Continuing Medical Education Questions: May 2023.

Article Title: Linaclotide Reduced Response Time for Irritable Bowel Syndrome with Constipation Symptoms: Analysis of Four Randomized Controlled Trials.

Short-term outcomes after peroral endoscopic myotomy, Heller myotomy, and pneumatic dilation in patients with achalasia: a nationwide analysis.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM), laparoscopic Heller myotomy (LHM), and pneumatic dilation (PD) are the most common modalities for management of achalasia. Our study aimed to directly compare their short-term outcomes and safety profile in a hospitalized cohort in the United States. METHODS: The National Readmission Database (2016-2019) was queried using International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify a cohort of inpatient admissions who underwent POEM, LHM, or PD. Baseline demographic variables, resource utilization, periprocedural outcomes, and 30-day readmissions were analyzed. A univariate and multivariate logistic regression model was used to compare odds of readmission with POEM as a reference. RESULTS: LHM was the most performed procedure (n = 9710) as compared with PD (n = 2453) and POEM (n = 1911). Patients undergoing PD were older with a higher Charlson Comorbidity Index. The 30-day readmission rate was 4.3%, 3.9%, and 12.6% for POEM, LHM, and PD, respectively. Compared with POEM, the adjusted odds of readmission for PD was 2.42 (95% confidence interval, 1.56-3.75). There was no statistically significant difference in odds of readmission for LHM (.91; 95% confidence interval, .62-1.33) compared with POEM. Within the 30-day readmitted population, 13.1% of PD and 3.4% of LHM patients required achalasia-related procedural intervention. The rate of bleeding (4.3%), blood transfusion (2.3%), and mortality were higher (1.1%) in PD as compared with POEM and LHM. CONCLUSIONS: In the United States, the risk of readmission and resource utilization are higher in patients with achalasia undergoing PD. The outcomes are comparable between POEM and LHM, but there is a significant difference between the utilization of these myotomy procedures.

Mesenchymal stem cell therapy for treatment of osteoradionecrosis of mandible in head and neck surgery patients - A way forward into the future with promising clinical Outcomes.

Managing osteoradionecrosis is an integral part of complication management in head and neck cancer patients. While essentially an infection, the management of this complication has a considerable task for head and neck surgeons. While various measures have been discussed for the management, stem cells injection therapy is a potential management option. Mesenchymal stem cell therapy provides the local tissue with growth factors and proliferative cells that can aid a radiated tissue in the healing process. The article intends to review the bedrock of the pathology, ranging from pathophysiological and the epidemiological concerns to sparking a potential discussion on the use of mesenchymal stem cell therapy in osteoradionecrosis of mandible in head and neck cancer surgery and thus the ensuing future of the regenerative medicine. Moreover, the article has considered the management option in a developing nation thus explaining the procedural as well as the financial pitfalls and has highlighted the potential loop holes to be addressed in the management of osteoradionecrosis with stem cell therapy.

Tuning the Electronic Structure of Cobalt Selenide on Copper Foam by Introducing a Ni Buffer Layer for Highly Efficient Electrochemical Water Splitting.

The development of a cost-effective, remarkably competent, and durable bifunctional electrocatalyst is the foremost requirement of water splitting to generate H2 fuel as a renewable energy technology. Three-dimensional porous copper foam (Cuf) when electrochemically decorated with transition metal selenide results in a highly active electrocatalyst for adequate water electrolysis. In terms of water splitting, the role of cobalt selenide and Cuf has already proven to be remarkable. The introduction of a Ni buffer layer between Cuf and cobalt selenide (Cuf@Ni-CoSe2) acts as a valve to enhance the electron thrust from the substrate to the material surface with no compromise in the overall material conductivity, which not only increases the efficiency and activity but also improves the stability of the catalyst. The self-supported synthesized catalyst material showed an admirable activity toward the oxygen evolution reaction and hydrogen evolution reaction in alkaline media. The performance of the catalyst was found to be significantly better than that of the noble catalyst RuO2. The catalyst was very stable up to 93 h and attained a full cell voltage of only 1.52 V at a current density of 10 mA cm-2. Therefore, for large-scale hydrogen production, this as-synthesized catalyst hss the potential to replace conventional fossil fuel-based energy systems.

Inter-Electronic Interaction between Ni and Mo in Electrodeposited Ni-Mo-P on 3D Copper Foam Enables Hydrogen Evolution Reaction at Low Overpotential.

Electrocatalytic hydrogen evolution reaction (HER) via water electrolysis has been considered the most effective and sustainable route to produce clean hydrogen. Designing and structure optimization are the two important parameters to develop an affordable, easy to fabricate, and stable non-noble metal electrocatalyst for the production of hydrogen as a clean, sustainable, and green fuel. Herein, we have synthesized Ni-Mo-P on copper foam (Cuf) via a facile single-step electrodeposition method, which can show stratospheric efficiency toward HER with a Tafel slope of 67 mV dec-1 and a very low overpotential of only 53 mV at a current density of 20 mA cm-2. Cuf acts as a conducting substrate support and the existence of the inter-electronic effect between Ni and Mo results in substantial catalytic activity toward hydrogen generation. In addition to this, the catalyst shows long time stability of around 97.5 h with almost negligible degradation under the applied overpotential for HER in alkaline media. This work features the significance of structure design and construction of non-noble metal catalysts via a simple method for efficient hydrogen generation.

(#WomeninDDW) Persistent Speaker Gender Gap at the Premier Digestive Disease Event.

BACKGROUND: Over the last few decades, advances have been made regarding gender equality starting from medical students to trainees, to leadership in academics. The female representation in specialty academic conferences not only reflects the existing gender disparities in that specialty but also can influence young female trainees to join that field. Digestive Disease Week (DDW) is the premier digestive disease event. We aimed to calculate the proportion of female representation among speakers and moderators at the DDW meetings held from 2018 to 2020. METHODS: The data for DDW 2018-2020 were collected via the online web-based planner. The gender of speakers of presentations and moderators of sessions were identified by a google search. We further categorized the data by each participating society (AGA, ASGE, AASLD, and SSAT), by presentation track, by session track, and total overall representation in each year. RESULTS: Despite the subject of the gender gap being in focus, the proportion of female moderators and speakers was low in DDW in the last 3 years. The female speakers constituted 31.6% in 2018, 33.8% in 2019 and 34.6% in 2020. There was slightly improved female representation in sessions of Inflammatory Bowel Disease, Stomach, and Small Bowel Disorders, Microbiome in GI & Liver disease, and Basic Science over the last 3 years. CONCLUSION: Based on our study and those referenced in this article, we believe that strategies to promote the inclusivity of female moderators and speakers at DDW provide a huge opportunity to influence gender equity within GI.

Celiac Disease Is Associated with Microscopic Colitis in Refractory Cases in Adults: A Systematic Review and Meta-Analysis of Observational Studies.

BACKGROUND: Microscopic colitis and Celiac disease have been shown to occur concomitantly, but their relationship has yet to be systematically evaluated. Some patients with refractory microscopic colitis may have simultaneous celiac disease, and the converse is also true. AIMS: We performed a systematic review and meta-analysis of observational studies to assess the prevalence and possible association between these two conditions. METHODS: PubMed, Embase, Cochrane, Web of Science, SciELO, and CINAHL Plus were systematically searched through January 26, 2021, to include relevant observational studies assessing the prevalence of microscopic colitis in celiac disease population or vice versa. DerSimonian-Laird approach using random effects was used to pool data and compare outcomes. Pooled prevalence, 95% confidence interval (CI), and p values (where applicable) were calculated. RESULTS: Five studies (with 2589 patients, age range 39.5-52 years and females 66.6%) and 21 studies (with 7186 patients, age range 46.4-65.8 years and females 76.3%) were included assessing the prevalence of microscopic colitis in refractory celiac disease and celiac disease in refractory microscopic colitis cohort. The overall prevalence was 4.5% (2.6-6.3%) and 6.7% (5.2-8.1%), respectively. Five studies showed higher odds of celiac disease diagnosis in the refractory microscopic colitis population compared to the control group (OR 8.12, CI 4.92-13.41, p < 0.001). CONCLUSION: Celiac disease and microscopic colitis are concomitantly prevalent in a subset of population with either refractory diagnosis. Clinicians should explore alternate diagnosis when one condition has been appropriately treated and patients continue to have refractory symptoms.

Comparison of clinical outcomes of multiple plastic stents and covered metal stent in refractory pancreatic ductal strictures in chronic pancreatitis- a systematic review and meta-analysis.

BACKGROUND: Symptomatic pancreatic duct (PD) strictures in chronic pancreatitis refractory to single plastic stenting are usually managed by placement of multiple plastic stents (MPS). Fully covered self-expanding metallic stents (FCSEMS) have also been used in the management of these patients. However, the overall efficacy and safety of different types of stents is unclear from the currently available studies. We performed this meta-analysis to assess the efficacy and complications from MPS and FCSEMS in patients with PD strictures refractory to treatment with single plastic stents. METHODS: Several electronic databases were searched for all the studies evaluating the outcome of placement of multiple plastic stents and fully covered metal stents in patients with PD strictures refractory to single plastic stenting. We calculated the Weighted Pooled Ratio (WPR) with Confidence Interval (CI) between the MPS and FCSEMS. RESULTS: A total of 13 studies (including 2 abstracts) were included in the analysis. MPS were placed in 106 patients and FCSEMS in 192 patients. Improvement in pain after stenting (P = 0.794), risk of recurrence of pain after removal of stent (P = 0.48) and stricture recurrence after stent removal (P = 0.52) were comparable between MPS and FCSEMS. Risk of endoscopic re-intervention was also comparable between metal stents and MPS. However, FCSEMS was associated with overall higher risk of adverse events (P < 0.0001). CONCLUSION: FCSEMS are comparable to multiple plastic stents in the treatment of symptomatic refractory PD strictures. However, use of FCSEMS is associated with increased risk of adverse events.

Efficacy and safety of supplemental intravenous lidocaine for sedation in gastrointestinal endoscopic procedures: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Some studies have shown that intravenous (IV) lidocaine reduces the dose requirement of propofol in GI endoscopic procedures. We conducted this study to evaluate the efficacy and safety of the combination of IV lidocaine and propofol compared with propofol alone in GI endoscopic procedures. METHODS: We reviewed several databases from inception to October 13, 2020, to identify randomized controlled trials (RCTs) that compared the role of IV propofol and lidocaine with IV propofol plus placebo for sedation in endoscopic procedures. Our outcomes of interest were the differences in total dose of propofol administered, procedure time, and intraoperative adverse events. For categorical variables, we calculated pooled risk ratios with 95% confidence intervals (CI); for continuous variables, we calculated standardized mean difference (SMD) with 95% CI. Data were analyzed using a random effect model. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework to ascertain the quality of evidence. RESULTS: We included 5 randomized controlled trials with 318 patients. We found that the total dose of propofol administered was significantly lower in the lidocaine group than the control group (SMD, -0.76; 95% CI, -1.09 to -0.42). We found no significant difference in procedure time (SMD, 0.16; 95% CI, -0.26 to 0.57) or adverse events (risk ratio, 0.60; 95% CI, 0.35-1.03) between the groups. There was moderate to substantial heterogeneity in the data. Quality of evidence based on the GRADE framework ranged from low to moderate. CONCLUSIONS: Moderate quality of evidence suggests that IV lidocaine decreases the dose of propofol administered for GI endoscopic procedures.

Role of routine second-look endoscopy in patients with acute peptic ulcer bleeding: meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Studies evaluating the role of routine second-look endoscopy in patients with acute upper GI bleed because of peptic ulcer disease (PUD) have reported conflicting results. This meta-analysis evaluates the usefulness of routine second-look endoscopy in these patients. METHODS: We reviewed several databases from inception to September 15, 2020 to identify randomized controlled trials (RCTs) that compared routine second-look endoscopy with no planned second-look endoscopy in patients with acute upper GI bleed because of PUD. Our outcomes of interest were recurrent bleeding, mortality, need for surgery, and mean number of units of blood transfused. For categorical variables, we calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs); for continuous variables, we calculated standardized mean difference with 95% CIs. Data were analyzed using a random effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to ascertain the quality of evidence. RESULTS: We included 9 RTCs comprising 1452 patients; 726 patients underwent planned/routine second-look endoscopy and 726 did not. We found no significant difference in recurrent bleeding (RR, .79; 95% CI, .51-1.23), need for surgery (RR, .58; 95% CI, .29-1.15), mortality (RR, .69; 95% CI, .33-1.45), or mean number of units of blood transfused (standardized mean difference, -.06; 95% CI, -.19 to .07). Quality of evidence ranged from low to moderate based on the GRADE framework. CONCLUSIONS: Single endoscopy with complete endoscopic hemostasis is not inferior to routine second-look endoscopy in reducing the risk of recurrent bleeding, mortality, or need for surgery in patients with acute upper GI bleed because of PUD.

One-year outcomes of supersaturated oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. OBJECTIVES: To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. METHODS: IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. RESULTS: Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. CONCLUSIONS: Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.

Endoscopic Gastrointestinal Anastomosis Using Lumen-apposing Metal Stent (LAMS) for Benign or Malignant Etiologies: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Endoscopic gastrointestinal anastomosis using lumen-apposing metal stents (EGAL) is a new technique that is used as an alternative method to bypass benign or malignant strictures. Endoscopists take advantage of 2 bowel loops that are close to each other and place a stent between the lumen of these 2 bowel loops. The authors performed this systematic review and meta-analysis to evaluate the efficacy and safety of this rising procedure. METHODS: Electronic database searches were conducted for full eligible articles that were published from the inception to July 2019 using the EGAL procedure to bypass malignant or benign obstruction or to restore bowel integrity after a gastrointestinal altering surgery. The primary outcome of this meta-analysis was to assess efficacy through technical and clinical success. Secondary outcomes were to assess safety through adverse events and to assess the rate of stent maldeployment and the rate of reintervention during the study period. RESULTS: Eight studies were eligible, providing data on 269 patients who underwent 271 EGAL procedures. The median age was 65 years (interquartile range: 63 to 66) with 46% male individuals. Out of 269 patients, 203 underwent EGALs because of malignant etiology and 66 underwent EGAL for benign etiology. The median duration of follow-up was 114 days (interquartile range: 78 to 121). Technical success rate was 94.1% [95% confidence interval (CI), 91.4%-96.9%]. Clinical success rate was 91.4% (95% CI, 88.1%-94.7%). Adverse events rate was 8.5% (95% CI, 4.7%-12.3%). Stent maldeployment rate was 9.5% (95% CI, 3.5%-15.4%) of the total performed EGALs and the reintervention rate was 6.0% (95% CI, 2.3%-9.8%). CONCLUSION: EGAL procedure has high efficacy and a relatively safe profile and it can be performed in selected patients. Comparison between EGAL and other conventional therapies is difficult because of the lack of randomized trials.

Do Water-aided Techniques Improve Serrated Polyp Detection Rate During Colonoscopy?: A Systematic Review With Meta-Analysis.

BACKGROUND AND STUDY AIMS: The utility of water-aided techniques (WT): water exchange (WE) and water immersion (WI) have been studied extensively in the literature for improving colonoscopy outcome metrics such as adenoma detection rate. Serrated polyps owing to their location and appearance have a high miss rate. The authors performed a systematic review and meta-analysis of studies comparing WT with the standard gas-assisted (GA) method to determine if there was any impact on serrated polyp detection rate (SPDR) and sessile serrated polyp detection rate. METHODS: The following databases were queried for this systematic review: Medline, EMBASE, Cochrane Library, CINAHL, and Web of Sciences. The authors only included randomized controlled trials (RCTs). The primary outcome was SPDR and secondary outcomes were sessile serrated polyp detection rate and cecal intubation rate. Risk ratios (RRs) were calculated for each outcome. A P-value <0.05 was considered to be statistically significant. RESULTS: A total of 4 RCTs (5 arms) with 5306 patients (2571 in the GA group and 2735 in the WT group) were included. The SPDR was significantly increased for the WT group compared with GA (6.1% vs. 3.8%; RR, 1.63; 95% confidence interval, 1.24-2.13; P<0.001; I2=22.7%). A subgroup analysis for WE technique also demonstrated improved SPDR compared with the GA method (4.9% vs. 3.2%; RR, 1.57; 95% confidence interval, 1.15-2.14; P=0.004; I2=6.1%). CONCLUSIONS: WT, particularly, the WE method results in improved SPDR. This technique should be encouraged in a clinical setting to detect these polyps to prevent interval colorectal cancer.

Role of Hospital Teaching Status on Outcomes of Patients with Inflammatory Bowel Disease: A Nationwide Analysis.

BACKGROUND: Data regarding hospitalization outcomes in patients with inflammatory bowel disease (IBD) with respect to hospital teaching status are largely unknown. AIMS: We aimed to investigate the impact of hospital teaching status on IBD hospitalization outcomes. METHODS: In this retrospective analysis, we queried the 2016 and 2017 National Inpatient Sample (NIS) databases using the International Classification of Diseases 10th revision (ICD-10) coding system. All adult patients with a principal diagnosis of IBD were included. We stratified the IBD group into ulcerative colitis (UC), Crohn's disease (CD), and complicated IBD. Our primary outcome was mortality. Statistical analysis was performed using STATA, version 16.0. RESULTS: Of the 189,950 adult patients with IBD, the majority were admitted to teaching hospitals (70.9%). There was no significant difference in mortality based upon hospital teaching status (aOR 1.18, p = 0.48); however, these patients had an increased mean length of stay (adjusted coefficient: 0.82, p < 0.01), charges (adjusted coefficient: $8732, p < 0.01), and costs ($2871, p < 0.01). On subgroup analysis, patients with UC admitted to teaching hospitals had a significantly increased in-hospital mortality (aOR 2.11, p < 0.05), while those admitted with CD did not (aOR 0.80, p = 0.4). Among patients with complicated IBD, 73.17% were admitted to teaching hospitals, and no significant difference in in-hospital mortality was seen (aOR 1.06, p = 0.8). CONCLUSION: While outcome differences are likely related to multiple unaccounted factors, greater efforts should be placed to cost-effectively manage patients with IBD at teaching institutions. Future studies are warranted to fully comprehend these variations.

Use of 2 Observers Increases Adenoma Detection Rate During Colonoscopy: Systematic Review and Meta-analysis.

Current efforts are directed toward improving quality metrics such as adenoma/polyp detection rates during colonoscopy to decrease the incidence of colorectal cancer.1 Previous studies have reported variable detection rates for adenomas/polyps during colonoscopy for active participation/observation by nurses, trainees, and/or technician (dual observer [DO] group) with an endoscopist.2,3 We performed a systematic review and meta-analysis to evaluate the detection rate of adenomas/polyps during colonoscopy via DO versus single observers (ie, endoscopist alone).

No Association Linking Short-Term Proton Pump Inhibitor Use to Dementia: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. We aimed to evaluate this proposed association further and to assess the quality of the evidence in its support. METHODS: We searched MEDLINE, EMBASE, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach. RESULTS: We identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5 to 10 years. There were 158,954 PPI users and 483,995 nonusers. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88-1.37); for Alzheimer dementia only, it was 1.06 (0.72-1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84-1.25) and for Alzheimer dementia only 0.96 (0.82-1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low. DISCUSSION: We found no evidence to support the proposed association between PPI use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.

Long-segment transverse myelitis in an immunocompetent patient due to varicella zoster virus reactivation.

Transverse myelitis is a segmental, full-thickness inflammation of the spinal cord with various etiologies including varicella zoster virus infection. Symptoms can manifest as sensory deficits, severe lower back pain radiating down the legs, bowel/bladder incontinence, and extremity weakness. This case report is unique in that it highlights a patient who developed long-segment transverse myelitis after a varicella zoster virus infection which has not been previously reported in the literature.

Rectal indomethacin with topical epinephrine versus indomethacin alone for preventing Post-ERCP pancreatitis - A systematic review and meta-analysis.

BACKGROUND: Recent studies have compared the utility of rectal indomethacin with topical epinephrine (IE) sprayed on duodenal papilla and rectal indomethacin alone (IS) to prevent post-ERCP pancreatitis (PEP) with conflicting results. We performed a systematic review and meta-analysis to evaluate the benefit of using the combination prophylaxis as oppose to rectal indomethacin alone. METHODS: The following database were searched for our systematic review: PubMed∖Medline, Embase, Cochrane, and Web of Science. We included both randomized controlled trials (RCTs) and cohort studies. Primary outcome was incidence of PEP and secondary outcomes were adverse events and mortality. RESULTS: A total of 3 studies (all RCTs) with 2244 patients (1132 in IS and 1112 in IE group) were included. The IE group did not demonstrate any significant benefit over IS group in preventing PEP (RR: 1.15, 95% CI 0.62-2.2), mortality (RR: 0.85, 95% CI 0.22-3.24) or overall adverse events (RR: 1.3, 95% CI 0.93-1.7). CONCLUSION: The combination of rectal indomethacin and topical epinephrine failed to demonstrate any benefit over indomethacin alone in preventing PEP, decreasing mortality and overall adverse events.

Mutation of chromatin regulators and focal hotspot alterations characterize human papillomavirus-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal cancer is a disease clinically and biologically distinct from smoking-related head and neck squamous cell carcinoma (HNSCC). Despite its rapidly increasing incidence, the mutational landscape of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) remains understudied. METHODS: This article presents the first mutational analysis of the 46 HPV+ OPSCC tumors within the newly expanded cohort of 530 HNSCC tumors from The Cancer Genome Atlas. A separate exome sequencing analysis was also performed for 46 HPV+ OPSCCs matched to their normal lymphocyte controls from the Johns Hopkins University cohort. RESULTS: There was a strikingly high 33% frequency of mutations within genes associated with chromatin regulation, including mutations in lysine methyltransferase 2C (KMT2C), lysine methyltransferase 2D (KMT2D), nuclear receptor binding SET domain protein 1 (NSD1), CREB binding protein (CREBBP), E1A-associated protein p300 (EP300), and CCCTC-binding factor (CTCF). In addition, the commonly altered genes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) and fibroblast growth factor receptor 3 (FGFR3) showed distinct domain-specific hotspot mutations in comparison with their HPV- counterparts. PIK3CA showed a uniquely high rate of mutations within the helicase domain, and FGFR3 contained a predominance of hotspot S249C alterations that were not found in HPV- HNSCC. CONCLUSIONS: This analysis represents one of the largest studies to date of HPV+ OPSCC and lends novel insight into the genetic landscape of this biologically distinct disease, including a high rate of mutations in histone- and chromatin-modifying genes, which may offer novel therapeutic targets.

Evaluation of intracoronary hyperoxemic oxygen therapy in acute anterior myocardial infarction: The IC-HOT study.

BACKGROUND: In the randomized AMIHOT-II trial, supersaturated oxygen [SSO2 ] delivered into the left anterior descending (LAD) artery via an indwelling intracoronary infusion catheter following primary percutaneous coronary intervention (PCI) significantly reduced infarct size in patients with anterior ST-segment elevation myocardial infarction (STEMI) but resulted in a numerically higher incidence of safety events. OBJECTIVES: The IC-HOT study evaluated the safety of SSO2 therapy selectively delivered to the left main coronary artery (LMCA) for 60 minutes after PCI in patients with anterior STEMI. METHODS: SSO2 therapy was administered to the LMCA after stent implantation in 100 patients with anterior STEMI and proximal or mid-LAD occlusion presenting within 6 hours of symptom onset. The primary endpoint was the 30-day composite rate of net adverse clinical events (NACE) (death, reinfarction, clinically driven target vessel revascularization, stent thrombosis, severe heart failure, or TIMI major/minor bleeding) compared against an objective performance goal of 10.7%. Cardiac magnetic resonance imaging was performed at 4 and 30 days to assess infarct size. RESULTS: SSO2 delivery was successful in 98% of patients. NACE at 30 days occurred 7.1% of patients (meeting the primary safety endpoint of the study); there were no deaths, only one stent thrombosis and one case of severe heart failure. Median [interquartile range] infarct size was 24.1% [14.4%, 31.6%] at 4 days and 19.4% [8.8%, 28.9%] at 30 days. CONCLUSION: Following primary PCI in acute anterior STEMI, infusion of SSO2 via the LMCA was feasible and was associated with a favorable early safety profile.