Divergent responses of human intestinal organoid monolayers using commercial in vitro cytotoxicity assays.

In vitro models, such as primary cells and continuous cell lines routinely used for evaluating drug candidates, have limitations in their translational relevance to human diseases. Organotypic cultures are increasingly being used to assess therapeutics for various cancers and infectious diseases. Monitoring drug cytotoxicity in cell cultures is crucial in drug development, and several commercially available kits for cytotoxicity assessment offer distinct advantages and limitations. Given the complexity of organoid cultures, including donor-driven variability, we investigated drug-treated, tissue stem cell-derived human intestinal organoid responses with commonly used cell cytotoxicity assay kits. Using seven different compounds, we compared the cytotoxicity assay performance of two different leaky membrane-based and two metabolism-based assays. Significant variability was seen in reported viability outcomes across assays and organoid lines. High baseline activity of lactate dehydrogenase (LDH) in four human intestinal organoid lines required modification of the standard LDH assay protocol. Additionally, the LDH assay reported unique resilience to damage in a genetically-modified line contrasting results compared to other assays. This study highlights factors that can impact the measurement of cell cytotoxicity in intestinal organoid models, which are emerging as valuable new tools for research and pre-clinical drug testing and suggest the need for using multiple assay types to ensure reliable cytotoxicity assessment.

Assessing the Impact of Neighborhood and Built Environment on Pediatric Perioperative Care: A Systematic Review of the Literature.

CONTEXT: Neighborhood and built environment encompass one key area of the Social Determinants of Health (SDOH) and is frequently assessed using area-level indices. OBJECTIVE: We sought to systematically review the pediatric surgery literature for use of commonly applied area-level indices and to compare their utility for prediction of outcomes. DATA SOURCES: A literature search was conducted using PubMed, Ovid MEDLINE, Ovid MEDLINE Epub Ahead of Print, PsycInfo, and an artificial intelligence search tool (1/2013-2/2023). STUDY SELECTION: Inclusion required pediatric surgical patients in the US, surgical intervention performed, and use of an area-level metric. DATA EXTRACTION: Extraction domains included study, patient, and procedure characteristics. RESULTS: Area Deprivation Index is the most consistent and commonly accepted index. It is also the most granular, as it uses Census Block Groups. Child Opportunity Index is less granular (Census Tract), but incorporates pediatric-specific predictors of risk. Results with Social Vulnerability Index, Neighborhood Deprivation Index, and Neighborhood Socioeconomic Status were less consistent. LIMITATIONS: All studies were retrospective and quality varied from good to fair. CONCLUSIONS: While each index has strengths and limitations, standardization on ideal metric(s) for the pediatric surgical population will help build the inferential power needed to move from understanding the role of SDOH to building meaningful interventions towards equity in care. TYPE OF STUDY: Systematic Review. LEVEL OF EVIDENCE: Level III.

Use of Signaling in Family Medicine Residency Interviewing.

BACKGROUND AND OBJECTIVES: Although signals have been used in the residency application process by other specialties, family medicine residency directors have not previously participated. With applicant signal information available for the first time in the 2023-2024 application cycle, the current study describes family medicine residency program directors' intended use of signals and provides benchmarking descriptive data that may help inform best practices and future studies. METHODS: A total of 691 of the 745 family medicine program directors in US family medicine residency programs accredited by the Accreditation Council for Graduate Medical Education were surveyed. We used ꭓ2 and Pearson correlation analyses to examine how program directors of family medicine residency programs intended to use signaling and their perceived impact of signaling on the residency interviewing process. RESULTS: Most program directors indicated that applicant signals would assist them in deciding who to invite for an interview and would be a positive factor in a holistic review process. However, program directors also noted that rotation experience or geographic ties would be more powerful inducements to interview or rank a specific candidate. Program directors did not indicate a belief that signals would decrease interview season stress or workload. CONCLUSIONS: Signals may play an important role in the residency application process for family medicine in 2023-2024. While signals are not anticipated to decrease application workload or stress, a signal may be an important mechanism for a specific applicant to distinguish themselves with a program.

Pyogenic Granuloma in a One-Year-Old Child: A Rare Entity.

Pyogenic granuloma (PG) is a benign vascular neoplasm seen in the first and second decades of life, and it has a female predilection. It presents as a small reddish exophytic lesion, gingiva being the most common site. This article describes an unusual presentation of PG in a one-year-old female child and highlights the importance of its early diagnosis and management to avoid discomfort and distress in these patients. The diagnosis was verified by histological examination, which revealed significant markers such as endothelial growth, vascular abundance, and chronic inflammatory cell infiltration. The chosen treatment protocol was surgical excision, which led to a successful outcome with no symptoms of recurrence, as confirmed by thorough follow-up examinations.

Advances in lung transplantation: 60 years on.

Lung transplantation is a well-established treatment for advanced lung disease, improving survival and quality of life. Over the last 60 years all aspects of lung transplantation have evolved significantly and exponential growth in transplant volume. This has been particularly evident over the last decade with a substantial increase in lung transplant numbers as a result of innovations in donor utilization procurement, including the use donation after circulatory death and ex-vivo lung perfusion organs. Donor lungs have proved to be surprisingly robust, and therefore the donor pool is actually larger than previously thought. Parallel to this, lung transplant outcomes have continued to improve with improved acute management as well as microbiological and immunological insights and innovations. The management of lung transplant recipients continues to be complex and heavily dependent on a tertiary care multidisciplinary paradigm. Whilst long term outcomes continue to be limited by chronic lung allograft dysfunction improvements in diagnostics, mechanistic understanding and evolutions in treatment paradigms have all contributed to a median survival that in some centres approaches 10 years. As ongoing studies build on developing novel approaches to diagnosis and treatment of transplant complications and improvements in donor utilization more individuals will have the opportunity to benefit from lung transplantation. As has always been the case, early referral for transplant consideration is important to achieve best results.

Factors impacting intent to seek treatment within youth at clinical high risk for psychosis.

Existing work indicates that there is unmet need for care in those at clinical high risk (CHR) for psychosis. However, research on the factors that drive treatment seeking behaviors in this population is limited. Further, it is unknown how help-seeking behavior in CHR individuals compares to those seen in mood disorders, who have a higher rate of treatment seeking behavior. Participants (n = 559) completed an assessment of their intent to seek mental health treatment, attenuated psychosis-risk symptoms, and psychiatric symptoms and diagnoses. Participants were divided into CHR (n = 91), Mood Disorders (MD) (n = 72), or Community Controls (CC) groups (n = 396), whose intent to seek treatment was compared. Associations between intent to seek treatment with past treatment, depression, anxiety, positive and negative symptoms, distress from symptoms, intelligence quotient (IQ) estimates, and insight were assessed in CHR individuals. Further, it was assessed how this differs for the MD group. The MD group reported higher intent to seek treatment than CHR individuals, which reported higher intent to seek treatment than the CC group. In those at CHR, previous treatment, greater depression and anxiety severity, and higher distress all independently predicted higher intent to seek treatment. Depression predicted intent to seek treatment in both MD and CHR individuals. Previous treatment predicted intent to seek treatment in those at CHR. Our findings suggest that depression and past treatment utilization are critical factors in increasing intent to seek treatment in those at CHR, potentially serving as important targets for engaging this population in treatment.

Protocol for the 2023 CERA Department Chair Survey.

Introduction: CERA, the Council of Academic Family Medicine Educational Research Alliance, is a program sponsored by the academic family medicine organizations with the goal of supporting and improving educational research in family medicine. CERA produces surveys of different groups in academic family medicine, including an annual survey of department chairs, and members can apply to add their question sets to these surveys. This article describes the methods and demographics of the 2023 CERA Department Chair Survey. Methods: The call for proposals for the CERA Department Chair Survey was open from April 3, 2023 through May 9, 2023. Fifteen proposals were received, and five were accepted for the final survey based on scoring by peer reviewers. The Institutional Review Board of the American Academy of Family Physicians approved the survey. The final survey, including question sets from five research teams and standard demographic questions, was sent to 227 department chairs in the United States and Canada. Results: Overall, 114 chairs responded to the survey, for a response rate of 50.2%. Demographic variables, including race/ethnicity, gender, age, and region of the country, did not differ between respondents and nonrespondents. Discussion: The CERA Department Chair Survey provides a framework for members of academic family medicine organizations to conduct survey research on topics that are important to the specialty. Advantages of the CERA process include a national sample and robust response rate. Disadvantages are primarily the limitation in number of survey questions and the fact that not all proposals are accepted.

Avoidant/restrictive food intake disorder prevalence is high in children with gastroparesis and functional dyspepsia.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) prevalence in children with gastroparesis (Gp) and/or functional dyspepsia (FD) is unknown. We aimed to identify ARFID prevalence and trajectory over 2 months in children with Gp, FD, and healthy children (HC) using two screening questionnaires. We also explored the frequency of a positive ARFID screen between those with/without delayed gastric emptying or abnormal fundic accommodation. METHODS: In this prospective longitudinal study conducted at an urban tertiary care hospital, patients ages 10-17 years with Gp or FD and age- and gender-matched HC completed two validated ARFID screening tools at baseline and 2-month follow-up: the Nine Item ARFID Screen (NIAS) and the Pica, ARFID, and Rumination Disorder Interview-ARFID Questionnaire (PARDI-AR-Q). Gastric retention and fundic accommodation (for Gp and FD) were determined from gastric emptying scintigraphy. KEY RESULTS: At baseline, the proportion of children screening positive for ARFID on the NIAS versus PARDI-AR-Q was Gp: 48.5% versus 63.6%, FD: 66.7% versus 65.2%, HC: 15.3% versus 9.7%, respectively; p < 0.0001 across groups. Of children who screened positive at baseline and participated in the follow-up, 71.9% and 53.3% were positive 2 months later (NIAS versus PARDI-AR-Q, respectively). A positive ARFID screen in Gp or FD was not related to the presence/absence of delayed gastric retention or abnormal fundic accommodation. CONCLUSIONS & INFERENCES: ARFID detected from screening questionnaires is highly prevalent among children with Gp and FD and persists for at least 2 months in a substantial proportion of children. Children with these disorders should be screened for ARFID.

Effect of the Emory Healthy Kitchen Collaborative on Employee Health Habits and Body Weight: A 12-Month Workplace Wellness Trial.

INTRODUCTION: Teaching kitchens are being used to facilitate lifestyle changes with a focus on culinary and nutrition programs to improve health behaviors. Less is known regarding their use as a worksite wellness program and their influence on employees' quality of life, body weight, and adoption of healthy behaviors. We evaluated changes in self-reported healthy behaviors, overall health, and weight during a one-year multidisciplinary teaching kitchen program. METHODS: Thirty-eight benefits-eligible employees were recruited, screened based on a priori eligibility criteria that prioritized elevated body mass index (BMI), co-morbid conditions, and high levels of motivation to make lifestyle changes, and consented to participate in The Emory Healthy Kitchen Collaborative. This 12-month program included a 10-week didactic and experiential curriculum followed by continued support and access to health coaching implemented in an academic health system university hospital workplace between 2019 and 2020. Comparative statistics, paired t-test, Mcnemar's tests, and Wilcoxon signed-rank tests were used to assess changes at four time points. RESULTS: Participants improved diet quality (p ≤ 0.0001), increased confidence in tasting new foods (p = 0.03), and increased mindful eating habits (p = 0.00002). Significant changes were seen in physical activity levels; aerobic activities (p = 0.007), strength resistance activities (p = 0.02), and participation in yoga (p = 0.002). Most participants weighed within 5 lbs. of their starting weight at 3 months (p = 0.57). CONCLUSIONS: A teaching kitchen intervention is an innovative model for improving employee health behaviors and general health self-perception.

Ethnoracial Risk Variation Across the Psychosis Continuum in the US: A Systematic Review and Meta-Analysis.

Importance: Studies suggest a higher risk of schizophrenia diagnoses in Black vs White Americans, yet a systematic investigation of disparities that include other ethnoracial groups and multiple outcomes on the psychosis continuum is lacking. Objective: To identify ethnoracial risk variation in the US across 3 psychosis continuum outcomes (ie, schizophrenia and other psychotic disorders, clinical high risk for psychosis [CHR-P], and psychotic symptoms [PSs] and psychotic experiences [PEs]). Data Sources: PubMed, PsycINFO and Embase were searched up to December 2022. Study Selection: Observational studies on ethnoracial differences in risk of 3 psychosis outcomes. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Using a random-effects model, estimates for ethnoracial differences in schizophrenia and PSs/PEs were pooled and moderation by sampling and setting was determined, along with the assessment of heterogeneity and risk of bias. Main Outcomes and Measures: Risk of schizophrenia and other psychotic disorder, CHR-P, and conversion to psychosis among CHR-P and PSs/PEs. Results: Of 64 studies in the systematic review, 47 were included in the meta-analysis comprising 54 929 people with schizophrenia and 223 097 with data on PSs/PEs. Compared with White individuals, Black individuals had increased risk of schizophrenia (pooled odds ratio [OR], 2.07; 95% CI, 1.64-2.61) and PSs/PEs (pooled standardized mean difference [SMD], 0.10; 95% CI, 0.03-0.16), Latinx individuals had higher risk of PSs/PEs (pooled SMD, 0.15; 95% CI, 0.08-0.22), and individuals classified as other ethnoracial group were at significantly higher risk of schizophrenia than White individuals (pooled OR, 1.81; 95% CI, 1.31-2.50). The results regarding CHR-P studies were mixed and inconsistent. Sensitivity analyses showed elevated odds of schizophrenia in Asian individuals in inpatient settings (pooled OR, 1.84; 95% CI, 1.19-2.84) and increased risk of PEs among Asian compared with White individuals, specifically in college samples (pooled SMD, 0.16; 95% CI, 0.02-0.29). Heterogeneity across studies was high, and there was substantial risk of bias in most studies. Conclusions and Relevance: Findings of this systematic review and meta-analysis revealed widespread ethnoracial risk variation across multiple psychosis outcomes. In addition to diagnostic, measurement, and hospital bias, systemic influences such as structural racism should be considered as drivers of ethnoracial disparities in outcomes across the psychosis continuum in the US.

Identifying Barriers to Precepting Health Professions Learners During the COVID-19 Pandemic.

Background and Objectives: The COVID-19 pandemic worsened the shortage of clinical training opportunities for health professions learners. During the pandemic, additional barriers to precepting health professions learners emerged. Understanding preceptors' perceptions of barriers is a first step to providing learners with the best clinical learning opportunities. Methods: In February 2021, the Emory Primary Care Consortium surveyed primary care providers eligible to precept health professions learners to determine their current precepting status and associated barriers encountered during and since COVID-19. Results: A total of 61 physicians and 11 nurse practitioners (NPs) or physician assistants (PAs) completed the survey. Of the 41 current preceptors, 29 precepted only MD students, 2 MD and PA students, 7 NP students only, and 3 PA students only. Of the 31 respondents who were not precepting, most (21) had precepted before March 2020 and not since. Pandemic-related precepting challenges included low patient volume (12), lack of comfort teaching in a telehealth setting (7), increased external pressure (eg, children at home; 8), and other reasons (12). Overall, 20 respondents were interested in training on incorporating students into the telehealth clinical workflow and 13 in training on teaching and providing feedback remotely. Conclusion: The COVID-19 pandemic placed additional burdens on preceptors in primary care. Preceptors could benefit from training on incorporating students into telehealth visits. Increased understanding of preceptor needs could lead to new resource offerings and improved future medical education.

Hypnotherapy as a medical treatment: Evidence-based or pseudoscience?

BACKGROUND: Hypnotherapy continues to be a controversial practice in medicine. It is surrounded by myth and misuses that instill doubts about its legitimacy and usefulness. PURPOSE: In this paper, we will distinguish pseudoscientific claims from evidence-based uses of hypnotherapy. RESULTS: The use and acceptability of hypnotherapy has varied over history. Pseudoscientific uses, based on outdated theories that it can access the unconscious mind, have delegitimized hypnotherapy. Modern theories that hypnosis uses common social, emotional, and cognitive processes combined with evidence-based methods have re-established the use of hypnotherapy in many physical and mental health disorders and symptoms. Currently it is a widely accepted and recommended treatment for irritable bowel syndrome, with evidence building for many other applications. CONCLUSION: Hypnotherapy, as a pseudoscience, can become unethical and cause distress for the patient and their families. Hypnotherapy, as an evidence-based treatment, can be used as a powerful tool to treat physical and psychological symptoms related to medical ailments.

Using social media for patient care, research, and professional development: A North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition position paper.

The advent of social media has changed numerous aspects of modern life, with users developing and maintaining personal and professional relationships, following and sharing breaking news and importantly, searching for and disseminating health information and medical research. In the present paper, we reviewed available literature to outline the potential uses, pitfalls and impacts of social media for providers, scientists and institutions involved in digestive health in the domains of patient care, research and professional development. We recommend that these groups become more active participants on social media platforms to combat misinformation, advocate for patients, and curate and disseminate valuable research and educational materials. We also recommend that societies such as NASPGHAN assist its members in accessing training on effective social media use and the creation and maintenance of public-facing profiles and that academic institutions incorporate substantive social media contributions into academic promotion processes.

Patient Perception of Telemedicine in Maternal-Fetal Medicine.

Background: Maternal-fetal medicine (MFM) is a medical subspecialty that cares for patients with high-risk pregnancies. Methods: An IRB-approved survey was offered to patients in MFM offices of a tertiary health care system from March 2022 to May 2022. Demographics and responses to 15 statements about telemedicine were collected via a 5-point Likert scale. Exploratory factor analysis was performed to identify factors affecting patient perception of the telemedicine experience. We sought to examine perception of telemedicine in MFM, identify factors affecting perception, and identify whether specific demographics were associated with patients who view telemedicine appointments favorably. Results: Surveys were completed by 327 of 347 (94%) patients. A total of 233 (71%) patients felt that the telemedicine experience was equal in quality to in-person appointments, and 257 (79%) were open to telemedicine appointments in the future. Exploratory factor analysis yielded two factors: "physician attentiveness" and "technology comfort." Telemedicine was viewed favorably or neutrally for both factors. Education (lower) and marital status (single) were associated with a favorable perception of physician attentiveness. Ethnicity (Hispanic), employment status (employed), and prior telemedicine experience were associated with a favorable perception of technology comfort. Conclusion: Most patients felt the quality of telemedicine appointments was equal to those completed in person. Physician attentiveness and technology comfort affect telemedicine perception. Specific patient demographic characteristics were associated with differing perceptions of telemedicine in MFM. Our findings suggest that telemedicine is positively viewed for MFM and can be used for improving health care delivery efficiency in MFM.

Muscle-specific, liver-detargeted adeno-associated virus gene therapy rescues Pompe phenotype in adult and neonate Gaa-/- mice.

Pompe disease (PD) is a neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency. Reduced GAA activity leads to pathological glycogen accumulation in cardiac and skeletal muscles responsible for severe heart impairment, respiratory defects, and muscle weakness. Enzyme replacement therapy with recombinant human GAA (rhGAA) is the standard-of-care treatment for PD, however, its efficacy is limited due to poor uptake in muscle and the development of an immune response. Multiple clinical trials are ongoing in PD with adeno-associated virus (AAV) vectors based on liver- and muscle-targeting. Current gene therapy approaches are limited by liver proliferation, poor muscle targeting, and the potential immune response to the hGAA transgene. To generate a treatment tailored to infantile-onset PD, we took advantage of a novel AAV capsid able to increase skeletal muscle targeting compared to AAV9 while reducing liver overload. When combined with a liver-muscle tandem promoter (LiMP), and despite the extensive liver-detargeting, this vector had a limited immune response to the hGAA transgene. This combination of capsid and promoter with improved muscle expression and specificity allowed for glycogen clearance in cardiac and skeletal muscles of Gaa-/- adult mice. In neonate Gaa-/- , complete rescue of glycogen content and muscle strength was observed 6 months after AAV vector injection. Our work highlights the importance of residual liver expression to control the immune response toward a potentially immunogenic transgene expressed in muscle. In conclusion, the demonstration of the efficacy of a muscle-specific AAV capsid-promoter combination for the full rescue of PD manifestation in both neonate and adult Gaa-/- provides a potential therapeutic avenue for the infantile-onset form of this devastating disease.