Targeting Iron - Respiratory Reciprocity Promotes Bacterial Death.

Discovering new bacterial signaling pathways offers unique antibiotic strategies. Here, through an unbiased resistance screen of 3,884 gene knockout strains, we uncovered a previously unknown non-lytic bactericidal mechanism that sequentially couples three transporters and downstream transcription to lethally suppress respiration of the highly virulent P. aeruginosa strain PA14 - one of three species on the WHO's 'Priority 1: Critical' list. By targeting outer membrane YaiW, cationic lacritin peptide 'N-104' translocates into the periplasm where it ligates outer loops 4 and 2 of the inner membrane transporters FeoB and PotH, respectively, to suppress both ferrous iron and polyamine uptake. This broadly shuts down transcription of many biofilm-associated genes, including ferrous iron-dependent TauD and ExbB1. The mechanism is innate to the surface of the eye and is enhanced by synergistic coupling with thrombin peptide GKY20. This is the first example of an inhibitor of multiple bacterial transporters.

Utilizing kidneys from a donor with bile-cast nephropathy.

Here we discuss the successful utilization of a pair of deceased donor kidneys with bile-cast nephropathy. The donor had a kidney donor profile index of 48% and an acute kidney injury requiring continuous renal replacement therapy. Peak donor bilirubin was 40.5 mg/dL, and renal wedge biopsies showed bile-cast nephropathy. Both recipients had delayed graft function lasting up to 4 weeks. The 4-month biopsies showed mild interstitial fibrosis, tubular atrophy, and a resolution of bile casts. These kidney allografts showed the reversible course of cholemic nephropathy and the potential for increasing the utilization of previously discarded kidneys.

Histiocytic Sarcoma Treated with Pembrolizumab: A Case Report and Literature Review.

Histiocytic sarcoma (HS) is a rare hematologic malignancy that has historically been treated with lymphoma-based regimens with a median survival of 6 months. We describe a case of a 51-year-old woman who presented with acute back pain and cord compression. She was diagnosed with HS with diffuse skeletal lesions and high expression of programmed death ligand 1 (PD-L1). She was subsequently treated with chemotherapy plus off-label use of pembrolizumab followed by allogeneic stem cell transplantation. Ultimately, the patient died in the setting of progression of disease 17 months after her stem cell transplantation and 26 months after her diagnosis. This article also presents a literature review of cases of HS treated with programmed death ligand inhibition.

Impact of Glomerulitis on Long-term Outcomes After Kidney Transplantation.

The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods: A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results: We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]' respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion: Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.

Alloantibodies after simultaneous liver-kidney transplant: A story of primary nonfunction, retransplantation, and antibody-mediated rejection.

Simultaneous liver-kidney transplant (SLKT) in the presence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSA) is a well-accepted practice. Herein, we describe the evolution of alloantibodies in a patient who received an SLKT. The pre-SLKT serum sample showed multiple strong DSA. As expected, all DSA cleared in a sample collected 4 days after the SLKT. Because of the primary nonfunction of the liver in the SLKT, the patient had a second liver transplant 4 days later. An abrupt increase in DSA levels against the kidney was detected 10 days after the second liver transplant. These DSA were refractory to treatment, and the transplanted kidney was lost due to antibody-mediated rejection (AMR). A detailed study of the HLA epitopes recognized by DSA and, after normalization with third-party alloantibodies to address the effect of multiple transfusions and liver allograft neutralization, showed that the elimination of these antibodies depended on the HLA antigens expressed by the transplanted liver cells. The return of DSA after removal of the first transplanted liver was associated with AMR in the transplanted kidney.

Progressive decline of function in renal allografts with normal 1-year biopsies: Gene expression studies fail to identify a classifier.

Histologic findings on 1-year biopsies such as inflammation with fibrosis and transplant glomerulopathy predict renal allograft loss by 5 years. However, almost half of the patients with graft loss have a 1-year biopsy that is either normal or has only interstitial fibrosis. The goal of this study was to determine if there was a gene expression profile in these relatively normal 1-year biopsies that predicted subsequent decline in renal function. Using transcriptome microarrays we measured intragraft mRNA levels in a retrospective Discovery cohort (170 patients with a normal/minimal fibrosis 1-year biopsy, 54 with progressive decline in function/graft loss and 116 with stable function) and developed a nested 10-fold cross-validated gene classifier that predicted progressive decline in renal function (positive predictive value = 38 ± 34%%; negative predictive value = 73 ± 30%, c-statistic = .59). In a prospective, multicenter Validation cohort (270 patients with Normal/Interstitial Fibrosis [IF]), the classifier had a 20% positive predictive value, 85% negative predictive value and .58 c-statistic. Importantly, the majority of patients with graft loss in the prospective study had 1-year biopsies scored as Normal or IF. We conclude predicting graft loss in many renal allograft recipients (i.e., those with a relatively normal 1-year biopsy and eGFR > 40) remains difficult.

Successful outcomes with transplanting kidneys from deceased donors with acute kidney injuryon temporary renal replacement therapy.

BACKGROUND AND OBJECTIVES: We aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT). MATERIALS AND METHODS: A total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney. RESULTS: The study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3-RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0, P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups, P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI. CONCLUSIONS: Transplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.

Transplant outcomes using kidneys from high KDPI acute kidney injury donors.

Kidney transplant (KT) outcomes from high kidney donor profile index (KDPI ≥85%) donors with acute kidney injury (AKI) remain underreported. KT from 172 high KDPI Acute Kidney Injury Network (AKIN) stage 0-1 donors and 76 high KDPI AKIN stage 2-3 donors from a single center were retrospectively assessed. The AKIN 2-3 cohort had more delayed graft function (71% vs. 37%, p < .001). At one year, there were no differences in the estimated glomerular filtration rate (44 ± 17 vs. 46 ± 18, p = .42) or fibrosis on protocol biopsy (ci, p = .85). Donor terminal creatinine (p = .59) and length of delayed graft function (p = .39) did not impact one-year eGFR. There were more primary nonfunction (PNF) events in the high KDPI AKIN 2-3 group (5.3% vs. 0.6%, p = .02). With a median follow-up of 3.8 years, one-year death-censored graft failure was 3.5% for AKIN 0-1 and 14.5% for AKIN 2-3 (HR 2.40, 95% CI 1.24-4.63, p = .01). Although AKIN stage 2-3 high KDPI kidneys had comparable one-year eGFR to AKIN stage 0-1 high KDPI kidneys, there were more PNF occurrences and one-year death-censored graft survival was reduced. Given these findings, additional precautions should be undertaken when assessing and utilizing kidneys from severe AKI high KDPI donors.

Lentivirus-Mediated Expression of Human Secreted Amyloid Precursor Protein-Alpha Promotes Long-Term Induction of Neuroprotective Genes and Pathways in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Secreted amyloid precursor protein-alpha (sAPPα) can enhance memory and is neurotrophic and neuroprotective across a range of disease-associated insults, including amyloid-ß toxicity. In a significant step toward validating sAPPα as a therapeutic for Alzheimer's disease (AD), we demonstrated that long-term overexpression of human sAPPα (for 8 months) in a mouse model of amyloidosis (APP/PS1) could prevent the behavioral and electrophysiological deficits that develop in these mice. OBJECTIVE: To explore the underlying molecular mechanisms responsible for the significant physiological and behavioral improvements observed in sAPPα-treated APP/PS1 mice. METHODS: We assessed the long-term effects on the hippocampal transcriptome following continuous lentiviral delivery of sAPPα or empty-vector to male APP/PS1 mice and wild-type controls using Affymetrix Mouse Transcriptome Assays. Data analysis was carried out within the Affymetrix Transcriptome Analysis Console and an integrated analysis of the resulting transcriptomic data was performed with Ingenuity Pathway analysis (IPA). RESULTS: Mouse transcriptome assays revealed expected AD-associated gene expression changes in empty-vector APP/PS1 mice, providing validation of the assays used for the analysis. By contrast, there were specific sAPPα-associated gene expression profiles which included increases in key neuroprotective genes such as Decorin, betaine-GABA transporter and protocadherin beta-5, subsequently validated by qRT-PCR. An integrated biological pathways analysis highlighted regulation of GABA receptor signaling, cell survival and inflammatory responses. Furthermore, upstream gene regulatory analysis implicated sAPPα activation of Interleukin-4, which can counteract inflammatory changes in AD. CONCLUSION: This study identified key molecular processes that likely underpin the long-term neuroprotective and therapeutic effects of increasing sAPPα levels in vivo.

Breast Cancer Metastasis Presenting as Colonic Polyps.

Breast cancer is the most common malignancy among women and is the second leading cause of cancer-related death among women in the United States. Rarely, breast cancer can metastasize to the gastrointestinal tract. We present a case of metastatic breast cancer diagnosed after finding metastatic lesions appearing as polyps during a colonoscopy.

Ambient Atmospheric Deposition of Anthropogenic Microfibers and Microplastics on the Western Periphery of Europe (Ireland).

Microfibers (mf) are the most common type of microplastic in the environment. Few studies have focused on their abundance in atmospheric deposition in background environments. In the current study, we collected wet-only and bulk rainfall from four precipitation chemistry monitoring stations, primarily located in coastal areas around Ireland. Anthropogenic mf were observed in all samples; the average deposition across the four study sites was 80 mf m-2 day-1. Wet-only mf deposition was 70 mf m-2 day-1 compared with bulk deposition of 100 mf m-2 day-1. The wet-only collectors were estimated to capture ∼70% of the bulk collectors, suggesting that dry deposition makes up at least 30% of total deposition. Meteorological variables, i.e., relative humidity, rainfall volume, wind speed, and wind direction, were significantly related to mf abundance, suggesting that rainfall washout and air mass movement are important predictors of mf deposition in background regions. In total, 15% of all anthropogenic mf were identified as plastic. The most abundant polymer type was polyester or polyethylene terephthalate at 71%, followed by polyacrylonitrile at 11%, polyethylene at 11%, and polypropylene at 4%. The average deposition of plastic mf was 12 mf m-2 day-1.

Association of elevated pre-operative HbA1c and post-operative complications in patients undergoing gynaecological oncology surgery.

HbA1c testing provides average blood glucose control, an elevated result may be associated with adverse post-operative outcomes. Our objective was to evaluate the association between elevated pre-operative HbA1c and post-operative complications in patients undergoing major gynaecological oncology surgery. HbA1c was measured pre-operatively in 364 patients. We identified 65 (16%) patients at risk of developing diabetes with borderline HbA1c measurements.Patients with borderline HbA1c (42-47 mmol/mol) had almost double the incidence of infections compared to patients with normal HbA1c (15.8% vs. 6.5%, p=.038). There were significantly less infections between patients with a normal HbA1c (<42 mmol/mol) and those with an HbA1c of over 42 mmol/mol (6.5% vs. 22.8%, p<.05). There was an association between elevated HbA1c and infective complications especially in patients with a borderline HbA1c. It is suggested that knowing HbA1c status, intervention can be made to prevent post-operative infective complications and improve outcomes.Impact statementWhat is already known on this subject? Obesity is a common risk factor for gynaecological cancer and elevated HbA1c. Chronically elevated HbA1c may lower immunity. An association has been shown previously between elevated HbA1c and post-operative complications.What the results of this study add? This study examined infective complications in patients undergoing gynaecological surgery; showing that patients with a borderline HbA1c (42-47 mmol/mol), especially those with a diagnosis of diabetes to be most at risk. This suggests that pre-operative HbA1c should be used routinely to guide care rather than diabetic status alone to prevent post-operative infections.What the implications are of these findings for clinical practice and/or further research? More research needs to be carried out to find the optimal pre-operative HbA1c targets to reduce post-operative infection rates. Work needs to be done in conjunction with general practitioners to help patients to reduce their HbA1c prior to treatment.

Changes in the transcriptome of circulating immune cells of a New Zealand cohort with myalgic encephalomyelitis/chronic fatigue syndrome.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a poorly understood disease affecting 0.2%-2% of the global population. To gain insight into the pathophysiology of ME/CFS in New Zealand, we examined the transcriptomes of peripheral blood mononuclear cells by RNA-seq analysis in a small well-characterized patient group (10 patients), with age/gender-matched healthy controls (10 control subjects). Twenty-seven gene transcripts were increased 1.5- to sixfold and six decreased three- to sixfold in the patient group ( P < 0.01). The top enhanced gene transcripts, IL8, NFΚBIA and TNFAIP3, are functionally related to inflammation, and significant changes were validated for IL8 and NFΚBIA by quantitative polymerase chain reaction (qPCR). Functional network analysis of the altered gene transcripts ( P < 0.01) detected interactions between the products related to inflammation, circadian clock function, metabolic dysregulation, cellular stress responses and mitochondrial function. Ingenuity pathway analysis ( P < 0.05) provided further insights into the dysfunctional physiology, highlighting stress and inflammation pathways. This analysis provides novel insights into the molecular changes in ME/CFS and contributes to the understanding of the pathophysiological mechanisms of the disease.

Anticoagulant-Related Nephropathy in Kidney Biopsy: A Single-Center Report of 41 Cases.

RATIONALE & OBJECTIVE: In 2009, the first case of acute kidney injury and occlusive red blood cell (RBC) tubular casts associated with a high international normalized ratio in a patient receiving warfarin was identified. This entity, named warfarin-related nephropathy, was later renamed anticoagulant-related nephropathy (ARN) after similar cases with other anticoagulants were described. We provide our 10-year experience with ARN based on a single-center kidney biopsy laboratory. STUDY DESIGN: The kidney pathology database at the Ohio State University Wexner Medical Center (OSUWMC) was searched for native kidney biopsy cases consistent with ARN. Clinical data were obtained from patient medical records. SETTING & PARTICIPANTS: Native kidney biopsies evaluated between January 1, 2009, and December 31, 2017 at OSUWMC. RESULTS: Among 8,636 native kidney biopsies reviewed at the OSUWMC, there were 41 (0.5%) patients for whom deterioration in kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not considered. There were 63% men and 95% were white; average age was 62 ± 14 years. Most were on warfarin therapy (N = 28), although cases were also attributed to direct-acting anticoagulants (N = 2), antiplatelet medications (N = 1), heparin or enoxaparin (N = 4), and disseminated intravascular coagulopathy (N = 6). Morphologically, there was acute tubular necrosis and RBC casts. The majority of biopsies had an underlying glomerular disease and many patients had positive serologic test results. In all these cases, the severity of kidney failure, RBC tubular casts, and hematuria were disproportionate to glomerular morphologic changes. LIMITATIONS: Selection bias in the decision to perform a kidney biopsy. CONCLUSIONS: ARN is an uncommon diagnosis in kidney pathology practice, but it should be considered when the number of RBC tubular casts is disproportionate to the severity of glomerular changes in a kidney biopsy in patients either receiving anticoagulation therapy or who presented with acute coagulopathy. Our data suggest that anticoagulation aggravates underlying glomerular diseases rather than directly affecting the glomerular filtration barrier.

A method to reduce variability in scoring antibody-mediated rejection in renal allografts: implications for clinical trials - a retrospective study.

Poor reproducibility in scoring antibody-mediated rejection (ABMR) using the Banff criteria might limit the use of histology in clinical trials. We evaluated the reproducibility of Banff scoring of 67 biopsies by six renal pathologists at three institutions. Agreement by any two pathologists was poor: 44.8-65.7% for glomerulitis, 44.8-67.2% for peritubular capillaritis, and 53.7-80.6% for chronic glomerulopathy (cg). All pathologists agreed on cg0 (n = 20) and cg3 (n = 9) cases, however, many disagreed on scores of cg1 or cg2. The range for the incidence of composite diagnoses by individual pathologists was: 16.4-22.4% for no ABMR; 17.9-47.8% for active ABMR; and 35.8-59.7% for chronic, active antibody-mediated rejection (cABMR). A "majority rules" approach was then tested in which the scores of three pathologists were used to reach an agreement. This increased consensus both for individual scores (ex. 67.2-77.6% for cg) and for composite diagnoses (ex. 74.6-86.6% cABMR). Modeling using these results showed that differences in individual scoring could affect the outcome assessment in a mock study of cABMR. We conclude that the Banff schema has high variability and a majority rules approach could be used to adjudicate differences between pathologists and reduce variability in scoring in clinical trials.

Circulating Plasma microRNAs are Altered with Amyloidosis in a Mouse Model of Alzheimer's Disease.

Pathological changes underlying Alzheimer's disease (AD) begin decades before the classical symptoms of memory loss become evident. As microRNAs are released from neurons and enter the bloodstream, circulating microRNAs may be reflective of AD progression and are ideal candidates as biomarkers for early-stage disease detection. Here, we provide a novel, in-depth analysis of how plasma microRNAs alter with aging, the most prominent risk factor for AD, and with development of amyloid-ß (Aß) plaque deposition. We assessed the circulating microRNAs in APPswe/PSEN1dE9 transgenic mice and wild-type controls at 4, 8 and 15 m (n = 8-10) using custom designed Taqman arrays representing 185 neuropathology-related microRNAs. We performed a linear mixed-effects model to investigate the effects of age and genotype on plasma microRNAs expression. Following this analysis, we found 8 microRNAs were significantly affected by age alone in wild-type animals and 12 microRNAs altered in APPswe/PSEN1dE9 mice, either prior to Aß plaque deposition (4 m) or during the development of AD-like pathogenesis (8 m or 15 m). Importantly, we found that differing sets of microRNAs were identified at each time point. Functional analysis of these data revealed that while common biological pathways, such as Inflammatory Response, were enriched throughout the disease process, Free Radical Scavenging, Immunological Disease, and Apoptosis Signaling were specifically enriched later in the disease process. Overall, this study reinforces that distinct biological processes underpin the early versus late stages of AD-like pathogenesis and highlights potential pre-symptomatic microRNAs biomarkers of neurodegeneration.

Ongoing activities to optimize the quality and efficiency of lipid-lowering agents in the Scottish national health service: influence and implications.

BACKGROUND: Prescribing of lipid-lowering agents (LLAs) has increased worldwide including in Scotland with increasing prevalence of coronary heart disease, and higher dose statins have been advocated in recent years. There have also been initiatives to encourage prescribing of generic versus patented statins to save costs without compromising care. There is a need to document these initiatives and outcomes to provide future direction. METHOD: Assessment of utilization (items dispensed) and expenditure of key LLAs (mainly statins) between 2001 and 2015 in Scotland alongside initiatives. RESULTS: Multiple interventions over the years have increased international nonproprietary name prescribing (99% for statins) and preferential prescribing of generic versus patented statins, and reduced inappropriate prescribing of ezetimibe. This resulted in a 50% reduction in expenditure of LLAs between 2001 and 2015 despite a 412% increase in utilization, increased prescribing of higher dose statins (71% in 2015) especially atorvastatin following generic availability, and reduced prescribing of ezetimibe (reduced by 72% between 2010 and 2015). As a result, the quality of prescribing has improved. CONCLUSION: Generic availability coupled with multiple measures has resulted in appreciable shifts in statin prescribing behavior and reduced ezetimibe prescribing, resulting in improvements in both the quality and efficiency of prescribing.

The fraction of cancer attributable to modifiable risk factors in England, Wales, Scotland, Northern Ireland, and the United Kingdom in 2015.

BACKGROUND: Changing population-level exposure to modifiable risk factors is a key driver of changing cancer incidence. Understanding these changes is therefore vital when prioritising risk-reduction policies, in order to have the biggest impact on reducing cancer incidence. UK figures on the number of risk factor-attributable cancers are updated here to reflect changing behaviour as assessed in representative national surveys, and new epidemiological evidence. Figures are also presented by UK constituent country because prevalence of risk factor exposure varies between them. METHODS: Population attributable fractions (PAFs) were calculated for combinations of risk factor and cancer type with sufficient/convincing evidence of a causal association. Relative risks (RRs) were drawn from meta-analyses of cohort studies where possible. Prevalence of exposure to risk factors was obtained from nationally representative population surveys. Cancer incidence data for 2015 were sourced from national data releases and, where needed, personal communications. PAF calculations were stratified by age, sex and risk factor exposure level and then combined to create summary PAFs by cancer type, sex and country. RESULTS: Nearly four in ten (37.7%) cancer cases in 2015 in the UK were attributable to known risk factors. The proportion was around two percentage points higher in UK males (38.6%) than in UK females (36.8%). Comparing UK countries, the attributable proportion was highest in Scotland (41.5% for persons) and lowest in England (37.3% for persons). Tobacco smoking contributed by far the largest proportion of attributable cancer cases, followed by overweight/obesity, accounting for 15.1% and 6.3%, respectively, of all cases in the UK in 2015. For 10 cancer types, including two of the five most common cancer types in the UK (lung cancer and melanoma skin cancer), more than 70% of UK cancer cases were attributable to known risk factors. CONCLUSION: Tobacco and overweight/obesity remain the top contributors of attributable cancer cases. Tobacco smoking has the highest PAF because it greatly increases cancer risk and has a large number of cancer types associated with it. Overweight/obesity has the second-highest PAF because it affects a high proportion of the UK population and is also linked with many cancer types. Public health policy may seek to mitigate the level of harm associated with exposure or reduce exposure levels-both approaches may effectively impact cancer incidence. Differences in PAFs between countries and sexes are primarily due to varying prevalence of exposure to risk factors and varying proportions of specific cancer types. This variation in turn is affected by socio-demographic differences which drive differences in exposure to theoretically avoidable 'lifestyle' factors. PAFs at UK country level have not been available previously and they should be used by policymakers in devolved nations. PAFs are estimates based on the best available data, limitations in those data would generally bias toward underestimation of PAFs. Regular collection of risk factor exposure prevalence data which corresponds with epidemiological evidence is vital for analyses like this and should remain a priority for the UK Government and devolved Administrations.

Smoking cessation and improvement in physical performance among young men.

Tobacco use among young adults is a major public health challenge. Near-term benefits of cessation may motivate active young people to quit or avoid smoking. Military basic training includes mandatory tobacco cessation, as well as uniform physical conditioning regimes, creating an opportunity to evaluate changes in physical performance metrics in direct relation to smoking cessation. These analyses included data from all men who completed Marine Corps recruit training in San Diego, California, between 2002 and 2006. Recruits reported tobacco use and other health metrics on a pretraining survey. Initial and final aerobic run-times were recorded over the 3-month training period. Multivariable linear regression analyses assessed changes in run-speed relative to pre-enlistment smoking history. Among 52,419 young men included in analyses, 13,248 (25.3%) reported smoking before enlistment. Average run-speeds improved among all groups of recruits; however, improvement was greater among prior smokers compared to recruits with no history of smoking (average increase of 0.31 vs. 0.21 miles per hour) and statistically significant in multivariate analyses. Smoking cessation in this cohort of young men resulted in improved physical aerobic performance, independent of other behavioral health characteristics. These data may be useful in promoting and motivating smoking cessation among young, active adults.