Age-specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition.

BACKGROUND: Data on the age-specific prevalence of Epstein-Barr virus (EBV) infection are relevant for determining when to administer a prophylactic vaccine. Comparison of demographic groups could identify factors associated with its acquisition. METHODS: The National Health and Nutrition Examination Surveys (NHANES) examine a representative sample of the US population. Serum specimens from NHANES participants 6-19 years old were tested for EBV antibody by enzyme immunoassay (EIA). A random portion was also tested by indirect immunofluorescence (IFA). Prevalence estimates and risk-factor comparisons used demographic data and sampling weights in logistic regression models. RESULTS: Serum specimens collected between 2003 and 2010 from 9338 individuals participating in NHANES were tested. The concordance between EIA and IFA findings was 96.7%. The overall age-adjusted EBV antibody prevalence declined from 72% in 2003-2004 to 65% in 2009-2010 (P = .027). The prevalence in 2009-2010 by age group was as follows: 6-8 years, 50%; 9-11 years, 55%; 12-14 years, 59%; 15-17 years, 69%; and 18-19 years, 89%. Within each race/ethnicity group, younger age, health insurance coverage, higher household income, and education level were significantly associated with a lower prevalence of EBV antibody. CONCLUSIONS: The EBV antibody prevalence declined in US individuals aged 6-19 years from 2003-2004 to 2009-2010, mainly because of the decrease among non-Hispanic white participants. The declining antibody prevalence over time and the consistently high observed prevalence among participants aged 12-19 years support broad use of EBV vaccine before 12 years of age.

Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students.

BACKGROUND: University students were studied prospectively to determine the incidence of and risk factors for acquisition of primary Epstein-Barr virus (EBV) infection and the virologic and immune correlates of disease severity. METHODS: EBV antibody-negative freshmen participated in monthly surveillance until graduation. If antibodies developed, proximate samples were assayed for viral load by polymerase chain reaction. Lymphocyte and natural killer (NK) cell numbers and activation were measured by flow cytometry, and plasma cytokine levels were measured by a multiplex assay. RESULTS: Of 546 students screened, 202 (37%) were antibody negative; 143 antibody-negative students were enrolled. During a median of 3 years of observation, 66 subjects experienced primary infection. Of these, 77% had infectious mononucleosis, 12% had atypical symptoms, and 11% were asymptomatic. Subjects reporting deep kissing with or without coitus had the same higher risk of infection than those reporting no kissing (P < .01). Viremia was transient, but median oral shedding was 175 days. Increases were observed in numbers of NK cells and CD8(+) T-cells but not in numbers of CD4(+) T-cells during acute infection. Severity of illness correlated positively with both blood EBV load (P = .015) and CD8(+) lymphocytosis (P = .0003). CONCLUSIONS: Kissing was a significant risk for primary EBV infection. A total of 89% of infections were symptomatic, and blood viral load and CD8(+) lymphocytosis correlated with disease severity.

Radiographic and Advanced Imaging Evaluation of Posterior Shoulder Instability.

PURPOSE OF REVIEW: Posterior shoulder instability is an uncommon but important cause of shoulder dysfunction and pain which may occur as the result of seizure, high energy trauma, or repetitive stress related to occupational or sport-specific activities. This current review details the imaging approach to the patient with posterior shoulder instability and describes commonly associated soft tissue and bony pathologies identified by radiographs, CT, and MR imaging. RECENT FINDINGS: Advances in MR imaging technology and techniques allow for more accurate evaluation of bone and soft tissue pathology associated with posterior shoulder instability while sparing patients exposure to radiation. Imaging can contribute significantly to the clinical management of patients with posterior shoulder instability by demonstrating the extent of associated injuries and identifying predisposing anatomic conditions. Radiologic evaluation should be guided by clinical history and physical examination, beginning with radiographs followed by CT and/or MRI for assessment of osseous and soft tissue pathology. Synthesis of a patient's clinical history, physical exam findings, and radiologic examinations should guide clinical management.

Imaging features of perinephric myxoid pseudotumors of fat.

OBJECTIVE: Retrospectively evaluate multimodality imaging features of perinephric myxoid pseudotumor of fat (PMPTF). METHODS: Institutional cases of PMPTF with CT, MRI and/or ultrasound evaluation from 1/1/2020 to 9/1/2023 were retrospectively reviewed. Patient demographics and clinical history were reviewed, and imaging features recorded. RESULTS: 14 patients with pathologically-proven PMPTF were identified (11 M, 3 F; mean age 66.7 ± 17.0 years; range 40-87 years). Three patients (18%) had bilateral lesions; a total of 17 PMPTFs were reviewed. 15/17 (88%) were biopsy-proven; two cases were diagnosed by imaging only in patients with a contralateral biopsy-proven PMPTF. All evaluable specimens were negative for MDM2 amplification. 11/17 (65%) occurred in patients with renal disease, including 4/17 (24%) in patients with renal transplant. 100% (17/17) had CT, 11/17 (65%) MRI, and 6/17 (35%) ultrasound. The mean largest lesion dimension was 10.9 ± 4.6 cm (range 4.3-17.0 cm). Of cases involving native kidneys, 7/13 (54%) presented as multifocal perinephric masses and 5/13 (38%) as a solitary perinephric mass. All four transplant cases presented as infiltrative-appearing masses involving the renal sinus with lesser perinephric involvement. 14/17 (82%) lesions contained macroscopic fat on CT and MRI and 3/17 (18%) showed no macroscopic fat, all involving renal transplants. All cases with MRI demonstrated T2 hyperintensity with signal dropout on opposed-phase imaging. 11/13 (85%) PMPTF showed no or equivocal CT enhancement. Enhancement was better seen on MRI in all cases evaluated by both CT and MRI. Of the six PMPTFs imaged by ultrasound, four (67%) were heterogeneously hypoechoic and two (33%) had mixed regions of hypo-, iso- and hyperechogenicity relative to adjacent renal parenchyma. CONCLUSIONS: PMPTF is a rare, benign, and underrecognized lesion that may mimic malignancy, particularly retroperitoneal well-differentiated liposarcoma. The imaging features of this unusual pseudosarcoma differ in native and transplanted kidneys. Improved awareness of this entity will facilitate appropriate patient management and avoid unnecessary intervention.

Effects of photoperiod and food restriction on the reproductive physiology of female California mice.

Many temperate-zone animals use changes in photoperiod to time breeding. Shorter term cues, like food availability, are integrated with photoperiod to adjust reproductive timing under unexpected conditions. Many mice of the genus Peromyscus breed in the summer. California mice (Peromyscus californicus), however, can breed year round, but tend to begin breeding in the winter. Glial cells may be involved in transduction of environmental signals that regulate gonadotrophin releasing hormone I (GnRH) activity. We examined the effects of diet and photoperiod on reproduction in female California mice. Mice placed on either short days (8L:16D) or long days (16L:8D) were food restricted (80% of normal intake) or fed ad libitum. Short day-food restricted mice showed significant regression of the reproductive system. GnRH-immunoreactivity was increased in the tuberal hypothalamus of long day-food restricted mice. This may be associated with the sparing effect long days have when mice are food restricted. The number of GFAP-immunoreactive fibers in proximity to GnRH nerve terminals correlated negatively with uterine size in ad libitum but not food restricted mice, suggesting diet may alter glial regulation of the reproductive axis. There was a trend towards food restriction increasing uterine expression of c-fos mRNA, an estrogen dependent gene. Similar to other seasonally breeding rodents, short days render the reproductive system of female California mice more susceptible to effects of food restriction. This may be vestigial, or it may have evolved to mitigate consequences of unexpectedly poor winter food supplies.

Magnetic resonance imaging of children following esophageal button battery removal: What are we looking for?

Despite society recommendations that cross-sectional imaging be obtained following removal of ingested button batteries, there is no published consensus on how it effectively guides clinical management. This single institution survey demonstrates a lack of uniformity by clinicians regarding which imaging findings impact management decisions, highlighting the need for further guidelines.

Confirmation of Cause of Death Via Comprehensive Autopsy and Whole Exome Molecular Sequencing in People With Epilepsy and Sudden Unexpected Death.

Background Sudden cardiac arrest is the leading mode of death in the United States. Epilepsy affects 1% of Americans; yet epidemiological data show a prevalence of 4% in cases of sudden cardiac arrest. Sudden unexpected death in epilepsy (SUDEP) may share features with sudden cardiac arrest. The objective of this study was to report autopsy and genomic findings in a large cohort of SUDEP cases. Methods and Results Mayo Clinic Sudden Death Registry containing cases (ages 0-90 years) of sudden unexpected and unexplained deaths 1960 to present was queried. Exome sequencing performed on decedent cases. From 13 687 cases of sudden death, 656 (4.8%) had a history of seizures, including 368 confirmed by electroencephalography, 96 classified as SUDEP, 58 as non-SUDEP, and 214 as unknown (insufficient records). Mean age of death in SUDEP was 37 (±19.7) years; 56 (58.3%) were male; 65% of deaths occurred at night; 54% were found in bed; and 80.6% were prone. Autopsies were obtained in 83 cases; bystander coronary artery disease was frequently reported as cause of death; nonspecific fibrosis was seen in 32.6% of cases, in structurally normal hearts. There were 4 cases of Dravet syndrome with pathogenic variants in SCN1A gene. Using whole exome sequencing in 11 cases, 18 ultrarare nonsynonymous variants were identified in 6 cases including CACNB2, RYR2, CLNB, CACNA1H, and CLCN2. Conclusions This study examined one of the largest single-center US series of SUDEP cases. Several cases were reclassified as SUDEP, 15% had an ECG when alive, and 11 (11.4%) had blood for whole exome sequencing analysis. The most frequent antemortem genetic finding was pathogenic variants in SCN1A; postmortem whole exome sequencing identified 18 ultrarare variants.

Safety and Effectiveness of Palliative Tunneled Peritoneal Drainage Catheters in the Management of Refractory Malignant and Non-malignant Ascites.

PURPOSE: To determine the safety and effectiveness of tunneled peritoneal catheters in the management of refractory malignant and non-malignant ascites. MATERIALS AND METHODS: An IRB-approved retrospective review was undertaken of patients who underwent ultrasound and fluoroscopy-guided tunneled peritoneal catheter placement for management of refractory malignant or non-malignant ascites between January 1, 2009, and March 14, 2014. RESULTS: A total of 137 patients (76 M/61 F, mean age 62.9 years) underwent tunneled peritoneal catheter placement for refractory malignant (N = 119; 86.9%) or non-malignant (N = 18; 13.1%) ascites. Technical success was 100% with no immediate complications. Nineteen patients (13.9%) experienced a total of 11 minor and 12 major complications. Nine patients developed a catheter-associated infection. The remaining complications included leakage at the dermatotomy site (N = 8), catheter dislodgement (N = 2), obstruction (N = 2), and groin pain (N = 2). Patients who developed a catheter-associated infection had a significantly longer catheter dwell time compared to those who did not develop an infection (median, 96.5 vs. 20 days; p < 0.01). Nine patients (6.6%) were lost to follow-up. Of the remaining 128 patients, 125 died and the majority had a catheter in place (90.4%) at the time of death. There was one catheter-associated death (bacterial peritonitis; 0.8%). The median time from catheter placement to death was significantly shorter in patients with malignant versus non-malignant ascites (18.5 vs. 85 days; p < 0.0001). CONCLUSIONS: Tunneled peritoneal drainage catheters are effective and relatively safe in the management of malignant and non-malignant ascites. Longer catheter dwell time may be a risk factor for catheter-associated infection, particularly in patients with a longer anticipated survival in the palliative setting.

Nodular fasciitis of the breast in an elderly woman.

Nodular fasciitis is a benign proliferation of fibroblasts and myofibroblasts most commonly found in the soft tissues of the upper extremities and the trunk of young to middle-aged adults. Nodular fasciitis is infrequently encountered in the breast and in the elderly. We report a case of a 69-year-old woman presenting with a palpable breast mass with imaging features that mimicked malignancy. Knowledge of this entity is important to allow proper radiological and pathologic concordance and patient management.

Prospective studies of infectious mononucleosis in university students.

We performed an intensive prospective study designed to obtain as much data as possible on the incubation and early illness periods of primary Epstein-Barr virus (EBV) infection. Undergraduate students who lacked EBV antibody and oral EBV DNA (EBV-naive) were seen every 2 weeks during their freshman year. Clinical and behavioral data, oral washes and venous blood were obtained. EBV antibodies were quantified by enzyme immunoassay and viral loads by PCR. During a median 8 months of observation, 14/85 subjects experienced primary EBV infections (24 cases/100 person-years). The only significant risk factor for acquisition of EBV infection was deep kissing (P=0.02). Eleven subjects had infectious mononucleosis with a median duration of 21 days. Two subjects were hospitalized. Infections were initially identified in 12 subjects by finding EBV DNA in oral cells before onset of symptoms and in 2 subjects by symptom reporting. EBV DNA and viral capsid antigen (VCA) IgM and gp350 IgG antibodies were present in the blood before onset of illness. To provide a more robust evaluation of primary EBV infection in undergraduate university students, we combined data on risk factors and antibody responses from this and an earlier study that used the exact same clinical and laboratory methods. The observation that the only significant risk factor for acquisition of EBV infection was deep kissing was confirmed. Most importantly, higher amounts of gp350 antibody correlated significantly with a lower severity of infectious mononucleosis (P<0.0001), which strengthens the rationale for a gp350-based prophylactic EBV vaccine.

The impact of donor viral replication at transplant on recipient infections posttransplant: a prospective study.

BACKGROUND: Organ donors are often implicated as the source of posttransplant recipient infection. We prospectively studied kidney and liver donor-recipient pairs to determine if donor viral replication of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK polyomavirus (BKV) at transplant was a risk factor for posttransplant recipient infection and disease. METHODS: Donors and recipients were studied for antibodies against CMV and EBV and for quantitative viral replication of CMV, EBV, and BKV in oral washes, urine, and whole blood pretransplant. Recipient testing continued every 3 months after transplantation. Demographic and clinical data on infections and graft and subject outcomes were obtained. RESULTS: The 98 donor-recipient pairs included 15 liver and 83 kidney transplants (18 of whom were children). No donor had detectable CMV replication; therefore, its impact on recipient CMV replication could not be analyzed. Donor EBV replication occurred in 22%, mostly in the oral wash and showed no impact on posttransplant recipient EBV replication (P=0.9) or EBV viremia (P=0.6) in kidney or liver recipients. Donor BKV replication occurred in 17%, mostly in the urine and although not associated with posttransplant recipient urinary BKV replication in recipients, it was associated with BKV viremia (P=0.02), and a significantly shorter time to BKV viremia (P=0.01) in kidney recipients. CONCLUSION: Donor replication of CMV or EBV did not impact posttransplant recipient viral replication in kidney or liver transplants. Donor urinary BKV replication is associated with recipient BKV viremia in kidney transplants.

Valganciclovir administration to kidney donors to reduce the burden of cytomegalovirus and Epstein-Barr virus transmission during transplantation.

BACKGROUND: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections are a significant cause of morbidity and mortality in transplant recipients and are often transmitted from the donor organ. METHODS: In a pilot prospective, randomized, double-blinded, placebo-controlled trial, we studied whether 14 days of pretransplant donor treatment with valganciclovir (valG) versus placebo reduced donor-to-recipient transmission, making posttransplant recipient prophylaxis more effective in reducing EBV and CMV disease. RESULTS: Seventeen D+ R- donor-recipient pairs were enrolled: 7 and 10 donors were randomized to valG and placebo, respectively. At study initiation, no donor had detectable CMV replication, five had EBV replication (two in valG, three in placebo group): EBV replication was undetectable during valG treatment, but resumed on stopping valG. Valganciclovir was tolerated without side effects or leukopenia. All recipients received routine posttransplant viral prophylaxis with valG. For recipients, viremia-free survival time, incidence, range, peak, and duration of CMV and EBV viremia were not significantly different between groups. There was no disease in the valG group but two serious viral diseases occurred in the placebo group (one CMV; one EBV-related posttransplant lymphoproliferative disorder). In the case of posttransplant lymphoproliferative disorder, the EBV DNA from the donor's oral wash and the recipient's lymphoid tissue biopsy had identical latent membrane protein 1 (LMP-1) sequence variations from the reference EBV strain, making it highly probable that the recipient's virus was of donor origin. CONCLUSION: Based on this pilot trial, we recommend an adequately powered study to determine if pretransplant donor treatment with valG can reduce posttransplant CMV and EBV disease with merely routine posttransplant recipient viral prophylaxis.

The effect of postnatal age on gentamicin pharmacokinetics in neonates.

STUDY OBJECTIVE: To determine if gentamicin serum concentrations obtained from newborns on day 2 of life versus days 3-4 yield significantly different pharmacokinetic parameter values. DESIGN: Retrospective chart review. SETTING: Neonatal intensive care unit. PATIENTS: Two hundred and sixty-seven infants who had peak and trough gentamicin serum concentrations determined on days 2, 3, or 4 of life. INTERVENTION: Determination of peak and trough serum gentamicin concentrations on days 2, 3, or 4 of life. MEASUREMENTS AND MAIN RESULTS: The elimination rate constant, serum half-life, volume of distribution, and clearance of gentamicin were calculated using a one-compartment pharmacokinetic model. Gestational age, birthweight, gentamicin dosage, peak and trough gentamicin concentrations, and hours after birth at which serum concentrations were drawn were recorded for all infants. Infants were stratified into three groups based on gestational age: 28 weeks or younger, older than 28 weeks but younger than 37 weeks, and 37 weeks or older. Birthweight and calculated pharmacokinetic parameters were compared by 2-tailed Student t test to determine if significant differences existed between pharmacokinetics parameters determined on day 2 of life versus days 3 or 4 within each of the gestational age groups. These analyses revealed only one significant difference between parameters assessed on day 2 versus days 3 or 4: at day 2, the mean trough concentration of gentamicin in infants of gestational age between 28 and 37 weeks was 1.63 +/- 0.44 mg/L, whereas at days 3 or 4, the same parameter for patients of the same gestational age was 1.4 +/- 0.48 mg/L (p=0.005). CONCLUSIONS: With one exception--elevated trough concentrations in infants in the gestational age group between 28 and 37 weeks--pharmacokinetic parameters calculated using gentamicin serum concentrations determined on day 2 of life are not significantly different from those derived from gentamicin serum concentrations determined on days 3 or 4. This suggests that gentamicin serum concentrations and subsequent dosage adjustments can be determined on day 2 of life.

Primary Epstein-Barr virus infection does not erode preexisting CD8⁺ T cell memory in humans.

Acute Epstein-Barr virus (EBV) infection results in an unusually robust CD8(+) T cell response in young adults. Based on mouse studies, such a response would be predicted to result in attrition of preexisting memory to heterologous infections like influenza A (Flu) and cytomegalovirus (CMV). Furthermore, many studies have attempted to define the lymphocytosis that occurs during acute EBV infection in humans, but it is unclear whether bystander T cells contribute to it. To address these issues, we performed a longitudinal prospective study of primary EBV infection in humans. During acute EBV infection, both preexisting CMV- and Flu-specific memory CD8(+) T cells showed signs of bystander activation, including up-regulation of granzyme B. However, they generally did not expand, suggesting that the profound CD8(+) lymphocytosis associated with acute EBV infection is composed largely of EBV-specific T cells. Importantly, the numbers of CMV- and Flu-specific T cells were comparable before and after acute EBV infection. The data support the concept that, in humans, a robust CD8(+) T cell response creates a new memory CD8(+) T cell niche without substantially depleting preexisting memory for heterologous infections.