Development and Implementation of a Virtual Clinical Skills Examination in General Psychiatry.

OBJECTIVE: During the COVID-19 pandemic, psychiatry programs have administered the Clinical Skills Evaluation (CSE) through videoconferencing. The authors evaluated the feasibility and appropriateness of administering virtual CSEs. METHODS: Virtual CSEs were administered to 11 general psychiatry residents on March 16, 2021. Teleconference software was used to connect faculty at work sites, residents at a simulation center, and volunteer patients at home. Before and after the CSE, residents and faculty were surveyed with Likert scale questions to evaluate their perceptions and experience. RESULTS: All virtual CSEs were completed successfully. Nine residents (82%) and 12 faculty (92%) responded to both surveys. Most participants (range, 67-83%) indicated that the virtual CSE was appropriate for assessing patient health and resident skills. Most participants (range, 56-100%) reported that the opening and closing of the interview, informational and affective cues, and rapport were adequately assessed. All participants agreed that suicidal and homicidal risks could be adequately assessed. Most faculty and residents (76%) believed that unique skills were required for telehealth interviews. Before the CSE, more faculty than residents believed that they received adequate training for the virtual CSE (P=.02); afterward, most participants thought that training was adequate (P=.46). More faculty than residents reported increased convenience with virtual assessments (both surveys, P<.01). CONCLUSION: Virtual CSEs were deemed feasible and appropriate. Further research is needed to identify the specific skills required to perform a virtual CSE and to clarify the potential limitations and benefits of this format.

Cardiac resynchronization therapy improves the ventricular function of patients with Fontan physiology.

Past studies have not detected consistent improvement in ventricular function (VFxn) following initiation of cardiac resynchronization therapy (CRT) in Fontan patients. However, these studies used qualitative assessments of VFxn and/or quantitative assessments of VFxn that rely upon anatomic and/or geometric assumptions that may not be valid in patients with single ventricles. To address this, we used quantitative indices of global VFxn (dP/dtic and the Tei index) that are not encumbered by the limitations associated with the indices used in previous studies of CRT in Fontan patients. METHODS: Patients with Fontan physiology who had received CRT therapy from 2004 to 2019 were included in the study. They were compared to a concurrent group of Fontan patients who had received standard dual-chamber pacemakers (DCPMs). RESULTS: VFxn was assessed at 3 time points: prior to, shortly after, and late after initiation of pacemaker therapy. Prior to initiation of pacemaker therapy, VFxn of the CRT patients tended to be worse than that of the DCPM patients. For both groups, VFxn appeared to be stable or slightly improved shortly after initiation of pacemaker therapy. In the CRT group, VFxn improved significantly between early and late follow-up. In contrast, VFxn in DCPM patients tended to decline during this period. Changes in VFxn correlated with concurrent changes in New York Heart Association classification. CONCLUSIONS: Quantitative assessments of VFxn using indices not confounded by complex cardiac anatomy, segmental wall motions abnormalities, or inappropriate geometric assumptions revealed that CRT in Fontan patients is associated with preservation or improvement VFxn compared to standard DCPM. Changes in VFxn correlate with concurrent changes in New York Heart Association classification.

Gram negative pyomyositis: Two case reports and a review of the literature.

Pyomyositis due to Gram negative bacteria is rare. Here we describe two cases in immunocompromised hosts. Both were bacteremic with a Gram-negative bacterium and had impaired immunity related to prolonged and ongoing chemotherapy for hematologic malignancies. Both eventually cleared the infection with a combination of local drainage and systemic antibiotics. This unusual diagnosis should be considered in an immunocompromised patient with muscle pain and fever.

Multi-omics driven predictions of response to acute phase combination antidepressant therapy: a machine learning approach with cross-trial replication.

Combination antidepressant pharmacotherapies are frequently used to treat major depressive disorder (MDD). However, there is no evidence that machine learning approaches combining multi-omics measures (e.g., genomics and plasma metabolomics) can achieve clinically meaningful predictions of outcomes to combination pharmacotherapy. This study examined data from 264 MDD outpatients treated with citalopram or escitalopram in the Mayo Clinic Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) and 111 MDD outpatients treated with combination pharmacotherapies in the Combined Medications to Enhance Outcomes of Antidepressant Therapy (CO-MED) study to predict response to combination antidepressant therapies. To assess whether metabolomics with functionally validated single-nucleotide polymorphisms (SNPs) improves predictability over metabolomics alone, models were trained/tested with and without SNPs. Models trained with PGRN-AMPS' and CO-MED's escitalopram/citalopram patients predicted response in CO-MED's combination pharmacotherapy patients with accuracies of 76.6% (p < 0.01; AUC: 0.85) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs. Then, models trained solely with PGRN-AMPS' escitalopram/citalopram patients predicted response in CO-MED's combination pharmacotherapy patients with accuracies of 75.3% (p < 0.05; AUC: 0.84) without and 77.5% (p < 0.01; AUC: 0.86) with SNPs, demonstrating cross-trial replication of predictions. Plasma hydroxylated sphingomyelins were prominent predictors of treatment outcomes. To explore the relationship between SNPs and hydroxylated sphingomyelins, we conducted multi-omics integration network analysis. Sphingomyelins clustered with SNPs and metabolites related to monoamine neurotransmission, suggesting a potential functional relationship. These results suggest that integrating specific metabolites and SNPs achieves accurate predictions of treatment response across classes of antidepressants. Finally, these results motivate functional investigation into how sphingomyelins might influence MDD pathophysiology, antidepressant response, or both.

Treatment of Major Depressive Disorder in Pediatric Populations.

Major depressive disorder (MDD) is a severe illness that afflicts about 16.6% of people over their lifetime. MDD is highly correlated with suicidality, and often first presents in adolescence. Unfortunately, many pediatric patients suffering from MDD go undiagnosed, and current evidence-based treatment options in the U.S. are limited to psychotherapy and two selective serotonin reuptake inhibitors approved by the United States Food and Drug Administration. Molecular mechanisms have been shown to play a role in MDD pathogenesis, progression, and response to medication, yet few studies have explored the role of these pathways in pediatric MDD. In this review, we outline the gravity and importance of MDD in pediatric patients, some challenges in diagnosis and treatment, current treatments available for pediatric patients, and research to investigate differences between pediatric and adult MDD. We hope that this review will provide an outline of the current understanding and treatment of MDD in pediatric patients, and provide thoughtful insights for future work that could advance our understanding of MDD in pediatric populations, and also identify new therapeutic strategies.

Fabrication of capillary-like structures with Pluronic F127® and Kerria lacca resin (shellac) in biocompatible tissue-engineered constructs.

The fabrication of large cellular tissue-engineered constructs is currently limited by an inability to manufacture internal vasculature that can be anastomosed to the host circulatory system. Creation of synthetic tissues with microvascular networks that adequately mimic the size and density of in vivo capillaries remains one of the foremost challenges within tissue engineering, as cells must reside within 200-300 µm of vasculature for long-term survival. In our previous work, we used a sacrificial microfibre technique whereby Pluronic® F127 fibres were embedded and then sacrificed within a collagen matrix, leaving behind a patent channel, which was subsequently seeded with endothelial and smooth muscle cells, forming a neointima and neomedia. We now have extended our technique and describe two approaches to synthesize a biocompatible tissue-engineered construct with macro-inlet and -outlet vessels, bridged by a dense network of cellularized microvessels, recapitulating the hierarchical organization of an arteriole, venule and capillary bed, respectively. Copyright © 2016 John Wiley & Sons, Ltd.

A Novel Three-Dimensional Platform to Investigate Neoangiogenesis, Transendothelial Migration, and Metastasis of MDAMB-231 Breast Cancer Cells.

BACKGROUND: A crucial step in the progression of cancer involves the transendothelial migration of tumor cells into the bloodstream and invasion at distant sites. Most in vitro models of malignant cell behavior do not account for the presence of and interaction with vascular cells. Three-dimensional platforms to further explore the factors responsible for metastatic cellular behavior are under intensive investigation. METHODS: Hydrogels with encapsulated MDAMB-231 breast cancer cells were fabricated with a central microchannel. The microchannel was lined with a co-culture of human umbilical vein endothelial cells and human aortic smooth muscle cells. For comparison, co-culture-seeded microchannels without breast cancer cells (MDAMB-negative) were fabricated. RESULTS: After 7 and 14 days, the endoluminal lining of encapsulated MDAMB-231 co-culture-seeded microchannels demonstrated aberrant endothelial cell and smooth muscle cell organization and breast cancer cell transendothelial migration. MDAMB-231 cells performed matrix remodeling, forming tumor aggregates within the bulk, migrating preferentially toward the hydrogel "neovessel." In contrast, MDAMB-negative constructs demonstrated maintenance of an intact endoluminal lining composed of endothelial cells and smooth muscle cells that organized into discrete layers. Furthermore, the thicknesses of the endoluminal lining of MDAMB-negative constructs were significantly greater than encapsulated MDAMB-231 co-culture-seeded constructs after 7 and 14 days (p = 0.012 and p < 0.001, respectively). CONCLUSION: The authors have created a powerful tool that may have tremendous impact on furthering our understanding of cancer recurrence and metastasis, shedding light on these poorly understood phenomena.

Fabrication and in vivo microanastomosis of vascularized tissue-engineered constructs.

Tissue engineering endeavors to create replacement tissues and restore function that may be lost through infection, trauma, and cancer. However, wide clinical application of engineered scaffolds has yet to come to fruition due to inadequate vascularization. Here, we fabricate hydrogel constructs using Pluronic(®) F127 as a sacrificial microfiber, creating microchannels within biocompatible, biodegradable type I collagen matrices. Microchannels were seeded with human umbilical vein endothelial cells (HUVEC) or HUVEC and human aortic smooth muscle cells (HASMC) in co-culture, generating constructs with an internal endothelialized microchannel. Histological analysis demonstrated HASMC/HUVEC-seeded constructs with a confluent lining after 7 days with preservation and further maturation of the lining after 14 days. Immunohistochemical staining demonstrated von Willebrand factor and CD31(+) endothelial cells along the luminal surface (neointima) and alpha-smooth muscle actin expressing smooth muscle cells in the subendothelial plane (neomedia). Additionally, the deposition of extracellular matrix (ECM) components, heparan sulfate and basal lamina collagen IV were detected after 14 days of culture. HUVEC-only- and HASMC/HUVEC-seeded microchannel-containing constructs were microsurgically anastomosed to rat femoral artery and vein and perfused, in vivo. Both HUVEC only and HUVEC/HAMSC-seeded constructs withstood physiologic perfusion pressures while their channels maintained their internal infrastructure. In conclusion, we have synthesized and performed microvascular anastomosis of tissue-engineered hydrogel constructs. This represents a significant advancement toward the generation of vascularized tissues and brings us closer to the fabrication of more complex tissues and solid organs for clinical application.

Routine, empathic and compassionate patient care: definitions, development, obstacles, education and beneficiaries.

RATIONALE: We believe that this study represents an innovative approach to clarifying the definitions of routine, empathic and compassionate health care, as well as of sympathy. We emphasize the importance of affective empathy and its intensification in the context of patient suffering (compassion), without abandoning the ideal of clinical equanimity. METHODS: We develop a pedagogical model for clinicians and trainees who are weaker in their empathic skills that includes four levels of growth. We clarify representative obstacles to empathic and compassionate care in education and clinical practice. We summarize the four beneficiaries of empathic and compassionate care (clinicians, patients, trainees, institutions). We suggest areas for future research, including the development of a compassion scale and conclude with a statement on how the conceptual and professional confusion we address adversely impacts patients and trainees. The article represents the consensus work of a group of health care professionals and students at Stony Brook University Hospital and School of Medicine who have been engaged in this project for several years through the Center for Medical Humanities, Compassionate Care, and Bioethics, established in August of 2008. CONCLUSIONS: We discern a shift away from concepts of clinical empathy and compassionate care that deny a significant place for an affective component and that idealize 'detachment'.