Wildlife ecological risk assessment in the 21st century: Promising technologies to assess toxicological effects.

Despite advances in toxicity testing and the development of new approach methodologies (NAMs) for hazard assessment, the ecological risk assessment (ERA) framework for terrestrial wildlife (i.e., air-breathing amphibians, reptiles, birds, and mammals) has remained unchanged for decades. While survival, growth, and reproductive endpoints derived from whole-animal toxicity tests are central to hazard assessment, nonstandard measures of biological effects at multiple levels of biological organization (e.g., molecular, cellular, tissue, organ, organism, population, community, ecosystem) have the potential to enhance the relevance of prospective and retrospective wildlife ERAs. Other factors (e.g., indirect effects of contaminants on food supplies and infectious disease processes) are influenced by toxicants at individual, population, and community levels, and need to be factored into chemically based risk assessments to enhance the "eco" component of ERAs. Regulatory and logistical challenges often relegate such nonstandard endpoints and indirect effects to postregistration evaluations of pesticides and industrial chemicals and contaminated site evaluations. While NAMs are being developed, to date, their applications in ERAs focused on wildlife have been limited. No single magic tool or model will address all uncertainties in hazard assessment. Modernizing wildlife ERAs will likely entail combinations of laboratory- and field-derived data at multiple levels of biological organization, knowledge collection solutions (e.g., systematic review, adverse outcome pathway frameworks), and inferential methods that facilitate integrations and risk estimations focused on species, populations, interspecific extrapolations, and ecosystem services modeling, with less dependence on whole-animal data and simple hazard ratios. Integr Environ Assess Manag 2024;20:725-748. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Toxicological effects assessment for wildlife in the 21st century: Review of current methods and recommendations for a path forward.

Model species (e.g., granivorous gamebirds, waterfowl, passerines, domesticated rodents) have been used for decades in guideline laboratory tests to generate survival, growth, and reproductive data for prospective ecological risk assessments (ERAs) for birds and mammals, while officially adopted risk assessment schemes for amphibians and reptiles do not exist. There are recognized shortcomings of current in vivo methods as well as uncertainty around the extent to which species with different life histories (e.g., terrestrial amphibians, reptiles, bats) than these commonly used models are protected by existing ERA frameworks. Approaches other than validating additional animal models for testing are being developed, but the incorporation of such new approach methodologies (NAMs) into risk assessment frameworks will require robust validations against in vivo responses. This takes time, and the ability to extrapolate findings from nonanimal studies to organism- and population-level effects in terrestrial wildlife remains weak. Failure to adequately anticipate and predict hazards could have economic and potentially even legal consequences for regulators and product registrants. In order to be able to use fewer animals or replace them altogether in the long term, vertebrate use and whole organism data will be needed to provide data for NAM validation in the short term. Therefore, it is worth investing resources for potential updates to existing standard test guidelines used in the laboratory as well as addressing the need for clear guidance on the conduct of field studies. Herein, we review the potential for improving standard in vivo test methods and for advancing the use of field studies in wildlife risk assessment, as these tools will be needed in the foreseeable future. Integr Environ Assess Manag 2024;20:699-724. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.

The blood-brain barrier (BBB) provides essential neuroprotection from environmental toxins and xenobiotics, through high expression of drug efflux transporters in endothelial cells of the cerebral capillaries. However, xenobiotic exposure, stress, and inflammatory stimuli have the potential to disrupt BBB permeability in fetal and post-natal life. Understanding the role and ability of the BBB in protecting the developing brain, particularly with respect to drug/toxin transport, is key to promoting long-term brain health. Drug transporters, particularly P-gp and BCRP are expressed in early gestation at the developing BBB and have a crucial role in developmental homeostasis and fetal brain protection. We have highlighted several factors that modulate drug transporters at the developing BBB, including synthetic glucocorticoid (sGC), cytokines, maternal infection, and growth factors. Some factors have the potential to increase expression and function of drug transporters and increase brain protection (e.g., sGC, transforming growth factor [TGF]-ß). However, others inhibit drug transporters expression and function at the BBB, increasing brain exposure to xenobiotics (e.g., tumor necrosis factor [TNF], interleukin [IL]-6), negatively impacting brain development. This has implications for pregnant women and neonates, who represent a vulnerable population and may be exposed to drugs and environmental toxins, many of which are P-gp and BCRP substrates. Thus, alterations in regulated transport across the developing BBB may induce long-term changes in brain health and compromise pregnancy outcome. Furthermore, a large portion of neonatal adverse drug reactions are attributed to agents that target or access the nervous system, such as stimulants (e.g., caffeine), anesthetics (e.g., midazolam), analgesics (e.g., morphine) and antiretrovirals (e.g., Zidovudine); thus, understanding brain protection is key for the development of strategies to protect the fetal and neonatal brain.

Fetal glucocorticoid exposure leads to sex-specific changes in drug-transporter function at the blood-brain barrier in juvenile guinea pigs.

Antenatal synthetic glucocorticoids (sGCs) are a life-saving treatment in managing pre-term birth. However, off-target effects of sGCs can impact blood-brain barrier (BBB) drug transporters essential for fetal brain protection, including P-glycoprotein (P-gp/Abcb1) and breast cancer resistance protein (BCRP/Abcg2). We hypothesized that maternal antenatal sGC treatment modifies BBB function in juvenile offspring in a sex-dependent manner. Thus, the objective of this study was to determine the long-term impact of a single or multiple courses of betamethasone on P-gp/Abcb1 and BCRP/Abcg2 expression and function at the BBB. Pregnant guinea pigs (N = 42) received 3 courses (gestation days (GDs) 40, 50, and 60) or a single course (GD50) of betamethasone (1 mg/kg) or vehicle (saline). Cerebral microvessels and brain endothelial cells (BEC) were collected from the post-natal day (PND) 14 offspring to measure protein, gene expression, and function of the drug transporters P-gp/Abcb1 and BCRP/Abcg2. P-gp protein expression was decreased (p < .05) in microvessels from male offspring that had been exposed to multiple courses and a single course of sGC, in utero. Multiple courses of sGC resulted in a significant decrease in P-gp function in BECs from males (p < .05), but not females. There was a very strong trend for increased P-gp function in males compared to females (p = .055). Reduced P-gp expression and function at the BBB of young male offspring following multiple prenatal sGC exposures, is clinically relevant as many drugs administered postnatally are P-gp substrates. These novel sex differences in drug transporter function may underlie potential sexual dimorphism in drug sensitivity and toxicity in the newborn and juvenile brain.

Impact of Patient Load on the Quality of Electronic Medical Record Documentation.

OBJECTIVE: American College of Graduate Medical Education (ACGME) recommends ongoing care of 10 patients per resident however its implication is unclear. We hypothesized EMR quality to vary based on patient load and call status. METHODS: We conducted a double-blind, single-center, retrospective observational study between 2017 and 2019 to investigate the quality and accuracy of resident documentation using the Responsible Electronic Documentation (RED) Checklist, a validated scoring system. RESULTS: A total of 234 independent charts were analyzed and 80 met scoring criteria. Average patients per residents was 4, 9.1, 7.2, and 5.5 on "call" day (D0), "post-call" day (D1), "mid-call" day (D2), and "pre-call" day (D3), respectively. Mean RED checklist scores were 68.1%, 57%, 68.6%, and 72.1% on the above call status. The difference in score between D3 and D1 was statistically significant (P = .00042). There was a negative correlation between score and number of patients per resident (r = -0.286, P = .010). CONCLUSION: EMR documentation quality is directly impacted by patient load and resident call status with the lowest documentation quality on post-call day, correlating with patient load.

DNA methylome signatures of prenatal exposure to synthetic glucocorticoids in hippocampus and peripheral whole blood of female guinea pigs in early life.

Synthetic glucocorticoids (sGC) are administered to women at risk of preterm delivery, approximately 10% of all pregnancies. In animal models, offspring exposed to elevated glucocorticoids, either by administration of sGC or endogenous glucocorticoids as a result of maternal stress, show increased risk of developing behavioral, endocrine, and metabolic dysregulation. DNA methylation may play a critical role in long-lasting programming of gene regulation underlying these phenotypes. However, peripheral tissues such as blood are often the only accessible source of DNA for epigenetic analyses in humans. Here, we examined the hypothesis that prenatal sGC administration alters DNA methylation signatures in guinea pig offspring hippocampus and whole blood. We compared these signatures across the two tissue types to assess epigenetic biomarkers of common molecular pathways affected by sGC exposure. Guinea pigs were treated with sGC or saline in late gestation. Genome-wide modifications of DNA methylation were analyzed at single nucleotide resolution using reduced representation bisulfite sequencing in juvenile female offspring. Results indicate that there are tissue-specific as well as common methylation signatures of prenatal sGC exposure. Over 90% of the common methylation signatures associated with sGC exposure showed the same directionality of change in methylation. Among differentially methylated genes, 134 were modified in both hippocampus and blood, of which 61 showed methylation changes at identical CpG sites. Gene pathway analyses indicated that prenatal sGC exposure alters the methylation status of gene clusters involved in brain development. These data indicate concordance across tissues of epigenetic programming in response to alterations in glucocorticoid signaling.

Four Distinct Cases of Multisystem Inflammatory Syndrome in Adults Associated With SARS-CoV-2 Infection at a Community Hospital in New Jersey.

Multisystem inflammatory syndrome (MIS) is a rare entity that usually presents with a constellation of symptoms such as fever, hypotension, gastrointestinal symptoms, cardiac dysfunction, or dermatological involvement, representing an inflammatory state. During the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, several cases of multisystem inflammatory syndrome in children (MIS-C) have been described in the literature. The Centers for Disease Control and Prevention (CDC) has acknowledged the increasing incidence of the same entity in adults, referred to as multisystem inflammatory syndrome in adults (MIS-A). This case series describes four patients who presented to the Monmouth Medical Center in New Jersey with symptoms suggestive of MIS-A associated with SARS-CoV-2 infection and their clinical outcomes. All patients were within the age group of 20-40 years with no underlying medical condition. The period between SARS-CoV-2 infection and the development of MIS-A varied from 10 days through a month. Presentations ranged from a mild flu-like illness to shock requiring vasopressors. A positive SARS-CoV-2 antibody test was essential for the diagnosis. Inflammatory markers, such as ferritin, D-dimer, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin-6 (IL-6), were elevated on admission. The Use of immunomodulatory agents, namely steroids and intravenous immunoglobulin (IVIG), resulted in positive clinical outcomes. Inflammatory markers and imaging on admission did not appear to predict the disease course. A positive SARS-CoV-2 polymerase chain reaction (PCR) did not appear to influence the response to treatment. Given the high probability of MIS-A with negative viral testing, the use of both antibody and viral testing with the addition of inflammatory markers may be essential to diagnose this SARS-CoV-2-associated condition.

Characterizing imidacloprid and metabolites in songbird blood with applications for diagnosing field exposures.

Neonicotinoids are the most widely used insecticides globally, but their rapid metabolism in vertebrates makes diagnosing wildlife exposure challenging. More detailed information on the pattern of imidacloprid metabolites over time could be used to better approximate the timing and level of exposure. Here, we applied recently developed sensitive analytical methods to measure imidacloprid (IMI) parent compound along with an expanded suite of metabolites (5-OH-IMI, IMI-olefin, desnitro-IMI, IMI-urea, 6-chloronicotinic acid, 5-AMCP, 6-OH nicotinic acid) and six other neonicotinoids in adult red-winged blackbirds (Agelaius phoeniceus) that were experimentally exposed to one of two field-realistic concentrations of imidacloprid (0.8 or 6.9 mg/kg bw). We measured concentrations in small (25 µL) plasma samples collected pre-exposure and at 1-, 6-, 24- and 48-h post-exposure. Imidacloprid was rapidly absorbed and metabolized within 48 h at both doses, with the largest decrease within 6 h post-exposure. The average proportion of parent IMI decreased from 68% of total detectable residues at 1-h to 34% at 6-h post-exposure. Two primary metabolites in blood were 5-OH-IMI and IMI-olefin, and 5-OH-IMI was the most persistent marker of exposure at 48-h. Desnitro-IMI was consistently detected following very recent (≤ 1-h) IMI exposure, and a higher ratio of parent IMI to metabolites also indicated recent exposure. Other metabolites were only detected in the higher dose group, and could be used as indicators of exposure to higher IMI concentrations. This sensitive analytical method and the observed metabolite patterns could be used to inform a growing body of field studies linking neonicotinoid exposure and effects in free-living birds.

COVID-19 patients in a tertiary US hospital: Assessment of clinical course and predictors of the disease severity.

INTRODUCTION: Patients with severe COVID-19 can develop ventilator-dependent acute hypoxic respiratory failure (VDAHRF), which is associated with a higher mortality rate. We evaluated the clinical course of hospitalized COVID-19 patients and compared them with the patients who received invasive mechanical ventilation. Characteristics of intubated patients who were successfully weaned from the ventilator were compared with the patients who failed to be extubated or died in the hospital. OBJECTIVE: To investigate the clinical course of hospitalized COVID-19 patients, and assess the possible predictors of the disease severity leading to VDAHRF. METHODS: This is a single-center, retrospective study. The first 129 patients (18 years or older) with COVID-19 admitted to Monmouth Medical Center from March 1st to April 25th, 2020 were included. RESULTS: Out of 129 patients, 23.25% (n = 30) required invasive mechanical ventilation, and of those, six patients were successfully weaned from the ventilator. Multivariable logistic regression analysis showed increased odds of intubation associated with hypoxemia (odds ratio 17.23, 95% CI 5.206-57.088; p < 0.0001), elevated d-dimer by one unit mg/L of FEU (odds ratio 1.515, 95% CI 5.206-57.088; p = 0.0430) and elevated ferritin by one unit ng/ml (odds ratio 1.001, 95% CI 1.000-1.001, p = 0.0051) on admission, adjusted for other covariates. CONCLUSIONS: Patients who required invasive mechanical ventilation were more likely to have older age, male gender, coronary artery disease, diabetes, and obesity. The patients who were successfully weaned from the ventilator were more likely to be younger in age, and none of them had heart failure or CAD.

Hilar lymphadenopathy, a novel finding in the setting of coronavirus disease (COVID-19): a case report.

BACKGROUND: As the outbreak of coronavirus disease 2019 (COVID-19) has progressed, computed tomography has emerged as an integral part of the diagnosis alongside reverse transcriptase-polymerase chain reaction assays. Frequently encountered imaging findings include peripheral airspace consolidations; bilateral ground-glass opacities; and, less commonly, cavitation. Hilar lymphadenopathy is a rarely reported finding in the setting of COVID-19. CASE PRESENTATION: A 73-year-old Caucasian woman presented to our hospital with fever and fatigue. She had a maximum body temperature of 102.3 °F with lymphopenia and thrombocytopenia. She was diagnosed with severe acute respiratory syndrome coronavirus 2 infection on the basis of a positive result from a reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab sample. Contrast-enhanced chest computed tomography revealed multifocal, subpleural ground-glass opacities with nodular consolidations bilaterally. Computed tomography also demonstrated atypical bilateral hilar lymphadenopathy, a rarely reported imaging feature of COVID-19. Chest computed tomography 1 month before the presentation did not show focal consolidations or lymphadenopathy. This indicated that the findings were due to the patient's severe acute respiratory syndrome coronavirus 2 infection. She received 5 days of oral hydroxychloroquine and experienced resolution of her symptoms. CONCLUSION: Chest computed tomography has been used extensively to diagnose and characterize the distinguishing radiological findings associated with viral pneumonia. It has emerged as an integral part of the diagnosis of COVID-19 alongside reverse transcriptase-polymerase chain reaction assays. Clinicians must be aware of uncommon clinical and radiological findings in order to diagnose this entity. Hilar lymphadenopathy is commonly seen with fungal infections, mycobacterial infections, and sarcoidosis. An extensive literature review found that bilateral hilar lymphadenopathy has not been reported in the setting of COVID-19. More data are needed to establish the clinical impact of this novel finding.

Incubation temperature and PCB-126 exposure interactively impair shorebird embryo and post-hatch development.

In oviparous wildlife, many critical physiological and behavioural components are strongly influenced by the embryonic and early post-hatch developmental environment. As such, early life stages in these species are highly vulnerable to both natural and anthropogenic stressors. For example, in birds, incubation temperature may influence the rate of egg development while also affecting contaminant metabolism and absorption in body tissues, resulting in potentially multiplicative impacts on embryonic and posthatch development. We tested the hypothesis that cumulative effects of early contaminant exposure and temperature stress can negatively affect avian development and may have interactive effects that are more detrimental than either stressor individually. Using a controlled egg injection and incubation study on killdeer (Charadrius vociferous), eggs were exposed to a known endocrine disruptor, 3,3',4,4',5-pentachlorobiphenyl (PCB-126) and incubated at either low (36 °C), intermediate (37.5 °C), or high (39 °C) temperatures. Our results indicated that eggs incubated at low temperature had earlier detection of heartbeat, longer incubation length, lower growth rate post-hatch, and higher post-hatch mortality, compared to eggs incubated under intermediate temperatures. Higher incubation temperatures resulted in shorter incubation length, earlier detection of heart rate and faster righting time. As predicted, embryo and chick mortality were greater in the PCB-dosed birds incubated at intermediate and high temperatures. Incidence of distended yolk sacs (%) also increased with PCB exposure in all temperature groups, with the largest increase in the high temperature group. Overall, our results show that low incubation temperature can cause greater adverse effects than PCB-126 exposure alone, but that negative effects of PCB-126 exposure are exacerbated by high incubation temperatures. These findings suggest that in natural settings, shorebird embryos may be more susceptible to contaminant exposure when incubated at temperatures either below or above the apparent optimum.

Continuous exposure to mercury during embryogenesis and chick development affects later survival and reproduction of zebra finch (Taeniopygia guttata).

Methylmercury (MeHg) is a global environmental contaminant that bioaccumulates and has multiple toxic modes of action. Aquatic species have traditionally been the focus of wildlife toxicological research on mercury, but terrestrial organisms, including passerine birds, can be exposed to similarly elevated levels of MeHg. In this study we exposed a model passerine, the zebra finch (Taeniopygia guttata), to MeHg in ovo, as chicks only, or with a combined 'in ovo + chick' treatment. We isolated exposure to specific developmental stages through the use of egg injections (3.2 µg Hg/g egg) and controlled oral dosing of chicks (0.24 µg Hg/g bw/day from day 1 to day 30). In ovo exposure to MeHg reduced hatching success, but there was no effect of MeHg on chick growth. We found that in ovo only or chick only exposure did not have long-term effects, but there was some evidence for longer-term effects of combined 'in ovo + chick' exposure on post-fledging survival and potentially sex-biased survival which resulted in very few 'in ovo + chick' exposed females surviving to breed. These females also had lower overall breeding productivity that was mainly due to lower hatching success of their offspring, not lower chick-rearing success. We found no effect of treatment on clutch size or latency to laying among females that did lay eggs. Our study suggests that combined embryonic and nestling MeHg exposure has compounding latent effects on productivity, likely through a mechanism that influences the ability of females to lay fertile eggs that hatch.

A neonicotinoid insecticide reduces fueling and delays migration in songbirds.

Neonicotinoids are neurotoxic insecticides widely used as seed treatments, but little is known of their effects on migrating birds that forage in agricultural areas. We tracked the migratory movements of imidacloprid-exposed songbirds at a landscape scale using a combination of experimental dosing and automated radio telemetry. Ingestion of field-realistic quantities of imidacloprid (1.2 or 3.9 milligrams per kilogram body mass) by white-crowned sparrows (Zonotrichia leucophrys) during migratory stopover caused a rapid reduction in food consumption, mass, and fat and significantly affected their probability of departure. Birds in the high-dose treatment stayed a median of 3.5 days longer at the site of capture after exposure as compared with controls, likely to regain fuel stores or recover from intoxication. Migration delays can carry over to affect survival and reproduction; thus, these results confirm a link between sublethal pesticide exposure and adverse outcomes for migratory bird populations.

In ovo exposure to brominated flame retardants Part I: Assessment of effects of TBBPA-BDBPE on survival, morphometric and physiological endpoints in zebra finches.

Tetrabromobisphenol A bis(2,3-dibromopropyl) ether (TBBPA-BDBPE) is an additive flame retardant used in polyolefins and polymers. It has been detected in biota, including in avian eggs, yet little is known of its effects. We assessed the pattern of TBBPA-BDBPE concentrations in songbird eggs over the incubation period, and the effects of embryonic exposure to TBBPA-BDBPE in a model songbird species, the zebra finch (Taeniopygia guttata). To assess concentrations during embryo development, eggs were injected on the day they were laid with the vehicle control (safflower oil) or 100 ng TBBPA-BDBPE/g egg, and whole egg contents were collected throughout embryonic development on day 0 (unincubated), 5, 10 and 13. To evaluate effects of embryonic exposure to TBBPA-BDBPE, eggs were injected at Hamburger-Hamilton stage 18 (∼80 h after initiation of incubation) with safflower oil only, 10, 50 or 100 ng TBBPA-BDBPE/g egg (albumin injection volume 1 µl/g). Eggs were monitored for hatching success, and nestlings were monitored for growth and survival. At 15 days post-hatch, tissues were collected to assess physiological effects. TBBPA-BDBPE was incorporated into the egg as the embryo developed, and concentrations started declining in late incubation, suggesting biotransformation by the embryo. There were no effects on hatching success, nestling survival, growth, organ somatic indices, or thyroid hormone homeostasis; however, there was evidence that body condition declined in a dose-dependent manner towards the end of the rapid nestling growth phase. This decreased body condition could be a delayed effect of early developmental exposure, or it may be the result of increased exposure to biotransformation products of TBBPA-BDBPE produced over the nestling period, which are predicted to be more bioaccumulative and toxic than the parent compound.

In ovo exposure to brominated flame retardants Part II: Assessment of effects of TBBPA-BDBPE and BTBPE on hatching success, morphometric and physiological endpoints in American kestrels.

Tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTPBE) are both brominated flame retardants (BFRs) that have been detected in birds; however, their potential biological effects are largely unknown. We assessed the effects of embryonic exposure to TBBPA-BDBPE and BTBPE in a model avian predator, the American kestrel (Falco sparverius). Fertile eggs from a captive population of kestrels were injected on embryonic day 5 (ED5) with a vehicle control or one of three doses within the range of concentrations that have been detected in biota (nominal concentrations of 0, 10, 50 or 100 ng/g egg; measured concentrations 0, 3.0, 13.7 or 33.5 ng TBBPA-BDBPE/g egg and 0, 5.3, 26.8 or 58.1 ng BTBPE/g egg). Eggs were artificially incubated until hatching (ED28), at which point blood and tissues were collected to measure morphological and physiological endpoints, including organ somatic indices, circulating and glandular thyroid hormone concentrations, thyroid gland histology, hepatic deiodinase activity, and markers of oxidative stress. Neither compound had any effects on embryo survival through 90% of the incubation period or on hatching success, body mass, organ size, or oxidative stress of hatchlings. There was evidence of sex-specific effects in the thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE. However, there were no effects of TBBPA-BDBPE on the thyroid system in kestrels. For the BTPBE study, a subset of high-dose eggs was collected throughout the incubation period to measure changes in BTBPE concentrations. There was no decrease in BTBPE over the incubation period, suggesting that BTBPE is slowly metabolized by kestrel embryos throughout their ∼28-d development. These two compounds, therefore, do not appear to be particularly toxic to embryos of the American kestrel.

Porphyromonas asaccharolytica as a Rare Causative Agent for Lemierre's Syndrome.

Lemierre's syndrome is a rare disease associated with significant morbidity and mortality. It begins with an oropharyngeal infection, which spreads locally to involve the internal jugular vein causing thrombophlebitis, followed by distant spread and metastatic infections. Affected individuals are commonly young adults. Causative organisms are usually oropharyngeal flora, most commonly being the anaerobe Fusobacterium necrophorum. Porphyromonas asaccharolytica is a rare etiological agent with only three cases being reported in the literature. This case report describes a previously healthy 22-year-old man who initially presented with acute tonsillitis and was later found to have left internal jugular vein thrombophlebitis along with bilateral septic emboli to the lungs. The patient was treated with a five-week course of ampicillin-sulbactam and metronidazole. Subsequent imaging also showed progression of internal jugular vein thrombus, for which warfarin was given for three months for anticoagulation.

Impact of Storage Lesion on Post-transfusion Rise in Hemoglobin.

BACKGROUND: The storage lesion is defined as the set of changes that occur in red blood cells (RBCs) during storage. Studies have shown that a prolonged storage period of RBCs is associated with increased destruction after transfusion. The aim of this study is to determine the impact of the storage lesion on the efficacy of RBC transfusions by comparing the mean rise in the hemoglobin of patients who received new vs old blood. METHODS: We did a retrospective chart review of all patients who received a single unit of pure red blood cell (PRBC) transfusion in a three-month period. Patients with hemolytic anemia and active bleeding were excluded. The storage lesion was estimated by calculating the number of days to expiration on the day of transfusion. Median days to expiration was calculated to be 11 days. Patients were divided into two groups based on days to expiration. Group A included patients who received old blood (days to expiration: 0-11) and group B included patients who received new blood (days to expiration: 11-38). The mean rise in hemoglobin between the two groups was compared using the paired t-test. RESULTS: The baseline characteristics of both groups were similar. There was no statistically significant difference in the mean rise in hemoglobin (1.01 vs 1.08- p-value 0.298), hematocrit (3.37 vs 3.61- p-value 0.249), and RBC count (0.42 vs 0.44- p-value 0.097) in the group that received old blood vs new blood, respectively. CONCLUSION: An RBC transfusion with a shorter storage period does not increase hemoglobin more than RBC with a longer storage period.

Possible Predictive Factors for In-hospital Cardiac Arrest in Patients with Cancer: A Retrospective Single Center Study.

BACKGROUND: Despite cancer being the second most common cause of death in the United States, more people are living longer after the diagnosis of cancer than before. Healthcare workers will be treating an increasing number of patients with cancer. Various studies have identified predictors of cardiac arrest in the general population, however, none have been done to identify such factors in cancer patients who form a more vulnerable group with lower survival rate following cardiac arrest. METHODS: We retrospectively analysed charts of all patients with active cancer who experienced in-hospital cardiac arrest (IHCA) and underwent cardio-pulmonary resuscitation (CPR) from January 2015 to December 2017 at our hospital (n=44, group A). We compared this group to 44 consecutive patients with active cancer admitted to the oncology unit who did not experience cardiac arrest (n=44, group B). We excluded patients in remission. RESULTS: Both the groups were comparable in terms of age (69 ± 14 vs 68 ± 15, p=0.776) and gender distribution (50% vs 56% males, p=0.521). Prevalence of coronary artery disease (CAD) (25% vs 11%, p=0.097), hypertension (68% vs 66%, p=0.821), hyperlipidaemia (34% in both groups, p=1.000), tobacco abuse (18% vs 27%, p=0.308), and diabetes mellitus (34% vs 23%, p=0.237) was not significantly different between the two groups. Group with cardiac arrest had significantly higher alanine aminotransferase (100 U/L ± 150 vs 47 U/L ± 87, p=0.043), alkaline phosphatase (288 U/L ± 512 vs 118 U/L ± 80, p=0.032), creatinine (1.8 mg/dl ± 1.74 vs 1.1 mg/dl ± 0.76, p=0.023), international normalised ratio (INR) (2.1 ± 1.5 vs 1.2 ± 0.5, p=0.005), and lower estimated -glomerular filtration rate (43 mL/min/1.73m2 ± 17 vs 51 mL/min/1.73m2 ± 15, p=0.022) on admission. Group A also had significantly higher incidence of sepsis during the hospital course as compared to group B (30% vs 2%, p<0.001). In group A, 11.4% survived to discharge as compared to 95.5% in group B. Significantly higher number of patients in group B were taking chemotherapy (77.27% vs 34.09%, p=0.000046) and radiation therapy (65.9% vs 22.72%, p=0.000046) as compared to group A. CONCLUSION: Cancer patients who experienced IHCA had worse renal and hepatic function; they were frequently diagnosed with sepsis and had similar cardiovascular risk factors as compared to cancer patients who did not experience cardiac arrest. Furthermore, a higher number of patients with active cancer who did not experience cardiac arrest were on chemotherapy, immunotherapy or radiation therapy.

Possible predictive factors for recovery of left ventricular systolic function in Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is a transient systolic dysfunction of the left ventricle which is usually seen in elderly women, often following a physical or emotional stressful event. Little is known about the prognostic factors affecting the recovery of systolic function. Thirty-six patients diagnosed with TTC from January 2006 to January 2017 at our hospital were included. Median time to recovery of ejection fraction (EF) was calculated to be 25 days. Early recovery of ejection fraction was defined as less than or equal to 25 days (group 1) and late recovery was defined as more than 25 days (group 2). Demographic and clinical factors were compared between the groups. Fifty percent patients had early recovery of EF with a mean time to recovery of 7.11 days and 50% had late recovery of ejection fraction with a mean time to recovery of 58.38 days. Younger age at presentation was associated with early recovery of systolic function (58.83 ± 2.7 years vs. 67.33 ± 2.7 years, p = 0 .032). Presence of an identifiable triggering event was associated with early recovery (83% in group 1 vs. 50% in group 2, p = 0.034). Generalized anxiety disorder was seen more commonly in the group with early recovery (78% in group 1 vs. 45% in group 2, p = 0.040). In conclusion, younger age, generalized anxiety disorder and presence of triggering event were seen more commonly in patients with early recovery of left ventricular systolic function in Takotsubo cardiomyopathy.

Embryonic exposure to environmentally relevant concentrations of a brominated flame retardant reduces the size of song-control nuclei in a songbird.

Environmental contaminants have the potential to act as developmental stressors and impair development of song and the brain of songbirds, but they have been largely unstudied in this context. 2,2',4,4',5-Pentabromodiphenyl ether (BDE-99) is a brominated flame retardant congener that has demonstrated endocrine disrupting effects, and has pervaded the global environment. We assessed the effects of in ovo exposure to environmentally relevant levels of BDE-99 on the neuroanatomy of the song-control system in a model songbird species, the zebra finch (Taeniopygia guttata). Embryos were exposed via egg injection to a vehicle control (DMSO), 10, 100, or 1000 ng BDE-99/g egg on the day the egg was laid. Chicks were raised to sexual maturity to investigate long-term effects of BDE-99 on the adult male brain. Three key song-control nuclei (Area X, HVC, RA) all showed a dose-dependent trend toward decreasing volume as BDE-99 concentration increased, and birds exposed to 1000 ng/g in ovo BDE-99 had significantly smaller song-control nuclei volume compared to control birds. High environmental concentrations of BDE-99 in avian tissues can be within that range and thus could affect development of the song-control system in birds, and potentially other processes. We previously found that BDE-99 exposure during the nestling period had no effect of on the song-control system, although it did have significant effects on some behaviural endpoints. Taken together, these results suggest that exposure to polybrominated diphenyl ether (PBDEs) during critical developmental windows can significantly alter neurological development. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018.