Emergency Department Initiative to Decrease High-flow Nasal Cannula Use for Admitted Patients with Bronchiolitis.

Background: Despite limited evidence, a high-flow nasal cannula (HFNC) is often used to treat mild to moderate (m/m) bronchiolitis. We aimed to decrease the rate of HFNC use in the pediatric emergency department (PED) for m/m bronchiolitis from a baseline of 37% to less than 18.5%. Methods: A multidisciplinary team created a bronchiolitis pathway and implemented it in December 2019. A respiratory score (RS) in the electronic medical record objectively classified bronchiolitis severity as mild, moderate, or severe. We tracked HFNC utilization in the PED among patients with m/m bronchiolitis as our primary outcome measure between December 2019 and December 2021. We monitored the percentage of patients with an RS as a process measure. Interventions through four plan-do-study-act cycles included updating the hospital oxygen therapy policy, applying the RS to all patients in respiratory distress, modifying the bronchiolitis order set, and developing a bronchiolitis-specific HFNC order. Results: Three hundred twenty-five patients were admitted from the PED with m/m bronchiolitis during the 11-month baseline period and 600 patients during the 25-month intervention period. The mean rate of HFNC utilization decreased from 37% to 17%. Despite a decrease in bronchiolitis encounters after the pandemic, in the spring of 2021, when volumes returned, we had a sustained HFNC utilization rate of 17%. RS entry increased from 60% to 73% in the intervention period. Conclusions: A clinical pathway for bronchiolitis can lead to decreased use of HFNC for m/m bronchiolitis. Consistent RS, order set development with decision support, and education led to sustained improvement despite pandemic-related volumes.

Combined genetic-pharmacologic inactivation of tightly linked ADAMTS proteases in temporally specific windows uncovers distinct roles for versican proteolysis and glypican-6 in cardiac development.

Extracellular matrix remodeling mechanisms are understudied in cardiac development and congenital heart defects. We show that matrix-degrading metalloproteases ADAMTS1 and ADAMTS5, are extensively co-expressed during mouse cardiac development. The mouse mutants of each gene have mild cardiac anomalies, however, their combined genetic inactivation to elicit cooperative roles is precluded by tight gene linkage. Therefore, we coupled Adamts1 inactivation with pharmacologic ADAMTS5 blockade to uncover stage-specific cooperative roles and investigated their potential substrates in mouse cardiac development. ADAMTS5 blockade was achieved in Adamts1 null mouse embryos using an activity-blocking monoclonal antibody during distinct developmental windows spanning myocardial compaction or cardiac septation and outflow tract rotation. Synchrotron imaging, RNA in situ hybridization, immunofluorescence microscopy and electron microscopy were used to determine the impact on cardiac development and compared to Gpc6 and ADAMTS-cleavage resistant versican mutants. Mass spectrometry-based N-terminomics was used to seek relevant substrates. Combined inactivation of ADAMTS1 and ADAMTS5 prior to 12.5 days of gestation led to dramatic accumulation of versican-rich cardiac jelly and inhibited formation of compact and trabecular myocardium, which was also observed in mice with ADAMTS cleavage-resistant versican. Combined inactivation after 12.5 days impaired outflow tract development and ventricular septal closure, generating a tetralogy of Fallot-like defect. N-terminomics of combined ADAMTS knockout and control hearts identified a cleaved glypican-6 peptide only in the controls. ADAMTS1 and ADAMTS5 expression in cells was associated with specific glypican-6 cleavages. Paradoxically, combined ADAMTS1 and ADAMTS5 inactivation reduced cardiac glypican-6 and outflow tract Gpc6 transcription. Notably, Gpc6-/- hearts demonstrated similar rotational defects as combined ADAMTS inactivated hearts and both had reduced hedgehog signaling. Thus, versican proteolysis in cardiac jelly at the canonical Glu441-Ala442 site is cooperatively mediated by ADAMTS1 and ADAMTS5 and required for proper ventricular cardiomyogenesis, whereas, reduced glypican-6 after combined ADAMTS inactivation impairs hedgehog signaling, leading to outflow tract malrotation.

Correlation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer's Disease.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer's disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, both of which are brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s, and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, positron emission tomography (PET) imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified the densities of two synaptic proteins, the presynaptic protein Synaptosome Associated Protein 25 (SNAP25) and the postsynaptic protein postsynaptic density protein 95 (PSD95) in the human brain, using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate gyrus, hippocampus, frontal, primary visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI), and subjects with dementia that have different levels of Alzheimer's pathology. SNAP25 is significantly reduced in ADD when compared to controls in the frontal cortex, visual cortex, and cingulate, while the hippocampus showed a smaller, non-significant reduction, and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to controls without dementia, although in the hippocampus, this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques, and Mini Mental State Examination (MMSE) scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. The differences were less marked in the entorhinal cortex and the hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Factors associated with US caregivers' uptake of pediatric COVID-19 vaccine by race and ethnicity.

OBJECTIVES: To assess differences in willingness to vaccinate children against COVID-19, and factors that may be associated with increased acceptance, among US caregivers of various racial and ethnic identities who presented with their child to the Emergency Department (ED) after emergency use authorization of vaccines for children ages 5-11. STUDY DESIGN: A multicenter, cross-sectional survey of caregivers presenting to 11 pediatric EDs in the United States in November-December 2021. Caregivers were asked about their identified race and ethnicity and if they planned to vaccinate their child. We collected demographic data and inquired about caregiver concerns related to COVID-19. We compared responses by race/ethnicity. Multivariable logistic regression models served to determine factors that were independently associated with increased vaccine acceptance overall and among racial/ethnic groups. RESULTS: Among 1916 caregivers responding, 54.67% planned to vaccinate their child against COVID-19. Large differences in acceptance were noted by race/ethnicity, with highest acceptance among Asian caregivers (61.1%) and those who did not specify a listed racial identity (61.1%); caregivers identifying as Black (44.7%) or Multi-racial (44.4%) had lower acceptance rates. Factors associated with intent to vaccinate differed by racial/ethnic group, and included caregiver COVID-19 vaccine receipt (all groups), caregiver concerns about COVID-19 (White caregivers), and having a trusted primary provider (Black caregivers). CONCLUSIONS: Caregiver intent to vaccinate children against COVID-19 varied by race/ethnicity, but race/ethnicity did not independently account for these differences. Caregiver COVID-19 vaccination status, concerns about COVID-19, and presence of a trusted primary provider are important in vaccination decisions.

Pseudomonas infection reduction in the ICU: a successful multidisciplinary quality improvement project.

Pseudomonas aeruginosa infection causes high morbidity and mortality, especially in immunocompromised patients. Pseudomonas can develop multidrug resistance. As a result, it can cause serious outbreaks in hospital and intensive care unit (ICU) settings, increasing both length of stay and costs. In the second quarter of 2020, in a community hospital's 15-bed ICU, the P. aeruginosa-positive sputum culture rate was unacceptably high, with a trend of increasing prevalence over the previous 3 quarters. We performed a multidisciplinary quality improvement (QI) initiative to decrease the P. aeruginosa-positive rate in our ICU. We used the Define, Measure, Analyze, Improve, and Control model of Lean Six Sigma for our QI initiative to decrease the P. aeruginosa-positive sputum culture rate by 50% over the following year without affecting the baseline environmental services cleaning time. A Plan-Do-Study-Act approach was used for key interventions, which included use of sterile water for nasogastric and orogastric tubes, adherence to procedure for inline tubing and canister exchanges, replacement of faucet aerators, addition of hopper covers, and periodic water testing. We analyzed and compared positive sputum culture rates quarterly from pre-intervention to post-intervention. The initial P. aeruginosa-positive culture rate of 10.98 infections per 1,000 patient-days in a baseline sample of 820 patients decreased to 3.44 and 2.72 per 1,000 patient-days in the following 2 post-intervention measurements. Environmental services cleaning time remained stable at 34 minutes. Multiple steps involving all stakeholders were implemented to maintain this progress. A combination of multidisciplinary efforts and QI methods was able to prevent a possible ICU P. aeruginosa outbreak.

Patients With Advanced Cancer and Minor Children: An Exploratory Study of Health-Related Quality of Life and Satisfaction With Care.

OBJECTIVES: Patients with advanced cancer and minor children experience high rates of depression and anxiety. However, associations between parental status and other aspects of the patient experience are not well understood. This study compared patient-reported outcomes of patients with and without minor children. SAMPLE & SETTING: This was a retrospective analysis of 448 adults with stage III or IV solid tumors from a public research registry. METHODS & VARIABLES: Multiple linear regression models or modified Poisson regression models were fitted to evaluate differences in health-related quality of life, global health, and patient satisfaction scores between patients living with and without minors. RESULTS: One in five patients lived with minor children. They reported significantly worse health-related quality of life, global physical health, and global mental health. They also expressed lower satisfaction with time spent with their provider, communication, and financial aspects. IMPLICATIONS FOR NURSING: Patients with minor children may benefit from earlier identification and support for their psychosocial needs and concerns.

Brugada pattern in adolescent with acute myocarditis due to SARS-CoV-2.

Brugada syndrome is a genetic disorder characterized by abnormal findings on electrocardiogram (ECG) that can precipitate ventricular tachyarrhythmias and sudden cardiac death. Most clinical manifestations of Brugada syndrome are related to life-threatening tachyarrhythmias, such as ventricular fibrillation or polymorphic ventricular tachycardia, but Brugada syndrome can also present with syncope or less likely palpitations. Our case is of a previously healthy 17-year-old visiting from Puerto Rico who presented to the emergency department (ED) with a syncopal episode preceded by sore throat, dizziness, and lightheadedness without palpitations. The ED evaluation found a normal complete blood count and basic metabolic panel. The patient tested positive for COVID-19 by polymerase chain reaction. An ECG was performed that showed the Brugada pattern, which was later confirmed by cardiology. Although Brugada syndrome and pattern are well known to the medical population, the findings of Brugada pattern in the setting of COVID-19 is not well described. Recognition and treatment are important, as Brugada syndrome can lead to life-threatening arrhythmias and sudden cardiac death.

Should COVID-19 vaccines be mandated in schools? - an international caregiver perspective.

OBJECTIVES: Caregiver attitudes toward mandating COVID-19 vaccines for their children are poorly understood. We aimed to determine caregiver acceptability of COVID-19 vaccine mandates for schools/daycares and assess if opposition to mandates would result in removal of children from the educational system. STUDY DESIGN: Perform a cross-sectional, anonymous survey of adult caregivers with children ≤ 18 years presenting to 21 pediatric emergency departments in the United States, Canada, Israel, and Switzerland, November 1st through December 31st, 2021. The primary outcome was caregiver acceptance rates for school vaccine mandates, and the secondary outcomes included factors associated with mandate acceptance and caregiver intention to remove the child from school. RESULTS: Of 4,393 completed surveys, 37% of caregivers were opposed to any school vaccine mandate. Caregiver acceptance was lowest for daycare settings (33%) and increased as the child's level of education increased, college (55%). 26% of caregivers report a high likelihood (score of 8-10 on 0-10 scale) to remove their child from school if the vaccine became mandatory. Child safety was caregivers' greatest concern over vaccine mandates. A multivariable model demonstrated intent to vaccinate their child for COVID-19 (OR = 8.9, 95% CI 7.3 to 10.8; P < 0.001) and prior COVID-19 vaccination for the caregiver (OR = 3.8, 95% CI 3.0 to 4.9; P < 0.001) had the greatest odds of increasing mandate acceptance for any school level. CONCLUSIONS: Many caregivers are resistant to COVID-19 vaccine mandates for schools, and acceptance varies with school level. One-fourth of caregivers plan to remove their child from the educational system if vaccines become mandated.

SARS-CoV-2 Brain Regional Detection, Histopathology, Gene Expression, and Immunomodulatory Changes in Decedents with COVID-19.

Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.

Implementation of a Provider's Asthma-specific Note to Optimize Billing in the Pediatric Emergency Department.

There is broad variability in provider documentation for asthma encounters within the pediatric emergency department. Inadequate provider documentation leads to discrepancies between the ideal current procedural terminology (CPT) code and the assigned CPT code based on the care provided. Multiple studies demonstrate improvement in medical provider documentation after implementing standardized documentation templates and educational programs. The primary aim of this project was to improve the concordance between the ideal CPT code and assigned CPT code from a baseline of 71% to 85% in 12 months. Methods: We introduced an asthma-specific note template in January 2018. We reviewed a random sample of 20 encounters per month to compare the ideal and assigned CPT codes in the baseline and intervention periods. The primary outcome measure was the percentage of encounters with agreement between ideal and assigned billing. The secondary outcome measure was the percentage of encounters with intravenous magnesium that were billed for critical care. The process measure was asthma note usage. Provider education and Plan-Do-Study-Act (PDSA) cycles continued throughout the intervention period. We used statistical process control to measure changes over time. Results: We reviewed 740 patient encounters over a 12-month baseline and 25-month intervention period. The average agreement between ideal and assigned CPT code increased from 71% to 89%, with 84% usage of the asthma note template. The percentage of critical care billing for intravenous magnesium increased from 15% to 55%. Conclusion: Implementation of an asthma-specific provider note template in the pediatric emergency department improved billing optimization and critical care billing.

Hemispheric Asymmetry and Atypical Lobar Progression of Alzheimer-Type Tauopathy.

The spread of neurofibrillary tau pathology in Alzheimer disease (AD) mostly follows a stereotypical pattern of topographical progression but atypical patterns associated with interhemispheric asymmetry have been described. Because histopathological studies that used bilateral sampling are limited, this study aimed to assess interhemispheric tau pathology differences and the presence of topographically atypical cortical spreading patterns. Immunohistochemical staining for detection of tau pathology was performed in 23 regions of interest in 57 autopsy cases comparing bilateral cortical regions and hemispheres. Frequent mild (82% of cases) and occasional moderate (32%) interhemispheric density discrepancies were observed, whereas marked discrepancies were uncommon (7%) and restricted to occipital regions. Left and right hemispheric tau pathology dominance was observed with similar frequencies, except in Braak Stage VI that favored a left dominance. Interhemispheric Braak stage differences were observed in 16% of cases and were more frequent in advanced (IV-VI) versus early (I-III) stages. One atypical lobar topographical pattern in which occipital tau pathology density exceeded frontal lobe scores was identified in 4 cases favoring a left dominant asymmetry. We speculate that asymmetry and atypical topographical progression patterns may be associated with atypical AD clinical presentations and progression characteristics, which should be tested by comprehensive clinicopathological correlations.

Olfactory Bulb and Amygdala Gene Expression Changes in Subjects Dying with COVID-19.

In this study we conducted RNA sequencing on two brain regions (olfactory bulb and amygdala) from subjects who died from COVID-19 or who died of other causes. We found several-fold more transcriptional changes in the olfactory bulb than in the amygdala, consistent with our own work and that of others indicating that the olfactory bulb may be the initial and most common brain region infected. To some extent our results converge with pseudotime analysis towards common processes shared between the brain regions, possibly induced by the systemic immune reaction following SARS-CoV-2 infection. Changes in amygdala emphasized upregulation of interferon-related neuroinflammation genes, as well as downregulation of synaptic and other neuronal genes, and may represent the substrate of reported acute and subacute COVID-19 neurological effects. Additionally, and only in olfactory bulb, we observed an increase in angiogenesis and platelet activation genes, possibly associated with microvascular damages induced by neuroinflammation. Through coexpression analysis we identified two key genes (CAMK2B for the synaptic neuronal network and COL1A2 for the angiogenesis/platelet network) that might be interesting potential targets to reverse the effects induced by SARS-CoV-2 infection. Finally, in olfactory bulb we detected an upregulation of olfactory and taste genes, possibly as a compensatory response to functional deafferentation caused by viral entry into primary olfactory sensory neurons. In conclusion, we were able to identify transcriptional profiles and key genes involved in neuroinflammation, neuronal reaction and olfaction induced by direct CNS infection and/or the systemic immune response to SARS-CoV-2 infection.

Comparison of selected serum biochemistry measurements between the Nova Prime Plus VET, Nova pHOx Ultra, and Beckman Coulter AU680 analyzers in dogs.

BACKGROUND: Blood gas chemistry analyzers typically produce results faster and use smaller sample volumes than reference chemistry analyzers. However, results may not be comparable between blood gas chemistry analyzers and reference chemistry analyzers or between different models of blood gas chemistry analyzers. This could suggest the use of separate reference intervals and, thus, has implications when making clinical decisions. OBJECTIVE: We aimed to perform method comparison studies to evaluate selected canine serum biochemical values obtained using the Nova Stat Profile Prime Plus VET (Prime Plus VET), Stat Profile Nova pHOx Ultra (Ultra), and Beckman Coulter AU680 (Beckman) analyzers. We hypothesized that the three analyzers would be identical within inherent imprecision. METHODS: Jugular venous blood samples were collected from 103 endurance-trained sled dogs, and serum was harvested and stored for analysis. Results for serum chloride, potassium, sodium, creatinine, and urea nitrogen concentrations obtained from the Prime Plus VET and Ultra analyzers were compared with results from the Beckman analyzer, which was considered to be a reference method. Results for serum chloride, potassium, sodium, creatinine, urea nitrogen, and L-lactate concentrations obtained from the Prime Plus VET and Ultra analyzers were compared. Passing-Bablok regression and Bland-Altman plots were used for method comparison. RESULTS: Significant (P < 0.05) constant or proportional bias was found for many analytes for all three method comparison studies. CONCLUSIONS: Due to the presence of statistically significant differences between all three analyzers that may be clinically relevant, it is recommended that reference intervals be created for new blood gas analyzers, even when similar methodologies are used.

Vagus Nerve and Stomach Synucleinopathy in Parkinson's Disease, Incidental Lewy Body Disease, and Normal Elderly Subjects: Evidence Against the "Body-First" Hypothesis.

BACKGROUND: Braak and others have proposed that Lewy-type α-synucleinopathy in Parkinson's disease (PD) may arise from an exogenous pathogen that passes across the gastric mucosa and then is retrogradely transported up the vagus nerve to the medulla. OBJECTIVE: We tested this hypothesis by immunohistochemically staining, with a method specific for p-serine 129 α-synuclein (pSyn), stomach and vagus nerve tissue from an autopsy series of 111 normal elderly subjects, 33 with incidental Lewy body disease (ILBD) and 53 with PD. METHODS: Vagus nerve samples were taken adjacent to the carotid artery in the neck. Stomach samples were taken from the gastric body, midway along the greater curvature. Formalin-fixed paraffin-embedded sections were immunohistochemically stained for pSyn, shown to be highly specific and sensitive for α-synuclein pathology. RESULTS: Median disease duration for the PD group was 13 years. In the vagus nerve none of the 111 normal subjects had pSyn in the vagus, while 12/26 ILBD (46%) and 32/36 PD (89%) subjects were pSyn-positive. In the stomach none of the 102 normal subjects had pSyn while 5/30 (17%) ILBD and 42/52 (81%) of PD subjects were pSyn-positive. CONCLUSION: As there was no pSyn in the vagus nerve or stomach of subjects without brain pSyn, these results support initiation of pSyn in the brain. The presence of pSyn in the vagus nerve and stomach of a subset of ILBD cases indicates that synucleinopathy within the peripheral nervous system may occur, within a subset of individuals, at preclinical stages of Lewy body disease.

Acute Brain Ischemia, Infarction and Hemorrhage in Subjects Dying with or Without Autopsy-Proven Acute Pneumonia.

Stroke is one of the most serious complications of Covid-19 disease but it is still unclear whether stroke is more common with Covid-19 pneumonia as compared to non-Covid-19 pneumonia. We investigated the concurrence rate of autopsy-confirmed acute brain ischemia, acute brain infarction and acute brain hemorrhage with autopsy-proven acute non-Covid pneumonia in consecutive autopsies in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study of normal aging and neurodegenerative diseases. Of 691 subjects with a mean age of 83.4 years, acute pneumonia was histopathologically diagnosed in 343 (49.6%); the concurrence rates for histopathologically-confirmed acute ischemia, acute infarction or subacute infarction was 14% and did not differ between pneumonia and non-pneumonia groups while the rates of acute brain hemorrhage were 1.4% and 2.0% of those with or without acute pneumonia, respectively. In comparison, in reviews of Covid-19 publications, reported clinically-determined rates of acute brain infarction range from 0.5% to 20% while rates of acute brain hemorrhage range from 0.13% to 2%. In reviews of Covid-19 autopsy studies, concurrence rates for both acute brain infarction and acute brain hemorrhage average about 10%. Covid-19 pneumonia and non-Covid-19 pneumonia may have similar risks tor concurrent acute brain infarction and acute brain hemorrhage when pneumonia is severe enough to cause death. Additionally, acute brain ischemia, infarction or hemorrhage may not be more common in subjects dying of acute pneumonia than in subjects dying without acute pneumonia.

Acacia Gum Is Well Tolerated While Increasing Satiety and Lowering Peak Blood Glucose Response in Healthy Human Subjects.

Acacia gum (AG) is a non-viscous soluble fiber that is easily incorporated into beverages and foods. To determine its physiological effects in healthy human subjects, we fed 0, 20, and 40 g of acacia gum in orange juice along with a bagel and cream cheese after a 12 h fast and compared satiety, glycemic response, gastrointestinal tolerance, and food intake among treatments. Subjects (n = 48) reported less hunger and greater fullness at 15 min (p = 0.019 and 0.003, respectively) and 240 min (p = 0.036 and 0.05, respectively) after breakfast with the 40 g fiber treatment. They also reported being more satisfied at 15 min (p = 0.011) and less hungry with the 40 g fiber treatment at 30 min (p = 0.012). Subjects reported more bloating, flatulence, and GI rumbling on the 40 g fiber treatment compared to control, although values for GI tolerance were all low with AG treatment. No significant differences were found in area under the curve (AUC) or change from baseline for blood glucose response, although actual blood glucose with 20 g fiber at 30 min was significantly less than control. Individuals varied greatly in their postprandial glucose response to all treatments. AG improves satiety response and may lower peak glucose response at certain timepoints, and it is well tolerated in healthy human subjects. AG can be added to beverages and foods in doses that can help meet fiber recommendations.

Mapping of SARS-CoV-2 Brain Invasion and Histopathology in COVID-19 Disease.

The coronavirus SARS-CoV-2 (SCV2) causes acute respiratory distress, termed COVID-19 disease, with substantial morbidity and mortality. As SCV2 is related to previously-studied coronaviruses that have been shown to have the capability for brain invasion, it seems likely that SCV2 may be able to do so as well. To date, although there have been many clinical and autopsy-based reports that describe a broad range of SCV2-associated neurological conditions, it is unclear what fraction of these have been due to direct CNS invasion versus indirect effects caused by systemic reactions to critical illness. Still critically lacking is a comprehensive tissue-based survey of the CNS presence and specific neuropathology of SCV2 in humans. We conducted an extensive neuroanatomical survey of RT-PCR-detected SCV2 in 16 brain regions from 20 subjects who died of COVID-19 disease. Targeted areas were those with cranial nerve nuclei, including the olfactory bulb, medullary dorsal motor nucleus of the vagus nerve and the pontine trigeminal nerve nuclei, as well as areas possibly exposed to hematogenous entry, including the choroid plexus, leptomeninges, median eminence of the hypothalamus and area postrema of the medulla. Subjects ranged in age from 38 to 97 (mean 77) with 9 females and 11 males. Most subjects had typical age-related neuropathological findings. Two subjects had severe neuropathology, one with a large acute cerebral infarction and one with hemorrhagic encephalitis, that was unequivocally related to their COVID-19 disease while most of the 18 other subjects had non-specific histopathology including focal ß-amyloid precursor protein white matter immunoreactivity and sparse perivascular mononuclear cell cuffing. Four subjects (20%) had SCV2 RNA in one or more brain regions including the olfactory bulb, amygdala, entorhinal area, temporal and frontal neocortex, dorsal medulla and leptomeninges. The subject with encephalitis was SCV2-positive in a histopathologically-affected area, the entorhinal cortex, while the subject with the large acute cerebral infarct was SCV2-negative in all brain regions. Like other human coronaviruses, SCV2 can inflict acute neuropathology in susceptible patients. Much remains to be understood, including what viral and host factors influence SCV2 brain invasion and whether it is cleared from the brain subsequent to the acute illness.

Increased Risk of Autopsy-Proven Pneumonia with Sex, Season and Neurodegenerative Disease.

There has been a markedly renewed interest in factors associated with pneumonia, a leading cause of death worldwide, due to its frequent concurrence with pandemics of influenza and Covid-19 disease. Reported predisposing factors to both bacterial pneumonia and pandemic viral lower respiratory infections are wintertime occurrence, older age, obesity, pre-existing cardiopulmonary conditions and diabetes. Also implicated are age-related neurodegenerative diseases that cause parkinsonism and dementia. We investigated the prevalence of autopsy-proven pneumonia in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study, between the years 2006 and 2019 and before the beginning of the Covid-19 pandemic. Of 691 subjects dying at advanced ages (mean 83.4), pneumonia was diagnosed postmortem in 343 (49.6%). There were 185 subjects without dementia or parkinsonism while clinicopathological diagnoses for the other subjects included 319 with Alzheimer's disease dementia, 127 with idiopathic Parkinson's disease, 72 with dementia with Lewy bodies, 49 with progressive supranuclear palsy and 78 with vascular dementia. Subjects with one or more of these neurodegenerative diseases all had higher pneumonia rates, ranging between 50 and 61%, as compared to those without dementia or parkinsonism (40%). In multivariable logistic regression models, male sex and a non-summer death both had independent contributions (ORs of 1.67 and 1.53) towards the presence of pneumonia at autopsy while the absence of parkinsonism or dementia was a significant negative predictor of pneumonia (OR 0.54). Male sex, dementia and parkinsonism may also be risk factors for Covid-19 pneumonia. The apolipoprotein E4 allele, as well as obesity, chronic obstructive pulmonary disease, diabetes, hypertension, congestive heart failure, cardiomegaly and cigarette smoking history, were not significantly associated with pneumonia, in contradistinction to what has been reported for Covid-19 disease.

Addressing the needs of parents with advanced cancer: Attitudes, practice behaviors, and training experiences of oncology social workers.

OBJECTIVE: Advanced cancer patients who are parents of minor children experience heightened psychosocial distress. Oncology social workers (OSWs) are essential providers of psychosocial support to parents with advanced cancer. Yet, little is known about the experiences and approaches of OSWs in addressing these patients' unique needs. The purpose of this study was to characterize the attitudes, practice behaviors, and training experiences of OSWs who provide psychosocial care for advanced cancer patients with minor children. METHOD: Forty-one OSWs participated in a cross-sectional survey addressing multiple facets of their psychosocial care for parents with advanced cancer. The five assessed domains of psychosocial support were communication support, emotional support, household support, illness and treatment decision-making support, and end-of-life planning. RESULTS: Participants reported greatest confidence in counseling patients on communication with children about illness and providing support to co-parents about parenting concerns. OSWs reported less confidence in counseling parents on end-of-life issues and assisting families with non-traditional household structures. The majority of participants reported needing more time in their clinical practice to sufficiently address parents' psychosocial needs. Nearly 90% of participants were interested in receiving further training on the care of parents with advanced cancer. SIGNIFICANCE OF RESULTS: To improve the care of parents with advanced cancer, it is critical to understand how the psychosocial oncology workforce perceives its clinical practice needs. Study findings suggest an opportunity for enhanced training, particularly with respect to end-of-life needs and in response to the changing household structure of American families.