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.

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.

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.

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.

Variations in Groundwater Level and Microtopography Influence Desert Plant Communities in Shallow Aquifer Areas.

An improved understanding of the relationships among vegetation, groundwater level, and microtopography is crucial for making well-informed management decisions in areas with shallow groundwater resources. We measured plant species abundance/composition and richness in relation to depth to groundwater (DTW) and microtopography in Owens Valley, California, particularly in areas where DTW ranged from 0 to 4 m. Sampling occurred along 67 vegetation transects across three community types. Relationships between DTW and community composition were evaluated using non-metric multidimensional scaling (NMS), while non-parametric multiplicative regression was used to relate DTW and microtopography to species abundance. The dominant gradient in species composition (NMS Axis 1) explained ~51% of variation in our distance matrix and was most strongly associated (r = 0.55) with DTW. The graminoids Juncus arcticus, Leymus triticoides, and Distichlis spicata had strong affinities toward areas with the shallowest DTW (<1.5 m). One salt-adapted species Sporobolus airoides and one shrub Ericameria nauseosa dominated areas with intermediate DTW (1.5-2.0 m), whereas the shrubs Atriplex torreyi, Sarcobatus vermiculatus, and Artemisia tridentata were dominant in areas with deeper DTW (>2.0 m). Variation in microtopography affected species abundance and increased species richness for vegetation communities at either extreme of the water table gradient, shallow, and deep DTW but not the intermediate DTW. Findings indicate that desert plant communities from shallow aquifers have adapted to different DTW and microtopography conditions and that considering those adaptations may be important to manage groundwater and vegetation resources in these areas.

Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality.

BACKGROUND & AIMS: Among candidates listed for liver transplant (LT), the model for end-stage liver disease (MELD) score may not capture acute-on-chronic liver failure (ACLF) severity. Data on the interaction between ACLF and MELD score in predicting waitlist mortality are scarce. METHODS: We analyzed the UNOS database (01/2002 to 06/2018) for LT listings in adults with cirrhosis and ACLF (without hepatocellular carcinoma). ACLF grades 1, 2, 3a, and 3b- were defined using the modified EASL-CLIF criteria. RESULTS: Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-day waitlist mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b, respectively). Using a Fine and Gray regression model, we identified an interaction between MELD and ACLF grade, with ACLF having a higher impact at lower MELD scores. Other variables included candidate's age, sex, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (n = 9,181) stratified the validation cohort (n = 9,235) into quartiles: Q1 (score <10.42), Q2 (10.42-12.81), Q3 (12.82-15.50), and Q4 (>15.50). Waitlist mortality increased with each quartile from 13%, 18%, 23%, and 36%, respectively. Observed vs. expected waitlist mortality deciles in the validation cohort showed good calibration (goodness of fit p = 0.98) and correlation (R = 0.99). CONCLUSION: Among selected candidates who have ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-day waitlist mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support consideration of both MELD and ACLF when prioritizing transplant candidates and allocating liver grafts. LAY SUMMARY: In patients with cirrhosis listed for liver transplantation, the presence of multiorgan failure, a condition referred to as acute-on-chronic liver failure, is associated with high waiting list mortality rates. Current organ allocation policy disadvantages patients with this condition. This study describes and validates a new scoring method that performs better than the currently available scoring systems. Further validation of this approach may reduce the deaths of patients with cirrhosis and acute-on-chronic liver failure on the transplant waiting list.

Dysphagia Megalatriensis: An Uncommon Cause of Dysphagia.

Dysphagia megalatriensis is a rarely reported entity of cardiovascular dysphagia. Affected patients present with dysphagia to solid foods and regurgitation secondary to esophageal compression from an enlarged left atrium (LA). Here we report a case of a 68-year-old man with long standing atrial fibrillation who presented with chest pressure, bloating and dysphagia to solids. Esophagogastroduodenoscopy revealed a large area of extrinsic compression of the middle third of the esophagus that varied with cardiac contractions. Computerized tomography of the chest did not reveal any masses and transthoracic echocardiogram showed moderate LA enlargement. Based on those findings, a diagnosis of cardiac dysphagia was made. While severe LA enlargement is usually reported in cardiac dysphagia, our patient developed symptoms with moderate LA enlargement. Surgical intervention, dietary modifications, treatment of the underlying cause of LA enlargement and enteric tube feeding are available treatment options for cardiovascular dysphagia.

BALAD and BALAD-2 predict survival of hepatocellular carcinoma patients: a North American cohort study.

BACKGROUND: The BALAD score and BALAD-2 class derived from bilirubin, albumin, AFP, AFP-L3, and des-gamma-carboxyprothrombin (DCP) are effective in predicting mortality in HCC, but have not been validated in North America. METHODS: 148 HCC patients from 2000 to 2015 who had all five biomarkers tested at diagnosis were included. Hazard ratios (HR) were calculated. RESULTS: 75 patients died during a median follow-up of 21.9 months. 1-and 3-year survival rates were 70.8% and 47.6%. 114 (77%) had cirrhosis. The HR (95%CI) for death were 1.24 (0.42-3.67), 1.79 (0.61-5.26), 2.83 (0.95-8.38), and 7.19 (2.26-22.91) for BALAD scores 1, 2, 3, and 4 vs. BALAD 0. The HR (95%CI) for death were 1.25 (0.65-2.40), 1.75 (0.94-3.23), and 6.20 (3.29-11.68) for BALAD-2 classes 2, 3, and 4 vs. BALAD-2 class 1. A multivariate model incorporating maximal tumor diameter, tumor number, neutrophil-lymphocyte ratio, and BALAD had HR of 1.43 (1.14-1.81) per increase of 1 BALAD score. A similar model with BALAD-2 had HR of 1.50 (1.18-1.90) per increase of 1 BALAD-2 class. CONCLUSION: BALAD models at diagnosis can predict the survival of HCC patients in North America. AFP, AFP-L3, and DCP reflect tumor progression and metastasis of HCC and distinguish the BALAD model from other predictive models.

Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation.

Early detection improves hepatocellular carcinoma (HCC) outcomes, but better noninvasive surveillance tools are needed. We aimed to identify and validate methylated DNA markers (MDMs) for HCC detection. Reduced representation bisulfite sequencing was performed on DNA extracted from 18 HCC and 35 control tissues. Candidate MDMs were confirmed by quantitative methylation-specific PCR in DNA from independent tissues (74 HCC, 29 controls). A phase I plasma pilot incorporated quantitative allele-specific real-time target and signal amplification assays on independent plasma-extracted DNA from 21 HCC cases and 30 controls with cirrhosis. A phase II plasma study was then performed in 95 HCC cases, 51 controls with cirrhosis, and 98 healthy controls using target enrichment long-probe quantitative amplified signal (TELQAS) assays. Recursive partitioning identified best MDM combinations. The entire MDM panel was statistically cross-validated by randomly splitting the data 2:1 for training and testing. Random forest (rForest) regression models performed on the training set predicted disease status in the testing set; median areas under the receiver operating characteristics curve (AUCs; and 95% confidence interval [CI]) were reported after 500 iterations. In phase II, a six-marker MDM panel (homeobox A1 [HOXA1], empty spiracles homeobox 1 [EMX1], AK055957, endothelin-converting enzyme 1 [ECE1], phosphofructokinase [PFKP], and C-type lectin domain containing 11A [CLEC11A]) normalized by beta-1,3-galactosyltransferase 6 (B3GALT6) level yielded a best-fit AUC of 0.96 (95% CI, 0.93-0.99) with HCC sensitivity of 95% (88%-98%) at specificity of 92% (86%-96%). The panel detected 3 of 4 (75%) stage 0, 39 of 42 (93%) stage A, 13 of 14 (93%) stage B, 28 of 28 (100%) stage C, and 7 of 7 (100%) stage D HCCs. The AUC value for alpha-fetoprotein (AFP) was 0.80 (0.74-0.87) compared to 0.94 (0.9-0.97) for the cross-validated MDM panel (P < 0.0001). Conclusion: MDMs identified in this study proved to accurately detect HCC by plasma testing. Further optimization and clinical testing of this promising approach are indicated.

The outcomes of Clostridioides difficile infection in patients with diverticular disease: a nationwide analysis.

Background: Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections. It contributes to significant morbidity and mortality among hospitalized patients in the United States. Prior studies suggest worse outcomes of CDI in patients with diverticulitis and increased risk for recurrent CDI. We conducted this study to evaluate the outcomes of CDI in patients with diverticular disease from a nationwide data sample (2012-2015).Methods: The National Inpatient Sample (NIS) database between January 2012 and September 2015 was queried for CDI admissions using the International Classification of Diseases, Ninth Edition, Clinical Modification [ICD-9-CM] codes 008.45, 562.11, 562.10, 562.12, and 562.13 for diagnoses of CDI and diverticular disease.Results: The study included 1,327,595 patients who were admitted between 2012 and 2105 for CDI. Out of all of the patients, 84,170 (6.34%) had a concurrent diagnosis of diverticular disease. After adjusting for confounding variables, the in-hospital mortality was lower [odd ratio (OR): 0.48, 95% CI: 0.44-0.52, p < .001] for patients with diverticular disease. The length of stay (LOS) was longer [10.5 versus 9.3 days, p < .001] and mean cost of hospitalization was significantly higher in patients without a history of diverticular disease.Discussion: In a nationwide population study, admissions with CDI, patients with a concurrent diagnosis of diverticular disease had lower in-hospital mortality. The observed results are different from prior studies and might be attributed to a higher burden of normal flora in those patients and increased use of antibiotic stewardship program across many hospitals nationwide.

Chemical Meningitis and Status Epilepticus Caused by Accidental Epidural Administration of Digoxin.

Intrathecal administration of digoxin occurs very rarely. Some case reports of inadvertently administering it when performing spinal/epidural anesthesia were described. We report for the first time a case of a chemical meningitis and status epilepticus caused by accidental epidural administration of digoxin. A 26-year-old female underwent epidural anesthesia for a planned cesarean section (CS). Post operatively the patient became lethargic, agitated and encephalopathic, she was intubated and transferred to our hospital intensive care unit (ICU). She had seizures on admission. Electroencephalogram (EEG) was performed and showed generalized slowing and status epilepticus with a focus noted in the right temporal region which resolved after antiepileptic medication administration. A lumbar puncture (LP) was performed; cerebro-spinal fluid (CSF) was suggestive for meningitis. However, there was no evidence for viral or bacterial infections. Within a day of admission, the referring hospital informed us that the patient received 250 mcg of digoxininadvertently-through epidural injection. The patient remained intubated for four days. She became more responsive and alert and was eventually extubated. After extubation, the patient was responsive and full neurological exam and brain imaging were normal. She was discharged from the hospital after seven days.

Screening for Impaired Glucose Tolerance (Prediabetes) and Prevention of Type 2 Diabetes.

The enormous implications caused by type 2 diabetes on patients, families and health systems in the U.S. require health care providers to apply measures that reduce its burden. Scientific evidence clearly shows that proper screening of populations at risk, implementation of interventions proven beneficial in preventing type 2 diabetes and the use of modern technology in educating patients to adopt a healthier lifestyle are paramount in decreasing the incidence of type 2 diabetes. In this article, we try to answer some of the questions raised by both patients and health care providers about how lifestyle modifications can play a key role in ameliorating and reversing impaired glucose tolerance and type 2 diabetes.

Delayed Anaphylaxis to Mammalian Meat: A Fascinating Disease and Captivating Story.

Delayed anaphylaxis to mammalian meat is a newly recognized IgE-mediated syndrome associated with Lone Star tick bites. IgE-mediated anaphylaxis classically occurs within one hour of exposure to the allergen, which is typically a protein epitope. However, in this disease, circulating antibodies to a carbohydrate, alpha-gal (galactose-alpha-1,3-galactose), stimulate the anaphylactic cascade with hives, diarrhea, abdominal cramps, respiratory distress and anaphylactic shock developing after ingestion of beef, pork or lamb meat. The delayed onset of symptoms three to six hours after ingestion of meat is unique. Recognition and understanding of this disease is important for treating and educating patients with suggestive symptoms. Avoidance of red meat is the recommended therapy.

Combination of Sitagliptin and Insulin against Type 2 Diabetes Mellitus with Neuropathy in Rats: Neuroprotection and Role of Oxidative and Inflammation Stress.

AIMS: The present study evaluated the effects of sitagliptin-insulin against type 2 diabetes mellitus with neuropathy in rats and possible neuroprotective mechanisms. METHODS: Diabetes was induced in 32 adult male albino rats by 6-week high-fat high-sugar diet followed by streptozotocin 30 mg/kg intraperitoneal injection. For 4 weeks thereafter, diabetic rats were divided into 4 groups, each group receiving one of the following daily: vehicle (untreated diabetic), insulin 10 IU/kg SC, sitagliptin 30 mg/kg PO or sitagliptin-insulin. We assessed systolic blood pressure (SBP), blood glucose, serum insulin and advanced glycation end-products (AGEs), thermal hyperalgesia and sciatic nerve tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD) and malondialdehyde (MDA) and sciatic histopathology. RESULTS: Compared to untreated and insulin-treated groups, sitagliptin decreased SBP, serum AGEs and sciatic MDA and TNF-α, and increased serum insulin and sciatic SOD, but insulin decreased blood glucose more. Sitagliptin-insulin (greater than sitagliptin or insulin alone) superiorly decreased and increased the above respective parameters, and ameliorated hyperalgesia and sciatic histopathological changes, but was similar to insulin in decreasing blood glucose, and similar to sitagliptin in rising serum insulin. CONCLUSIONS: Sitagliptin-insulin combination produced hypoglycemic and neuroprotective effect and ameliorated hyperalgesia, oxidative stress and inflammation more than either drug alone. This combination might have clinical efficacy in uncontrolled type 2 diabetes with neuropathy.