[Incidental finding aortitis: how to handle it?] / Découverte fortuite d'une aortite : quelle prise en charge ?

Aortitis may be an incidental finding at imaging. It refers to inflammation of the aortic wall and sometimes may be hard to differentiate with the periaortitis, inflammation of tissues around the vessel. Their clinical presentation is as varied as their etiologies. Appropriate early management is essential for improving patient prognosis, as the diagnostic approach remains challenging.

Une aortite, inflammation de la paroi de l'aorte, est parfois décrite à l'imagerie. Elle peut être confondue avec une périaortite, l'inflammation des tissus autour du vaisseau. La présentation clinique de ces deux atteintes est aussi diverse que leurs causes. Comme la prise en charge thérapeutique adéquate dépend de la maladie sous-jacente, un choix réfléchi d'examens paracliniques est essentiel pour améliorer le pronostic du patient.

Barriers and Opportunities for the MCH Workforce to Support Hurricane Preparedness, Response, and Recovery in Florida.

OBJECTIVES: In recent years, catastrophic hurricanes have devastated numerous areas, prompting a need to build resilience particularly in at-risk populations that rely on health care and social services. The Maternal and Child Health (MCH) workforce covers a wide breadth of services to pregnant women, families, and children with special health care needs. Research has noted the need to strengthen this workforce with training and skills to help their patients and clients prepare, respond, and recover from disasters. METHODS: Focus groups and interviews with 35 Florida parents and professionals impacted by Hurricanes Irma, Maria, and Michael were conducted to evaluate the stressors placed on systems of care serving mothers and infants in Florida. Journey mapping was used to explore opportunities for improving MCH training and services. RESULTS: Results highlight the importance of increased communication and collaboration between families and providers, coordination among health care and social services providers, effective public messaging, tailored preparedness materials and processes, and the need for post-disaster mental health services and employment resources. CONCLUSION: Ultimately, hurricane preparation and mitigation are key for improving community resilience and these efforts should be tailored to MCH populations as well as delivered by the providers who know their needs best.

Missing out on precious time: Extending paid parental leave for parents of babies admitted to neonatal intensive or special care units for prolonged periods.

In Australia, approximately 18% of newborn babies are admitted to a neonatal intensive or special care nursery. While most babies admitted to a neonatal intensive or special care nursery are discharged home within a few weeks, around 6% of babies spend more than 2 weeks in hospital. For the parents of these babies, much of their leave entitlements (Australian Government Paid Parental Leave Scheme is up to18 weeks for the primary care giver and up to 2 weeks for partners) are used before their baby comes home from hospital. The time babies and parents spend together in the early developmental period, during the hospitalisation and when the baby is discharged home, is crucial for optimal child development and bonding. Yet care givers who have a baby admitted to neonatal intensive or special care for extended periods are not currently entitled to any extra parental leave payments in Australia. We recommend the Australian Paid Parental Leave Act is changed to allow primary carers access to 1 week of extra parental leave pay for every week in hospital (for babies admitted to hospital for more than 2 weeks), up to a maximum of 14 weeks. For fathers and partners of these babies, we recommend an additional 2 weeks of extra Dad and Partner Pay. The net cost, taking into account likely productivity benefits, would be less than 1.5% of the current cost of the scheme and would improve health and socio-economic outcomes for the baby, family and society.

Challenges for the disaster workforce during a compound hurricane-pandemic.

The COVID-19 pandemic has created new workforce considerations for emergency management community in addressing cumulative and cascading disasters. This research identifies how emergency management planning for both the changing dynamics of COVID-19 and the upcoming hurricane season may change under a compound threat. Many jurisdictions have faced challenges in providing adequate staffing of shelters before the pandemic. Now, fatigue among staff further exacerbates these challenges as resources are stretched thin. Six workshops, involving 265 national, state, and local leaders, staff, experts, and advocates from 22 states, and a range of disciplines (disaster planning, public health, social services, academia, and healthcare), were convened to identify concerns and potential strategies to address staffing, training, logistics, and support. Strategies proposed to increase the number and skill set of staff available involve increased reliance upon volunteers and nonprofit organizations. Mental health resources, personal protective equipment, sanitation supplies, and defining roles within emergency shelters were recommended to reduce fatigue and redistribute responsibilities. Findings illuminate additional research avenues regarding assessing the underlying stressors contributing to the planning process and effective means of implementing these interventions to bolster emergency management shelter operations during a prolonged pandemic and in the future.

An impacted live fish in the oropharynx of an 8-year-old child

OBJECTIVE: To present an atypical case of a live fish lodged in the throat of a pediatric patient and discuss its management.METHODS:Design: Case ReportSetting: Tertiary Government HospitalPatient: OneRESULT: An 8-year-old girl swallowed a live fish when she accidentally fell in a body of water. Failed attempts to remove the live fish prompted consult in the emergency room of our hospital, where removal of the foreign body was successfully done using Mixter right angle forceps assisted with a gloved finger. Transient cyanosis and unresponsiveness during extraction was overcome with oxygen by mask and she regained consciousness. She was allowed to go home as no other untoward events or complications were observed.CONCLUSION: All ingested foreign bodies particularly in children require immediate attention. The survival of patients with upper aerodigestive and airway foreign bodies depends on early recognition and prompt multidisciplinary management.

Adult acute epiglottitis: An eight - year experience in a Philippine tertiary government hospital

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> To review cases of adult acute epiglottis in a tertiary government hospital and describe the clinical presentations, diagnostics performed, management and outcomes. <br /><strong>METHODS:</strong><br /><strong>Design:</strong> Retrospective Chart Review<br /><strong>Setting:</strong> Tertiary Government Hospital<br /><strong>Participants:</strong> Records of patients admitted by or referred to the Department of Otolaryngology Head and Neck Surgery with a diagnosis of acute epiglottis from January 2008 to August 2014 were identified from the department census and charts were retrieved from the Hospital Record Section and evaluated according to inclusion and exclusion criteria. Information regarding demographic data, clinical features, laboratory and other diagnostic examinations, medical management, and length of hospital stay were collected.<br /><strong>RESULTS:</strong> There were 20 cases in 7 years and 8 months. Most were male, 18 to 37-years-old, presenting with dysphagia, odynophagia and a swollen epiglottis on laryngoscopy. Abnormal soft-tissue lateral radiographs of the neck and leukocytosis were seen in 73% and 83%, respectively. Intravenous antibiotics and corticosteroids were administered in all cases, and mean hospital stay was 11.2 days.<br /><strong>CONCLUSION:</strong> Adult acute epiglottis should be highly suspected in patients presenting with dysphagia, odynophagia, and muffling of the voice even with a normal oropharyngeal examination. History of respiratory infection, co-morbidities, smoking and alcohol intake, concomitant laryngeal pathology and supraglottic structure insults contribute to development of the disease. Laryngoscopy is still the gold standard in diagnosis. Airway protection is mandatory but prophylactic intubation or tracheostomy are not advised. Intravenous antibiotics are necessary and corticosteroids may be of benefit. </p>

A pharmacogenetic candidate gene study of tenofovir-associated Fanconi syndrome.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a widely used antiretroviral agent with favorable efficacy, safety, and tolerability profiles. However, renal adverse events, including the rare Fanconi syndrome (FS), may occur in a small subset of patients treated for HIV infections. OBJECTIVES: The aim of this study was to identify genetic variants that may be associated with TDF-associated FS (TDF-FS). METHODS: DNA samples collected from 19 cases with TDF-FS and 36 matched controls were sequenced, and genetic association studies were conducted on eight candidate genes: ATP-binding cassette (ABC) transporters ABCC2 (MRP2) and ABCC4 (MRP4), solute carrier family members SLC22A6 (OAT1) and SLC22A8 (OAT3), adenylate kinases 2 (AK2) and 4 (AK4), chloride transporter CIC-5 CLCN5, and Lowe syndrome protein OCRL. The functional effects of a single nucleotide polymorphism (SNP) predicted to alter the transport of tenofovir were then investigated in cells expressing an identified variant of ABCC4. RESULTS: The case group showed a trend toward a higher proportion of rare alleles. Six SNPs in ABCC2 (three SNPs), ABCC4 (one SNP), and OCRL (two SNPs) were associated with TDF-FS case status; however, this association did not remain significant after correction for multiple testing. Six SNPs, present in OCRL (four SNPs) and ABCC2 (two SNPs), were significantly associated with increased serum creatinine levels in the cases, and this association remained significant after multiple test correction (P < 2 × 10). One synonymous SNP in ABCC2 (rs8187707, P = 2.10 × 10, ß = -73.3 ml/min/1.73 m(2)) was also significantly associated with the decreased estimated glomerular filtration rate of creatinine among cases. However, these results were driven by rare SNPs present in a small number of severely affected cases. Finally, a previously uncharacterized, nonsynonymous SNP, rs11568694, that was predicted to alter MRP4 function had no significant effect on tenofovir cellular accumulation in vitro. CONCLUSION: Although no single predictive genetic marker for the development of TDF-FS was identified, the findings from our study suggest that rare variants in multiple genes involved in the renal handling of tenofovir, and/or renal cell homeostasis, may be associated with increased susceptibility to TDF-FS.

Functional characterization and haplotype analysis of polymorphisms in the human equilibrative nucleoside transporter, ENT2.

The equilibrative nucleoside transporter 2 (ENT2; SLC29A2) is a bidirectional transporter that is involved in the disposition of naturally occurring nucleosides as well as a variety of anticancer and antiviral nucleoside analogs. The goal of the current study was to evaluate the function of genetic variants in ENT2 in cellular assays and to determine the haplotype structure of the coding and flanking intronic region of the gene. As part of a large study focused on genetic variation in membrane transporters (Leabman et al., 2003), DNA samples from ethnically diverse populations (100 African-Americans, 100 European-Americans, 30 Asians, 10 Mexicans, and 7 Pacific Islanders) were screened for variants in membrane transporters, including SLC29A2. Fourteen polymorphic sites in SLC29A2 were found, including 11 in the coding region. Five protein-altering variants were identified: three nonsynonymous variants, and two deletions. Each of the protein-altering variants was found at a very low frequency, occurring only once in the sample population. The nonsynonymous variants and the deletions were constructed via site-directed mutagenesis and were subsequently characterized in Xenopus laevis oocytes. All variants were able to take up inosine with the exception of ENT2-Delta845-846, which resulted in a frameshift mutation that prematurely truncated the protein. ENT2 showed very infrequent variation compared with most other transporter proteins studied, and it was found that five haplotypes were sufficient to describe the entire sample set. The low overall genetic diversity in SLC29A2 makes it unlikely that variation in the coding region contributes significantly to clinically observed differences in drug response.

The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and functional genomics.

The human organic anion transporter, OAT3 (SLC22A8), plays a critical role in renal drug elimination, by mediating the entry of a wide variety of organic anions, including a number of commonly used pharmaceuticals, into the renal proximal tubular cells. To understand the nature and extent of genetic variation in OAT3, and to determine whether such variation affects its function, we identified OAT3 variants in a large, ethnically diverse sample population and studied their transport activities in cellular assays. We identified a total of 10 distinct coding-region variants, which altered the encoded amino acid sequence, in DNA samples from 270 individuals (80 African-Americans, 80 European-Americans, 60 Asian-Americans, and 50 Mexican-Americans). The overall prevalence of these OAT3 variants was relatively low among the screened population, with only three variants having allele frequencies of >1% in a particular ethnic group. Clones of each variant were created by site-directed mutagenesis, expressed in HEK-293 cells, and tested for function using the model substrates, estrone sulfate (ES) and cimetidine (CIM). The results revealed a high degree of functional heterogeneity among OAT3 variants, with three variants (p. Arg149Ser, p. Gln239Stop, and p. Ile260Arg) that resulted in complete loss of function, and several others with significantly reduced function. One of the more common variants (p. Ile305Phe), found in 3.5% of Asian-Americans, appeared to have altered substrate specificity. This variant exhibited a reduced ability to transport ES, but a preserved ability to transport CIM. These data suggest that genetic variation in OAT3 may contribute to variation in the disposition of drugs.

Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1).

OBJECTIVES: The organic anion transporter, OAT1 (SLC22A6), plays a role in the renal elimination of many drugs and environmental toxins. The goal of this study was to identify and functionally characterize OAT1 variants as a first step towards understanding whether genetic variation in OAT1 may contribute to interindividual differences in renal elimination of xenobiotics. METHODS: As part of a larger study, 276 DNA samples from an ethnically diverse population were screened and 12 coding region variants of OAT1 were identified. The non-synonymous variants were then constructed and characterized in Xenopus laevis oocytes. A small family-based clinical study was conducted to determine the renal elimination of a model OAT1 substrate, adefovir (an antiviral agent) in human subjects who possessed a non-functional variant, OAT1-R454Q. RESULTS: Six non-synonymous variants were identified; two (OAT1-R50 H and OAT1-R293W) were present at > or = 1% in at least one ethnic population. These two variants exhibited normal uptake of p-aminohippurate, ochratoxin A and methotrexate assayed in X. laevis oocytes. One variant, OAT1-R454Q, was non-functional with respect to the above substrates. In the clinical study, there was no significant decrease in the renal secretory clearance of adefovir in family members heterozygous for OAT1-454Q in comparison to those with the reference transporter, OAT1-454R. CONCLUSIONS: These data indicate that the coding region of OAT1 has low genetic and functional diversity and suggest that coding region variants of OAT1 may not contribute substantially to interindividual differences in renal elimination of xenobiotics.

Natural variation in human membrane transporter genes reveals evolutionary and functional constraints.

Membrane transporters maintain cellular and organismal homeostasis by importing nutrients and exporting toxic compounds. Transporters also play a crucial role in drug response, serving as drug targets and setting drug levels. As part of a pharmacogenetics project, we screened exons and flanking intronic regions for variation in a set of 24 membrane transporter genes (96 kb; 57% coding) in 247 DNA samples from ethnically diverse populations. We identified 680 single nucleotide polymorphisms (SNPs), of which 175 were synonymous and 155 caused amino acid changes, and 29 small insertions and deletions. Amino acid diversity (pi(NS)) in transmembrane domains (TMDs) was significantly lower than in loop domains, suggesting that TMDs have special functional constraints. This difference was especially striking in the ATP-binding cassette superfamily and did not parallel evolutionary conservation: there was little variation in the TMDs, even in evolutionarily unconserved residues. We used allele frequency distribution to evaluate different scoring systems (Grantham, blosum62, SIFT, and evolutionarily conservedevolutionarily unconserved) for their ability to predict which SNPs affect function. Our underlying assumption was that alleles that are functionally deleterious will be selected against and thus under represented at high frequencies and over represented at low frequencies. We found that evolutionary conservation of orthologous sequences, as assessed by evolutionarily conservedevolutionarily unconserved and SIFT, was the best predictor of allele frequency distribution and hence of function. European Americans had an excess of high frequency alleles in comparison to African Americans, consistent with a historic bottleneck. In addition, African Americans exhibited a much higher frequency of population specific medium-frequency alleles than did European Americans.