Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA): The presidential initiative to combat environmental injustice in allergy and immunology-a Work Group Report of the AAAAI VAEDIA task force.

Many vulnerable people lose their health or lives each year as a result of unhealthy environmental conditions that perpetuate medical conditions within the scope of allergy and immunology specialists' expertise. While detrimental environmental factors impact all humans globally, the effect is disproportionately more profound in impoverished neighborhoods. Environmental injustice is the inequitable exposure of disadvantaged populations to environmental hazards. Professional medical organizations such as the American Academy of Allergy, Asthma & Immunology (AAAAI) are well positioned to engage and encourage community outreach volunteer programs to combat environmental justice. Here we discuss how environmental injustices and climate change impacts allergic diseases among vulnerable populations. We discuss pathways allergists/immunologists can use to contribute to addressing environmental determinants by providing volunteer clinical service, education, and advocacy. Furthermore, allergists/immunologists can play a role in building trust within these communities, partnering with other patient advocacy nonprofit stakeholders, and engaging with local, state, national, and international nongovernmental organizations, faith-based organizations, and governments. The AAAAI's Volunteerism Addressing Environmental Disparities in Allergy (VAEDIA) is the presidential task force aiming to promote volunteer initiatives by creating platforms for discussion and collaboration and by funding community-based projects to address environmental injustice.

Prebirth effects of climate change on children's respiratory health.

PURPOSE OF REVIEW: To date, there is no evidence that humanity will implement appropriate mitigation measures to avoid the catastrophic impact of climate change on the planet and human health. Vulnerable populations such as pregnant women and children will be the most affected. This review highlights epidemiologic data on climate change-related prenatal environmental exposures affecting the fetus and children's respiratory health. RECENT FINDINGS: Research on outcomes of prenatal exposure to climate change-related environmental changes and pediatric pulmonary health is limited. In addition to adverse pregnancy outcomes known to affect lung development, changes in lung function, increased prevalence of wheezing, atopy, and respiratory infections have been associated with prenatal exposure to increased temperatures, air pollution, and maternal stress. The mechanisms behind these changes are ill-defined, although oxidative stress, impaired placental functioning, and epigenetic modifications have been observed. However, the long-term impact of these changes remains unknown. SUMMARY: The detrimental impact of the climate crisis on pediatric respiratory health begins before birth, highlighting the inherent vulnerability of pregnant women and children. Research and advocacy, along with mitigation and adaptation measures, must be implemented to protect pregnant women and children, the most affected but the least responsible for the climate crisis.

An Examination of the Intersection of Climate Change, the Physician Specialty Workforce, and Graduate Medical Education in the U.S.

Issue: As U.S. healthcare systems plan for future physician workforce needs, the systemic impacts of climate change, a worldwide environmental and health crisis, have not been factored in. The current focus on increasing the number of trained physicians and optimizing efficiencies in healthcare delivery may be insufficient. Graduate medical education (GME) priorities and training should be considered in order to prepare a climate-educated physician workforce. Evidence: We used a holistic lens to explore the available literature regarding the intersection of future physician workforce needs, GME program priorities, and resident education within the larger context of climate change. Our interinstitutional, transdisciplinary team brought perspectives from their own fields, including climate science, climate and health research, and medical education to provide recommendations for building a climate-educated physician workforce. Implications: Acknowledging and preparing for the effects of climate change on the physician workforce will require identification of workforce gaps, changes to GME program priorities, and education of trainees on the health and societal impacts of climate change. Alignment of GME training with workforce considerations and climate action and adaptation initiatives will be critical in ensuring the U.S. has a climate-educated physician workforce capable of addressing health and healthcare system challenges. This article offers a number of recommendations for physician workforce priorities, resident education, and system-level changes to better prepare for the health and health system impacts of climate change.

Climate change and global issues in allergy and immunology.

The steady increase in global temperatures, resulting from the combustion of fossil fuels and the accumulation of greenhouse gases (GHGs), continues to destabilize all ecosystems worldwide. Although annual emissions must be halved by 2030 and reach net zero by 2050 to limit some of the most catastrophic impacts associated with a warming planet, the world's efforts to curb GHG emissions fall short of the commitments made in the 2015 Paris Agreement. To this effect, July 2021 was recently declared the hottest month ever recorded in 142 years. The ramifications of these changes for global temperatures are complex and further promote outdoor air pollution, pollen exposure, and extreme weather events. Besides worsening respiratory health, air pollution promotes atopy and susceptibility to infections. The effects of GHGs on pollen affect the frequency and severity of asthma and allergic rhinitis. Changes in temperature, air pollution, and extreme weather events exert adverse multisystemic health effects and disproportionally affect disadvantaged and vulnerable populations. This review article is an update for allergists and immunologists about the health impacts of climate change that are already evident in our daily practices. It is also a call to action and advocacy, including to integrate climate change-related mitigation, education, and adaptation measures to protect our patients and avert further injury to our planet.

Utility of a commercial PCR assay and a clinical prediction rule for detection of toxigenic Clostridium difficile in asymptomatic carriers.

A commercial PCR assay of perirectal swab specimens detected 17 (68%) of 25 asymptomatic carriers of toxigenic Clostridium difficile, including 93% with skin and/or environmental contamination. A clinical prediction rule, followed by PCR screening, could be used to identify carriers at high risk of C. difficile shedding.

Functional and immune response to respiratory syncytial virus infection in aged BALB/c mice: a search for genes determining disease severity.

BACKGROUND: Recent studies have demonstrated that respiratory syncytial virus (RSV) is a significant cause of morbidity and mortality in the elderly. The cellular mechanisms that determine the host's susceptibility and severity of the disease are not well understood. In this study, we sought a mouse model of human respiratory disease by studying the functional and cellular response to RSV in aged animals. METHODS: Aged BALB/c mice (>10 months of age) were infected with human RSV (strain A2) and compared with sham-infected mice. Clinical progress of the illness was monitored by daily assessment of weight changes and mortality. The animals were sacrificed four days postinfection. Lung pathology was obtained and viral titers were measured by plaque assay. Gene expression profiles were studied from lung tissue RNA using gene array. RESULTS: RSV produced significant clinical illness in aged mice as evidenced by a 15% weight loss and a 10% mortality rate. Lung pathology revealed inflammatory changes with a predominance of neutrophils and diffuse alveolar damage. Microarray analysis revealed variable profiles of gene activation/downregulation at day 4 postinfection. RSV infection resulted in a proinflammatory response. Surprisingly, some of the genes involved in antigen-processing pathway were downregulated, specifically, genes implicated in the major histocompatibility complex (MHC) class II pathway. CONCLUSIONS: Our findings indicate that RSV infection produces profound functional and cellular changes in aged mice thus resembling the human disease described in the elderly. Further studies will be needed to understand the cellular mechanisms involved in the host response to RSV in aged mice.

Effect of an enhanced medical home on serious illness and cost of care among high-risk children with chronic illness: a randomized clinical trial.

IMPORTANCE: Patient-centered medical homes have not been shown to reduce adverse outcomes or costs in adults or children with chronic illness. OBJECTIVE: To assess whether an enhanced medical home providing comprehensive care prevents serious illness (death, intensive care unit [ICU] admission, or hospital stay >7 days) and/or reduces costs among children with chronic illness. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of high-risk children with chronic illness (≥3 emergency department visits, ≥2 hospitalizations, or ≥1 pediatric ICU admissions during previous year, and >50% estimated risk for hospitalization) treated at a high-risk clinic at the University of Texas, Houston, and randomized to comprehensive care (n = 105) or usual care (n = 96). Enrollment was between March 2011 and February 2013 (when predefined stopping rules for benefit were met) and outcome evaluations continued through August 31, 2013. INTERVENTIONS: Comprehensive care included treatment from primary care clinicians and specialists in the same clinic with multiple features to promote prompt effective care. Usual care was provided locally in private offices or faculty-supervised clinics without modification. MAIN OUTCOMES AND MEASURES: Primary outcome: children with a serious illness (death, ICU admission, or hospital stay >7 days), costs (health system perspective). Secondary outcomes: individual serious illnesses, medical services, Medicaid payments, and medical school revenues and costs. RESULTS: In an intent-to-treat analysis, comprehensive care decreased both the rate of children with a serious illness (10 per 100 child-years vs 22 for usual care; rate ratio [RR], 0.45 [95% CI, 0.28-0.73]), and total hospital and clinic costs ($16,523 vs $26,781 per child-year, respectively; cost ratio, 0.58 [95% CI, 0.38-0.88]). In analyses of net monetary benefit, the probability that comprehensive care was cost neutral or cost saving was 97%. Comprehensive care reduced (per 100 child-years) serious illnesses (16 vs 44 for usual care; RR, 0.33 [95% CI, 0.17-0.66]), emergency department visits (90 vs 190; RR, 0.48 [95% CI, 0.34-0.67]), hospitalizations (69 vs 131; RR, 0.51 [95% CI, 0.33-0.77]), pediatric ICU admissions (9 vs 26; RR, 0.35 [95% CI, 0.18-0.70]), and number of days in a hospital (276 vs 635; RR, 0.36 [95% CI, 0.19-0.67]). Medicaid payments were reduced by $6243 (95% CI, $1302-$11,678) per child-year. Medical school losses (costs minus revenues) increased by $6018 (95% CI, $5506-$6629) per child-year. CONCLUSIONS AND RELEVANCE: Among high-risk children with chronic illness, an enhanced medical home that provided comprehensive care to promote prompt effective care vs usual care reduced serious illnesses and costs. These findings from a single site of selected patients with a limited number of clinicians require study in larger, broader populations before conclusions about generalizability to other settings can be reached. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02128776.

Characteristics and outcomes of Clostridioides difficile infection after a change in the diagnostic testing algorithm.

BACKGROUND: Polymerase chain reaction (PCR) testing for the detection of C. difficile is a highly sensitive test. Some clinical laboratories have included a 2-step testing algorithm utilizing PCR plus toxin enzyme immunoassays (EIAs) to increase specificity. OBJECTIVE: To determine the risk factors and outcomes of C. difficile PCR-positive/toxin-positive encounters compared to PCR-positive/toxin-negative encounters. DESIGN: Retrospective study. SETTING: A Veterans' Affairs hospital. METHODS: A retrospective case-control study of patient encounters with a positive C. difficile test by PCR and either a toxin EIA-positive assay (ie, cases) or toxin EIA-negative assay (ie, controls). Clinically relevant exposures and risk factors were determined to assess CDI recurrence at 30 days. Available encounter stool specimens were cultured for C. difficile and were subjected to restriction endonuclease analysis (REA) strain typing. RESULTS: Among 130 C. difficile PCR-positive patient encounters, 80 (61.5%) were toxin EIA negative and 50 (38.5%) were toxin EIA positive. Encounters that were toxin positive were more frequently treated (96.0%) compared to toxin-negative encounters (71.3%; P < .01). A multivariable logistic regression model revealed that toxin-negative encounters were less likely to suffer a recurrent CDI episode within 30 days (odds ratio [OR], 0.20, 95% confidence interval [CI], 0.05-0.83). Additionally, a higher C. difficile PCR cycle threshold predicted a lower risk of CDI recurrence at 30 days. (OR, 0.82; 95% CI, 0.68-0.98). During the study period, the REA group Y strain accounted for most toxin-negative encounters (32.5%; P = .05), whereas REA group BI strain accounted for most toxin-positive encounters (24.3%; P = .02). CONCLUSIONS: A testing strategy of PCR plus toxin EIA helped predict recurrent CDI.

Important clinical advances in the understanding of Clostridium difficile infection.

PURPOSE OF REVIEW: Clostridium difficile remains an important cause of infectious colitis, particularly in healthcare facilities. This review summarizes recent advances in the epidemiology, diagnosis, and treatment of this endemic pathogen. RECENT FINDINGS: C. difficile infection (CDI) hospitalizations and mortality rates have increased over the last decade. The BI/NAP1/027 strain has been responsible for epidemics with increased severity and mortality and is now endemic in many settings, particularly North America. Concurrent antibiotics have now been shown to decrease the cure rates for anti-C. difficile therapy and increase the risk of recurrence. Although studies implicate proton pump inhibitors as a risk for CDI, the magnitude of and the biological basis for that risk remain unclear. Molecular diagnostic techniques are rapid and sensitive but highlight the importance of using appropriate clinical testing criteria. Fidaxomicin is a promising new therapy associated with decreased recurrence; infections due to BI strains, however, are associated with inferior outcomes regardless of the treatment agent. Fecal transplantation continues to have impressive success rates for patients with recurrent CDI, and a new colon-sparing surgical procedure presents an intriguing suggested alternative to total colectomy in severe, complicated cases. SUMMARY: Elucidating CDI risk factors, identifying rapid, accurate diagnostic tools, and validating new treatment approaches remains an urgent priority.

Effect of the COVID-19 Pandemic on Rates and Epidemiology of Clostridioides difficile Infection in One VA Hospital.

The COVID-19 pandemic was associated with increases in some healthcare-associated infections. We investigated the impact of the pandemic on the rates and molecular epidemiology of Clostridioides difficile infection (CDI) within one VA hospital. We anticipated that the potential widespread use of antibiotics for pneumonia during the pandemic might increase CDI rates given that antibiotics are a major risk for CDI. Hospital data on patients with CDI and recurrent CDI (rCDI) were reviewed both prior to the COVID-19 pandemic (2015 to 2019) and during the pandemic (2020-2021). Restriction endonuclease analysis (REA) strain typing was performed on CD isolates recovered from stool samples collected from October 2019 to March 2022. CDI case numbers declined by 43.2% in 2020 to 2021 compared to the annual mean over the previous 5 years. The stool test positivity rate was also lower during the COVID-19 pandemic (14.3% vs. 17.2%; p = 0.013). Inpatient hospitalization rates declined, and rates of CDI among inpatients were reduced by 34.2% from 2020 to 2021. The mean monthly cases of rCDI also declined significantly after 2020 [3.38 (95% CI: 2.89-3.87) vs. 1.92 (95% CI: 1.27-2.56); p = <0.01]. Prior to the pandemic, REA group Y was the most prevalent CD strain among the major REA groups (27.3%). During the first wave of the pandemic, from 8 March 2020, to 30 June 2020, there was an increase in the relative incidence of REA group BI (26.7% vs. 9.1%); After adjusting for CDI risk factors, a multivariable logistic regression model revealed that the odds of developing an REA group BI CDI increased during the first pandemic wave (OR 6.41, 95% CI: 1.03-39.91) compared to the pre-pandemic period. In conclusion, the incidence of CDI and rCDI decreased significantly during the COVID-19 pandemic. In contrast, REA BI (Ribotype 027), a virulent, previously epidemic CD strain frequently associated with hospital transmission and outbreaks, reappeared as a prevalent strain during the first wave of the pandemic, but subsequently disappeared, and overall CDI rates declined.

Evaluating the Impact of a Urinalysis to Reflex Culture Process Change in the Emergency Department at a Veterans Affairs Hospital.

Background: Although automated urine cultures (UCs) following urinalysis (UA) are often used in emergency departments (EDs) to identify urinary tract infections (UTIs), results are often reported as no organism growth or the growth of clinically insignificant organisms, leading to the overdetection and overtreatment of asymptomatic bacteriuria (ASB). Methods: A process change was implemented at a US Department of Veterans Affairs medical center ED that automatically cancelled UCs if UAs had < 5 white blood cells per high-power field (WBC/HPF). An option for do not cancel (DNC) UC was available. Data were prospectively collected for 3 months postimplementation and included UA/UC results, presence of UTI symptoms, antibiotics prescribed, and health care utilization. Results: Postintervention, 684 UAs (37.2%) were evaluated from ED visits. Postintervention, of 255 UAs, 95 (37.3%) were negative with UC cancelled, 95 (37.3%) were positive with UC processed, 43 (16.9%) were ordered as DNC, and 22 (8.6%) were ordered without a UC. UC processing despite a negative UA significantly decreased from 100% preintervention to 38.6% postintervention (P < .001). Inappropriate prescribing of antibiotics for ASB was reduced from 10.2% preintervention to 1.9% postintervention (odds ratio = 0.17; P = .01). In patients with negative UA specimens, antibiotic prescribing decreased by 25.3% postintervention. No reports of outpatient, ED, or hospital visits for symptomatic UTI were found within 7 days of the initial UA postintervention. Conclusions: The UA to reflex culture process change resulted in a significant reduction in processing of inappropriate UCs and unnecessary antibiotic use for ASB. There were no missed UTIs or other adverse patient outcomes.

Pulmonary Manifestations of Immunodeficiency and Immunosuppressive Diseases Other than Human Immunodeficiency Virus.

Immune deficiencies may alter normal lung function and protective mechanisms, resulting in a myriad of pulmonary manifestations. Primary immunodeficiencies involve multiple branches of the immune system, and defects may predispose to recurrent upper and lower respiratory infections by common pathogens; opportunistic infections; and autoimmune, inflammatory, and malignant processes that may result in interstitial pneumonias. Secondary immunodeficiencies may result from neoplasms or their treatment, organ transplant and immunosuppression, and from autoimmune diseases and their treatments. Primary and secondary immunodeficiencies and their pulmonary manifestations may be difficult to diagnose and treat. A multidisciplinary approach to evaluation is essential.

Association of Air Pollution and Heat Exposure With Preterm Birth, Low Birth Weight, and Stillbirth in the US: A Systematic Review.

Importance: Knowledge of whether serious adverse pregnancy outcomes are associated with increasingly widespread effects of climate change in the US would be crucial for the obstetrical medical community and for women and families across the country. Objective: To investigate prenatal exposure to fine particulate matter (PM2.5), ozone, and heat, and the association of these factors with preterm birth, low birth weight, and stillbirth. Evidence Review: This systematic review involved a comprehensive search for primary literature in Cochrane Library, Cochrane Collaboration Registry of Controlled Trials, PubMed, ClinicalTrials.gov website, and MEDLINE. Qualifying primary research studies included human participants in US populations that were published in English between January 1, 2007, and April 30, 2019. Included articles analyzed the associations between air pollutants or heat and obstetrical outcomes. Comparative observational cohort studies and cross-sectional studies with comparators were included, without minimum sample size. Additional articles found through reference review were also considered. Articles analyzing other obstetrical outcomes, non-US populations, and reviews were excluded. Two reviewers independently determined study eligibility. The Arskey and O'Malley scoping review framework was used. Data extraction was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Findings: Of the 1851 articles identified, 68 met the inclusion criteria. Overall, 32 798 152 births were analyzed, with a mean (SD) of 565 485 (783 278) births per study. A total of 57 studies (48 of 58 [84%] on air pollutants; 9 of 10 [90%] on heat) showed a significant association of air pollutant and heat exposure with birth outcomes. Positive associations were found across all US geographic regions. Exposure to PM2.5 or ozone was associated with increased risk of preterm birth in 19 of 24 studies (79%) and low birth weight in 25 of 29 studies (86%). The subpopulations at highest risk were persons with asthma and minority groups, especially black mothers. Accurate comparisons of risk were limited by differences in study design, exposure measurement, population demographics, and seasonality. Conclusions and Relevance: This review suggests that increasingly common environmental exposures exacerbated by climate change are significantly associated with serious adverse pregnancy outcomes across the US.

Sequential introduction of a multistep testing algorithm and nucleic acid amplification testing leading to an increase in Clostridioides difficile detection and a trend toward increased strain diversity.

BACKGROUND: Most clinical microbiology laboratories have replaced toxin immunoassay (EIA) alone with multistep testing (MST) protocols or nucleic acid amplification testing (NAAT) alone for the detection of C. difficile. OBJECTIVE: Study the effect of changing testing strategies on C. difficile detection and strain diversity. DESIGN: Retrospective study. SETTING: A Veterans' Affairs hospital. METHODS: Initially, toxin EIA testing was replaced by an MST approach utilizing a glutamate dehydrogenase (GDH) and toxin EIA followed by tcdB NAAT for discordant results. After 18 months, MST was replaced by a NAAT-only strategy. Available patient stool specimens were cultured for C. difficile. Restriction endonuclease analysis (REA) strain typing and quantitative in vitro toxin testing were performed on recovered isolates. RESULTS: Before MST (toxin EIA), 79 of 708 specimens (11%) were positive, and after MST (MST-A), 121 of 517 specimens (23%) were positive (P < .0001). Prior to NAAT-only testing (MST-B), 80 of the 490 specimens (16%) were positive by MST, and after NAAT-only testing was implemented, 67 of the 368 specimens (18%) were positive (P = nonsignificant). After replacing toxin EIA testing, REA strain group diversity increased (8, 13, 13, and 10 REA groups in the toxin EIA, MST-A, MST-B, and NAAT-only periods, respectively) and in vitro toxin concentration decreased. The average log10 toxin concentration of the isolates were 2.08, 1.88, 1.20 and 1.55 ng/mL for the same periods, respectively. CONCLUSIONS: MST and NAAT had similar detection rates for C. difficile. Compared to toxin testing alone, they detected increased diversity of C. difficile strains, many of which were low toxin producing.

Clusters of nontuberculous mycobacteria linked to water sources at three Veterans Affairs medical centers.

OBJECTIVE: To characterize nontuberculous mycobacteria (NTM) associated with case clusters at 3 medical facilities. DESIGN: Retrospective cohort study using molecular typing of patient and water isolates. SETTING: Veterans Affairs Medical Centers (VAMCs). METHODS: Isolation and identification of NTM from clinical and water samples using culture, MALDI-TOF, and gene population sequencing to determine species and genetic relatedness. Clinical data were abstracted from electronic health records. RESULTS: An identical strain of Mycobacterium conceptionense was isolated from 41 patients at VA Medical Centers (VAMCs A, B, and D), and from VAMC A's ICU ice machine. Isolates were initially identified as other NTM species within the M. fortuitum clade. Sequencing analyses revealed that they were identical M. conceptionense strains. Overall, 7 patients (17%) met the criteria for pulmonary or nonpulmonary infection with NTM, and 13 of 41 (32%) were treated with effective antimicrobials regardless of infection or colonization status. Separately, a M. mucogenicum patient strain from VAMC A matched a strain isolated from a VAMC B ICU ice machine. VAMC C, in a different state, had a 4-patient cluster with Mycobacterium porcinum. Strains were identical to those isolated from sink-water samples at this facility. CONCLUSION: NTM from hospital water systems are found in hospitalized patients, often during workup for other infections, making attribution of NTM infection problematic. Variable NTM identification methods and changing taxonomy create challenges for epidemiologic investigation and linkage to environmental sources.

Reinforcement of an infection control bundle targeting prevention practices for Clostridioides difficile in Veterans Health Administration nursing homes.

BACKGROUND: Clostridioides difficile infection (CDI) causes significant morbidity in nursing home residents. Our aim was to describe adherence to a bundled CDI prevention initiative, which had previously been deployed nationwide in Veterans Health Administration (VA) long-term care facilities (LTCFs), and to improve compliance with reinforcement. METHODS: A multicenter pre- and post-reinforcement of the VA bundle consisting of environmental management, hand hygiene, and contact precautions was conducted in 6 VA LTCFs. A campaign to reinforce VA bundle components, as well as to promote select antimicrobial stewardship recommendations and contact precautions for 30 days, was employed. Hand hygiene, antimicrobial usage, and environmental contamination, before and after bundle reinforcement, were assessed. RESULTS: All LTCFs reported following the guidelines for cleaning and contact precautions until diarrhea resolution pre-reinforcement. Environmental specimens rarely yielded C difficile pre- or post-reinforcement. Proper hand hygiene across all facilities did not change with reinforcement (pre 52.51%, post 52.18%), nor did antimicrobial use (pre 87-197 vs. post 84-245 antibiotic days per 1,000 resident-days). LTCFs found it challenging to maintain prolonged contact precautions. DISCUSSION: Variation in infection prevention and antimicrobial prescribing practices across LTCFs were identified and lessons learned. CONCLUSIONS: Introducing bundled interventions in LTCFs is challenging, given the available resources, and may be more successful with fewer components and more intensive execution with feedback.

Changes in intestinal Toll-like receptors and cytokines precede histological injury in a rat model of necrotizing enterocolitis.

It is unclear whether the broad inflammatory response shown in neonatal necrotizing enterocolitis (NEC) is the cause or the effect of tissue injury. Toll-like receptors (TLRs) on intestinal dendritic, mononuclear, and epithelial cells recognize bacterial ligands and damaged tissues, thus activating the inflammatory response. The present study aimed to determine whether active TLR signaling would precede histological injury in NEC. Newborn rat pups were divided into four groups: dam fed, dam fed-hypoxic, formula fed, and formula fed-hypoxic (NEC). The ileal tissues were evaluated for NEC scores at 24, 48, 72, and 120 h. Quantitative real-time reverse transcription-polymerase chain reaction and immunohistochemistry were used to measure and localize intestinal TLRs. Cytokines were assessed by a multispot cytokine array. Among the four groups, ileal injury was seen only after 72 h of formula feeding and hypoxia. We found selective induction of mRNA levels in NEC compared with dam-fed controls for TLR2 > TLR4 > TLR1 = TLR3, TLR7, and TLR9 > TLR6 (P < 0.01); TLR5 was downregulated (P < 0.01). All TLR changes started at 48 h, before any histological evidence of NEC. Both Th1-type cytokines (IFN-gamma, IL-1beta, TNF-alpha, and KC/GRO) and Th2-type cytokines (IL-4, IL-5 and IL-13) were significantly increased in NEC but also in nondamaged formula-fed rat ileum. In conclusion, the intestinal expression of TLRs and cytokines precedes histological injury in the experimental NEC.

The emerging role of immune dysfunction in mitochondrial diseases as a paradigm for understanding immunometabolism.

Immunometabolism aims to define the role of intermediary metabolism in immune cell function, with bioenergetics and the mitochondria recently taking center stage. To date, the medical literature on mitochondria and immune function extols the virtues of mouse models in exploring this biologic intersection. While the laboratory mouse has become a standard for studying mammalian biology, this model comprises part of a comprehensive approach. Humans, with their broad array of inherited phenotypes, serve as a starting point for studying immunometabolism; specifically, patients with mitochondrial disease. Using this top-down approach, the mouse as a model organism facilitates further exploration of the consequences of mutations involved in mitochondrial maintenance and function. In this review, we will discuss the emerging phenotype of immune dysfunction in mitochondrial disease as a model for understanding the role of the mitochondria in immune function in available mouse models.

Transmission of Clostridium difficile from asymptomatically colonized or infected long-term care facility residents.

OBJECTIVE: To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions. DESIGN: A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS). SETTING: Veterans Affairs hospital and affiliated LTCF.ParticipantsThe study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases. RESULTS: Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases. CONCLUSIONS: Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.