Weight loss outcomes for patients undergoing conversion to Roux-en-Y-gastric bypass after sleeve gastrectomy.

BACKGROUND: Despite excellent reported outcomes after laparoscopic sleeve gastrectomy (LSG), a percentage of patients go on to have a secondary bariatric surgery to manage side-effects or address weight regain after LSG. Reported weight loss outcomes for patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB) after previous LSG are variable. We sought to determine the weight-loss outcomes of patients undergoing LRYGB after LSG in the largest bariatric surgical network in Canada and to determine whether outcomes differ according to indications for conversion. METHODS: The Bariatric Registry is a multi-center database with prospectively collected standardized data on patients undergoing bariatric surgery at ten Bariatric Centers of Excellence within the Ontario Bariatric Network in Ontario, Canada. A retrospective analysis was performed of patients who underwent LRYGB after previous LSG between 2012 and 2019. Weight loss outcomes were compared between patients who underwent LRYGB for insufficient weight loss/weight regain and those who underwent conversion to LRYGB for other reasons. RESULTS: Excluding patients with multiple revisions and those without follow-up data, 48 patients were included in the analysis: 33 patients (69%) underwent conversion to LRGYB for insufficient weight loss/weight regain (Group 1) and 15 patients (31%) underwent conversion for other reasons (Group 2). Mean body mass index (BMI) measured pre-LSG, pre-LRYGB, and at mid-term follow-up after LRYGB was 61, 48, and 43 kg/m2 in Group 1 and 51, 39, and 34 kg/m2 in Group 2, respectively. ΔBMI and %total weight loss (TWL) at mid-term follow-up were not significantly different between the groups. CONCLUSIONS: Conversion to LRYGB after previous LSG resulted in an additional loss of 4 kg/m2 in BMI points at mid-term follow-up. Patients lost a similar number of BMI points and cumulative %TWL was similar regardless of reason for conversion. This can help inform surgical decision-making in the setting of weight regain after LSG.

Cost of postoperative complications after general surgery at a major Canadian academic centre.

BACKGROUND: In a fiscally constrained health care environment, the need to reduce unnecessary spending is paramount. Postoperative complications contribute to hospital costs and utilization of health care resources. OBJECTIVE: The purpose of this observational study was to identify the cost associated with complications of common general surgery procedures performed at a major academic hospital in Toronto, Ontario. METHODS: The institutional National Surgical Quality Improvement Program database was used to identify complications in patients who underwent general surgical procedures at our institution from April 2015 to February 2018. A mix of elective and emergent cases was included: bariatric surgery, laparoscopic appendectomy, laparoscopic cholecystectomy, thyroidectomy, right hemicolectomy and ventral incisional hernia repair. The total cost for each visit was calculated by adding all the aggregate costs of inpatient care. Median total costs and the breakdown of cost components were compared in cases with and without complications. RESULTS: A total of 2713 patients were included. Nearly 6% of patients experienced at least one complication, with an incidence ranging from 1.1% after bariatric surgery to 23.8% after right hemicolectomy. The most common type of complication varied by procedure. Median total costs were significantly higher in cases with complications, with a net increase ranging from $2989 CAD (35% increase) after bariatric surgery to $10 459 CAD (161% increase) after ventral incisional hernia repair. CONCLUSION: Postoperative complications after both elective and emergent general surgery procedures add substantially to hospital costs. Quality improvement initiatives targeted at decreasing postoperative complications could significantly reduce costs in addition to improving patient outcomes.

Telesimulation for remote simulation and assessment.

Telesimulation (TS), the process of using the internet to link educators and trainees at locations remote from one another, harnesses the powers of technology to enable access to high-quality simulation-based education and assessment to learners across the globe. From its first uses in the teaching and assessment of laparoscopic skills to more recent interpretations during the current pandemic, TS has shown promise in helping educators to address pressing dilemmas in medical education.

Risk-to-Benefit Ratio of Venous Thromboembolism Prophylaxis for Neurosurgical Procedures at a Quaternary Referral Center.

BACKGROUND: Pharmacological prophylaxis for venous thromboembolism (VTE) in the neurosurgical population is still a matter of debate, as the risk-to-benefit ratio is not well defined. OBJECTIVE: To further evaluate the risk-to-benefit ratio of VTE prophylaxis (VTEP) for all neurosurgical procedures. METHODS: A prospective evaluation was performed after the initiation of a VTEP protocol for 11 436 patients undergoing neurosurgical procedures over 24 mo. Unless a bleeding complication was present, 5000 international units of subcutaneous heparin every 8 h was ordered on postoperative day (POD) 1 for spine, POD2 for cranial, and by POD4 for subdural, intracerebral, and epidural hematoma cases. Incidence of VTE and any subsequent bleeding complications were noted. RESULTS: A total of 70 VTEs (0.6% overall) were documented (28 deep vein thrombosis, 42 pulmonary embnolism). The highest rates of VTE were associated with deformity (6.7%); open cerebrovascular (6.5%); subdural, intracerebral, and epidural hematoma (3.2%); spinal trauma (2.4%); and craniotomy for tumor (1.6%) cases. Seven cases of deep vein thrombosis progressed to pulmonary embolisms, and 66 of 70 VTEs occurred while on pharmacological VTEP. Fifty-four bleeding complications occurred on or after POD2 following initiation of VTEP. These bleeding complications consisted of any new clinically or radiographically observed hemorrhages. Twenty-eight of the 54 delayed bleeding complications required operative intervention with 1 mortality. Forty-five patients were on anticoagulation when the initial bleeding event occurred. Overall, an estimated 0.5% incidence of delayed bleeding complications was noted with 99.4% of patients within the study cohort remaining VTE free. CONCLUSION: This VTEP protocol was determined to afford a good risk-to-benefit ratio for a wide variety of neurosurgical procedures.

Predictors of acute posttraumatic stress disorder symptoms following civilian trauma: highest incidence and severity of symptoms after assault.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with significant morbidity following injury. The incidence and risk factors for PTSD are not well described in the civilian trauma population. We proposed to screen all trauma patients in the outpatient trauma clinic for acute PTSD symptoms and identify risk factors for PTSD. METHODS: We prospectively screened 1,386 injured patients who presented for follow-up in trauma clinic (January 2009 to September 2010) using an established PTSD screening test (PTSD Checklist-Civilian, PCL-C). A PCL-C score of ≥35, with a known sensitivity of >85% for PTSD, was considered screen-positive (PCL-C-POS). Backward stepwise logistic regression was used to determine independent risk factors for PCL-C-POS. RESULTS: Over 25% of trauma clinic patients met the threshold for positive PTSD screen (PCL-C-POS). The highest incidence (43%) was in patients who sustained assault (blunt or penetrating). Regression analysis revealed that age <55 years, female gender, motor vehicle collision, and assaultive mechanism (blunt or penetrating, excluding self-inflicted or accidental injury) were independent predictors of PCL-C-POS status. As the severity of symptoms increased (higher PCL-C scores), the risk associated with assaultive mechanism significantly increased in a dose-response fashion (p < 0.05). CONCLUSIONS: This study confirms the high incidence of acute PTSD symptoms in trauma patients and supports the feasibility of PTSD screening in the outpatient trauma clinic. Among all mechanisms of injury, patients who sustain interpersonal violence are at the highest risk of developing acute PTSD symptoms. These results suggest that PTSD screening in outpatient trauma clinic may allow early detection and referral of patients with PTSD. LEVEL OF EVIDENCE: II.

Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype.

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the CFTR gene that impair the function of CFTR, a cAMP-regulated anion channel. In the small intestine loss of CFTR function creates a dehydrated, acidic luminal environment which is believed to cause an accumulation of mucus, a phenotype characteristic of CF. CF mice have small intestinal bacterial overgrowth, an altered innate immune response, and impaired intestinal transit. We investigated whether lubiprostone, which can activate the CLC2 Cl- channel, would improve the intestinal phenotype in CF mice. METHODS: Cftr(tm1UNC) (CF) and wildtype (WT) littermate mice on the C57BL/6J background were used. Lubiprostone (10 µg/kg-day) was administered by gavage for two weeks. Mucus accumulation was estimated from crypt lumen widths in periodic acid-Schiff base, Alcian blue stained sections. Luminal bacterial load was measured by qPCR for the bacterial 16S gene. Gastric emptying and small intestinal transit in fasted mice were assessed using gavaged rhodamine dextran. Gene expression was evaluated by Affymetrix Mouse430 2.0 microarray and qRT-PCR. RESULTS: Crypt width in control CF mice was 700% that of WT mice (P < 0.001). Lubiprostone did not affect WT crypt width but, unexpectedly, increased CF crypt width 22% (P = 0.001). Lubiprostone increased bacterial load in WT mice to 490% of WT control levels (P = 0.008). Conversely, lubiprostone decreased bacterial overgrowth in CF mice by 60% (P = 0.005). Lubiprostone increased gastric emptying at 20 min postgavage in both WT (P < 0.001) and CF mice (P < 0.001). Lubiprostone enhanced small intestinal transit in WT mice (P = 0.024) but not in CF mice (P = 0.377). Among other innate immune markers, expression of mast cell genes was elevated 4-to 40-fold in the CF intestine as compared to WT, and lubiprostone treatment of CF mice decreased expression to WT control levels. CONCLUSIONS: These results indicate that lubiprostone has some benefits for the CF intestinal phenotype, especially on bacterial overgrowth and the innate immune response. The unexpected observation of increased mucus accumulation in the crypts of lubiprostone-treated CF mice suggests the possibility that lubiprostone increases mucus secretion.

Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.

BACKGROUND: Cystic fibrosis (CF) has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC), Cftr knockout). METHODOLOGY: Wild type (WT) and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole) or were treated acutely with a mast cell activator (compound 48/80). Gastrointestinal transit was measured using gavage of a fluorescent tracer. RESULTS: In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice. CONCLUSIONS: The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis.

Laminin compensation in collagen alpha3(IV) knockout (Alport) glomeruli contributes to permeability defects.

Alport disease is caused by mutations in genes encoding the alpha3, alpha4, or alpha5 chains of type IV collagen, which form the collagenous network of mature glomerular basement membrane (GBM). In the absence of alpha3, alpha4, alpha5 (IV) collagen, alpha1, alpha2 (IV) collagen persists, which ordinarily is found only in GBM of developing kidney. In addition to dysregulation of collagen IV, Alport GBM contains aberrant laminins, which may contribute to the progressive GBM thickening and splitting, proteinuria, and renal failure seen in this disorder. This study sought to characterize further the laminin dysregulation in collagen alpha3(IV) knockout mice, a model of Alport disease. With the use of confocal microscopy, laminin alpha1 and alpha5 abundance was quantified, and it was found that they co-distributed in significantly large amounts in areas of GBM thickening. In addition, labeling of entire glomeruli for laminin alpha5 was significantly greater in Alport mice than in wild-type siblings. Reverse transcriptase-PCR from isolated glomeruli demonstrated significantly more laminin alpha5 mRNA in Alport mice than in wild-type controls, indicating upregulated transcription of Lama5. For testing glomerular barrier function, ferritin was injected into 2-wk-old Alport and control mice, and GBM was examined by electron microscopy. Highest ferritin levels were seen in Alport GBM thickenings beneath effaced podocyte foot processes, but morphologically normal GBM was significantly permeable as well. We concluded that (1) ultrastructurally normal Alport GBM residing beneath differentiated podocyte foot processes is inherently and abnormally permeable, and (2) upregulation of Lama5 transcription and concentration of laminin alpha1 and alpha5 within Alport GBM thickenings contribute to abnormal permeabilities.

Effects of laxative and N-acetylcysteine on mucus accumulation, bacterial load, transit, and inflammation in the cystic fibrosis mouse small intestine.

The accumulation of mucus in affected organs is characteristic of cystic fibrosis (CF). The CF mouse small intestine has dramatic mucus accumulation and exhibits slower interdigestive intestinal transit. These factors are proposed to play cooperative roles that foster small intestinal bacterial overgrowth (SIBO) and contribute to the innate immune response of the CF intestine. It was hypothesized that decreasing the mucus accumulation would reduce SIBO and might improve other aspects of the CF intestinal phenotype. To test this, solid chow-fed CF mice were treated with an osmotic laxative to improve gut hydration or liquid-fed mice were treated orally with N-acetylcysteine (NAC) to break mucin disulfide bonds. Treatment with laxative or NAC reduced mucus accumulation by 43% and 50%, respectively, as measured histologically as dilation of the intestinal crypts. Laxative and NAC also reduced bacterial overgrowth in the CF intestine by 92% and 63%, respectively. Treatment with laxative normalized small intestinal transit in CF mice, whereas NAC did not. The expression of innate immune response-related genes was significantly reduced in laxative-treated CF mice, whereas there was no significant effect in NAC-treated CF mice. In summary, laxative and NAC treatments of CF mice reduced mucus accumulation to a similar extent, but laxative was more effective than NAC at reducing bacterial load. Eradication of bacterial overgrowth by laxative treatment was associated with normalized intestinal transit and a reduction in the innate immune response. These results suggest that both mucus accumulation and slowed interdigestive small intestinal transit contribute to SIBO in the CF intestine.

Eradication of small intestinal bacterial overgrowth in the cystic fibrosis mouse reduces mucus accumulation.

OBJECTIVES: Mucus accumulation in cystic fibrosis (CF) is involved in blockage of the distal small intestine. Because expression of mucin genes and mucus secretion can be increased by infection and previous work indicated that small intestinal bacterial overgrowth occurs in CF, we tested whether reduction of bacterial load by antibiotic treatment would reduce mucin gene expression and mucus accumulation in the CF mouse small intestine. METHODS: CF transmembrane conductance regulator null (cftr (tm1UNC)) and wild type littermates were treated with ciprofloxacin and metronidazole for 3 weeks. Muc2 and Muc3 gene expression were measured by quantitative reverse-transcriptase polymerase chain reaction. Periodic acid Schiff (PAS) staining and morphometry were used to measure the size of mucus droplets within goblet cells and dilation of the intestinal crypt lumen, as estimates of mucus secretion and accumulation. RESULTS: Antibiotic treatment did not significantly affect Muc2 and Muc3 gene expression in CF mice. In untreated CF mice, the crypt lumen was almost sevenfold wider than wild type. Antibiotic treatment of CF mice reduced the intensity of PAS crypt lumen staining, and the lumen width was decreased by approximately 25%. The area occupied by PAS-positive material in goblet cells was significantly greater in tissues from antibiotic treated mice. CONCLUSIONS: Eradication of bacterial overgrowth in CF mice significantly decreased mucus secretion and accumulation in intestinal crypts without an effect on mucin gene expression. It is proposed that bacterial overgrowth stimulates mucus secretion, which contributes to its accumulation in the small intestine. Control of bacterial overgrowth is expected to reduce mucus accumulation and may improve intestinal function and overall health in CF.

Expression of pro-Muclin in pancreatic AR42J cells induces functional regulated secretory granules.

It is not clear how protein cargo is sorted to and retained in forming regulated secretory granules (RSG). Here, the sulfated mucin-type glycoprotein pro-Muclin was tested for its ability to induce RSG in the poorly differentiated rat pancreatic cell line AR42J. AR42J cells express RSG content proteins, but they fail to make granules. Adenovirus-pro-Muclin-infected AR42J cells store amylase, accumulate RSG, and respond to hormonal stimulation by secreting the stored protein. Expression of pro-Muclin combined with the inducing effect of dexamethasone resulted in a significant enhancement of the efficiency of regulated secretion. The effect of pro-Muclin was a strong decrease in constitutive secretion compared with dexamethasone-induction alone. A pro-Muclin construct missing the cytosolic tail domain was less effective at improving the efficiency of regulated secretion compared with the full-length construct. Increased expression of cargo (using adenovirus amylase) also modestly enhanced regulated secretion, indicating that part of pro-Muclin's effect may be due to increased expression of cargo protein. Overall, the data show that pro-Muclin acts as a sorting receptor that can induce RSG, and that its cytosolic tail is important in this process.