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1.
Biomed J ; 45(4): 654-664, 2022 08.
Article in English | MEDLINE | ID: mdl-34314900

ABSTRACT

BACKGROUND: Tuberculosis (TB) is a disease with worldwide presence and a major cause of death in several developing countries. Current diagnostic methodologies often lack specificity and sensitivity, whereas a long time is needed to obtain a conclusive result. METHODS: In an effort to develop better diagnostic methods, this study aimed at the discovery of a biomarker signature for TB diagnosis using a Nuclear Magnetic Resonance based metabolomics approach. In this study, we acquired 1H NMR spectra of blood serum samples of groups of healthy subjects, individuals with latent TB and of patients with pulmonary and extra-pulmonary TB. The resulting data were treated with uni- and multivariate statistical analysis. RESULTS: Six metabolites (inosine, hypoxanthine, mannose, asparagine, aspartate and glutamate) were validated by an independent cohort, all of them related with metabolic processes described as associated with TB infection. CONCLUSION: The findings of the study are according with the WHO Target Product Profile recommendations for a triage test to rule-out active TB.


Subject(s)
Aspartic Acid , Tuberculosis , Asparagine , Biomarkers , Glutamates , Humans , Hypoxanthines , Inosine , Magnetic Resonance Spectroscopy , Mannose , Metabolomics/methods , Tuberculosis/diagnosis
2.
Emerg Microbes Infect ; 9(1): 1131-1139, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32486916

ABSTRACT

Although 23% of world population is infected with Mycobacterium tuberculosis (M. tb), only 5-10% manifest the disease. Individuals surely exposed to M. tb that remain asymptomatic are considered potential latent TB (LTB) cases. Such asymptomatic M. tb.-exposed individuals represent a reservoir for active TB cases. Although accurate discrimination and early treatment of patients with active TB and asymptomatic M. tb.-exposed individuals are necessary to control TB, identifying those individuals at risk of developing active TB still remains a tremendous clinical challenge. This study aimed to characterize the differences in the serum metabolic profile specifically associated to active TB infected individuals or to asymptomatic M. tb.-exposed population. Interestingly, significant changes in a specific set of metabolites were shared when comparing either asymptomatic house-hold contacts of active TB patients (HHC-TB) or active TB patients (A-TB) to clinically healthy controls (HC). Furthermore, this analysis revealed statistically significant lower serum levels of aminoacids such as alanine, lysine, glutamate and glutamine, and citrate and choline in patients with A-TB, when compared to HHC-TB. The predictive ability of these metabolic changes was also evaluated. Although further validation in independent cohorts and comparison with other pulmonary infectious diseases will be necessary to assess the clinical potential, this analysis enabled the discrimination between HHC-TB and A-TB patients with an AUC value of 0.904 (confidence interval 0.81-1.00, p-value < 0.0001). Overall, the strategy described in this work could provide a sensitive, specific, and minimally invasive method that could eventually be translated into a clinical tool for TB control.


Subject(s)
Latent Tuberculosis/diagnosis , Latent Tuberculosis/metabolism , Metabolomics/methods , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/metabolism , Biomarkers/blood , Carrier State/diagnosis , Carrier State/microbiology , Humans , Latent Tuberculosis/blood , Magnetic Resonance Spectroscopy , Mycobacterium tuberculosis/metabolism , Prospective Studies , Tuberculosis, Pulmonary/blood
3.
Benef Microbes ; 9(5): 697-706, 2018 Sep 18.
Article in English | MEDLINE | ID: mdl-29888656

ABSTRACT

A combination of Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R and Lactobacillus rhamnosus CLR2 was compared to placebo for relief of symptoms of irritable bowel syndrome (IBS). A total of 113 subjects at 3 clinical sites were randomised in a 2:1 ratio and followed for 12 weeks. Subjects ingested either 2 capsules of active study product, containing 50×109 cfu of live organisms, or 2 placebo capsules daily. Endpoints included improvement in abdominal pain, days of pain, distention, stool consistency and frequency, quality of life (QOL), and adequate relief (AR) of IBS symptoms. IBS subtypes constipation (IBS-C), diarrhoea (IBS-D), and mixed (IBS-M) were evaluated separately; the effect of gender was also examined. For all efficacy endpoints improvement of 30% or more vs placebo was considered clinically significant. With the exception of pain intensity and AR, the endpoints demonstrated a therapeutic advantage of active over placebo for IBS symptoms in at least some subject subgroups. The IBS-D and female subgroups showed the largest and most consistent effects. Stool frequency and consistency were evaluated in the IBS-C and IBS-D subgroups, and improvement of active vs placebo was noted in both. QOL improvement was seen overall and in specific domains. Adverse events (AEs) were limited to 7 subjects; all were of mild or moderate intensity except one, severe cramping. Four AEs in the same subject in the placebo group were judged to be related to study product; these resolved by the end of study. There were no serious AEs.


Subject(s)
Irritable Bowel Syndrome/drug therapy , Lacticaseibacillus casei/physiology , Lacticaseibacillus rhamnosus/physiology , Lactobacillus acidophilus/physiology , Probiotics/administration & dosage , Quality of Life , Adult , Double-Blind Method , Female , Humans , Male , Middle Aged , Probiotics/adverse effects , Prospective Studies , Treatment Outcome
5.
Mymensingh Med J ; 26(2): 451-454, 2017 04.
Article in English | MEDLINE | ID: mdl-28588186

ABSTRACT

The supplementary motor area (SMA-proper) is important for the programming and execution of motor, speech, and other elaborative functions. SMA is frequently involved by brain tumors (particularly WHO grade II gliomas). Surgery in this area can be followed by the 'SMA syndrome', characterised by contralateral akinesia and mutism. We present a case of Falcine meningioma in the region of the right SMA which developed SMA syndrome. Our patient showed complete recovery of neurological function but the process was slow with a specific pattern.


Subject(s)
Brain Neoplasms , Glioma , Motor Cortex , Brain Neoplasms/surgery , Glioma/surgery , Humans , Motor Cortex/physiopathology , Postoperative Complications , Postoperative Period , Syndrome
6.
Mymensingh Med J ; 26(1): 202-204, 2017 01.
Article in English | MEDLINE | ID: mdl-28260777

ABSTRACT

Calvarial Tuberculosis (CTB) is very rare form of TB. A 35 year old lady presented with a painless bony swelling over the right frontal area with an enlarged pre-auricular lymphnode. The CT revealed an expansile lytic lesion involving right frontal bone with minimal dural enhancement. In the presence of normal ESR, no past history of Tuberculosis, an expansile lytic lesion with intradural enhancement and previous inconclusive FNAC of pre-auricular lymphnode; she underwent surgical excision which revealed caseous granulation suggestive of TB.


Subject(s)
Tuberculosis, Osteoarticular , Adult , Female , Humans , Lymph Nodes , Musculoskeletal Pain/etiology , Tuberculosis, Osteoarticular/complications , Tuberculosis, Osteoarticular/diagnosis , Tuberculosis, Osteoarticular/surgery
7.
Aliment Pharmacol Ther ; 45(2): 291-299, 2017 01.
Article in English | MEDLINE | ID: mdl-27859421

ABSTRACT

BACKGROUND: High-resolution manometry has become the preferred choice of oesophagologists for oesophageal motor assessment, but the learning curve among trainees remains unclear. AIM: To determine the learning curve of high-resolution manometry interpretation. METHODS: A prospective interventional cohort study was performed on 18 gastroenterology trainees, naïve to high-resolution manometry (median age 32 ± 4.0 years, 44.4% female). An intake questionnaire and a 1-h standardised didactic session were performed at baseline. Multiple 1-h interpretation sessions were then conducted periodically over 15 months where 10 studies were discussed; 5 additional test studies were provided for interpretation, and results were compared to gold standard interpretation by the senior author. Hypothetical management decisions based on trainee interpretation were separately queried. Accuracy was compared across test interpretations and sessions to determine the learning curve, with a goal of 90% accuracy. RESULTS: Baseline accuracy was low for abnormal body motor patterns (53.3%), but higher for achalasia/outflow obstruction (65.9%). Recognition of achalasia reached 90% accuracy after six sessions (P = 0.01), while overall accurate management decisions reached this threshold by the 4th session (P < 0.001). Based on our data, the threshold of 90% accuracy for recognition of any abnormal from normal pattern was reached after 30 studies (3rd session) but fluctuated. Diagnosis of oesophageal body motor patterns remained suboptimal; accuracy of advisability of fundoplication improved, but did not reach 90%. CONCLUSIONS: High-resolution manometry has a steep learning curve among trainees. Achalasia recognition is achieved early, but diagnosis of other abnormal motor patterns and management decisions require further supervised training.


Subject(s)
Esophageal Achalasia/diagnosis , Esophagus/physiopathology , Gastroenterology/education , Adult , Esophageal Achalasia/physiopathology , Esophagus/surgery , Female , Fundoplication , Gastroenterology/methods , Humans , Learning Curve , Male , Manometry/methods , Surveys and Questionnaires
8.
Mymensingh Med J ; 25(3): 564-6, 2016 07.
Article in English | MEDLINE | ID: mdl-27612908

ABSTRACT

Extradural and epicranial pneumatocele is a rare condition. It may complicate with CSF rhinorrhoea and meningitis which can have a fatal outcome. We present a case of delayed post-operative extradural and epicranial pneumatocele in the frontal region following primary repair of the anterior skull base for a traumatic compound craniofacial injury with CSF leakage. There was no evidence of meningitis or raised ICP. As the patient was neurologically stable; he was managed conservatively and had a spontaneous resolution of the pneumatocele.


Subject(s)
Cerebrospinal Fluid Rhinorrhea , Pneumocephalus , Humans , Male , Pneumocephalus/complications , Remission, Spontaneous
9.
Dis Esophagus ; 29(8): 1013-1019, 2016 Nov.
Article in English | MEDLINE | ID: mdl-26471871

ABSTRACT

Symptom reflux association (SRA) assesses symptoms associated with reflux events defined by pH <4.0, but limited symptoms associate with reflux events. We evaluated the impact of alternate pH thresholds on SRA in a large ambulatory pH database. Acid exposure time (AET), reflux events, and associated symptoms (within 2 minutes following a reflux event) were extracted from ambulatory pH studies performed off antireflux therapy (722 patients, 49.1 ± 0.5 years, 66.8% F) over a 7-year period. Symptom association probability (SAP) and symptom index (SI) were calculated at pH 3.5, 4.0, 4.5, and 5. Receiver operating characteristics (ROC) were generated using SRA at any pH as gold standard; areas under the curve (AUCs) were determined. Discordant cases were reanalyzed to determine changes in SRA and predictors of change using multivariate regression. At pH 4.0, 41% had a positive SAP, and 34% had a positive SI. While there was sustained gain in SI positivity from acidic to more weakly acidic pH thresholds, SAP positivity was highest at pH 4.5. On ROC analysis, performance characteristics were best at pH 4.0 (AUC 0.97) for SAP, and at pH 4.5 and 5.0 (AUC 0.92-0.94) for SI. On multivariate logistic regression adjusting for age, gender, and change in AET and reflux events, only number of associated symptoms predicted change in SRA (P < 0.0001). Changing pH thresholds for reflux events augments SRA by increasing reflux events associated with existing symptoms, while symptom recording remains the principal determinant of SRA.


Subject(s)
Chest Pain/etiology , Cough/etiology , Gastroesophageal Reflux/complications , Heartburn/etiology , Cross-Sectional Studies , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/metabolism , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Retrospective Studies
10.
Scand J Immunol ; 79(3): 197-205, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24313289

ABSTRACT

Cytokine gene polymorphisms are known to be associated with functional differences in cytokine regulation and may affect host susceptibility to tuberculosis (TB). Contacts are important group in developing tuberculosis infection and are 10-60 times more likely to develop TB than general population. The present study was carried out in patients with TB (N = 176), their household contacts (HHC; N = 155) from Free Chest TB Clinic PPM DOTS (1TU) covering 500,000 population at Mahavir Hospital and Research Centre, Hyderabad, and healthy controls (HC; N = 170) also included. The association of single-nucleotide polymorphisms (SNPs) in the promoter region of TNF-α (-308G/A), IL-2 (-330T/G), IL-4 (-589C/T) and in exon region of TGF-ß1 (+869T/C) genes was assessed by ARMS & PCR-RFLP using specific primers in the above-mentioned subjects. The differences in allelic or genotypic frequencies of TNF-α (-308G/A) between patients, their HHC and HC were not statistically significant (P > 0.05). IL-2 (-330T/G) TG genotype was significantly different between patients, HHC compared to HC (P < 0.002, OR-1.997, 95%CI-1.260-3.168, P < 0.03, OR-1.602, 955CI-1.003-2.561).IL-4 (-589C/T) CC genotype was significantly different between patients and HC (P < 0.03, OR-1.791, 95%CI-1.009-3.189) as well as between HHC and HC at P < 0.0001, OR-2.56, 95%CI-1.448-4.545. In addition, the TGF-ß 1 (+869T/C) TC genotype was significantly associated with susceptibility to tuberculosis in patients when compared against HC(P < 0.0001, OR-3.416, 95%CI-2.063-5.670) and HHC (P < 0.0001, OR-2.357, 95%CI-1.439-3.868), respectively.MDR analysis indicated that TT genotype of TGF-ß1 with TT and CT genotypes of IL-4 showed high risk with GA, TT genotypes of TNF-α, IL-2, respectively. Our results suggest that IL-2 (-330T/G), IL-4 (-589 C/T) and TGF-ß1 (+869T/C) gene polymorphisms may be associated with TB susceptibility.


Subject(s)
Interleukin-2/genetics , Interleukin-4/genetics , Transforming Growth Factor beta1/genetics , Tuberculosis/genetics , Tumor Necrosis Factor-alpha/genetics , Adult , Alleles , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Male , Polymorphism, Restriction Fragment Length/genetics , Polymorphism, Single Nucleotide , Promoter Regions, Genetic/genetics , Tuberculosis/diagnosis
11.
Scand J Immunol ; 79(2): 113-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24219580

ABSTRACT

Vitamin D, an immunomodulator of macrophage function, can activate human antimycobacterial activity. Vitamin D deficiency (VDD) is associated with an impaired mycobacterial immunity and susceptibility to tuberculosis. It has been found that vitamin D and its receptor may be essential for immune function. In this study, we examined the serum 25(OH) vitamin D levels and its receptor (VDR) polymorphisms with susceptibility to tuberculosis in patients, household contacts and healthy controls. Serum 25(OH) vitamin D levels were measured in 75 cases (25 patients, 25 household contacts and 25 healthy controls), and polymorphisms (BsmI and FokI) were carried out in 335 cases (110 patients, 110 household contacts and 115 healthy controls). The proportion of serum 25(OH) vitamin D deficiency and insufficiency was high in patients (44, 58%) and household contacts (40, 48%) compared to controls (48%). The BB and Bb genotypes of BsmI were significantly associated in patients (P < 0.014; OR: 0.509; CI: 0.265-0.876) (P < 0.001; OR: 2.351; CI: 1.368-4.041) and household contacts (P < 0.04; OR: 0.575; CI: 0.336-0.985); (P < 0.002; OR: -2.267; CI: 1.32-3.895) when compared to healthy controls. The diplotype and MDR analysis showed the high-risk genotypes of BsmI and FokI polymorphisms. Vitamin D deficiency and its association with VDR gene polymorphisms may be useful to identify the high-risk group individuals.


Subject(s)
Polymorphism, Genetic , Receptors, Calcitriol/genetics , Tuberculosis, Pulmonary/etiology , Vitamin D/analogs & derivatives , Adolescent , Adult , Deoxyribonucleases, Type II Site-Specific/metabolism , Disease Susceptibility , Female , Haplotypes , Humans , Male , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/genetics , Vitamin D/blood
12.
Dis Esophagus ; 27(7): 623-9, 2014.
Article in English | MEDLINE | ID: mdl-24006939

ABSTRACT

Previously developed novel probe-based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high-grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low-grade dysplasia/high-grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4-82.3). The accuracy was higher when pathologists had 'high confidence' in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53-0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1-90.7) and the specificity was 70% (95% CI: 61.91-77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.


Subject(s)
Adenocarcinoma/pathology , Barrett Esophagus/pathology , Endoscopy, Digestive System/methods , Esophageal Neoplasms/pathology , Precancerous Conditions/pathology , Adenocarcinoma/diagnosis , Barrett Esophagus/diagnosis , Esophageal Neoplasms/diagnosis , Humans , Learning Curve , Microscopy, Confocal , Neoplasm Grading , Observer Variation , Pathology , Precancerous Conditions/diagnosis , Sensitivity and Specificity
13.
Scand J Immunol ; 78(3): 221-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23672492

ABSTRACT

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (M. tb), and it remains one of the major bacterial infections worldwide. Innate immunity is an important arm of antimycobacterial host defence mechanism that senses various pathogen-associated molecular patterns (PAMP) of microbes by a variety of pattern recognition receptors (PRRs). As per the recent discovery, Toll-like receptors (TLRs) play a crucial role in the recognition of M. tb, this immune activation occurs only in the presence of functional TLRs. Variants of TLRs may influence their expression, function and alters the recognition or signalling mechanism, which leads to the disease susceptibility. Hence, the identification of mutations in these receptors could be used as a marker to screen the individuals who are at risk. In this review, we discuss TLR SNPs and their signalling mechanism to understand the susceptibility to TB for better therapeutic approaches.


Subject(s)
Immunity, Innate/genetics , Mycobacterium tuberculosis/immunology , Toll-Like Receptors/genetics , Toll-Like Receptors/immunology , Tuberculosis/immunology , Genetic Predisposition to Disease , Humans , Myeloid Differentiation Factor 88/metabolism , Polymorphism, Single Nucleotide , Signal Transduction/immunology , Toll-Like Receptors/metabolism , Tuberculosis/genetics
15.
Endoscopy ; 45(2): 86-92, 2013.
Article in English | MEDLINE | ID: mdl-23307148

ABSTRACT

BACKGROUND AND STUDY AIMS: It is uncertain if needle gauge impacts the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of pancreatic mass lesions. Our aim was to use meta-analysis to more robustly define the diagnostic accuracy of EUS-FNA for pancreatic masses using 22 G and 25 G needles. PATIENTS AND METHODS: Studies were identified by searching nine medical databases for reports published between 1994 and 2011, using a reproducible search strategy comprised of relevant terms. Only studies comparing the overall diagnostic accuracy of 22 G vs. 25 G EUS needles that used surgical histology or at least 6 months clinical follow up for a gold standard were included. Two reviewers independently scored the identified studies for methodology and abstracted pertinent data. When required, the original investigators were contacted to provide additional data. Pooling was conducted by both fixed-effects and random-effects models. Diagnostic characteristics (sensitivity, specificity, positive and negative likelihood ratios) with 95% confidence intervals (CIs) were calculated. RESULTS: Eight studies involving 1292 subjects met the defined inclusion criteria. Of the 1292 patients, 799 were in the 22 G group and 565 were in the 25 G group (both needles were used in 72 patients). The pooled sensitivity and specificity of the 22 G needle were 0.85 (95%CI 0.82-0.88) and 1 (95%CI 0.98-1) respectively. The pooled sensitivity and specificity of the 25 G needle were 0.93 (95%CI 0.91-0.96) and 0.97 (95%CI 0.93-0.99) respectively. The bivariate generalized linear random-effect model indicated that the 25 G needle is associated with a higher sensitivity (P = 0.0003) but comparable specificity (P = 0.97) to the 22 G needle. CONCLUSIONS: This meta-analysis suggests 25 G needle systems are more sensitive than 22 G needles for diagnosing pancreatic malignancy.


Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Needles , Pancreatic Neoplasms/pathology , Humans , Sensitivity and Specificity
16.
Dis Esophagus ; 26(2): 124-9, 2013.
Article in English | MEDLINE | ID: mdl-22404535

ABSTRACT

Standard endoscopy is an insensitive test for gastroesophageal reflux disease (GERD). Narrow band imaging (NBI) endoscopy enhances visualization of the distal esophagus. NBI patterns like intrapapillary capillary loop (IPCL) dilatation, tortuosity, and increased number; microerosions; increased vascularity at the squamocolumnar junction (SCJ); ridge-villous pattern below the SCJ; and presence of columnar islands in the distal esophagus have been suggested as features of GERD. We evaluated the effect of proton pump inhibitor (PPI) therapy on NBI findings in GERD patients. Patients prospectively underwent NBI upper endoscopy before and after PPI therapy. NBI findings were recorded at each endoscopy. Twenty-one patients with GERD symptoms (mean age 60.0 years; males 90.5%; white 90.5%) were studied. After PPI therapy, there was a significant reduction in the proportion of patients with the following NBI features: IPCL tortuosity (90% vs. 4.8%, P < 0.0001), dilated IPCLs (86% vs. 9.5%, P < 0.0001), and increased vascularity at the SCJ (43% vs. 9.5%, P= 0.0082). PPI led to healing of all microerosions (71% vs. 0%, P < 0.0001) and disappearance of ridge-villous patterns below the SCJ (14% vs. 0%, P < 0.0001). There was no significant change in the proportion of patients with increased numbers of IPCLs pre- and post-PPI therapy (71% vs. 48%, P= 0.09) or columnar islands in the distal esophagus (38% vs. 29%, P= 0.31). In patients with GERD symptoms, NBI features suggestive of GERD respond to PPI; suggesting these features are truly acid-mediated. These findings need to be confirmed by randomized controlled trials.


Subject(s)
Esomeprazole/therapeutic use , Esophagoscopy/methods , Esophagus/pathology , Gastroesophageal Reflux/drug therapy , Narrow Band Imaging , Proton Pump Inhibitors/therapeutic use , Adult , Aged , Drug Administration Schedule , Female , Gastroesophageal Reflux/pathology , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Single-Blind Method , Treatment Outcome
17.
Aliment Pharmacol Ther ; 35(9): 1080-7, 2012 May.
Article in English | MEDLINE | ID: mdl-22428660

ABSTRACT

BACKGROUND: Both simple proportions and statistical tests are utilised for symptom-reflux association. We systematically compared three such tests in a clinical setting. AIM: To compare the three commonly used symptom reflux association tests in a large cohort of patients undergoing ambulatory pH monitoring for the evaluation of oesophageal symptoms. METHODS: Ambulatory pH data from 772 symptomatic subjects (49.1 ± 0.5 years; 479 F) tested off therapy were assessed for acid exposure time (AET, elevated when pH <4 for ≥4%), symptom index (SI, ≥50% when positive), and symptom association probability (SAP) and Ghillebert probability estimate (GPE, P < 0.05 when positive). Test concordance and discordance were individually assessed; discordance between statistical tests was minor if one had P < 0.1 while the other was positive. Logistic regression determined independent predictors of test discordance. RESULTS: The SAP, GPE and SI were positive in 42.7%, 39.3% and 33.9% respectively. GPE performed extremely well compared to SAP (sensitivity 0.95, specificity 0.91), with major discordance in only 2.8%. Positive concordance was significantly higher when AET was abnormal. GPE underestimated symptom association compared to SAP, whereas SAP was subject to symptom over-counting in 33.3% of discordant cases. GPE-SAP discordance was associated with higher AET (7.5% vs. 5.1%) and more symptoms (19.3 vs. 10.7, P > 0.001 for each comparison with concordant tests); both remained significant on logistic regression analysis (P ≤ 0.003). SI was discordant with SAP when symptoms were extremely frequent (median 19, IQR 10-32) or limited (median 1, IQR 1-2), and concordant when median 6 symptoms (IQR 3-12) were recorded. CONCLUSIONS: The GPE can be used interchangeably with SAP in symptom reflux association. SI has uncertain value with very high and very low symptom counts.


Subject(s)
Esophageal pH Monitoring , Gastroesophageal Reflux/diagnosis , Female , Gastroesophageal Reflux/physiopathology , Humans , Hydrogen-Ion Concentration , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity
18.
Endoscopy ; 43(9): 745-51, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21833901

ABSTRACT

BACKGROUND AND STUDY AIMS: The clinical utility of narrow-band imaging (NBI) for Barrett's esophagus is limited by the multiplicity of classification schemes. We evaluated the interobserver agreement and accuracy of a new consensus-driven simplified binary classification of NBI surface patterns.


Subject(s)
Adenocarcinoma/pathology , Barrett Esophagus/classification , Barrett Esophagus/pathology , Esophageal Neoplasms/pathology , Esophagus/pathology , Precancerous Conditions/pathology , Adult , Aged , Aged, 80 and over , Esophagoscopy , Female , Humans , Image Enhancement , Male , Metaplasia , Middle Aged , Mucous Membrane/pathology , Observer Variation , Predictive Value of Tests , Reproducibility of Results
19.
Aliment Pharmacol Ther ; 33(11): 1202-8, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21453401

ABSTRACT

BACKGROUND: Mechanisms of symptom perception among patients with gastro-oesophageal reflux disease (GERD) remain to be fully elucidated. AIM: To correlate quantitative reflux symptom scores with microscopic oesophageal histopathology. METHODS: Prior to endoscopy, patients with reflux symptoms completed a validated reflux disease questionnaire (score 0-36). Erosive oesophagitis (EO) was graded using the LA classification. Oesophageal biopsies were graded 0-2 for basal cell hyperplasia, papillary elongation, dilated intercellular spaces (DIS), necrosis or erosion, eosinophils and neutrophils by a blinded gastrointestinal pathologist as previously described. Additionally, lymphocyte density was also evaluated. Pearson's correlation coefficients were computed. RESULTS: Thirty-two EO and 21 non-erosive reflux disease (NERD) patients were prospectively enrolled. For EO vs. NERD, mean reflux symptom scores (10.7 vs. 8.8, P=0.35) and histology scores were similar (4.29 vs. 4.25; P=0.9). However, when symptom scores were compared with histology scores, a correlation was found in the EO group, but not in the NERD group (r=0.34, P=0.05 vs. r=0.22, P=0.36). On further analysis, DIS was associated with symptom scores in the EO group (P≤0.001), but not in the NERD group (P=N.S.). Similarly, lymphocyte density was associated with symptom scores in the EO group (r=0.56, P=0.0009), but not in the NERD group (r=0.002, P=0.9). CONCLUSIONS: Although mean symptom and histology scores were similar in the EO and NERD groups, a significant correlation of symptom scores with histology scores, DIS and lymphocytes was found in the former, but not in the latter. EO and NERD patients may have different symptom perception mechanisms and thus, dissimilar symptom resolution rates with acid suppression.


Subject(s)
Gastroesophageal Reflux/pathology , Heartburn/physiopathology , Adult , Aged , Biopsy , Endoscopy, Gastrointestinal/methods , Extracellular Space/physiology , Female , Gastroesophageal Reflux/complications , Heartburn/etiology , Humans , Hydrogen-Ion Concentration , Lymphocytes/physiology , Male , Middle Aged , Prospective Studies , Severity of Illness Index , Statistics as Topic , Surveys and Questionnaires
20.
Am J Gastroenterol ; 106(6): 1055-63, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21407181

ABSTRACT

OBJECTIVES: Risk stratification of Barrett's esophagus (BE) using biomarkers remains an important goal. We evaluated feasibility and clinical accuracy of novel microRNA (miRNA) biomarkers for prediction of BE dysplasia. METHODS: Paired fresh-frozen and hematoxylin/eosin specimens from a prospective tissue repository where only biopsies with the lesion of interest (i.e., intestinal metaplasia (IM) or high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC)) occupying >50% of biopsy area were included. Tissue miRNA expression was determined by microarrays and validated by quantitative reverse transcription-PCR (qRT-PCR). Three groups were compared-group A, IM tissues from BE patients without dysplasia; group B, IM tissues from group C patients; and group C, dysplastic tissues from BE patients with HGD/EAC. RESULTS: Overall, 22 BE patients, 11 with and without dysplasia (mean age 64 ± 8.2 and 63 ± 11.6 years, respectively, all Caucasian males) were evaluated. Nine miRNAs were identified by high-throughout analysis (miR-15b, -21, -192, -205, 486-5p, -584, -1246, let-7a, and -7d) and qRT-PCR confirmed expression of miR-15b, -21, 486-5p, and let-7a. Two of 4 miRNAs (miR-145 and -203, but not -196a and -375) previously described in BE patients also exhibited differential expression. Sensitivity and specificity of miRNAs for HGD/EAC were miR-15b: 87 and 80%, miR-21: 93 and 70%, miR-203: 87 and 90%, miR-486-5p: 82 and 55%, and miR-let-7a: 88 and 70%. MiRNA-15b, -21, and -203 exhibited field effects (i.e., groups A and B tissues while histologically similar yet exhibited different miRNA expression). CONCLUSIONS: This pilot study demonstrates feasibility of miRNAs to discriminate BE patients with and without dysplasia with reasonable clinical accuracy. However, the specific miRNAs need to be evaluated further in future prospective trials.


Subject(s)
Barrett Esophagus/genetics , Barrett Esophagus/pathology , MicroRNAs/analysis , Precancerous Conditions/genetics , Precancerous Conditions/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Aged , Biomarkers/analysis , Biopsy, Needle , Cross-Over Studies , Disease Progression , Feasibility Studies , Female , Gene Expression Regulation , Genetic Markers , Humans , Immunohistochemistry , Linear Models , Male , Microarray Analysis , Middle Aged , Pilot Projects , Predictive Value of Tests , Reverse Transcriptase Polymerase Chain Reaction , Risk Assessment
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