Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center.

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

Clinical utilization of microperimetry in ophthalmic surgery: A narrative review.

Microperimetry is an emerging technology that provides concurrent analysis of retinal structure and function by combining retinal sensitivity and fixation analysis with fundus imaging. We summarize the substantial evidence validating the evolving role of microperimetry as an adjunctive assessment of visual function in the perioperative setting. We show that microperimetry provides useful complementary information to other established imaging and functional modalities in the perioperative setting for a wide range of vitreoretinal surgical procedures, as well as in cataract and refractive surgeries. This includes preoperative uses such as prognostication of visual and anatomical outcomes, timing of surgical intervention, and assessment of patient suitability for surgery-as well as postoperative uses including quantification of visual recovery, investigation of unexplained postoperative vision loss, and informing expected long term functional outcomes.

Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study.

Previous research has shown that ≤60 min hypoxic exposure improves subsequent glycaemic control, but the optimal level of hypoxia is unknown and data are lacking from individuals with overweight. We undertook a cross-over pilot feasibility study investigating the effect of 60-min prior resting exposure to different inspired oxygen fractions (CON FI O2  = 0.209; HIGH FI O2  = 0.155; VHIGH FI O2  = 0.125) on glycaemic control, insulin sensitivity, and oxidative stress during a subsequent oral glucose tolerance test (OGTT) in males with overweight (mean (SD) BMI = 27.6 (1.3) kg/m2 ; n = 12). Feasibility was defined by exceeding predefined withdrawal criteria for peripheral blood oxygen saturation (SpO2 ), partial pressure of end-tidal oxygen or carbon dioxide and acute mountain sickness (AMS), and dyspnoea symptomology. Hypoxia reduced SpO2 in a stepwise manner (CON = 97(1)%; HIGH = 91(1)%; VHIGH = 81(3)%, p < 0.001), but did not affect peak plasma glucose concentration (CON = 7.5(1.8) mmol∙L-1 ; HIGH = 7.7(1.1) mmol∙L-1 ; VHIGH = 7.7(1.1) mmol∙L-1 ; p = 0.777; η2  = 0.013), plasma glucose area under the curve, insulin sensitivity, or metabolic clearance rate of glucose (p > 0.05). We observed no between-conditions differences in oxidative stress (p > 0.05), but dyspnoea and AMS symptoms increased in VHIGH (p < 0.05), with one participant meeting the withdrawal criteria. Acute HIGH or VHIGH exposure prior to an OGTT does not influence glucose homeostasis in males with overweight, but VHIGH is associated with adverse symptomology and reduced feasibility.

A rare case of epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland: case report and review of the literature.

A 92-year-old man presented with progressively worsening eye pain, diplopia on lateral gaze and blurred vision for the past 12 months. Radiological imaging confirmed a large left lacrimal gland lesion. The patient subsequently underwent a superio-lateral orbitotomy with left dacryoadenectomy and tumor removal, histopathology subsequently confirmed an epithelial-myoepithelial carcinoma arising ex pleomorphic adenoma of the lacrimal gland. Epithelial-myoepithelial carcinoma is a rare lacrimal gland tumour and the authors believe this case to be the first reported in the Australian population and associated with prolonged eye pain.

Metronidazole for treatment of norovirus in pediatric transplant recipients.

BACKGROUND: Norovirus is a common cause of gastroenteritis in both immunocompetent and immunocompromised hosts. In transplant recipients, it can lead to prolonged shedding and chronic diarrhea. Treatment with nitazoxanide, oral immunoglobulin, or mammalian target of rapamycin inhibitors has shown varying degrees of benefit in case reports and case series. Prior studies have shown that the commensal gastrointestinal bacterial flora may influence the pathogenesis of norovirus infection. Metronidazole is often used to modulate gastrointestinal flora and was trialed in our hospital for norovirus in some immunocompromised patients after observing an association with anecdotal improvement. METHODS: We retrospectively reviewed episodes of norovirus in the stool of 38 patients with a history of solid organ or stem cell transplantation between July 2014 and March 2019. RESULTS: There were 85 positive norovirus tests among the 38 patients. In 25 of the 85 positive norovirus tests, nitazoxanide was given, with clinical improvement in 15 of these episodes (60%). Eight positive tests were treated with metronidazole alone, in all cases after a course of nitazoxanide had been used. Improvement was observed for 6 of these episodes (75%). CONCLUSION: Further investigation of the use of metronidazole for norovirus gastroenteritis in transplant recipients is warranted.

Migration of retained tarsal bee stinger onto the ocular surface causing superficial keratopathy.

We report a case of keratopathy due to retained stinger elements following a bee sting and envenomation of the ocular adnexa. A 48-year-old woman presented with a 2-day history of right-sided eye pain, photophobia, and reduced visual acuity. Six days prior to presentation, she had been stung on the right upper eyelid by a bee. Her usual practitioner had removed the stinger and commenced a course of oral antibiotics. Anterior segment examination revealed coarse linear abrasions and superficial punctate keratitis with associated epithelial edema. Eversion of the right upper eyelid revealed the presence of retained stinger lancets near the medial eyelid margin. The retained stinger was removed, and the patient responded well to treatment with topical antibiotics, steroids, and cycloplegia.

Disinfection byproducts formed during drinking water treatment reveal an export control point for dissolved organic matter in a subalpine headwater stream.

Changes in climate, season, and vegetation can alter organic export from watersheds. While an accepted tradeoff to protect public health, disinfection processes during drinking water treatment can adversely react with organic compounds to form disinfection byproducts (DBPs). By extension, DBP monitoring can yield insights into hydrobiogeochemical dynamics within watersheds and their implications for water resource management. In this study, we analyzed temporal trends from a water treatment facility that sources water from Coal Creek in Crested Butte, Colorado. These trends revealed a long-term increase in haloacetic acid and trihalomethane formation over the period of 2005-2020. Disproportionate export of dissolved organic carbon and formation of DBPs that exceeded maximum contaminant levels were consistently recorded in association with late spring freshet. Synoptic sampling of the creek in 2020 and 2021 identified a biogeochemical hotspot for organic carbon export in the upper domain of the watershed that contained a prominent fulvic acid-like fluorescent signature. DBP formation potential analyses from this domain yielded similar ratios of regulated DBP classes to those formed at the drinking water facility. Spectrometric qualitative analyses of pre and post-reacted waters with hypochlorite indicated lignin-like and condensed hydrocarbon-like molecules were the major reactive chemical classes during chlorine-based disinfection. This study demonstrates how drinking water quality archives combined with synoptic sampling and targeted analyses can be used to identify and understand export control points for dissolved organic matter. This approach could be applied to identify and characterize analogous watersheds where seasonal or climate-associated organic matter export challenge water treatment disinfection and by extension inform watershed management and drinking water treatment.

Live virus vaccination following pediatric liver transplantation: Outcomes from two academic children's hospitals.

Pediatric liver transplant (LT) recipients are often transplanted at a young age, precluding them from receiving live virus vaccinations (LVV) such as varicella (VZV) vaccine and measles, mumps and rubella. This places them at profound risk for vaccine preventable illness. We sought to detail safety of vaccination. This was a retrospective cohort study of pediatric LT recipients at two children's hospitals. Among 204 LT recipients included in the study, 97 received at least one LVV after LT. Six patients who did not receive LVV after transplant had evidence of vaccine-preventable infection following vaccination (one disseminated VZV disease, five VZV-related rash), while one patient who received LVV after transplant developed a diffuse VZV-related rash. Rejection rates were the same between those that did and did not receive a live virus vaccine post-transplant. There were no serious adverse events caused by vaccination post-transplant. LVV following LT was safe at our two institutions, although there exist limitations in our study due to its retrospective study design. Larger scale studies should be performed to evaluate the effectiveness of LVV in relation to immunosuppression.

Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma.

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.

Incidence of CMV Infection and Disease and Adverse Events Associated with Antiviral Therapy in a Retrospective Cohort of Allogeneic Hematopoietic Cell Transplant Recipients at an Academic Children's Hospital.

BACKGROUND: Cytomegalovirus (CMV) is a significant source of morbidity and mortality among transplant recipients; the epidemiology is less understood in pediatric hematopoietic cell transplantation (HCT) cohorts. Furthermore, there is a paucity of data related to CMV prophylactic and preemptive strategies. METHODS: A single-center retrospective observational cohort of allogeneic HCT recipients at the Children's Hospital of Philadelphia January 1, 2004-December 31, 2017 was constructed. Subjects were followed for 180 days after transplant to determine whether they had CMV infection or disease. Data on antiviral therapy were collected as were outcomes of CMV disease and adverse events (AEs) related to the antiviral therapy. RESULTS: Between January 2004 and March 2017, 345 allogeneic HCTs in 333 patients undergoing CMV surveillance testing were identified. CMV DNAemia was detected during the 180-day follow-up in 89 (25.8%) HCTs. CMV recipient-positive transplants were most likely to have CMV infection (47%). Infection rates were high for those receiving a CMV-specific prophylaxis regimen (50%). CMV DNAemia progressed to CMV disease 11.2% of the time. Of 224 subjects receiving CMV-specific prophylaxis, 19.2% experienced ≥1 AE. Of 53 receiving preemptive therapy during any CMV DNAemia episode, 32.1% experienced ≥1 AE. CONCLUSIONS: CMV infection is common in pediatric allogeneic HCT recipients. The CMV-specific prophylaxis regimen employed in this cohort did not effectively prevent DNAemia, progression to CMV disease was uncommon, and AEs from prophylaxis and preemptive therapy were frequent. Novel approaches that reduce the impact of CMV on pediatric allogeneic HCT recipients are needed.

COVID-19 cumulative incidence, asymptomatic infections, and fatality in Long Island, NY, January-August 2020: A cohort of World Trade Center responders.

BACKGROUND: New York City and Long Island, NY were early foci of the COVID-19 epidemic in the US. The effects of COVID-19 on different sub-populations, and its key epidemiologic parameters remain unknown or highly uncertain. We investigated the epidemiology of COVID-19 from January to August of 2020 in an established academic monitoring cohort of N = 9,697 middle-aged World Trade Center responders residing in Long Island, NY. METHODS: A seroprevalence survey and a series of cross-sectional surveys were nested in a prospective cohort study. Measures included IgG antibody testing, SARS-CoV-2 polymerase chain reaction (PCR) testing, review of electronic medical records, and surveys of symptoms. Correlates of infection were analyzed with multivariable logistic regression. RESULTS: The cohort was predominantly men in their mid-fifties; 6,597 cohort members were successfully contacted (68%); 1,042 (11%) individuals participated in the seroprevalence survey; and 369 individuals (5.6% of 6,597 study participants) underwent PCR testing. The estimated standardized cumulative incidence was 21.9% (95%CI: 20.1-23.9%), the asymptomatic proportion was 16.4% (36/219; 95%CI: 11.8-22.0%), the case hospitalization ratio was 9.4% (36/385; 95%CI: 6.6-12.7%), the case fatality ratio was 1.8% (7/385; 95%CI: 0.7-3.7%), and the hospitalization fatality ratio was 8.3% (3/36; 95%CI: 1.8-22.5%). Confirmed SARS-CoV-2 infection was associated with younger age, race/ethnicity, and being currently employed. CONCLUSIONS: The results of the present study suggest a high cumulative incidence of SARS-CoV-2 among WTC responders in the spring and summer of 2020 and contribute to narrowing the plausible range of the proportion of infections that exhibit no symptoms. An increased risk of infection among younger employed individuals is likely to reflect a higher probability of exposure to the virus, and the racial disparities in the infection risk warrant further investigation.

Trisomy 21 and Coronavirus Disease 2019 in Pediatric Patients.

We present 4 pediatric patients with trisomy 21 (T21) and associated comorbidities who developed coronavirus disease 2019 requiring hospitalization. A review of the literature revealed that comorbidities associated with T21 may predispose patients to severe disease. Children with T21 should be considered high risk and monitored carefully if infected with severe acute respiratory syndrome coronavirus 2.

The Role of Probiotics, Prebiotics and Synbiotics in Combating Multidrug-Resistant Organisms.

The prevalence of multidrug-resistant organisms is increasing worldwide, posing a unique challenge to global health care systems. Novel approaches are needed to combat the spread of infection with these organisms. The enteric microbiome, and in particular the resistome, offers a unique target in both the prevention of infection with these organisms and the acquisition and spread within the community. We highlight a novel approach to combat multidrug-resistant organisms: the use of prebiotics, probiotics, and synbiotics to manipulate the microbiome and resistome. This review summarizes the published literature and clinical trials related to these products to date, with a focus on efficacious trials. It highlights the probable mechanism of action for each product, as well as its safety profile in selective populations. Ultimately, although further research is needed before a definitive statement can be made on the efficacy of any of these 3 interventions, the literature to date offers new hope and a new tool in the arsenal in the fight against bacterial drug resistance.

Predicting sedimentary bedrock subsurface weathering fronts and weathering rates.

Although bedrock weathering strongly influences water quality and global carbon and nitrogen budgets, the weathering depths and rates within subsurface are not well understood nor predictable. Determination of both porewater chemistry and subsurface water flow are needed in order to develop more complete understanding and obtain weathering rates. In a long-term field study, we applied a multiphase approach along a mountainous watershed hillslope transect underlain by marine shale. Here we report three findings. First, the deepest extent of the water table determines the weathering front, and the range of annually water table oscillations determines the thickness of the weathering zone. Below the lowest water table, permanently water-saturated bedrock remains reducing, preventing deeper pyrite oxidation. Secondly, carbonate minerals and potentially rock organic matter share the same weathering front depth with pyrite, contrary to models where weathering fronts are stratified. Thirdly, the measurements-based weathering rates from subsurface shale are high, amounting to base cation exports of about 70 kmolc ha-1 y-1, yet consistent with weathering of marine shale. Finally, by integrating geochemical and hydrological data we present a new conceptual model that can be applied in other settings to predict weathering and water quality responses to climate change.

Myths and Misconceptions: Varicella-Zoster Virus Exposure, Infection Risks, Complications, and Treatments.

Varicella zoster and herpes zoster are infections caused by the highly contagious varicella-zoster virus (VZV). Despite widespread availability of vaccines against VZV, as well as varicella vaccination rates >95%, VZV remains a public health concern because of several common myths and misconceptions. Because of the success of routine varicella vaccination programs, some people mistakenly believe that varicella and herpes zoster are now no longer a threat to public health. Another common misconception is that shingles is less infectious than varicella; however, clinical evidence indicates otherwise. Several knowledge gaps exist around VZV transmission and the availability and use of varicella zoster immune globulin (human) for postexposure prophylaxis against VZV. To help reduce the incidence of severe disease in high-risk individuals (eg, elderly people, pregnant women, unvaccinated persons, infants, and immunocompromised children and adults), this article addresses misbeliefs and broadens awareness of VZV exposure, infection risks, complications, and treatments.

Sporadic and endemic Burkitt lymphoma have frequent FOXO1 mutations but distinct hotspots in the AKT recognition motif.

FOXO1 has an oncogenic role in adult germinal center-derived lymphomas, in which mutations, predominately within the AKT recognition motif, cause nuclear retention of FOXO1, resulting in increased cell proliferation. To determine the prevalence and distribution of FOXO1 mutations in pediatric Burkitt lymphoma (BL), we sequenced a large number of sporadic and endemic BL patient samples. We report a high frequency of FOXO1 mutations in both sporadic and endemic BL at diagnosis, occurring in 23/78 (29%) and 48/89 (54%) samples, respectively, as well as 8/16 (50%) cases at relapse. Mutations of T24 were the most common in sporadic BL but were rare in endemic cases, in which mutations of residue S22, also within the AKT recognition motif, were the most frequent. FOXO1 mutations were almost always present in the major tumor cell clone but were not associated with outcome. Analysis of other recurrent mutations reported in BL revealed that FOXO1 mutations were associated with mutations of DDX3X and ARID1A, but not MYC, TCF3/ID3, or members of the phosphatidylinositol 3-kinase signaling pathway. We further show common nuclear retention of the FOXO1 protein, irrespective of mutation status, suggesting alternative unknown mechanisms for maintaining FOXO1 transcriptional activity in BL. CRISPR/Cas9 knockout of FOXO1 in an endemic cell line produced a significant decrease in cell proliferation, supporting an oncogenic role for FOXO1 in endemic BL. Thus, FOXO1 is frequently mutated in both sporadic and endemic BL and may offer a potential therapeutic target for pediatric BL patients worldwide.

Changes in Australian practice patterns for glaucoma management.

IMPORTANCE: The demand for glaucoma care is projected to increase significantly with the ageing population. BACKGROUND: To characterize trends in Australian practice patterns for glaucoma management over the 15-y period between 2003 and 2017. DESIGN: Retrospective audit. SAMPLES: The Medicare eligible population. METHODS: Audit of Medicare Benefits Schedule item number reimbursements in the private healthcare sector, and dispensed Pharmaceutical Benefits Scheme (PBS) prescriptions. MAIN OUTCOME MEASURES: Number, unadjusted cost and services per capita in the enrolled population. RESULTS: The number of medication prescriptions peaked in 2015, but then declined by 14.9%. PBS expenditure on glaucoma medications has been falling since 2012. There was a 9.2-fold increase in fixed-combination prescriptions and 281-fold increase in unpreserved medication prescriptions. In 2017, optometrists generated 1.86% of glaucoma prescriptions. Reimbursements for computerized perimetry increased dramatically for optometrists, and in 2017 optometrist-initiated perimetry exceeded ophthalmologist-initiated perimetry by 35.3%. There were significant increases in laser procedure rates, including laser trabeculoplasty (4.61-fold), laser iridotomy (2.55-fold) and cyclodestructive procedures (2.33-fold). There was a 3.83-fold increase in glaucoma drainage device insertions. Ab interno trabecular microbypass procedures increased 715% from 2014 to 2017. Adjusted for Medicare population, trabecular microbypass is performed at more than twice the rate of primary filtering operations. CONCLUSIONS AND RELEVANCE: This is the first time that glaucoma medication use and expenditure have declined since auditing began in 1992. Glaucoma laser procedures, drainage device implantation and trabecular microbypass increased substantially over the study period. In contrast, the rate of primary filtering operations increased in proportion to population growth. The increase in overall cost of glaucoma care has primarily been driven by computerized perimetry; however, this has been partially offset by a decline in medication expenditure.

From self-defeating to other defeating: Examining the effects of leader procrastination on follower work outcomes.

This research examines the influence of leader procrastination on employee attitudes and behaviours. While previous studies have typically viewed procrastination as a form of self-defeating behaviour, this research explores its effects on others in the workplace. In Study 1, using data collected from 290 employees, we demonstrate the discriminant and relative predictive validity of leader procrastination on leadership effectiveness compared with laissez-faire leadership and directive leadership. In Study 2, based on dyadic data collected in three phases from 250 employees and their 23 supervisors, we found that leader procrastination was associated with follower discretionary behaviour (organizational citizenship behaviour and deviant behaviour). Additionally, job frustration was found to mediate the relationship between leader procrastination and follower outcomes. The quality of the leader-follower relationship, as a boundary condition, was shown to mitigate the detrimental effects of leader procrastination. Together, the findings suggest that leader procrastination is a distinct form of negative leadership behaviour that represents an important source of follower job frustration. PRACTITIONER POINTS: Leader procrastination is different from laissez-faire and directive leadership and can be detrimental to followers.Job frustration mediates the relationship between leader procrastination and follower discretionary behaviour.Organizations should facilitate high-quality LMX relationships as a method for mitigating the negative effects of leader procrastination.