A Staphylococcal Glucosaminidase Drives Inflammatory Responses by Processing Peptidoglycan Chains to Physiological Lengths.

The peptidoglycan of Staphylococcus aureus is a critical cell envelope constituent and virulence factor that subverts host immune defenses and provides protection against environmental stressors. Peptidoglycan chains of the S. aureus cell wall are processed to characteristically short lengths by the glucosaminidase SagB. It is well established that peptidoglycan is an important pathogen-associated molecular pattern (PAMP) that is recognized by the host innate immune system and promotes production of proinflammatory cytokines, including interleukin-1ß (IL-1ß). However, how bacterial processing of peptidoglycan drives IL-1ß production is comparatively unexplored. Here, we tested the involvement of staphylococcal glucosaminidases in shaping innate immune responses and identified SagB as a mediator of IL-1ß production. A ΔsagB mutant fails to promote IL-1ß production by macrophages and dendritic cells, and processing of peptidoglycan by SagB is essential for this response. SagB-dependent IL-1ß production by macrophages is independent of canonical pattern recognition receptor engagement and NLRP3 inflammasome-mediated caspase activity. Instead, treatment of macrophages with heat-killed cells from a ΔsagB mutant leads to reduced caspase-independent cleavage of pro-IL-1ß, resulting in accumulation of the pro form in the macrophage cytosol. Furthermore, SagB is required for virulence in systemic infection and promotes IL-1ß production in a skin and soft tissue infection model. Taken together, our results suggest that the length of S. aureus cell wall glycan chains can drive IL-1ß production by innate immune cells through a previously undescribed mechanism related to IL-1ß maturation.

Comparing Patient Selection and 30-day Outcomes Between Single Anastomosis Gastric Bypass and Roux-en-Y Gastric Bypass: a Retrospective Cohort Study of 47,384 Patients.

PURPOSE: Single anastomosis gastric bypass (SAGB) offers a novel bariatric procedure with increasing popularity. However, its adoption, patient selection, and short-term safety remain poorly characterized. MATERIALS AND METHODS: The 2020 Metabolic and Bariatric Accreditation and Quality Improvement Program (MBSAQIP) was analyzed comparing SAGB to Roux-en-Y gastric bypass (RYGB). Bivariate analysis and multivariable logistic regression models compared difference between groups and factors associated with 30-day serious complications and mortality. RESULTS: Overall, 47,384 patients were evaluated, with 1344 (2.8%) undergoing SAGB. SAGB patients had a higher BMI (45.2 ± 7.6 kg/m2 vs 44.6 ± 7.9 kg/m2, p = 0.006) and younger age (44.3 ± 12.1 years vs. 45.4 ± 11.5 years, p = 0.0008) than RYGB patients respectively. SAGB patients were less likely to have GERD (42.6% SAGB vs. 45.7% RYGB, p = 0.02), sleep apnea (37.8% SAGB vs. 41.1% RYGB, p = 0.02), and chronic steroid use (1.3% SAGB vs. 2.2% RYGB, p = 0.04). There were no significant difference in diabetes, hypertension, or dyslipidemia rates. Operative length for SAGB was significantly less than for RYGB (101 ± 53.7 min SAGB vs. 131.5 ± 63.3 min RYGB, p < 0.0001). SAGB was independently associated with decreased serious complications (4.7% vs. 8.4%, p < 0.0001) within 30 days compared to RYGB. Additionally, SAGB patients were less likely to experience reoperation (1.6% vs. 2.6%, p = 0.03), and readmission (2.2 vs. 5.8%, p < 0.0001) compared to RYGB respectively. CONCLUSIONS: Compared to RYGB, patients undergoing SAGB were younger with marginally higher BMI. After adjusting for comorbidities, SAGB was associated with decreased odds of serious complications. Ongoing prospective studies analyzing long-term outcomes following SAGB remain needed.

The plant streptolysin S (SLS)-associated gene B confers nitroaromatic tolerance and detoxification.

Nitroaromatic compounds, as the important chemical feedstock, have caused widespread environmental contaminations, and exhibited high toxicity and mutagenic activity to nearly all living organisms. The clean-up of nitroaromatic-contaminated soil and water has long been a major international concern. Here, we uncovered the role of a novel nitroreductase family gene, streptolysin S (SLS)-associated gene B (SagB), in enhancing nitroaromatic tolerance and detoxification of plants, and its potential application in phytoremediation of nitroaromatic contaminations. The expression of both the Arabidopsis and rice SagB genes is significantly induced by multiple hazardous nitroaromatic substances, including explosive pollutant 2,4,6-trinitrotoluene (TNT), natural compound 1-nitropyrene (1-NP) and herbicide pendimethalin (Pen). In vitro and in vivo evidences revealed that plant SagBs possess activities in degradation of these nitroaromatic substances. Arabidopsis and rice transgenic assays suggested that plant SagB genes increase tolerance and detoxification of nitroaromatic through facilitating its transformation to the amino derivative. More importantly, overexpression of plant SagBs increase their ability in TNT uptake, and remove more TNT from the growth culture. Our findings shed novel insights into a plant endogenous nitroreductase-mediated nitroaromatic tolerance and detoxification, and provide a new gene target for phytoremediation of nitroaromatic-contaminated environments.

Measuring the small bowel length may decrease the incidence of malnutrition after laparoscopic one-anastomosis gastric bypass with tailored bypass limb.

BACKGROUND: Laparoscopic one (single)-anastomosis gastric bypass (OAGB) is an effective and durable treatment for morbidly obese patients. However, the ideal length of the small bowel bypass remains controversial. OBJECTIVES: The study aimed to report the clinical results of using a tailored bypass based on the total length of the small bowel. SETTING: Academic medical center. METHODS: Since 2005, we have performed OAGB with tailored limb according to preoperative body mass index. From July 2014, we modified our technique, measuring the whole small bowel length to keep the common channel at least 400-cm long. Data from 470 patients treated with the new technique (Group II) were compared with those of a matched group treated with tailored bypass only (Group I). The preoperative clinical data and outcomes were analyzed. All clinical data were prospectively collected and stored. RESULTS: Both groups had similar clinical profiles at baseline. All procedures were completed laparoscopically. Group II had a significant longer operation time (161.9 versus 122.6 min; P < .001), but shorter hospital stay (2.9 versus 5.3 d; P < .001) and lower complication rate (.2% versus 1.5%; P = .002) than Group I. One year after surgery, the mean body mass index (27.4 versus 26.8 kg/m2; P = .244), percent total weight loss (32.0% versus 34.0%; P = .877), and diabetes remission rate (84.7% versus 84.1%; P = .876) were comparable between the 2 groups. However, Group II patients had a significantly lower incidence of anemia (5.9% versus 11.1%; P < .001), secondary hyperparathyroidism (21.7% versus 33.8%; P < .001) and hypoalbuminemia (1.5% versus 2.8%; P < .001) than did Group I. CONCLUSION: Routine measurement of the whole bowel length to keep the common channel at least 400-cm long may reduce the incidence of malnutrition after OAGB with tailored limb bypass, without compromising efficacy in weight loss and diabetes resolution.

Laparoscopic gastric bypass for the treatment of type 2 diabetes: a comparison of Roux-en-Y versus single anastomosis gastric bypass.

BACKGROUND: In recent years, gastric bypass surgery has been found to have therapeutic potential for the treatment of type 2 diabetes (T2D). However, the difference between 2 bypass procedures, Roux-en-Y gastric bypass (RYGB) and another single anastomosis gastric bypass (SAGB), is not clear. OBJECTIVE: To evaluate the differences between SAGB and RYGB in the efficacy of T2D remission in obese patients. SETTING: Tertiary teaching hospital. METHODS: Outcomes of 406 (259 women and 147 male) patients who had undergone RYGB (157) or SAGB (249) for the treatment of T2D with 1-year follow-up were assessed. The remission of T2D after surgery was evaluated in matched groups, including body mass index (BMI) and the ABCD scoring system, which comprises patient age, BMI, C-peptide levels, and duration of T2D (yr). RESULTS: The weight loss of the SAGB patients at 1 year after surgery was better than the RYGB patients (24.1% [8.4%] versus 30.7% [8.7%]; P<.001). The mean BMI decreased from 39.9 (8.0) to 27.4 (4.6) kg/m2 in SAGB patients at 1 year after surgery and decreased from 34.5 (6.6) to 26.2 (4.2) kg/m2 in the RYGB patients. The mean glycated hemoglobin A1C (HbA1C) decreased from 8.6% to 6.2% of the RYGB group and from 8.6% to 5.5% of the SAGB group. Eighty-seven (55.4%) patients of the RYGB group and 204 (81.9%) of the SAGB group achieved complete remission of T2D (HbA1C<6.0%) at 1 year after surgery (P<.001). SAGB exhibited significantly better glycemic control than RYGB surgery in selected groups stratified by different BMI and ABCD score. At 5 years after surgery, SAGB still had a better remission of T2D than RYGB (70.5% versus 39.4%; P = .002). Multivariate analysis confirms that both SAGB and ABCD score are independent predictors of T2D remission after bypass surgery. CONCLUSIONS: Both RYGB and SAGB are effective metabolic surgery. SAGB carries a higher power on T2D remission than RYGB in a small group of patients. ABCD score is useful in T2D patient classification and selection for different procedures.

Short-Term Results of Revisional Single-Anastomosis Gastric Bypass After Sleeve Gastrectomy for Weight Regain.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) has become the most performed bariatric procedure as of 2015. However, inadequate weight loss may present the need for revisional procedures. OBJECTIVES: The objective of this study was to analyze the efficacy of single-anastomosis gastric bypass (SAGB) in attaining successful weight loss following an initial LSG. METHODS: A retrospective analysis was performed on all patients who underwent LSG at Amiri Hospital, Kuwait from 2008 to 2017. A list was obtained of those who underwent revisional SAGB surgery after initial LSG, and their demographics were analyzed. RESULTS: A total of 31 patients underwent revisional SAGB bariatric surgery after initial LSG, of which 87.1% were female. Prior to LSG, the mean weight of the patients was 127.5 kg and the mean BMI was 49.0 kg/m2. The mean weight loss after initial LSG was 43.8 kg, while the average duration until patients underwent revisional SAGB was 5.1 years. The cause for revision was weight regain (86.2%), inadequate weight loss (10.3%), or the development of a complication (reflux) (6.5%). Prior to undergoing revisional SAGB, the weight and BMI of the patients were 110.9 kg and 42.6 kg/m2, respectively. This demonstrated a %excess weight loss of 14.5, 31.9, 48.0, and 58.9% 2 weeks, 3 months, 6 months, and 1-year post-SAGB, respectively. Three (10.3%) morbidities were reported and thereafter successfully resolved. CONCLUSION: Revisional SAGB bariatric surgery is a safe and effective method in the short-term basis for the management of inadequate primary LSG.

A 12-Month Review of Revisional Single Anastomosis Gastric Bypass for Complicated Laparoscopic Adjustable Gastric Banding for Body Mass Index over 35.

BACKGROUND: In many countries, laparoscopic adjustable gastric banding (LAGB) was previously the most commonly performed bariatric procedure due to its operative safety and early efficacy. This procedure is now superseded because of doubtful long-term results and late complications. Many people eventually required revisional bariatric surgery such as conversion to single anastomosis gastric bypass (SAGB). This study aims to assess the safety and durability of single-stage conversion from LAGB to SAGB in patients who are intolerant to LAGB and who also fail to lose weight, or re-gain weight. METHODS: Seventy-four patients with BMI > 35 kg m-2 were selected from a prospective bariatric database between July 2012 and December 2015 for revisional laparoscopic SAGB surgery and were followed up at 6 weeks, 3, 6 and 12 months after their operation. RESULTS: The mean BMI at 6 weeks, then 3, 6 and 12 months were 41.6 ± 7.66, 38.8 ± 7.54, 35.4 ± 7.10 and 33.2 ± 7.34 kg m-2, respectively. The mean percentage EWL at 6 weeks then 3, 6 and 12 months were 21.0 ± 9.12, 37.8 ± 12.5, 55.1 ± 15.8 and 67.0 ± 19.6%, respectively. Postoperative follow-up at these times were 97, 85, 69 and 46%, respectively. Early (< 30 day) morbidity was 20.3% with major complications of CD grade 3a or more of 13.5%. CONCLUSIONS: This study demonstrates that single-stage revisional SAGB after a failed LAGB achieved good short-term weight loss and low 30-day morbidity.