Applications of ChatGPT and Large Language Models in Medicine and Health Care: Benefits and Pitfalls.

Background: The use of large language models like ChatGPT is becoming increasingly popular in health care settings. These artificial intelligence models are trained on vast amounts of data and can be used for various tasks, such as language translation, summarization, and answering questions. Observations: Large language models have the potential to revolutionize the industry by assisting medical professionals with administrative tasks, improving diagnostic accuracy, and engaging patients. However, pitfalls exist, such as its inability to distinguish between real and fake information and the need to comply with privacy, security, and transparency principles. Conclusions: Careful consideration is needed to ensure the responsible and ethical use of large language models in medicine and health care. The development of [artificial intelligence] is as fundamental as the creation of the microprocessor, the personal computer, the Internet, and the mobile phone. It will change the way people work, learn, travel, get health care, and communicate with each other. Bill Gates1.

Long Noncoding RNA GAS5 Contained in Exosomes Derived from Human Adipose Stem Cells Promotes Repair and Modulates Inflammation in a Chronic Dermal Wound Healing Model.

Chronic recalcitrant wounds result from delayed or slowed healing processes. Underlying inflammation is a substantial risk factor for impaired dermal wound healing and often leads to chronic wound-related sequelae. Human adipose stem cells (hASCs) have shown tremendous potential in regenerative medicine. The goal of this project was to improve the outcome of chronic wounds by harvesting the exosomes from hASCs for therapeutic intervention. The results demonstrate that long noncoding RNA GAS5 is highly enriched in hASC exosomes and, further, that GAS5 is central to promoting wound repair in vitro. To evaluate the outcome of wound healing in a chronic low-grade inflammatory environment, lipopolysaccharide-treated HDF cells were evaluated for their response to hASC exosome treatment. Ingenuity pathway analysis identified inflammation pathways and genes affected by exosomes in a GAS5-dependent manner. Using siRNA to deplete GAS5 in HDF, the results demonstrated that Toll-like receptor 7 (TLR7) expression levels were regulated by GAS5. Importantly, the results demonstrate that GAS5 regulates inflammatory pathway genes in a chronic inflammation environment. The results presented here demonstrate that hASC exosomes are a viable therapeutic that accelerate the healing of chronic recalcitrant wounds.

Real-time artificial intelligence-based histologic classification of colorectal polyps with augmented visualization.

BACKGROUND AND AIMS: Artificial intelligence (AI)-based computer-aided diagnostic (CADx) algorithms are a promising approach for real-time histology (RTH) of colonic polyps. Our aim is to present a novel in situ CADx approach that seeks to increase transparency and interpretability of results by generating an intuitive augmented visualization of the model's predicted histology over the polyp surface. METHODS: We developed a deep learning model using semantic segmentation to delineate polyp boundaries and a deep learning model to classify subregions within the segmented polyp. These subregions were classified independently and were subsequently aggregated to generate a histology map of the polyp's surface. We used 740 high-magnification narrow-band images from 607 polyps in 286 patients and over 65,000 subregions to train and validate the model. RESULTS: The model achieved a sensitivity of .96, specificity of .84, negative predictive value (NPV) of .91, and high-confidence rate (HCR) of .88, distinguishing 171 neoplastic polyps from 83 non-neoplastic polyps of all sizes. Among 93 neoplastic and 75 non-neoplastic polyps ≤5 mm, the model achieved a sensitivity of .95, specificity of .84, NPV of .91, and HCR of .86. CONCLUSIONS: The CADx model is capable of accurately distinguishing neoplastic from non-neoplastic polyps and provides a histology map of the spatial distribution of localized histologic predictions along the delineated polyp surface. This capability may improve interpretability and transparency of AI-based RTH and offer intuitive, accurate, and user-friendly guidance in real time for the clinical management and documentation of optical histology results.

Multilevel Regulation of Protein Kinase CδI Alternative Splicing by Lithium Chloride.

Lithium chloride (LiCl) is commonly used in treatment of mood disorders; however, its usage leads to weight gain, which promotes metabolic disorders. Protein kinase C delta (PKCδ), a serine/threonine kinase, is alternatively spliced to PKCδI and PKCδII in 3T3-L1 cells. We previously demonstrated that PKCδI is the predominantly expressed isoform in 3T3-L1 preadipocytes. Here, we demonstrate that LiCl treatment decreases PKCδI levels, increases formation of lipid droplets, and increases oxidative stress. Hence, we investigated the molecular mechanisms underlying the regulation of PKCδI alternative splicing by LiCl. We previously demonstrated that the splice factor SFRS10 is essential for PKCδI splicing. Our results demonstrate that glycogen synthase kinase 3 beta (GSK3ß) phosphorylates SFRS10, and SFRS10 is in a complex with long noncoding RNA NEAT1 to promote PKCδI splicing. Using PKCδ splicing minigene and RNA immunoprecipitation assays, our results demonstrate that upon LiCl treatment, NEAT1 levels are reduced, GSK3ß activity is inhibited, and SFRS10 phosphorylation is decreased, which leads to decreased expression of PKCδI. Integration of the GSK3ß signaling pathway with the ribonucleoprotein complex of long noncoding RNA (lncRNA) NEAT1 and SFRS10 enables fine-tuning of PKCδI expression during adipogenesis. Knowledge of the molecular pathways impacted by LiCl provides an understanding of the ascent of obesity as a comorbidity in disease management.

Predictors of postendoscopic retrograde cholangiopancreatography pancreatitis, analysis of more than half a million procedures performed nationwide over the last 15 years.

BACKGROUND AND AIM: Post-ERCP pancreatitis (PEP) is the most common complication following endoscopic retrograde cholangiopancreatography (ERCP). It is still controversial whether the presence of a trainee would increase the risk of PEP. Additionally, the effects of demographic factors and comorbidities on the risk and severity of PEP are not fully understood. Our aim was to evaluate these factors using national database. METHODS: Nationwide Inpatient Sample 2000-2014 was used to identify adult patients admitted with biliary obstruction without acute pancreatitis and had an inpatient ERCP. PEP was defined as having a subsequent diagnosis of acute pancreatitis. The presence of major organs failure marked moderate-severe PEP. Demographic information, hospital characteristics, and ERCP intervention types were collected. RESULTS: We included 654 394 patients. Overall PEP rate was 5.4%. The PEP rate was lower in teaching (4.8%) compared with nonteaching (6.2%, P < 0.001) hospitals. The highest PEP rate was observed among patients undergoing Sphincter of Oddi Manometry (15.1%, odds ratio [OR] = 2.5, P < 0.001) as compared to diagnostic cholangiography (4.4%). Asians and Hispanics had higher rate of PEP (10% and 7.9%, respectively) compared with Caucasians and African Americans (4.9% and 5%, respectively, P < 0.001). Multivariate analysis showed that after controlling for the ERCP intervention types, Asians and Hispanics continued to have higher odds of PEP (OR = 1.3, P < 0.001). Seventeen percent of patients were classified as moderate-severe PEP. Older patients (OR = 3.2, P < 0.001), males (OR = 1.4, P < 0.001), and high comorbidities (1.3, P < 0.001) were major predictors of moderate-severe PEP. CONCLUSION: No evidence of higher PEP rates in teaching hospitals. Asians and Hispanics had higher PEP rates. Although ERCP intervention type is the major PEP predictor, its severity is dependent on patient characteristics.

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

Colonic stasis and chronic constipation: Demystifying proposed risk factors for colon polyp formation in a spinal cord injury veteran population.

BACKGROUND AND AIMS: Patients with spinal cord injury (SCI) suffer significant morbidity from neurogenic bowel. Chronic constipation has long-been a proposed risk factor for polyp development. We performed a retrospective cohort study in veterans with SCI to assess polyp presence in the setting of colonic stasis. METHODS: All consecutive patients at the James A. Haley Veterans Affairs Hospital with SCI and neurogenic bowel who completed screening colonoscopy between January 1, 2004 to June 30, 2013 were included. Colonoscopies were excluded if they were aborted, not completed to the cecum, of less than adequate preparation, or if polypectomy was precluded. Patient data included level, duration, and completeness of SCI. Polyp data included number, location, and histology. RESULTS: 325 patients ultimately met inclusion criteria. Most were male (96%). The average age at screening colonoscopy was 62.8 years. The majority of patients had injury to the cervical spine (41.5%). Colon polyps were detected in 130 patients (40%). Adenomatous change was seen in 95 (73%) of these patients. The adenoma detection rate (ADR) across all patients was 29.2%. Polyp presence and ADR demonstrated no statistically significant correlation with level, degree, or duration of SCI. Only patient age at time of screening colonoscopy had a significant correlation with polyp and adenoma presence (P<0.05). CONCLUSIONS: SCI had no statistically significant correlation with polyp or adenoma presence. The ADR in our veteran SCI population with chronic constipation is comparable with that reported in the general population.

Safety of gastrointestinal endoscopy with conscious sedation in obstructive sleep apnea.

AIM: To perform a systematic review and meta-analysis to assess the safety of conscious sedation in patients with obstructive sleep apnea (OSA). METHODS: A comprehensive electronic search of MEDLINE and EMBASE was performed from inception until March 1, 2015. In an effort to include unpublished data, abstracts from prior gastroenterological society meetings as well as other reference sources were interrogated. After study selection, two authors utilizing a standardized data extraction form collected the data independently. Any disagreements between authors were resolved by consensus among four authors. The methodological quality was assessed using the Newcastle Ottawa tool for observational studies. The primary variables of interest included incidence of hypoxia, hypotension, tachycardia, and bradycardia. Continuous data were summarized as odds ratio (OR) and 95%CI and pooled using generic inverse variance under the random-effects model. Heterogeneity between pooled studies was assessed using the I2 statistic. RESULTS: Initial search of MEDLINE and EMBASE identified 357 citations. A search of meeting abstracts did not yield any relevant citations. After systematic review and exclusion consensus meetings, seven studies met the a priori determined inclusion criteria. The overall methodological quality of included studies ranged from moderate to low. No significant differences between OSA patients and controls were identified among any of the study variables: Incidence of hypoxia (7 studies, 3005 patients; OR = 1.11; 95%CI: 0.73-1.11; P = 0.47; I2 = 0%), incidence of hypotension (4 studies, 2125 patients; OR = 1.10; 95%CI: 0.75-1.60; P = 0.63; I2 = 0%), incidence of tachycardia (3 studies, 2030 patients; OR = 0.94; 95%CI: 0.53-1.65; P = 0.28; I2 = 21%), and incidence of bradycardia (3 studies, 2030 patients; OR = 0.88; 95%CI: 0.63-1.22; P = 0.59; I2 = 0%). CONCLUSION: OSA is not a significant risk factor for cardiopulmonary complications in patients undergoing endoscopic procedures with conscious sedation.

Safety of Gastrointestinal Endoscopy With Conscious Sedation in Patients With and Without Obstructive Sleep Apnea.

BACKGROUND AND STUDY AIMS: Patients with obstructive sleep apnea (OSA) undergoing endoscopy with sedation are considered by practitioners to be at a higher risk for cardiopulmonary complications. The aim of the present study was to evaluate the safety of conscious sedation in patients with OSA undergoing gastrointestinal endoscopy. PATIENTS AND METHODS: This is an IRB-approved prospective cohort study performed at the James A. Haley VA. A total of 248 patients with confirmed moderate or severe OSA by polysomnography and 252 patients without OSA were enrolled. Cardiopulmonary variables such as heart rate, blood pressure, and level of blood oxygen saturation were recorded at 3-minute intervals throughout the endoscopic procedure. RESULTS: In total, 302 colonoscopies, 119 esophagogastroduodenoscopies, 6 flexible sigmoidoscopies, and 60 esophagogastroduodenoscopy/colonoscopies were performed. None of the patients in the study required endotracheal intubation, pharmacologic reversal, or experienced an adverse outcome as a result of changes in blood pressure, heart rate, or blood oxygen saturation. There were no significant differences in the rate of tachycardia (P=0.749), bradycardia (P=0.438), hypotension (systolic/diastolic, P=0.460; mean arterial pressure, P=0.571), or hypoxia (P=0.787) between groups. The average length of time spent in each procedure and the average dose of sedation administered also did not differ significantly between the groups. CONCLUSIONS: Despite the presumed increased risk of cardiopulmonary complications, patients with OSA who undergo endoscopy with conscious sedation have clinically insignificant variations in cardiopulmonary parameters that do not differ from those without OSA. Costly preventative measures in patients with OSA are not warranted.

Role of small bowel capsule endoscopy in the diagnosis and management of iron deficiency anemia in elderly: a comprehensive review of the current literature.

Iron deficiency anemia (IDA) is common and often under recognized problem in the elderly. It may be the result of multiple factors including a bleeding lesion in the gastrointestinal tract. Twenty percent of elderly patients with IDA have a negative upper and lower endoscopy and two-thirds of these have a lesion in the small bowel (SB). Capsule endoscopy (CE) provides direct visualization of entire SB mucosa, which was not possible before. It is superior to push enteroscopy, enteroclysis and barium radiography for diagnosing clinically significant SB pathology resulting in IDA. Angioectasia is one of the commonest lesions seen on the CE in elderly with IDA. The diagnostic yield of CE for IDA progressively increases with advancing age, and is highest among patients over 85 years of age. Balloon assisted enteroscopy is used to treat the lesions seen on CE. CE has some limitations mainly lack of therapeutic capability, inability to provide precise location of the lesion and false positive results. Overall CE is a very safe and effective procedure for the evaluation of IDA in elderly.

Association between colonic diverticulosis and prevalence of colorectal polyps.

INTRODUCTION: Diverticulosis and colorectal polyps increase in frequency as the population ages. Proposed common mechanisms for both include lack of dietary fiber, increased saturated fats, and slow colonic transit time. The association of diverticulosis and colorectal polyps has been previously reported with conflicting results. Despite sharing common epidemiologic predisposing factors, the association between diverticulosis and colon polyps remains unclear and needs better clarification. AIM: The primary aim of our study is to evaluate if there is any association between diverticular disease and colorectal polyps. MATERIALS AND METHODS: This is a retrospective cohort study. All consecutive patients who underwent colonoscopy between January 2009 and December 2011 were included, except those with history of inflammatory bowel disease, polyposis syndrome, and poor bowel preparation. Univariate and multivariate logistic regression analysis was conducted to analyze the association between colon polyps and diverticulosis. Hyperplastic polyps were excluded from the statistical analysis, and only pre-cancerous adenomas were included. RESULTS: A total of 2,223 patients met the inclusion criteria. The prevalence of colorectal polyps in patients with diverticulosis was significantly higher than those without diverticulosis (odds ratio (OR) 1.54; 95 % confidence interval (CI) 1.27-1.80, p = 0.001). This association was found significant for all locations of polyps and all histological subtypes. There was also a statistically significant association between age, presence of diverticulosis, and colorectal polyps (OR 1.03; 95 % CI 1.02-1.04). The incidence of colorectal polyps increases as age advances in patients with diverticulosis, with the highest association in patients >70 years of age (OR 3.55; 95 % CI 2.50-5.04). There was no significant association between indication for colonoscopy and presence of colorectal polyps in patients with diverticulosis (OR 0.98; 95 % CI 0.95-1.01). The incidence of diverticulitis was low (<1 %), and there was no association between diverticulitis and colon polyps. CONCLUSION: There is a significant association between diverticulosis and synchronous pre-cancerous colorectal polyps (adenomas). Patients with diverticulosis have a higher risk of colorectal polyps as compared to those without. This observation needs further validation by a large prospective cohort study.

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma.

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient's demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liver disease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.

Safety of conscious sedation in patients with sleep apnea in a veteran population.

OBJECTIVES: Due to the presumed higher risk of cardiopulmonary complications in patients with obstructive sleep apnea (OSA), many endoscopy centers consider OSA a contraindication to using conscious sedation. We evaluated the safety of conscious sedation during endoscopy for patients with OSA in a veteran population, and compared this to patients without OSA. METHODS: Polysomnography studies were reviewed from 2004 to 2009 to identify 200 patients with OSA who had undergone endoscopy. Controls included the last 200 consecutive endoscopies in this institution for patients without OSA. Sixty-three upper endoscopies, 136 colonoscopies, and one enteroscopy were included in the OSA group. Sixty-five upper endoscopies, 133 colonoscopies, one sigmoidoscopy, and one endoscopic ultrasound comprised the control group. Data obtained included demographics, medications prescribed, and any complication noted in the procedure report. RESULTS: No complications occurred in the control group. In the OSA group, a patient experienced oxygen desaturation during an upper endoscopy and required oxygen supplementation. The procedure was completed and did not require an extended stay in the endoscopy suite. CONCLUSION: This study demonstrated that endoscopy can be safely done in OSA patients using conscious sedation, and the complication rate is not significantly different than patients without OSA.