Social and Demographic Influences of Trust in Cancer Information Among Brooklyn, New York Residents.

Little is known regarding the patterns of trust sources for cancer information among diverse populations in the US, which is particularly poignant during the current era of misinformation. Our objective to assess trust from different sources among a sample of Brooklyn, New York residents. Using data from the NCI funded Brooklyn Cancer Health Impact Program, we examined HINTS validated questions examining trust in cancer information across 9 sources. Logistic regression models were used to examine associations with cancer information trust sources. For trust in government health agencies, participants who had less than a college degree were almost 30% less likely to report high levels of trust (aOR: 0.71; 95% CI: 0.52-0.98), participants who reported a household income under $50,000 were 35% less likely report high levels of trust (aOR: 0.65; 95% CI: 0.47-0.89). Participants whose primary language was Spanish were significantly less likely to trust government (aOR: 0.45; 95% CI: 0.29-0.70), newspapers and magazines (aOR: 0.54; 95% CI, 0.34-0.84), and charitable organizations (aOR: 0.48; 95% CI, 0.31-0.75) compared to participants whose primary was English. New York is the most populous city in the US, a city of immigrants, and it is important for healthcare and public health professionals to explore how they can utilize media to provide accurate scientific evidence to combat cancer misinformation.

The role of staphopain a in Staphylococcus aureus keratitis.

Staphylococcus aureus is a common bacterial isolate from cases of microbial keratitis. The virulence factors that contribute to its pathogenicity during this disease have not been fully resolved. The aim of the current study was to examine the effects of the extracellular protease Staphopain A on corneal virulence. Two strains were used, one Staph 38 that gives a high pathology score during keratitis and a less virulent strain ATCC 8325-4. The effect of inhibition of Staphopain by general or specific protease inhibitors on adhesion of strains to fibronectin-coated glass or PMMA was determined. This was followed by an analysis of the effect of Staphopain A on the ability of the bacteria to adhere to and invade corneal epithelial cells. Finally, the effect of inhibiting Staphopain A on pathogenesis in a mouse model of keratitis was studied. Staphopain A increased the adhesion of strains to fibronectin-coated substrata and inhibition of Staphopain A reduced adhesion. The inhibition of Staphopain A by staphostatin A significantly decreased both association with and invasion into human corneal epithelial cells by 15-fold for strain Saur38. Inhibition of Staphopain A significantly reduced the pathology associated with S. aureus keratitis, reducing the infecting numbers of bacteria from 1.8x105 to <1x104 cells/cornea (p ≤ 0.001), significantly reducing the corneal pathology score (p ≤ 0.038) and reducing the numbers of infiltrating PMNs. This study shows that Staphopain increases adhesion and invasion of corneal cells due to increasing fibronectin binding and its inhibition has a significant impact on pathogenicity of S. aureus during keratitis.

Identification of pathogenic factors potentially involved in Staphylococcus aureus keratitis using proteomics.

Staphylococcus is a leading cause of microbial keratitis, characterized by destruction of the cornea by bacterial exoproteins and host-associated factors. The aim of this study was to compare extracellular and cell-associated proteins produced by two different isolates of S. aureus, a virulent clinical isolate (Staph 38) and a laboratory strain (Staphylococcus aureus 8325-4) of weaker virulence in the mouse keratitis model. Proteins were analyzed using 2D polyacrylamide gel electrophoresis and identified by subsequent mass spectrometry. Activity of staphylococcal adhesins was assessed by allowing strains to bind to various proteins adsorbed onto polymethylmethacrylate squares. Thirteen proteins in the extracellular fraction and eight proteins in the cell-associated fractions after bacterial growth were produced in increased amounts in the clinical isolate Staph 38. Four of these proteins were S. aureus virulence factor adhesins, fibronectin binding protein A, staphopain, glyceraldehyde-3-phosphate dehydrogenase 2 and extracellular adherence protein. The clinical isolate Staph 38 adhered to a greater extent to all mammalian proteins tested, indicating the potential of the adhesins to be active on its surface. Other proteins with increased expression in Staph 38 included potential moonlighting proteins and proteins involved in transcription or translation. This is the first demonstration of the proteome of S. aureus isolates from keratitis. These results indicate that the virulent clinical isolate produces more potentially important virulence factors compared to the less virulent laboratory strain and these may be associated with the ability of a S. aureus strain to cause more severe keratitis.

The role of CXC chemokine receptor 2 in Staphylococcus aureus keratitis.

Staphylococcus aureus is a leading cause of corneal infection. CXC receptor 2 binding chemokines have been implicated in the pathogenesis of Pseudomonas aeruginosa keratitis. The role of this receptor in immune responses during Staphylococcus keratitis remains to be fully understood. Corneas of CXC receptor 2 knockout and wild-type mice (Cmkar -/- & Cmkar +/+) were scratched and 1 × 10(8) cfu/ml of strain Staph 38 applied. Twenty-four hours post-infection, mice were sacrificed and eyes harvested for enumeration of bacteria and measurement of myeloperoxidase levels. Production of inflammatory mediators, cellular adhesion molecules and chemokines in response to infection were investigated by ELISA, and PCR. 24 h after challenge with S. aureus, Cmkar -/- mice had developed a more severe response with a 50-fold higher bacterial load than WT mice. PMNs failed to penetrate the corneas of Cmkar -/- mice. However, concentrations of KC, MIP-2, IL-1ß and IL-6 were significantly elevated (6-13 fold) in Cmkar-/- mice. The concentration of LTB4 was decreased (2 fold). Cmkar-/- mice failed to upregulate mRNA for VCAM-1 or PECAM-1 in response to infection, but had constitutively higher levels of ICAM-1. A lack of CXC receptor 2 lead to an inability to control bacterial numbers as a result of failure of PMNs to penetrate the cornea to the site of infection, even when chemokines were more highly produced. These results imply that CXCR2-mediated signaling through upregulation of adhesion molecules is essential to margination of PMNs in this infection model.

Racial and Ethnic Inequities in Cancer Care Continuity During the COVID-19 Pandemic Among Those With SARS-CoV-2.

Importance: Racially and ethnically minoritized US adults were disproportionately impacted by the COVID-19 pandemic and experience poorer cancer outcomes, including inequities in cancer treatment delivery. Objective: To evaluate racial and ethnic disparities in cancer treatment delays and discontinuations (TDDs) among patients with cancer and SARS-CoV-2 during different waves of the COVID-19 pandemic in the United States. Design, Setting, and Participants: This cross-sectional study used data from the American Society of Clinical Oncology Survey on COVID-19 in Oncology Registry (data collected from April 2020 to September 2022), including patients with cancer also diagnosed with SARS-CoV-2 during their care at 69 US practices. Racial and ethnic differences were examined during 5 different waves of the COVID-19 pandemic in the United States based on case surge (before July 2020, July to November 2020, December 2020 to March 2021, April 2021 to February 2022, and March to September 2022). Exposures: Race and ethnicity. Main Outcomes and Measures: TDD was defined as any cancer treatment postponed more than 2 weeks or cancelled with no plans to reschedule. To evaluate TDD associations with race and ethnicity, adjusted prevalence ratios (aPRs) were estimated using multivariable Poisson regression, accounting for nonindependence of patients within clinics, adjusting for age, sex, body mass index, comorbidities, cancer type, cancer extent, and SARS-CoV-2 severity (severe defined as death, hospitalization, intensive care unit admission, or mechanical ventilation). Results: A total of 4054 patients with cancer and SARS-CoV-2 were included (143 [3.5%] American Indian or Alaska Native, 176 [4.3%] Asian, 517 [12.8%] Black or African American, 469 [11.6%] Hispanic or Latinx, and 2747 [67.8%] White; 2403 [59.3%] female; 1419 [35.1%] aged 50-64 years; 1928 [47.7%] aged ≥65 years). The analysis focused on patients scheduled (at SARS-CoV-2 diagnosis) to receive drug-based therapy (3682 [90.8%]), radiation therapy (382 [9.4%]), surgery (218 [5.4%]), or transplant (30 [0.7%]), of whom 1853 (45.7%) experienced TDD. Throughout the pandemic, differences in racial and ethnic inequities based on case surge with overall TDD decreased over time. In multivariable analyses, non-Hispanic Black (third wave: aPR, 1.56; 95% CI, 1.31-1.85) and Hispanic or Latinx (third wave: aPR, 1.35; 95% CI, 1.13-1.62) patients with cancer were more likely to experience TDD compared with non-Hispanic White patients during the first year of the pandemic. By 2022, non-Hispanic Asian patients (aPR, 1.51; 95% CI, 1.08-2.12) were more likely to experience TDD compared with non-Hispanic White patients, and non-Hispanic American Indian or Alaska Native patients were less likely (aPR, 0.37; 95% CI, 0.16-0.89). Conclusions and Relevance: In this cross-sectional study of patients with cancer and SARS-CoV-2, racial and ethnic inequities existed in TDD throughout the pandemic; however, the disproportionate burden among racially and ethnically minoritized patients with cancer varied across SARS-CoV-2 waves. These inequities may lead to downstream adverse impacts on cancer mortality among minoritized adults in the United States.

Optimizing presurgical education for patients with head and neck cancer receiving laryngectomy and free flap surgery: A qualitative study.

BACKGROUND: There has been limited study of oncology professionals' perspectives on optimizing delivery of presurgical education for individuals with head and neck cancer (HNC). Therefore, we assessed oncology professionals' perspectives about presurgical education for laryngectomy and free flap surgeries, which have a significant impact on patients' quality of life. METHODS: Interviews were conducted with 27 oncology professionals from an NCI-designated Comprehensive Cancer Center and a community oncology setting. RESULTS: Participants identified six recommendations to improve presurgical education: (1) establishing preoperative consultations with allied health professionals; (2) educating patients and providers on the concept of team-based care; (3) optimizing education through multimodal strategies; (4) connecting patients with other HNC surgical patients; (5) preparing caregivers for their role; and (6) educating patients on insurance navigation. CONCLUSIONS: Study findings demonstrate gaps in the timing, content, and mode of delivery for presurgical education and suggest strategies for further evaluation in future studies.

Support Through Remote Observation and Nutrition Guidance (STRONG), a digital health intervention to reduce malnutrition among pancreatic cancer patients: A study protocol for a pilot randomized controlled trial.

Background: Malnutrition is a common and distressing condition among pancreatic cancer patients. Fewer than a quarter of pancreatic cancer patients receive medical nutrition therapy (MNT), important for improving nutritional status, weight maintenance, quality of life and survival. System, provider, and patient level barriers limit access to MNT. We propose to examine the feasibility of a 12-week multi-level, digital health intervention designed to expand MNT access among pancreatic cancer patients. Methods: Individuals with advanced pancreatic cancer starting chemotherapy (N = 80) will be 1:1 randomized to the intervention or usual care. The Support Through Remote Observation and Nutrition Guidance (STRONG) intervention includes system-level (e.g., routine malnutrition and screening), provider-level (e.g., dietitian training and web-based dashboard), and patient-level strategies (e.g., individualized nutrition plan, self-monitoring of dietary intake via Fitbit, ongoing goal monitoring and feedback). Individuals receiving usual care will be referred to dietitians based on their oncologists' discretion. Study assessments will be completed at baseline, 4-, 8-, 12-, and 16-weeks. Results: Primary outcomes will be feasibility (e.g., recruitment, retention, assessment completion) and acceptability. We will collect additional implementation outcomes, such as intervention adherence, perceived usability, and feedback on intervention quality via an exit interview. We will collect preliminary data on outcomes that may be associated with the intervention including malnutrition, quality of life, treatment outcomes, and survival. Conclusion: This study will advance our knowledge on the feasibility of a digital health intervention to reduce malnutrition among individuals with advanced pancreatic cancer. Trial registration: NCT05675059, registered on December 9, 2022.

Breast Density Analysis Using Digital Breast Tomosynthesis.

We evaluated an automated percentage of breast density (BD) technique (PDa) with digital breast tomosynthesis (DBT) data. The approach is based on the wavelet expansion followed by analyzing signal dependent noise. Several measures were investigated as risk factors: normalized volumetric; total dense volume; average of the DBT slices (slice-mean); a two-dimensional (2D) metric applied to the synthetic images; and the mean and standard deviations of the pixel values. Volumetric measures were derived theoretically, and PDa was modeled as a function of compressed breast thickness. An alternative method for constructing synthetic 2D mammograms was investigated using the volume results. A matched case-control study (n = 426 pairs) was analyzed. Conditional logistic regression modeling, controlling body mass index and ethnicity, was used to estimate odds ratios (ORs) for each measure with 95% confidence intervals provided parenthetically. There were several significant findings: volumetric measure [OR = 1.43 (1.18, 1.72)], which produced an identical OR as the slice-mean measure as predicted; [OR =1.44 (1.18, 1.75)] when applied to the synthetic images; and mean of the pixel values (volume or 2D synthetic) [ORs ~ 1.31 (1.09, 1.57)]. PDa was modeled as 2nd degree polynomial (concave-down): its maximum value occurred at 0.41×(compressed breast thickness), which was similar across case-control groups, and was significant from this position [OR = 1.47 (1.21, 1.78)]. A standardized 2D synthetic image was produced, where each pixel value represents the percentage of BD above its location. The significant findings indicate the validity of the technique. Derivations supported by empirical analyses produced a new synthetic 2D standardized image technique. Ancillary to the objectives, the results provide evidence for understanding the percentage of BD measure applied to 2D mammograms. Notwithstanding the findings, the study design provides a template for investigating other measures such as texture.

Breast density analysis of digital breast tomosynthesis.

Mammography shifted to digital breast tomosynthesis (DBT) in the US. An automated percentage of breast density (PD) technique designed for two-dimensional (2D) applications was evaluated with DBT using several breast cancer risk prediction measures: normalized-volumetric; dense volume; applied to the volume slices and averaged (slice-mean); and applied to synthetic 2D images. Volumetric measures were derived theoretically. PD was modeled as a function of compressed breast thickness (CBT). The mean and standard deviation of the pixel values were investigated. A matched case-control (CC) study (n = 426 pairs) was evaluated. Odd ratios (ORs) were estimated with 95% confidence intervals. ORs were significant for PD: identical for volumetric and slice-mean measures [OR = 1.43 (1.18, 1.72)] and [OR = 1.44 (1.18, 1.75)] for synthetic images. A 2nd degree polynomial (concave-down) was used to model PD as a function of CBT: location of the maximum PD value was similar across CCs, occurring at 0.41 × CBT, and PD was significant [OR = 1.47 (1.21, 1.78)]. The means from the volume and synthetic images were also significant [ORs ~ 1.31 (1.09, 1.57)]. An alternative standardized 2D synthetic image was constructed, where each pixel value represents the percentage of breast density above its location. Several measures were significant and an alternative method for constructing a standardized 2D synthetic image was produced.

Financial toxicity among head and neck cancer patients and their caregivers: A cross-sectional pilot study.

Objectives: Head and neck cancer (HNC) patients experience greater financial toxicity than other cancer patients. Research on financial toxicity has concentrated on patients despite many informal caregivers sharing finances and reducing work hours to provide patient care. Thus, our pilot study: (1) assessed the feasibility of financial toxicity screening of HNC patients and their caregivers, and (2) described financial toxicity levels of HNC patients and their caregivers. Methods: We surveyed English-speaking adult HNC patients initiating treatment at a National Cancer Institute-designated Comprehensive Cancer Center and their informal caregivers. This survey assessed demographics and financial toxicity through the Comprehensive Score for Financial Toxicity (COST) measure (0-44 range; lower score indicates higher financial toxicity). Screening feasibility was defined as ≥50% consent rate and ≥60% data completion rate. Results: Our sample included 27 HNC patients and 9 caregivers. They both had slightly lower consent and completion rates than our goals. Patients reported a median COST score of 27 while caregivers reported a median COST score of 16. Approximately 25.9% of patients and 44.4% of caregivers reported high financial toxicity (COST < 17.5). Caregivers reported high concerns about their future financial health and their ability to control the amount of their financial contributions to the patient's care. Conclusions: Patients and caregivers may require additional outreach approaches beyond emailed questionnaires to screen for their financial toxicity systematically. Future research is needed to replicate our results to determine whether differences in financial toxicity occur between patients and caregivers and identify areas of focus for interventions. Level of evidence: IV.

Oncology Providers' and Professionals' Experiences With Suicide Risk Screening Among Patients With Head and Neck Cancer: A Qualitative Study.

PURPOSE: There has been limited study of the implementation of suicide risk screening for patients with head and neck cancer (HNC) as a part of routine care. To address this gap, this study assessed oncology providers' and professionals' perspectives about barriers and facilitators of implementing a suicide risk screening among patients with HNC. MATERIALS AND METHODS: All patients with HNC with an in-person visit completed a suicide risk screening on an electronic tablet. Patients reporting passive death wish were then screened for active suicidal ideation and referred for appropriate intervention. Interviews were conducted with 25 oncology providers and professionals who played a key role in implementation including nurses, medical assistants, patient access representatives, advanced practice providers, physicians, social workers, and informatics staff. The interview guide was based on the Consolidated Framework for Implementation Research. Interviews were transcribed and analyzed for themes. RESULTS: Participants identified multilevel implementation barriers, such as intervention level (eg, patient difficulty with using a tablet), process level (eg, limited nursing engagement), organizational level (eg, limited clinic Wi-Fi connectivity), and individual level (eg, low clinician self-efficacy for interpreting and acting upon patient-reported outcome scores). Participants noted facilitators, such as effective care coordination across nursing and social work staff and the opportunity for patients to be screened multiple times. Participants recommended strengthening patient and clinician education and providing patients with other modalities for data entry (eg, desktop computer in the waiting room). CONCLUSION: Participants identified important intervention modifications that may be needed to optimize suicide risk screening in cancer care settings.

Cancer Screening Among Rural and Urban Clinics During COVID-19: A Multistate Qualitative Study.

PURPOSE: The effects of COVID-19 have been understudied in rural areas. This study sought to (1) identify cancer screening barriers and facilitators during the pandemic in rural and urban primary care practices, (2) describe implementation strategies to support cancer screening, and (3) provide recommendations. METHODS: A qualitative study was conducted (N = 42) with primary care staff across 20 sites. Individual interviews were conducted through videoconference from August 2020 to April 2021 and recorded, transcribed, and analyzed using deductive and inductive coding (hybrid approach) in NVivo 12 Plus. Practices included federally qualified health centers, tribal health centers, rural health clinics, hospital/health system-owned clinics, and academic medical centers across 10 states including urban (55%) and rural (45%) sites. Staff included individuals serving in the dual role of health care provider and administrator (21.4%), health care administrator (23.8%), physician (19.0%), advanced practice provider (11.9%), or resident (23.8%). The interviews assessed perceptions about cancer screening barriers and facilitators, implementation strategies, and future recommendations. RESULTS: Participants reported multilevel barriers to cancer screening including policy-level (eg, elective procedure delays), organizational (eg, backlogs), and individual (eg, patient cancellation). Several facilitators to screening were noted, such as home-based testing, using telehealth, and strong partnerships with referral sites. Practices used strategies to encourage screening, such as incentivizing patients and providers and expanding outreach. Rural clinics reported challenges with backlogs, staffing, telehealth implementation, and patient outreach. CONCLUSION: Primary care staff used innovative strategies during the pandemic to promote cancer screening. Unresolved challenges (eg, backlogs and inability to implement telehealth) disproportionately affected rural clinics.

Health insurance literacy among head and neck cancer patients and their caregivers: A cross-sectional pilot study.

Objective: Health insurance literacy interventions may reduce financial burden and its effects on cancer patients and their caregivers. However, little is known about the health insurance literacy levels of head and neck cancer (HNC) patients and their caregivers. We assessed the feasibility of screening for health insurance literacy in a pilot study and described the health insurance literacy levels of HNC patients and their caregivers. Methods: We administered a survey that assessed demographics and subjective and objective health insurance literacy to HNC patients and their caregivers. Subjective health insurance literacy was measured through the Health Insurance Literacy Measure (score range: 0-84). Objective health insurance literacy was measured through correct answers to a previously developed 10-question knowledge test. Due to a small sample size, inferential statistics were not used; we instead descriptively reported findings. Results: The pilot included 48 HNC patients and 13 caregivers. About 44.4% of patients and 30.8% of caregivers demonstrated low health insurance literacy (HILM ≤60). On the 10-item knowledge test, patients had an average of 6.8 (SD: 2.3) correct responses and caregivers had 7.8 (SD: 1.1) correct responses. Calculating out-of-pocket costs for out-of-network services was challenging; only 9.5% of patients and 0% of caregivers answered correctly. Conclusion: Additional outreach strategies may be needed to supplement screening for health insurance literacy. Areas of focus for interventions include improving understanding of how to calculate financial responsibility for health care services and filing an appeal for health insurance claim denial. Level of Evidence: IV.

Soft contact lens disinfection solution efficacy: clinical Fusarium isolates vs. ATCC 36031.

PURPOSE: To compare the disinfecting efficacy of five soft contact lens multipurpose disinfection solutions (MPDS) against Fusarium solani clinical isolates and the ISO standard ATCC 36031 strain. METHODS: Three commercially available and two recalled MPDS were tested using the ISO/CD 14,729 stand-alone test for contact lens care products against 10 ocular isolates of F. solani and the ATCC 36031 strain. The effect of filtering the fungal suspension before incubating in MPDS was also tested. An average log reduction in colony forming units at the manufacturer's minimum recommended disinfection time was determined and compared with criteria for stand-alone disinfection products for each MPDS against each strain. RESULTS: No difference between filtered and unfiltered fungal suspensions was observed for the ISO standard, whereas in one MPDS the representative clinical isolate showed significantly increased resistance when unfiltered. All but one solution met the stand-alone criteria of 1.0-log reduction of colony forming units against the recommended ISO standard strain ATCC 36031. However, there was wide variation in the ability of MPDS to meet the ISO disinfection criteria when tested against clinical isolates. Among the commercially available MPDS, the two polyquaternium-based solutions showed a higher disinfecting efficacy than the biguanide-based solution. The two recalled solutions showed a lower disinfecting efficacy than the polyquaternium-based solutions. Further, the clinical isolates were significantly more resistant to disinfection than was the recommended ISO strain. CONCLUSIONS: The effect of filtering the fungal suspension to remove hyphae seems to be relevant in the clinical isolate tested, but not in the ISO strain. Clinical isolates were significantly more resistant to disinfection than the recommended ISO strain in the presence of both the commercially available and the recalled MPDS. The use of clinical isolates in stand-alone disinfection testing is indicated. Because there were significant differences in increased resistance exhibited by clinical isolates and in a mixed (unfiltered) culture the use of a single laboratory strain may be insufficient to provide assurance that the disinfection solution will be effective against clinical isolates.

Characteristics of Patients With Cancer and COVID-19 Who Discontinued Cancer Treatment.

This cross-sectional study evaluates the prevalence of and characteristics associated with discontinuation of cancer treatment among patients who received a diagnosis of COVID-19 during their treatment planning.

The role of CXC chemokine receptor 2 in Pseudomonas aeruginosa corneal infection.

Pseudomonas is one of the leading causes of contact lens-related microbial keratitis. Despite the use of antibiotics, the host inflammatory response continues to cause damage to the cornea, which may lead to blindness. CXCR2-binding chemokines have been implicated in the pathogenesis of Pseudomonas keratitis, and the exact role of this receptor remains to be elucidated. Corneas of CXCR2 knockout and wild-type mice (Cmkar 2-/- and Cmkar 2+/+) were scratched, and 2x10(6) CFU/mL Pseudomonas 6294 or 6206 was added to corneas. Twenty-four hours postinfection, mice were killed, and eyes were harvested for enumeration of bacteria, myeloperoxidase (MPO) levels, and inflammatory mediators. Cmkar 2-/- had 20- to 100-fold more bacteria than Cmkar 2+/+ mice. There were no differences in MPO levels between gene knockout and Cmkar 2+/+ mice. Histology revealed PMN were restricted to the limbal area. Levels of CXCR2 chemokines (keratinocyte-derived chemokine and MIP-2) were elevated significantly in gene knockout mice. A lack of CXCR2 leads to an inability to control bacterial numbers as a result of the inability of PMN to reach the site of infection in the avascular cornea. These results imply that CXCR2 is critical to the extravasation of neutrophils into the avascular cornea.

Staphylococcus aureus ocular isolates from symptomatic adverse events: antibiotic resistance and similarity of bacteria causing adverse events.

BACKGROUND: Staphylococcus is the leading cause of microbial keratitis. Staphylococcus aureus isolated from ocular infections with resistance to a wide range of antibiotics, including the commonly prescribed fluoroquinolones, is emerging. The aim of this study was to determine the current antibiotic susceptibilities of ocular S. aureus isolates and also determine whether isolates from different adverse events or those with similar antimicrobial susceptibilities are related. METHODS: A collection of 55 S. aureus strains from ocular adverse events were analysed for antibiotic susceptibility using disc diffusion (CDS method) and typed using PCR-ribotyping and pulsed-field gel electrophoresis (PFGE). RESULTS: S. aureus isolated from symptomatic ocular adverse events in the USA exhibited greater resistance to antibiotics than did those isolated from symptomatic ocular adverse events in Australia or India (p<0.05). A larger proportion of ulcerative keratitis isolates was found to be resistant to antibiotics than isolates from conjunctivitis. PFGE analysis separated related isolates determined by ribotype, on the basis of the adverse event caused by the isolate. Isolates were related within geographical regions and adverse event types. CONCLUSIONS: Similar isolates within a geographical location cause adverse events but there is a genetic difference between isolates causing corneal adverse events and those causing conjunctivitis. Isolates from corneal adverse events were more resistant to antibiotics, with those from the USA exhibiting the greatest resistance. This suggests that virulence may correlate with increased resistance to antibiotics.

A protective role for IL-6 in staphylococcal microbial keratitis.

PURPOSE: To determine whether interleukin-6 (IL-6) plays a protective role in Staphylococcus aureus keratitis in a gene knockout (gko) mouse model and to determine whether IL-6 may be used as a therapy to modulate host responses and control bacterial infection, thereby reducing scarring. METHODS: The eyes of IL-6 gko mice and wild-type mice were challenged topically with S. aureus and examined at 24 hours after infection. Keratitis was examined clinically and histologically. Bacterial and polymorphonuclear leukocytes (PMNs) were enumerated, and cytokine and chemokine levels were determined by ELISA. Exogenous IL-6 was administered to both IL-6 gko and wild-type mice, and clinical parameters were determined. RESULTS: IL-6 gko mice showed more severe disease, with increased bacterial counts and PMNs, than did wild-type mice. Changes in levels of chemokines and cytokines were also observed. Administration of exogenous IL-6 resulted in an improved outcome in IL-6 gko mice, with a threefold reduction in bacterial load. CONCLUSIONS: The data suggest an important regulatory role for IL-6 in modulating excessive inflammatory responses and in controlling bacterial proliferation. IL-6 may play a role in the priming and activation of neutrophils. It could represent a broad-spectrum therapy to improve outcomes in patients who have these potentially blinding infections.

Effect of Salicylic Acid on the Membrane Proteome and Virulence of Pseudomonas aeruginosa.

PURPOSE: This study aimed to determine the effect of salicylic acid on the membrane proteome, sensitivity to antibiotics, and production of microbial keratitis by Pseudomonas aeruginosa. METHODS: P. aeruginosa 6294 was grown in the presence or absence of 30 mM salicylic acid. Bacterial membrane proteins were extracted in carbonate buffer, separated using two-dimensional gel electrophoresis and identified by mass spectrometry. The minimum inhibitory concentration (MIC) of various antibiotics was determined using P. aeruginosa 6294 grown in presence or absence of salicylic acid. The scratch mouse model of microbial keratitis was used to determine whether treatment with 30 mM salicylic acid could improve the outcome of infection. RESULTS: Growth in salicylic acid altered the membrane proteome of P. aeruginosa 6294. Eighteen proteins, including OprF, OprD, MexA, OprG, PilQ, and flagellin-type A protein, were downregulated, six proteins, including OprM and OprB, were upregulated, and nine proteins were unaffected by growth in salicylic acid. Growth in salicylic acid slightly increased the resistance to carbapenem antibiotics but did not affect MICs of the other antibiotics tested. Salicylic acid treatment significantly reduced the clinical score of eyes and bacterial load in eyes during microbial keratitis but had no effect on numbers of infiltrating neutrophils. CONCLUSION: Salicylic acid altered the membrane proteins of P. aeruginosa, slightly increased the resistance of the bacterium to carbapenem antibiotics only, and was able to reduce the pathogenicity associated with P. aeruginosa infection of mouse corneas. Salicylic acid may be useful as an antimicrobial agent in the treatment of Pseudomonas keratitis.

Interleukin-4 is not critical to pathogenesis in a mouse model of Pseudomonas aeruginosa corneal infection.

PURPOSE: To determine the contribution of interleukin-4 (IL-4) to the initial host response during corneal infection with Pseudomonas aeruginosa in a mouse model. METHODS: Corneas of 6- to 8-week-old IL-4(-/-) and wild-type mice were topically challenged with P. aeruginosa. Ocular tissue was collected 24 hr and 7 days postchallenge. Viable bacterial counts, myeloperoxidase assays, cytokine levels, and clinical and histological examinations were performed. RESULTS: During challenge with P. aeruginosa, no differences were observed clinically, histologically, or in bacterial load between IL-4(-/-) and wild-type mice at either time point. However, differences in cytokine levels of IL-6, KC, and IL-10 were observed. CONCLUSIONS: The data presented indicate that IL-4, a central Th2 cytokine, may not be critical to the pathogenesis or bacterial clearance in this model of P. aeruginosa bacterial keratitis during the early stages of the infectious process.