Dye Chromoendoscopy Outperforms High-Definition White Light Endoscopy in Dysplasia Detection for Patients With Inflammatory Bowel Disease: An Updated Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Whether dye spray chromoendoscopy (DCE) adds value in surveillance colonoscopy with high-definition (HD) scopes remains controversial. This updated meta-analysis compares dysplasia detection using DCE and high-definition white light endoscopy (HD-WLE) in patients with inflammatory bowel disease (IBD) undergoing surveillance colonoscopy. METHODS: A comprehensive search was performed for randomized controlled trials (RCT) comparing HD-WLE and DCE in patients with IBD. The primary outcome was to compare the proportion of patients with at least 1 dysplastic lesion detected by DCE vs HD-WLE. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using the random-effects model, with I2 > 60% indicating substantial heterogeneity. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence (CoE). RESULTS: Six RCT involving 978 patients were analyzed (DCE = 479 vs HD-WLE = 499 patients). DCE detected significantly more patients with dysplasia than HD-WLE (18.8% vs 9.4%), OR 1.94 (95% CI 1.21-3.11, I2 = 28%, P = 0.006, high CoE). This remained significant after excluding 2 RCT published as abstracts. A sensitivity analysis excluding a noninferiority RCT with a single experienced operator eliminated the results' heterogeneity, OR 2.46 (95% CI 1.56-3.90, I2 = 0%). Although high-grade dysplasia detection was numerically higher in the DCE group (2.8% vs 1.1%), the difference was statistically insignificant, OR 2.21 (95% CI 0.64-7.62, I2 = 0%, low CoE). DISCUSSION: Our updated meta-analysis supports DCE as a superior strategy in overall dysplasia detection in IBD, even with HD scopes. When expertise is available, DCE should be considered for surveillance colonoscopy in patients with high-risk IBD, with the acknowledgment that virtual chromoendoscopy shows equivalence in recent studies. Further multicenter trials with multiple endoscopists with varying expertise levels and longer-term outcome data showing a reduction in cancer or cancer-related death are needed.

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.

Efficacy, Safety, and Cost-effectiveness of Bezlotoxumab in Preventing Recurrent Clostridioides difficile Infection : Systematic Review and Meta-analysis.

INTRODUCTION: Clostridioides difficile infection (CDI) remains a global health challenge. Bezlotoxumab (BEZ) is a monoclonal antibody against C. difficile toxin B. Two randomized controlled trials (RCTs), MODIFY I and II, confirmed BEZ efficacy in preventing recurrent Clostridioides difficile infection (rCDI). However, there are safety concerns about its use in patients with a history of congestive heart failure. Observational studies have since been conducted, and it is important to explore the consistency of BEZ efficacy, cost-effectiveness, and its safety utilizing these real-world data. METHODS: We performed a systematic review and meta-analysis to pool the rate of rCDI in patients receiving BEZ and explore its efficacy and safety in preventing rCDI compared with control. We searched PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through April 2023 for relevant RCTs or observational studies assessing BEZ in preventing rCDI. Single-arm studies describing experience with BEZ in preventing rCDI were also included for proportion meta-analysis. A proportion meta-analysis with a random-effects model was used to pool the rCDI rate with its corresponding 95% CI. In a meta-analysis of efficacy, we generated the relative risk (RR) to compare BEZ versus control in preventing rCDI. RESULTS: Thirteen studies including 2 RCTs and 11 observational studies totaling 2337 patients, of which 1472 received BEZ, were included in the analysis. Of the constituent studies, 5 (1734 patients) compared BEZ versus standard-of-care (SOC). Pooled rate of rCDI in patients receiving BEZ was 15.8% (95% CI: 14%-17.8%), and was 28.9% (95% CI: 24%-34.4%) in the SOC. BEZ significantly reduced rCDI risk compared with SOC [RR=0.57 (95% CI: 0.45-0.72, I2 =16%)]. There was no difference in the overall mortality or heart failure risk. Of the 9 included cost-effectiveness analyses, 8 demonstrated BEZ+SOC cost-effectiveness compared with SOC alone. DISCUSSION: Our meta-analysis comprising real-world data revealed lower rCDI in patients receiving BEZ and supported its efficacy and safety when added to SOC therapy. The results were consistent across various subgroups. Available cost-effectiveness analyses mostly support BEZ+SOC cost-effectiveness compared with SOC alone.

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.

Impact of Legislation on Brominated Flame Retardant Concentrations in UK Indoor and Outdoor Environments: Evidence for Declining Indoor Emissions of Some Legacy BFRs.

Concentrations of polybrominated diphenyl ethers, hexabromocyclododecane (HBCDD), and novel brominated flame retardants (NBFRs) were measured in indoor dust, indoor air, and outdoor air in Birmingham, UK. Concentrations of ΣBFRs ranged from 490 to 89,000 ng/g, 46-14,000 pg/m3, and 22-11,000 pg/m3, respectively, in UK indoor dust, indoor air, and outdoor air. BDE-209 and decabromodiphenyl ethane (DBDPE) were the main contributors. The maximum concentration of DBDPE (10,000 pg/m3) in outdoor air is the highest reported anywhere to date. In contrast with previous studies of outdoor air in Birmingham, we observed significant correlations between concentrations of tri- to hepta-BDEs and HBCDD and temperature. This may suggest that primary emissions from ongoing use of these BFRs have diminished and that secondary emissions (e.g., evaporation from soil) are now a potentially major source of these BFRs in outdoor air. Conversely, the lack of significant correlations between temperature and concentrations of BDE-209 and DBDPE may indicate that ongoing primary emissions from indoor sources remain important for these BFRs. Further research to clarify the relative importance of primary and secondary sources of BFRs to outdoor air is required. Comparison with earlier studies in Birmingham reveals significant (p < 0.05) declines in concentrations of legacy BFRs, but significant increases for NBFRs over the past decade. While there appear minimal health burdens from BFR exposure for UK adults, dust ingestion of BDE-209 may pose a significant risk for UK toddlers.

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.

Guanidine dicycloamine-based analogs: green chemistry synthesis, biological investigation, and molecular docking studies as promising antibacterial and antiglycation leads.

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

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.

Novel Insights into the Dermal Bioaccessibility and Human Exposure to Brominated Flame Retardant Additives in Microplastics.

In this study, we optimized and applied an in vitro physiologically based extraction test to investigate the dermal bioaccessibility of polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCDD), incorporated as additives in different types of microplastics (MPs), and assess human dermal exposure to these chemicals. The dermal bioaccessibility of PBDEs in polyethylene (PE) MPs was significantly higher (P < 0.05) than in polypropylene (PP) MPs. Both log Kow and water solubility influenced the dermal bioaccessibility of PBDEs. For HBCDDs in polystyrene MPs, the dermally bioaccessible fractions were 1.8, 2.0, and 1.6% of the applied dose for α-, ß-, and γ-HBCDDs, respectively. MP particle size and the presence of cosmetic formulations (antiperspirant, foundation, moisturizer and sunscreen) influenced the bioaccessibility of PBDEs and HBCDDs in MP matrices at varying degrees of significance. Human exposure to ∑PBDEs and ∑HBCDDs via dermal contact with MPs ranged from 0.02 to 22.2 and 0.01 to 231 ng (kg bw)-1 d-1 and from 0.02 to 6.27 and 0.2 to 65 ng (kg bw)-1 d-1 for adults and toddlers, respectively. Dermal exposure to PBDEs and HBCDDs in MPs is substantial, highlighting for the first time the significance of the dermal pathway as a major route of human exposure to additive chemicals in microplastics.

Dermal bioaccessibility of perfluoroalkyl substances from household dust; influence of topically applied cosmetics.

PFAS are known contaminants of indoor dust. Despite the adherence of such dust to skin, the dermal penetration potential of PFAS is not well understood. By applying in vitro physiologically based extraction tests, the bioaccessibility of 17 PFAS from indoor dust to synthetic human sweat sebum mixtures (SSSM) was assessed. The composition of the SSSM substantially impacted the bioaccessibility of all target compounds. PFAS bioaccessibility in a 1:1 sweat:sebum mixture ranged from 54 to 92% for perfluorocarboxylic acids (PFCAs) and 61-77% for perfluorosulfonic acids (PFSAs). Commonly applied cosmetics (foundation, sunscreen, moisturiser, and deodorant) significantly impacted the dermal bioaccessibility of target PFAS, e.g., the presence of moisturiser significantly decreased the total bioaccessibility of both PFCAs and PFSAs. Preliminary human exposure estimates revealed dermal contact with indoor dust could contribute as much as pathways such as drinking water and dust ingestion to an adult's daily intake of PFAS. While further research is needed to assess the percutaneous penetration of PFAS in humans, the current study highlights the potential substantial contribution of dermal exposure to human body burdens of PFAS and the need for further consideration of this pathway in PFAS risk assessment studies.

Endoscopic full-thickness resection for upper gastrointestinal tract lesions: a systematic review and meta-analysis.

INTRODUCTION: Endoscopic full-thickness resection (EFTR) is used to resect difficult superficial mucosal lesions and sub-epithelial lesions (SELs). We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of EFTR for upper gastrointestinal tract (GIT) lesions. METHODS: We conducted a comprehensive literature search of MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov, and Scopus databases for studies published in the English language that addressed outcomes of EFTR for upper GIT lesions through November 2021. The weighted pooled rates with the 95% confidence interval (CI) were calculated. Cochran Q test and I statistics were used to calculate heterogeneity. RESULTS: We identify 740 articles on the initial search and six studies met the inclusion criteria. 140 patients (45.7% females) with 142 lesions were analyzed. Four studies used the full-thickness resection device (FTRD®). EFTR was performed for 26 adenomas, 97 SELs, six adenocarcinomas, and ten full-thickness biopsies. The overall technical success rate was 86.9% (CI 79.8-94%, I 2 = 38.9%), R0 resection was 80% (CI 67.6-92.3%, I 2 = 75.6%), and the overall adverse events rate was 18.6% (9.8-27.2%, I 2 = 49.4%). Major adverse events included six episodes of major bleeding, three micro-perforations, one large duodenal perforation, and one case of mucosal damage from FTRD®. At 3-6 months follow-up, there were only two cases of recurrence (R0 was not achieved in both). CONCLUSION: EFTR has a high technical and clinical success rate in managing upper GIT lesions with an acceptable safety profile. Large prospective studies comparing EFTR with conventional endoscopic resection techniques are needed.

Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis.

BACKGROUND: Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors. METHODS: We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. We used CMA software for statistical analysis. RESULTS: Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42-60%, I2 = 91%), viral hepatitis was 13.1% (95% CI 9.7-17.6%, I2 = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8-18%, I2 = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4-13.6%, I2 = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9-44.8, P value < 0.0001, I2 = 64% Q 11.1). DISCUSSION: This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000 IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.

Choledocholithiasis Can Present with Marked Transaminases Elevation: Systematic Review and Meta-Analysis.

BACKGROUND: Extreme transaminase elevation > 1000 international units per liter (IU/L) is typically caused by hepatocellular injury due to ischemia, drugs, or viral infection. Acute choledocholithiasis can also present with marked transaminase elevation mimicking severe hepatocellular injury, contrary to the presumed cholestatic pattern. METHODS: We searched PubMed/Medline, EMBASE, Cochrane Library, and Google Scholar for studies reporting the proportion of marked elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1000 IU/L in patients with common bile duct (CBD) stones. A proportion meta-analysis with a corresponding 95% confidence interval (CI) was used to pool the proportion of patients with extreme transaminase elevation. I2 was used to examine heterogeneity. We used CMA software utilizing a random effect model for statistical analysis. RESULTS: Three studies (n = 1328 patients) were included in our analysis. The reported frequency of ALT or AST > 1000 IU/L in choledocholithiasis patients ranged between 6 and 9.6%, with pooled frequency of 7.8% (95% CI 5.5-10.8%, I2 61%). The frequency of patients with ALT or AST > 500 IU/L was higher, ranging between 28 and 47%, with pooled frequency of 33.1% (95% CI 25.3-42%, I2 88%). CONCLUSION: This is the first meta-analysis to study prevalence of severe hepatocellular injury in patients with CBD stones. Results revealed that approximately one-third of patients with choledocholithiasis present with ALT or AST > 500 IU/L. Furthermore, levels > 1000 IU/L are not uncommon. An elaborate work-up for alternative etiologies of severe transaminase elevation is likely unwarranted in cases with clear evidence of choledocholithiasis.

Differential cellular localization of lectins in the testes of dromedary camel (Camelus dromedarius) during active and inactive breeding seasons.

The reproductive activity of the male dromedary camel (Camelus dromedarius) as a seasonal breeder is affected by various seasonal changes that reflect on the reproductive performance. In the current study, we explored a differential cellular localization of lectins in eight dromedary camel testes utilizing lectin histochemistry (LHC). The glycoconjugates' localizations were detected within the testicular tissue utilizing 13 biotin-labeled lectins (PNA, ConA, LCA, RCA120, GS IB4, WGA, BPL, DBA, ECA, PHA-E4, UEA-1, PTL-II, and SBA) distributed into six sets. The cellular structures revealed diverse lectins distribution that may reflect various glycoproteins' structures and their compositional modifications during spermatogenesis. Some of the investigated lectins were restricted to acrosomes of spermatids that will help study different stages during the spermatogenic cycle of dromedary camel, particularly PNA, and ECA. The statistical analysis showed a marked positive correlation between the response intensity of various lectins and the breeding season (P < 0.05). We can conclude that lectins have a fundamental role during camel spermatogenesis and are associated with the reproductive activity of dromedary camel.

The oral microbiome of treated and untreated chronic HCV infection: A preliminary study.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection is a debilitating disease that is lately treated using direct-acting antivirals (DAAs). Changes in the oral microbiome were detected in other liver diseases; however, oral microbiome was never investigated in patients having chronic HCV infection, whether pre- or post-treatment. MATERIALS AND METHODS: This case-control preliminary study enrolled three equal groups: Group (I): untreated HCV patients; group (II): HCV patients who achieved viral clearance after DAA administration; and group (III): healthy controls. For each participant, a buccal swab was harvested and its 16S rRNA was sequenced. RESULTS: The oral microbiome of chronic HCV patients had a significantly distinct bacterial community compared to healthy controls, characterized by high diversity and abundance of certain pathogenic species. These changes resemble that of oral lichen planus patients. After treatment by DAAs, the oral microbiome shifted to a community with partial similarity to both the diseased and the healthy ones. CONCLUSIONS: Chronic HCV is associated with dysbiotic oral microbiome having abundant pathogenic bacteria. With HCV clearance by DAAs, the oral microbiome shifts to approach the healthy composition.

Collagen cross-linking as monotherapy in experimentally induced corneal abscess in rabbits.

BACKGROUND AND PURPOSE: Collagen cross-linking (CXL) has evolved as an essential therapeutic approach for corneal infections, allowing for rapidly eliminating the infecting microorganism while reducing inflammation. This study aims to evaluate the efficacy of CXL as a monotherapy for managing infectious keratitis caused by Fusarium solani and Pseudomonas aeruginosa. MATERIALS AND METHODS: Forty-eight white New Zealand rabbits weighing approximately 1.5-2 KG were included. The cornea of one eye of each rabbit was inoculated with either Fusarium solani or Pseudomonas aeruginosa. Group A served as a control and was subdivided into two subgroups, A1 and A2; each subgroup consisted of 8 eyes and was injected with either Fusarium solani or Pseudomonas aeruginosa, respectively. Group B (16 eyes) was inoculated with Fusarium solani, while group C (16 eyes) were inoculated with Pseudomonas aeruginosa. All animals in Group B and C received CXL treatment one week after inoculation of the organisms and after corneal abscess formation was confirmed. At the same time, animals in Group A were left untreated. RESULTS: There was a statistically significant reduction in the number of colony-forming units (CFU) in Group B following CXL. No growth existed in any samples at the end of the 4th week. There was a statistically significant difference in the number of CFU between group B and the control group (p < 0.001). In group C, there was a statistically significant reduction in the CFU at the end of the first week after CXL. However, there was regrowth in all samples afterward. All 16 models in Group C showed uncountable and extensive growth during the subsequent follow-ups. There was no statistically significant difference between the number of CFU in Group C and the control group. Histopathology showed lesser corneal melting in CXL-treated Pseudomonas aeruginosa. CONCLUSIONS: Collagen cross-linking is promising monotherapy and alternative treatment in managing infective keratitis caused by Fusarium solani but is less effective in Pseudomonas aeruginosa as monotherapy.

Evaluation of factors affecting patients' refusal of HCV treatment in a cohort of Egyptian patients.

BACKGROUND: Treatment refusal, defined as active refusal of a patient to receive treatment despite physician recommendations, has not been extensively evaluated before in hepatitis C virus in the era of direct acting antivirals. OBJECTIVE: To investigate the reasons for refusal to receive hepatitis C virus treatment in Egypt. METHODS: an observational study conducted between July 2018 and November 2019 in Egypt. Enrollment was done to all patients who refused to get hepatitis C virus treatment during the national screening and treatment campaign. Reasons for their refusal were identified using a questionnaire as an instrument for data collection. RESULTS: Out of the 220 280 Egyptian hepatitis C virus patients who did not show up to start treatment and were contacted to get therapy, only 84 patients (0.038%) refused to receive treatment. The main reason for their refusal was having concerns about treatment (82.14%) and their main concern was the fear of adverse events (85.5%). Other causes of refusal were non-satisfactory experience at treatment centers (13.09%) and patients preferred to receive complementary and alternative medicines (4.7%). Most patients (65.4%) trusted the efficacy of directly acting antivirals for hepatitis C. None of the study participants was found to suffer from any psychiatric morbidity and the average score of the GHQ-12 was 10.7155. CONCLUSION: Proper health education and awareness regarding hepatitis C virus treatment safety and efficacy is needed to increase treatment acceptance rates.

Screening and determinant of suspected developmental delays among Egyptian preschool-aged children: a cross-sectional national community-based study.

BACKGROUND: Early childhood life is critical for optimal development and is the foundation of future well-being. Genetic, sociocultural, and environmental factors are important determinants of child development. AIM: The objectives were to screen for suspected developmental delays (DDs) among Egyptian preschool children, and to explore the determinants of these delays based on sociodemographic, epidemiological, maternal, and child perinatal risk factors. METHODS: A national Egyptian cross-sectional developmental screening of a representative sample of preschool children (21,316 children) aged 12 to 71 months. The Revised Denver Prescreening Developmental Questionnaire (R-PDQ) followed by the Denver Developmental Screening Test, 2nd edition (DDST) was used. RESULTS: Each screened child manifested at least one of six developmental categories. Either typical development, gross motor delay (GM), fine motor adaptive delay (FMA), Language delay (L), Personal-social delay (PS), or multiple DDs. The prevalence of preschool children with at least one DD was 6.4%, while 4.5% had multiple DDs. Developmental language delay was the most prevalent, affecting 4.2% of children. The least affected domain was GM (1.9% of children). Boys were more likely to have DD than girls. Children in urban communities were more likely to have at least one DD than those in rural areas (OR = 1.28, 95%CI: 1.14-1.42), and children of middle social class than of low or high social class (OR = 1.49, 95%CI: 1.30-1.70 & OR = 1.40, 95%CI: 1.23-1.59 respectively). The strong perinatal predictors for at least one DD were children with a history of postnatal convulsions (OR = 2.68, 95%CI: 1.97-3.64), low birth weight (OR = 2.06, 95%CI: 1.69-2.52), or history of postnatal cyanosis (OR = 1.77, 95%CI: 1.26-2.49) and mothers had any health problem during pregnancy (OR = 1.73, 95%CI: 1.44-2.07). Higher paternal and maternal education decreased the odds of having any DD by 43% (OR = 0.57, 95% CI: 0.47-0.68) and 31% (OR = 0.69, 95%CI: 0.58-0.82) respectively. CONCLUSION: This study demonstrates a considerable attempt to assess the types and the prevalence of DD among preschool children in Egypt. Perinatal factors are among the most common determinants of DD in preschool children and the majority could be preventable risk factors.