Effects of Milkfat on the Gut Microbiome of Patients After Bariatric Surgery, a Pilot Study.

BACKGROUND: The efficacy of bariatric surgery may be in part attributed to altered metabolism via new gut microbiome. Milkfat may promote the growth of microbes that are beneficial in long-term weight loss. Understanding the specific gut microbiome changes after surgery and their relationship to milkfat consumption may yield important strategies for managing obesity after bariatric procedures. METHODS: In this pilot study, stool samples were collected from nine patients before and at the time of surgery, and at 1, 3, and 6 months post-surgery. At each time-point, dairy consumption was determined from dietary surveys. 16 s rRNA gene sequencing was performed followed by alpha diversity analysis. Comparisons of relative abundances of microbial taxa and analyses of fatty acids changes were performed. RESULTS: Bariatric surgery led to enrichment of (i) Roseburia, associated with weight loss and (ii) Christensenellaceae, inversely related to body mass index. High milk-fat consumption correlated with enrichment of Blautia, inversely associated with visceral fat accumulation. Faecalibacterium, possibly associated with obesity, increased in patients with low milk-fat consumption. Butter was associated with decreased alpha diversity in all subjects (p-value = 0.038) and the frequency of its use was associated with decreased alpha diversity in patients (correlation = - 0.68, p-value = 0.042). Low-milk-fat consumers showed higher concentration of saturated fatty acids. CONCLUSIONS: Our results suggest that incorporating dairy products in post-bariatric-surgery dietary plans may help cultivate a gut microbiome that is effective in regulating fat storage as well as digesting beneficial metabolites. These observations will be helpful for the management of obesity in general population as well.

Examining the Rate of Clostridioides (Formerly Clostridium) Difficile Infection Pre- and Post-COVID-19 Pandemic: An Institutional Review.

Background/ Rationale Clostridioides difficile infection (CDI) is transmitted via the fecal-oral route and is implicated in antibiotic-associated colitis. Similar to CDI, patients with coronavirus disease 2019 (COVID-19) require early identification and isolation, appropriate personal protective equipment, and environmental disinfection to prevent further transmission. In light of this similarity between isolation and protective requirements to prevent transmission of these diseases, we aim to investigate whether there was a decrease in the incidence of CDI during the peak periods of the COVID-19 pandemic compared to historical rates. Methods This is a single-center retrospective analysis of the rates of CDI in our institution. COVID-19 time periods were identified from March 2020 to January 2021 and peak periods (with >50 active patients per day) were defined. The non-COVID-19 periods were July 2017 to February 2020. Rates of CDI were also directly compared across the yearly time period. CDI rates were presented in a per 1000 patient days format. Rates were analyzed per year and during the COVID-19 peaks at our institution. Mann-Whitney U test was used to compare rates between two time periods, while differences across multiple time intervals were analyzed using the Kruskal-Wallis test. Results The median (interquartile range [IQR]) of CDI rates of infection per 1000 patient days for the non-COVID time period from July 2017 to February 2020 was 0.34 (0.23-0.45) while COVID time periods had higher 0.44 (0.25-0.51) rates of CDI although this was not statistically significant (p=0.224). However, there was a statistically significant difference (p=0.036) with COVID peak periods having higher rates of CDI 0.49(0.39-0.74) vs 0.34(0.23-0.44). Overall, there was no statistically significant difference in the rates of CDI across years or time periods (p=0.396). Discussion/Conclusion There was no difference in the rates of hospital-acquired CDI between COVID-19 and non-COVID-19 time periods at our institution.

Risk of Hepatobiliary-Gastrointestinal Malignancies and Appropriate Cancer Surveillance in Patients With Primary Sclerosing Cholangitis.

Patients with primary sclerosing cholangitis (PSC) are at risk of hepatobiliary and gastrointestinal cancers. Increased risk of cancer is a result of the chronic, progressive fibro-inflammatory state which ultimately results in the destruction of biliary ducts. PSC is often associated with inflammatory bowel disease (IBD). Patients with PSC are at significant risk of cholangiocarcinoma (CCA), gall bladder malignancy and those with IBD are at increased risk of colorectal cancer. It is important to implement cancer surveillance protocols in these patients. The aim of these protocols is the prevention or early detection of cancerous or pre-cancerous lesions. Given that PSC is rare, large prospective studies evaluating the risk of malignancy in these patients are not available. A great deal of uncertainty exists regarding how to best implement cancer surveillance in these patients. About 50% of deaths in PSC patients are due to malignancy and many patients eventually progress to end-stage liver disease and succumb to hepatic failure. In this review, we cover cancer surveillance strategies in PSC patients based on existing literature and expert opinions.

Designing strategies for eradication of Helicobacter pylori based on prevalence patterns of infection and antibiotic resistance in a low-income, medically underserved community in the United States.

BACKGROUND: Regional variation in Helicobacter pylori resistance patterns is a significant contributing factor for the ineffectiveness of traditional treatments. To improve treatment outcomes, we sought to create an individualized, susceptibility-driven therapeutic approach among our patient population, which is one of the poorest in the nation. It is medically underserved, minority-predominant and has high incidence of H pylori infection. METHODS: We compiled various factors involved in the antibiotic resistance of H pylori from literature. We then created a predictive model to customize therapies based on analyzed data from 2,014 H pylori patients with respect to several of these factors. The predictions of the model were further tested with analysis of patient stool samples. RESULTS: A clear pattern of H pylori prevalence and antibiotic resistance was observed in our patients. We observed that majority of H pylori patients were women (62%) and over the age of 40 years (80%). 30% and 36% of the H pylori patients were African American and Hispanic, respectively. A median household income of less than $54,000, past H pylori infection, previous use of certain antibiotics for any infection decreased the chance of eradication. Results of the stool testing were consistent with model predictions (90% accuracy). CONCLUSION: This model demonstrates the predictive accuracy of H pylori infection and antibiotic resistance based on patient attributes and previous treatment history. It will be useful to formulate customized treatments with predicted outcomes to minimize failures. Our community attributes may contribute toward broad applicability of model for other similar communities.

Identification of Novel Therapeutic Molecular Targets in Inflammatory Bowel Disease by Using Genetic Databases.

PURPOSE: Utilization of genetic databases to identify genes involved in ulcerative colitis (UC), Crohn's disease (CD), and their extra-intestinal manifestations. METHODS: Protein coding genes involved in ulcerative colitis (3783 genes), Crohn's disease (3980 genes), uveitis (1043 genes), arthritis (5583 genes), primary sclerosing cholangitis (PSC) (1313 genes), and pyoderma gangrenosum (119 genes) were categorized using four genetic databases. These include Genecards: The Human Gene Database (www.genecards.org), DisGeNET (https://www.disgenet.org/), The Comparative Toxicogenomics Database (http://ctdbase.org/) and the Universal Protein Resource (https://www.uniprot.org/). NDex, Network Data Exchange (http://www.ndexbio.org/), was then utilized for mapping a unique signal pathway from the identified shared genes involved in the above disease processes. RESULTS: We have detected a unique array of 20 genes with the highest probability of overlay in UC, CD, uveitis, arthritis, pyoderma gangrenosum, and PSC. Figure 1 represents the interactome of these 20 protein coding genes. Of note, unique immune modulators in different disease processes are also noted. Interleukin-25 (IL-25) and monensin-resistant homolog 2 (MON-2) are only noted in UC, CD, pyoderma gangrenosum, and arthritis. Arachidonate 5-lipoxygenase (ALOX5) is involved in UC, CD, and arthritis. SLCO1B3 is exclusively involved with pyoderma gangrenosum, UC, and CD. As expected, TNF involvement is noted in CD, UC, PSC, and arthritis. Table 1 depicts the detailed result. CONCLUSION: Our work has identified a distinctive set of genes involved in IBD and its associated extra-intestinal disease processes. These genes play crucial roles in mechanisms of immune response, inflammation, and apoptosis and further our understanding of this complex disease process. We postulate that these genes play a critical role at intersecting pathways involved in inflammatory bowel disease, and these novel molecules, their upstream and downstream effectors, are potential targets for future therapeutic agents.

Rate and Predictors of Interval Esophageal and Gastric Cancers after Esophagogastroduodenoscopy in the United States.

BACKGROUND AND AIMS: In the United States, little is known about the rates of interval upper gastrointestinal (GI) cancer (possibly missed out) after an esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported interval cancer rates of 7-26%. We aimed to study the rate and predictors of interval upper GI cancers in the United States. METHODS: Using the random 5% sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients diagnosed with esophageal or gastric cancer during 2000-2007. EGD performed within 36 months prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6-36 months after EGD were defined as interval (vs. detected) cancers. The chi-square test and the multivariate logistic model were used in statistical analysis. RESULTS: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were diagnosed with interval cancers 6-36 months after EGD. The rate of interval cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non-gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI 0.25-0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28-0.997) were associated with a lower likelihood of interval cancers. Sensitivity analyses limited to outpatient EGDs or interval cancers 6-30 months after EGDs led to similar results. CONCLUSIONS: The rate of interval cancers after EGD is the same as the rate of colonoscopy among Medicare patients in the United States. EGDs performed by gastroenterologists and in in-patient settings were associated with a lesser likelihood of interval cancers.

A genetic database can be utilized to identify potential biomarkers for biphenotypic hepatocellular carcinoma-cholangiocarcinoma.

BACKGROUND: Biphenotypic hepatocellular carcinoma-cholangiocarcinoma (HCC-CC) is an uncommon primary liver neoplasm. Due to limitations in radiologic imaging for the diagnosis of this condition, biopsy is a common method for diagnosis, which is invasive and holds potential complications. To identify alternative means for obtaining the diagnosis and assessing the prognosis of this condition, we evaluated biomarkers for biphenotypic HCC-CC using a genetic database. METHODS: To evaluate the genetic associations with each variable we utilized GeneCards(®), The Human Gene Compendium (http://www.genecards.org). The results of our search were entered into the Pathway Interaction Database from the National Cancer Institute (PID-NCI) (http://pid.nci.nih.gov), to generate a biomolecule interaction map. RESULTS: The results of our query yielded 690 genes for HCC, 98 genes for CC and 50 genes for HCC-CC. Genes depicted in this analysis demonstrate the role of hormonal regulation, embryonic development, cell surface adhesion, cytokeratin stability, mucin production, metalloproteinase regulation, Ras signaling, metabolism and apoptosis. Examples of previously described markers included hepatocyte growth factor (HGF), mesenchymal epithelial transition (MET) and Kirsten rat sarcoma viral oncogene homolog (KRAS). Novel markers included phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), GPC3, choline kinase alpha (CHKA), prostaglandin-endoperoxide synthase 2 (PTGS2), telomerase reverse transcriptase (TERT), myeloid cell leukemia 1 (MCL1) and N-acetyltransferase 2 (NAT2). CONCLUSIONS: GeneCards is a useful research tool in the genetic analysis of low frequency malignancies. Utilizing this tool we identified several biomarkers are methods for diagnosing HCC-CC. Finally, utilizing these methods, HCC-CC was found to be predominantly a subtype of CC.

The Acute Physiology and Chronic Health Evaluation IV, a New Scoring System for Predicting Mortality and Complications of Severe Acute Pancreatitis.

OBJECTIVES: Severe acute pancreatitis is associated with significant morbidity/mortality; thus, the ability to predict hospital course is imperative. An updated version of the Acute Physiology and Chronic Health Evaluation II (APACHE), APACHE IV, has recently been validated. Unlike other versions, APACHE IV uses hepatobiliary parameters and accounts for multiple comorbid conditions and sedation. The intention of this study was to examine APACHE IV for predicting mortality and secondary outcomes for pancreatitis in a prospective cohort. In addition, we compared APACHE IV to APACHE II, Bedside Index for Severity in Acute Pancreatitis, and Ranson criterion. METHODS: We prospectively collected physiologic parameters for each scoring system in 266 patients with severe acute pancreatitis from August 2011 to April 2014. Prognostic value of each score was determined using the area under the receiver operating characteristic curve. RESULTS: Among 266 patients, 59% were men, 52% were white, and 36.5% had alcohol-induced pancreatitis. Mortality occurred in 15 (5.6%), and an APACHE IV of 44 or greater predicted mortality in 100% of cases. The receiver operating characteristic curve for APACHE IV was 0.93 (confidence interval [CI], 0.88-0.97); APACHE II, 0.87 (CI, 0.80-0.94); Bedside Index for Severity in Acute Pancreatitis, 0.86 (CI, 0.78-0.94); and Ranson criterion, 0.90 (CI, 0.94-0.96). CONCLUSION: The APACHE IV is a valid means for predicting mortality and disease-related complications in acute pancreatitis.

Impact of Video Laryngoscopy on Advanced Airway Management by Critical Care Transport Paramedics and Nurses Using the CMAC Pocket Monitor.

Accurate endotracheal intubation for patients in extremis or at risk of physiologic decompensation is the gold standard for emergency medicine. Field intubation is a complex process and time to intubation, number of attempts, and hypoxia have all been shown to correlate with increases in morbidity and mortality. Expanding laryngoscope technology which incorporates active video, in addition to direct laryngoscopy, offers providers improved and varied tools to employ in management of the advanced airway. Over a nine-year period a helicopter emergency medical services team, comprised of a flight paramedic and flight nurse, intended to intubate 790 patients. Comparative data analysis was performed and demonstrated that the introduction of the CMAC video laryngoscope improved nearly every measure of success in airway management. Overall intubation success increased from 94.9% to 99.0%, first pass success rates increased from 75.4% to 94.9%, combined first and second pass success rates increased from 89.2% to 97.4%, and mean number of intubation attempts decreased from 1.33 to 1.08.

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs.

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using "deuterium-enabled chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics.

Mediastinal extension of pancreatic pseudocyst--a case with review of topic and management guidelines.

Pancreatic pseudocyst is a common complication of acute and chronic pancreatitis. Extension of a pancreatic pseudocyst into the mediastinum is rare. We present a case of a 43-year-old male with a history of pancreatitis, who presented with dysphagia and was found to have a pancreatic pseudocyst. The pseudocyst was extending to the mediastinum and compressing the esophagus. It was successfully drained externally by computed tomography-guided catheter intervention. Depending on the location and size, patients may present with dyspnea, chest pain, palpitations, or dysphagia; sometimes with hemoptysis, acute respiratory compromise, or cardiogenic shock. There are no recommended guidelines for management. Watchful waiting for spontaneous regression, medical therapy, or drainage internally or externally with endoscopic, percutaneous, or open surgical approach are available options. Based on our own experience and literature review of such cases, we present a management strategy that can limit both complications and recurrence rate. This case emphasizes the importance of the possibility of mediastinal extension of a pancreatic pseudocyst and provides reference guidelines to approach the same.

Suboptimal response to ferrous sulfate in iron-deficient patients taking omeprazole.

Iron deficiency anemia is commonly encountered in outpatient practice. Gastric acid is one of the important factors for optimum absorption of iron. Proton pump inhibitors are very commonly prescribed medications. One of the debated effects of proton pump inhibitors is on oral iron absorption. Their effect on absorption of oral iron supplementation in iron-deficient patients has not been studied. At the Cooper Hematology Outpatient office, we reviewed charts of iron-deficient anemic patients who were on omeprazole for the last 4 years. Fifty patients having no apparent ongoing blood loss, having other causes of anemia especially that of chronic diseases ruled out, and on omeprazole while starting ferrous sulfate therapy for iron deficiency were selected for chart review. The iron-study results at the start of oral ferrous sulfate therapy and at 3 months follow-up were compared to evaluate the response of ferrous sulfate. The mean hemoglobin change was 0.8 ± 1.2 g/L. The mean change in ferrtin values was 10.2 ± 7.8 µg/L. Only 16% of the patients had a normal response to hemoglobin levels (rise of >2 g/dL), and only 40% had a normal response to ferritin levels (rise of >20 µg/dL). The average age of patients having a suboptimal response to both hemoglobin and ferritin was significantly higher compared with that of the patients with an optimal response. Omeprazole and possibly all proton pump inhibitors decrease the absorption of oral iron supplementation. Iron-deficient patients taking proton pump inhibitors may have to be treated with high dose iron therapy for a longer duration or with intravenous iron therapy.

Does the urgency of endoscopic retrograde cholangiopancreatography (ercp)/percutaneous biliary drainage (pbd) impact mortality and disease related complications in ascending cholangitis? (deim-i study).

BACKGROUND: The Tokyo Guidelines have greatly impacted the management of ascending cholangitis. Though ERCP is the favored modality for biliary decompression, no evidence exists for the timing of ERCP. The DEIM-I study set out to determine if the time from patient presentation to biliary decompression impacted in hospital all cause mortality in ascending cholangitis. METHOD: DEIM-I cohort study was a single-blinded and consisted of 250 subjects with moderate to severe ascending cholangitis who underwent ERCP/PBD. Subjects were randomized into quartiles based upon time from presentation until ERCP/PBD. The primary outcome utilized logistic regression to estimate relative risk (RR) of all cause, in hospital mortality with time to procedure as the predictive covariate. Secondary outcomes were analyzed using multivariate logistic regression and included; multiple organ failure (MOF), sepsis, systemic inflammatory response syndrome (SIRS), surgical incidence, hospital readmission and length of stay (LOS). RESULTS: The risk for hospital mortality was significantly less when biliary drainage was performed within 11 h, compared to >42 h (RR 0.34, 95%CI 0.12 to 0.99, p=0.049). Hospital readmission was lower in subjects who underwent biliary decompression less than 11 h, when compared to those greater than 22 h. Subjects who underwent biliary decompression within 21 h had significant higher risk for surgery compared to those 22-42 h. CONCLUSION: The relative risk of all cause in hospital mortality was lower in subjects who underwent biliary decompression in under 11 h compared to greater than 42 h.

Breathing easier--good news from air medicine.

Safety in transport is a major concern. Air medical crashes are in the public eye, but a greater risk of transport may be in the clinical care provided along the way. While the media focuses on the drama of helicopters landing on scene, the greatest and most common risk actually occurs during inter-hospital transport. For too long, transport has been a black hole in clinical medicine and the real rate of adverse events is unknown. New work from the University of Pennsylvania should make us all breathe a little easier.

2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as broad-spectrum inhibitors of human herpesvirus polymerases.

A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent antivirals against human herpesviruses. These compounds demonstrate broad-spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with high specificity compared to human DNA polymerases.