Faculty Bibliography

Little is known regarding the impact of immigrant acculturation on the gut microbiome. We characterized differences in the gut microbiome between racially/ethnically diverse US immigrant and US-born groups, and determined the impact of dietary acculturation on the microbiome. Stool samples were collected from 863 US residents, including US-born (315 White, 93 Black, 40 Hispanic) and foreign-born (105 Hispanic, 264 Korean) groups. We determined dietary acculturation from dissimilarities based on food frequency questionnaires, and used 16S rRNA gene sequencing to characterize the microbiome. Gut microbiome composition differed across study groups, with the largest difference between foreign-born Koreans and US-born Whites, and significant differences also observed between foreign-born and US-born Hispanics. Differences in sub-operational taxonomic unit (s-OTU) abundance between foreign-born and US-born groups tended to be distinct from differences between US-born groups. Bacteroides plebeius, a seaweed-degrading bacterium, was strongly enriched in foreign-born Koreans, while Prevotella copri and Bifidobacterium adolescentis were strongly enriched in foreign-born Koreans and Hispanics, compared with US-born Whites. Dietary acculturation in foreign-born participants was associated with specific s-OTUs, resembling abundance in US-born Whites; e.g., a Bacteroides plebeius s-OTU was depleted in highly diet-acculturated Koreans. In summary, we observed that US nativity is a determinant of the gut microbiome in a US resident population. Dietary acculturation may result in loss of native species in immigrants, though further research is necessary to explore whether acculturation-related microbiome alterations have consequences for immigrant health.

Patients with systemic lupus erythematosus (SLE) are at increased risk for infection including opportunistic infections. Fungal infection in particular can be difficult to diagnose and treat and often can be life-threatening in the immunocompromised patient. We present a case in which a patient with SLE presented to the hospital with shortness of breath and cough. Throughout the hospital course, the patient's condition continued to decline leading to acute respiratory failure, and eventually, the patient expired. Postmortem autopsy revealed invasive fungal aspergillosis infection involving the heart, lungs, and brain. Earlier diagnosis and treatment with empiric antifungals may improve survival in these patients.

Plazomicin was tested against 697 recently acquired carbapenem resistant Klebsiella pneumoniae isolates from the Great Lakes Region of the United States. Plazomicin MIC₅₀ and MIC₉₀ values were 0.25 and 1 mg/L, respectively; 680 isolates were susceptible (97.6%, MIC ≤ 2 mg/L), 9 intermediate (1.3%, MIC 4mg/L), and 8 resistant (1.1%, MIC > 32 mg/L). Resistance was associated with rmtF-, rmtB- or armA-encoded 16S ribosomal RNA methyltransferases, in all but one isolate.

Hypervirulent Klebsiella pneumoniae strains are the major causes of liver abscesses throughout East Asia, and these strains are usually antibiotic susceptible. Recently, multidrug resistant and hypervirulent (MDR-HV) K. pneumoniae strain emerged, arisen by hypervirulent strains acquiring antimicrobial resistance determinants or the transfer of a virulence plasmid into a classic MDR strain. In this study, we characterized the clinical and microbiological properties of K. pneumoniae liver abscess (KPLA) caused by MDR-HV strains in Taiwan. Patients with community-onset KPLA were retrospectively identified at Taipei Veterans General Hospital during January 2013 and May 2018. Antimicrobial resistance mechanisms, capsular types, and sequence types were determined. MDR-HV strains and their parental antimicrobial-susceptible strains further underwent whole genome sequencing (WGS) and in vivo mice lethality test. Thirteen MDR-HV strains were identified from a total of 218 KPLA episodes. MDR-HV strains resulted in similar outcomes to antimicrobial-susceptible strains. All MDR-HV strains were traditional hypervirulent clones carrying virulence capsular types. The major resistance mechanisms were the overexpression of efflux pumps and/or the acquisition of ESBL or AmpC β-lactamase genes. WGS showed two hypervirulent strains evolved to MDR phenotype after having a mutation in ramR and acquiring a SHV-12-bearing plasmid, respectively. Both the MDR-HV strains retained high virulence in comparison to their parental strains. The spread of MDR-HV K. pneumoniae strains in the community raises significant public concerns, and measures should be taken to prevent the further acquisition of carbapenemase and other resistance genes among these strains in order to avoid the occurrence of untreatable KPLA.

The continued use of pyrazinamide in the treatment of tuberculosis in the absence of a rapid, accurate and standardized pyrazinamide drug susceptibility assays is of great concern. While whole genome sequencing holds promise, it is not yet feasible option in low resource settings as it requires expensive instruments and bioinformatic analysis. We investigated the diagnostic performance of a closed-tube Linear-After-The-Exponential (LATE)-PCR assay for pyrazinamide susceptibility in Mycobacterium tuberculosis. Based on a set of 654 clinical Mycobacterium tuberculosis culture isolates with known mutations throughout the pncA gene as determined by Sanger sequencing, the assay displays excellent sensitivity of 96.9% (95% CI: 95.2-98.6) and specificity of 97.9% (95% CI: 96.1-99.7). In a subset of 384 isolates with phenotypic drug susceptibility testing, we also observed high sensitivity of 98.9% (95% CI: 97.5-100) but lower specificity of 91.8% (95% CI: 87.9-95.8) when compared to phenotypic drug susceptibility testing. We conclude that the LATE PCR assay offers both a rapid and accurate prediction of pyrazinamide susceptibility.

BACKGROUND:Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. METHODS:CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227. FINDINGS/RESULTS:1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died. INTERPRETATION/CONCLUSIONS:Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales. FUNDING/BACKGROUND:National Institutes of Health.

OBJECTIVE:This analysis examined whether specific social, physical, and financial factors were associated with diet quality among older, community-dwelling women. METHODS:This cross-sectional analysis was conducted in a subset of 6,094 community-dwelling Women's Health Initiative participants who completed a food frequency questionnaire, administered from 2012 to 2013, and a self-administered supplemental questionnaire, administered approximately 1 year later. The supplemental questionnaire included five questions assessing social, physical, and financial factors related to eating. Diet quality was assessed with the Healthy Eating Index-2010 (HEI-2010; range of 0-100; higher score indicates a higher quality diet). The total HEI-2010 score was calculated by summing individual scores representing the intake of nine adequacy components (beneficial food groups) and three moderation components (food groups to limit). Associations of responses to the five questions on the supplemental questionnaire with HEI-2010 scores were examined with multiple linear regression, adjusting for relevant covariates. RESULTS:Mean ± standard deviation age of participants was 78.8 ± 6.7 years. Reporting eating fewer than two meals per day, having dental or other mouth problems causing problems with eating, and not always being able to shop, cook, or feed oneself were associated with statistically significantly lower HEI-2010 scores, compared with those not reporting these issues, after multivariable adjustment: 5.37, 2.98, and 2.39 lower scores, respectively (all P values <0.0001). Reporting eating alone most of the time and not always having enough money to buy food were not associated with HEI-2010 scores. CONCLUSIONS:Among older, community-dwelling women, eating fewer than two meals per day, dental and other mouth problems, and diminished ability to shop for food, prepare meals, and feed oneself were associated with lower diet quality. These are potential targets for interventions to improve diet quality in older women. : Video Summary:http://links.lww.com/MENO/A561.

Background/UNASSIGNED:Endoscopic ultrasound-guided fine-needle aspiration and biopsy (EUS-FNA/FNB) has been traditionally used for making a tissue diagnosis. Several newer techniques are emerging as a viable alternative to EUS-FNA/FNB, including mucosal incision-assisted biopsy (MIAB), with a view to increasing the diagnostic yield for upper gastrointestinal (GI) subepithelial tumors (SETs). We conducted a systematic review and meta-analysis to describe the overall diagnostic yield of MIAB for upper GI SETs. Methods/UNASSIGNED:Multiple electronic databases (MEDLINE, EMBASE and Google Scholar) and conference abstracts were comprehensively searched. The primary outcome of our meta-analysis was the overall diagnostic yield of the MIAB. The secondary outcome was to study complications in terms of perforation and clinically significant bleeding. The meta-analysis was performed using a DerSimonian and Laird random-effect model. Results/UNASSIGNED:=57.43%) and no perforations were reported. Conclusions/UNASSIGNED:MIAB is a safe and effective technique for the diagnosis of upper GI SETs and can be considered as a viable alternative to EUS-FNA/FNB. MIAB can be performed during routine endoscopy and no advanced equipment is required.

BACKGROUND:Previous studies have shown that patients have specific expectations regarding physician dress. Japan has a cultural background that is in many ways distinct from western countries. Thus, physician attire may have a different impact in Japan. METHODS:We conducted a multicenter, cross-sectional study to examine patients' preferences for and perceptions of physician attire in Japan. The questionnaire was developed using photographs of either a male or female physician dressed in seven different forms of attire, and it was randomly distributed to inpatients and outpatients. Respondents were asked to rate the provider pictured; they were also asked to provide preferences for different forms of attire in varied clinical settings. Preference was evaluated for five domains (knowledgeable, trustworthy, caring, approachable, and comfortable). We also assessed variation in preferences for attire by respondent characteristics. RESULTS:A total of 1,233 (61%) patients indicated that physician dress was important, and 950 (47%) patients agreed that it influenced their satisfaction with care. Compared with all forms, casual attire with a white coat was the most preferred dress. Older patients more often preferred formal attire with a white coat in primary care and hospital settings. In addition, physician attire had a greater impact on older respondents' satisfaction and experience. CONCLUSION/CONCLUSIONS:The majority of Japanese patients indicated that physician attire is important and influenced their satisfaction with care. Geography, settings of care, and patient age appear to play a role in patient preferences.