Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

BACKGROUND AND AIM: Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. MATERIALS AND METHODS: From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. RESULTS: The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10(9)/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. CONCLUSIONS: King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Emerging role for colorectal cancer screening in Asian countries.

BACKGROUND AND AIM: Colorectal cancer (CRC) is one of the leading causes of cancer related mortality globally. Though Asia has traditionally been considered a relatively low incidence area for colorectal cancer, the incidence is reportedly increasing. The Asia Pacific Working Group for Colorectal Cancer has recommended screening of individuals at average risk starting from 50 years of age. Based on these recommendations we conducted a pilot study to assess the need and feasibility of a colorectal cancer screening program in the state of Qatar. METHODS AND RESULTS: We screened 1385 individuals by fecal immunochemical testing for occult blood, at the primary health center level and positive cases were referred for colonoscopy. Among those who tested positive for fecal occult blood, we picked up five patients with cancers and seven with neoplastic polyps. CONCLUSION: Our results compare with the yield of screening programs in western countries thus suggesting an emerging role for colorectal cancer screening in Asian countries.

Transcutaneous electrical stimulation of auricular branch of the vagus nerve effectively and rapidly modulates the EEG patterns in patients with possible electrographic status epilepticus.

BACKGROUND: Invasive vagal nerve stimulation (iVNS) is a known treatment approach for patients with refractory epilepsy. Transcutaneous auricular vagus nerve stimulation (tVNS) was developed to overcome the side effects and surgical complications of iVNS. tVNS is proven beneficial in refractory epilepsy. The effectiveness of tVNS, however, has never been studied in patients with Status Epilepticus. In this study, we explored the effect of tVNS in three patients with possible electrographic status epilepticus. OBJECTIVES: To compare the EEG pattern before, during and after tVNS in three patients with possible electrographic status epilepticus. METHODS: Three consecutive patients with possible electrographic status epilepticus were included after due consenting process. In addition to the standard care, tVNS was applied on the left ear over the cymba concha in two sessions, 6 h apart, with each session for 45 min. Continuous EEG monitoring was performed as standard of care and the findings before, during and after tVNS were documented. RESULTS: The duration of status epilepticus at the time of inclusion of Patients 1, 2, and 3 was 6 weeks, 7 days, and 5 days respectively. All were in coma and on multiple antiseizure medications. Patient 1 and 3 were on anesthetic infusions. Before stimulation, one patient had burst suppression pattern and two had generalized periodic discharges at 1 Hz frequency. We observed a significant reduction/resolution of ongoing EEG patterns in all three patients during the stimulation. The abnormal patterns re-emerged approximately 20 min post cessation of tVNS. No stimulation-related side effects were detected. There was no change in clinical status, but all three patients had severe underlying conditions. SIGNIFICANCE: Transcutaneous auricular Vagus Nerve Stimulation (tVNS) is a potential noninvasive adjuvant therapy that can modulate EEG patterns in patients with Status epilepticus. Larger studies in early SE are needed to assess its clinical benefits.

Effectiveness of High-Intensity Interval Training and Continuous Moderate-Intensity Training on Blood Pressure in Physically Inactive Pre-Hypertensive Young Adults.

The likelihood of pre-hypertensive young adults developing hypertension has been steadily increasing in recent years. Despite the fact that aerobic exercise training (AET) has demonstrated positive results in lowering high blood pressure, the efficacy of different types of AET among pre-hypertensive young adults has not been well-established. The objective of this study was to evaluate the effectiveness of high-intensity interval training (HIIT) and continuous moderate-intensity training (CMT) on the blood pressure (BP) of physically inactive pre-hypertensive young adults. In total, 32 adults (age 20.0 ± 1.1 years and BMI 21.5 ± 1.8) were randomly assigned to three groups: HIIT, CMT and control (CON). The HIIT and CMT groups participated in 5 weeks of AET, while the CON group followed a DASH diet plan only. The HIIT protocol consisted of a 1:4 min work to rest ratio of participants, at an 80−85% heart rate reserve (HR-reserve) and a 40−60% HR-reserve, respectively, for 20 min; the CMT group exercised at 40−60% of their HR-reserve continuously for 20 min. In both the HIIT and CMT groups, systolic blood pressure (SBP) (3.8 ± 2.8 mmHg, p = 0.002 vs. 1.6 ± 1.5 mmHg, p = 0.011) was significantly reduced, while significant reductions in the diastolic blood pressure (DBP) (2.9 ± 2.2 mmHg, p = 0.002) and mean arterial pressure (MAP) (3.1 ± 1.6 mmHg, p < 0.0005) were noted only in the HIIT group. No significant differences in SBP (−0.4 ± 3.7 mmHg, p = 0.718), DBP (0.4 ± 3.4 mmHg, p = 0.714), or MAP (0.1 ± 2.5 mmHg, p = 0.892) were observed in the CON group. Both HIIT and CMT decreased BP in physically inactive pre-hypertensive young adults; however, HIIT yielded more beneficial results in terms of reducing the SPB, DBP and MAP.

High Adenoma Detection Rates in Fecal Immunochemical Test-Based Colorectal Cancer Screening: Interim Results of the National Bowel Cancer Screening Program in Qatar.

INTRODUCTION: Colorectal cancer is one of the most common cancers globally. Recent reductions in mortality rates have been primarily attributed to screening programs. The State of Qatar established a national bowel cancer screening program in 2016. METHODOLOGY: Fecal immunochemical testing (FIT) was used for average-risk individuals aged 50 to 74 years. Fecal immunochemical testing -positive participants were referred for total colonoscopy to detect polyps and cancers. RESULTS: Among 32,751 FIT invitees, 11,130 took the test, and 758 (6%) of those were FIT positive. Of these, 375 (56.13%) participants underwent a colonoscopy, and polyps were detected in 198 (52.8%) and cancers in 19 (5.1%) participants. The adenoma detection rate exceeded 40%. DISCUSSION AND CONCLUSION: The high yield of polyps and cancers in the screening program justifies an active, resource-intensive, and organized bowel cancer screening effort. The high adenoma detection rate in a FIT-based program warrants recalibration of target adenoma detection rates in screening programs.

Myalgia during interferon therapy--does it warrant monitoring muscle enzymes?

Myositis during interferon therapy is a known but rare adverse event. However the clinician may overlook the symptom-complex of proximal muscle weakness and myalgia, seen in myositis, since myalgia is a commonly reported side effect of therapy. In this context then, is there a role for monitoring muscle enzymes to detect subclinical myositis in patients on interferon therapy? We prospectively monitored the creatine kinase (CK) and lactate dehydrogenase (LD) levels in all our patients who reported myalgia during treatment and noted that muscle enzymes remained within normal range throughout the duration of treatment. This excluded the possibility of subclinical myositis in myalgic patients and thus led us to conclude that routine monitoring of muscles enzymes is neither necessary nor beneficial.

A second arterial conduit to the circumflex circulation significantly improves survival after coronary artery bypass surgery.

OBJECTIVES: Conventional coronary artery bypass surgery involves the use of a single left internal mammary artery to the left anterior descending artery and saphenous vein grafts reserved for other sites. This retrospective propensity-matched study investigated the impact of a second arterial conduit to the left-sided circulation on early and long-term survival after coronary artery bypass surgery. METHODS: Data were retrospectively collected from 2004 to 2014 for all revascularizations with at least 1 arterial and/or 1 venous graft to the circumflex circulation, in addition to an internal mammary artery to the left anterior descending artery. Propensity-matched groups were created based on baseline characteristics. Hazard functions were estimated using Cox multivariable regression, and the Kaplan-Meier survival curves were compared between the matched cohorts. RESULTS: A total of 1226 patients with a venous conduit to the left-sided circulation were successfully matched to an equal number of patients with an arterial conduit. Regression analysis identified a second arterial conduit, logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE), pulmonary disease, left ventricular ejection fraction, New York Heart Association (NYHA) Class and previous myocardial infarction as significant predictors of survival. A second arterial graft to the left circumflex circulation was a predictor of improved survival (hazard ratio 0.64, 95% confidence interval 0.51-0.80; P < 0.001). There were significant early and late survival benefits (arterial vs venous: 98.2% vs 96.3%, P = 0.003 at 1 year; 82.4% vs 62.2%, P < 0.001 at 10 years) from a second arterial conduit to the circumflex circulation. CONCLUSIONS: There are significant early and late incremental survival benefits from a second arterial conduit to the circumflex circulation.

Larvicidal efficacy of Adiantobischrysene from Adiantum latifolium against Oryctes rhinoceros through disrupting metamorphosis and impeding microbial mediated digestion.

BACKGROUND: Oryctes rhinoceros Linn. (Coleoptera: Scarabaeidae) is a serious pest of coconuts and other palms. Symbiotic gut bacteria play significant roles in the digestion of cellulosic materials as well as in some other physiological processes essential for the existence of O. rhinoceros larvae. The study was undertaken to isolate a compound with antibacterial and larvicidal activities from the leaves of Adiantum latifolium Lam. following a bioassay-guided method. RESULTS: Methanol extract (ME) of dry leaf powder of A. latifolium showed larvicidal activity against third-instar O. rhinoceros (LD50 , 5018 mg/kg) with antibacterial activity on its gut microbiota. An in vitro study showed the bacteria Bacillus cereus, Micrococcus lylae, Stenotrophomonas maltophilia, Kocuria rosea, Burkholderia mallei, Staphylococcus epidermidis, S. arlettae and Corynebacterium afermentans identified from the larval gut were sensitive to ME. Bioactivity-guided isolation of the compound by liquid-liquid extraction and column chromatography resulted in Adiantobischrysene which showed antibacterial and larvicidal activity (LD50 , 8.4 mg/kg) and led to weight loss and precocious metamorphosis in larvae. An enzyme immunoassay showed a large peak in 20-hydroxyecdysone that commits larvae to precocious metamorphosis. CONCLUSION: This study demonstrated that the antibacterial and metamorphosis disrupting activity of Adiantobischrysene make it a natural pesticidal compound against O. rhinoceros. © 2018 Society of Chemical Industry.

Augmentation of tibial fixation of soft-tissue grafts in anterior cruciate ligament reconstruction.

PURPOSE: Fixation of the tibial aspect of soft-tissue grafts in anterior cruciate ligament (ACL) reconstruction is problematic. Augmentation of the interference fit in screw application is seen as a means of improving fixation. This study aims to determine the effect of mesh augmentation of interference screw application in ACL reconstruction. METHODS: Forty cadaveric ovine hind limbs were harvested at necropsy. A quadrupled hamstring tendon graft (QHT), used in human ACL reconstruction, was simulated. Metal and bioresorbable interference screws were used for tibial fixation in the presence or absence of mesh augmentation. Anterior translation of the reconstruction was determined via radiostereometric analysis; specimens were then subjected to tensile loading, with load to failure and mechanism of failure recorded. RESULTS: There was no improvement in biomechanical properties observed for either the metal or bioresorbable screws with mesh as evaluated by load to failure or anterior translation in this cadaveric model. CONCLUSIONS: The use of a synthetic mesh, encompassing the strands of a QHT and interference screw, did not significantly improve the strength or rigidity of the simulated ACL reconstruction performed. CLINICAL RELEVANCE: Metal interference screws have provided a more secure fixation in the QHT when compared with bioresorbable screws. Augmentation of the reconstruction, by the application of mesh in the tibial tunnel, proved difficult to apply with no observed benefit to either the mechanical or radiologic attributes of the reconstruction.

A prospective randomized comparison of Medtronic Mosaic and Carpentier-Edwards-SAV in the aortic position: an interim report.

BACKGROUND AND AIM OF THE STUDY: The study aim was to compare prospectively the clinical performance and long-term durability of the Medtronic Mosaic and Carpentier-Edwards porcine (CE-SAV) bioprostheses in the aortic position over 10 years. METHODS: Between January 2001 and July 2003, a total of 242 patients undergoing bioprosthetic aortic valve replacement (AVR) were prospectively randomized to receive either Medtronic Mosaic (n = 126) or CE-SAV (n = 116) valves, and followed up annually. RESULTS: The mean follow up period was 1.7 +/- 0.8 years; total follow up was 411 patient-years. Early mortality and 40-month actuarial survival were 5.5% and 93 +/- 1% for the Mosaic valve, and 2.6% and 90 +/- 1% for the CE-SAV. Among patients, 78% showed symptomatic improvement in their NYHA functional class after AVR. To date there have been no structural failures, and one patient required reoperation for prosthetic valve (Mosaic) endocarditis. Early thromboembolic events occurred in 2.9% of patients (two Mosaic, five CE-SAV). Echocardiographic evaluations between the two valves demonstrated comparable hemodynamic performance for a given size at one year after surgery. CONCLUSION: At this stage of the study there were no differences in clinical or hemodynamic outcome in patients undergoing AVR using either the Mosaic or CE-SAV porcine xenograft.

Spontaneous rupture of giant gastric stromal tumor into gastric lumen.

BACKGROUND: Gastrointestinal stromal tumors (GIST) constitute a large majority of mesenchymal tumors of the gastrointestinal (GI) tract, which express the c-kit proto-oncogene protein, a cell membrane receptor with tyrosine kinase activity. GI stromal tumors of the stomach are usually associated with bleeding, abdominal pain or a palpable mass. CASE PRESENTATION: A 75-year-old male presented with upper abdominal pain and palpable mass. Computed tomographic (CT) scan of the abdomen showed a large mass arising in the posterior aspect of fundus, body, and greater curvature of the stomach. Second day after the admission, there was significant reduction in the size of the tumor, clinically as well as radiologically. Endoscopic biopsy showed large bulge in fundus and corpus of the stomach posteriorly with an opening in the posterior part of the corpus, and biopsy from the edge of the opening reveled GIST. Patient underwent curative resection. CONCLUSION: Spontaneous ruptured of giant gastric stromal tumor is very rare presentation of stomach GIST. Thorough clinical examination and timely investigation can diagnose rare complication.

Skeletal infections in cirrhotics.

There are few reports of skeletal infections in patients with cirrhosis. We present two such cases, both with alcoholic liver disease, seen over a period of one year. The first, a 46-year-old man, presented as pyrexia of unknown origin, and was found to have pyogenic discitis; he responded to antibiotic and surgery. The second, a 42-year-old man, presented with chest wall abscess and was diagnosed to have tubercular osteomyelitis; he expired despite treatment with non-hepatotoxic anti-tubercular drugs.

Factors determining successful outcome following pneumatic balloon dilation in achalasia cardia.

BACKGROUND: Pneumatic balloon dilation is a popular method of treating patients with achalasia cardia. It may be useful to know the factors that predict response to this treatment. AIM: To determine predictors of outcome following pneumatic balloon dilation in patients with achalasia cardia. METHODS: Records of 62 patients who had undergone pneumatic dilation using Rigiflex balloon dilators (Boston Scientific, Boston, MA, USA) were reviewed. Follow-up data were available for 52 patients. Data from patients with and without improvement in symptoms were compared. RESULTS: Of the 52 patients (age mean 44 [range 11-68] years; 27 male; median symptom duration 20 [4-90] months], 42 (81%) patients had response in symptoms after balloon dilatation. On univariate analysis, the responders more often had age> 40 years (26/42 [62%] versus 1/10 [10%], p=0.003), and less often had lower esophageal sphincter pressure> 50 mmHg (8/10 [80%] versus 10/42 [24%], p=0.0007) and mid-esophageal body hypocontraction (7/10 [70%] versus 12/24 [29%] p=0.01) than the non-responders. On multivariate analysis only age

Does emerging Clarithromycin resistance signal an obituary to empirical standard triple therapy for Helicobacter pylori infection?

Despite 30 years of its discovery, the ideal therapeutic regimen against Helicobacter pylori is still evasive. Clarithromycin-based standard triple therapy which has been considered the first line empirical therapy has been failing in many parts of the world, due to rising resistance against Clarithromycin, forcing the use of alternate regimens. In this context, we studied the local antibiotic resistance patterns against H. pylori and its impact on standard triple therapy in our region. All patients undergoing diagnostic upper endoscopy during the study period and detected to be positive for rapid urease test (RUT) underwent cultures of gastric mucosal specimens and had their antibiotic resistance patterns mapped out. Standard triple therapy was administered to those tested positive for H. pylori by RUT and eradication rates checked by urea breath test 4 weeks after the completion of treatment. Eradication rates with Clarithromycin-based standard triple therapy were suboptimal with a success of only (71.28%). H. pylori culture and antibiotic susceptibility studies showed high resistance to Clarithromycin (21.2%), Metronidazole (78.1%), and Levofloxacin (15%). However, the resistance to Amoxicillin (2.9%), Tetracycline (0%), and Rifabutin (4.5%) were low. Standard triple therapy is failing in our region due to high Clarithromycin resistance. We need to abandon empirical and blind triple therapy without post-treatment testing and devise alternate effective treatment strategies against H. pylori based on the local resistance patterns observed.

Clinical Application of AIMS65 Scores to Predict Outcomes in Patients with Upper Gastrointestinal Hemorrhage.

BACKGROUND/AIMS: To evaluate the ability of the recently proposed albumin, international normalized ratio (INR), mental status, systolic blood pressure, age >65 years (AIMS65) score to predict mortality in patients with acute upper gastrointestinal bleeding (UGIB). METHODS: AIMS65 scores were calculated in 251 consecutive patients presenting with acute UGIB by allotting 1 point each for albumin level <30 g/L, INR >1.5, alteration in mental status, systolic blood pressure ≤90 mm Hg, and age ≥65 years. Risk stratification was done during the initial 12 hours of hospital admission. RESULTS: Intensive care unit (ICU) admission, endoscopic therapy, or surgery were required in 51 patients (20.3%), 64 (25.5%), and 12 (4.8%), respectively. The predictive accuracy of AIMS65 scores ≥2 was high for blood transfusion (area under the receiver operator characteristic curve [AUROC], 0.59), ICU admission (AUROC, 0.61), and mortality (AUROC, 0.74). The overall mortality was 10.3% (n=26), and was 3%, 7.8%, 20%, 36%, and 40% for AIMS65 scores of 0, 1, 2, 3, and 4, respectively; these values were significantly higher in those with scores ≥2 (30.9%) than in those with scores <2 (4.5%, p<0.001). CONCLUSIONS: AIMS65 is a simple, accurate, non-endoscopic risk score that can be applied early (within 12 hours of hospital admission) in patients with acute UGIB. AIMS65 scores ≥2 predict high in-hospital mortality.

Noninvasive biomarkers FibroTest and ActiTest versus liver biopsy in chronic hepatitis C patients: the Middle East experience.

BACKGROUND: The aim of this study was to compare noninvasive biomarkers, FibroTest and ActiTest in predicting fibrosis stage and inflammation grade in chronic hepatitis C (CHC) patients with liver biopsy (LB). METHODS: In 107 patients with CHC, levels of six serum biomarkers (alanine aminotransferase, γ-glutamyl transpeptidase, total bilirubin, haptoglobin, apolipoprotein, α-2 macroglobulin) were determined at the time of LB. LB was evaluated by Metavir score for fibrosis and inflammation. Voluntary blood donors (n=106) were taken as controls for the study. RESULTS: Fibrosis estimated by Fibrotest was significantly higher in patients compared to control group. The observed area under the receiver operating characteristic curve (AUROC) for advanced fibrosis (F3, F4) adjusted according to the observed difference between advanced and non-advanced fibrosis prevalence (DANA) was 0.80 (0.69-0.88) and the AUROC for cirrhosis (F4) was 0.94 (0.86-0.98). ActiTest AUROC for moderate to severe activity (A2A3) was 0.72 (0.61-0.81), and for severe activity (A3) was 0.88 (0.78-0.93). The diagnostic values in the group of good quality biopsy (n=41) showed Fibrotest AUROC (DANA-adjusted): for advanced fibrosis 0.90 (0.72-0.99); for cirrhosis 0.93 (0.76-0.98); and ctiTest AUROC: for moderate/severe activity 0.86 (0.67-0.94); and for severe activity 0.90 (0.76-0.93). There was good concordance between FibroTest and LB (with discordance for two or more stages in <20% for advanced fibrosis and <10% for cirrhosis) and between ActiTest and LB. Specificity for FibroTest and ActiTest in the control population were 95% and 100% respectively. CONCLUSIONS: Fibrotest and ActiTest had high observed and standardized diagnostic values for predicting fibrosis and activity respectively.

Screening for hepatitis C in average and high-risk populations of Qatar using rapid point-of-care testing.

BACKGROUND: Screening for hepatitis C has been found to be beneficial in high-risk individuals and 'baby boomers'. OBJECTIVE: Our aim was to screen for hepatitis C in average and high-risk individuals and compare the disease characteristics and response to treatment among the screened group (SG) and non-screened group (NSG). METHOD: Community-based screening for hepatitis C was done in the average and high-risk populations of Qatar. Screening was done using rapid point-of-care testing. All patients with stage 1 fibrosis on liver biopsy were treated with pegylated interferon and ribavirin. RESULTS: In total, 13,704 people were screened and 272 (2%, 95% CI (1.8-2.2%) had positive antibodies to hepatitis C. During the same period, 237 non-screened patients (NSG) with hepatitis C were referred for treatment. Alanine and aspartate aminotransferases (ALT, AST) and overall fibrosis were significantly lower in the SG as compared with the NSG (p = 0.04, 0.04 and 0.01, respectively). The response to treatment was similar in the SG as compared with the NSG (sustained viral response 61.7 % versus 69.1%, p = 0.55). Average-risk patients had significantly lower ALT levels (p = 0.04) but had similar response to treatment as the high-risk individuals (sustained viral response 63.2 % versus 61%, p = 0.87). CONCLUSION: Screening detects hepatitis C with lesser fibrosis but does not result in better response to pegylated interferon and ribavirin as compared with non-screened patients.