Characterization and Risk Factors for Early Biliary Complications Following Elective Bariatric Surgery: an Mbsaqip Analysis

Obesity Surgery - Patients undergoing bariatric surgery are at risk of postoperative biliary complications. This study aims to characterize biliary complications occurring within 30 days...     

Evaluation of Metabolic Outcomes Following SADI-S: a Systematic Review and Meta-analysis

Obesity Surgery - Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) offers a novel bariatric procedure. This systematic review and meta-analysis evaluates observational and...     

Early regulation of c-myc mRNA by 1,25-dihydroxyvitamin D3 in human myelomonocytic U937 cells

The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3; 10 nmol/l) on the human monomyelocytic cell line U937 were investigated. Addition of 1,25-(OH)2D3 led to a decrease in cell proliferation which fell at 72 h to 67.8 +/- 4.3% (mean +/- S.E.M.) of control values. The presence of CD14, a surface marker found on mature monocytes/macrophages but not on U937 cells, was detectable as early as 18 h and peaked at 48 h, when 63.6 +/- 4.2% of the cells were positive. However, changes in c-myc mRNA levels were detected earlier, starting within 4 h of exposure to the hormone and being reduced to 38 +/- 8.2% of control values of 24 h. These effects were reversible after removal of the hormone, with the same sequence of events seen following addition of the hormone. There was first an increase in c-myc mRNA levels, starting within 2 h and reaching control values by 24 h. These changes were followed by loss of CD14 which became undetectable after 72 h. Proliferation recovered slowly and incompletely, since it was 81.7 +/- 0.7% of control after 72 h. A constant reciprocal relationship between c-myc mRNA and CD14 levels was found both in the presence and after removal of 1,25-(OH)2D3. Regulation of U937 cell proliferation and maturation by 1,25-(OH)2D3 is thus preceded by early modulation of c-myc mRNA.     

The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli

Forty pediatric patients with idiopathic hemolytic uremic syndrome (HUS) were investigated for evidence of infection by Verotoxin-producing Escherichia coli (VTEC). Fecal VTEC (belonging to at least six different O serogroups including O26, O111, O113, O121, O145, and O157) or specifically neutralizable free-fecal Verotoxin (VT) or both were detected in 24 (60%) patients but were not detected in 40 matched controls. Ten of 15 of the former developed fourfold or greater rises in VT-neutralizing antibody titers, as did six other patients who were negative for both fecal VTEC and VT. A total of 30 (75%) patients had evidence of VTEC infection by one or more criteria. We concluded that a significant association exists between idiopathic HUS and infection by VTEC. The detection of free-fecal VT was the most important procedure for the early diagnosis of this infection because, in our study, VTEC were never isolated in the absence of fecal VT, whereas fecal VT was often present even when VTEC were undetectable.     

Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions

Hemolytic uremic syndrome (HUS), which is the most common cause of acute renal failure in infants and small children, is caused by verotoxin (VT)-producing Escherichia coli infection. Endothelial injury determines microvascular thrombosis and evidence is available from recent studies that suggests that leukocyte activation participates in endothelial damage. We studied here the effect of VT-1 on leukocyte adhesion to vascular endothelium under physiologic flow conditions. Human umbilical vein endothelial cells (HUVECs) were incubated for 24 hours with VT-1 (0.1, 1, and 10 pmol/L) and then exposed to a total leukocyte suspension in a parallel plate flow chamber under laminar flow conditions (1.5 dynes/cm2). Adherent cells were counted by digital image processing. Results showed that VT-1 dose-dependently increased the number of adhering leukocytes to HUVECs as compared with unstimulated cells. The adhesive response elicited by VT-1 was comparable to that of interleukin-1 beta (IL-1 beta), one of the most potent inducers of endothelial cell adhesiveness. Exposure of HUVECs to VT-1 did not affect the number of rolling leukocytes, which was similar to that of control values. To examine the role of adhesion molecules in VT-1-induced leukocyte adhesion, HUVECs were incubated with mouse monoclonal antibodies against E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) before adhesion assay. Functional blocking of E-selectin, ICAM-1, and VCAM-1 on endothelial cells significantly inhibited VT-1-induced increase in leukocyte adhesion. In some experiments, before VT-1 incubation, HUVECs were pretreated for 24 hours with tumor necrosis factor alpha (TNF alpha; 100 U/mL), which is known to increase VT receptor expression on HUVECs. The number of adhering leukocytes on HUVECs exposed to TNF alpha and VT-1 significantly increased as compared with HUVECs incubated with VT-1 and TNF alpha alone. These results suggest that VT-1 modulates leukocyte-endothelium interaction, thus increasing leukocyte adhesion and upregulating adhesive proteins on endothelial surface membrane.     

Binding of the receptor for 1,25-dihydroxyvitamin D3 to the 5'-flanking region of the bovine parathyroid hormone gene

Receptors for 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) were prepared from bovine parathyroid glands and incubated with fragments of DNA of the 5'-flanking region of the bovine parathyroid hormone (PTH) gene covering 1700 base pairs (bp) upstream of the initiation site. In filter binding assays, incubation of the DNA fragment spanning -700 to +50 bp with 200 micrograms cytosolic protein gave 288 +/- 63% (mean +/- S.D.) of binding in the absence of protein. In contrast, there was no significant reaction with the -1350 to -700 bp fragment, nor was there binding of the receptor to a fragment of DNA covering the coding region of the PTH gene. Substitution of bovine serum albumin for the receptor preparation did not induce binding to the -700 to +50 bp fragment. The receptor-binding site was further defined to -700 to -100 bp as deletion of the -100 to +50 bp did not reduce receptor binding. Reaction of receptors further purified by sucrose density ultracentrifugation with a monoclonal antibody in immunoblots revealed a single species with a molecular mass of approximately 50,000 Da, which was absent in preparations of cos-1 cells. Autoradiography following incubation of receptors immobilized on nitrocellulose filters with the -700 to +50 bp fragment indicated a single reactive band coincident with the band in the immunoblot. The DNA fragment did not bind to filters containing preparations of cos-1 cells. Extraction of the receptors in the presence or absence of 1,25-(OH)2D3 (4 nmol/l) or the presence of KCl (150 mmol/l) in the incubation medium had no significant effect on DNA binding to the protein in this assay. (ABSTRACT TRUNCATED AT 250 WORDS)     

Client and family engagement in rehabilitation research: a framework for health care organizations

Purpose: To describe the development and implementation of an organizational framework for client and family-centered research.

Method: Case report.

Results: While patient-centered care is now well established, patient-centered research remains underdeveloped. This is particularly true at the organizational level (e.g., hospital based research institutes). In this paper we describe the development of an organizational framework for client and family centered research at Holland Bloorview Kids Rehabilitation Hospital in Toronto, Canada.

Conclusion: It is our hope that, by sharing our framework other research institutions can learn from our experience and develop their own research patient/client/family engagement programs.

• Implications for rehabilitation

• Family engagement in rehabilitation research

• ?Rehabilitation research is crucial to the development and improvement of rehabilitative care.

• ?The relevance, appropriateness, and accountability of research to patients, clients and families could be improved.

• ?Engaging clients and families as partners in all aspects of the research process is one way to address this problem.

• ?In this paper, we describe a framework for engaging clients and families in research at the organizational level.

     

A Review of Laparoscopic Sleeve Gastrectomy for Morbid Obesity

Laparoscopic sleeve gastrectomy (LSG) is an innovative approach to the surgical management of morbid obesity. Weight loss may be achieved by restrictive and endocrine mechanisms. Early data suggest LSG is efficacious in the management of morbid obesity and may have an important role either as a staged or definitive procedure. A systematic review of the literature analyzing the clinical and operational outcomes of LSG was completed to further define the status of LSG as an emerging treatment modality for morbid obesity. Data from LSG were compared to benchmark clinical data and local operational data from laparoscopic adjustable gastric band (LAGB) and laparoscopic gastric bypass (LRYGB). Fifteen studies (940 patients) were identified following systematic review. The percent excessive weight loss (%EWL) for LSG varied from 33% to 90% and appeared to be sustained up to 3 years. The mortality rate was 0-3.3% and major complications ranged from 0% to 29% (average 12.1%). Operative time ranged from 49 to 143 min (average 100.4 min). Hospital stay varied from 1.9 to 8 days (average 4.4 days). The operational impact of LSG has not been described in the literature. According to data from the Royal Alexandra Hospital, the estimated total cost of LSG was 10,317 CAD as compared to LAGB (10,317 CAD as compared to LAGB (7,536 CAD) and LRYGB ($11,666 CAD). These costs did not include further surgical interventions which may be required for an undefined group of patients after LSG. Early, non-randomized data suggest that LSG is efficacious in the surgical management of morbid obesity. However, it is not clear if weight loss following LSG is sustainable in the long term and therefore it is not possible to determine what percent of patients may require further revisional surgery following LSG. The operational impact of LSG as a staged or definitive procedure is poorly defined and must be analyzed further in order to establish its overall health care costs and operational impact. Although LSG is a promising treatment option for patients with morbid obesity, its role remains undefined and it should be considered an investigational procedure that may require revision in a subset of patients.     

Safety and efficacy of combination therapy with fludarabine, mitoxantrone, and rituximab followed by yttrium-90 ibritumomab tiuxetan and maintenance rituximab as front-line therapy for patients with follicular or marginal zone lymphoma

BackgroundWe conducted a single-institution phase II clinical trial evaluating the safety and efficacy of combination chemoimmunotherapy followed by radioimmunotherapy consolidation and rituximab maintenance as front-line treatment in indolent lymphomas.Patients and MethodsWe enrolled 20 patients with intermediate- to high-risk follicular lymphoma and 2 patients with marginal zone lymphoma. Treatment consisted of 4-6 cycles of FM (fludarabine 25 mg/m² on days 1-3, mitoxantrone 12 mg/m² on day 1 of each 28-day cycle). The protocol was amended after enrolling the first 4 patients to include rituximab 375 mg/m² on day 1. After 6-8 weeks, responders received ⁹⁰Y-ibritumomab tiuxetan (Zevalin) followed by maintenance rituximab (375 mg/m² weekly × 4 doses, repeated every 6 months for 2 years).ResultsAfter R-FM, the overall response rate was 95% with a complete response rate (CR) of 45% (n = 10), a partial response (PR) rate of 50% (n = 11), and stable disease in 1 patient. Nineteen patients received ⁹⁰Y-ibritumomab tiuxetan with a 60% conversion rate of PR to CR, resulting in an improved CR of 79% (n = 15) and a PR of 21% (n = 4). Fifteen patients proceeded to rituximab maintenance resulting in 3 patients with PR converting to CR. At median follow-up of 49.6 months, median progression-free survival (PFS) was 47.2 months and median overall survival (OS) was not reached in an intent-to-treat analysis. The most common adverse effects were hematologic, with 2 patients experiencing treatment-related myelodysplastic syndrome (MDS), evolving to acute myelogenous leukemia (AML) in 1 patient.ConclusionR-FM with ⁹⁰Y-ibritumomab tiuxetan consolidation and rituximab maintenance is well tolerated, improving CR rates and maintaining durable responses in patients with untreated indolent lymphomas.     

Recurrent haemophagocytic syndrome in an HIV-infected patient

We describe a case of recurrent haemophagocytic syndrome (HS) in an HIV-infected patient.The first episode was associated with active human herpesvirus 8 infection and progressive Kaposi's sarcoma which was successfully treated with splenectomy, foscarnet and chemotherapy. The second episode was triggered by a Clostridium difficile colitis and resolved completely after treatment with metronidazole only. Recurrent HS has rarely been described in adult patients out of the setting of relapsing malignancy or autoimmune disease.The chronic immune dysregulation and suppression due to HIV-infection may predispose our patient to development of associated HS. Prognosis of HS remains poor, especially in HIV-infected patients. Rapidly unmasking the causative factor and timely instauration of adequate treatment are critical and may improve outcome.