Estimating Waterborne Infectious Disease Burden by Exposure Route, United States, 2014.

More than 7.15 million cases of domestically acquired infectious waterborne illnesses occurred in the United States in 2014, causing 120,000 hospitalizations and 6,600 deaths. We estimated disease incidence for 17 pathogens according to recreational, drinking, and nonrecreational nondrinking (NRND) water exposure routes by using previously published estimates. In 2014, a total of 5.61 million (95% credible interval [CrI] 2.97-9.00 million) illnesses were linked to recreational water, 1.13 million (95% CrI 255,000-3.54 million) to drinking water, and 407,000 (95% CrI 72,800-1.29 million) to NRND water. Recreational water exposure was responsible for 36%, drinking water for 40%, and NRND water for 24% of hospitalizations from waterborne illnesses. Most direct costs were associated with pathogens found in biofilms. Estimating disease burden by water exposure route helps direct prevention activities. For each exposure route, water management programs are needed to control biofilm-associated pathogen growth; public health programs are needed to prevent biofilm-associated diseases.

Dysregulated Neutrophil Phenotype and Function in Hospitalised Non-ICU COVID-19 Pneumonia.

Rationale: Infection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based on transcriptomics or single functional assays. Cell functions are interwoven pathways, and understanding the effect across the spectrum of neutrophil function may identify therapeutic targets. Objectives: Examine neutrophil phenotype and function in 41 hospitalised, non-ICU COVID-19 patients versus 23 age-matched controls (AMC) and 26 community acquired pneumonia patients (CAP). Methods: Isolated neutrophils underwent ex vivo analyses for migration, bacterial phagocytosis, ROS generation, NETosis and receptor expression. Circulating DNAse 1 activity, levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI were measured and correlated to clinical outcome. Serial sampling on day three to five post hospitalization were also measured. The effect of ex vivo PI3K inhibition was measured in a further cohort of 18 COVID-19 patients. Results: Compared to AMC and CAP, COVID-19 neutrophils demonstrated elevated transmigration (p = 0.0397) and NETosis (p = 0.0332), and impaired phagocytosis (p = 0.0036) associated with impaired ROS generation (p < 0.0001). The percentage of CD54+ neutrophils (p < 0.001) was significantly increased, while surface expression of CD11b (p = 0.0014) and PD-L1 (p = 0.006) were significantly decreased in COVID-19. COVID-19 and CAP patients showed increased systemic markers of NETosis including increased cfDNA (p = 0.0396) and impaired DNAse activity (p < 0.0001). The ex vivo inhibition of PI3K γ and δ reduced NET release by COVID-19 neutrophils (p = 0.0129). Conclusions: COVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration and NETosis, and impaired antimicrobial responses. These changes highlight that targeting neutrophil function may help modulate COVID-19 severity.

Inflammation, ageing and diseases of the lung: Potential therapeutic strategies from shared biological pathways.

Lung diseases disproportionately affect elderly individuals. The lungs form a unique environment: a highly elastic organ with gaseous exchange requiring the closest proximity of inhaled air containing harmful agents and the circulating blood. The lungs are highly susceptible to senescence, with age and 'inflammageing' creating a pro-inflammatory environment with a reduced capacity to deal with challenges. While lung diseases may have disparate causes, the burden of ageing and inflammation provides a common process that can exacerbate seemingly unrelated pathologies. However, these shared pathways may also provide a common route to treatment, with increased interest in drugs that target ageing processes across respiratory diseases. In this review, we will examine the evidence for the increased burden of lung disease in older adults, the structural and functional changes seen with advancing age and assess what our expanding knowledge of inflammation and ageing pathways could mean for the treatment of lung disease. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

Extensively Drug-Resistant Typhoid Fever in the United States.

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

Ongoing Outbreak of Extensively Drug-Resistant Campylobacter jejuni Infections Associated With US Pet Store Puppies, 2016-2020.

Importance: Extensively drug-resistant Campylobacter jejuni infections cannot be treated with any commonly recommended antibiotics and pose an increasing public health threat. Objectives: To investigate cases of extensively drug-resistant C jejuni associated with pet store puppies and describe the epidemiologic and laboratory characteristics of these infections. Design, Setting, and Participants: In August 2017, health officials identified, via survey, patients with C jejuni infections who reported contact with puppies sold by pet stores. In conjunction with state and federal partners, the Centers for Disease Control and Prevention investigated cases of culture-confirmed C jejuni infections in US patients with an epidemiologic or molecular association with pet store puppies between January 1, 2016, and February 29, 2020. Available records from cases occurring before 2016 with genetically related isolates were also obtained. Main Outcomes and Measures: Patients were interviewed about demographic characteristics, health outcomes, and dog exposure during the 7 days before illness onset. Core genome multilocus sequence typing was used to assess isolate relatedness, and genomes were screened for resistance determinants to predict antibiotic resistance. Isolates resistant to fluoroquinolones, macrolides, and 3 or more additional antibiotic classes were considered to be extensively drug resistant. Cases before 2016 were identified by screening all sequenced isolates submitted for surveillance using core genome multilocus sequence typing. Results: A total of 168 patients (median [interquartile range] age, 37 [19.5-51.0] years; 105 of 163 female [64%]) with an epidemiologic or molecular association with pet store puppies were studied. A total of 137 cases occurred from January 1, 2016, to February 29, 2020, with 31 additional cases dating back to 2011. Overall, 117 of 121 patients (97%) reported contact with a dog in the week before symptom onset, of whom 69 of 78 (88%) with additional information reported contact with a pet store puppy; 168 isolates (88%) were extensively drug resistant. Traceback investigation did not implicate any particular breeder, transporter, distributer, store, or chain. Conclusions and Relevance: Strains of extensively drug-resistant C jejuni have been circulating since at least 2011 and are associated with illness among pet store customers, employees, and others who come into contact with pet store puppies. The results of this study suggest that practitioners should ask about puppy exposure when treating patients with Campylobacter infection, especially when they do not improve with routine antibiotics, and that the commercial dog industry should take action to help prevent the spread of extensively drug-resistant C jejuni from pet store puppies to people.

New Pharmacological Tools to Target Leukocyte Trafficking in Lung Disease.

Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

Myalgia as a Symptom of Envenomation by the Eastern Coral Snake, Micrurus Fulvius: A Case Report.

We present the case of a patient who developed myalgia as the primary symptom of envenomation by the eastern coral snake, Micrurus fulvius. The patient was evaluated and treated in the emergency department. Physical examination did not demonstrate any neuromuscular abnormalities. On consultation with the poison control center, the patient's myalgia was determined to be an effect of envenomation, and 5 vials of North American coral snake antivenin were administered. The patient was admitted to the intensive care unit where his symptoms resolved. He was discharged the following day after remaining asymptomatic for 24 h.

Mitigating Health Risks to Reopen a Clinical Research Laboratory During the COVID-19 Pandemic: A Framework.

BACKGROUND: The COVID-19 pandemic has led to many countries implementing lockdown procedures, resulting in the suspension of laboratory research. With lockdown measures now easing in some areas, many laboratories are preparing to reopen. This is particularly challenging for clinical research laboratories due to the dual risk of patient samples carrying the virus that causes COVID-19, SARS-CoV-2, and the risk to patients being exposed to research staff during clinical sampling. To date, no confirmed transmission of the virus has been confirmed within a laboratory setting; however, operating processes and procedures should be adapted to ensure safe working of samples of positive, negative, or unknown COVID-19 status. OBJECTIVE: In this paper, we propose a framework for reopening a clinical research laboratory and resuming operations with the aim to maximize research capacity while minimizing the risk to research participants and staff. METHODS: This framework was developed by consensus among experienced laboratory staff who have prepared to reopen a clinical research laboratory. RESULTS: Multiple aspects need to be considered to reopen a clinical laboratory. We describe our process to stratify projects by risk, including assessment of donor risk and COVID-19 clinical status, the COVID-19 status of the specific sample type, and how to safely process each sample type. We describe methods to prepare the laboratory for safe working including maintaining social distancing through signage, one-way systems and access arrangements for staff and patients, limiting staff numbers on site and encouraging home working for all nonlaboratory tasks including data analysis and writing. Shared equipment usage was made safe by adapting booking systems to allow for the deployment of cleaning protocols. All risk assessments and standard operating procedures were rewritten and approved by local committees, and staff training was initiated to ensure compliance. CONCLUSIONS: Laboratories can adopt and adapt this framework to expedite reopening a clinical laboratory during the current COVID-19 pandemic while mitigating the risk to research participants and staff.

Importance of validating antibody panels: Anti-PD-L1 clone binds AF700 fluorophore.

Researchers routinely use antibodies to assess the expression levels of proteins on the surface or intracellularly in a variety of different cell types. In this current study we highlight the importance of careful validation of antibodies for analysis of protein expression by flow cytometry and how failure to do so can significantly impact the interpretation of the data generated leading to false-positive results. There has been increasing awareness of the role the programmed death receptor 1 (PD-1) pathway plays in health and disease and a potential that programme death ligand 1 (PD-L1) may play a role in inflammatory disease. We aimed to investigate PD-L1 expression on human neutrophils isolated from healthy individuals and patients diagnosed with chronic obstructive pulmonary disease (COPD). We observed an increase in surface expression of PD-L1 by human neutrophils when incubated with AlexaFluor™700-conjugated anti-CD16. Through careful interrogation and antibody validation, we found a novel interaction between a commercially available anti-PD-L1 antibody and the AlexaFluor™700 fluorophore, resulting in this observed increase in PD-L1 signal. Surface expression of PD-L1 was not observed on neutrophils from healthy volunteers or patients with COPD when clone 29E.2A3 of anti-PD-L1 was not used with AlexaFluor™700-conjugated anti-CD16. This highlights the importance of robust antibody validation to ensure antibody compatibility in the context of multi-parametric flow cytometry panels. We also show that, without these validation experiments, novel neutrophil phenotypes could be falsely reported - an important consideration when there is increasing interest in neutrophil heterogeneity.

Update on Extensively Drug-Resistant Salmonella Serotype Typhi Infections Among Travelers to or from Pakistan and Report of Ceftriaxone-Resistant Salmonella Serotype Typhi Infections Among Travelers to Iraq - United States, 2018-2019.

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target.

Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington.

BACKGROUND: Long-term care facilities are high-risk settings for severe outcomes from outbreaks of Covid-19, owing to both the advanced age and frequent chronic underlying health conditions of the residents and the movement of health care personnel among facilities in a region. METHODS: After identification on February 28, 2020, of a confirmed case of Covid-19 in a skilled nursing facility in King County, Washington, Public Health-Seattle and King County, aided by the Centers for Disease Control and Prevention, launched a case investigation, contact tracing, quarantine of exposed persons, isolation of confirmed and suspected cases, and on-site enhancement of infection prevention and control. RESULTS: As of March 18, a total of 167 confirmed cases of Covid-19 affecting 101 residents, 50 health care personnel, and 16 visitors were found to be epidemiologically linked to the facility. Most cases among residents included respiratory illness consistent with Covid-19; however, in 7 residents no symptoms were documented. Hospitalization rates for facility residents, visitors, and staff were 54.5%, 50.0%, and 6.0%, respectively. The case fatality rate for residents was 33.7% (34 of 101). As of March 18, a total of 30 long-term care facilities with at least one confirmed case of Covid-19 had been identified in King County. CONCLUSIONS: In the context of rapidly escalating Covid-19 outbreaks, proactive steps by long-term care facilities to identify and exclude potentially infected staff and visitors, actively monitor for potentially infected patients, and implement appropriate infection prevention and control measures are needed to prevent the introduction of Covid-19.

Companion Animals and Health in Older Populations: A Systematic Review.

OBJECTIVES: . The aim of this systematic literature review (SLR) was to investigate the effect of companion animals (whether simply as pets or used in more formal intervention approaches) on the physical and mental health of older adults (aged 60+). METHODS: . The reviewers identified key search terms and conducted a systematic search of the PsycINFO and PubMed databases. The 70 articles reviewed were evaluated through tabular and thematic analysis. RESULTS: . In 52 of the studies examined, companion animals positively contributed to the mental and/or physical health of older adults. With respect to mental health, involvement with a companion animal improved participant quality of life and effectively attenuated symptoms of depression, anxiety, cognitive impairment, and the behavioral and psychiatric symptoms of dementia (BPSD). In relation to physical health, marked increases in physical activity and improvements in blood pressure and heart rate variability were the only consistent physical health improvements observed from companion animal interactions. CONCLUSIONS: . Animal companionship can benefit the mental and physical health of older adults, although more and better controlled research on this topic is required. CLINICAL IMPLICATIONS: . Use of companion animals has the potential to be an effective treatment or adjunct therapy to improve the health status and quality of life of older individuals.

Neutrophil phenotypes in chronic lung disease.

Introduction: Neutrophils are the most abundant inflammatory cells in the lungs of patients with chronic lung diseases, especially COPD, yet despite this, patients often experience repeated chest infections. Neutrophil function may be altered in disease, but the reasons are unclear. In chronic disease, sequential pro-inflammatory and pro-repair responses appear distorted. As understanding of neutrophil heterogeneity has expanded, it is suggested that different neutrophil phenotypes may impact on health and disease. Areas covered: In this review, the definition of cellular phenotype, the implication of neutrophil surface markers and functions in chronic lung disease and the complex influences of external, local and genetic factors on these changes are discussed. Literature was accessed up to the 19 July 2019 using: PubMed, US National Library of Medicine National Institutes of Health and the National Centre for Biotechnology Information. Expert opinion: As more is learned about neutrophils, the further we step from the classical view of neutrophils being unrefined killing machines to highly complex and finely tuned cells. Future therapeutics may aim to normalize neutrophil function, but to achieve this, knowledge of phenotypes in humans and how these relate to observed pathology and disease processes is required.

Prehabilitation Before Major Abdominal Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery. METHODS: EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference. RESULTS: Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46-0.87 I2 34%, p = 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23-0.68, I2 = 0%, p = 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD -2.39 95% CI -4.86 to 0.08 I2 = 0%, p = 0.06) or change in 6MWT distance (WMD 9.06 95% CI -35.68, 53.81 I2 = 88%, p = 0.69) was observed. CONCLUSIONS: Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.

Energy Expenditure After Liver Resection: Validation of a Mobile Device for Estimating Resting Energy Expenditure and an Investigation of Energy Expenditure Change After Liver Resection.

BACKGROUND: Resting energy expenditure (REE) is the major component of total energy expenditure. REE is traditionally performed by indirect calorimetry (IC) and is not well investigated after liver surgery. A mobile device (SenseWear Armband [SWA]) has been validated when estimating REE in other clinical settings but not liver resection. The aims of this study are to validate SWA vs IC, quantify REE change following liver resection, and determine factors associated with REE change. MATERIALS AND METHODS: Patients listed for open liver resection prospectively underwent IC and SWA REE recordings pre- and postoperatively. In addition, the SWA was worn continuously postoperatively to estimate daily REE for the first 5 postoperative days. To determine acceptability of the SWA, validation analysis was performed. To assess REE change, peak postoperative REE was compared with preoperative levels. Factors associated with REE change were also analyzed. RESULTS: SWA showed satisfactory validity compared with IC when estimating REE, although postoperatively, the 95% levels of agreement (-5.56 to 3.18 kcal/kg/d) may introduce error. Postoperative REE (median, 23.5 kcal/kg/d; interquartile range [IQR], 22.6-25.7 kcal/kg/d) was significantly higher than predicted REE (median, 19.7 kcal/kg/d; IQR, 19.1-21.0 kcal/kg/d; P < .0001). Median REE rise was 11% (IQR, -1% to 25%). Factors associated with REE rise of >11% were age ( P = .017) and length of operation ( P = .03). CONCLUSIONS: SWA offers a suitable alternative to IC when estimating postoperative REE, but the magnitude of the error (8.74 kcal/kg/d) could hinder its accuracy. REE quantification after liver resection is important to identify patients who could be prone to energy imbalance and therefore malnutrition.

Short-term outcomes after liver resection for malignant and benign disease in the age of ERAS.

INTRODUCTION: Enhanced Recovery After Surgery protocols have been implemented effectively after liver resection and provide benefits in terms of general morbidity rates. In order to optimise peri-operative care protocols and minimise morbidity, further investigation is required to identify factors associated with poor outcome after liver resection. METHODS: A retrospective analysis of patients undergoing liver resection and enhanced recovery care between January 2006 and September 2012 was conducted. Data were collected on patient outcome and demographics, operative and pathological details. Univariate and multivariate analyses were performed to determine independent predictors of adverse outcome. RESULTS: 603 patients underwent liver resection during the study period. Morbidity and mortality rates were 34.3% and 1.5% respectively. The only predictor of major morbidity was extended resection (OR 4.079; 95% CI 2.177-7.642). CONCLUSIONS: Extended resection is associated with major morbidity. When determining optimum peri-operative care, ERAS protocols must incorporate care components that can mitigate against morbidity associated with extended resection.

CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure.

BACKGROUND & AIMS: Liver regeneration requires functional liver macrophages, which provide an immune barrier that is compromised after liver injury. The numbers of liver macrophages are controlled by macrophage colony-stimulating factor (CSF1). We examined the prognostic significance of the serum level of CSF1 in patients with acute liver injury and studied its effects in mice. METHODS: We measured levels of CSF1 in serum samples collected from 55 patients who underwent partial hepatectomy at the Royal Infirmary Edinburgh between December 2012 and October 2013, as well as from 78 patients with acetaminophen-induced acute liver failure admitted to the Royal Infirmary Edinburgh or the University of Kansas Medical Centre. We studied the effects of increased levels of CSF1 in uninjured mice that express wild-type CSF1 receptor or a constitutive or inducible CSF1-receptor reporter, as well as in chemokine receptor 2 (Ccr2)-/- mice; we performed fate-tracing experiments using bone marrow chimeras. We administered CSF1-Fc (fragment, crystallizable) to mice after partial hepatectomy and acetaminophen intoxication, and measured regenerative parameters and innate immunity by clearance of fluorescent microbeads and bacterial particles. RESULTS: Serum levels of CSF1 increased in patients undergoing liver surgery in proportion to the extent of liver resected. In patients with acetaminophen-induced acute liver failure, a low serum level of CSF1 was associated with increased mortality. In mice, administration of CSF1-Fc promoted hepatic macrophage accumulation via proliferation of resident macrophages and recruitment of monocytes. CSF1-Fc also promoted transdifferentiation of infiltrating monocytes into cells with a hepatic macrophage phenotype. CSF1-Fc increased innate immunity in mice after partial hepatectomy or acetaminophen-induced injury, with resident hepatic macrophage as the main effector cells. CONCLUSIONS: Serum CSF1 appears to be a prognostic marker for patients with acute liver injury. CSF1 might be developed as a therapeutic agent to restore innate immune function after liver injury.