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Personalized medicine in functional gastrointestinal disorders:Understanding pathogenesis to increase diagnostic and treatment efficacy

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World Journal of Gastroenterology 2019年第10期25卷 1185-1196页

作者： Xiao Jing Wang michael camilleri Division of Gastroenterology and Hepatology Clinical Enteric Neuroscience Translational and Epidemiological ResearchMayo Clinic

There is overwhelming evidence that functional gastrointestinal disorders(FGIDs) are associated with specific mechanisms that constitute important targets for personalized treatment. There are specific mechanisms in patients presenting with functional upper gastrointestinal symptoms(UGI Sx). Among patients with UGI Sx, approximately equal proportions(25%) of patients have delayed gastric emptying(GE), reduced gastric accommodation(GA), both impaired GE and GA,or neither, presumably due to increased gastric or duodenal sensitivity.Treatments targeted to the underlying pathophysiology utilize prokinetics,gastric relaxants, or central neuromodulators. Similarly, specific mechanisms in patients presenting with functional lower gastrointestinal symptoms, especially with diarrhea or constipation, are recognized, including at least 30% of patients with functional constipation pelvic floor dyssynergia and 5% has colonic inertia(with neural or interstitial cells of Cajal loss in myenteric plexus); 25% of patients with diarrhea-predominant irritable bowel syndrome(IBSD) has evidence of bile acid diarrhea; and, depending on ethnicity, a varying proportion of patients has disaccharidase deficiency, and less often sucrose-isomaltase deficiency. Among patients with predominant pain or bloating, the role of fermentable oligosaccharides, disaccharides, monosaccharides and polyols should be considered. Personalization is applied through pharmacogenomics related to drug pharmacokinetics, specifically the role of CYP2 D6, 2 C19 and 3 A4 in the use of drugs for treatment of patients with FGIDs. Single mutations or multiple genetic variants are relatively rare, with limited impact to date on the understanding or treatment of FGIDs. The role of mucosal gene expression in FGIDs, particularly in IBS-D, is the subject of ongoing research. In summary, the time for personalization of FGIDs, based on deep phenotyping, is here;pharmacogenomics is relevant in the use of central neuromodulators. There is still unclear impact of the role of gen

关键词： Gastrointestinal symptoms Gastric emptying Gastric accommodation Diarrhea Constipation Irritable bowel syndrome Bile acid diarrhea Phenotypes Pharmacogenomics Prokinetics Neuromodulators

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Current and future impact of clinical gastrointestinal research on patient care in diabetes mellitus

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World Journal of Diabetes 2018年第11期9卷 180-189页

作者： Timothy R Koch Timothy R Shope michael camilleri Center for Advanced Laparoscopic General and Bariatric Surgery MedStar Washington Hospital Center and Georgetown University School of Medicine Division of Gastroenterology and Hepatology Mayo Clinic

The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus

关键词： Obesity Gastric emptying Diabetes mellitus Gastric bypass Bariatric surgery Weight loss

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Nitrogen enhanced drainage of CO2 rich coal seams for mining

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International Journal of Mining Science and Technology 2017年第5期27卷 755-761页

作者： Luke D.Connell Regina Sander michael camilleri Deasy Heryanto Zhejun Pan Nicholas Lupton CSIRO Energy ClaytonVictoria 3169Australia

Coal seams with high CO_2 gas contents can be difficult to drain gas for outburst management. Coal has a high affinity for CO_2 with adsorption capacities typically twice that of CH_4. This paper presents an analysis of nitrogen injection into coal to enhance drainage of high CO_2 gas contents. Core flooding experiments were conducted where nitrogen was injected into coal core samples from two Australian coal mining basins with initial CO_2 gas contents and pressures that could be encountered during underground mining. Nitrogen effectively displaced the CO_2 with mass balance analysis finding there was only approximately 6%–7% of the original CO_2 gas content residual at the end of the core flood. Using a modified version of the SIMED II reservoir simulator, the core flooding experiments were history matched to determine the nitrogen and methane sorption times. It was found that a triple porosity model(a simple extension of the Warren and Root dual porosity model) was required to accurately describe the core flood observations. The estimated model properties were then used in reservoir simulation studies comparing enhanced drainage with conventional drainage with underground in seam boreholes. For the cases considered, underground in seam boreholes were found to provide shorter drainage lead times than enhanced drainage to meet a safe gas content for outburst management.

关键词： Gas drainage High CO2 ECBM Reservoir simulation

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糖尿病性胃轻瘫

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糖尿病天地(临床) 2008年第1期2卷 24-29页

作者： michael camilleri 李兴荣光 Miles and Shirley Fiterman Center for Digestive Diseases Mayo Clinic College of MedicineRochesterMN

一位36岁的男性病人,1型糖尿病病史20年,并有糖尿病视网膜病变,周围感觉神经病变以及糖尿病肾病。近几个月时感恶心,并呕吐未消化的食物和胆汁,体重下降4公斤。进食1小时后给患者做体格检查,卧位血压130/ 80mmHg,但立位血压是110/60mmH... 详细信息

一位36岁的男性病人,1型糖尿病病史20年,并有糖尿病视网膜病变,周围感觉神经病变以及糖尿病肾病。近几个月时感恶心,并呕吐未消化的食物和胆汁,体重下降4公斤。进食1小时后给患者做体格检查,卧位血压130/ 80mmHg,但立位血压是110/60mmHg。上腹胀但腹肌软,未闻及振水音。如何评价和治疗该

关键词：胃轻瘫胃肠道症状营养物质糖尿病患者神经病变胰高糖素胰高血糖素高血糖胃排空延迟胃潴留替加色罗餐后红霉素抗菌素食物

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Dental anomalies in first-degree relatives of transposed canine probands

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International Journal of Oral Science 2015年第3期7卷 169-173页

作者： Adriana Bartolo Neville Calleja Fraser McDonald Simon camilleri Broadstreet Dental Centre Department of Public Health Medical School University of Malta Dental Institute Department of Orthodontics Kings College London

The aim of this study was to investigate and compare the inheritance pattern and prevalence of inheritable dental anomalies in a sample of patients with maxillary canine—first premolar transposition and their first-degree relatives with a sample of palatally displaced canine families. Thirty-five consecutive maxillary canine—first premolar transposition probands and 111 first-degree relatives were matched to 35 consecutive palatally displaced canine probands and 115 first-degree relatives. These were assessed for palatally displaced canines and incisor-premolar hypodontia. Parental age at birth of the proband was also noted. The results revealed that（i） there is no difference in the overall prevalence of palatally displaced canine or incisor-premolar hypodontia between the groups of relatives;（ii） first-degree relatives of bilateral palatally displaced canine probands have a higher prevalence of palatally displaced canine and incisor-premolar hypodontia than those with unilateral palatally displaced canine; and（iii） maternal age at birth of the maxillary canine—first premolar transposition probands was significantly higher than that of the palatally displaced canine probands.The results suggest that maxillary canine—first premolar transposition and palatally displaced canine are unlikely to be different genetic entities and also indicate environmental or epigenetic influences on dental development.

关键词： ectopic epigenomics genetics hypodontia orthodontics tooth eruption

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New endoscopy advances to refine adenoma detection rate for colorectal cancer screening:None is the winner

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World Journal of Gastrointestinal Oncology 2017年第10期9卷 402-406页

作者： Marcello Maida Salvatore camilleri Michele Manganaro Serena Garufi Giuseppe Scarpulla Section of Gastroenterology S.Elia-M.Raimondi Hospital93100 CaltanissettaItaly

Colorectal cancer(CRC) is the third most common cancer in males and second in females, and globally the fourth cause for cancer death worldwide. Oncological screening of CRC has a major role in the management of the disease and it is mostly performed by colonoscopy. Anyway, effectiveness of endoscopic screening for CRC strictly depends on adequate detection and removal of potentially precancerous lesions, and accuracy of colonoscopy in detection of adenomas is still suboptimal. For this reason, several technological advances have been implemented in order to improve the diagnostic sensitivity of colonoscopy in adenoma detection. Among these:(1) Visual technologies such as chromoendoscopy and narrow band imaging;(2) optical innovation as high definition endoscopy, full-spectrum endoscopy or Third Eye Retroscope; and(3) mechanical advances as Cap assisted colonoscopy, Endocuff, Endoring and G-Eye endoscope. All these technologies advances have been tested over time by clinical studies with mixed results. Which of them is more likely to be successful in the next future?

关键词： Colorectal cancer screening Colonoscopy Adenoma detection rate Diagnostic advances

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IZZY camilleri：挫折成就的女人

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服装设计师 2007年第3期 60-67页

作者：蓓蓓 Izzy camilleri

每个国家都会出现一些改变人们视线的设计师，他们的创意和巧思，把时尚界渲染得五光十色，多姿多彩，我们称之为“新锐力量”，与其他人的年少成名相比，Izzy camilleri用了近20年的时间才成就了自己的梦想，在经历了人太多的磨难，太... 详细信息

每个国家都会出现一些改变人们视线的设计师，他们的创意和巧思，把时尚界渲染得五光十色，多姿多彩，我们称之为“新锐力量”，与其他人的年少成名相比，Izzy camilleri用了近20年的时间才成就了自己的梦想，在经历了人太多的磨难，太多的危机之后的2006年，她以加拿大人独有的勇气与乐观精神，获得了“加拿大年度最佳设计师”的头衔。

关键词：女人挫折设计师加拿大

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Elevated levels of the pollutant PM2.5 in crowded subways of cities with high COVID-19 related mortality-when COVID-19 went underground

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Infectious Diseases Research 2021年第3期2卷 35-41页

作者： Yves Muscat Baron Liberato camilleri Mater Dei Hospital University of Malta Medical SchoolMsidaMalta

Background:Recent literature indicates that the pollutant,particulate matter PM2.5,may have an impact on COVID-19 related infection and mortality.Genes coding for SARS-CoV-2 has been found adherent to PM2.5 and possibly the COVID-19/PM2.5 complex may be involved in the transmission and the exacerbation of COVID-19 infection.PM2.5 levels in deep underground subways have been found up to 90 times higher than roads closer to the surface.Method:The levels of PM2.5 were retrieved from literature assessing particulate matter PM2.5 measured on subway platforms in two groups of cities.These cities were differentiated by the COVID-19 population percentage mortality rate(0.007%vs 0.19%)(P<0.0004).Data regarding the number of stations,length of the networks(km)and the annual ridership were also obtained from literature related to underground commuting.Results:The population percentage mortality related to SARS-CoV-2 infection correlated significantly for both minimum(P<0.01)and maximum(P<0.00001)levels of PM2.5.The cities’subways with low COVID-19 mortality had minimum platform PM2.5 levels of 27.4(SD+/-17.2μg/m3)compared to 63.4μg/m3(SD+/-10.8μg/m3)in cities with high SARS-CoV-2 associated mortality(P<0.01).Subway maximum levels of PM2.5 in cities with low COVID-19 mortality was 53.4μg/m3(SD+/-21.8μg/m3)while that of underground networks with high COVID-19 mortality had maximum platform PM2.5 levels of 172.1μg/m3(SD+/-98μg/m3)(P<0.001).Conclusion:Underground networks may have inherent characteristics accelerating spread of SARSCoV-2 infection and consequent mortality.The highly elevated levels of PM2.5 in overcrowded subways with extensive reach,may have acted as a co-factor to disseminate the pandemic in a number of metropolises.

关键词： COVID-19/SARS-CoV-2 Mortality PM2.5 Subway/underground

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The Initial Implementation of the Sentinel Lymph Node Biopsy (SLNB) for Breast Cancer Management in Malta

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Journal of Cancer Therapy 2013年第3期4卷 765-773页

作者： camilleri Gail Borg Grima Karen Zarb Francis Department of Radiography Faculty of Health Sciences University of Malta Msida Malta Department of Radiography Faculty of Health Sciences University of Malta Msida Malta. Medical Imaging Department Mater Dei Hospital Msida Malta

Over the past two decades, the sentinel lymph node biopsy (SLNB) based on sentinel node (SN) being the first lymph node that harbors metastases, revolutionized breast cancer management. SLNB presents much less morbidity when compared to radical axillary lymph node dissection (ALND) where all nodes are dissected irrespective of their metastatic involvement. The purpose of this study was to evaluate the effectiveness of SLNB by investigating whether the histological characteristics of the SNs identified using scintigraphy are predictive of the histological characteristics of the ALN basin. Methods: Fifty-five female breast cancer patients underwent lymphoscintigraphy and SLNB followed by ALND. The histological status of the SN/s was correlated to the histological status of the ALNs to determine whether the SN accurately stages the ALNs in breast cancer. Results: During surgery, SNs were successfully isolated in 52 out of 55 cases (94.5%) (range, 0 to 9). No SNs were identified in 3 cases (5.5%). Results demonstrate a significant association (p = 0.05) between the metastatic status of SNs and the corresponding ALNs in 42 out of 52 patients (80.8%), but with a high false-negative rate (FNR) of 37.5%. Conclusion: The findings of this study show that the sentinel node concept provides the benefits of SLNB in the majority of instances. However, further work is required in reducing the FNR. Once the effectiveness of SLNB as a staging technique is locally established, the need of ALND in SN-negative patients would be limited, thus improving the quality of life of Maltese breast cancer patients.

关键词： Breast Cancer Sentinel Node Lymphoscintigraphy Sentinel Lymph node Biopsy Axillary Lymph Node Dissection

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Effectiveness of very low-volume preparation for colonoscopy:A prospective, multicenter observational study

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World Journal of Gastroenterology 2020年第16期26卷 1950-1961页

作者： Marcello Maida Emanuele Sinagra Gaetano Cristian Morreale Sandro Sferrazza Giuseppe Scalisi Dario Schillaci Marco Ventimiglia Fabio Salvatore Macaluso Giovanni Vettori Giuseppe Conoscenti Concetta Di Bartolo Serena Garufi Domenico Catarella Michele Manganaro Clara Maria Virgilio Salvatore camilleri Gastroenterology and Endoscopy Unit S.Elia-Raimondi HospitalCaltanissetta 93100Italy Gastroenterology and Endoscopy Unit Istituto San Raffaele GiglioCefalu 90015Italy Gastroenterology and Endoscopy Unit Santa Chiara HospitalTrento 38014Italy Gastroenterology Unit ARNAS GaribaldiCatania 95100Italy Gastroenterology Unit Basarocco HospitalNiscemi 93015CaltanissettaItaly Department of Internal Medicine Villa Sofia-Cervello HospitalPalermo 90100Italy

BACKGROUND The effectiveness of colonoscopy strictly depends on adequate bowel cleansing.Recently,a 1 L polyethylene glycol plus ascorbate(PEG-ASC)solution(Plenvu;Norgine,Harefield,United Kingdom)has been introduced on the evidence of three phase-3 randomized controlled trials,but it had never been tested in the real-life.AIM To assess the effectiveness and tolerability of the 1 L preparation compared to 4 L and 2 L-PEG solutions in a real-life setting.METHODS All patients undergoing a screening or diagnostic colonoscopy after a 4,2 or 1 L PEG preparation,were consecutively enrolled in 5 Italian centers from September 2018 to February 2019.The primary endpoints of the study were the assessment of bowel cleansing success and high-quality cleansing of the right colon.The secondary endpoints were the evaluation of tolerability,adherence and safety of the different bowel preparations.Bowel cleansing was assessed through the Boston Bowel Preparation Scale.Adherence was defined as consumption of at least 75%of each dose,while tolerability was evaluated through a semiquantitative scale.Safety was systematically monitored through adverse events reporting.RESULTS Overall,1289 met the inclusion criteria and were enrolled in the study.Of these,490 patients performed a 4 L-PEG preparation(Selgesse^■),566 a 2 L-PEG cleansing(Moviprep^■or Clensia^■)and 233 a 1 L-PEG preparation(Plenvu^■).Bowel cleansing by Boston Bowel Preparation Scale was 6.5±1.5 overall and 6.3±1.5,6.2±1.5,7.3±1.5(P<0.001)in the subgroups of 4 L,2 L and 1 L-PEG preparation,respectively.Cleansing success was achieved in 72.4%,74.1%and 90.1%(P<0.001),while a high-quality cleansing of the right colon in 15.9%,12.0%and 41.4%(P<0.001)for 4 L,2 L and 1 L-PEG preparation groups,respectively.The 1 L preparation was the most tolerated compared to the 2 and 4 L-PEG solutions in the absence of serious adverse events within any of the three groups.Multiple regression models confirmed 1 L PEG-ASC preparation as an independent predictor of overall cleansing success,high-

关键词： Colonoscopy Bowel preparation Polyethylene glycol Polyethylene glycolplus ascorbate Effectiveness Tolerability

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