Optimizing the consent process for emergent laparoscopic cholecystectomy using an interactive digital education platform: a randomized control trial.

BACKGROUND: Informed consent is essential for any surgery. The use of digital education platforms (DEPs) can enhance patient understanding of the consent discussion and is a method to standardize the consent process in elective, ambulatory settings. The use of DEP as an adjunct to standard verbal consent (SVC) has not been studied in an acute care setting. METHODS: We conducted a prospective randomized control trial with patients presenting to the emergency department of a tertiary care hospital with acute biliary pathology requiring a laparoscopic cholecystectomy (LC) between August 2021 and April 2023. Participants were randomized 1:1 to receive either a DEP module with SVC or SVC alone. Baseline procedure-specific knowledge and self-reported understanding of risks and benefits of LC were collected using a questionnaire. Primary outcome was immediate post-intervention knowledge assessed using a 21-question multiple choice questionnaire. Secondary outcomes were delayed procedure-specific knowledge and participants' satisfaction with the consent discussion. RESULTS: We recruited 79 participants and randomized them 1:1 into the intervention group (DEP + SVC, n = 40) and the control group (SVC, n = 39). Baseline demographics and baseline procedure-specific knowledge were similar between groups. The immediate post-intervention knowledge was significantly higher for participants in the intervention versus the control group with a Cohen's d effect size of 0.68 (85.2(10.6)% vs. 78.2(9.9)%; p = 0.004). Similarly, self-reported understanding of risks and benefits of LC was significantly greater for participants in the intervention versus the control group with a Cohen's effect size of 0.76 (68.5(16.4)% vs. 55.1(18.8)%; p = 0.001). For participants who completed the delayed post-intervention assessment (n = 29), there continued to be significantly higher retention of acquired knowledge in the intervention group with a Cohen's effect size of 0.61 (86.5(8.5)% vs. 79.8 (13.1)%; p = 0.024). There was no difference in participants' self-reported satisfaction with the consent discussion between groups (69.5(6.7)% vs. 67.2(7.7)%; p = 0.149). CONCLUSION: The addition of digital education platform to standard verbal consent significantly improves patient's early and delayed understanding of risks and benefits of LC in an acute care setting.

Trauma resident exposure in Canada and operative numbers (TraumaRECON): a national multicentre retrospective review of operative and nonoperative trauma teaching.

BACKGROUND: General surgeons play an important role in the provision of trauma care in Canada and the current extent of their trauma experience during training is unknown. We sought to quantify the operative and nonoperative educational experiences among Canadian general surgery trainees. METHODS: We conducted a multicentre retrospective study of major operative exposures experienced by general surgery residents, as identified using institutional trauma registries and subsequent chart-level review, for 2008-2018. We also conducted a site survey on trauma education and structure. RESULTS: We collected data on operative exposure for general surgery residents from 7 programs and survey data from 10 programs. Operations predominantly occurred after hours (73% after 1700 or on weekends) and general surgery residents were absent from a substantial proportion (25%) of relevant trauma operations. The structure of trauma education was heterogeneous among programs, with considerable site-specific variability in the involvement of surgical specialties in trauma care. During their training, graduating general surgery residents each experienced around 4 index trauma laparotomies, 1 splenectomy, 1 thoracotomy, and 0 neck explorations for trauma. CONCLUSION: General surgery residents who train in Canada receive variable and limited exposure to operative and nonoperative trauma care. These data can be used as a baseline to inform the application of competency-based medical education in trauma care for general surgery training in Canada.

Primary Intensivists and Nurses for Long-Stay Patients: A Survey of Practices and Perceptions at Academic PICUs.

OBJECTIVES: To determine the prevalence of the utilization of primary intensivists and primary nurses for long-stay patients in large, academic PICU and ascertain how these practices are operationalized and perceived. DESIGN: A cross-sectional survey. SETTING: U.S. PICUs with accredited Pediatric Critical Care Medicine fellowships. SUBJECTS: One senior physician and one senior nurse at each institution. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Separate but largely analogous questionnaires for intensivists and nurses were created using an iterative process to enhance content/face validity and readability. Sixty-seven intensivists (representing 93% of the 72 institutions with fellowship programs and their PICUs) and 59 nurses (representing 82%) responded. Twenty-four institutions utilize primary intensivists; 30 utilize primary nurses; and 13 utilize both. Most institutions use length of stay and/or other criteria (e.g., medical complexity) for eligibility. Commonly, not all patients that meet eligibility criteria receive primaries. Primary providers are overwhelmingly volunteers, and often only a fraction of providers participate. Primary intensivists at a large majority (>75%) of institutions facilitate information sharing and decision-making, attend family/team meetings, visit patients/families regularly, and are otherwise available upon request. Primary nurses at a similar majority of institutions provide consistent bedside care, facilitate information sharing, and attend family/team meetings. A large majority of respondents thought that primary intensivists increase patient/family satisfaction, reduce their stress, improve provider communication, and reduce conflict, whereas primary nurses similarly increase patient/family satisfaction. More than half of respondents shared that these practices can sometimes require effort (e.g., time and emotion), complicate decision-making, and/or reduce staffing flexibility. CONCLUSIONS: Primary practices are potential strategies to augment rotating PICU care models and better serve the needs of long-stay and other patients. These practices are being utilized to varying extents and with some operationalization uniformity at large, academic PICUs.

Understanding the contributions of VPS35 and the retromer in neurodegenerative disease.

Perturbations of the endolysosomal pathway have been suggested to play an important role in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Specifically, VPS35 and the retromer complex play an important role in the endolysosomal system and are implicated in the pathophysiology of these diseases. A single missense mutation in VPS35, Asp620Asn (D620N), is known to cause late-onset, autosomal dominant familial PD. In this review, we focus on the emerging role of the PD-linked D620N mutation in causing retromer dysfunction and dissect its implications in neurodegeneration. Additionally, we will discuss how VPS35 and the retromer are linked to AD, amyotrophic lateral sclerosis, and primary tauopathies. Interestingly, reduced levels of VPS35 and other retromer components have been observed in post-mortem brain tissue, suggesting a role for the retromer in the pathophysiology of these diseases. This review will provide a comprehensive dive into the mechanisms of VPS35 dysfunction in neurodegenerative diseases. Furthermore, we will highlight outstanding questions in the field and the retromer as a therapeutic target for neurodegenerative disease at large.

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

A Single-Centered Randomized Controlled Trial of Primary Pediatric Intensivists and Nurses.

Background: For long-stay patients (LSP) in pediatric intensive care units (PICU), frequently rotating providers can lead to ineffective information sharing and retention, varying goals and timelines, and delayed decisions, likely contributing to prolonged admissions. Primary intensivists (one physician serves as a consistent resource for the patient/family and PICU providers) and primary nurses (a small team of PICU nurses provide consistent bedside care) seek to augment usual transitory PICU care, by enhancing continuity and, potentially, decreasing length of stay (LOS). Methods: A single-centered, partially blinded randomized controlled trial of primary intensivists and nurses versus usual care. PICU patients admitted for or expected to be admitted for >10 days and who had ≥1 complex chronic condition were eligible. A block randomization with 1:1 allocation was used. The primary outcome was PICU LOS. Multiple secondary outcomes were explored. Results: Two hundred LSPs were randomized-half to receive primaries and half to usual care. The two groups were not significantly different in their baseline and admission characteristics. LSPs randomized to receive primaries had a shorter, but non-significant, mean LOS than those randomized to usual care (32.5 vs. 37.1 days, respectively, p = .19). Compared to LSPs in the usual care group, LSPs in the primary group had fewer unplanned intubations. Among LSPs that died, DNR orders were more prevalent in the primary group. Other secondary outcome and balance metrics were not significantly different between the two groups. Conclusion: Primary intensivists and nurses may be an effective strategy to counteract transitory PICU care and serve the distinctive needs of LSPs. However, additional studies are needed to determine the ways and to what extent they may accomplish this.

The effect of water temperature on orthostatic tolerance: a randomised crossover trial.

PURPOSE: Bolus water drinking, at room temperature, has been shown to improve orthostatic tolerance (OT), probably via sympathetic activation; however, it is not clear whether the temperature of the water bolus modifies the effect on OT or the cardiovascular responses to orthostatic stress. The aim of this study was to assess whether differing water temperature of the water bolus would alter time to presyncope and/or cardiovascular parameters during incremental orthostatic stress. METHODS: Fourteen participants underwent three head-up tilt (HUT) tests with graded lower body negative pressure (LBNP) continued until presyncope. Fifteen minutes prior to each HUT, participants drank a 500 mL bolus of water which was randomised, in single-blind crossover fashion, to either room temperature water (20 °C) (ROOM), ice-cold water (0-3 °C) (COLD) or warm water (45 °C) (WARM). Cardiovascular parameters were monitored continuously. RESULTS: There was no significant difference in OT in the COLD (33 ± 3 min; p = 0.3321) and WARM (32 ± 3 min; p = 0.6764) conditions in comparison to the ROOM condition (31 ± 3 min). During the HUT tests, heart rate and cardiac output were significantly reduced (p < 0.0073), with significantly increased systolic blood pressure, stroke volume, cerebral blood flow velocity and total peripheral resistance (p < 0.0054), in the COLD compared to ROOM conditions. CONCLUSIONS: In healthy controls, bolus cold water drinking results in favourable orthostatic cardiovascular responses during HUT/LBNP without significantly altering OT. Using a cold water bolus may result in additional benefits in patients with orthostatic intolerance above those conferred by bolus water at room temperature (by ameliorating orthostatic tachycardia and enhancing vascular resistance responses). Further research in patients with orthostatic intolerance is warranted.

Parkinson's disease-linked D620N VPS35 knockin mice manifest tau neuropathology and dopaminergic neurodegeneration.

Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene represent a cause of late-onset, autosomal dominant familial Parkinson's disease (PD). A single missense mutation, D620N, is considered pathogenic based upon its segregation with disease in multiple families with PD. At present, the mechanism(s) by which familial VPS35 mutations precipitate neurodegeneration in PD are poorly understood. Here, we employ a germline D620N VPS35 knockin (KI) mouse model of PD to formally establish the age-related pathogenic effects of the D620N mutation at physiological expression levels. Our data demonstrate that a heterozygous or homozygous D620N mutation is sufficient to reproduce key neuropathological hallmarks of PD as indicated by the progressive degeneration of nigrostriatal pathway dopaminergic neurons and widespread axonal pathology. Unexpectedly, endogenous D620N VPS35 expression induces robust tau-positive somatodendritic pathology throughout the brain as indicated by abnormal hyperphosphorylated and conformation-specific tau, which may represent an important and early feature of mutant VPS35-induced neurodegeneration in PD. In contrast, we find no evidence for α-synuclein-positive neuropathology in aged VPS35 KI mice, a hallmark of Lewy body pathology in PD. D620N VPS35 expression also fails to modify the lethal neurodegenerative phenotype of human A53T-α-synuclein transgenic mice. Finally, by crossing VPS35 KI and null mice, our data demonstrate that a single D620N VPS35 allele is sufficient for survival and early maintenance of dopaminergic neurons, indicating that the D620N VPS35 protein is fully functional. Our data raise the tantalizing possibility of a pathogenic interplay between mutant VPS35 and tau for inducing neurodegeneration in PD.

The Changing Landscape in Pediatric Hospitals: A Multicenter Study of How Pediatric Chronic Critical Illness Impacts NICU Throughput.

OBJECTIVE: Pediatric inpatient bed availability is increasingly constrained by the prolonged hospitalizations of children with medical complexity. The sickest of these patients are chronic critically ill and often have protracted intensive care unit (ICU) stays. Numbers and characteristics of infants with chronic critical illness are unclear, which undermines resource planning in ICU's and general pediatric wards. The goal of this study was to describe infants with chronic critical illness at six academic institutions in the United States. STUDY DESIGN: Infants admitted to six academic medical centers were screened for chronic, critical illness based on a combination of prolonged and repeated hospitalizations, use of medical technology, and chronic multiorgan involvement. Data regarding patient and hospitalization characteristics were collected. RESULTS: Just over one-third (34.8%) of pediatric inpatients across the six centers who met eligibility criteria for chronic critical illness were <12 months of age. Almost all these infants received medical technology (97.8%) and had multiorgan involvement (94.8%). Eighty-six percent (115/134) had spent time in an ICU during the current hospitalization; 31% were currently in a neonatal ICU, 34% in a pediatric ICU, and 17% in a cardiac ICU. Among infants who had been previously discharged home (n = 55), most had been discharged with medical technology (78.2%) and nearly all were still using that technology during the current readmission. Additional technologies were commonly added during the current hospitalization. CONCLUSION: Advanced strategies are needed to plan for hospital resource allocation for infants with chronic critical illness. These infants' prolonged hospitalizations begin in the neonatal ICU but often transition to other ICUs and general inpatient wards. They are commonly discharged with medical technology which is rarely weaned but often escalated during subsequent hospitalizations. Identification and tracking of these infants, beginning in the neonatal ICU, will help hospitals anticipate and strategize for inpatient bed management. KEY POINTS: · 35% of inpatients with chronic critical illness are infants.. · Nearly 90% of these infants spend some time in an intensive care unit.. · 78% are discharged with medical technology..

Differential T-Cell Reactivity to Endemic Coronaviruses and SARS-CoV-2 in Community and Health Care Workers.

Herein we measured CD4+ T-cell responses against common cold coronaviruses (CCC) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk health care workers (HCW) and community controls. We observed higher levels of CCC-reactive T cells in SARS-CoV-2-seronegative HCW compared to community donors, consistent with potential higher occupational exposure of HCW to CCC. We further show that SARS-CoV-2 T-cell reactivity of seronegative HCW was higher than community controls and correlation between CCC and SARS-CoV-2 responses is consistent with cross-reactivity and not associated with recent in vivo activation. Surprisingly, CCC T-cell reactivity was decreased in SARS-CoV-2-infected HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses, either directly or indirectly. This result was unexpected, but consistently detected in independent cohorts derived from Miami and San Diego. CD4+ T-cell responses against common cold coronaviruses (CCC) are elevated in SARS-CoV-2 seronegative high-risk health care workers (HCW) compared to COVID-19 convalescent HCW, suggesting that exposure to SARS-CoV-2 might interfere with CCC responses and/or cross-reactivity associated with a protective effect.

Experience, Perceptions, and Recommendations Concerning COVID-19-Related Clinical Research Adjustments.

BACKGROUND: During the COVID-19 public health emergency, the FDA and NIH altered clinical trial requirements to protect participants and manage study conduct. Given their detailed knowledge of research protocols and regular contact with patients, clinicians, and sponsors, clinical research professionals offer important perspectives on these changes. METHODS: We developed and distributed an anonymous survey assessing COVID-19-related clinical trial adjustment experiences, perceptions, and recommendations to Clinical Research Office personnel at the Harold C. Simmons Comprehensive Cancer Center. Responses were compared using the Fisher exact test. RESULTS: A total of 94 of 109 contacted research personnel (87%) responded. Among these individuals, 58% had >5 years' professional experience in clinical research, and 56% had personal experience with a COVID-19-related change. Respondents perceived that these changes had a positive impact on patient safety; treatment efficacy; patient and staff experience; and communication with patients, investigators, and sponsors. More than 90% felt that positive changes should be continued after COVID-19. For remote consent, telehealth, therapy shipment, off-site diagnostics, and remote monitoring, individuals with personal experience with the specific change and individuals with >5 years' professional experience were numerically more likely to recommend continuing the adjustment, and these differences were significant for telehealth (P=.04) and therapy shipment (P=.02). CONCLUSIONS: Clinical research professionals perceive that COVID-19-related clinical trial adjustments positively impact multiple aspects of study conduct. Those with greatest experience-both specific to COVID-19-related changes and more generally-are more likely to recommend that these adjustments continue in the future.

Are patients truly informed? A retrospective chart review of the documentation of informed consent in laparoscopic cholecystectomy.

Background: Research on informed consent (IC) has traditionally focused on the documentation of the discussion with patients of potential complications. We sought to examine the completeness of documentation for all elements of IC for laparoscopic cholecystectomy (LC): potential complications, alternatives to LC and details of the procedure. Differences in the documentation of IC for elective and emergent LC were examined. Methods: A retrospective chart review of patients undergoing LC at our institution between 2015 and 2017 was performed. Completeness of documentation was defined as documentation of all 3 elements of IC in the clinic note, the operating room note or the consent form itself. Data were analyzed descriptively. We compared documention for emergent and elective cases as well as documentation by residents and attending physicians using t tests. Results: A total of 270 patients were included in the analysis. Only 5 (2%) had complete documentation of all elements of IC. Documentation of potential complications was noted in 232 cases (86%), of which 58 (25%) were elective and 174 (75%) were emergent. Details were noted in 28 (10%) cases, of which 21 (75%) were elective and 7 (25%) were emergent. Alternatives were documented the least frequently: they were documented in 23 cases (9%), of which 20 (87%) were elective and 3 (13%) were emergent. Residents performed better than attending physicians in documenting IC discussions in clinic notes and on consent forms, but not in operating room notes. Conclusion: Documentation of the elements of IC for LC was poor. Potential complications were the most frequently documented element of IC; alternatives and details were often omitted. Future studies comparing audiotaped IC conversations with the documentation of IC are warranted. The use of procedure-specific consent forms for LC may facilitate documentation.

Contexte: La recherche sur le consentement éclairé (CÉ) s'est longtemps intéressée surtout à la consignation du contenu des discussions avec les patients au sujet des complications potentielles. Nous avons voulu examiner l'exhaustivité de la consignation de tous les éléments du CÉ pour la cholécystectomie laparoscopique (CL) : complications potentielles, solutions de rechange à la CL et détails de l'intervention. Nous avons observé des différences dans la consignation des éléments du CÉ pour la CL urgente et non urgente. Méthodes: Nous avons procédé à un examen rétrospectif des dossiers de patients soumis à une CL dans notre établissement entre 2015 et 2017. La consignation au dossier était jugée complète lorsque les 3 éléments du CÉ étaient présents dans la note clinique, la note opératoire ou le formulaire de consentement lui-même. Nous avons effectué une analyse descriptive des données, et nous avons comparé la consignation des éléments pour les cas urgents et non urgents, effectuée par les résidents et les médecins traitants au moyen de tests t. Résultats: Au total, 270 patients ont été inclus dans l'analyse. Tous les éléments du CÉ étaient adéquatement consignés pour seulement 5 (2 %) d'entre eux. Les complications potentielles ont été consignées dans 232 cas (86 %), dont 58 (25 %) étaient non urgents et 174 (75 %) étaient urgents. Les détails de l'intervention ont été notés dans 28 cas (10 %), dont 21 (75 %) étaient non urgents et 7 (25 %) étaient urgents. Ce sont les solutions de rechange qui ont été le moins souvent consignées : elles ont été notées dans 23 cas (9 %), dont 20 (87 %) étaient non urgents et 3 (13 %) étaient urgents. Les résidents ont mieux fait que les médecins traitants pour ce qui est de consigner les discussions sur le CÉ dans les notes cliniques et les formulaires de CÉ, mais non dans les notes opératoires. Conclusion: La consignation des éléments du CÉ pour la CL a été faible. Les complications potentielles ont été l'élément du CÉ le plus souvent consigné au dossier; les solutions de rechange et les détails de l'intervention ont souvent été omis. Il faudra procéder à d'autres études pour comparer le contenu des discussions sur le CÉ enregistrées sur bande audio et sa consignation. L'utilisation de formulaires de CÉ spécifiques aux interventions pourrait faciliter la consignation de leurs éléments.

Thoracic duct embolization via chest tube for a patient with postoperative traumatic chylothorax.

We present the case of a 53-year-old man who experienced a postoperative chyle leak after minimally invasive esophagectomy with mass ligation of the thoracic duct; conservative management failed. Interventional radiology was unsuccessful initially in accessing the cisterna chyli with conventional methods, yet ethiodized oil was noted at the tip of his right chest tube. The chest tube and its tract were used as an avenue to access the thoracic duct and successfully facilitate its embolization.

Parkin mediates the ubiquitination of VPS35 and modulates retromer-dependent endosomal sorting.

Mutations in a number of genes cause familial forms of Parkinson's disease (PD), including mutations in the vacuolar protein sorting 35 ortholog (VPS35) and parkin genes. In this study, we identify a novel functional interaction between parkin and VPS35. We demonstrate that parkin interacts with and robustly ubiquitinates VPS35 in human neural cells. Familial parkin mutations are impaired in their ability to ubiquitinate VPS35. Parkin mediates the attachment of an atypical poly-ubiquitin chain to VPS35 with three lysine residues identified within the C-terminal region of VPS35 that are covalently modified by ubiquitin. Notably, parkin-mediated VPS35 ubiquitination does not promote the proteasomal degradation of VPS35. Furthermore, parkin does not influence the steady-state levels or turnover of VPS35 in neural cells and VPS35 levels are normal in the brains of parkin knockout mice. These data suggest that ubiquitination of VPS35 by parkin may instead serve a non-degradative cellular function potentially by regulating retromer-dependent sorting. Accordingly, we find that components of the retromer-associated WASH complex are markedly decreased in the brain of parkin knockout mice, suggesting that parkin may modulate WASH complex-dependent retromer sorting. Parkin gene silencing in primary cortical neurons selectively disrupts the vesicular sorting of the autophagy receptor ATG9A, a WASH-dependent retromer cargo. Parkin is not required for dopaminergic neurodegeneration induced by the expression of PD-linked D620N VPS35 in mice, consistent with VPS35 being located downstream of parkin function. Our data reveal a novel functional interaction of parkin with VPS35 that may be important for retromer-mediated endosomal sorting and PD.

Mold inhalation causes innate immune activation, neural, cognitive and emotional dysfunction.

Individuals living or working in moldy buildings complain of a variety of health problems including pain, fatigue, increased anxiety, depression, and cognitive deficits. The ability of mold to cause such symptoms is controversial since no published research has examined the effects of controlled mold exposure on brain function or proposed a plausible mechanism of action. Patient symptoms following mold exposure are indistinguishable from those caused by innate immune activation following bacterial or viral exposure. We tested the hypothesis that repeated, quantified doses of both toxic and nontoxic mold stimuli would cause innate immune activation with concomitant neural effects and cognitive, emotional, and behavioral symptoms. We intranasally administered either 1) intact, toxic Stachybotrys spores; 2) extracted, nontoxic Stachybotrys spores; or 3) saline vehicle to mice. As predicted, intact spores increased interleukin-1ß immunoreactivity in the hippocampus. Both spore types decreased neurogenesis and caused striking contextual memory deficits in young mice, while decreasing pain thresholds and enhancing auditory-cued memory in older mice. Nontoxic spores also increased anxiety-like behavior. Levels of hippocampal immune activation correlated with decreased neurogenesis, contextual memory deficits, and/or enhanced auditory-cued fear memory. Innate-immune activation may explain how both toxic mold and nontoxic mold skeletal elements caused cognitive and emotional dysfunction.

Purulent vaginal discharge diagnosed in pasture-based Holstein-Friesian cows at 21 days postpartum is influenced by previous lactation milk yield and results in diminished fertility.

In a subset of dairy cows, prolonged pathological uterine inflammation results in purulent vaginal discharge (PVD), which can have negative consequences for both fertility and milk production. However, unlike for intensive systems, analysis of the effects of PVD in predominantly pasture-based herds is limited. The objective of this study was to assess the effect of PVD in spring-calving, pasture-based dairy cows on production and reproduction indices, stratified according to previous full-lactation milk yield. We assessed clinical disease as defined by vaginal mucus score (VMS) in 440 Holstein-Friesian cows from 5 farms. Cows were categorized as healthy (VMS 0) or having PVD (VMS 1-3) at 21 d postpartum. We recorded 305-d milk, milk protein, and milk fat yields (kg) before and after disease diagnosis, as well as fertility data, such as services per conception and the calving-conception period (CCP). Using SAS 9.4 (SAS Institute Inc., Cary, NC), we analyzed data using PROC MIXED, PROC PHREG, and PROC LOGISTIC to determine the least squares means differences and hazard and odds ratios between the groups, respectively. Overall, a 60% prevalence of PVD was recorded at 21 d postpartum. Milk yield and milk constituents were similar between all VMS categories and between healthy cows and cows with PVD. Although cows in the 4 VMS categories had statistically similar CCP, cows with PVD had a significantly longer CCP than healthy cows on average (9 d). The hazard ratio for cows with PVD was 0.66, indicating a 34% higher risk of a prolonged CCP than healthy cows. Odds ratio analysis determined that cows with PVD were 3 times more likely not to conceive at all, twice as likely not to conceive at first service, twice as likely not to conceive by 100 d postpartum, and 3 times more likely to fail to conceive before 150 d postpartum compared with healthy cows. Cows were retrospectively categorized as having low or high milk yield, based on whether they were above or below the median 305-d milk yield of the study population (6,571 kg) in the lactation before vaginal mucus scoring. Based on a univariate odds ratio, high-yield cows were 1.6 times more likely to present with PVD in the subsequent lactation. The number of services per conception did not differ between healthy and PVD cows in the low- and high-yield groups. In the high-yield group, cows with PVD were 4.9 times more likely not to conceive, 2.7 times more likely to require multiple services to conceive, 2.1 times more likely to remain not pregnant by 100 d postpartum, and 4.4 times more likely to remain not pregnant by 150 d postpartum. The CCP was also significantly longer in cows with PVD than their healthy counterparts (115.9 ± 4.9 and 104 ± 7.4 d, respectively). In conclusion, PVD significantly increased the CCP in all cows, but to a greater extent in cows with a high milk yield in the lactation before disease diagnosis.

Diagnosis to death: family experiences of paediatric heart disease.

CHD remains one of the leading causes of mortality of children in the United States. There is limited research about the experience of parents from the diagnosis of their child with CHD through the death of their child. A prior study has shown that adults with heart failure go through a series of four transitions: 1) learning the diagnosis, 2) reframing the new normal, 3) taking control of the illness, and 4) understanding death is inevitable. In our qualitative study, we performed semi-structured interviews with parents who have a child die of CHD to determine whether the four transitions in adults apply to parents of children with CHD. We found that these four transitions were present in the parents we interviewed and that there were two novel transitions, one that proceeded the first Jones et al transition ("Prenatal diagnosis") and one that occurred after the final Jones et al transition ("Adjustment after death"). It is our hope that identification of these six transitions will help better support families of children with CHD.

Clinical Ethics Consultations during the COVID-19 Pandemic Surge at a New York City Medical Center.

The COVID-19 pandemic swept through New York City swiftly and with devastating effect. The crisis put enormous pressure on all hospital services, including the clinical ethics consultation team. This report describes the recent experience of the ethics consultants and Columbia University Irving Medical Center during the COVID-19 surge and compares the case load and characteristics to the corresponding period in 2019. By reporting this experience, we hope to supplement the growing body of COVID-19 scientific literature and provide details of the human toll the virus took on our hospitals and communities. We also aim to highlight the role of the clinical ethics consultant as well as areas of policy and law that may need to be addressed in order to be better prepared for a future public health crisis.

Communication and decision-making regarding children with critical cardiac disease: a systematic review of family preferences.

Critical heart disease in the pediatric population is associated with high morbidity and mortality. Research around the most effective communication and decision-making strategies is lacking. This systematic review aims to summarise what is known about parent preference for communication and decision-making in children with critical heart disease. Database searches included key words such as family, pediatric heart disease, communication, and decision-making. A total of 10 studies fit our inclusion criteria: nine were qualitative studies with parent interviews and one study was quantitative with a parent survey. We found three main themes regarding physician-parent communication and decision-making in the context of paediatric heart disease: (1) amount, timing, and content of information provided to parents; (2) helpful physician characteristics and communication styles; and (3) reinforcing the support circle for families.