Marcus Reddy

Expression and function of the K+ channel KCNQ genes in human arteries

BACKGROUND AND PURPOSE KCNQ‐encoded voltage‐gated potassium channels (Kv7) have recently been identified as important anti‐constrictor elements in rodent blood vessels but the role of these channels and the effects of their modulation in human arteries remain unknown. Here, we have assessed KCNQ gene expression and function in human arteries ex vivo.

Incidence of type 2 diabetes after bariatric surgery: population-based matched cohort study

BACKGROUND The effect of currently used bariatric surgical procedures on the development of diabetes in obese people is not well defined. We aimed to assess the effect of bariatric surgery on development of type 2 diabetes in a large population of obese individuals. METHODS We did a matched cohort study of adults (age 20–100 years) identified from a UK-wide database of family practices, who were obese (BMI ≥30 kg/m2) and did not have diabetes. We enrolled 2167 patients who had undergone bariatric surgery between Jan 1, 2002, and April 30, 2014, and matched them--according to BMI, age, sex, index year, and HbA1c--with 2167 controls who had not had surgery. Procedures included laparoscopic gastric banding (n=1053), gastric bypass (795), and sleeve gastrectomy (317), with two procedures undefined. The primary outcome was development of clinical diabetes, which we extracted from electronic health records. Analyses were adjusted for matching variables, comorbidity, cardiovascular risk factors, and use of antihypertensive and lipid-lowering drugs. FINDINGS During a maximum of 7 years of follow-up (median 2·8 years [IQR 1·3–4·5]), 38 new diagnoses of diabetes were made in bariatric surgery patients and 177 were made in controls. By the end of 7 years of follow-up, 4·3% (95% CI 2·9–6·5) of bariatric surgery patients and 16·2% (13·3–19·6) of matched controls had developed diabetes. The incidence of diabetes diagnosis was 28·2 (95% CI 24·4–32·7) per 1000 person-years in controls and 5·7 (4·2–7·8) per 1000 person-years in bariatric surgery patients; the adjusted hazard ratio was 0·20 (95% CI 0·13–0·30, p<0·0001). This estimate was robust after varying the comparison group in sensitivity analyses, excluding gestational diabetes, or allowing for competing mortality risk. INTERPRETATION Bariatric surgery is associated with reduced incidence of clinical diabetes in obese participants without diabetes at baseline for up to 7 years after the procedure. FUNDING UK National Institute for Health Research.

Impact of bariatric surgery on clinical depression. Interrupted time series study with matched controls

BACKGROUND Obesity is associated with depression. This study aimed to evaluate whether clinical depression is reduced after bariatric surgery (BS). METHODS Obese adults who received BS procedures from 2002 to 2014 were sampled from the UK Clinical Practice Research Datalink. An interrupted time series design, with matched controls, was conducted from three years before, to a maximum of seven years after surgery. Controls were matched for body mass index (BMI), age, gender and year of procedure. Clinical depression was defined as a medical diagnosis recorded in year, or an antidepressant prescribed in year to a participant ever diagnosed with depression. Adjusted odds ratios (AOR) were estimated. RESULTS There were 3045 participants (mean age 45.9; mean BMI 44.0kg/m(2)) who received BS, including laparoscopic gastric banding in 1297 (43%), gastric bypass in 1265 (42%), sleeve gastrectomy in 477 (16%) and six undefined. Before surgery, 36% of BS participants, and 21% of controls, had clinical depression; between-group AOR, 2.02, 95%CI 1.75-2.33, P<0.001. In the second post-operative year 32% had depression; AOR, compared to time without surgery, 0.83 (0.76-0.90, P<0.001). By the seventh year, the prevalence of depression increased to 37%; AOR 0.99 (0.76-1.29, P=0.959). LIMITATIONS Despite matching there were differences in depression between BS and control patients, representing the highly selective nature of BS. CONCLUSIONS Depression is frequent among individuals selected to undergo bariatric surgery. Bariatric surgery may be associated with a modest reduction in clinical depression over the initial post-operative years but this is not maintained.

Staple line reinforcement during laparoscopic sleeve gastrectomy: Does it affect clinical outcomes?

Although laparoscopic sleeve gastrectomy (LSG) is safe and efficacious treatment for morbid obesity, this procedure is associated with major staple line complications including leakage and bleeding. Staple-line reinforcement (SLR) either through suturing or buttressing with biological or synthetic material has been suggested as a method to prevent these complications. A Best Evidence Topic was constructed to address the question of whether SLR reduced these and other complications. MEDLINE, EMBASE and CINAHL searches up to October 2012 returned 97 unique results, of which nine (one meta-analysis, two randomised controlled trials (RCTs), six prospective cohort studies) provided the best evidence to answer this clinical question. We conclude that current evidence suggests that staple-line reinforcement reduces the incidence of leakage and postoperative complications than non-reinforcement but does not significantly reduce bleeding complications. However, we cannot as yet recommend staple-line reinforcement as the strength of the presented evidence is limited by the variable quality of the published studies. The full-length publication of several abstracts of randomised, controlled trials presented at various recent conferences is awaited. This may provide more data on the effect of staple-line reinforcement on other outcomes largely neglected by currently available studies.

Laparoscopic common bile duct exploration versus pre or post-operative ERCP for common bile duct stones in patients undergoing cholecystectomy: Is there any difference?

A best evidence topic in surgery was written according to a structured protocol. The question addressed was: in patients with symptomatic gallstones and concomitant common bile duct (CBD) stones, is a single-stage surgical strategy (laparoscopic cholecystectomy (LC) with common bile duct exploration) preferable, or a two-stage procedure involving LC with pre or post-operative endoscopic retrograde cholangiography (ERCP)? Two hundred and six papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. A recent large meta-analysis concluded no significant difference in the clinical effectiveness or complication rate of either strategy. Three recent smaller studies concurred with this conclusion; however each noted improved cost-effectiveness of the single-stage approach advocating its use as the superior strategy when local resources and expertise are available. We conclude that for patients with symptomatic gallstones and concomitant choledocholithiasis, a single-stage surgical procedure is equivalent to two-stage LC and ERCP in terms of clinical outcomes, is associated with a shorter overall hospital stay and may be more cost-effective. On this basis a single-stage procedure is recommended for management of symptomatic gallstones and choledocholithiasis where local resources and expertise permit.

Costs and Outcomes of Increasing Access to Bariatric Surgery: Cohort Study and Cost-Effectiveness Analysis Using Electronic Health Records

Objectives To estimate costs and outcomes of increasing access to bariatric surgery in obese adults and in population subgroups of age, sex, deprivation, comorbidity, and obesity category. Methods A cohort study was conducted using primary care electronic health records, with linked hospital utilization data, for 3,045 participants who underwent bariatric surgery and 247,537 participants who did not undergo bariatric surgery. Epidemiological analyses informed a probabilistic Markov model to compare bariatric surgery, including equal proportions with adjustable gastric banding, gastric bypass, and sleeve gastrectomy, with standard nonsurgical management of obesity. Outcomes were quality-adjusted life-years (QALYs) and net monetary benefits at a threshold of £30,000 per QALY. Results In a UK population of 250,000 adults, there may be 7,163 people with morbid obesity including 1,406 with diabetes. The immediate cost of 1,000 bariatric surgical procedures is £9.16 million, with incremental discounted lifetime health care costs of £15.26 million (95% confidence interval £15.18–£15.36 million). Patient-years with diabetes mellitus will decrease by 8,320 (range 8,123–8,502). Incremental QALYs will increase by 2,142 (range 2,032–2,256). The estimated cost per QALY gained is £7,129 (range £6,775–£7,506). Net monetary benefits will be £49.02 million (range £45.72–£52.41 million). Estimates are similar for subgroups of age, sex, and deprivation. Bariatric surgery remains cost-effective if the procedure is twice as costly, or if intervention effect declines over time. Conclusions Diverse obese individuals may benefit from bariatric surgery at acceptable cost. Bariatric surgery is not cost-saving, but increased health care costs are exceeded by health benefits to obese individuals.

Is the LINX reflux management system an effective treatment for gastro-oesophageal reflux disease?

A best evidence topic in surgery was written according to a structured protocol. The question addressed whether LINX™ Reflux management system is an efficacious treatment for patients with symptoms of gastro-oesophageal reflux disease (GORD) not controlled by proton pump inhibitors (PPI). Forty-eight LINX-related papers were identified using the reported search, of which three represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. All three studies were prospective case studies. They demonstrated that LINX is an efficacious treatment for GORD patients with good short and medium term outcomes and an acceptable safety profile. Further studies are required to determine its long term outcomes and its relative efficacy as compared to other established treatments.

Objective assessment of the core laparoscopic skills course.

Objective. The demand for laparoscopic surgery has led to the core laparoscopic skills course (CLSC) becoming mandatory for trainees in UK. Virtual reality simulation (VR) has a great potential as a training and assessment tool of laparoscopic skills. The aim of this study was to determine the role of the CLSC in developing laparoscopic skills using the VR. Design. Prospective study. Doctors were given teaching to explain how to perform PEG transfer and clipping skills using the VR. They carried out these skills before and after the course. During the course they were trained using the Box Trainer (BT). Certain parameters assessed. Setting. Between 2008 and 2010, doctors attending the CLSC at St Georges Hospital. Participants. All doctors with minimal laparoscopic experience attending the CLSC. Results. Forty eight doctors were included. The time taken for the PEG skill improved by 52%, total left hand and right hand length by 41% and 48%. The total time in the clipping skill improved by 57%. Improvement in clips applied in the marked area was 38% and 45% in maximum vessel stretch. Conclusions. This study demonstrated that CLSC improved some aspects of the laparoscopic surgical skills. It addresses Practice-based Learning and patient care.

Resident phenotypically modulated vascular smooth muscle cells in healthy human arteries

Vascular interstitial cells (VICs) are non‐contractile cells with filopodia previously described in healthy blood vessels of rodents and their function remains unknown. The objective of this study was to identify VICs in human arteries and to ascertain their role. VICs were identified in the wall of human gastro‐omental arteries using transmission electron microscopy. Isolated VICs showed ability to form new and elongate existing filopodia and actively change body shape. Most importantly sprouting VICs were also observed in cell dispersal. RT‐PCR performed on separately collected contractile vascular smooth muscle cells (VSMCs) and VICs showed that both cell types expressed the gene for smooth muscle myosin heavy chain (SM‐MHC). Immunofluorescent labelling showed that both VSMCs and VICs had similar fluorescence for SM‐MHC and αSM‐actin, VICs, however, had significantly lower fluorescence for smoothelin, myosin light chain kinase, h‐calponin and SM22α. It was also found that VICs do not have cytoskeleton as rigid as in contractile VSMCs. VICs express number of VSMC‐specific proteins and display features of phenotypically modulated VSMCs with increased migratory abilities. VICs, therefore represent resident phenotypically modulated VSMCs that are present in human arteries under normal physiological conditions.

Does closure of the mesenteric defects during antecolic laparoscopic gastric bypass for morbid obesity reduce the incidence of symptomatic internal herniation

A best evidence topic in surgery was written according to a structured protocol. The question asked was whether the closure of the mesenteric defects during laparoscopic gastric bypass via antecolic approach for morbid obesity reduces the incidence of symptomatic internal herniation. 251 papers were found using the reported search strategy of which three papers best represented the answer to the question. All three studies showed that by closuring the mesenteric defects, resulted in a reduction in the incidence of symptomatic internal hernias. One study showed there to be new complications arising from primary closure, but this was undetermined statistically. The evidence still however remains limited regarding the need for closure of mesenteric defects in gastric bypass operations. We recommend there is a need for large scale randomized control trials with suitable follow up for patients.