Recurrent Bacteremia Caused by a “Flexispira”-Like Organism in a Patient with X-Linked (Bruton’s) Agammaglobulinemia

Helicobacter spp., except for Helicobacter cinaedi, have only rarely been reported in cases of septicemia. A patient with X-linked (Bruton's) agammaglobulinemia was found to have persistent sepsis with a Helicobacter-like organism despite multiple courses of antibiotics. His periods of sepsis were associated with leg swelling thought to be consistent with cellulitis. The organism was fastidious and required a microaerophilic environment containing H(2) for growth. Optimal growth was observed at 35 to 37 degrees C on sheep blood, CDC anaerobe, and Bordet-Gengou agars. Serial subcultures every 4 to 5 days were required to maintain viability. The organism was strongly urease positive and showed highest relatedness to Helicobacter-like organisms with the vernacular name "Flexispira rappini" by 16S rRNA gene sequence analysis. Genomic DNA hybridization studies, however, found 24 to 37% relatedness to "F. rappini" and even less to other Helicobacter spp. Although the organism phenotypically resembles "Flexispira" and Helicobacter, it is thought to represent a new taxon. The patient's infection was eventually cleared with a prolonged (5-month) course of intravenous imipenem and gentamicin.     

Human infections caused by Brevibacterium casei, formerly CDC groups B-1 and B-3.

Forty-one clinical strains of CDC coryneform groups B-1 and B-3 were compared biochemically, by analysis of cell wall sugars, amino acids, and cellular fatty acids, and by DNA relatedness to the type strains of Brevibacterium casei, Brevibacterium epidermidis, and Brevibacterium linens. Twenty-two strains were shown to be B. casei, while five other strains formed a phenotypically inseparable genomospecies in the same genus. The remaining isolates were genetically heterogeneous, and most are probably members of the genus Brevibacterium. They were not further identified, but they were biochemically distinguishable from B. casei. Eleven of the clinical strains of B. casei were isolated from blood, and two each were isolated from cerebrospinal fluid and from pleural fluid. At least five isolates were from multiple blood or cerebrospinal fluid cultures. To our knowledge, these strains are the first described clinical isolates identified as B. casei, which was previously considered to be a nonpathogenic species.     

Phenotypic characteristics, fatty acid composition, and isoprenoid quinone content of CDC group IIg bacteria.

Eleven strains of eugonic, nonoxidative, gram-negative rods isolated from clinical specimens formed a distinct group that was designated CDC group IIg. Five of the 11 isolates were from wounds. The phenotypic characteristics of CDC group IIg were most similar to those of Weeksella species, with the major difference being that CDC group IIg strains grew on MacConkey agar in 1 to 2 days, did not hydrolyze gelatin, and did not produce urease. All 11 strains of CDC group IIg possessed a distinct fatty acid profile that was characterized by large amounts (19 to 29%) of 18:1 omega 7c, 16:0, and 16:1 omega 7c, moderate amounts (6 to 10%) of 3-OH-14:0 and 14:0, and smaller amounts (1 to 2%) of 18:2, 18:0, and 3-OH-16:0. This fatty acid profile differs from those of Weeksella species by the absence of branched-chain fatty acids. CDC group IIg contains ubiquinone-8, as opposed to menaquinone-6 in Weeksella species. The isolates were susceptible to a variety of antimicrobial agents, including the aminoglycosides, tetracyclines, quinolones, sulfonamides, and polymyxin B.     

CDC group IIc: phenotypic characteristics, fatty acid composition, and isoprenoid quinone content.

Twenty strains of glucose-utilizing, small gram-negative slightly pleomorphic rods that grew well aerobically and that were isolated from clinical specimens formed a phenotypically similar group that was designated CDC group IIc. The phenotypic characteristics of CDC group IIc were most similar to those of CDC groups IIe and IIh, the major differences being that CDC group IIc produced acid from sucrose, hydrolyzed esculin, and usually reduced nitrate. The CDC group IIc strains were analyzed by gas-liquid chromatography for their cellular fatty acid compositions, and all contained relatively large amounts of isobranched hydroxy and nonhydroxy acids. High-performance liquid chromatography and mass spectrometry analysis of the quinone extract showed menaquinone-6 as the major component. Both the cellular fatty acid and isoprenoid quinone compositions were consistent with the profiles of CDC groups IIe and IIh. Thirty percent of the isolates were from human blood.     

Biomarkers for exposure to ambient air pollution--comparison of carcinogen-DNA adduct levels with other exposure markers and markers for oxidative stress

Human exposure to genotoxic compounds present in ambient air has been studied using selected biomarkers in nonsmoking Danish bus drivers and postal workers. A large interindividual variation in biomarker levels was observed. Significantly higher levels of bulky carcinogen-DNA adducts (75.42 adducts/10(8) nucleotides) and of 2-amino-apidic semialdehyde (AAS) in plasma proteins (56.7 pmol/mg protein) were observed in bus drivers working in the central part of Copenhagen, Denmark. In contrast, significantly higher levels of AAS in hemoglobin (55.8 pmol/mg protein), malondialdehyde in plasma (0. 96 nmol/ml plasma), and polycyclic aromatic hydrocarbon (PAH)-albumin adduct (3.38 fmol/ microg albumin) were observed in the suburban group. The biomarker levels in postal workers were similar to the levels in suburban bus drivers. In the combined group of bus drivers and postal workers, negative correlations were observed between bulky carcinogen-DNA adduct and PAH-albumin levels (p = 0.005), and between DNA adduct and [gamma]-glutamyl semialdehyde (GGS) in hemoglobin (p = 0.11). Highly significant correlations were found between PAH-albumin adducts and AAS in plasma (p = 0.001) and GGS in hemoglobin (p = 0.001). Significant correlations were also observed between urinary 8-oxo-7, 8-dihydro-2'-deoxyguanosine and AAS in plasma (p = 0.001) and PAH-albumin adducts (p = 0.002). The influence of the glutatione S-transferase (GST) M1 deletion on the correlation between the biomarkers was studied in the combined group. A significant negative correlation was only observed between bulky carcinogen-DNA adducts and PAH-albumin adducts (p = 0.02) and between DNA adduct and urinary mutagenic activity (p = 0.02) in the GSTM1 null group, but not in the workers who were homozygotes or heterozygotes for GSTM1. Our results indicate that some of the selected biomarkers can be used to distinguish between high and low exposure to environmental genotoxins.     

Human corneal epithelial cell adhesion to laminins.

PURPOSE. To analyze alpha-integrin mediated adhesion of human corneal epithelial cells to placental and EHS laminin isoforms. METHODS. Western blot analysis was used to partially characterize commercially available preparations of laminin isolated from the mouse EHS sarcoma and from human placenta. Using the human corneal epithelial cell line HCE-T, adhesion to laminin isoforms and fibronectin was determined using a colorimetric adhesion assay. alpha-integrin sub-unit modulation of corneal epithelial cell interaction with laminin isoforms was analyzed using immunofluorescence microscopy and adhesion assays incorporating functional blocking antibodies. RESULTS. In short-term adhesion assays, the preferred substrate for HCE-T attachment is placental laminin. Immunofluorescence microscopy reveals that alpha-integrin protein localization patterns are not significantly different in HCE-T interacting with EHS or placental laminin. However, in short-term assays alpha3 integrin plays a major role, and alpha2 integrin a minor role, in mediating HCE-T adhesion to laminin. alpha6 integrin does not appear to mediate adhesion to either substrate. CONCLUSIONS. These studies demonstrate that human corneal epithelial cells are capable of rapid adhesion to, and enhanced spreading on, laminin isoforms not characteristically resident in the adult corneal basement membrane. This characteristic of human corneal epithelium may explain, at least in part, why amniotic membrane transplantation is proving to be clinically useful for human ocular surface reconstruction.     

Impact of Race and Socioeconomic Status on Outcomes in Patients Hospitalized with COVID-19

BackgroundThe impact of race and socioeconomic status on clinical outcomes has not been quantified in patients hospitalized with coronavirus disease 2019 (COVID-19).ObjectiveTo evaluate the association between patient sociodemographics and neighborhood disadvantage with frequencies of death, invasive mechanical ventilation (IMV), and intensive care unit (ICU) admission in patients hospitalized with COVID-19.DesignRetrospective cohort study.SettingFour hospitals in an integrated health system serving southeast Michigan.ParticipantsAdult patients admitted to the hospital with a COVID-19 diagnosis confirmed by polymerase chain reaction.Main MeasuresPatient sociodemographics, comorbidities, and clinical outcomes were collected. Neighborhood socioeconomic variables were obtained at the census tract level from the 2018 American Community Survey. Relationships between neighborhood median income and clinical outcomes were evaluated using multivariate logistic regression models, controlling for patient age, sex, race, Charlson Comorbidity Index, obesity, smoking status, and living environment.Key ResultsBlack patients lived in significantly poorer neighborhoods than White patients (median income: $34,758 (24,531–56,095) vs. $63,317 (49,850–85,776), p < 0.001) and were more likely to have Medicaid insurance (19.4% vs. 11.2%, p < 0.001). Patients from neighborhoods with lower median income were significantly more likely to require IMV (lowest quartile: 25.4%, highest quartile: 16.0%, p < 0.001) and ICU admission (35.2%, 19.9%, p < 0.001). After adjusting for age, sex, race, and comorbidities, higher neighborhood income ($10,000 increase) remained a significant negative predictor for IMV (OR: 0.95 (95% CI 0.91, 0.99), p = 0.02) and ICU admission (OR: 0.92 (95% CI 0.89, 0.96), p < 0.001).ConclusionsNeighborhood disadvantage, which is closely associated with race, is a predictor of poor clinical outcomes in COVID-19. Measures of neighborhood disadvantage should be used to inform policies that aim to reduce COVID-19 disparities in the Black community.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06527-1.KEY WORDS: COVID-19, disparities, disadvantage, socioeconomic status, race     

Pressure on Sports Medicine Clinicians to Prematurely Return Collegiate Athletes to Play After Concussion

Context

 Anecdotal and qualitative evidence has suggested that some clinicians face pressure from coaches and other personnel in the athletic environment to prematurely return athletes to participation after a concussion. This type of pressure potentially can result in compromised patient care.

Objective

 To quantify the extent to which clinicians in the collegiate sports medicine environment experience pressure when caring for concussed athletes and whether this pressure varies by the supervisory structure of the institution''s sports medicine department, the clinician''s sex, and other factors.

Design

 Cross-sectional study.

Setting

 Web-based survey of National College Athletic Association member institutions.

Patients or Other Participants

 A total of 789 athletic trainers and 111 team physicians from 530 institutions.

Main Outcome Measure(s)

 We asked participants whether they had experienced pressure from 3 stakeholder populations (other clinicians, coaches, athletes) to prematurely return athletes to participation after a concussion. Modifying variables that we assessed were the position (athletic trainer, physician) and sex of the clinicians, the supervisory structure of their institutions'' sports medicine departments, and the division of competition in which their institutions participate.

Results

 We observed that 64.4% (n = 580) of responding clinicians reported having experienced pressure from athletes to prematurely clear them to return to participation after a concussion, and 53.7% (n = 483) reported having experienced this pressure from coaches. Only 6.6% (n = 59) reported having experienced pressure from other clinicians to prematurely clear an athlete to return to participation after a concussion. Clinicians reported greater pressure from coaches when their departments were under the supervisory purview of the athletic department rather than a medical institution. Female clinicians reported greater pressure from coaches than male clinicians did.

Conclusions

 Most clinicians reported experiencing pressure to prematurely return athletes to participation after a concussion. Identifying factors that are associated with variability in pressure on clinicians during concussion recovery can inform potential future strategies to reduce these pressures.Key Words: conflict of interest, organizational structure, sex, college

Key Points

• More than half of sports medicine clinicians had experienced pressure from coaches and athletes to return athletes to participation prematurely after a concussion.
• Clinicians experienced greater pressure from coaches at schools where the sports medicine department reported to the athletic department than at schools where the sports medicine department reported to an independent medical institution.
• Female clinicians experienced greater pressure from coaches than male clinicians experienced.
• More research is needed to determine how pressure affects clinical practice and whether pressure on clinicians affects return-to-participation decisions.

Addressing the health burden of mild traumatic brain injury from sport is increasingly considered a public health priority.¹ More than 450 000 college students participate in organized interscholastic sports each year.^2,3 Among collegiate athletes in contact and collision sports, Daneshvar et al⁴ estimated that 43 concussions are sustained per 100 000 athlete-exposures to a game or practice, which is nearly twice the rate of diagnosed concussions sustained by high school athletes competing in the same sports. This estimate likely understates the true incidence of concussions because many are undiagnosed.^5–8 Recent evidence^9–14 has suggested that repeated concussive and subconcussive brain trauma can lead to neurologic problems later in life, including changes in cognition and behavior.Conflict of interest in the care of concussed athletes is a topic of growing ethical discourse.^15–19 Writing for the Chronicle of Higher Education about US collegiate sport, Wolverton²⁰ painted a picture of colleges fraught with pressure on physicians and athletic trainers (ATs) from coaches and athletic administrators. A total of 101 clinicians who provide patient care for football teams in the National Collegiate Athletic Association (NCAA) Division I Football Bowl Subdivision participated in the non–peer-reviewed study, and more than half reported that they had “felt pressure from football coaches to return concussed players to action before they were medically ready.”²⁰ Some of this pressure was attributed to conflicts of interest inherent in the organizational structure and incentives of sports medicine departments. In some instances, ATs reported directly to head football coaches.²⁰ Even in substantially lower-stakes youth sports, Bramley et al²¹ reported that a sample of hockey coaches indicated they would be more likely to allow an athlete who had sustained a concussion to continue participating if the game was considered important, such as for a championship. Consequently, clinicians in collegiate sports medicine departments may find themselves in a challenging situation: having ethical responsibilities to provide appropriate medical care to their patients while facing perceived or real pressure from their employers to return athletes to participation.^15–19,22 In a survey of sports medicine physicians in New Zealand, Anderson and Gerrard²³ observed that whereas all respondents expressed a sense of responsibility to their athlete patients, 72% also believed they had a responsibility to the team coach, and 55% believed they had a responsibility to team management.The National Athletic Trainers'' Association recently released a consensus statement detailing best practices for sports medicine management in secondary schools and colleges, including the advantages and disadvantages of different models of supervisory relationships in sports medicine.²⁴ Supervisory models in which ATs or team physicians are employed by athletic departments are described as having the potential for conflict of interest in the medical care provided to athletes. Pecci and Laursen²⁵ and Laursen²⁶ have advocated for sports medicine departments to be nested within medical units, such as university health centers, rather than athletic departments. They suggested that this organizational structure would reduce real and perceived conflicts of interest in the care of athletes and would have additional benefits, such as easier access to other health care providers and more centralized oversight of medical care.^25,26 Whereas these arguments are intuitive, no researchers have conducted an empirical evaluation of whether supervisory structure is systematically associated with different types of pressure on clinicians regarding the care of collegiate athletes who have sustained concussions.Another potentially important variable that could modify the pressure that clinicians experience is their sex. Approximately half of all ATs are women, but women represent only about one-quarter of full-time staff ATs and only 1 in 8 head ATs in collegiate sports medicine departments.^27–30 Some investigators³¹ have suggested that male and female ATs may have different experiences interacting with coaches and other ATs in the collegiate athletic environment. Mazerolle et al³¹ conducted qualitative interviews with 14 female NCAA Division I ATs and described how they “often encountered gender discrimination when working with a team sport coached by a man.” They described a perception that coaches view female ATs as “more sympathetic and less pragmatic” than male ATs and that this judgment undermines the coaches'' confidence in the care they provide athletes. This differential perception is reinforced by 2 surveys^32,33 in which male collegiate athletes reported being more comfortable receiving care from male ATs. Stereotypical judgments about women in the workplace tend to be strongest when women are an underrepresented minority, as is the case with female ATs in collegiate sports environments, and can inform the control strategies of individuals in positions of power.³⁴ Quantifying the extent to which pressure is experienced in the care of concussed athletes and whether it is modified by clinician characteristics such as sex are important steps in understanding whether institution-level intervention is needed.Therefore, the purpose of our study was to obtain empirical evidence about whether clinicians who provide care to US collegiate sports teams experienced pressure to prematurely clear athletes for participation after a concussion. We hypothesized that clinicians in sports medicine departments reporting to the athletic department would experience greater pressure from coaches and athletes than clinicians in departments reporting to medical institutions and that female clinicians would experience greater pressure from coaches and athletes than male clinicians would experience.