Improving Pancreatic Cyst Management: Artificial Intelligence-Powered Prediction of Advanced Neoplasms through Endoscopic Ultrasound-Guided Confocal Endomicroscopy.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Artificial Intelligence in the Diagnosis and Treatment of Pancreatic Cystic Lesions and Adenocarcinoma.

Pancreatic cancer is projected to become the second leading cause of cancer-related mortality in the United States by 2030. This is in part due to the paucity of reliable screening and diagnostic options for early detection. Amongst known pre-malignant pancreatic lesions, pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent. The current standard of care for the diagnosis and classification of pancreatic cystic lesions (PCLs) involves cross-sectional imaging studies and endoscopic ultrasound (EUS) and, when indicated, EUS-guided fine needle aspiration and cyst fluid analysis. However, this is suboptimal for the identification and risk stratification of PCLs, with accuracy of only 65-75% for detecting mucinous PCLs. Artificial intelligence (AI) is a promising tool that has been applied to improve accuracy in screening for solid tumors, including breast, lung, cervical, and colon cancer. More recently, it has shown promise in diagnosing pancreatic cancer by identifying high-risk populations, risk-stratifying premalignant lesions, and predicting the progression of IPMNs to adenocarcinoma. This review summarizes the available literature on artificial intelligence in the screening and prognostication of precancerous lesions in the pancreas, and streamlining the diagnosis of pancreatic cancer.

Stereotactic Body Radiation Therapy (SBRT) Plus Immune Checkpoint Inhibitors (ICI) in Hepatocellular Carcinoma and Cholangiocarcinoma.

The combination of stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (ICI) must be explored to treat advanced primary liver tumors such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Limited retrospective reviews and case reports/series suggest this combination can be effective and safe in both cancer types. With ICIs moving into the first line (IMbrave 150, HIMALAYA, and TOPAZ-1) to manage these cancers, identifying a suitable population for this approach is challenging. Patients with macrovascular invasion (MVI)-positive HCC (especially if larger veins are involved) or recurrent HCCs post-locoregional therapies (such as transarterial radioembolization (TARE), transarterial chemoembolization (TACE), or ablation), as well as those ineligible for bevacizumab or tyrosine kinase inhibitors (TKIs), should be the focus of exploring this combination in HCC. Unresectable or oligometastatic CCA patients who cannot tolerate gemcitabine/cisplatin (GC) or those who progressed on GC without durvalumab and do not have targetable mutations could also be considered for this approach. In both HCC and CCA disease groups, SBRT plus ICI can be examined post-ICI as these two modalities act synergistically to enhance anti-tumor activity (based on pre-clinical studies). Large-scale randomized trials are needed to identify the subsets of primary liver cancers suitable for this approach and to clearly define its clinical benefit.

Treatments Administered to the First 9152 Reported Cases of COVID-19: A Systematic Review.

The emergence of SARS-CoV-2/2019 novel coronavirus (COVID-19) has created a global pandemic with no approved treatments or vaccines. Many treatments have already been administered to COVID-19 patients but have not been systematically evaluated. We performed a systematic literature review to identify all treatments reported to be administered to COVID-19 patients and to assess time to clinically meaningful response for treatments with sufficient data. We searched PubMed, BioRxiv, MedRxiv, and ChinaXiv for articles reporting treatments for COVID-19 patients published between 1 December 2019 and 27 March 2020. Data were analyzed descriptively. Of the 2706 articles identified, 155 studies met the inclusion criteria, comprising 9152 patients. The cohort was 45.4% female and 98.3% hospitalized, and mean (SD) age was 44.4 years (SD 21.0). The most frequently administered drug classes were antivirals, antibiotics, and corticosteroids, and of the 115 reported drugs, the most frequently administered was combination lopinavir/ritonavir, which was associated with a time to clinically meaningful response (complete symptom resolution or hospital discharge) of 11.7 (1.09) days. There were insufficient data to compare across treatments. Many treatments have been administered to the first 9152 reported cases of COVID-19. These data serve as the basis for an open-source registry of all reported treatments given to COVID-19 patients at www.CDCN.org/CORONA . Further work is needed to prioritize drugs for investigation in well-controlled clinical trials and treatment protocols.

What to do with medialized tympanostomy tubes? A survey of pediatric otolaryngologists.

INTRODUCTION: Tympanostomy tube placement is the most common surgical procedure performed in children. Medial migration of a tympanostomy tube is a rare occurrence where the tube migrates into the middle ear cavity as opposed to its normal extrusion into the external auditory canal. Whether medialized tympanostomy tubes should be surgically removed in asymptomatic patients is controversial. The objective of this study was to determine experience and management approach of medialized tympanostomy tubes among pediatric otolaryngologists. METHODS: A 12-question cross-section survey was designed and distributed to the American Society of Pediatric Otolaryngology (ASPO) members. The survey study was granted McGill University institutional review board and ASPO research committee approval. The survey data were filtered and cross-tabulated. Descriptive statistics were generated. RESULTS: 128 pediatric otolaryngologists completed the 12-question survey. The majority of respondents had experienced at least one case of medialized tympanostomy tube (90.6%). The majority of patients (82.0%) were asymptomatic. 74 out of 128 respondents (57.8%) indicated that they would not remove a medialized tube in an asymptomatic patient. However, 7.0% of those respondents clarified that they would proceed to surgical removal if the patient were undergoing general anesthesia for another surgery. 30.5% of respondents indicated that they would surgically remove the tube even if the patient were asymptomatic. 6.3% of respondents indicated that opted management in children would be based on a shared decision with parents. Most respondents (80.5%) did not experience complications with surgical removal nor with elected observation. CONCLUSION: There is no consensus among pediatric otolaryngologists regarding the necessity of surgically removing a medialized tympanostomy tube in asymptomatic patients. The survey suggests that both options are acceptable. If observation is chosen, it is important that parents are well informed of the potential long-term sequelae of a medialized tube and advised to consult if symptoms occur.

Patient Engagement in Randomized Controlled Tai Chi Clinical Trials among the Chronically Ill.

BACKGROUND: Physicians encounter various symptom-based complaints each day. While physicians strive to support patients with chronic illnesses, evidence indicates that patients who are actively involved in their health care have better health outcomes and sometimes lowers costs. AIM: This article is to analyze how patient engagement is described when complex interventions such as Tai Chi were delivered in Randomized Controlled clinical Trials (RCTs). It reviews the dynamic patient- physician relationship in chronic illness management and to illustrate the patient engagement process, using Tai Chi as an example intervention. METHODS: RCTs are considered the gold standard in clinical research. This study is a qualitative analysis of RCTs using Tai Chi as an intervention. A systematic literature search was performed to identify quality randomized controlled clinical trials that investigated the effects of Tai Chi. Selected clinical trials were classified according to research design, intervention style, patient engagement, and outcomes. Patient engagement was classified based on levels of patient participation, compliance, and selfmanagement. The chronic health conditions included in this paper are Parkinson's disease, polyneuropathy, hypertension, stroke, chronic insomnia, chronic heart failure, fibromyalgia, osteoarthritis, central obesity, depression, deconditioning in the elderly, or being pre-clinically disabled. RESULTS AND CONCLUSION: We found that patient engagement, as a concept, was not well defined in literature. It covers a wide range of related terms, such as patient involvement, participation, shared decision- making, patient activation, adherence, compliance, and self-management. Tai Chi, as a very complex practice system, is to balance all aspects of a patient's life; however, the level of patient engagement is difficult to describe using conventional clinical trial design. To accurately illustrate the effect of a complex intervention, novel research design must explore ways to measure patient engagement in the intervention in order to clarify its specific role on health.

The Role of Tai Chi in Mental Health Management-Lessons Learned from Clinical Trials.

BACKGROUND: Many people seek alternative treatments to reduce stress and to manage anxiety. To counsel people appropriately, physicians need to understand current evidence and recognize both the value and defects in the facts. OBJECTIVE: To review the effect of Tai Chi interventions on improvement of mental health and to learn lessons from current evidence through various clinical studies. METHODS: A literature search was performed to identify research studies that assessed Tai Chi's mental health benefits. Selected studies were classified according to research design, outcome measures, and results. They were qualitatively assessed based on Tai Chi's significant influence on mental health in the areas of mood, stress, and anxiety level. RESULTS: After screening in citations that mentioned Tai Chi as an intervention, we found 21 clinical studies, all of which included at least one outcome measure of mental health or a testing system that included a mental health component. Our results show low evidence of recommending Tai Chi intervention to all patients who seek improvement in mental health despite that many positive effects of Tai Chi practice on mood and anxiety were found in different clinical trials. CONCLUSION: Considering the fact that Tai Chi is a gentle exercise, well suited for people with various physical capabilities, especially the elderly, health care providers may consider recommending it to people with mental health issues and seek alternative treatment besides routine medical care. Nonetheless, clinicians should be aware of the limitations due to incomplete understanding of Tai Chi as an intervention. Better evidence and stronger clinical trial designs are needed to further investigate Tai Chi's role in improving mental health.

Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects.

Mutations in ß-catenin (CTNNB1) have been implicated in cancer and mental disorders. Recently, loss-of-function mutations of CTNNB1 were linked to intellectual disability (ID), and rare mutations were identified in patients with autism spectrum disorder (ASD). As a key regulator of the canonical Wnt pathway, CTNNB1 plays an essential role in neurodevelopment. However, the function of CTNNB1 in specific neuronal subtypes is unclear. To understand how CTNNB1 deficiency contributes to ASD, we generated CTNNB1 conditional knockout (cKO) mice in parvalbumin interneurons. The cKO mice had increased anxiety, but had no overall change in motor function. Interestingly, CTNNB1 cKO in PV-interneurons significantly impaired object recognition and social interactions and elevated repetitive behaviors, which mimic the core symptoms of patients with ASD. Surprisingly, deleting CTNNB1 in parvalbumin-interneurons enhanced spatial memory. To determine the effect of CTNNB1 KO in overall neuronal activity, we found that c-Fos was significantly reduced in the cortex, but not in the dentate gyrus and the amygdala. Our findings revealed a cell type-specific role of CTNNB1 gene in regulation of cognitive and autistic-like behaviors. Thus, this study has important implications for development of therapies for ASDs carrying the CTNNB1 mutation or other ASDs that are associated with mutations in the Wnt pathway. In addition, our study contributes to a broader understanding of the regulation of the inhibitory circuitry.