The Postoperative Airway Compromise Score-First Steps to Developing a Postoperative Tool for the Assessment of Upper Airway-Related Complications Following Anterior Cervical Spine Surgery.

BACKGROUND: Acute upper airway compromise is a rare but catastrophic complication after anterior cervical discectomy and fusion. This study aims to develop a score to identify patients at risk of acute postoperative airway compromise (PAC). METHODS: Potential risk factors for acute PAC were selected by a modified Delphi process. Ten patients with acute PAC were identified of 1466 patients who underwent elective anterior cervical discectomy and fusion between July 2014 and May 2019. A comparison group was created by a randomized selection process (non-PAC group). Factors associated with PAC and a P value of < 0.10 were entered into a logistic regression model and coefficients contributed to each risk factor's overall score. Calibration of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Quantitative discrimination was calculated, and the final model was internally validated with bootstrap sampling. RESULTS: We identified 18 potential risk factors from our Delphi process, of which 6 factors demonstrated a significant association with airway compromise: age >65 years, current smoking status, American Society of Anesthesiologists class >2, history of a bleeding disorder, surgery of upper subaxial cervical spine (above C4), and duration of surgery >179 minutes. The final prediction model included 5 predictors with very strong performance characteristics. These 5 factors formed the PAC score, with a range from 0 to 100. A score of 20 yielded the greatest balance of sensitivity (80%) and specificity (88%). CONCLUSIONS: The acute PAC score demonstrates strong performance characteristics. The PAC score might help identify patients at risk of upper airway compromise caused by surgical site abnormalities.

HLA Mismatching Favoring Host-Versus-Graft NK Cell Activity Via KIR3DL1 Is Associated With Improved Outcomes Following Lung Transplantation.

Chronic lung allograft dysfunction (CLAD) is linked to rejection and limits survival following lung transplantation. HLA-Bw4 recipients of HLA-Bw6 grafts have enhanced host-versus-graft (HVG) natural killer (NK) cell activity mediated by killer cell immunoglobulin-like receptor (KIR)3DL1 ligand. Because NK cells may promote tolerance by depleting antigen-presenting cells, we hypothesized improved outcomes for HLA-Bw4 recipients of HLA-Bw6 grafts. We evaluated differences in acute cellular rejection and CLAD-free survival across 252 KIR3DL1+ recipients from University of California, San Francisco (UCSF). For validation, we assessed survival and freedom from bronchiolitis obliterans syndrome (BOS), retransplantation, or death in 12 845 non-KIR typed recipients from the United Network for Organ Sharing (UNOS) registry. Cox proportional hazards models were adjusted for age, gender, ethnicity, transplant type, and HLA mismatching. HVG-capable subjects in the UCSF cohort had a decreased risk of CLAD or death (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.36-0.88) and decreased early lymphocytic bronchitis. The HVG effect was not significant in subjects with genotypes predicting low KIR3DL1 expression. In the UNOS cohort, HVG-capable subjects had a decreased risk of BOS, retransplant, or death (HR 0.95, 95% CI 0.91-0.99). Survival improved with the higher-affinity Bw4-80I ligand and in Bw4 homozygotes. Improved outcomes in HVG-capable recipients are consistent with a protective NK cell role. Augmentation of NK activity could supplement current immunosuppression techniques.

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study.

Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study from 2010 to 2016, we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-min walk test exercise capacity as predictors of HRQL change. Among 211 initial participants (92% of those eligible), LT improved HRQL by all 5 measures (p < 0.05) and all but SF12-Mental Health improved by threefold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p < 0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net benefits of LT.

Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. METHODS: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. RESULTS: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. CONCLUSIONS: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.

Ceruminous adenocarcinoma: An analysis of the Surveillance Epidemiology and End Results (SEER) database.

OBJECTIVES: Ceruminous adenocarcinoma is a rare malignancy. However, due to the paucity of cases, this has been difficult to study. Using a population-based national database, patient demographics and survival trends were analyzed to further elucidate the management of this malignancy. METHODS: The SEER database was queried for patients diagnosed with ceruminous adenocarcinoma between 1973 and 2010. RESULTS: Twenty-two patients were identified in the database. The average age of diagnosis was between 60 and 64 years. All of the patients underwent surgical resection of the primary malignancy. Eight patients (36%) also had postoperative radiation. CONCLUSIONS: Ceruminous adenocarcinoma is uncommon but may not have as poor a prognosis as previously thought. Surgical resection alone appears to be a reasonable treatment option. Larger prospective studies are needed, but database analysis like this may provide clarity on the management of uncommon diseases.

Effect of a second primary thyroid carcinoma on patients with head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to characterize the timing, histology, and behavior of second primary thyroid carcinoma (SPTC) developing after a diagnosis of head and neck squamous cell carcinoma (HNSCC). METHODS: We conducted a retrospective review of the Surveillance, Epidemiology, and End Results (SEER) 9 database. RESULTS: Patients with HNSCC who develop SPTC die 1.6 times sooner than those without SPTC. This effect is only seen if SPTC presents >6 months after diagnosis of HNSCC. Models were adjusted for age, sex, year of diagnosis, and location of HNSCC. There was no effect of prior radiation therapy on either mortality rates or time to development of thyroid cancer in patients with SPTC. The type of thyroid carcinoma that developed was similar between cohorts. CONCLUSION: The development of SPTC in patients with HNSCC results in decreased overall length of survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E890-E894, 2016.

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.

Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube.

Bronchoalveolar lavage cell immunophenotyping facilitates diagnosis of lung allograft rejection.

Supplementary methods to identify acute rejection and to distinguish rejection from infection may improve clinical outcomes for lung allograft recipients. We hypothesized that distinct bronchoalveolar lavage (BAL) cell profiles are associated with rejection and infection. We retrospectively compared 2939 BAL cell counts and immunophenotypes against concomitantly obtained transbronchial biopsies and microbiologic studies. We randomly assigned 317 subjects to a derivation or validation cohort. BAL samples were classified into four groups: infection, rejection grade ≥A1, both or neither. We employed generalized estimating equation and survival modeling to identify clinical predictors of rejection and infection. We found that CD25(+) and natural killer cell percentages identified a twofold increased odds of rejection compared to either the infection or the neither infection nor rejection groups. Also, monocytes, lymphocytes and eosinophil percentages were independently associated with rejection. A four-predictor scoring system had high negative predictive value (96-98%) for grade ≥A2 rejection, predicted future rejection in the validation cohort and predicted increased risk of bronchiolitis obliterans syndrome in otherwise benign samples. In conclusion, BAL cell immunophenotyping discriminates between infection and acute rejection and predicts future outcomes in lung transplant recipients. Although it cannot replace histopathology, immunophenotyping may be a clinically useful adjunct.

Scedosporium prolificans pericarditis and mycotic aortic aneurysm in a lung transplant recipient receiving voriconazole prophylaxis.

Despite the adoption of antifungal prophylaxis, fungal infections remain a significant concern in lung transplant recipients. Indeed, some concern exists that such prophylaxis may increase the risk of infection with drug-resistant fungal organisms. Here, we describe a case of disseminated Scedosporium prolificans infection, presenting as pericarditis, which developed in a lung transplant patient receiving prophylactic voriconazole for 8 months. The epidemiology and clinical presentation of S. prolificans infections are reviewed, and controversies surrounding antifungal prophylaxis and the development of resistant infections are discussed.

Automated processing integrated with a microflow cytometer for pathogen detection in clinical matrices.

A spinning magnetic trap (MagTrap) for automated sample processing was integrated with a microflow cytometer capable of simultaneously detecting multiple targets to provide an automated sample-to-answer diagnosis in 40 min. After target capture on fluorescently coded magnetic microspheres, the magnetic trap automatically concentrated the fluorescently coded microspheres, separated the captured target from the sample matrix, and exposed the bound target sequentially to biotinylated tracer molecules and streptavidin-labeled phycoerythrin. The concentrated microspheres were then hydrodynamically focused in a microflow cytometer capable of 4-color analysis (two wavelengths for microsphere identification, one for light scatter to discriminate single microspheres and one for phycoerythrin bound to the target). A three-fold decrease in sample preparation time and an improved detection limit, independent of target preconcentration, was demonstrated for detection of Escherichia coli 0157:H7 using the MagTrap as compared to manual processing. Simultaneous analysis of positive and negative controls, along with the assay reagents specific for the target, was used to obtain dose-response curves, demonstrating the potential for quantification of pathogen load in buffer and serum.

Social networking and professionalism in otolaryngology residency applicants.

OBJECTIVES/HYPOTHESIS: To assess compliance with Accreditation Council for Graduation Medical Education standards of professionalism among otolaryngology residency applicants with publicly searchable Facebook profiles. STUDY DESIGN: Case series. METHODS: Applicants to an otolaryngology residency program were searched on the Facebook website. Multiple matches were narrowed by available information until the correct individual was identified. Searches were performed in a manner that would not allow access to restricted information, thus showing only what would be accessible publicly. Four reviewers evaluated all profiles and generated a professionalism score. Scores were collated with National Resident Matching Program data and match results to identify significant associations. RESULTS: Of the 234 applicants to our institution, 119 had Facebook profiles. Of these, 85 profiles contained information beyond simple demographics. Eleven percent of applicant profiles contained pictures or text that at least one reviewer felt could be perceived as unprofessional. There were six profiles with content considered to be concerning and one profile that contained clear violations of professional boundaries. Professionalism score did not correlate with whether the applicant matched, was interviewed, or received a place on the rank list. Age, gender, marital status, and Step 1 score did not correlate with a lower professionalism score. Our series included 61% of all otolaryngology applicants. CONCLUSIONS: Publicly available Facebook profiles with questionable content existed for 11% of otolaryngology applicants in this series. This finding did not affect applicants' match outcomes, nor was it predicted by any data available on the applicants' applications.

Cytomegalovirus disease and infection in lung transplant recipients in the setting of planned indefinite valganciclovir prophylaxis.

BACKGROUND: The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid. METHODS: We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months). RESULTS: Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development. CONCLUSIONS: Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.

Outcomes of intubation in difficult airways due to head and neck pathology.

The purpose of this study was to examine the impact of surgical pathology, anesthesiologist experience, and airway technique on surgically relevant outcomes in patients identified by preoperative laryngoscopy to have a difficult airway due to head and neck pathology. We prospectively recorded a series of 152 difficult airway cases due to head and neck pathology out of 2,145 direct laryngoscopies undertaken between November 2005 and June 2008. One of two senior anesthesiologists specializing in head and neck procedures intubated 101 (66.4%) of the 152 patients and did so 3.3 minutes faster (p = 0.51), with better oxygenation (87.3 vs. 81.8%; p = 0.02) and fewer airway plan changes (p = 0.001) than did other, nonspecialist anesthesiologists. Predictors of failure of the first intubation plan included: cancer diagnosis (p = 0.02), previous radiotherapy (p = 0.03), and supraglottic lesions (p = 0.03). Glottic/subglottic lesions required the most intubation attempts (p = 0.02). Awake fiberoptic intubation was the most common method used (44.7%) but resulted in a change in the airway plan in 6 cases (8.8%). Gas induction maintained the best oxygenation (p = 0.01). Awake tracheostomy was infrequent (1.3%) and took the longest (p = 0.006). We concluded that difficult airways due to head and neck pathology require teamwork and a backup plan. An anesthesiologist specializing in head and neck procedures may help to avoid adverse outcomes associated with cancer, especially previously irradiated supraglottic/glottic lesions, leading to a less frequent need for awake tracheostomy.

Human umbilical cord blood cells alter blood and spleen cell populations after stroke.

The human umbilical cord blood (HUCB) mononuclear cell (MNC) fraction is a mixed population of cells that induces functional repair in rodent models of stroke when injected intravenously (i.v.). The transplanted cells are found in the infarcted hemisphere and the spleen. The goal of this project was to determine the nature of the interaction between the HUCB MNCs cells and splenic immune cells. Male Sprague Dawley rats underwent permanent middle cerebral artery occlusion (MCAO) and received i.v. injection of either vehicle (MCAO only), HUCB MNCs or MNCs depleted of CD14+ monocytes, CD133+ stem cells or CD19+ B cells 48 hours post-stroke. At 72 hours post-MCAO, the animals were euthanized and the spleens and blood MNCs harvested for flow cytometry and mitogen proliferation assays. All HUCB cell preparations decreased the percentage of T cells in the spleen and monocytes in the blood (p < 0.05). MNCs depleted of CD14+ and CD19+ decreased the percentage of macrophage (p < 0.001), while CD133 depleted MNCs increased the percentage of macrophage in spleen (p < 0.001); MNC did not alter the macrophage population from the level observed after MCAO. Only HUCB MNC significantly decreased Concanavalin A (ConA)-induced T cell stimulation (p < 0.05). These results suggest that the effects of HUCB MNC in the spleen are not due to a single HUCB population, but the interaction of all the subpopulations together.

Survival following lung transplantation for silicosis and other occupational lung diseases.

BACKGROUND: Information is scant assessing outcomes in lung transplantation (LT) in advanced occupational lung diseases (OLD). AIMS: To analyse survival after LT for OLD. METHODS: Using data from the US Organ Procurement and Transplantation Network Registry (OPTN-R), we identified subjects aged ≥ 18 years transplanted for OLD from 2005 to 2010. OPTN-R selected referents of corresponding age, sex and body mass index (BMI) who underwent LT for other diagnoses were also identified. Post-LT survival time was estimated with Cox proportional hazard models. Baseline age, BMI, forced expiratory volume in 1 s, creatinine, lung allocation score, donor age, donor lung ischaemic time and transplant type (single versus bilateral) were included as covariates. Time-dependent covariates were used to model differences in relative risk over time. RESULTS: Thirty-seven males underwent LT for silicosis (n = 19) or other OLD (n = 18) during the analytic period (0.5% of all LTs). For non-silicotic OLD, 6-month and 1- and 3-year survival estimates were 66, 55 and 55%, compared with the silicotic group (86, 86 and 76%) and referent group (89, 84 and 67%). During the first year post-transplant, those with OLD (silicosis and others combined) manifested an overall 2-fold increased mortality risk [hazard ratio (HR) 2.3, 95% CI 1.3-4.4; P < 0.05] compared to referents. In stratified analysis, this increased risk of death was restricted to those with non-silicotic OLD (HR 3.1, 95% CI 1.5-6.6; P < 0.01). Poorer survival was limited to the first year post-LT. CONCLUSIONS: Subjects undergoing LT for OLD other than silicosis may be at increased risk of death in the first year post-transplantation.

Incidence and outcomes of stricture formation postlaryngectomy.

OBJECTIVE: Postlaryngectomy stricture formation and dysphagia negatively affect quality of life and result in nutritional compromise. Understanding risk factors and successful treatment strategies may improve treatment outcomes. STUDY DESIGN: Historical cohort study. SETTING: Tertiary care medical center. SUBJECTS AND METHODS: Patients at a tertiary care center who underwent a total laryngectomy between 2003 and 2009 (N = 263) were evaluated in a retrospective manner. Patient demographics, comorbidities, tobacco and alcohol usage, dietary outcomes, feeding tube dependence, and treatment modalities were assessed. Management strategies and outcomes were evaluated. RESULTS: Strictures developed in 19% (n = 49) of patients, and the majority (82%) occurred in the first year. Incidences of stricture formation were similar for primary (19%) and salvage laryngectomy (19%) patients. Patients undergoing salvage laryngectomy were 2 times more likely to be reconstructed with a free flap, whereas those undergoing a primary laryngectomy were 3 times more likely to be closed primarily. Tubed flap reconstruction significantly increased the incidence of stricture formation compared to primary closure (P = .02) in salvage laryngectomy cases. In primary laryngectomy patients, stricture formation did not correlate with flap reconstruction (P = .34) or adjuvant radiation therapy (P = .79). Patients who required a single dilation had better dietary outcomes compared to patients who required serial dilations (P = .14). There was no difference in overall disease-free survival in primary vs salvage laryngectomy patients (P = .95). CONCLUSION: Rates of stricture formation were the same in patients undergoing salvage compared to primary total laryngectomy.

The impact of pretransplant mechanical ventilation on short- and long-term survival after lung transplantation.

Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan-Meier methods. Risk of death was estimated by hazard ratios employing time-dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short-term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.

Lipopolysacchride-treated mammary carcinomas secrete proinflammatory chemokines and exhibit reduced growth rates in vivo, but not in vitro.

Toll-like receptors (TLR) are pattern recognition receptors that play a pivotal role in the initiation of immune responses. Here we report that the murine mammary carcinoma 4T1 constitutively expressed genes encoding TLR2, 3, 4 and 5. Moreover, treatment of the 4T1 cell line with peptidoglycan (PGN), polyinosinic-polycytidylic acid (Poly(I:C)) or lipopolysaccharide (LPS), agonists for TLR2, 3 or 4 respectively, induced nuclear translocation of NFkappaB and secretion of CCL2, CCL5 and CXCL1 in a dose dependent manner. Although treating the tumor cells with the TLR agonists did not modulate growth or viability of the tumor cells in vitro, 4T1 exhibited a decreased growth rate in vivo following treatment with LPS that was dependent upon the presence of CD8(+) T cells. Analysis of 3 additional murine mammary carcinomas revealed that they also secreted CCL2, CCL5 and CXCL1 in response to TLR agonist treatment, and LPS treated 168 and SM1 tumors exhibited decreased growth rates in vivo, but not in vitro. These data indicated that 4 out of 4 murine mammary carcinomas secreted proinflammatory chemokines following treatment with TLR agonists, and 3 out of 4 of the mammary carcinomas responded to LPS treatment in a manner that decreased tumor growth in vivo.