Adenomas and Sessile Serrated Lesions in 45- to 49-Year-Old Individuals Undergoing Colonoscopy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Colorectal cancer (CRC) screening is now recommended at the age of 45 years in the United States. However, information regarding the adenomas detection rate (ADR) and sessile serrated lesions (SSLs) in 45- to 49-year-old individuals is limited. In addition, the impact of lowering the screening age to 45 years on the ADR and the detection rate of SSLs is not well elucidated. This systematic review and meta-analysis aims to report the overall ADR and SSL detection rate in 45- to 49-year-old individuals undergoing colonoscopy. METHODS: We searched MEDLINE, EMBASE, SCOPUS, Web of Science, ClinicalTrials.gov , and the Cochrane database from inception through October 2022 to identify studies reporting on ADR and SSL detection rates in 45- to 49-year-old individuals undergoing colonoscopies for all indications. This approach acknowledges the possibility of including individuals undergoing diagnostic colonoscopies or those with increased risk factors for CRC. We also conducted a separate analysis examining ADR in average-risk individuals undergoing screening colonoscopy. The pooled rates with their corresponding 95% confidence intervals (CIs) were generated using the fixed-effects model. I2 was used to adjudicate heterogeneity. RESULTS: Sixteen studies met the inclusion criteria. All studies were retrospective except one; 3 had data from national/local registries. There were 41,709 adenomas detected across 150,436 colonoscopies. The pooled overall ADR was 23.1% (95% CI 19.7%-27.0%, I2 = 98.6%). The pooled ADR in individuals with average risk of CRC from 7 studies was 28.2% (95% CI 24.6%-32.0%, I2 = 96.5%). The pooled overall SSL detection rate from 6 studies was 6.3% (95% CI 3.8%-10.5%, I2 = 97%). The included studies were heterogeneous because of differences in the inclusion and exclusion criteria and patient population. DISCUSSION: In 45- to 49-year-old individuals undergoing a colonoscopy for any indication, the ADR and SSL detection rates were 23.1% and 6.3%, respectively. We conclude that these outcomes in 45- to 49-year-olds are comparable with individuals aged 50-54 years.

Analysis of Reported Adverse Events Related to Hemospray: An FDA MAUDE Database Study.

BACKGROUND: Topical hemostatic powder is a mineral powder that forms an adherent barrier and coagulates active bleeding in the gastrointestinal (GI) tract. Hemospray is the first hemostatic powder approved by the Food and Drug Administration (FDA) in the United States. Hemospray has been increasingly used to manage GI bleeding. However, data on the adverse events of hemostatic powders are lacking. Therefore, we aim to report and analyze adverse events associated with Hemospray using the FDA's "Manufacturer and User Facility Device Experience" database. METHODS: We analyzed the postmarketing surveillance data from the FDA's Manufacturer and User Facility Device Experience database for Hemospray, initially known as TC-325, from June 2018 through April 2022. Results of the search were classified into device-related technical issues, patient-related adverse events and health care staff-related adverse events. RESULTS: Five hundred two medical device reporting claims were identified from June 2018 through April 2022. Seven duplicate claims were identified, and some claims included more than one event type. Therefore, there were 558 device-related problems, 28 patient-related adverse events, and 2 adverse events in health care staff members. The most common device-related problems were activation failure or failure to fire (n = 385, 70.0%) and obstruction of carbon dioxide flow (n = 121, 21.7). The most common patient-related adverse events included tissue injury or bleeding (n = 21) and perforation (n = 5). CONCLUSION: Although Hemospray is a valuable tool in the armamentarium for endoscopists in managing GI bleeding, endoscopists must be mindful of deice-related problems and potential patient-related adverse events.

Adverse Events and Device Failures Associated with Pancreatic Stents: A Comprehensive Analysis Using the FDA's MAUDE Database.

INTRODUCTION: Pancreatic duct stents (PDS) are widely used for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. However, there is a paucity of data regarding the adverse events associated with PDS placement. This study aims to investigate the reported adverse events and device failures related to PDS, utilizing the Manufacturer and User Facility Device Experience (MAUDE) database maintained by the U.S. Food and Drug Administration (FDA). METHODS: Post-marketing surveillance data from January 2013 to December 8, 2023, were extracted from the FDA's MAUDE database to analyze the reports pertaining to the use of commonly used PDS. The primary outcomes of interest were device issues and patient-related adverse events. Statistical analysis was performed using Microsoft Excel 2010, with the calculation of pooled numbers and percentages for each device and patient adverse event. RESULTS: A total of 579 device issues and 194 patient-related adverse events were identified. Device issues were primarily attributed to stent deformation (n = 72; 12.4%), followed by migration of the device into the pancreatic duct or expulsion out of the duct (n = 60; 10.4%), and stent fracture/breakage (n = 55; 9.4%). Among the patient-reported adverse events, inflammation was the most common (n = 26; 13.4%), followed by reports of stents becoming embedded in tissue (n = 21; 10.8%) and stent occlusion/obstruction (n = 16; 8.2%). The most prevalent device failures associated with Advanix stents were material deformation, with perforation (n = 3, 30%) being the most frequently reported adverse event. Concerning Geenen stents, migration or expulsion of the device (n = 34, 16.9%) constituted the most common device-related adverse events, while inflammation (n = 20, 16.7%) was the most frequently reported patient-related issue. For Zimmon stents, migration or expulsion of the device (n = 22, 8.8%) were the most frequently reported device-related problems, whereas perforation (n = 7, 10.9%) and bleeding (n = 7, 10.9%) were the most frequent patient-related adverse events. CONCLUSION: Our findings highlight important device and patient adverse events that endoscopists and referring providers should be aware of before considering pancreatic stent placement.

Cold snare endoscopic mucosal resection for colon polyps: a systematic review and meta-analysis.

BACKGROUND: Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. METHODS: We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. RESULTS: 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, I2  = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, I2  = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, I2  = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, I2  = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, I2  = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, I2  = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, I2  = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, I2  = 0 %), respectively. CONCLUSION: CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.

Efficacy and Safety of Cold Snare Endoscopic Mucosal Resection (CS-EMR) for Nonampullary Duodenal Polyps: Systematic Review and Meta-Analysis.

INTRODUCTION: There is an increasing interest in cold snare endoscopic mucosal resection (CS-EMR), and studies have shown its safety and efficacy for colonic polyps. This meta-analysis aims to assess the safety and efficacy of CS-EMR for the removal of duodenal adenomas. METHODS: We conducted a comprehensive literature search of several databases, from inception through February 2023, for studies that addressed outcomes of CS-EMR for nonampullary duodenal adenomas. We used the random-effects model for the statistical analysis. The weighted pooled rates were used to summarize the technical success, polyp recurrence, bleeding, and perforation events. Cochran Q test and I2 statistics adjudicated heterogeneity. RESULTS: Six studies were included in the analysis. In all, 178 duodenal polyps were resected using CS-EMR. The pooled rates were 95.8% (95% CI 89.1-98.5%, I2=21.5%) for technical success and 21.2% (95% CI 8.5-43.6%, I2=78%) for polyp recurrence. With regards to CS-EMR safety, the pooled rates were 4.2% (95% CI 1.6-10.5%, I2=12%) for immediate bleeding, 3.4% (95% CI 1.5-7.6%, I2=0%) for delayed bleeding, 2.8% (95% CI 1.1-6.7%, I2=0%) for perforation, and 2% (95% CL 0.5-7.5%, I2=0%) for post-polypectomy syndrome. Rates were not significantly different for large adenomas. Three studies reported data on CS-EMR and conventional EMR. Compared with conventional EMR, CS-EMR had lower odds of delayed bleeding, OR 0.11 (CI 0.02-0.62, P value 0.012, I2=0%). CONCLUSION: Our findings suggest that CS-EMR is a safe and effective strategy for the resection of nonampullary duodenal adenomas, with an acceptable recurrence rate. Data from larger randomized controlled studies are needed to validate our findings.

Dissuasive cigarettes as a tobacco control measure: a scoping review.

OBJECTIVE: The aim was to identify and review the research literature on dissuasive cigarettes, including key concepts, types, sources of evidence and research gaps. DATA SOURCES: PubMed, Scopus and Web of Science databases were searched up to January 2023 with no language or date restrictions. All study designs were included. Reference lists of the identified studies were manually searched. Studies on tobacco products other than cigarettes or on external cigarette packaging alone were excluded. STUDY SELECTION: Two reviewers screened titles and abstracts independently using eligibility criteria. The full text of the selected articles was subsequently screened independently by two reviewers to confirm eligibility. DATA EXTRACTION: Two reviewers independently extracted data from all studies using data abstraction forms. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. DATA SYNTHESIS: We identified 24 original studies, 3 review articles and 4 commentary articles. Research on dissuasive cigarettes was reported from Australia, New Zealand, Europe and North America. We presented results in four themes: the concept of dissuasive cigarettes; approaches and types; potential benefits, barriers and concerns; and current research gaps. CONCLUSIONS: Dissuasive cigarettes represent a promising strategy that could be used in tobacco control. Parallel implementation with plain packaging would be feasible and synergistic.

Histological, haematological, and thyroid hormones toxicity of female rats orally exposed to CuO/ZnO core/shell nanoparticles synthesized by Ar plasma jets.

Advancements in nanomedicine helped scientists design a new class of nanoparticles known as hybrid nanoparticles (core/shell) for diagnostic and therapeutic purposes. An essential requirement for the successful use of nanoparticles in biomedical applications is their low toxicity. Therefore, toxicological profiling is necessary to understand the mechanism of nanoparticles. The current study aimed to assess the toxicological potential of CuO/ZnO core/shell nanoparticles with a size of 32 nm in Albino female rats. In vivo toxicity was evaluated by oral administration of 0, 5, 10, 20, and 40 (mg/L) of CuO/ZnO core/shell nanoparticles to a female rate for 30 consecutive days. During the time of treatment, no deaths were observed. The toxicological evaluation revealed significant (p < 0.01) alteration in white blood cells (WBC) at a 5 (mg/L) dose. Also, increase in red blood cells (RBC) at 5, 10 (mg/L) doses, while hemoglobin (Hb) levels and hematocrit (HCT) increased at all doses. This maybe indicates that the CuO/ZnO core/shell nanoparticles stimulated the rate of blood corpuscle generation. The anaemia diagnostic indices (mean corpuscular volume MCV and mean corpuscular haemoglobin MCH) remained unchanged throughout the experiment for all the doses tested 5, 10, 20, and 40 (mg/L). According to the results of this study, exposure to CuO/ZnO core/shell NPs deteriorates the Triiodothyronine hormone (T3) and a Thyroxine hormone (T4) activated by Thyroid-Stimulating Hormone (TSH), which is generated and secreted from the pituitary gland. There is possibly related to an increase in free radicals and a decrease in antioxidant activity. Significant (p < 0.01) growth retardation in all groups treated due to rats' infection by Hyperthyroidism induced by thyroxine (T4) level increase. Hyperthyroidism is a catabolic state related to increased energy consumption, protein turnover, and lipolysis. Usually, these metabolic effects result in weight reduction and a decrease in fat storage and lean body mass. The histological examination indicates that the low concentrations of CuO/ZnO core/shell nanoparticles are safe for desired biomedical applications.

The Role of Red Cell Distribution Width as a Prognostic Marker in Chronic Liver Disease: A Literature Review.

Liver disease is one of the leading public health problems faced by healthcare practitioners regularly. As such, there has been a search for an inexpensive, readily available, non-invasive marker to aid in monitoring and prognosticating hepatic disorders. Recently, red blood cell distribution width (RDW) has been found to be associated with various inflammatory conditions with implications for its use as a potential marker for assessing disease progression and prognosis in multiple conditions. Multiple factors effect red blood cell production whereby a dysfunction in any process can lead to anisocytosis. Furthermore, a chronic inflammatory state leads to increased oxidative stress and produces inflammatory cytokines causing dysregulation and increased intracellular uptake and use of both iron and vitamin B12, which leads to a reduction in erythropoiesis causing an increase in RDW. This literature review reviews in-depth pathophysiology that may lead to an increase in RDW and its potential correlation with chronic liver diseases, including hepatitis B, hepatitis C, hepatitis E, non-alcoholic fatty liver disease, autoimmune hepatitis, primary biliary cirrhosis, and hepatocellular carcinoma. In our review, we examine the use of RDW as a prognostic and predictive marker for hepatic injury and chronic liver disease.

Relation Between Baseline CXCR1 Expression And Neoadjuvant Chemotherapy Response In Breast Cancer Patients.

Objectives: To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. RESULTS: Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response. CONCLUSIONS: There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

Effect of hyperbaric oxygen treatment on diabetic foot ulcers: A meta-analysis.

The meta-analysis aimed to assess the effect of hyperbaric oxygen treatment on diabetic foot ulcers. Using dichotomous or contentious random or fixed effect models, the outcomes of this meta-analysis were examined and the odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were computed. 17 examinations from 1992 to 2022 were enrolled for the present meta-analysis, including 7219 people with diabetic foot ulcers. Hyperbaric oxygen treatment had a significantly higher healed ulcer (OR, 14.39; 95% CI, 4.02-51.52, p < 0.001), higher adverse event (OR, 2.14; 95% CI, 1.11-4.11, p = 0.02), lower mortality (OR, 0.22; 95% CI, 0.07-0.71, p = 0.01) and higher ulcer area reduction (MD, 23.39; 95% CI, 11.79-34.99, p < 0.001) compared to standard treatment in patients with diabetic foot ulcers. However, hyperbaric oxygen treatment and standard treatment had no significant difference in amputation (OR, 0.62; 95% CI, 0.22-1.75, p = 0.37), major amputation (OR, 0.59; 95% CI, 0.18-1.92, p = 0.38), minor amputation (OR, 0.64; 95% CI, 0.15-2.66, p = 0.54) and healing time (MD, -0.001; 95% CI, -0.76 to 0.75, p = 0.99) in patients with diabetic foot ulcers. The examined data revealed that hyperbaric oxygen treatment had a significantly higher healed ulcer, adverse event, and ulcer area reduction and lower mortality, however, there was no significant difference in amputation and healing time compared to standard treatment in patients with diabetic foot ulcers. Yet, attention should be paid to its values since most of the selected examinations had a low sample size and some of the comparisons had a low number of selected studies.

Endoscopic Ultrasound Guided Fine-Needle Aspiration for Solid Lesions in Chronic Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with chronic pancreatitis (CP) are at a higher risk of developing pancreatic adenocarcinoma compared the general population with an estimated 5% risk of developing pancreatic cancer in 20 years. Endoscopic ultrasound fine needle aspiration (EUS-FNA) of solid pancreatic lesions (SPL) has an excellent sensitivity (85-90%) and specificity (98-100%) for diagnosing pancreatic malignancy. However, data on the performance characteristics of EUS-FNA in CP are mixed. AIMS: In this systematic review and meta-analysis, we aim to examine data from published studies on the diagnostic performance of EUS-FNA in detecting pancreatic malignancy in CP. METHODS: We conducted a comprehensive search of MEDLINE, Cochrane, EMBASE, Scopus databases for studies published in English language that reported performance characteristics of EUS-FNA for SPL up to November 2020. Two reviewers independently conducted screening, full text review and data extraction according to the PRISMA guidelines. Quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. The parameters of interest were sensitivity, specificity, negative, and positive likelihood ratios. Cochran Q test and I statistics were used to determine the between-study heterogeneity. Funnel plots were used to describe publication bias. RESULTS: A total of 6753 studies were identified on initial search. Studies that reported EUS-FNA of cystic pancreas lesions were excluded. Eight studies met the inclusion criteria. Seven studies were retrospective, and one was prospective. A total of 593 patients with CP underwent EUS-FNA for SPL. The pooled sensitivity of EUS-FNA was 65% (95% CI 52.6-75.6%, I2 = 44%), specificity was 96.8% (75-99.7%, I2 = 89%), negative likelihood ratio (NLR) 41.4 (11.1-149.6, I2 = 70%), positive likelihood ratio (PLR) 24.1 (2.8-208, I2 = 90%). The pooled data from seven studies that compared 901 non-CP vs. 127 CP showed that the sensitivity of EUS-FNA in diagnosing pancreatic malignancy was 91.5 vs. 65.3% [OR (95% CI) 5.5 (2.9-10.2), I2: 31.8%]. The specificity pooled from six studies [333 non-CP vs. 357 CP] was 95.9% vs. 82.4%, [OR (95% CI) 1.3 (0.2-9.8), I2 = 73%]. The risk of bias was serious in one study, low in four studies and moderate in three studies. CONCLUSION: This pooled meta-analysis shows a low sensitivity of EUS-FNA in diagnosing malignancy in CP patients with SPL in comparison to patients without CP. Modalities such as EUS-fine needle biopsy have high sensitivity and specificity for diagnosing pancreatic cancer and should be considered in patients with CP and suspected pancreatic malignancy.

Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates.

(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75−160 mg/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), α-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15−92%) biofilm inhibition/reduction percentage capacity at the concentration of 1−10 mg/mL. Gene expression analysis showed that salicylaldehyde, α-methyl-trans-cinnamaldehyde, and α-bromo-trans-cinnamaldehyde resulted in a significant (p < 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.

HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study.

AIMS/HYPOTHESIS: The prevalence of atherosclerosis is increased in type 1 diabetes despite normal-to-high HDL-cholesterol levels. The cholesterol efflux capacity (CEC) of HDL is a better predictor of cardiovascular events than static HDL-cholesterol. This cross-sectional study addressed the hypothesis that impaired HDL function contributes to enhanced CVD risk within type 1 diabetes. METHODS: We compared HDL particle size and concentration (by NMR), total CEC, ATP-binding cassette subfamily A, member 1 (ABCA1)-dependent CEC and ABCA1-independent CEC (by determining [3H]cholesterol efflux from J774-macrophages to ApoB-depleted serum), and carotid intima-media thickness (CIMT) in 100 individuals with type 1 diabetes (37.6 ± 1.2 years; BMI 26.9 ± 0.5 kg/m2) and 100 non-diabetic participants (37.7 ± 1.1 years; 27.1 ± 0.5 kg/m2). RESULTS: Compared with non-diabetic participants, total HDL particle concentration was lower (mean ± SD 31.01 ± 8.66 vs 34.33 ± 8.04 µmol/l [mean difference (MD) -3.32 µmol/l]) in participants with type 1 diabetes. However, large HDL particle concentration was greater (9.36 ± 3.98 vs 6.99 ± 4.05 µmol/l [MD +2.37 µmol/l]), resulting in increased mean HDL particle size (9.82 ± 0.57 vs 9.44 ± 0.56 nm [MD +0.38 nm]) (p < 0.05 for all). Total CEC (14.57 ± 2.47%CEC/4 h vs 12.26 ± 3.81%CEC/4 h [MD +2.31%CEC/4 h]) was greater in participants with type 1 diabetes relative to non-diabetic participants. Increased HDL particle size was independently associated with increased total CEC; however, following adjustment for this in multivariable analysis, CEC remained greater in participants with type 1 diabetes. Both components of CEC, ABCA1-dependent (6.10 ± 2.41%CEC/4 h vs 5.22 ± 2.57%CEC/4 h [MD +0.88%CEC/4 h]) and ABCA1-independent (8.47 ± 1.79% CEC/4 h vs 7.05 ± 1.76% CEC/4 h [MD +1.42% CEC/4 h]) CEC, were greater in type 1 diabetes but the increase in ABCA1-dependent CEC was less marked and not statistically significant in multivariable analysis. CIMT was increased in participants with type 1 diabetes but in multivariable analysis it was only associated negatively with age and BMI. CONCLUSIONS/INTERPRETATION: HDL particle size but not HDL-cholesterol level is independently associated with enhanced total CEC. HDL particle size is greater in individuals with type 1 diabetes but even after adjusting for this, total and ABCA1-independent CEC are enhanced in type 1 diabetes. Further studies are needed to understand the mechanisms underlying these effects, and whether they help attenuate progression of atherosclerosis in this high-risk group. Graphical abstract.

Acidity constant and DFT-based modelling of pH-responsive alendronate loading and releasing on propylamine-modified silica surface.

A computational methodology that couples the acidity (Ka) and density functional theory (DFT) calculations has been developed to explain the pH-dependent drug loading on and releasing from mesoporous silica nanoparticles. The model has been validated by investigating the pH-dependent loading and releasing of a bisphosphonate drug molecule, alendronate, on a propylamine-modified quartz surface (101), a model for functionalized mesoporous silica nanoparticles. The pH-dependent interacting molecular species are the neutral and anionic forms of the drug molecule, silanol group of quartz surface and the functional group in the case of functionalized quartz surface. The interaction energies of all the molecular species of alendronate with silica surface are calculated by using the DFT-based CASTEP method. Five molecular states of alendronate (D0, D-, D2-, D3- and D4-), two for silica surface (S0 and S-) and two for propylamine (P+ and P0) are considered. Ten possible combinations of interactions of alendronate with silica surface and twenty for alendronate and propylamine-functionalized silica surfaces are calculated. The relative probability of interaction of a particular pair of drug and surface combination at a particular pH is weighed by the product of their fractions, the latter is calculated by using the Handerson-Hasselbach equation. The total interaction energies at a particular pH are calculated by summing the possible individual interaction energies. The variation of total interaction energy with pH shows that the functional group of propylamine lowers the interaction energy at lower pH values (1-5), thus favouring adsorption or loading of the drug and increases the interaction energy at higher pH values (pH > 8) and thus favours desorption or release of the drug. This is in agreement with experimental results where it is shown that propylamine-functionalized mesoporous silica nanoparticles load alendronate in the pH range of 1-5 and release at pH = 8. This method can be used to predict the pH-dependent drug loading and releasing of a particular combination of drug and on a particular drug delivery system.

Patterns and Effects of Admission Hyperglycemia and Inflammatory Response in Trauma Patients: A Prospective Clinical Study.

BACKGROUND: The constellation of the initial hyperglycemia, proinflammatory cytokines and severity of injury among trauma patients is understudied. We aimed to evaluate the patterns and effects of on-admission hyperglycemia and inflammatory response in a level 1 trauma center. We hypothesized that higher initial readings of blood glucose and cytokines are associated with severe injuries and worse in-hospital outcomes in trauma patients. METHODS: A prospective, observational study was conducted for adult trauma patients who were admitted and tested for on-admission blood glucose, hemoglobin A1c, interleukin (IL)-6, IL-18 and hs-CRP. Patients were categorized into four groups [non-diabetic normoglycemic, diabetic normoglycemic, diabetic hyperglycemic (DH) and stress-induced hyperglycemic (SIH)]. The inflammatory markers were measured on three time points (admission, 24 h and 48 h). Generalized estimating equations (GEE) were used to account for the correlation for the inflammatory markers. Pearson's correlation test and logistic regression analysis were also performed. RESULTS: During the study period, 250 adult trauma patients were enrolled. Almost 13% of patients presented with hyperglycemia (50% had SIH and 50% had DH). Patients with SIH were younger, had significantly higher Injury Severity Score (ISS), higher IL-6 readings, prolonged hospital length of stay and higher mortality. The SIH group had lower Revised Trauma Score (p = 0.005), lower Trauma Injury Severity Score (p = 0.01) and lower GCS (p = 0.001). Patients with hyperglycemia had higher in-hospital mortality than the normoglycemia group (12.5% vs 3.7%; p = 0.02). A significant correlation was identified between the initial blood glucose level and serum lactate, IL-6, ISS and hospital length of stay. Overall rate of change in slope 88.54 (95% CI:-143.39-33.68) points was found more in hyperglycemia than normoglycemia group (p = 0.002) for IL-6 values, whereas there was no statistical significant change in slopes of age, gender and their interaction. The initial IL-6 levels correlated with ISS (r = 0.40, p = 0.001). On-admission hyperglycemia had an adjusted odds ratio 2.42 (95% CI: 1.076-5.447, p = 0.03) for severe injury (ISS > 12) after adjusting for age, shock index and blood transfusion. CONCLUSIONS: In trauma patients, on-admission hyperglycemia correlates well with the initial serum IL-6 level and is associated with more severe injuries. Therefore, it could be a simple marker of injury severity and useful tool for patient triage and risk assessment. TRIAL REGISTRATION: This study was registered at the ClinicalTrials.gov (Identifier: NCT02999386), retrospectively Registered on December 21, 2016. https://clinicaltrials.gov/ct2/show/NCT02999386 .

Validation of ERICVA Risk Score as a Predictor of One Year Amputation-Free Survival of Patients with Critical Limb Ischemia.

BACKGROUND: The ERICVA score was derived to predict amputation-free survival in patients with critical limb ischemia (CLI). It may be a useful tool to stratify patients in trials of novel interventions to treat CLI but, as yet, it has not been externally validated. METHODS: A prospective database of CLI patients was developed during prescreening of patients for a phase 1 stem cell therapy clinical trial. The primary outcome was amputation free survival (AFS) at 1 year. Both the full ERICVA scale (11 parameters) and simplified ERICVA scale (5 parameters) were validated. Data analysis was performed by calculation of the area under the receiver operating characteristic (ROC) curve examining the predictive value of the scores. The Chi-square test was used to examine the association between risk group and one-year AFS and the cumulative survival of the three risk groups was compared using Kaplan Meier survival curves. RESULTS: A series of 179 CLI patients were included in the analysis. The Chi-square test of independence showed a significant association between the risk group (high, medium and low) and one-year AFS outcome (P = 0.0007). Kaplan-Meier survival curve showed significant difference in one-year AFS between the three risk groups (log-rank P < 0.001). The area under the curve (AUC) was found to be 0.63 and 0.61 for the full and simplified score, respectively. The sensitivity of the full score was 0.44 with specificity of 0.84. The simplified score had a sensitivity of 0.28 and specificity of 0.92. CONCLUSION: The ERICVA risk score system was found to have a fair validity but cannot be considered reliable as a single predictor of one year AFS of CLI patients. The simplified score had an AUC almost identical to the full score and can accordingly replace the full score.

Baseline MMP expression in periapical granuloma and its relationship with periapical wound healing after surgical endodontic treatment.

BACKGROUND: Matrix metalloproteinases (MMPs) catalyzes the degradation of the extracellular matrix components and have a major role in many physiological processes including wound healing. In the current study, we examined the correlation of baseline MMPs 1, 2, 7, and 9 expressions with periapical wound healing after surgical endodontic treatment. METHODS: 27 patients aged between 15 and 57 years presenting with chronic apical periodontitis or chronic apical abscess of an anterior tooth with previously attempted or failed root canal treatment were included in this study. During surgical endodontic treatment, tissue from the periapical lesion sample was collected and used for gross histopathological analysis as well as mRNA expression analysis of MMPs 1, 2, 7, and 9. Patients were recalled for follow-up after 6  months to evaluate the healing status both clinically and radiographically and healing was correlated with baseline MMP expression. RESULTS: Out of 27 patients, healing was observed in 15 patients at the end of 6 months, and in 21 patients after 12 months.. Six patients showed no healing even after 12 months. Analysis of baseline MMP 1, 2, 7, and 9 expression levels with healing status showed the mean relative expression of MMP2 and MMP9 to be considerably increased in the non-healing group as compared to the healing group. CONCLUSION: Overexpression of MMP2 and MMP9 may be considered as a potential prognostic biomarker for periapical wound healing after surgical endodontic treatment. However, further studies are desirable to establish its precise relationship with periapical wound healing.

Diagnosis, management and outcome of Spinal Cord Injury without Radiographic Abnormalities (SCIWORA) in adult patients with trauma: a case series.

BACKGROUND: Spinal cord injury without radiographic abnormality (SCIWORA) in adults causes diagnostic and prognostic dilemma as radiography and/or computed tomography does not clearly detect bone lesions during the initial assessment. Herein, we report our experience on 11 spinal cord injury cases without radiographic abnormality, regarding the clinicoradiological features, management, and outcomes. METHODS: We conducted a case series of adult patients with SCIWORA who were admitted at the level 1 trauma center at Hamad General Hospital from January 2008 to July 2018. All patients underwent initial head and spine X-ray imaging, computed tomography, magnetic resonance imaging, and 12 months of clinical follow-up. RESULTS: Eleven patients (mean age, 46.5 ± 14.4 years) met the criteria of SCIWORA. The neurologic status on admission and 12 months after hospital discharge were classified according to the American Spinal Injury Association (ASIA) impairment scale (AIS). On admission, 6 (54.5%) patients had ASIA grade C: 2 (18.2%) each had AIS grade D and B and 1 (9.1%) had AIS grade A. Five cases were treated conservatively with rehabilitation and physiotherapy, and five were treated surgically by anterior cervical discectomy with fusion. One patient who declined surgery was managed with a sternal occipital mandibular immobilizer brace and underwent rehabilitation. CONCLUSION: SCIWORA requires higher clinical suspicion and thorough neurological and radiologic assessment to prevent secondary spinal cord injuries and complications.

Epidemiological and clinical characteristics of fall-related injuries: a retrospective study.

BACKGROUND: Fall-related injuries are important public health problem worldwide. We aimed to describe the epidemiological and clinical characteristics of fall-related injuries in a level 1 trauma center. METHOD: A retrospective analysis of Qatar Trauma Registry data was conducted on patients admitted for fall-related injuries between 2010 and 2017. Comparative analyses of data by gender, age-groups and height of falls were performed to describe the epidemiological and clinical characteristics of patients, and in-hospital outcomes. RESULTS: A total of 4040 patients with fall-related injuries were identified in the study duration which corresponds to the rate of 2.34 per 10,000 population. Although the rate of fall-related injuries decreased over the years, the average number of patients per year remained high accounting for 32% of the hospitalized patients with moderate to severe injuries. Most of the injuries affected the head (36%) followed by spines (29%) and chest (23%). Males were predominant (89%), more likely to fall at workplace, fall from a greater height and have polytrauma than females. The working age-group (20-59 years) constituted the majority of injured (73%) and were more likely to fall at workplace, and to fall from higher heights compared to the older adults who sustained more fall at home. Overall in-hospital mortality was 3%. Outcomes including longer hospital length of stay and mortality were generally correlated with the height of fall except for the fall at home. CONCLUSION: Fall-related injuries remain as significant burden even in a level 1 trauma center. Variations in the pattern of injuries by age, gender and height of fall provide important information for targeted preventive measures.

Environmental policy stringency, related technological change and emissions inventory in 20 OECD countries.

Since the parties to Paris agreement ink ambitious emissions reduction targets, there is a growing debate - whether the existing environmental regulations have potential to spur enough technological base that could help to achieve the targets by 2030? Thus, this study attempts to empirically investigate the role of stringent environmental regulations towards environmentally friendly technological innovation, carbon emissions, GDP, exports and imports for 20 OECD countries. The results find long-run equilibrium relationship among the variables and suggest that the current environmental regulations encourage green innovation in the panel countries. Furthermore, stringent environmental policies couple with environmentally friendly innovation are impetus to sustainable development. Exports and imports have little to contribute green innovation but, exports reduce carbon emissions in the short-run only and imports are emissions intensive. The study suggests that the OECD countries need to revisit trade related environmental regulations.