Predictive Value and Limitations of the Placenta Accreta Index: A Systematic Review.

Our systematic review highlights that multiparametric PAI score assessment is a consistent tool with high sensitivity and specificity for prenatal prediction for placenta accreta spectrum (PAS) in high-risk population with anterior placenta previa or low-lying placenta and prior cesarean deliveries. A systematic search was conducted on November 1, 2022, of MEDLINE via PubMed, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar to identify relevant studies (PROSPERO ID # CRD42022368211). A total of 11 articles met our inclusion criteria, representing the data of a total of 1,044 cases. Women with PAS had an increased mean PAI total score, compared to those without PAS. Limitations of the PAI are most studies were conducted in developing countries in high-risk population which limit the global generalizability of findings. Heterogeneity of reported data did not allow to perform meta-analysis.

Hepatic infarction in pregnancy: a systematic review.

OBJECTIVE: Hepatic infarction is a rare complication of pregnancy most often associated with hemolysis, elevated liver enzymes, and low platelets syndrome. The objective of this review is to identify risk factors, present signs and symptoms, identify methods of diagnosis, and identify best management practices on the basis of published case reviews. DATA SOURCES: PubMed and MEDLINE (Ovid) databases were searched for citations regarding hepatic infarction in pregnancy or the postpartum period from database inception until the study date of December 18, 2023. Key words included "liver infarction" or "hepatic infarction" and "pregnancy" or "obstetrics." STUDY ELIGIBILITY CRITERIA: Case reviews or case series published in the English language were included. Our study was registered with the Prospective Register of Systematic Reviews (registration number CRD42023488176) and was conducted in accordance with the published Prospective Register of Systematic Reviews and Meta-analyses Of Observational Studies in Epidemiology guidelines. METHODS: Included papers were evaluated for bias using a previously published tool. RESULTS: A total of 38 citations documenting 50 pregnancies published between 1979 and 2023 were included. Of these, 34% had a history of hypertensive disease, 26% had antiphospholipid syndrome, and 22% had a history of thrombus. Of those without a preexisting diagnosis of antiphospholipid syndrome, 24% tested positive during hospitalization. Most patients presented with epigastric or right upper quadrant pain (78%), and 32% and 16% had severe blood pressure or mild blood pressure, respectively. Sixty-four percent of patients presented with transaminitis. Forty-six percent of patients delivered preterm, and 32% of pregnancies ended in intrauterine fetal demise, abortion, or early termination of pregnancy for maternal benefit. Computed tomography scans were used to confirm diagnosis of hepatic infarction in 58% of cases, magnetic resonance imaging in 14%, and ultrasound in 6%. In cases that described management, treatment was always multimodal, including antihypertensives (18%), therapeutic anticoagulation (45%), blood product transfusion (36%), plasma exchange or intravenous immunoglobulin (20%), and steroids (39%). Transfer to the intensive care unit was required in 20% of cases. CONCLUSION: Hepatic infarction should be considered in all cases of hemolysis, elevated liver enzymes, and low platelets syndrome, but specifically in patients with a history of antiphospholipid syndrome who present with epigastric or right upper quadrant pain. The diagnosis can usually be confirmed with a computed tomography scan alone, and management should be prompt with supportive care, therapeutic anticoagulation, and steroids.

Impact of Race/Ethnicity and Insurance Status on Obstetric Outcomes: Secondary Analysis of the NuMoM2b Study.

OBJECTIVE: This study aimed to investigate the impact of race/ethnicity and insurance status on obstetric outcomes in nulliparous women. STUDY DESIGN: Secondary analysis of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-To-Be. Obstetric outcomes included the development of a hypertensive event during pregnancy, need for a cesarean section, delivery of a preterm neonate, and postpartum hemorrhage. RESULTS: Of 7,887 nulliparous women, 64.7% were non-Hispanic White (White), 13.4% non-Hispanic Black (Black), 17.8% Hispanic, and 4.1% were Asian. Black women had the highest rates of developing new-onset hypertension (32%) and delivering preterm (11%). Cesarean deliveries were the highest in Asian (32%) and Black women (32%). Individuals with government insurance were more likely to deliver preterm (11%) and/or experience hemorrhage after delivery. In multivariable analyses, race/ethnicity was associated with hypertension and cesarean delivery. More important, the adjusted odds ratios for preventable risk factors, such as obesity, diabetes, and severe anemia were greater than the adjusted odds ratios for race/ethnicity in terms of poor maternal outcome. CONCLUSION: Although disparities were observed between race/ethnicity and obstetric outcomes, other modifiable risk factors played a larger role in clinical differences. KEY POINTS: · Race or insurance alone had mixed associations with maternal morbidities.. · Race and insurance had low associations with maternal morbidities.. · Other, modifiable risk factors may be more important.. · Both social and biological factors impact health disparities..

Sociodemographic predictors of COVID-19 vaccine hesitancy and leading concerns with COVID-19 vaccines among pregnant women at a South Texas clinic.

OBJECTIVE: COVID-19 vaccination rates among pregnant women remain low, despite increased risk of COVID-19-related illness and death and demonstrated vaccine safety and efficacy in this population. The objective of this study is to identify sociodemographic predictors of COVID-19 vaccine hesitancy and elucidate important concerns among the pregnant population in light of evolving conversations regarding COVID-19. METHODS: A prospective survey of pregnant women at a single urban clinic in South Texas was conducted August to September 2021 to identify predictors of COVID-19 vaccine hesitancy among the pregnant population. Collected variables included demographics, COVID-19 beliefs, tetanus-diphtheria-pertussis (Tdap)/influenza vaccine hesitancy, and primary vaccine concerns. Statistical analyses included Fisher's exact test, asymptotic two-sample Brown-Mood median test, and multinomial logistic regression. RESULTS: One hundred and nine participants completed the survey, 35 vaccinated and 74 unvaccinated, with a response rate of 91.6%. Women who were COVID-19 vaccine hesitant were more likely to be younger (28.0 vs. 31.0 years, p < .004) and further along in pregnancy (30.0 vs. 20.0 weeks, p = .001). They were also more likely to report influenza (odds ratio (OR) 6.3; 95% confidence interval (CI) 2.5-17.1) and Tdap (OR 4.1; 95% CI 1.75-10.7) vaccine hesitancy. Furthermore, women who were vaccine hesitant were more likely to believe they did not have enough information to confidently make their decision (OR 4.0; 95% CI 1.4-11.4). Primary concerns with COVID-19 vaccines included: short- and long-term side effects on the pregnancy, personal long-term side effects, and harmful ingredients. CONCLUSIONS: COVID-19 vaccine hesitant pregnant women were more likely to be younger, hesitant toward other vaccines, and concerned with pregnancy impact and harmful ingredients. Personal knowledge of other vaccinated pregnant women was associated with significantly higher vaccine acceptance rates. Access to vaccines and concerns about quality control were not cited as reasons for vaccine hesitancy, in contrast to earlier studies on this topic.

Comparison of obstetric to institutional antibiogram as an approach to advance antimicrobial stewardship in maternal care.

OBJECTIVE: To create an antibiogram derived exclusively from our obstetric population and compare the clinical isolates and susceptibilities to our institutional antibiogram. METHODS: Data collected by the University Hospital Clinical Microbiology Laboratory in SSC Soft from 01/01/2018 to 12/31/2018 was used to generate our institutional antibiogram. For comparison, we created an obstetric (OB) antibiogram using all clinical isolates collected during the same time interval from OB triage, labor & delivery, antepartum and postpartum wards. The antibiotic susceptibilities of the OB clinical isolates were compared to the institutional clinical isolates. RESULTS: In total, we identified 929 clinical isolates from our OB population in 2018. Urine was the predominant source of clinical isolates (76.3%). The remaining sources included wound (10.1%), genital (9.0%), blood and other fluids (4.6%). Escherichia coli (E. coli) accounted for nearly half of all isolates (48.7%) followed by Group B Streptococcus (10.7%), Enterococcus spp. (9%), and Klebsiella pneumoniae (7.2%). There was no difference in susceptibilities of Gram-positive organisms in the OB antibiogram compared to the institutional antibiogram. Conversely, common Gram-negative organisms demonstrated less antibiotic resistance in the OB antibiogram compared to the institutional antibiogram. Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were significantly more susceptible in the OB antibiogram compared to the institutional antibiogram to most antimicrobials tested. CONCLUSION: Compared to our institutional antibiogram, gram-negative clinical isolates in our OB population exhibit less antibiotic resistance. Creation of an OB-specific antibiogram, which more accurately reflects antibiotic resistance patterns within our unique patient population, may promote appropriate antimicrobial use by assisting in more informed antibiotic selection and limit unnecessary use of broad-spectrum antibiotics.

The pathophysiologic, diagnostic, and therapeutic aspects of posterior reversible encephalopathy syndrome during pregnancy.

Posterior reversible encephalopathy syndrome (PRES) is a neurological condition with a wide range of symptoms, including visual disturbances, headache, vomiting, seizures, and altered consciousness. This review describes the pathophysiology of PRES, as well as the clinical, diagnostic, and therapeutic intervention during pregnancy. The gold standard for diagnosis of PRES is Magnetic Resonance Imaging (MRI), helping to differentiate it from other similar conditions. The aim of this paper is to review the principal aspects of PRES, general care, blood pressure control, and seizures prevention while avoiding potential injuries to the mother and fetus in the event of pregnancy. We concluded that PRES can be effectively treated and reversed if prompt diagnostic action is made, and adequate care is initiated.

Eltrombopag for Treating Thrombocytopenia after Allogeneic Stem Cell Transplantation.

Thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-SCT) can pose significant problems in management of patients. Eltrombopag is a small-molecule thrombopoietin receptor agonist that has been approved for use in immune thrombocytopenic purpura and aplastic anemia; but its use after allo-SCT is limited. Between 2014 and 2017, we treated 13 patients with eltrombopag for poor platelet engraftment without evidence of relapse at the time of initiation, including 6 patients with primary platelet engraftment failure and 7 with secondary platelet engraftment failure. Eltrombopag was started at an initial dose of 25 or 50 mg per day, and dose adjustments were made in accordance with the manufacturer's recommendation. The cumulative incidence of platelet recovery to ≥50,000/µL without the need for transfusion for at least 7 days was defined as response. The overall response rate was 62% (n = 8). Of the 6 patients with primary isolated platelet failure, 3 (50%) responded, and of the 7 patients with secondary platelet failure, 5 (71%) responded. The median time to response was 33 days (range, 11 to 68 days). In addition, no significant differences in platelet recovery were noted in patients with adequate and decreased bone marrow megakaryocytic reserve (60% and 67%, respectively). Although eltrombopag was well tolerated, and no patient discontinued treatment because of adverse events, only 3 patients were alive at the end of the observation period, with relapse and graft-versus-host disease accounting for majority of the deaths. This suggested that despite the relatively good overall response rate to eltrombopag, inadequate platelet engraftment is a harbinger of poor outcome in allo-SCT.

Elevated A20 contributes to age-dependent macrophage dysfunction in the lungs.

Advanced age is associated with chronic low-grade inflammation (i.e. inflamm-aging) and poor macrophage function that includes a weak pro-inflammatory cytokine response to bacteria and diminished phagocytosis (i.e. age-dependent macrophage dysfunction [ADMD]). One reason for this is that ADMD is associated with poor NFκB and MAPK activation following Toll-like receptor stimulation. Herein, we tested the hypothesis that inflamm-aging induces production of A20, a cytosolic and homeostatic suppressor of the NFκB and MAPK signaling cascades that deubiquitinates (i.e. inactivates) the common upstream signaling molecule TRAF6, and this is responsible for ADMD. Western blots and immunohistochemistry comparing tissues from young, mature, and aged C57BL/6 mice indicated that A20 was strongly elevated in the lungs of aged mice but not in other tissues. Elevated A20 was also detected in alveolar macrophages (AM) from aged mice. In contrast CYLD, a second deubiquitinase that also negatively regulates the NFκB pathway was decreased with aging. Following co-incubation of AM with the bacteria Streptococcus pneumoniae, TRAF6 polyubiquitination was diminished in AM isolated from aged versus young mice. A20 production was inducible in the J774A.1 macrophage cell line and C57BL/6AM by overnight incubation with TNFα but not IL-6. Retrovirus-induced expression of A20 in J774A.1 cells resulted in their diminished production of IL-6 following exposure to S. pneumoniae but had no effect on levels of phagocytosis. Overnight incubation of AM from young mice with TNFα also resulted in a dampened IL-6 response to S. pneumoniae. Finally, dietary supplementation of aged mice with anti-inflammatory n-3 polyunsaturated fatty acids in the form of fish oil lowered lung A20 levels and enhanced resistance, including a 100-fold reduction in bacterial titers in the lungs, to experimental challenge with S. pneumoniae. We conclude that elevated A20 due to TNFα partially explains the ADMD phenotype and that ADMD is potentially reversible.

Goal setting with type 2 diabetes: a hermeneutic analysis of the experiences of diabetes educators.

PURPOSE: The purpose of this study was to explicate and interpret common experiences of diabetes educators (DEs) with patient goal setting for patients with type 2 diabetes in diabetes education. METHODS: Transcripts (n = 10) from semi-structured interviews were analyzed using a hermeneutic phenomenological approach to more deeply explore the accounts of DEs' goal setting with patients with type 2 diabetes. RESULTS: The overarching pattern that emerged was "Striking a Balance," which subsumed 4 subthemes: Applying Theoretical-Practical Principles When Setting Goals, Identifying Idealistic-Realistic Expectations, Creating Patient-Educator-Centered Plans, and Readying-Living With Goal Setting. The pattern, "Striking a Balance," revealed a common meaning of DEs as experiences requiring balance and nuance in goal setting with patients. IMPLICATIONS: The results of this study combined with the tenets of the self-determination theory can provide the DEs with real-life exemplars and a theoretical framework to encourage their patients to self-manage, increase intrinsic motivation, and improve adherence related to their lifestyle changes and glycemic control. DEs, as facilitators of change, can implement these changes with flexible and reciprocal activities with their patients. The DEs owned these activities and they are: "building the bond," "sharing the session," "readying for change," "sending them home," and "bringing them back."

Age-related defects in TLR2 signaling diminish the cytokine response by alveolar macrophages during murine pneumococcal pneumonia.

Alveolar macrophages (AMs) are the first immune cells to respond to an invading pathogen and coordinate the inflammatory response within the lungs. Studies suggest that macrophages exhibit age-related deficiencies in Toll-like receptor (TLR) function; however, the impact of this dysfunction during pneumonia, the leading cause of infectious death in the elderly, and the underlying mechanisms responsible remain unclear. We examined disease severity in young, mature, and aged BALB/cBy mice following intratracheal infection with the Gram-positive bacteria Streptococcus pneumoniae (Spn). Both mature and aged mice failed to clear bacteria and as a result had increased mortality, tissue damage and vascular leakage. Early production of TNFα, IL-1ß, and IL-6 during pneumonia declined with age and was associated with an inability of isolated AMs to respond to pneumococcal cell wall (CW) and ethanol-killed Spn ex vivo. Total levels of TLR1 were unaffected by age and TLR2 surface expression was slightly yet significantly increased on aged AMs suggesting that intracellular TLR signaling defects were responsible for the age-related decline in cytokine responsiveness. Following infection of isolated AMs with live Spn, a significant age-related decline in TLR2-induced phosphorylation of p65 NFκB, JNK and p38 MAPK, and an increase in ERK phosphorylation was observed by immunoblotting. These data are the first to demonstrate that TLR2-dependent recognition of Spn by aged AMs is impaired and is associated with a delayed pro-inflammatory cytokine response in vivo along with enhanced susceptibility to pneumococcal pneumonia.

Impact of oral simvastatin therapy on acute lung injury in mice during pneumococcal pneumonia.

BACKGROUND: Recent studies suggest that the reported protective effects of statins (HMG-CoA reductase inhibitors) against community-acquired pneumonia (CAP) and sepsis in humans may be due to confounders and a healthy user-effect. To directly test whether statins are protective against Streptococcus pneumoniae, the leading cause of CAP, we examined the impact of prolonged oral simvastatin therapy at physiologically relevant doses in a mouse model of pneumococcal pneumonia. BALB/c mice were placed on rodent chow containing 0 mg/kg (control), 12 mg/kg (low simvastatin diet [LSD]; corresponds to 1.0 mg/kg/day), or 120 mg/kg (high simvastatin diet [HSD]; corresponds to 10 mg/kg/day) simvastatin for four weeks, infected intratracheally with S. pneumoniae serotype 4 strain TIGR4, and sacrificed at 24, 36, or 42 h post-infection for assessment of lung histology, cytokine production, vascular leakage and edema, bacterial burden and bloodstream dissemination. Some mice received ampicillin at 12-h intervals beginning at 48 h post-infection and were monitored for survival. Immunoblots of homogenized lung samples was used to assess ICAM-1 production. RESULTS: Mice receiving HSD had reduced lung consolidation characterized by less macrophage and neutrophil infiltration and a significant reduction in the chemokines MCP-1 (P = 0.03) and KC (P = 0.02) and ICAM-1 in the lungs compared to control mice. HSD mice also had significantly lower bacterial titers in the blood at 36 (P = 0.007) and 42 (P = 0.03) hours post-infection versus controls. LSD had a more modest effect against S. pneumoniae but also resulted in reduced bacterial titers in the lungs and blood of mice after 42 h and a reduced number of infiltrated neutrophils. Neither LSD nor HSD mice had reduced mortality in a pneumonia model where mice received ampicillin 48 h after challenge. CONCLUSIONS: Prolonged oral simvastatin therapy had a strong dose-dependent effect on protection against S. pneumoniae as evidenced by reduced neutrophil infiltration, maintenance of vascular integrity, and lowered chemokine production in the lungs of mice on HSD. Statin therapy also protected through reduced bacterial burden in the lungs. Despite these protective correlates, mortality in the simvastatin-receiving cohorts was equivalent to controls. Thus, oral simvastatin at physiologically relevant doses only modestly protects against pneumococcal pneumonia.

Cellular senescence increases expression of bacterial ligands in the lungs and is positively correlated with increased susceptibility to pneumococcal pneumonia.

Cellular senescence is an age-associated phenomenon that promotes tumor invasiveness owing to the secretion of proinflammatory cytokines, proteases, and growth factors. Herein we demonstrate that cellular senescence also potentially increases susceptibility to bacterial pneumonia caused by Streptococcus pneumoniae (the pneumococcus), the leading cause of infectious death in the elderly. Aged mice had increased lung inflammation as determined by cytokine analysis and histopathology of lung sections. Immunoblotting for p16, pRb, and mH2A showed that elderly humans and aged mice had increased levels of these senescence markers in their lungs vs. young controls. Keratin 10 (K10), laminin receptor (LR), and platelet-activating factor receptor (PAFr), host proteins known to be co-opted for bacterial adhesion, were also increased. Aged mice were found to be highly susceptible to pneumococcal challenge in a PsrP, the pneumococcal adhesin that binds K10, dependent manner. In vitro senescent A549 lung epithelial cells had elevated K10 and LR protein levels and were up to 5-fold more permissive for bacterial adhesion. Additionally, exposure of normal cells to conditioned media from senescent cells doubled PAFr levels and pneumococcal adherence. Genotoxic stress induced by bleomycin and oxidative stress enhanced susceptibility of young mice to pneumonia and was positively correlated with enhanced p16, inflammation, and LR levels. These findings suggest that cellular senescence facilitates bacterial adhesion to cells in the lungs and provides an additional molecular mechanism for the increased incidence of community-acquired pneumonia in the elderly. This study is the first to suggest a second negative consequence for the senescence-associated secretory phenotype.

Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice.

Rapamycin was administered in food to genetically heterogeneous mice from the age of 9 months and produced significant increases in life span, including maximum life span, at each of three test sites. Median survival was extended by an average of 10% in males and 18% in females. Rapamycin attenuated age-associated decline in spontaneous activity in males but not in females. Causes of death were similar in control and rapamycin-treated mice. Resveratrol (at 300 and 1200 ppm food) and simvastatin (12 and 120 ppm) did not have significant effects on survival in male or female mice. Further evaluation of rapamycin's effects on mice is likely to help delineate the role of the mammalian target of rapamycin complexes in the regulation of aging rate and age-dependent diseases and may help to guide a search for drugs that retard some or all of the diseases of aging.

Dysregulated inflammation as a risk factor for pneumonia in the elderly.

Advances in modern medicine have led to an increase in the median life span and an expansion of the world's population over the age of 65. With increasing numbers of the population surviving to the extreme of age, those at risk for the development of pneumonia will approach 2 billion by the year 2050. Numerous age-related changes in the lung likely contribute to the enhanced occurrence of pneumonia in the elderly. Inflammation in the elderly has been shown to increase risk prior to infection; age-associated inflammation enhances bacterial ligand expression in the lungs which increases the ability of bacteria to attach and invade host cells. Conversely, the elaboration of the acute inflammatory response during early infection has been found to decrease with age resulting in a delayed immune response and diminished bacterial killing. Finally, the resolution of the inflammatory response during the convalescent stage back to "baseline" is often prolonged in the elderly and associated with negative outcomes, such as adverse cardiac events. The focus of this review will be to discuss our current understanding of the potential mechanisms by which dysregulated inflammation (both prior to and following an infectious insult) enhances susceptibility to and severity of community acquired pneumonia (CAP) in the elderly with an emphasis on pneumococcal pneumonia, the leading cause of CAP.

Consensual pupillary light response in the red-eared slider turtle (Trachemys scripta elegans).

Purpose of this study was to determine if the turtle has a consensual pupillary light response (cPLR), and if so, to compare it to its direct pupillary light response (dPLR). One eye was illuminated with different intensities of light over a four log range while keeping the other eye in darkness. In the eye directly illuminated, pupil diameter was reduced by as much as approximately 31%. In the eye not stimulated by light, pupil diameter was also reduced but less to approximately 11%. When compared to the directly illuminated eye, this generated a ratio, cPLR-dPLR, equal to 0.35. Ratio of slopes for log/linear fits to plots of pupil changes versus retinal irradiance for non-illuminated (-1.27) to illuminated (-3.94) eyes closely matched at 0.32. cPLR had time constants ranging from 0.60 to 1.20min; however, they were comparable and not statistically different from those of the dPLR, which ranged from 1.41 to 2.00min. Application of mydriatic drugs to the directly illuminated eye also supported presence of a cPLR. Drugs reduced pupil constriction by approximately 9% for the dPLR and slowed its time constant to 9.58min while simultaneous enhancing constriction by approximately 6% for the cPLR. Time constant for the cPLR at 1.75min, however, was not changed. Results support that turtle possesses a cPLR although less strong than its dPLR.

Statins protect against fulminant pneumococcal infection and cytolysin toxicity in a mouse model of sickle cell disease.

Sickle cell disease (SCD) is characterized by intravascular hemolysis and inflammation coupled to a 400-fold greater incidence of invasive pneumococcal infection resulting in fulminant, lethal pneumococcal sepsis. Mechanistically, invasive infection is facilitated by a proinflammatory state that enhances receptor-mediated endocytosis of pneumococci into epithelial and endothelial cells. As statins reduce chronic inflammation, in addition to their serum cholesterol-lowering effects, we hypothesized that statin therapy might improve the outcome of pneumococcal infection in SCD. In this study, we tested this hypothesis in an experimental SCD mouse model and found that statin therapy prolonged survival following pneumococcal challenge. The protective effect resulted in part from decreased platelet-activating factor receptor expression on endothelia and epithelia, which led to reduced bacterial invasion. An additional protective effect resulted from inhibition of host cell lysis by pneumococcal cholesterol-dependent cytotoxins (CDCs), including pneumolysin. We conclude therefore that statins may be of prophylactic benefit against invasive pneumococcal disease in patients with SCD and, more broadly, in settings of bacterial pathogenesis driven by receptor-mediated endocytosis and the CDC class of toxins produced by Gram-positive invasive bacteria.

Age-associated inflammation and toll-like receptor dysfunction prime the lungs for pneumococcal pneumonia.

BACKGROUND: Aging is associated with increased inflammation and risk of community-acquired pneumonia. Streptococcus pneumoniae co-opts the nuclear factor kappa B (NFkB)-regulated proteins polymeric immunoglobulin receptor (pIgR) and platelet-activating factor receptor (PAFr) to attach and invade cells. We sought to determine whether aging and chronic inflammation were associated with increased pIgR and PAFr levels in the lungs and increased susceptibility to S. pneumoniae infection. METHODS: Lung protein and messenger RNA levels were quantitated using Western blot and quantitative polymerase chain reaction. NFkB activation was measured by electrophoretic mobility shift assay. Cytokine levels were measured by cytometric bead analysis. To model chronic inflammation, mice were implanted with osmotic pumps that delivered tumor necrosis factor-alpha. RESULTS: Aged mice and those infused with tumor necrosis factor-alpha had increased levels of pIgR and PAFr in their lungs and were more susceptible to S. pneumoniae infection. During pneumonia, aged mice had reduced levels of pIgR and PAFr and less NFkB activation, despite greater bacterial burden. We determined that aged mice had decreased amounts of lung Toll-like receptors 1, 2, and 4 and reduced capacity to respond to S. pneumoniae with proinflammatory cytokine production. CONCLUSIONS: Aged mice and, potentially, elderly humans are more susceptible to pneumonia because of a priming effect of chronic inflammation and Toll-like receptor dysfunction.