Reduced mortality and morbidity associated with metformin and SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus and cirrhosis.

INTRODUCTION: Evidence for dual antidiabetic therapy in type 2 diabetes mellitus patients with cirrhosis is limited. This study compared 5-year mortality, composite hepatic decompensation risk, and hepatocellular carcinoma occurrence in patients with diabetes and cirrhosis who were either on metformin monotherapy or on dual metformin and sodium-glucose co-transporter-2 inhibitor (SGLT2-I) therapy. METHODS: This retrospective study used the TriNetX Research Network to identify propensity score-matched patients treated with either metformin or dual metformin and SGLT2-I therapy. Our outcomes were all-cause mortality, a composite of hepatic decompensation events, and hepatocellular carcinoma (HCC) occurrence over 5 years. We estimated hazard ratios within each cohort with 95% confidence intervals (CI) and Kaplan-Meier estimates for time-to-event distributions with Log-rank tests. We were able to stratify our cohorts by age, sex, race, and ethnicity. We further investigated a subset of diabetic patients with cirrhosis due to MASH. RESULTS: In our propensity score-matched cohorts of type 2 diabetes patients with cirrhosis, those on dual metformin and SGLT2-I therapy had decreased risk for mortality (HR 0.57, 95%CI 0.41-0.81), reduced composite risk of becoming decompensated (HR 0.63, 95%CI 0.43-0.93) and less than half the risk for developing HCC (HR 0.43, 95%CI 0.21-0.88) compared to those on mono metformin therapy. We did not find a difference between mono or dual therapy treatment for mortality, decompensation, or HCC risks in the subset of patients with MASH cirrhosis. CONCLUSION: Dual metformin and SGLT2-I treatment in type 2 diabetes patients with cirrhosis are associated with improved mortality and hepatic complications.

Dual metformin and glucagon-like peptide-1 receptor agonist therapy reduces mortality and hepatic complications in cirrhotic patients with diabetes mellitus.

Background: Type 2 diabetes (T2DM) can accelerate the progression of cirrhosis. The potential for oral diabetes medications to counteract the mortality and morbidity of chronic liver diseases is unclear. Methods: We compared the effectiveness of dual metformin and glucagon-like peptide-1 receptor agonists (GLP1-RA) vs. metformin treatment alone in reducing mortality and hepatic complications in cirrhotic patients with T2DM. We evaluated propensity score-matched cohorts of T2DM and cirrhosis patients treated with metformin or dual metformin and GLP1-RA therapy. Data were obtained from the TriNetX Research Network. Our outcomes were all-cause mortality, composite risk of hepatic decompensation, and hepatocellular carcinoma (HCC). Results: Compared to patients on metformin alone, dual metformin and GLP1-RA therapy users had a lower risk for both death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.42-0.89; P=0.011) and hepatic decompensation (HR 0.65, 95%CI 0.46-0.93; P=0.02) over 5 years. Patients on dual therapy had a lower risk for HCC (HR 0.44, 95%CI 0.26-0.74; P=0.001) compared to mono-metformin therapy patients. Conclusion: In our multicenter retrospective study, dual therapy was associated with better mortality and morbidity in cirrhosis patients with T2DM compared to those on metformin alone.

Intestinal Endometriosis Leading to Recurrent Hematochezia.

Endometriosis occurs when endometrial tissue existing outside of the endometrial cavity has an inflammatory response, which can lead to swelling and scarring, generally in the abdominopelvic cavity. It commonly presents in reproductive-age women and very infrequently presents in postmenopausal women. We report a case of a 51-year-old woman who underwent a hysterectomy a decade before presentation with new-onset intermittent proctalgia and hematochezia. Her colonoscopy showed a sigmoid polyp, which was confirmed to be endometriosis on histopathology. This case highlights intestinal endometriosis as a rare differential to be considered in women, regardless of age, with abnormal rectal bleeding.

Young-onset colon cancer among people living with HIV in metropolitan Atlanta.

PURPOSE: Colon cancer is a leading cause of cancer-related morbidity and mortality in the USA. We sought to better characterize colon cancer among a predominantly Black cohort with and without HIV. METHODS: We retrospectively reviewed all patients (n = 1482) diagnosed with colon cancer between 2015 and 2019 at a large urban tertiary teaching hospital using ICD-9 and ICD-10 codes. In this cohort, 114 (7.7%) of the patients also had HIV. Descriptive summaries were performed for gender, age, race/ethnicity, insurance status, tobacco/alcohol use, and BMI. RESULTS: Among patients with colon cancer only, 50.51% (n = 691) were men and 49.49% (n = 677) were women. Among patients with both HIV and colon cancer, 78.95% (n = 90) were men and 21.05% (n = 24) were women (p-value < 0.001). The mean age of the colon cancer patient sample was 61.62 years for those without HIV and 51.31 years for those with HIV (p-value < 0.001). Persons with both HIV and colon cancer were more likely to have a lower BMI (p-value < 0.001) and a history of smoking and alcohol use (p-value < 0.001), compared to patients with colon cancer only. When accounting for BMI, tobacco, and alcohol use, those with HIV were 10 years younger than those without HIV, 95% CI, 7.3-13; p < 0.001. CONCLUSIONS: In this study, HIV positive status was a risk factor for developing colon cancer at a younger age. Larger observational studies with multivariable analysis should be done to better describe the risk of colon cancer and HIV.

Fellowship program directors and trainees across the United States find parental leave policies to be inconsistent, inaccessible, and inadequate.

INTRODUCTION: Determine the consistency, accessibility, and adequacy of parental leave policies for adult and pediatric medicine fellowship programs. METHODS: We administered a 40-question survey to fellowship program directors (PDs) and trainees in adult and pediatric cardiology, hematology/oncology, gastroenterology, and pulmonology/critical care fellowship programs in the United States. We used Chi-square tests to compare proportions for categorical variables and t-tests to compare means for continuous variables. RESULTS: A total of 190 PDs from 500 programs (38.0%) and 236 trainees from 142 programs (28.4%) responded. Most respondents did not believe that parental leave policies were accessible publicly (322/426; 75.6%), on password-protected intranet (343/426; 80.5%), or upon request (240/426; 56.3%). The PDs and trainees broadly felt that parental leave for fellows should be 5-10 weeks (156/426; 36.6%) or 11-15 weeks (165/426; 38.7%). A majority of PDs felt that there was no increased burden upon other fellows (122/190; 64.2%) or change in overall well-being (110/190; 57.9%). When asked about the biggest barrier to parental leave support, most PDs noted time constrains of fellowship (101/190; 53.1%) and the limited number of fellows (43/190; 22.6%). Trainees similarly selected the time constraints of training (88/236; 37.3%), but nearly one-fifth chose the culture in medicine (44/236; 18.6%). There were no statistically significant differences in answers based on the respondents' sex, specialty, or subspecialty. DISCUSSION: Parental leave policies are broadly in place, but did not feel these were readily accessible, standardized, or of optimum length. PDs and trainees noted several barriers that undermine support for better parental leave policies, including time constraints of fellowship, the limited number of fellows for coverage, and workplace culture. Standardization of parental leave policies is advisable to allow trainees to pursue fellowship training and care for their newborns without undermining their educational experiences.

Short-term aspirin and statin chemoprophylaxis did not reduce the risk of developing advanced adenomatous polyps in Black patients.

BACKGROUND: Chemoprevention of colorectal neoplasia with aspirin and statins is under-investigated in Black patients. Since Black patients suffer disproportionately from colon cancer incidence and mortality compared to other populations, we investigated the utility of aspirin and statin in reducing advanced adenomatous polyp (AAP) risk in Black patients. METHODS: We carried out a retrospective cohort study of screening colonoscopies performed at a large urban academic center from 1/1/2011 through 12/31/2019. We analyzed self-identified Black patients with > 1 colonoscopy and no personal history of either inflammatory bowel disease or colon cancer syndromes. Our primary endpoint was first AAP development after index colonoscopy among Black patients taking both aspirin and a statin compared to those taking one or neither medication. We used multivariate logistic regression modeling to investigate our outcomes. RESULTS: We found data on chemoprophylaxis use in 560 patients. The mean observation period between index colonoscopy and AAP identification was 4 years. AAP developed in 106/560 (19%) of our cohort. We found no difference in AAP risk among Black patients taking both chemoprevention medications compared to partial or no chemoprophylaxis (20% vs 18% respectively, p = 0.49). This finding remained after adjusting for age, body mass index, and tobacco use (odds ratio 1.04, 95% CI 0.65-1.67; p = 0.87). CONCLUSIONS: Short-term aspirin-statin chemoprevention did not reduce the risk of AAP development in our cohort of Black patients. Larger and long-term prospective investigations are needed to investigate the utility of chemoprophylaxis in this population. TRIAL REGISTRATION: Not applicable.

Can Sex and Seniority Predict the Quality of a Journal Reviewer's Manuscript Critique?

PURPOSE: To evaluate reviewers' timeliness and review quality for the International Journal of Radiation Oncology, Biology, Physics (IJROBP) by sex and seniority. METHODS AND MATERIALS: The IJROBP editorial office provided data on 3962 individuals invited to review manuscripts from 2011 through 2014. We identified 1657 reviewers who had been invited to provide a review on at least 3 occasions during the study period and compared review timeliness and scoring between male and female reviewers. We confirmed the reviewers' sex after having unblinded their names based on our personal acquaintance with them and via an Internet search on their department websites. We then did a subset analysis of 124 US-based reviewers who had returned a "major revision" decision. We used the Review Quality Instrument (RQI) to rate their reviews. We used odds ratios and t tests to look for differences in mean RQI scores and factors that might be associated with quality-in particular, Hirsch indices (h indices) and year of first certification. RESULTS: Of the 1657 reviewers of interest, 1245 (75.1%) were men and 412 (24.9%) were women. We found no statistically significant differences between men and women in the time to respond to invitations. There were no statistically significant differences in timeliness or review reminders based on sex. Our subset analysis showed no difference in quality (RQI scores) based on the reviewers' sex, h index, or year of first certification. CONCLUSIONS: Women and men render reviews of equal quality regardless of seniority and h index, yet women have been invited less frequently to review. This is likely because of the underrepresentation of women in radiation oncology. A more balanced academic population is needed to address this continuing disparity of women's representation in academic publishing.

Endoscopic Ultrasound-Guided Fine Needle Biopsy Needles Provide Higher Diagnostic Yield Compared to Endoscopic Ultrasound-Guided Fine Needle Aspiration Needles When Sampling Solid Pancreatic Lesions: A Meta-Analysis.

BACKGROUND/AIMS: Studies comparing the utility of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for solid pancreatic lesions have been inconclusive with no clear superiority. The aim of this meta-analysis was to compare the diagnostic accuracy and safety between the two sampling techniques. METHODS: We performed a systematic search of randomized controlled trials published between 2012 and 2019. The primary outcome was overall diagnostic accuracy. Secondary outcomes included adverse event rates, cytopathologic and histopathologic accuracy, and the mean number of passes required to obtain adequate tissue between FNA and FNB needles. Fixed and random effect models with pooled estimates of target outcomes were developed. RESULTS: Eleven studies involving 1,365 participants were included for analysis. When compared to FNB, FNA had a significant reduction in diagnostic accuracy (81% and 87%, p=0.005). In addition, FNA provided reduced cytopathologic accuracy (82% and 89%, p=0.04) and an increased number of mean passes required compared to FNB (2.3 and 1.6, respectively, p<0.0001). There was no difference in adverse event rate between FNA and FNB needles (1.8% and 2.3% respectively, p=0.64). CONCLUSION: FNB provides superior diagnostic accuracy without compromising safety when compared to FNA. FNB should be readily considered by endosonographers when evaluating solid pancreatic masses.

Potential Molecular Targets in the Setting of Chemoradiation for Esophageal Malignancies.

Although the development of effective combined chemoradiation regimens for esophageal cancers has resulted in statistically significant survival benefits, the majority of patients treated with curative intent develop locoregional and/or distant relapse. Further improvements in disease control and survival will require the development of individualized therapy based on the knowledge of host and tumor genomics and potentially harnessing the host immune system. Although there are a number of gene targets that are amplified and proteins that are overexpressed in esophageal cancers, attempts to target several of these have not proven successful in unselected patients. Herein, we review our current state of knowledge regarding the molecular pathways implicated in esophageal carcinoma, and the available agents for targeting these pathways that may rationally be combined with standard chemoradiation, with the hope that this commentary will guide future efforts of novel combinations of therapy.

Racial Disparities with Esophageal Cancer Mortality at a High-Volume University Affiliated Center: An All ACCESS Invitation.

BACKGROUND: Esophageal cancer (EC) has a dismal prognosis with 5-year survival < 19%. Black patients with EC have higher mortality than white patients, but the cause of this disparity is unclear. We sought to investigate the impact of race upon overall mortality (OM) among EC patients at our institution. METHODS: We performed a single-center retrospective review of all patients diagnosed with EC between January 2010 through December 2016 with follow-up through October 2017. We compared the difference among categorical variables and mortality using Fisher's exact test. Odds ratios (OR) and hazard regression (HR) were constructed to analyze treatment options by race. The Kaplan-Meier method was used to plot OM curves by race. We also used a logistic regression analysis to construct a predictive model for mortality based on histology and race. RESULTS: We identified 77 patients (62% male) diagnosed with EC. There was no difference in treatments offered based on race. After adjusting for age, histology and stage, we found mortality was significantly higher in blacks when compared to whites (HR 14.07, 95% CI [2.33-129.70] p < 0.008). Our predictive model revealed that blacks had a higher probability of mortality at all stages of EC. CONCLUSIONS: We found race to be an independent risk factor for OM in EC patients. This likely reflects differences in healthcare utilization or access, as evidenced by higher prevalence of Stage IV EC in black patients. Continued investigation is needed to address this disparity locally and nationally.

Comparative outcomes of endoscopic ultrasound-guided cystogastrostomy for peripancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Endoscopic ultrasound-guided cystogastrostomy has become the first-line treatment for symptomatic peripancreatic fluid collections. The aim of this study is to analyze the efficacy and safety of cystogastrostomy via a meta-analysis of the literature. METHODS: We performed a systematic search of PubMed and Medline databases for studies published from January 2005 to May 2018. We included randomized controlled trials along with retrospective and prospective observational studies reporting endoscopic ultrasound-guided cystogastrostomy stent placement for peripancreatic fluid collections. The primary outcome for our meta-analysis was complete peripancreatic fluid collection resolution on imaging. Our secondary outcomes included comparative efficacy and safety of the procedure for pseudocysts and walled-off pancreatic necrosis using metal and plastic stents. RESULTS: Seventeen articles involving 1708 patients met our inclusion criteria for meta-analysis. Based upon the random effects model, the pooled technical success rate of cystogastrostomy was 88% (95% confidence interval = 83-92 with I 2 = 85%). There was no difference in the technical success rate between pancreatic pseudocysts and walled-off pancreatic necrosis (91% and 86%, respectively p = nonsignificant). The adverse event rates for metal and plastic stents were equivalent (14% and 18%, respectively, p = nonsignificant). CONCLUSION: Endoscopic ultrasound-guided cystogastrostomy stents are effective in the treatment of pancreatic pseudocysts and walled-off pancreatic necrosis. We found no difference in technical success or adverse event rates of drainage based on peripancreatic fluid collection type or stent used.

Successes and Failures of Combined Modalities in Upper Gastrointestinal Malignancies: New Directions.

Upper gastrointestinal malignancies generally have moderate to poor cure rates, even in the earliest stages, thereby implying that both local and systemic treatments have room for improvement. Therapeutic options are broadening, however, with the development of new immunotherapies and targeted agents, which can have synergistic effects with radiotherapy. Here we discuss the current state of combined modality therapy for upper gastrointestinal malignancies, specifically recent successes and setbacks in trials of radiation therapy with targeted therapies, vaccines, immunotherapies, and chemotherapies.

Feasibility and safety of cavity-directed stereotactic radiosurgery for brain metastases at a high-volume medical center.

OBJECTIVE: Our objective was to report safety and efficacy of stereotactic radiosurgery (SRS) to the surgical bed following resection of brain metastases. METHODS: Eighty-seven consecutive patients who underwent cavity-directed SRS to the operative bed for the treatment of brain metastases between 2002 and 2010 were evaluated. SRS required a gadolinium-enhanced, high-resolution, T1-weighted magnetic resonance imaging for tumor targeting and delivered a median dose of 18 Gy (14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain irradiation was reserved for salvage. Patients were followed every 3 months with clinical examination and magnetic resonance imaging. Overall survival, local and regional recurrence, and factors affecting these outcomes were evaluated using Kaplan-Meier and log-rank analyses. RESULTS: The median imaging follow-up was 7.1 months, with >40% of patients having imaging for ≥1 year. Local control at 1 and 2 years was 82% and 75%, respectively. Cavity recurrence was more common with a tumor diameter >3 cm (P < .020) or resection cavity volume >14 mL (P < .050). One-year local control for tumors <2 cm, 2 cm to 3 cm, and >3 cm were 100%, 86%, and 72%, respectively. Neither subtotal resection nor target margins >2 mm to 3 mm affected local control. The median overall survival was 14.3 months with actuarial 5-year survival of 20%. Actuarial regional central nervous system recurrence was 44% at 1 year. On univariate analysis, only the presence of extracranial disease was associated with survival (P < .001) and central nervous system failure (P < .030). CONCLUSIONS: Excellent local control is achievable with cavity-directed SRS in well-selected patients, particularly for lesions with diameter <3 cm and resection cavity volumes <14 mL. Long-term survival is possible for select patients.

Clinical Approaches to Immunotherapy in Non-Small Cell Lung Cancer: Current and Future Perspectives.

Lung cancer is among the most prevalent and deadly cancers. Although the development of targeted drugs, erlotinib and crizotinib, has improved lung cancer management, survival rates of lung cancer patients have not shown significant improvement over the past decade. Better therapeutic options are required to treat lung cancer patients. Immunotherapy is a maturing and rapidly growing field, which has recently contributed many novel strategies for addressing cancer treatment. Here, we discuss the current state of cancer vaccines, immune checkpoint blockers, and adoptive cellular therapies, as novel clinical treatment strategies for non-small cell lung cancer. The durability of clinical activity in a subset of patients has led to a great deal of excitement and optimism.

Complex chronic conditions in Rhode Island's pediatric populace: implications for palliative and hospice services, 2000-2012.

BACKGROUND: Pediatric patients with complex chronic conditions (CCC) can benefit from pediatric palliative and hospice care (PP/HC) services. PP/HC can be delivered in a variety of health care settings and for a multitude of conditions, but data on hospitalization patterns and on secondary illnesses in pediatric CCC patients remains scant. OBJECTIVE: The study objective was to describe mortality trends for Rhode Island resident children aged 0-17 years, along with the demographics, subtypes, sites of death, and comorbidities of those with CCC. METHODS: This was a retrospective cohort study using demographic, hospitalization, and clinical data from all Rhode Island Department of Health death certificates from 2000 to 2012. RESULTS: Among the 1422 Rhode Island children aged 0-17 years old who died from 2000 to 2012, CCCs accounted for 27% (279/1049) of medically related deaths and 62% (145/233) of such deaths after infancy. CCC deaths were more likely at home (OR 5.202, 95% CI 2.984-9.203, p<0.001) and to have had a secondary cause of death documented (OR 3.032, 95% CI 2.259-4.067, p<0.001) than were other medically related deaths. Infants with CCCs were more likely to die in an inpatient setting (OR 5.141, 95% CI 2.718-10.026, p<0.001), whereas 1-17 year-olds with CCCs were more likely to die at home (OR 5.346, 95% CI 2.200-14.811, p<0.001) or in an emergency department (OR 3.281, 95% CI 1.363-8.721, p<0.040). CONCLUSIONS: CCCs constitute a significant proportion of medically related pediatric deaths in Rhode Island and are associated with both secondary comorbidities and death at home. Specialized, multidisciplinary services are warranted and PP/HC is crucial for patient and family support.

Syncope as the presenting feature of splenic rupture after colonoscopy.

Splenic rupture is a rare, catastrophic complication of colonoscopy and an exceptional cause of syncope. This injury is believed to be from direct trauma or tension on the splenocolic ligament with subsequent capsule avulsion or else from direct instrument-induced splenic injury. Diagnosis requires a high index of suspicion that may be absent because presentation can be subtle, nonspecific, and delayed anywhere from hours to days and therefore not easily attributed to a recent endoscopy. We describe a case of syncope as the initial manifestation of splenic rupture after colonoscopy. Our patient's pain was delayed; his discomfort was mild and not localized to the left upper quadrant. Clinicians should consider syncope, lightheadedness, and drop in hemoglobin in absence of rectal bleeding following a colonoscopy as possible warning signs of imminent or emergent splenic injury.