Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India.

Objectives: Fecal microbiota transplantation (FMT) is an emerging option for recurrent or refractory Clostridium difficile-associated diarrhea (CDAD). We describe a single-center experience of FMT in hematopoietic stem cell transplant (HSCT) recipients with CDAD in India. Methods: A prospective observational study of HSCT recipients with CDAD who received FMT in our center. Results: A total of 13 patients were included. All the patients were allogenic HSCT recipients; FMT was performed in seven patients due to refractory CDAD, in five patients due to the presence of both CDAD and graft vs host disease (GVHD), and in 1 patient due to recurrent CDAD. The approach to FMT was colonoscopic in 10 (77%) patients. Only one patient reported bacteremia and one patient had candidemia, both of which were unrelated to FMT. Of the 10 patients who had complete resolution of CDAD, only one patient presented with a recurrence of CDAD within 8 weeks post-FMT. Conclusion: This is the first study from India using FMT as a therapeutic modality for CDAD in the setting of HSCT. Here we demonstrate that FMT in India is an effective option, especially when patients have refractory CDAD, recurrent CDAD, or both GVHD and CDAD. Further studies should explore the efficacy and feasibility of FMT in India. How to cite this article: Prayag PS, Patwardhan SA, Ajapuje PS, Melinkeri S, Gadhikar H, Palnitkar S, et al. Fecal Microbiota Transplantation for Clostridium difficile-associated Diarrhea in Hematopoietic Stem Cell Transplant Recipients: A Single-center Experience from a Tertiary Center in India. Indian J Crit Care Med 2024;28(2):106-110.

Quarantining From Professional Identity: How Did COVID-19 Impact Professional Identity Formation in Undergraduate Medical Education?

Introduction: Professional Identity Formation (PIF) entails the integration of a profession's core values and beliefs with an individual's existing identity and values. Within undergraduate medical education (UGME), the cultivation of PIF is a key objective. The COVID-19 pandemic brought about substantial sociocultural challenges to UGME. Existing explorations into the repercussions of COVID-19 on PIF in UGME have predominantly adopted an individualistic approach. We sought to examine how the COVID-19 pandemic influenced PIF in UGME from a sociocultural perspective. This study aims to provide valuable insights for effectively nurturing PIF in future disruptive scenarios. Methods: Semi structured interviews were conducted with medical students from the graduating class of 2022 (n = 7) and class of 2023 (n = 13) on their medical education experiences during the pandemic and its impact on their PIF. We used the Transformation in Medical Education (TIME) framework to develop the interview guide. Direct content analysis was used for data analysis. Results: The COVID-19 pandemic significantly impacted the UGME experience, causing disruptions such as an abrupt shift to online learning, increased social isolation, and limited in-person opportunities. Medical students felt disconnected from peers, educators, and the clinical setting. In the clerkship stage, students recognized knowledge gaps, producing a "late blooming" effect. There was increased awareness for self-care and burnout prevention. Discussion: Our study suggests that pandemic disruptors delayed PIF owing largely to slower acquisition of skills/knowledge and impaired socialization with the medical community. This highlights the crucial role of sociocultural experiences in developing PIF in UGME. PIF is a dynamic and adaptable process that was preserved during the COVID-19 pandemic.

Challenges facing standardised patients representing equity-deserving groups: Insights from health care educators.

INTRODUCTION: Health professions training programmes increasingly rely on standardised patient (SP) programmes to integrate equity-deserving groups into learning and assessment opportunities. However, little is known about the optimal approach, and many SP programmes struggle to meet these growing needs. This study explored insights from health care educators working with SP programmes to deliver curricular content around equity-deserving groups. METHODS: We interviewed 14 key informants in 2021 who were involved in creating or managing SP-based education. Verbatim transcripts were analysed in an iterative coding process, anchored by qualitative content analysis methodology and informed by two theoretical frameworks: sociologic translation and simulation design. Repeated cycles of data collection and analyses continued until themes could be constructed, aligned with existing theories and grounded in empirical data, with sufficient relevance and robustness to inform educators and curricular leads. RESULTS: Three themes were constructed: (i) creating safety for SPs paid to be vulnerable, (ii) fidelity as an issue broader than who plays the role and (iii) engaging equity-deserving groups. SP work involving traditionally marginalised groups risk re-traumatization, highlighting the importance of (i) informed consent in recruiting SPs, (ii) separating role portrayal from lived experiences, (iii) adequately preparing learners and facilitators, (iv) creating time-outs and escapes for SPs and (v) building opportunity for de-roling with community support. CONCLUSIONS: SP programmes are well positioned to be allies and advocates to equity-deserving groups and to collaborate and share governance of the educational development process from its outset. SP programmes can support the delivery of curricular content around equity-deserving groups by advocating with curricular leadership, building relationships with community partners, facilitating co-creation and co-delivery of educational content and building safety into simulation.

Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea.

STUDY OBJECTIVES: To explore the association of continuous positive airway pressure (CPAP) adherence with clinical outcomes in patients with type 2 diabetes and obstructive sleep apnea in a real-world setting. METHODS: This was a retrospective study of patients with type 2 diabetes diagnosed with obstructive sleep apnea between 2010 and 2017. CPAP adherence (usage for ≥ 4 h/night for ≥ 70% of nights) was determined from the first CPAP report following the polysomnography. Data including estimated glomerular filtration rate, hemoglobin A1c, systolic and diastolic blood pressure, lipid panel, and incident cardiovascular/peripheral vascular/cerebrovascular events were extracted from medical records. Mixed-effects linear regression modeling of longitudinal repeated measures within patients was utilized for continuous outcomes, and logistic regression modeling was used for binary outcomes. Models were controlled for age, sex, body mass index, medications, and baseline levels of outcomes. RESULTS: Of the 1,295 patients, 260 (20.7%) were CPAP adherent, 318 (24.5%) were CPAP nonadherent, and 717 (55.3%) had insufficient data. The follow-up period was, on average, 2.5 (1.7) years. Compared to those who were CPAP nonadherent, those who were adherent had a significantly lower systolic blood pressure (ß = -1.95 mm Hg, P = .001) and diastolic blood pressure (ß = -2.33 mm Hg, P < .0001). Among the patients who were CPAP adherent, a 17% greater CPAP adherence was associated with a 2 mm Hg lower systolic blood pressure. Lipids, hemoglobin A1c, estimated glomerular filtration rate, and incident cardiovascular/peripheral vascular/cerebrovascular events were not different between the 2 groups. CONCLUSIONS: Achieving CPAP adherence in patients with type 2 diabetes and obstructive sleep apnea was associated with significantly lower blood pressure. Greater CPAP use within patients who were adherent was associated with lower systolic blood pressure. CITATION: Sheth U, Monson RS, Prasad B, et al. Association of continuous positive airway pressure adherence with complications in patients with type 2 diabetes and obstructive sleep apnea. J Clin Sleep Med. 2021;17(8):1563-1569.

Evaluation of the underlying causes of papilledema in children.

OBJECTIVE: The purpose of this retrospective study was to identify the types and relative frequencies of intracranial disorders in pediatric patients who present with papilledema. DESIGN: Retrospective case series. PARTICIPANTS AND METHODS: This study was conducted in 2 pediatric ophthalmology clinics, both providing community-based care in a large inner-city urban center in the U.S. Pediatric patients aged between 0 and 16 years diagnosed with papilledema and who had an underlying etiology identified were included in the study. Patient demographic data, ophthalmologic examination findings, and diagnostic work-up results were identified from clinical records. RESULTS: The mean age of 38 study patients (19 female, 19 male) was 8.6 ± 4.8 years. Of the 38 patients, 16 (42.1%) had idiopathic intracranial hypertension (IIH) as the underlying cause of the papilledema, 7 (18.4%) had a craniosynostosis disorder, 6 (15.8%) had intracranial tumours, 2 (5.3%) had primary hydrocephalus, and 1 (2.6%) patient each had transverse sinus thrombosis related to sinusitis, hypertensive crisis, subdural hematoma, intracranial abscess, Lyme disease, presumed neurosarcoidosis, and acute disseminated encephalomyelitis. Of the 6 intracranial tumours, 2 (33.3%) presented in the sellar/parasellar region, 2 (33.3%) in the posterior fossa, and 2 (33.3%) were in cortical locations. CONCLUSION: Clinicians should have a high index of suspicion for IIH and brain tumours in children presenting with papilledema. Patients with craniosynostosis should have routine eye examinations to monitor for asymptomatic papilledema. Understanding the relative incidence of etiologies for papilledema highlights the urgency of appropriate work-up and the need to consider low-frequency etiologies.

Combination scaffolds of salmon fibrin, hyaluronic acid, and laminin for human neural stem cell and vascular tissue engineering.

UNLABELLED: Human neural stem/progenitor cells (hNSPCs) are good candidates for treating central nervous system (CNS) trauma since they secrete beneficial trophic factors and differentiate into mature CNS cells; however, many cells die after transplantation. This cell death can be ameliorated by inclusion of a biomaterial scaffold, making identification of optimal scaffolds for hNSPCs a critical research focus. We investigated the properties of fibrin-based scaffolds and their effects on hNSPCs and found that fibrin generated from salmon fibrinogen and thrombin stimulates greater hNSPC proliferation than mammalian fibrin. Fibrin scaffolds degrade over the course of a few days in vivo, so we sought to develop a novel scaffold that would retain the beneficial properties of fibrin but degrade more slowly to provide longer support for hNSPCs. We found combination scaffolds of salmon fibrin with interpenetrating networks (IPNs) of hyaluronic acid (HA) with and without laminin polymerize more effectively than fibrin alone and generate compliant hydrogels matching the physical properties of brain tissue. Furthermore, combination scaffolds support hNSPC proliferation and differentiation while significantly attenuating the cell-mediated degradation seen with fibrin alone. HNSPCs express two fibrinogen-binding integrins, αVß1 and α5ß1, and several laminin binding integrins (α7ß1, α6ß1, α3ß1) that can mediate interaction with the scaffold. Lastly, to test the ability of scaffolds to support vascularization, we analyzed human cord blood-derived endothelial cells alone and in co-culture with hNSPCs and found enhanced vessel formation and complexity in co-cultures within combination scaffolds. Overall, combination scaffolds of fibrin, HA, and laminin are excellent biomaterials for hNSPCs. STATEMENT OF SIGNIFICANCE: Interest has increased recently in the development of biomaterials as neural stem cell transplantation scaffolds to treat central nervous system (CNS) injury since scaffolds improve survival and integration of transplanted cells. We report here on a novel combination scaffold composed of fibrin, hyaluronic acid, and laminin to support human neural stem/progenitor cell (hNSPC) function. This combined biomaterial scaffold has appropriate physical properties for hNSPCs and the CNS, supports hNSPC proliferation and differentiation, and attenuates rapid cell-mediated scaffold degradation. The hNSPCs and scaffold components synergistically encourage new vessel formation from human endothelial cells. This work marks the first report of a combination scaffold supporting human neural and vascular cells to encourage vasculogenesis, and sets a benchmark for biomaterials to treat CNS injury.

Early events in herpes simplex virus lifecycle with implications for an infection of lifetime.

Affecting a large percentage of human population herpes simplex virus (HSV) types -1 and -2 mainly cause oral, ocular, and genital diseases. Infection begins with viral entry into a host cell, which may be preceded by viral "surfing" along filopodia. Viral glycoproteins then bind to one or more of several cell surface receptors, such as herpesvirus entry mediator (HVEM), nectin-1, 3-O sulfated heparan sulfate (3-OS HS), paired immunoglobulin-like receptor α, and non-muscle myosin-IIA. At least five viral envelope glycoproteins participate in entry and these include gB, gC, gD and gH-gL. Post-entry, these glycoproteins may also facilitate cell-to-cell spread of the virus, which helps in the evasion of physical barriers as well as several components of the innate and adaptive immune responses. The spread may be facilitated by membrane fusion, movement across tight junctions, transfer across neuronal synapses, or the recruitment of actin-containing structures. This review summarizes some of the recent advances in our understanding of HSV entry and cell-to-cell spread.