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1.
Br J Surg ; 109(9): 812-821, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35727956

ABSTRACT

BACKGROUND: Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. METHODS: MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. RESULTS: Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. CONCLUSION: This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.


Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Humans , Length of Stay , Pancreas/surgery , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Pancreatic Fistula/surgery , Pancreaticoduodenectomy/adverse effects , Pancreaticojejunostomy , Postoperative Complications/prevention & control , Postoperative Complications/surgery , Retrospective Studies , Risk Factors
2.
Surgery ; 172(1): 319-328, 2022 07.
Article in English | MEDLINE | ID: mdl-35221107

ABSTRACT

BACKGROUND: The complexity of pancreaticoduodenectomy and fear of morbidity, particularly postoperative pancreatic fistula, can be a barrier to surgical trainees gaining operative experience. This meta-analysis sought to compare the postoperative pancreatic fistula rate after pancreatoenteric anastomosis by trainees or established surgeons. METHODS: A systematic review of the literature was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with differences in postoperative pancreatic fistula rates after pancreatoenteric anastomosis between trainee-led versus consultant/attending surgeons pooled using meta-analysis. Variation in rates of postoperative pancreatic fistula was further explored using risk-adjusted outcomes using published risk scores and cumulative sum control chart analysis in a retrospective cohort. RESULTS: Across 14 cohorts included in the meta-analysis, trainees tended toward a lower but nonsignificant rate of all postoperative pancreatic fistula (odds ratio: 0.77, P = .45) and clinically relevant postoperative pancreatic fistula (odds ratio: 0.69, P = .37). However, there was evidence of case selection, with trainees being less likely to operate on patients with a pancreatic duct width <3 mm (odds ratio: 0.45, P = .05). Similarly, analysis of a retrospective cohort (N = 756 cases) found patients operated by trainees to have significantly lower predicted all postoperative pancreatic fistula (median: 20 vs 26%, P < .001) and clinically relevant postoperative pancreatic fistula (7 vs 9%, P = .020) rates than consultant/attending surgeons, based on preoperative risk scores. After adjusting for this on multivariable analysis, the risks of all postoperative pancreatic fistula (odds ratio: 1.18, P = .604) and clinically relevant postoperative pancreatic fistula (odds ratio: 0.85, P = .693) remained similar after pancreatoenteric anastomosis by trainees or consultant/attending surgeons. CONCLUSION: Pancreatoenteric anastomosis, when performed by trainees, is associated with acceptable outcomes. There is evidence of case selection among patients undergoing surgery by trainees; hence, risk adjustment provides a critical tool for the objective evaluation of performance.


Subject(s)
Anastomosis, Surgical , Pancreaticoduodenectomy , Surgeons , Anastomosis, Surgical/adverse effects , Humans , Pancreatic Fistula/epidemiology , Pancreatic Fistula/prevention & control , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Retrospective Studies , Risk Adjustment , Surgeons/education
3.
HPB (Oxford) ; 24(7): 1110-1118, 2022 07.
Article in English | MEDLINE | ID: mdl-35101359

ABSTRACT

BACKGROUND: Morbidity and mortality from post-pancreatectomy haemorrhage (PPH) remains high. The International Study Group of Pancreatic Surgery (ISGPS) published guidelines to standardise definitions of PPH severity, management and reporting. This study aimed to i) identify the number of studies reporting PPH using ISGPS guidelines (Grade A, B or C) and ii) describe treatment modality success by grade. METHODS: A systematic literature review was performed, identifying studies reporting PPH by ISGPS Grade and their subsequent management. RESULTS: Of 62 studies reporting on PPH management, 17 (27.4%) stratified by ISGPS guidelines and included 608 incidences of PPH: 48 Grade A, 274 Grade B (62 early, 166 late, 46 unspecified) and 286 Grade C. 96% of Grade A PPH were treated conservatively. Of 62 early Grade B, 54.8% were managed conservatively and 37.1% surgically. Late Grade B were managed non-operatively in 25.3% (42/166), with successful endoscopy in 90.9% (10/11) and angiography in 90.3% (28/31). In Grade C, endoscopic treatment was successful in 64.4% (29/45) and angiography in 90.8% (108/119). Surgical intervention was required in 43.5% early Grade B, 7.8% late Grade B and 33.2% Grade C. CONCLUSION: PPH grading is underreported and despite guidelines, inconsistencies remain when using definitions and reporting of outcomes.


Subject(s)
Pancreatectomy , Postoperative Hemorrhage , Angiography , Humans , Pancreatectomy/adverse effects , Postoperative Hemorrhage/diagnosis , Postoperative Hemorrhage/etiology , Postoperative Hemorrhage/therapy , Time Factors , Treatment Outcome
4.
HPB (Oxford) ; 24(2): 277-285, 2022 02.
Article in English | MEDLINE | ID: mdl-34301475

ABSTRACT

BACKGROUND: Pre-operative biliary bacterial colonisation (bacterobilia) is considered a risk factor for infectious complications after pancreaticoduodenectomy (PD). This study aimed to investigate the role of the PD biliary microbiome grown in the development of post-PD complications. METHODS: In a retrospective study of 162 consecutive patients undergoing PD (2008-2018), intra-operative bile cultures were analyzed and sensitivities compared to pre-anesthetic antibiotics and thirty-day post-surgery complications. RESULTS: Bacterobilia was present in 136 patients (84%). Most bile cultures grew bacteria resistant to pre-operative antibiotics (n = 112, 82%). Patients with bacterobilia had significantly higher rates of major complication than patients without (P = 0.017), as well as higher rates of surgical-site infections (SSI) (P = 0.010). Patients with negative bile cultures (n = 26) had significantly lower rates of major complication and SSI than those growing sensitive (n = 24) or non-sensitive (n = 112) bacteria (major complication P = 0.029 and SSI P = 0.011). CONCLUSION: Positive bile cultures were associated with a higher incidence of major complications and SSI. Patients with sterile bile cultures had the lowest risk of post-operative complications and efforts to reduce rates of bacterobilia, such as limitation of biliary instrumentation, should be considered. Sensitivity to antibiotics had no effect upon the rate of post-operative complications, but this may reflect low cohort numbers.


Subject(s)
Pancreaticoduodenectomy , Preoperative Care , Bile/microbiology , Humans , Pancreatectomy/adverse effects , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Surgical Wound Infection/diagnosis , Surgical Wound Infection/epidemiology
6.
HPB (Oxford) ; 24(3): 287-298, 2022 03.
Article in English | MEDLINE | ID: mdl-34810093

ABSTRACT

BACKGROUND: Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. It is unclear which scores have undergone external validation and are the most accurate. The aim of this study was to identify risk scores for POPF, and assess the clinical validity of these scores. METHODS: Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. RESULTS: Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so included in the meta-analysis, (Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores). Overall predictive accuracies were similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. CONCLUSION: Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.


Subject(s)
Pancreatic Fistula , Pancreaticoduodenectomy , Humans , Pancreas/surgery , Pancreatic Fistula/diagnosis , Pancreatic Fistula/etiology , Pancreatic Fistula/surgery , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Risk Assessment , Risk Factors
7.
Gut ; 70(6): 1061-1069, 2021 06.
Article in English | MEDLINE | ID: mdl-33547182

ABSTRACT

OBJECTIVE: There is emerging evidence that the pancreas may be a target organ of SARS-CoV-2 infection. This aim of this study was to investigate the outcome of patients with acute pancreatitis (AP) and coexistent SARS-CoV-2 infection. DESIGN: A prospective international multicentre cohort study including consecutive patients admitted with AP during the current pandemic was undertaken. Primary outcome measure was severity of AP. Secondary outcome measures were aetiology of AP, intensive care unit (ICU) admission, length of hospital stay, local complications, acute respiratory distress syndrome (ARDS), persistent organ failure and 30-day mortality. Multilevel logistic regression was used to compare the two groups. RESULTS: 1777 patients with AP were included during the study period from 1 March to 23 July 2020. 149 patients (8.3%) had concomitant SARS-CoV-2 infection. Overall, SARS-CoV-2-positive patients were older male patients and more likely to develop severe AP and ARDS (p<0.001). Unadjusted analysis showed that SARS-CoV-2-positive patients with AP were more likely to require ICU admission (OR 5.21, p<0.001), local complications (OR 2.91, p<0.001), persistent organ failure (OR 7.32, p<0.001), prolonged hospital stay (OR 1.89, p<0.001) and a higher 30-day mortality (OR 6.56, p<0.001). Adjusted analysis showed length of stay (OR 1.32, p<0.001), persistent organ failure (OR 2.77, p<0.003) and 30-day mortality (OR 2.41, p<0.04) were significantly higher in SARS-CoV-2 co-infection. CONCLUSION: Patients with AP and coexistent SARS-CoV-2 infection are at increased risk of severe AP, worse clinical outcomes, prolonged length of hospital stay and high 30-day mortality.


Subject(s)
COVID-19 , Pancreatitis , COVID-19/diagnosis , COVID-19/epidemiology , Cohort Studies , Comorbidity , Disease Progression , Female , Humans , Intensive Care Units/statistics & numerical data , International Cooperation , Length of Stay/statistics & numerical data , Male , Middle Aged , Mortality , Organ Dysfunction Scores , Outcome Assessment, Health Care , Pancreatitis/diagnosis , Pancreatitis/mortality , Pancreatitis/physiopathology , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , SARS-CoV-2/isolation & purification , Severity of Illness Index
8.
BMJ Open Gastroenterol ; 6(1): e000336, 2019.
Article in English | MEDLINE | ID: mdl-31645990

ABSTRACT

OBJECTIVE: Current surveillance strategies for duodenal adenomatosis in familial adenomatous polyposis (FAP) miss malignancies and underestimate cancer risk in ampullary disease. This study aimed to evaluate the utility of endoscopic ultrasound (EUS) in the assessment of FAP patients with duodenal and/or ampullary polyposis referred for surgical intervention. DESIGN: A retrospective analysis of FAP patients undergoing index EUS between December 2006 and May 2015 was performed. Follow-up was completed in January 2018, including review of all EUS procedures and surgical interventions (median follow-up 6 years). RESULTS: Fifty-five patients underwent 188 EUS procedures. Six patients (11%) developed malignancy (three duodenal, three ampullary). Ampullary cancer risk was underestimated by Spigelman stage and overestimated by Kashiwagi classification. Ultrasound findings were poor predictors of malignancy, with common bile duct dilatation being the only finding present in one EUS prior to a diagnosis of ampullary cancer. The best predictors of ampullary malignancy were an ampullary polyp size >3 cm and an increase >1 cm in ampullary polyp size. Ampullary polyp size >3 cm provided the best predictive value, correctly identifying two of the three cases of ampullary cancer and both patients with high-grade dysplasia. EUS biopsy failed to detect malignancy later confirmed by surgical histology in two patients. CONCLUSION: EUS surveillance confers little additional benefit to standard endoscopic surveillance in FAP patients. The best predictor of ampullary malignancy is an ampullary polyp >3 cm; this could be regarded as a relative indication for surgery.

9.
Obes Surg ; 28(5): 1377-1384, 2018 05.
Article in English | MEDLINE | ID: mdl-29236206

ABSTRACT

BACKGROUND: A lack of clarity remains over the optimal strategy for the management of laparoscopic adjustable gastric band (LAGB) slippage, which, although rare (around 3% in our experience), can when acute result in obstruction, gastric erosion or ischaemia. Typically, slipped bands are removed acutely. The aim of this study was to explore outcomes following immediate or delayed resiting of slipped LAGBs in a single centre, comparing simple repositioning with retunnelling and replacement. METHODS: A retrospective analysis of computerised records, notes and prospectively maintained bariatric databases was undertaken to identify all patients with a slipped LAGB in a single centre. RESULTS: Thirty-two patients required operative intervention following a diagnosis of slipped LAGB (median time from initial LAGB insertion to slippage 2.9 years). Two (6%) patients underwent band removal and 30 (94%), band revision surgery (25 immediately and five at a planned but expedited procedure).Twenty-four (77%) patients underwent insertion of a new LAGB via a de novo retrogastric tunnel, five (21%) of which required further future operative intervention; whereas, six (23%) patients underwent repositioning of the existing LAGB within the same tunnel, five (83%) of which underwent further operative intervention (log-rank test p = 0.0001). Following LAGB revision, there was no significant further change in BMI (median + 1 kg/m2; range - 13 to + 10 kg/m2). CONCLUSION: Resiting of slipped LAGBs is safe and maintains weight loss. Although a significant risk of future operative intervention remains, this can be reduced via the creation of a de novo retrogastric tunnel for band resiting.


Subject(s)
Bariatric Surgery/adverse effects , Obesity, Morbid/surgery , Reoperation/statistics & numerical data , Adult , Aged , Female , Humans , Laparoscopy/methods , Male , Middle Aged , Reoperation/methods , Retrospective Studies , Weight Loss , Young Adult
10.
Br J Hosp Med (Lond) ; 78(5): 266-272, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28489438

ABSTRACT

With increasing demand for organ transplantation and patients deteriorating or dying on the waiting list, organs are now being increasingly used from donors previously considered too marginal. This requires improvements to donor management during the retrieval process, and of the organ during transport and subsequent implantation, in order to maintain outcomes.


Subject(s)
Liver Transplantation/methods , Organ Preservation/methods , Tissue and Organ Procurement , Waiting Lists , Brain Death/diagnosis , Humans , United Kingdom
11.
BMJ Open Respir Res ; 4(1): e000165, 2017.
Article in English | MEDLINE | ID: mdl-28321311

ABSTRACT

INTRODUCTION: Skeletal muscle impairment is an important feature of chronic obstructive pulmonary disease (COPD). Renin-angiotensin system activity influences muscle phenotype, so we wished to investigate whether it affects the response to pulmonary rehabilitation. METHODS: Two studies are described; in the first, the response of 168 COPD patients (mean forced expiratory volume in one second 51.9% predicted) to pulmonary rehabilitation was compared between different ACE insertion/deletion polymorphism genotypes. In a second, independent COPD cohort (n=373), baseline characteristics and response to pulmonary rehabilitation were compared between COPD patients who were or were not taking ACE inhibitors or angiotensin receptor antagonists (ARB). RESULTS: In study 1, the incremental shuttle walk distance improved to a similar extent in all three genotypes; DD/ID/II (n=48/91/29) 69(67)m, 61 (76)m and 78 (78)m, respectively, (p>0.05). In study 2, fat free mass index was higher in those on ACE-I/ARB (n=130) than those who were not (n=243), 17.8 (16.0, 19.8) kg m-2 vs 16.5 (14.9, 18.4) kg/m2 (p<0.001). However change in fat free mass, walking distance or quality of life in response to pulmonary rehabilitation did not differ between groups. CONCLUSIONS: While these data support a positive association of ACE-I/ARB treatment and body composition in COPD, neither treatment to reduce ACE activity nor ACE (I/D) genotype influence response to pulmonary rehabilitation.

12.
Ann Surg ; 261(1): 180-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24743610

ABSTRACT

OBJECTIVES: We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. BACKGROUND: The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP. METHODS: Five hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality. RESULTS: The angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046). CONCLUSIONS: The association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.


Subject(s)
Pancreatitis/genetics , Renin-Angiotensin System/genetics , Vitamin D/genetics , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Male , Middle Aged , Pancreatitis, Alcoholic/genetics , Peptidyl-Dipeptidase A/genetics , Polymorphism, Single Nucleotide , Renin/genetics , Young Adult
13.
Sci Rep ; 3: 2467, 2013.
Article in English | MEDLINE | ID: mdl-23959064

ABSTRACT

The circulating, endocrine renin-angiotensin system (RAS) is important to circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse roles, including metabolic regulation. Indeed, inhibition of RAS is associated with improved cellular oxidative capacity. Recently it has been suggested that an intra-mitochondrial RAS directly impacts on metabolism. Here we sought to rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased proteomic approaches were applied to purified mitochondrial sub-fractions from rat liver, and the impact of AngII on mitochondrial function assessed. Whilst high-affinity AngII binding sites were found in the mitochondria-associated membrane (MAM) fraction, no RAS components could be detected in purified mitochondria. Moreover, AngII had no effect on the function of isolated mitochondria at physiologically relevant concentrations. We thus found no evidence of endogenous mitochondrial AngII production, and conclude that the effects of AngII on cellular energy metabolism are not mediated through its direct binding to mitochondrial targets.


Subject(s)
Angiotensin II/pharmacology , Angiotensin II/pharmacokinetics , Mitochondria, Liver/metabolism , Receptor, Angiotensin, Type 1/metabolism , Renin-Angiotensin System/physiology , Animals , Cells, Cultured , Mitochondria, Liver/drug effects , Rats , Renin-Angiotensin System/drug effects
14.
Expert Opin Med Diagn ; 7(5): 487-99, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23971898

ABSTRACT

INTRODUCTION: The worldwide incidence of biliary tract carcinoma (BTC, tumours of the bile ducts and gall-bladder) continues to rise, with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection. AREAS COVERED: This article reviews currently available biomarkers for the diagnosis and prognosis of BTC, as well as recently published studies describing novel serum, bile and urinary biomarkers. EXPERT OPINION: The incorporation of novel analysis techniques, such as digital image analysis and fluorescence in situ hybridization, into existing management algorithms enhances the accuracy of brush cytology taken at the time of therapeutic endoscopy. However, a key goal is the discovery of reliable non-invasive biomarkers with high sensitivity and specificity. Recent advances in gene sequencing and expression, clonal evolution and tumour heterogeneity in other cancers should advance understanding of BTC tumour biology and facilitate biomarker discovery.


Subject(s)
Biliary Tract Neoplasms/diagnosis , Biomarkers, Tumor/analysis , Biliary Tract Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Humans , Prognosis
15.
Crit Care ; 16(5): R173, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-23025890

ABSTRACT

INTRODUCTION: Delayed patient admission to the intensive care unit (ICU) due to lack of bed availability is a common problem, but the effect on patient outcome is not fully known. METHODS: A retrospective study was performed using departmental computerised records to determine the effect of delayed ICU admission and temporary management within the operating theatre suite on patient outcome. Emergency surgical and medical patients admitted to the ICU (2003 to 2007) were divided into delay (more than three hours from referral to admission) and no-delay (three or fewer hours from referral to admission) groups. Our primary outcome measure was length of ICU stay. Secondary outcome measures were mortality rates and duration of organ support. RESULTS: A total of 1,609 eligible patients were included and 149 (9.3%) had a delayed admission. The delay and no-delay groups had similar baseline characteristics. Median ICU stay was 5.1 days (delay) and 4.5 days (no-delay) (P = 0.55) and ICU mortality was 26.8% (delay) and 24.2% (no-delay) (P = 0.47). Following adjustment for demographic and baseline characteristics there was no difference in either length of ICU stay or mortality rates between groups. ICU admission delay was associated with both an increased requirement for advanced respiratory support (92.3% delay vs. 76.4% no-delay, P <0.01) and a longer time spent ventilated (median four days delay vs. three days no-delay, P = 0.04). CONCLUSIONS: No significant difference in length of ICU stay or mortality rate was demonstrated between the delay and no-delay cohorts. Patients within the delay group had a significantly greater requirement for advanced respiratory support and spent a longer time ventilated.


Subject(s)
Intensive Care Units/trends , Length of Stay/trends , Patient Admission/trends , Referral and Consultation/trends , Adult , Aged , Cohort Studies , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Time Factors , Treatment Outcome
16.
J Appl Physiol (1985) ; 112(7): 1122-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22241057

ABSTRACT

Uncoupling proteins 2 and 3 (UCP2 and UCP3) may negatively regulate mitochondrial ATP synthesis and, through this, influence human physical performance. However, human data relating to both these issues remain sparse. Examining the association of common variants in the UCP3/2 locus with performance phenotypes offers one means of investigation. The efficiency of skeletal muscle contraction, delta efficiency (DE), was assessed by cycle ergometry in 85 young, healthy, sedentary adults both before and after a period of endurance training. Of these, 58 were successfully genotyped for the UCP3-55C>T (rs1800849) and 61 for the UCP2-866G>A (rs659366) variant. At baseline, UCP genotype was unrelated to any physical characteristic, including DE. However, the UCP2-866G>A variant was independently and strongly associated with the DE response to physical training, with UCP2-866A allele carriers exhibiting a greater increase in DE with training (absolute change in DE of -0.2 ± 3.6% vs. 1.7 ± 2.8% vs. 2.3 ± 3.7% for GG vs. GA vs. AA, respectively; P = 0.02 for A allele carriers vs. GG homozygotes). In multivariate analysis, there was a significant interaction between UCP2-866G>A and UCP3-55C>T genotypes in determining changes in DE (adjusted R(2) = 0.137; P value for interaction = 0.003), which was independent of the effect of either single polymorphism or baseline characteristics. In conclusion, common genetic variation at the UCP3/2 gene locus is associated with training-related improvements in DE, an index of skeletal muscle performance. Such effects may be mediated through differences in the coupling of mitochondrial energy transduction in human skeletal muscle, but further mechanistic studies are required to delineate this potential role.


Subject(s)
Ion Channels/genetics , Mitochondrial Proteins/genetics , Muscle Strength/genetics , Muscle Strength/physiology , Physical Exertion/genetics , Physical Exertion/physiology , Alleles , Analysis of Variance , Body Height/physiology , Body Weight/physiology , Female , Gene-Environment Interaction , Genetic Variation , Genotype , Humans , Male , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Myocardium , Phenotype , Physical Fitness/physiology , Polymorphism, Single Nucleotide , Uncoupling Protein 2 , Uncoupling Protein 3 , Young Adult
17.
Hepatobiliary Pancreat Dis Int ; 11(1): 107-10, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22251478

ABSTRACT

BACKGROUND: Brunner's gland adenoma (BGA) is an unusual benign neoplasm arising from Brunner's glands in the duodenum. When symptomatic it presents either with duodenal obstruction or bleeding. However, pancreatitis secondary to ampullary obstruction from a BGA is very rare. METHODS: A 23-year-old female presented with recurrent episodes of "idiopathic" pancreatitis. She was extensively investigated and was found to have a large polypoid BGA, intermittently obstructing the ampulla. This created a ball-valve effect causing secondary intermittent obstruction of the pancreatic duct resulting in pancreatitis. The condition was cured surgically, through transduodenal excision of the BGA. We reviewed the surgical literature pertaining to these unusual and similar causes of obstructive pancreatitis, not related to gallstones. RESULTS: BGA of the duodenum is a rare cause of pancreatitis. Extensive investigations should be carried out in all cases of unexplained pancreatitis before classifying the condition as "idiopathic". Discovery of a lesion of this nature gives an opportunity to provide a permanent surgical cure. CONCLUSIONS: BGA adds an unusual etiology for pancreatitis. All patients with pancreatitis should undergo extensive investigations before being termed "idiopathic". Surgical excision of the BGA provides a definitive curative treatment for the adenoma and pancreatitis.


Subject(s)
Adenoma/complications , Brunner Glands , Cholestasis/etiology , Duodenal Neoplasms/complications , Intestinal Polyps/complications , Pancreatitis/etiology , Adenoma/diagnosis , Adenoma/surgery , Ampulla of Vater/pathology , Brunner Glands/pathology , Brunner Glands/surgery , Cholestasis/surgery , Duodenal Neoplasms/diagnosis , Duodenal Neoplasms/surgery , Endoscopy, Gastrointestinal , Female , Humans , Intestinal Polyps/diagnosis , Intestinal Polyps/surgery , Pancreatitis/surgery , Recurrence , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
18.
Int J Cardiol ; 157(2): 180-4, 2012 May 31.
Article in English | MEDLINE | ID: mdl-21195489

ABSTRACT

BACKGROUND: A substantial proportion of patients suffer prolonged length of intensive care unit stay (PLOS) or prolonged mechanical ventilation (PMV) following coronary artery bypass grafting (CABG). Identifying factors associated with PLOS and PMV would aid in patient risk stratification. We sought to identify the factors associated with PLOS and PMV following CABG. METHODS: Participants were patients undergoing first-time elective CABG. All were observed until discharge and clinical data were collected on a standardized proforma. PLOS and PMV were defined a priori as >2 days and >12 h respectively, based on centre norms. RESULTS: Of the 439 patients in the study, 105 (23.9%) had PLOS and 111 (25.2%) had PMV. Independent predictors of PMV were age, diabetes, previous myocardial infarction (MI), New York Heart Association (NYHA) class and statin use. The only independent predictor of PLOS was the duration of preceding hypertension. CONCLUSION: The factors associated with PMV and PLOS in our study are easily attainable, routine clinical details and may be built into bed management algorithms. Confirmation of the association of preceding hypertension and subsequent investigation of the possible mechanism mediating this association, is suggested.


Subject(s)
Hypertension/epidemiology , Hypertension/therapy , Intensive Care Units/trends , Length of Stay/trends , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Respiration, Artificial/adverse effects , Respiration, Artificial/trends , Risk Factors , Time Factors
19.
J Appl Physiol (1985) ; 112(4): 615-26, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22114178

ABSTRACT

The skeletal response to short-term exercise training remains poorly described. We thus studied the lower limb skeletal response of 723 Caucasian male army recruits to a 12-wk training regime. Femoral bone volume was assessed using magnetic resonance imaging, bone ultrastructure by quantitative ultrasound (QUS), and bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA) of the hip. Left hip BMD increased with training (mean ± SD: 0.85 ± 3.24, 2.93 ± 4.85, and 1.89 ± 2.85% for femoral neck, Ward's area, and total hip, respectively; all P < 0.001). Left calcaneal broadband ultrasound attenuation rose 3.57 ± 0.5% (P < 0.001), and left and right femoral cortical volume by 1.09 ± 4.05 and 0.71 ± 4.05%, respectively (P = 0.0001 and 0.003), largely through the rise in periosteal volume (0.78 ± 3.14 and 0.59 ± 2.58% for right and left, respectively, P < 0.001) with endosteal volumes unchanged. Before training, DXA and QUS measures were independent of limb dominance. However, the dominant femur had higher periosteal (25,991.49 vs. 2,5572 mm(3), P < 0.001), endosteal (6,063.33 vs. 5,983.12 mm(3), P = 0.001), and cortical volumes (19,928 vs. 19,589.56 mm(3), P = 0.001). Changes in DXA, QUS, and magnetic resonance imaging measures were independent of limb dominance. We show, for the first time, that short-term exercise training in young men is associated not only with a rise in human femoral BMD, but also in femoral bone volume, the latter largely through a periosteal response.


Subject(s)
Bone and Bones/physiology , Exercise/physiology , Absorptiometry, Photon , Adolescent , Aging/physiology , Bone Density , Bone and Bones/anatomy & histology , Bone and Bones/diagnostic imaging , Calcification, Physiologic , Functional Laterality , Humans , Magnetic Resonance Imaging , Male , Prospective Studies , Ultrasonography , Young Adult
20.
HPB (Oxford) ; 14(1): 20-5, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22151447

ABSTRACT

INTRODUCTION: Surgical resection remains the only potentially curative treatment for colorectal liver metastases (CLM). However, involvement of both the hepatic lobes or extrahepatic disease (EHD) can be a contra-indication for resection. The aim of the present study was to examine the addition of combined positron emission and computed tomography (PET/CT) to CLM staging to assess the effects upon staging and management. METHODS: All CLM patients referred to a single centre between January 2005 and January 2009 were prospectively included. All underwent routine staging (clinical examination and computed tomography), followed by a whole body (18) fluoro-deoxy-glucose ((18)FDG)-PET/CT scan and Fong clinical risk score calculation. RESULTS: Sixty-four patients were included [63% male with a median age of 63 years (age range 32-79 years)]. The addition of PET/CT led to disease upstaging in 20 patients (31%) and downstaging in two patients (3%). EHD was found in 24% of low-risk patients (Fong score 0-2) as compared with 44% of high-risk patients (Fong score 3-5) (P= 0.133). There was a trend towards a greater influence upon management in patients with a low score (44% vs. 17%; P= 0.080). CONCLUSION: The addition of PET/CT led to management changes in over one-third of patients but there was no correlation between alterations in staging or management and the Fong clinical risk score; suggesting that PET/CT should be utilized, where available, in the pre-operative staging of CLM patients.


Subject(s)
Colorectal Neoplasms/pathology , Fluorodeoxyglucose F18 , Liver Neoplasms/diagnosis , Multimodal Imaging/methods , Positron-Emission Tomography , Tomography, X-Ray Computed , Adult , Aged , Colorectal Neoplasms/diagnostic imaging , Diagnosis, Differential , Female , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging/methods , Prospective Studies , Radiopharmaceuticals , Reproducibility of Results , Sensitivity and Specificity
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