Association of Primary Versus Rotating Nephrologist Model of Care in Hemodialysis Programs with Patient Outcomes.

SIGNIFICANCE STATEMENT: Nephrologist staffing models for patients receiving hemodialysis vary widely. Patients may be cared for continuously by a single primary nephrologist or by a group of nephrologists on a rotating basis. It remains unclear whether these differing care models influence clinical outcomes. In this population-based cohort study of more than 14,000 incident patients on maintenance hemodialysis from Ontario, Canada, we found no difference in mortality, kidney transplantation, home dialysis initiation, hospitalizations, or emergency department visits when care was provided by a single primary nephrologist or a rotating group of nephrologists. These results suggest that primary nephrologist models do not necessarily improve objective clinical outcomes, providing reassurance to patients, providers, and administrators that both models are acceptable options.

NOVEL SIMPLEXVIRUS (SIMPLEXVIRUS DOLICHOTINEALPHA1) ASSOCIATED WITH FATALITY IN FOUR PATAGONIAN MARA (DOLICHOTIS PATAGONUM).

Four of seven Patagonian maras (Dolichotis patagonum) at a zoological institution developed acute neurologic signs that progressed to tetraparesis and death. All affected were young adult females (10 mon-5 yr old) that presented over 11 d. Clinical signs were rapidly progressive and unresponsive to supportive therapies. Two of the four individuals were found deceased 4 d after hospitalization. Two individuals were euthanized due to poor prognosis and decline after 6 and 8 d, respectively. Simultaneously, an additional mara developed mild and self-resolving clinical signs, including a kyphotic gait and paraparesis. On gross examination, there were widespread petechiae and ecchymoses of the skeletal muscle, myocardium, skin, pericardium, urinary bladder mucosa, and spinal cord. On histopathology, all animals had necrotizing myelitis and rhombencephalitis, with intranuclear viral inclusions in three individuals. Electron microscopy confirmed herpesviral replication and assembly complexes in neurons and oligodendrocytes. Consensus PCR performed on spinal cord, brainstem, or cerebellum revealed a novel Simplexvirus most closely related to Simplexvirus leporidalpha 4. The virus was amplified and sequenced and is referred to as Simplexvirus dolichotinealpha1. It is unknown whether this virus is endemic in Patagonian mara or whether it represents an aberrant host species. Clinicians should be aware of this virus and its potential to cause severe, rapidly progressive, life-threatening disease in this species.

Development of a Chief Resident Medical Procedure Service: a 10-Year Experience.

BACKGROUND: Lack of experienced faculty to supervise internal medicine (IM) residents is a significant barrier to establishing a medical procedure service (MPS). AIM: Describe the development and 10-year outcomes of an MPS led by IM chief residents. SETTING: University-based IM residency program affiliated with a county and Veterans Affairs hospital. PARTICIPANTS: Categorical IM interns (n=320) and 4th-year IM chief residents (n=48) from 2011 to 2022. PROGRAM DESCRIPTION: The MPS operated on weekdays, 8 am-5 pm. After training and sign-off by the MPS director, chief residents trained and supervised interns in ultrasound-guided procedures during a 4-week rotation. PROGRAM EVALUATION: From 2011 to 2022, our MPS received 5967 consults and 4465 (75%) procedures were attempted. Overall procedure success, complication, and major complication rates were 94%, 2.6%, and 0.6%, respectively. Success and complication rates for paracentesis (n=2285) were 99% and 1.1%, respectively; 99% and 4.2% for thoracentesis (n=1167); 76% and 4.5% for lumbar puncture (n=883); 83% and 1.2% for knee arthrocentesis (n=85); and 76% and 0% for central venous catheterization (n=45). The rotation was rated 4.6 out of 5 for overall learning quality. DISCUSSION: A chief resident-led MPS is a practical and safe approach for IM residency programs to establish an MPS when experienced attending physicians are unavailable.

Gonococcal Infection and Ventriculoperitoneal Shunts.

ABSTRACT: Neisseria gonorrhoea e and Chlamydia trachomatis are pathogens commonly isolated in pelvic inflammatory disease. Neisseria gonorrhoea e may uncommonly spread outside the urogenital tract to cause complications. We present 2 cases of adolescents with ventriculoperitoneal shunt infection due to N. gonorrhoea e, requiring shunt externalization.

Asthma as a risk factor for hospitalization in children with COVID-19: A nested case-control study.

BACKGROUND: Most pediatric studies of asthma and COVID-19 to date have been ecological, which offer limited insight. We evaluated the association between asthma and COVID-19 at an individual level. METHODS: Using data from prospective clinical registries, we conducted a nested case-control study comparing three groups: children with COVID-19 and underlying asthma ("A+C" cases); children with COVID-19 without underlying disease ("C+" controls); and children with asthma without COVID-19 ("A+" controls). RESULTS: The cohort included 142 A+C cases, 1110 C+ controls, and 140 A+ controls. A+C cases were more likely than C+ controls to present with dyspnea and wheezing, to receive pharmacologic treatment including systemic steroids (all p < .01), and to be hospitalized (4.9% vs. 1.7%, p = .01). In the adjusted analysis, A+C cases were nearly 4 times more likely to be hospitalized than C+ controls (adjusted OR = 3.95 [95%CI = 1.4-10.9]); however, length of stay and respiratory support level did not differ between groups. Among A+C cases, 8.5% presented with an asthma exacerbation and another 6.3% developed acute exacerbation symptoms shortly after testing positive for SARS-CoV-2. Compared to historic A+ controls, A+C cases had less severe asthma, were less likely to be on controller medications, and had better asthma symptom control (all p < .01). CONCLUSIONS: In our cohort, asthma was a risk factor for hospitalization in children with COVID-19, but not for worse COVID-19 outcomes. SARS-CoV-2 does not seem to be a strong trigger for pediatric asthma exacerbations. Asthma severity was not associated with higher risk of COVID-19.

Utility of RSV rapid diagnostic assays in hospitalized children in Amman, Jordan.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections in children worldwide and a frequent cause of hospitalization. Rapid diagnostic assays (RDAs) are available for RSV and they help guide management; however, they are underutilized in developing countries. We compared molecular diagnostics to RSV RDA in hospitalized children in Amman, Jordan. MATERIALS AND METHODS: Children under 2 years of age, admitted with fever and/or respiratory symptoms were enrolled prospectively from March 2010 to 2012. Demographic and clinical data were collected through parent/guardian interviews and medical chart abstraction. RSV RDAs were performed, and nasal/throat swabs were tested for RSV using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: RSV RDA and PCR were performed on specimens from 1271 subjects. RSV RDA had a sensitivity of 26% and a specificity of 99%, with positive and negative predictive values of 98.6% and 43%, respectively. RDA-positive patients had fewer days of symptoms at presentation and were more likely to have a history of prematurity, lower birth weight, require supplemental oxygen, and a longer hospitalization as compared with subjects with negative RDA. Multivariate analysis showed only lower birth weight, lack of cyanosis on examination, and lower cycle threshold to be independently associated with positive RDA (p ≤ .001). CONCLUSION: RSV RDAs had high specificity, but low sensitivity as compared with qRT-PCR. Positive RDA was associated with patients with a more severe disease, as indicated by oxygen use, longer length of stay, and higher viral load. Implementation of RDAs in developing countries could be an inexpensive and expedient method for predicting RSV disease severity and guiding management.

Performance of SARS-CoV-2 antigen testing in symptomatic and asymptomatic adults: a single-center evaluation.

BACKGROUND: Antigen testing offers rapid and inexpensive testing for SARS-CoV-2 but concerns regarding performance, especially sensitivity, remain. Limited data exists for use of antigen testing in asymptomatic patients; thus, performance and reliability of antigen testing remains unclear. METHODS: 148 symptomatic and 144 asymptomatic adults were included. A nasal swab was collected for testing by Quidel Sofia SARS IFA (Sofia) as point of care. A nasopharyngeal swab was also collected and transported to the laboratory for testing by Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV RT-PCR (Cepheid). RESULTS: Overall, Sofia had good agreement with Cepheid (> 95%) in adults, however was less sensitive. Sofia had a sensitivity of 87.8% and 33.3% for symptomatic and asymptomatic patients, respectively. Among symptomatic patients, testing > 5 days post symptom onset resulted in lower sensitivity (82%) when compared with testing within 5 days of symptom onset (90%). Of the four Sofia false-negative results in the asymptomatic cohort, 50% went on to develop COVID-19 disease within 5 days of testing. Specificity in both symptomatic and asymptomatic cohorts was 100%. CONCLUSIONS: Sofia has acceptable performance in symptomatic adults when tested < 5 days of symptom onset. Caution should be taken when testing patients with ≥ 5 days of symptoms. The combination of low prevalence and reduced sensitivity results in relatively poor performance of in asymptomatic patients. NAAT-based diagnostic assays should be considered in when antigen testing is unreliable, particularly in symptomatic patients with > 5 days of symptom onset and asymptomatic patients.

The Frequency of Routine Blood Sampling and Patient Outcomes Among Maintenance Hemodialysis Recipients.

RATIONALE & OBJECTIVE: Surveillance blood work is routinely performed in maintenance hemodialysis (HD) recipients. Although more frequent blood testing may confer better outcomes, there is little evidence to support any particular monitoring interval. STUDY DESIGN: Retrospective population-based cohort study. SETTING & PARTICIPANTS: All prevalent HD recipients in Ontario, Canada, as of April 1, 2011, and a cohort of incident patients commencing maintenance HD in Ontario, Canada, between April 1, 2011, and March 31, 2016. EXPOSURE: Frequency of surveillance blood work, monthly versus every 6 weeks. OUTCOMES: The primary outcome was all-cause mortality. Secondary outcomes were major adverse cardiovascular events, all-cause hospitalization, and episodes of hyperkalemia. ANALYTICAL APPROACH: Cox proportional hazards with adjustment for demographic and clinical characteristics was used to evaluate the association between blood testing frequency and all-cause mortality. Secondary outcomes were evaluated using the Andersen-Gill extension of the Cox model to allow for potential recurrent events. RESULTS: 7,454 prevalent patients received care at 17 HD programs with monthly blood sampling protocols (n=5,335 patients) and at 8 programs with blood sampling every 6 weeks (n=2,119 patients). More frequent monitoring was not associated with a lower risk for all-cause mortality compared to blood sampling every 6 weeks (adjusted HR, 1.16; 95% CI, 0.99-1.38). Monthly monitoring was not associated with a lower risk for any of the secondary outcomes. Results were consistent among incident HD recipients. LIMITATIONS: Unmeasured confounding; limited data for center practices unrelated to blood sampling frequency; no information on frequency of unscheduled blood work performed outside the prescribed sampling interval. CONCLUSIONS: Monthly routine blood testing in HD recipients was not associated with a lower risk for death, cardiovascular events, or hospitalizations as compared with testing every 6 weeks. Given the health resource implications, the frequency of routine blood sampling in HD recipients deserves careful reassessment.

New Cluster of Acute Flaccid Myelitis in Western Pennsylvania.

Acute flaccid myelitis is a debilitating illness characterized by acute onset of limb weakness, with one or more spinal segments displaying magnetic resonance imaging-confirmed gray matter lesions. Since the first outbreak in 2014, tracking by the Centers for Disease Control and Prevention has demonstrated biennial epidemics in the United States, with a current outbreak occurring in 2018. The cases of 3 children with acute flaccid myelitis who were initially thought to have common nonneurologic diagnoses are presented. Emergency physicians need to be vigilant to recognize the subtleties of acute flaccid myelitis because the illness progression is rapid and therapy is nuanced.

Emerging arboviruses and implications for pediatric transplantation: A review.

Recent years have brought a rise in newly emergent viral infections, primarily in the form of previously known arthropod-transmitted viruses that have increased significantly in both incidence and geographical range. Of particular note are DENV, CHIKV, and ZIKV, which are transmitted mostly by Aedes species of mosquitoes that exhibit a wide and increasing global distribution. Being important pathogens for the general population, these viruses have the potential to be devastating in the international transplant community, with graft rejection and death as possible outcomes of infection. In this review, we discuss the current state of knowledge for these viruses as well as repercussions of infection in the solid organ and HSCT population, with a focus, when possible, on pediatric patients.

Coronavirus replicase-reporter fusions provide quantitative analysis of replication and replication complex formation.

UNLABELLED: The replication of coronaviruses occurs in association with multiple virus-induced membrane structures that evolve during the course of infection; however, the dynamics of this process remain poorly understood. Previous studies of coronavirus replication complex organization and protein interactions have utilized protein overexpression studies and immunofluorescence of fixed cells. Additionally, live-imaging studies of coronavirus replicase proteins have used fluorescent reporter molecules fused to replicase proteins, but expressed from nonnative locations, mostly late-transcribed subgenomic mRNAs, in the presence or absence of the native protein. Thus, the timing and targeting of native replicase proteins expressed in real time from native locations in the genome remain unknown. In this study, we tested whether reporter molecules could be expressed from the replicase polyprotein of murine hepatitis virus as fusions with nonstructural protein 2 or 3 and whether such reporters could define the targeting and activity of replicase proteins during infection. We demonstrate that the fusion of green fluorescent protein and firefly luciferase with either nonstructural protein 2 or 3 is tolerated and that these reporter-replicase fusions can be used to quantitate replication complex formation and virus replication. The results show that the replicase gene has flexibility to accommodate a foreign gene addition and can be used directly to study replicase complex formation and evolution during infection as well as to provide highly sensitive and specific markers for protein translation and genome replication. IMPORTANCE: Coronaviruses are a family of enveloped, positive-sense RNA viruses that are important agents of disease, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus. Replication is associated with multiple virus-induced membrane structures that evolve during infection; however, the dynamics of this process remain poorly understood. In this study, we tested whether reporter molecules expressed from native locations within the replicase polyprotein of murine hepatitis virus as fusions with nonstructural proteins could define the expression and targeting of replicase proteins during infection in live cells. We demonstrate that the replicase gene tolerates the introduction of green fluorescent protein or firefly luciferase as fusions with replicase proteins. These viruses allow early quantitation of virus replication as well as real-time measurement of replication complexes.

Brief report: Borderline personality symptoms and perceived caregiver criticism in adolescents.

Despite findings of an association between adolescent psychopathology and perceived parental criticism, the relation between adolescent borderline personality disorder (BPD) symptoms and perceived parental criticism has not been examined. Given the centrality of interpersonal sensitivity to BPD (relative to other forms of psychopathology), we hypothesized that adolescent BPD symptoms would be uniquely related to perceived caregiver criticism, above and beyond other forms of psychopathology and general emotion dysregulation. Adolescents (N = 109) in a residential psychiatric treatment facility completed self-report measures of BPD symptoms, perceived caregiver criticism, emotion dysregulation, and symptoms of depression, anxiety, and posttraumatic stress disorder. Results revealed a unique relation of adolescent BPD symptoms to perceived caregiver criticism, above and beyond age, gender, and other forms of psychopathology. Findings suggest that adolescent BPD symptoms may have unique relevance for adolescents' perceptions of caregivers' attitudes and behaviors, increasing the likelihood of negative perceptions.

The amphibious fish Kryptolebias marmoratus uses different strategies to maintain oxygen delivery during aquatic hypoxia and air exposure.

Despite the abundance of oxygen in atmospheric air relative to water, the initial loss of respiratory surface area and accumulation of carbon dioxide in the blood of amphibious fishes during emersion may result in hypoxemia. Given that the ability to respond to low oxygen conditions predates the vertebrate invasion of land, we hypothesized that amphibious fishes maintain O2 uptake and transport while emersed by mounting a co-opted hypoxia response. We acclimated the amphibious fish Kryptolebias marmoratus, which are able to remain active for weeks in both air and water, for 7 days to normoxic brackish water (15‰, ~21kPa O2; control), aquatic hypoxia (~3.6kPa), normoxic air (~21 kPa) or aerial hypoxia (~13.6kPa). Angiogenesis in the skin and bucco-opercular chamber was pronounced in air- versus water-acclimated fish, but not in response to hypoxia. Aquatic hypoxia increased the O2-carrying capacity of blood via a large (40%) increase in red blood cell density and a small increase in the affinity of hemoglobin for O2 (P50 decreased 11%). In contrast, air exposure increased the hemoglobin O2 affinity (decreased P50) by 25% without affecting the number of red blood cells. Acclimation to aerial hypoxia both increased the O2-carrying capacity and decreased the hemoglobin O2 affinity. These results suggest that O2 transport is regulated both by O2 availability and also, independently, by air exposure. The ability of the hematological system to respond to air exposure independent of O2 availability may allow extant amphibious fishes, and may also have allowed primitive tetrapods to cope with the complex challenges of aerial respiration during the invasion of land.

A Machine-Learning Approach to Assess Factors Associated With Hospitalization of Children and Youths in Psychiatric Crisis.

OBJECTIVE: The authors used a machine-learning approach to model clinician decision making regarding psychiatric hospitalization of children and youths in crisis and to identify factors associated with the decision to hospitalize. METHODS: Data consisted of 4,786 mobile crisis response team assessments of children and youths, ages 4.0-19.5 years (mean±SD=14.0±2.7 years, 56% female), in Nevada. The sample assessments were split into training and testing data sets. A random-forest machine-learning algorithm was used to identify variables related to the decision to hospitalize a child or youth after the crisis assessment. Results from the training sample were externally validated in the testing sample. RESULTS: The random-forest model had good performance (area under the curve training sample=0.91, testing sample=0.92). Variables found to be important in the decision to hospitalize a child or youth were acute suicidality, followed by poor judgment or decision making, danger to others, impulsivity, runaway behavior, other risky behaviors, nonsuicidal self-injury, psychotic or depressive symptoms, sleep problems, oppositional behavior, poor functioning at home or with peers, depressive or schizophrenia spectrum disorders, and age. CONCLUSIONS: In crisis settings, clinicians were found to mostly focus on acute factors that increased risk for danger to self or others (e.g., suicidality, poor judgment), current psychiatric symptoms (e.g., psychotic symptoms), and functioning (e.g., poor home functioning, problems with peer relationships) when deciding whether to hospitalize or stabilize a child or youth. To reduce psychiatric hospitalization, community-based services should target interventions to address these important factors associated with the need for a higher level of care among youths in psychiatric crisis.

Contemporary enterovirus-D68 isolates infect human spinal cord organoids.

Enterovirus D68 (EV-D68) is a nonpolio enterovirus associated with severe respiratory illness and acute flaccid myelitis (AFM), a polio-like illness causing paralysis in children. AFM outbreaks have been associated with increased circulation and genetic diversity of EV-D68 since 2014, although the virus was discovered in the 1960s. The mechanisms by which EV-D68 targets the central nervous system are unknown. Since enteroviruses are human pathogens that do not routinely infect other animal species, establishment of a human model of the central nervous system is essential for understanding pathogenesis. Here, we describe two human spinal cord organoid (hSCO)-based models for EV-D68 infection derived from induced, pluripotent stem cell (iPSC) lines. One hSCO model consists primarily of spinal motor neurons, while the another model comprises multiple neuronal cell lineages, including motor neurons, interneurons, and glial cells. These hSCOs can be productively infected with contemporary strains, but not a historic strain, of EV-D68 and produce extracellular virus for at least 2 weeks without appreciable cytopathic effect. By comparison, infection with hSCO with another enterovirus, echovirus 11, causes significant structural destruction and apoptosis. Together, these findings suggest that EV-D68 infection is not the sole mediator of neuronal cell death in the spinal cord in those with AFM and that secondary injury from the immune response likely contributes to pathogenesis. IMPORTANCE AFM is a rare condition that causes significant morbidity in affected children, often contributing to life-long sequelae. It is unknown how EV-D68 causes paralysis in children, and effective therapeutic and preventative strategies are not available. Mice are not native hosts for EV-D68, and thus, existing mouse models use immunosuppressed or neonatal mice, mouse-adapted viruses, or intracranial inoculations. To complement existing models, we report two hSCO models for EV-D68 infection. These three-dimensional, multicellular models comprised human cells and include multiple neural lineages, including motor neurons, interneurons, and glial cells. These new hSCO models for EV-D68 infection will contribute to understanding how EV-D68 damages the human spinal cord, which could lead to new therapeutic and prophylactic strategies for this virus.

The complete acute and post-acute care course of children affected by acute flaccid myelitis in Western Pennsylvania: A case series.

Acute flaccid myelitis (AFM) is a "polio-like" neurologic disorder of the spinal cord gray matter characterized by asymmetric, flaccid limb weakness of rapid onset following prodromal viral illness. It has affected the pediatric population of the United States since 2014, but there is a paucity of literature describing the post-acute comprehensive rehabilitation management that maximizes functional outcomes for patients. This case series attempts to mitigate this by describing the complete acute and post-acute care course of six children diagnosed with AFM in Western Pennsylvania. It is critical that pediatric rehabilitation medicine providers be knowledgeable about the complex medical and rehabilitation management for patients with AFM.

Shortwave infrared diffuse optical wearable probe for quantification of water and lipid content in emulsion phantoms using deep learning.

Significance: The shortwave infrared (SWIR, ∼900 to 2000 nm) holds promise for label-free measurements of water and lipid content in thick tissue, owed to the chromophore-specific absorption features and low scattering in this range. In vivo water and lipid estimations have potential applications including the monitoring of hydration, volume status, edema, body composition, weight loss, and cancer. To the best of our knowledge, there are currently no point-of-care or wearable devices available that exploit the SWIR wavelength range, limiting clinical and at-home translation of this technology. Aim: To design and fabricate a diffuse optical wearable SWIR probe for water and lipid quantification in tissue. Approach: Simulations were first performed to confirm the theoretical advantage of SWIR wavelengths over near infrared (NIR). The probe was then fabricated, consisting of light emitting diodes at three wavelengths (980, 1200, 1300 nm) and four source-detector (S-D) separations (7, 10, 13, 16 mm). In vitro validation was then performed on emulsion phantoms containing varying concentrations of water, lipid, and deuterium oxide (D2O). A deep neural network was developed as the inverse model for quantity estimation. Results: Simulations indicated that SWIR wavelengths could reduce theoretical water and lipid extraction errors from ∼6% to ∼1% when compared to NIR wavelengths. The SWIR probe had good signal-to-noise ratio (>32 dB up to 10 mm S-D) and low drift (<1.1% up to 10 mm S-D). Quantification error in emulsion phantoms was 2.1±1.1% for water and -1.2±1.5% for lipid. Water estimation during a D2O dilution experiment had an error of 3.1±3.7%. Conclusions: This diffuse optical SWIR probe was able to quantify water and lipid contents in vitro with good accuracy, opening the door to human investigations.

Setting the Stage for the Next Great Vaccine Success Story.

In this Commentary, the article by Rosenfeld et al. "Cross-Reactive Antibody Responses against Nonpoliovirus Enteroviruses" is put into context of the historic poliovirus epidemics and resultant vaccination success story as it compares to the current state of acute flaccid myelitis; the relationship to nonpoliovirus enteroviruses (EVs), in particular EV-D68 and EV-A71; and the potential for successful vaccination strategies. The discovery of cross-protective antibody neutralization among polio and nonpolio enteroviruses, specifically EV-D68, opens future questions about EV-D68 vaccination strategies, circulation patterns of nonpolio enteroviruses, and the interpretation of EV-D68 serostudies.

Performance of the Sofia SARS-CoV-2 Rapid Antigen Test in Symptomatic and Asymptomatic Pediatric Patients.

The sensitivity and specificity of SARS-CoV-2 antigen tests have not been widely assessed in children. We evaluated children presenting to outpatient care with Quidel Sofia SARS-CoV-2 antigen test (Sofia-Ag-RDT) compared against Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV reverse transcriptase-polymerase chain reaction test from November 2020 to April 2021. Sofia-Ag-RDT had the highest sensitivity in symptomatic (82%; 95% confidence interval, 68%-91%) children.