Eating Behaviour Predicts Weight Loss Six Months after Bariatric Surgery: A Longitudinal Study.

Bariatric surgery is currently the most durable weight loss solution for patients with morbid obesity. The extent of weight loss achieved, however, is subject to variation due to various factors, including patients' behaviour. In this study, we aimed to identify pre- and post-surgical predictors of weight loss following bariatric surgery. This prospective study included 57 participants who went through bariatric surgery (laparoscopic Roux-en-Y gastric bypass: n = 30; laparoscopic sleeve gastrectomy: n = 23; one anastomosis gastric bypass-mini gastric bypass: n = 4) in two tertiary referral hospitals. Consenting participants were assessed prior to surgery (T0), and three months (T1) and six months (T2) after surgery. The assessment included interview and anthropometric measurements. The interview was done with the aid of instruments, including the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression screening and the Dutch Eating Behaviour Questionnaire (DEBQ) for eating behaviour assessment. Baseline comorbidity status was obtained from medical records. A Generalised Estimating Equation (GEE) was developed to determine predictors of weight loss. Participants in the study were mostly women (n = 37, 65%) with a mean age of 39.4 (SD = 10.01) years. The mean excess BMI loss (EBMIL) and total weight loss (TWL) at the sixth month was 63.31% and 23.83%, respectively. Anxiety, depression, and external eating scores reduced over time. Advancing age, high BMI, and higher scores for emotional and external eating emerged as significant negative predictors for TWL%. It can be concluded that the patients experienced substantial weight loss after surgery. Continuous monitoring of psychological well-being and eating behaviour are essential for optimal weight loss.

Esophageal squamous cell carcinomas in a Malaysian cohort show a lack of association with human papillomavirus.

OBJECTIVE: With an age-standardized incidence rate of 2 per 100 000, esophageal cancer is not common among Malaysians, but they are nevertheless important due to its poor prognosis. The study is to clarify whether the human papillomavirus (HPV) is associated with esophageal cancer in Malaysians as there has been no report to date on this in Malaysians and other South East Asians. METHODS: Altogether 67 esophageal squamous cell carcinomas histologically diagnosed between 1 January 2004 and 31 December 2014 at the Department of Pathology, University of Malaya Medical Center, Malaysia were considered for HPV analysis using two commercially available methods, polymerase chain reaction with flow-through hybridization (21 HPV GenoArray Diagnostic Kit) and multiplex real-time polymerase chain reaction (Anyplex II HPV28 Detection). The DNA amplifiability of the formalin-fixed, paraffin-embedded tumor was checked by amplification of a 268 bp segment of the human ß-globin gene (GH20/PC04) prior to HPV detection. RESULTS: HPV detection was finally carried out in 51 patients. HPV16 was detected in the moderately differentiated, stage IV lower esophageal tumor of a 32-year-old Malaysian-born Chinese woman by both methods. Except for a predilection for Indians, the clinical characteristics of esophageal squamous cell carcinomas in this Malaysian cohort were generally similar to those of other populations. CONCLUSION: It appears that HPV is rare and an unlikely oncovirus in esophageal squamous cell carcinomas of Malaysians.

The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy - Reaping Benefits from Metabolic Crosstalk.

The prevalence of colorectal cancer (CRC) is on a steady rise over the years, with the World Health Organization (WHO) reporting CRC as the fourth leading cause of cancer-related death worldwide. While treatment modalities may differ in accordance to the staging and severity of the disease itself, chemotherapy is almost unavoidable in most cases. Though effective in its mode of action, chemotherapy is commonly associated with undesirable side effects that negatively affects the patient in terms of quality of life, and in some cases may actually interfere with their treatment regimens, thus escalating to poor prognosis. Gastrointestinal disturbances is a major side effect of chemotherapy and in CRC, gastrointestinal disturbances may be further aggravated and grave in nature mainly due to the affected site, being the gastrointestinal tract. The use of complementary therapies as adjuncts to alleviate the side effects of chemotherapy in CRC patients is gaining prominence with dietary supplements being the most commonly employed adjunct. Some of the frequently used dietary supplements for CRC patients are probiotics, omega-3 fatty acid and glutamine. The successful crosstalk between these dietary supplements with important metabolic pathways is crucial in the alleviation of chemotherapy side effects.

Strain-specific probiotic (microbial cell preparation) and omega-3 fatty acid in modulating quality of life and inflammatory markers in colorectal cancer patients: a randomized controlled trial.

AIM: Colorectal cancer patients on chemotherapy usually have elevated levels of inflammatory markers and experience numerous side effects from chemotherapy thereby leading to poor quality of life. Omega-3 fatty acid and microbial cell preparation (MCP) have been known to provide significant benefits in patients on chemotherapy. The aim of this study was to determine the effect of supplementation of omega-3 fatty acid and MCP in quality of life, chemotherapy side effects and inflammatory markers in colorectal cancer patients on chemotherapy. METHODS: A double-blind randomized study was carried out with 140 colorectal cancer patients on chemotherapy. Subjects were separated into two groups to receive either placebo or MCP [30 billion colony-forming unit (CFUs) per sachet] at a dose of two sachets daily for 4 weeks, and omega-3 fatty acid at a dose of 2 g daily for 8 weeks. Outcomes measured were quality of life, side effects of chemotherapy and levels of inflammatory markers such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein. RESULTS: The supplementation with MCP and omega-3 fatty acid improved the overall quality of life and alleviated certain side effects of chemotherapy. The supplementation with MCP and omega-3 fatty acid also managed to reduce the level of IL-6 (P = 0.002). There was a significant rise in the placebo group's serum TNF-α (P = 0.048) and IL-6 (P = 0.004). CONCLUSION: The combined supplementation with MCP and omega-3 fatty acid may improve quality of life, reduce certain inflammatory biomarkers and relieve certain side effects of chemotherapy in colorectal patients on chemotherapy.

Psychometric Properties of the Malay Version of the Dutch Eating Behaviour Questionnaire (DEBQ) in a Sample of Malaysian Adults Attending a Health Care Facility.

OBJECTIVE: This study aims to investigate the psychometric properties of the Malay version of the Dutch Eating Behaviour Questionnaire (DEBQ) among Malaysian adults. METHOD: The Malay version of the DEBQ instrument was administered to 398 outpatients (269 women and 129 men) at the University of Malaya Medical Centre (UMMC). Confirmatory Factor Analysis (CFA) was conducted to study the construct validity of the instrument. Composite reliability coefficient, Raykov's rho, was used to determine the internal consistency. RESULTS: The proposed three-factor structure for the DEBQ instrument was appropriate, although three items (Items 21, 14 and 27) showed problematic loadings with inappropriate model fit and were removed. The modified version had an appropriate model fit χ2/df = 2.129, TLI = 0.908, CFI = 0.918, RMSEA = 0.053 (90%CI = 0.048-0.058), close-fit P-value = 0.136 and satisfactory internal consistency of 0.914 for emotional eating scale, 0.819 for external eating scale and 0.856 for restrained eating scale. DISCUSSION: The Malay version of the DEBQ is a valid instrument to study eating behaviour traits among Malaysian adults. Further research is warranted to determine if Items 14 and 27 are appropriate for the Malaysian population.

Pre-surgical Administration of Microbial Cell Preparation in Colorectal Cancer Patients: A Randomized Controlled Trial.

INTRODUCTION: Disruption of normal gut function is a common side effect post abdominal surgery. It may result in reduced tolerance to oral nutrition and progress to postoperative ileus. Microbial cell preparation is beneficial as a pre-surgical nutritional supplement to aid in bowel recovery and promote the return of normal gut function following abdominal surgery. The aim of this study was to evaluate the efficacy of pre-surgical administration of microbial cell preparation in promoting the return of normal gut function. METHOD: The study is a randomized, double-blind, placebo-controlled trial. In total, 40 patients were recruited. Patients were randomized to receive either microbial cell preparation (n = 20) or placebo (n = 20) for 7 days prior to elective surgery. The primary end point was the time to return of normal gut function, while the secondary end point was the duration of hospital stay. RESULTS: The treatment group demonstrated significantly faster return of normal gut function with a median of 108.5 h (80-250 h) which was 48 h earlier than the placebo group at a median of 156.5 h (94-220 h), p = 0.022. The duration of hospital stay in the treatment group was also shorter at a median of 6.5 days (4-30 days), in comparison to the placebo group at 13 days (5-25 days), p = 0.012. CONCLUSION: Pre-surgical administration of microbial cell preparation promotes the return of normal gut function in patients after colorectal cancer surgery, thus associated with faster recovery and shorter duration of hospital stay.

Inflammatory reaction to fish oil coated polypropylene mesh used for laparoscopic incisional hernia repair: a case report.

BACKGROUND: Polypropylene meshes are widely used in hernia repairs. Hernia meshes have been developed incorporating coatings of active agents. One commercially available mesh has a fish oil coating which is promoted as having anti-inflammatory properties. We report a case, a symptomatic foreign body granuloma reaction associated with a fish oil coated polypropylene mesh, which required eventual mesh explantation. CASE PRESENTATION: A 61-year old lady with previous peptic ulcer disease underwent a laparoscopic intraperitoneal placement of mesh for incisional hernia utilising a fish oil coated polypropylene mesh. The patient presented 3 months after the procedure complaining of dyspepsia and pain at the operative site. There was no discharge. The patient was managed conservatively. She presented 10 months post-operatively with progressively worsening symptoms and a hard palpable mass in the epigastrium. Abdominal laparoscopy revealed dense adhesive disease around the mesh with exudates. Adhesiolysis, mesh explantation and a partial gastrectomy was performed. Histopathological examination revealed a foreign body granuloma formation to the mesh. CONCLUSION: In-vivo studies looking at intraperitoneal mesh placement with fish oil coatings including data on surgical outcomes such as fistula and adhesive characteristics are scarce in the literature. Further monitoring and studies are required to investigate the safety and efficacy profile of this mesh type in in-vivo models.

High-resolution oesophageal manometry and 24-hour impedance-pH study in systemic sclerosis patients: association with clinical features, symptoms and severity.

OBJECTIVES: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients. METHODS: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated. RESULTS: Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030). CONCLUSIONS: The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24-hour pH study should be considered more frequently in the assessment of SSc patients.

Microbial cell preparation in enteral feeding in critically ill patients: A randomized, double-blind, placebo-controlled clinical trial.

Gut failure is a common condition in critically ill patients in the intensive care unit (ICU). Enteral feeding is usually the first line of choice for nutrition support in critically ill patients. However, enteral feeding has its own set of complications such as alterations in gut transit time and composition of gut eco-culture. The primary aim of this study was to investigate the effect of microbial cell preparation on the return of gut function, white blood cell count, C-reactive protein levels, number of days on mechanical ventilation, and length of stay in ICU. A consecutive cohort of 60 patients admitted to the ICU in University Malaya Medical Centre requiring enteral feeding were prospectively randomized to receive either treatment (n = 30) or placebo (n = 30). Patients receiving enteral feeding supplemented with a course of treatment achieved a faster return of gut function and required shorter duration of mechanical ventilation and shorter length of stay in the ICU. However, inflammatory markers did not show any significant change in the pretreatment and posttreatment groups. Overall, it can be concluded that microbial cell preparation enhances gut function and the overall clinical outcome of critically ill patients receiving enteral feeding in the ICU.

Incidental Splenic Granuloma Due to Burkholderia pseudomallei: A Case of Asymptomatic Latent Melioidosis?

We report a rare case of an asymptomatic latent melioidosis lesion in a posttraumatic splenectomy specimen from a diabetic patient. The 2-cm yellowish, lobulated lesion was found in the splenic parenchyma well away from the traumatized areas. Microscopically, it consisted of a central area of necrosis and exudate surrounded by macrophages, epithelioid cells, lymphocytes, and occasional multinucleated giant cells. Burkholderia bacilli were detected by a novel in situ hybridization (ISH) assay, and confirmed by polymerase chain reaction and sequencing to be Burkholderia pseudomallei. As melioidosis was not suspected initially, bacterial culture was not done but electron microscopy showed morphologically viable and dividing bacilli in the lesion. Moreover, the surgical wound became infected with B. pseudomallei several days post-surgery. After treatment with ceftazidime and trimethoprim/sulfamethoxazole, the wound infection cleared. We believe this could be a unique case of asymptomatic latent melioidosis in the spleen. In endemic countries, chronic granulomas should be investigated for B. pseudomallei infection, and if available, ISH may be helpful for diagnosis.

Laparoscopic sleeve gastrectomy in Asia: Long term outcome and revisional surgery.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a popular stand-alone bariatric surgery, despite a paucity of long-term data. Hence, this study is to report the long-term outcome of LSG as primary bariatric procedure and the result of revisional surgery. METHODS: With retrospective analysis of a prospective bariatric database, participants who defaulted clinic follow-up were interviewed by telephone. A total of 667 LSG was performed as primary bariatric procedure (2006-2012) with mean age of 34.5 ± 9.7 years old, female 74.7%, mean body mass index (BMI) 37.3 ± 8.1 kg/m(2). A 36-F bougie was used for all cases. RESULTS: There were 61 patients available with long-term data. The weight loss outcome at 1 year, 2 years, 3 years, 4 years, and 5 years showed a mean BMI 26.3, 25.2, 25.3, 27.1, and 26.2 with mean excess weight loss (EWL) 76.0%, 79.6%, 77.3%, 73.4%, and 72.6% respectively. However, 17% patients developed de novo gastro-esophageal reflux disease (GERD). Eighteen patients (2.2%) needed surgical revisions due to weight regain (n = 6), persistent type 2 diabetes mellitus (T2DM; n = 2), stricture (n = 2), and GERD (n = 8). The revision resulted in an additional mean excess weight loss of 23.8% with mean BMI 24.9 kg/m(2) at 6 months postoperatively. There was a 23.7% mean reduction of HbA1c with one patient who was in complete diabetic remission at 1 year. CONCLUSION: Our results showed LSG is a durable bariatric procedure with > 70% EWL at 5 years despite a high incidence of GERD. The need for revision of LSG is low and mainly for GERD.

The mRNA expression of soluble urokinase plasminogen activator surface receptor in human adipose tissue is positively correlated with body mass index.

suPLAUR is the transcript variant that encodes the soluble form of the urokinase plasminogen activator surface receptor (suPLAUR). This soluble protein has been shown to enhance leukocyte migration and adhesion, and its circulatory level is increased in inflammatory states. In this pilot study, we used RNA-Seq to examine the splicing pattern of PLAUR in omental adipose tissues from obese and lean individuals. Of the three transcript variants of the PLAUR gene, only the proportion of suPLAUR (transcript variant 2) increases in obesity. After removing the effects of gender and age, the expression of suPLAUR is positively correlated with body mass index. This observation was validated using RT-qPCR with an independent cohort of samples. Additionally, in our RNA-Seq differential expression analysis, we also observed, in obese adipose tissues, an up-regulation of genes encoding other proteins involved in the process of chemotaxis and leukocyte adhesion; of particular interest is the integrin beta 2 (ITGB2) that is known to interact with suPLAUR in leukocyte adhesion. These findings suggest an important role for suPLAUR in the recruitment of immune cells to obese adipose tissue, in the pathogenesis of obesity.

Posterior parasagittal in-plane ultrasound-guided infraclavicular brachial plexus block-a case series.

BACKGROUND: The brachial plexus at the infraclavicular level runs deeper compared to its course proximally, giving rise to impaired needle visualisation due to the steep angle of needle insertion with the current ultrasound-guided approach. A new posterior parasagittal in-plane ultrasound-guided infraclavicular approach was introduced to improve needle visibility. However no further follow up study was done. METHODS: We performed a case series and a cadaveric dissection to assess its feasibility in a single centre, University of Malaya Medical Centre, Kuala Lumpur, Malaysia from November 2012 to October 2013. After obtaining approval from the Medical Ethics Committee, University Malaya Medical Centre, 18 patients undergoing upper limb surgery were prospectively recruited. A cadaveric dissection was also performed. The endpoints of this study were the success rate, performance time, total anaesthesia-related time, quality of anaesthesia and any incidence of complications. RESULTS: All patients had 100 % success rate. The imaging time, needling time and performance time were comparable with previously published study. There were no adverse events encountered in this study. The cadaveric dissection revealed a complete spread of methylene blue dye over the brachial plexus. CONCLUSION: This study demonstrated that the posterior parasagittal in-plane approach is a feasible and reliable technique with high success rate. Future studies shall compare this technique with the conventional lateral parasagittal in-plane approach. TRIAL REGISTRATION: ClinicalTrials.gov NCT02312453 . Registered on 8 December 2014.

Fiber and prebiotic supplementation in enteral nutrition: A systematic review and meta-analysis.

AIM: To investigate fiber and prebiotic supplementation of enteral nutrition (EN) for diarrhea, fecal microbiota and short-chain fatty acids (SCFAs). METHODS: MEDLINE, EMBASE, Cochrane Library, CINAHL, Academic Search Premier, and Web of Science databases were searched for human experimental and observational cohort studies conducted between January 1990 and June 2014. The keywords used for the literature search were fiber, prebiotics and enteral nutrition. English language studies with adult patient populations on exclusive EN were selected. Abstracts and/or full texts of selected studies were reviewed and agreed upon by two independent researchers for inclusion in the meta-analysis. Tools used for the quality assessment were Jadad Scale and the Scottish Intercollegiate Guidelines Network Critical Appraisal of the Medical Literature. RESULTS: A total of 456 possible articles were retrieved, and 430 were excluded due to lack of appropriate data. Of the 26 remaining studies, only eight investigated the effects of prebiotics. Results of the meta-analysis indicated that overall, fiber reduces diarrhea in patients receiving EN (OR = 0.47; 95%CI: 0.29-0.77; P = 0.02). Subgroup analysis revealed a positive effect of fiber supplementation in EN towards diarrhea in stable patients (OR = 0.31; 95%CI: 0.19-0.51; P < 0.01), but not in critically ill patients (OR = 0.89; 95%CI: 0.41-1.92; P = 0.77). Prebiotic supplementation in EN does not improve the incidence of diarrhea despite its manipulative effect on bifidobacteria concentrations and SCFA in healthy humans. In addition, the effect of fiber and/or prebiotic supplementation towards fecal microbiota and SCFA remain disputable. CONCLUSION: Fiber helps minimize diarrhea in patients receiving EN, particularly in non-critically ill patients. However, the effect of prebiotics in moderating diarrhea is inconclusive.

Unexplained abdominal pain as a driver for inappropriate therapeutics: an audit on the use of intravenous proton pump inhibitors.

Background. Proton pump inhibitors (PPIs) are currently the most effective agents for acid-related disorders. However, studies show that 25-75% of patients receiving intravenous PPIs had no appropriate justification, indicating high rates of inappropriate prescribing. Objective. To examine the appropriate use of intravenous PPIs in accordance with guidelines and the efficacy of a prescribing awareness intervention at an Asian teaching institution. Setting. Prospective audit in a tertiary hospital in Malaysia. Method. Every 4th intravenous PPI prescription received in the pharmacy was screened against hospital guidelines. Interventions for incorrect indication/dose/duration were performed. Patients' demographic data, medical history and the use of intravenous PPI were collected. Included were all adult inpatients prescribed intravenous PPI. Main Outcome Measure. Proportion of appropriate IV PPI prescriptions. Results. Data for 106 patients were collected. Most patients were male [65(61.3%)], Chinese [50(47.2%)], with mean age ± SD = 60.3 ± 18.0 years. Most intravenous PPI prescriptions were initiated by junior doctors from the surgical [47(44.3%)] and medical [42(39.6%)] departments. Only 50/106(47.2%) patients had upper gastrointestinal endoscopy/surgery performed to verify the source of bleeding. Unexplained abdominal pain [81(76.4%)] was the main driver for prescribing intravenous PPIs empirically, out of which 73(68.9%) were for suspected upper gastrointestinal bleed. Overall, intravenous PPI was found to be inappropriately prescribed in 56(52.8%) patients for indication, dose or duration. Interventions on the use of intravenous PPI were most effective when performed by senior doctors (100%), followed by clinical pharmacists (50%), and inpatient pharmacists (37.5%, p = 0.027). Conclusion. Inappropriate intravenous PPI usage is still prevalent despite the enforcement of hospital guidelines. The promotion of prescribing awareness and evidence-based prescribing through education of medical staff could result in more judicious use of intravenous PPI and dose-optimization.

Association of glucokinase regulatory gene polymorphisms with risk and severity of non-alcoholic fatty liver disease: an interaction study with adiponutrin gene.

BACKGROUND: Recent genome-wide association studies demonstrated an association between single nucleotide polymorphisms (SNPs) on the glucokinase regulatory gene (GCKR) with hepatic steatosis. This study attempted to investigate the association of GCKR rs780094 and rs1260326 with susceptibility to non-alcoholic fatty liver disease (NAFLD) and its severity. METHODS: The genotypes were assessed on 144 histologically confirmed NAFLD patients and 198 controls using a Sequenom MassARRAY platform. RESULTS: The GCKR rs1260326 and rs780094 allele T were associated with susceptibility to NAFLD (OR 1.49, 95 % CI 1.09-2.05, p = 0.012; and OR 1.51, 95 % CI 1.09-2.09, p = 0.013, respectively), non-alcoholic steatohepatitis (NASH) (OR 1.55, 95 % CI 1.10-2.17, p = 0.013; and OR 1.56, 95 % CI 1.10-2.20, p = 0.012, respectively) and NASH with significant fibrosis (OR 1.50, 95 % CI 1.01-2.21, p = 0.044; and OR 1.52, 95 % CI 1.03-2.26, p = 0.038, respectively). Following stratification by ethnicity, significant association was seen in Indian patients between the two SNPs and susceptibility to NAFLD (OR 2.64, 95 % CI 1.28-5.43, p = 0.009; and OR 4.35, 95 % CI 1.93-9.81, p < 0.0001, respectively). The joint effect of GCKR with adiponutrin rs738409 indicated greatly increased the risk of NAFLD (OR 4.14, 95 % CI 1.41-12.18, p = 0.010). Histological data showed significant association of GCKR rs1260326 with high steatosis grade (OR 1.76, 95 % CI 1.08-2.85, p = 0.04). CONCLUSION: This study suggests that risk allele T of the GCKR rs780094 and rs1260326 is associated with predisposition to NAFLD and NASH with significant fibrosis. The GCKR and PNPLA3 genes interact to result in increased susceptibility to NAFLD.

Efficacy of microbial cell preparation in improving chronic constipation: a randomized, double-blind, placebo-controlled trial.

BACKGROUND & AIMS: Probiotics is an emerging therapeutic agent which may alleviate the symptoms of constipation. We evaluated the effectiveness of microbial cell preparation (Hexbio(®)) containing fructooligosaccharide, Bifidobacterium and Lactobacillus in improving stool frequency and symptoms of chronic constipation. METHODS: A total of 120 constipated adults diagnosed using Rome III criteria were randomized and given either microbial cell preparation or placebo to be consumed twice daily. Follow-up was done after a 7-day intervention based on a questionnaire which includes an assessment of symptom profile and a stool diary. RESULTS: During the intervention period, the stool frequency was higher (p = 0.001) in the treatment group. Subjects experienced less straining (p = 0.001) and sensation of incomplete evacuation (p < 0.001), as well as improved stool consistency (p < 0.001) compared to the placebo group. While a higher proportion of subjects in the treatment group had a reduction in anorectal blockage sensation and having to defecate by manual maneuvers, the differences were not statistically significant. CONCLUSION: The results suggest that microbial cell preparation is effective in improving stool frequency and stool consistency. Furthermore, it could reduce the symptoms of straining and sensation of incomplete evacuation in adults with chronic functional constipation. MREC REG NO: 866.59 (IRB, UMMC, Malaysia).

Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene.

BACKGROUND AND AIM: Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD. METHODS: A total of 144 biopsy-proven NAFLD and 198 controls were genotyped using the Sequenom MassARRAY platform. RESULTS: We observed a significant association between the LEPR rs1137100 and rs1137101 with susceptibility to NAFLD (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.18-2.28, P = 0.003; and OR 1.61, 95% CI 1.11-2.34, P = 0.013, respectively) and to non-alcoholic steatohepatitis (OR 1.49, 95% CI 1.05-2.12, P = 0.026; and OR 1.57, 95% CI 1.05-2.35, P = 0.029, respectively). The LEPR rs1137100 is also associated with simple steatosis (OR 2.27, 95% CI 1.27-4.08, P = 0.006). Analysis of gene-gene interaction revealed a strong interaction between the LEPR and PNPLA3 genes (empirical P = 0.001). The joint effect of LEPR and PNPLA3 greatly exacerbated the risk of NAFLD (OR 3.73, 95% CI 1.84-7.55, P < 0.0001). The G allele of rs1137100 is associated with lower fibrosis score (OR 0.47, 95% CI 0.28-0.78, P = 0.001). CONCLUSIONS: We report an association between variants of LEPR rs1137100 and rs1137101 with risk of NAFLD. This study suggests that rs1137100, specifically the G allele, is associated with a less severe form of liver disease in patients with NAFLD. The interaction between LEPR and PNPLA3 genes showed increased risk of NAFLD compared to either gene alone.

Comparable frequency of BRCA1, BRCA2 and TP53 germline mutations in a multi-ethnic Asian cohort suggests TP53 screening should be offered together with BRCA1/2 screening to early-onset breast cancer patients.

INTRODUCTION: Germline TP53 mutations cause an increased risk to early-onset breast cancer in Li-Fraumeni syndrome (LFS) families and the majority of carriers identified through breast cancer cohorts have LFS or Li-Fraumeni-like (LFL) features. However, in Asia and in many low resource settings, it is challenging to obtain accurate family history and we, therefore, sought to determine whether the presence of early-onset breast cancer is an appropriate selection criteria for germline TP53 testing. METHODS: A total of 100 patients with early-onset breast cancer (≤ 35 years) treated at University Malaya Medical Centre between 2003 and 2009, were analyzed for germline mutations in BRCA1, BRCA2 and TP53 by full DNA sequencing. Of the mutations identified, we examined their likely pathogenicity on the basis of prevalence in a case-control cohort, co-segregation analyses and loss of heterozygosity (LOH) in tumor tissues. RESULTS: We identified 11 BRCA1 (11%) and 6 BRCA2 (6%) germline carriers among early-onset breast cancer patients. Of the 83 BRCA-negative patients, we identified four exonic variants and three intronic variants in TP53. Of these, two exonic variants are clinically relevant (E346X and p. G334_R335dup6) and two novel missense mutations (A138V and E285K) are likely to be clinically relevant, on the basis of co-segregation and loss of heterozygosity (LOH). Notably, E285K was found in two unrelated individuals and haplotype analyses suggest a founder effect. Two of the three intronic variants are likely benign based on their prevalence in a control population. Clinically relevant TP53 germline mutations were identified in three of the four patients (75%) with a family history of at least two LFS-linked cancers (breast, bone or soft tissue sarcoma, brain tumors or adrenocortical cancer); 1 of the 17 patients (6%) with a family history of breast cancer only, and 1 of the 62 patients (< 2%) with no family history of breast or LFS-linked cancers. CONCLUSIONS: Our study reports germline BRCA1, BRCA2 and TP53 mutations are found in early-onset breast cancer patients at 11%, 6% and 5% respectively, suggesting that TP53 mutation screening should be considered for these patients. However, we find that even in low resource Asian settings where family history is poorly reported, germline TP53 mutations are found predominantly among breast cancer patients with a family history of LFS-linked cancers.