versus Roux-en-Y gastric bypass: a perioperative risk comparative analysis of the MBSAQIP Database (2015-2019).

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD/DS) is a procedure that has long been considered to have a higher early postoperative morbidity than Roux-En-Y gastric bypass (RYGB). However, patients who undergo BPD/DS have more baseline co-morbidities that may affect the reported early postoperative morbidity. OBJECTIVE: To compare 30-day postoperative morbidity and mortality between BPD/DS and RYGB propensity score-matched cohorts obtained from the MBSAQIP database. SETTING: Analysis of data obtained from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. METHODS: Retrospective analysis of 21-variable propensity score-matched patients in the BPD/DS and RYGB groups obtained from the MBSAQIP database between 2015 and 2019. Variables included age, sex, body mass index, American Society of Anesthesiologists (ASA) class, and pertinent medical co-morbidities. Data were analyzed for 30-day postoperative morbidity, mortality, reoperation, reintervention, and readmissions. RESULTS: Before matching, RYGB and BPD/DS cohorts contained 134 188 and 5079 patients, respectively. After multivariable propensity score matching, each cohort contained 5050 patients. The RYGB group had a higher rate of surgical-site infections than the BPD/DS group (1% versus .5%, P = .007) and a higher rate of blood product transfusions (1.1% versus .6%, P = .018). The rate of other early postoperative complications was similar between the 2 groups (P > .05). There was no statistically significant difference in the 30-day mortality, readmission rate, reoperation rate, or reintervention rate between the 2 groups (P > .05). CONCLUSION: When matched for baseline body mass index and co-morbidities, BPD/DS does not lead to a higher 30-day postoperative morbidity and mortality than RYGB. Patients can be counseled that in the short term, BPD/DS is as safe as RYGB.

Suppressive neutrophils require PIM1 for metabolic fitness and survival during chronic viral infection.

The immune response to a chronic viral infection is uniquely tailored to balance viral control and immunopathology. The role of myeloid cells in shaping the response to chronic viral infection, however, is poorly understood. We perform single-cell RNA sequencing of myeloid cells during acute and chronic lymphocytic choriomeningitis virus (LCMV) infection to address this question. Our analysis identifies a cluster of suppressive neutrophils that is enriched in chronic infection. Furthermore, suppressive neutrophils highly express the gene encoding Proviral integration site for Moloney murine leukemia virus-1 (PIM1), a kinase known to promote mitochondrial fitness and cell survival. Pharmacological inhibition of PIM1 selectively diminishes suppressive neutrophil-mediated immunosuppression without affecting the function of monocytic myeloid-derived suppressor cells (M-MDSCs). Decreased accumulation of suppressive neutrophils leads to increased CD8 T cell function and viral control. Mechanistically, PIM kinase activity is required for maintaining fused mitochondrial networks in suppressive neutrophils, but not in M-MDSCs, and loss of PIM kinase function causes increased suppressive neutrophil apoptosis.

Intraoperative Airway Management Considerations for Adult Patients Presenting With Tracheostomy: A Narrative Review.

Tracheotomy is a surgical procedure through which a tracheostomy, an opening into the trachea, is created. Indications for tracheostomy include facilitation of airway management during prolonged mechanical ventilation, treatment of acute upper airway obstruction when tracheal intubation is unfeasible, management of chronic upper airway obstructive conditions, and planned airway management for major head and neck surgery. Patients who have a recent or long-term tracheostomy may present for a variety of surgical or diagnostic procedures performed under general anesthesia or sedation/analgesia. Airway management of these patients can be challenging and should be planned ahead of time. Anesthesia personnel should be familiar with the different components of cuffed and uncuffed tracheostomy devices and their connectivity to the anesthesia circuits. An appropriate airway management plan should take into account the indication of the tracheostomy, the maturity status of the stoma, the type and size of tracheostomy tube, the expected patient positioning, and presence of patient's concurrent health conditions. Management of the patient with a T-tube is highlighted. Importantly, there is a need for multidisciplinary care involving anesthesiologists, surgical specialists, and perioperative nurses. The aim of this narrative review is to discuss the anesthesia care of patients with a tracheostomy. Key aspects on relevant tracheal anatomy, tracheostomy tubes/devices, alternatives of airway management, and possible complications related to tracheostomy are summarized with a recommendation for an algorithm to manage intraoperative tracheostomy tube dislodgement.

Peroxiredoxin 1 plays a primary role in protecting pancreatic ß-cells from hydrogen peroxide and peroxynitrite.

Both reactive nitrogen and oxygen species (RNS and ROS), such as nitric oxide, peroxynitrite, and hydrogen peroxide, have been implicated as mediators of pancreatic ß-cell damage during the pathogenesis of autoimmune diabetes. While ß-cells are thought to be vulnerable to oxidative damage due to reportedly low levels of antioxidant enzymes, such as catalase and glutathione peroxidase, we have shown that they use thioredoxin reductase to detoxify hydrogen peroxide. Thioredoxin reductase is an enzyme that participates in the peroxiredoxin antioxidant cycle. Peroxiredoxins are expressed in ß-cells and, when overexpressed, protect against oxidative stress, but the endogenous roles of peroxiredoxins in the protection of ß-cells from oxidative damage are unclear. Here, using either glucose oxidase or menadione to continuously deliver hydrogen peroxide, or the combination of dipropylenetriamine NONOate and menadione to continuously deliver peroxynitrite, we tested the hypothesis that ß-cells use peroxiredoxins to detoxify both of these reactive species. Either pharmacological peroxiredoxin inhibition with conoidin A or specific depletion of cytoplasmic peroxiredoxin 1 (Prdx1) using siRNAs sensitizes INS 832/13 cells and rat islets to DNA damage and death induced by hydrogen peroxide or peroxynitrite. Interestingly, depletion of peroxiredoxin 2 (Prdx2) had no effect. Together, these results suggest that ß-cells use cytoplasmic Prdx1 as a primary defense mechanism against both ROS and RNS.

Can insulin secreting pancreatic ß-cells provide novel insights into the metabolic regulation of the DNA damage response?

Insulin, produced by pancreatic ß-cells, is responsible for the control of whole-body glucose metabolism. Insulin is secreted by pancreatic ß-cells in a tightly regulated process that is controlled by the serum level of glucose, glucose sensing and glucose oxidative metabolism. The regulation of intermediary metabolism in ß-cells is unique as these cells oxidize glucose to CO2 on substrate supply while mitochondrial oxidative metabolism occurs on demand, for the production of intermediates or energy production, in most cell types. This review discusses recent findings that the regulation of intermediary metabolism by nitric oxide attenuates the DNA damage response (DDR) and DNA damage-dependent apoptosis in a ß-cell selective manner. Specific focus is placed on the mechanisms by which iNOS derived nitric oxide (low micromolar levels) regulates DDR activation via the inhibition of intermediary metabolism. The physiological significance of the association of metabolism, nitric oxide and DDR signaling for cancer biology and diabetes is discussed.

SurfaceGenie: a web-based application for prioritizing cell-type-specific marker candidates.

MOTIVATION: Cell-type-specific surface proteins can be exploited as valuable markers for a range of applications including immunophenotyping live cells, targeted drug delivery and in vivo imaging. Despite their utility and relevance, the unique combination of molecules present at the cell surface are not yet described for most cell types. A significant challenge in analyzing 'omic' discovery datasets is the selection of candidate markers that are most applicable for downstream applications. RESULTS: Here, we developed GenieScore, a prioritization metric that integrates a consensus-based prediction of cell surface localization with user-input data to rank-order candidate cell-type-specific surface markers. In this report, we demonstrate the utility of GenieScore for analyzing human and rodent data from proteomic and transcriptomic experiments in the areas of cancer, stem cell and islet biology. We also demonstrate that permutations of GenieScore, termed IsoGenieScore and OmniGenieScore, can efficiently prioritize co-expressed and intracellular cell-type-specific markers, respectively. AVAILABILITY AND IMPLEMENTATION: Calculation of GenieScores and lookup of SPC scores is made freely accessible via the SurfaceGenie web application: www.cellsurfer.net/surfacegenie. CONTACT: Rebekah.gundry@unmc.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

The Role of Metabolic Flexibility in the Regulation of the DNA Damage Response by Nitric Oxide.

In this report, we show that nitric oxide suppresses DNA damage response (DDR) signaling in the pancreatic ß-cell line INS 832/13 and rat islets by inhibiting intermediary metabolism. Nitric oxide is known to inhibit complex IV of the electron transport chain and aconitase of the Krebs cycle. Non-ß cells compensate by increasing glycolytic metabolism to maintain ATP levels; however, ß cells lack this metabolic flexibility, resulting in a nitric oxide-dependent decrease in ATP and NAD+ Like nitric oxide, mitochondrial toxins inhibit DDR signaling in ß cells by a mechanism that is associated with a decrease in ATP. Non-ß cells compensate for the effects of mitochondrial toxins with an adaptive shift to glycolytic ATP generation that allows for DDR signaling. Forcing non-ß cells to derive ATP via mitochondrial respiration (replacing glucose with galactose in the medium) and glucose deprivation sensitizes these cells to nitric oxide-mediated inhibition of DDR signaling. These findings indicate that metabolic flexibility is necessary to maintain DDR signaling under conditions in which mitochondrial oxidative metabolism is inhibited and support the inhibition of oxidative metabolism (decreased ATP) as one protective mechanism by which nitric oxide attenuates DDR-dependent ß-cell apoptosis.