Enfortumab-vedotin use for urothelial carcinoma in two patients on hemodialysis.

Enfortumab vedotin (EV) is a novel treatment option for patients with advanced/metastatic urothelial carcinoma who have progressed after chemotherapy and immunotherapy. Two patients at two different New England tertiary cancer care centers were treated with EV while concurrently receiving hemodialysis (HD), where a complete response to EV in both patients was noted. The use of EV in patients requiring HD is extrapolated from the available pharmacokinetic and pharmacodynamic literature on monoclonal antibodies in patients requiring HD. There is a paucity of data for the use of antibody-drug conjugates like EV in patients needing dialysis.

Medical student-led implementation of preclinical abortion didactic session at a California medical school.

BACKGROUND: Formal education surrounding abortion care during pre-clinical years of medical school is limited and will likely decrease with the overturning of Roe v. Wade. This study describes and evaluates the impact of an original abortion didactic session implemented during the pre-clinical years of medical school. METHODS: We implemented a didactic session at the University of California Irvine outlining abortion epidemiology, pregnancy options counseling, standard abortion care, and the current legislative landscape surrounding abortion. The preclinical session also included an interactive, small group case-based discussion. Pre-session and post-session surveys were obtained to evaluate changes in participants' knowledge and attitudes and to collect feedback for future sessions. RESULTS: 92 matched pre- and post-session surveys were completed and analyzed (response rate 77%). The majority of the respondents identified themselves as more "pro-choice" compared to "pro-life" on the pre-session survey. Results reflected significantly increased comfort discussing abortion care and significantly increased knowledge about abortion prevalence and techniques after the session. Qualitative feedback was overwhelmingly positive and reflected participants' appreciation for the focus on the medical aspects of abortion care as opposed to an ethical discussion. CONCLUSIONS: Abortion education targeted to preclinical medical students can be implemented effectively by a medical student cohort with institutional support.

Fatal hepatitis B reactivation in a patient receiving chemoradiation for cervical cancer.

INTRODUCTION: Hepatitis B virus (HBV) infection remains a global public health threat, with approximately 257 million people suffering from chronic HBV infection worldwide in 2015. HBV reactivation is a known complication of immunosuppressive therapy in people suffering with chronic HBV. Medications commonly associated with HBV reactivation include B-cell depleting agents and anthracycline derivatives. There have been very few documented cases of chemoradiation inducing HBV reactivation among scientific literature. CASE REPORT: A 44-year-old woman with chronic HBV infection and [FIGO] stage IIIB cervical cancer developed marked transaminitis and increased HBV viral load after receiving treatment with three doses of cisplatin and one dose of carboplatin with concurrent radiation for cervical cancer.Management and outcome: The patient was admitted for acute liver failure and quickly developed encephalopathy, with treatment complicated by coagulopathy, hypoglycemia, and metabolic acidosis. The patient remained unresponsive to maximal therapeutic efforts and was mechanically ventilated for airway protection. She subsequently died after experiencing ventricular tachycardia followed by asystole. DISCUSSION: There are currently no standardized guidelines for the screening of HBV infection or prophylaxis treatment algorithm for patients undergoing chemoradiation. When initiating treatment with immunosuppressive therapy, it is important to screen all patients for chronic HBV infection and to work with an interdisciplinary team of oncologists, hepatologists, and pharmacists to initiate prophylactic antiviral therapy and closely monitor to minimize the risk of HBV reactivation.

Vasectomy: An Opportunity for Obstetricians and Gynecologists.

Vasectomy is a safe, effective, and cost-effective contraceptive method, with a failure rate lower than that of female sterilization. Nevertheless, vasectomy is underutilized-only 6% of American women rely on vasectomy. Access to vasectomy may be limited by provider advocacy and availability. Obstetricians and gynecologists can increase both the acceptability of and access to this method if adequately trained to counsel about and provide the procedure. Although some concerns may persist surrounding obstetricians and gynecologists performing a vasectomy, increasing the availability and uptake of vasectomy avoids unnecessary surgical risks for female patients and promotes reproductive justice via shared contraceptive responsibility.

Characteristics and determinants of survival in oldest old nursing home residents admitted to hospital with an acute illness compared to their younger counterparts.

BACKGROUND AND OBJECTIVES: The clinical problems and needs of our oldest old (≥85 years) are often substantially different from those of younger patients, and are arguably different from younger elderly patients (age 65-84). With the increasing number of frail oldest olds residing in Nursing Homes (NH), we aim to identify differences in prognostic indicators and outcomes in this age group compared to younger NH residents. METHODS: We retrospectively identified all consecutive admissions from NHs to an Acute Medical Assessment Unit between January 2005 and December 2007. Admission prognostic indicators and outcomes at follow-up were compared between younger (<85) and older (≥85) age groups. Using multiple regression methods controlling for potential confounders, we compared in-hospital mortality and long-term survival after discharge between the groups. RESULTS: Three hundred and sixteen patients (mean age 84.3, SD 8.34 years) were included (68 % females). Admission characteristics were mostly similar between age groups. In-hospital mortality rates were not significantly different between groups, even after adjusting for possible confounders. Oldest old patients had a significantly greater hazard of dying after discharge (HR 1.37; 1.03-1.83) compared to the younger group after removing explanatory variables with more than 5 % missing data. CONCLUSION: Whilst the admission characteristics are similar between younger and older patients from NHs, there is evidence to suggest worse long-term survival prospects for oldest old patients.

The Effects of Pulmonary Risk Factors and Combination Thoracic Osseous Fractures on Mortality and Outcomes of Surgical Stabilization of Rib Fractures.

BACKGROUND: Rib fixation for traumatic rib fractures is advocated to decrease morbidity and mortality in select patient populations. We intended to investigate the effect of combination osseous thoracic injuries on mortality with the hypothesis that combination injuries will worsen overall mortality and that SSRF will improve outcomes in combination injuries and in high-risk patients. METHODS: Patients with rib fractures were identified from the Trauma Quality Improvement Project registry from 2019. Patients were then divided into rib fracture(s) alone or in combination with sternal, thoracic vertebra, or scapula fracture. Patients were also categorized into those with COPD and smokers. Patients with AIS >3 outside of thorax were excluded. Patients were subcategorized into those who had rib fixation verse nonoperative management for all subgroups. Analysis was performed to evaluate the efficacy of rib fixation. RESULTS: A total of 111,066 patients were included for analysis. The overall mortality was 1.4%. Patients with COPD had over double the mortality risk, with an overall mortality of 3.4%. Combination injuries did not appear to increase mortality. SSRF did not decrease mortality; however, the number of patients in this group was too small to complete statistical analysis. The overall complication rate was 0.43%. There was a trend towards an increase in extrapulmonary complications in the group that underwent surgical fixation. DISCUSSION: Mortality from rib fractures with concomitant osseous thoracic fracture appears to be low. However, mortality is increased in patients with COPD regardless of rib fracture pattern. The number of patients who underwent SSRF was too small to make a statistical comparison.

OPTIMAL Breast Cancer Care: Effect of an Outpatient Pharmacy Team to Improve Management and Adherence to Oral Cancer Treatment.

PURPOSE: Since the approval of cyclin-dependent kinase 4/6 inhibitors in 2015, this oral cancer (OC) therapy has been combined with oral endocrine therapy as first-line treatment in metastatic hormone receptor-positive breast cancer, adding unique toxicity and complexity to the successful administration of this oral medication. Implementation of OC is challenging because of delays in treatment and nonadherence and is worse among vulnerable patient populations. Pharmacists may mitigate these barriers with facilitation of prior authorizations, communication with pharmacies, toxicity management, adherence counseling, and optimization of dosing schedules and regimens. MATERIALS AND METHODS: We conducted a quality improvement project to decrease the average number of treatment day delays during the first six cycles of OC. Patients were enrolled on the OPTIMAL protocol, a high-touch pharmacy intervention incorporating pharmacists within outpatient oncology clinic visits with the providers. Pharmacists met with patients, identified individual barriers to treatment, and performed counseling including toxicity and adherence assessments. RESULTS: A preintervention assessment identified an average treatment day delay of 7.7 (range, 3.2-15.3) days during the first six cycles of OC. During the intervention period, 53 patients were enrolled on the OPTIMAL protocol and experienced an average treatment day delay of 2.1 (0.6-4) days, P < .0001. Delays were characterized as modifiable and unmodifiable. Pharmacists documented 640 interventions, including medication reconciliations and clinical recommendations. Forty-two patients reported treatment-related toxicities, resulting in 33 therapy and 20 dose modifications. CONCLUSION: Our initiative to incorporate pharmacists in clinic visits at an outpatient breast cancer clinic was associated with decreased treatment day delays during the first six cycles of treatment. Pharmacists performed a multitude of meaningful interventions to facilitate treatment in a particularly vulnerable population and play a valuable role in comanaging patients.

An evaluation of the effectiveness of induction programmes on foundation doctor preparedness: a rapid review of the literature.

There is an increase in mortality when medical graduates replace the previous cohort of foundation doctors. As of 2012, it is now mandatory for new doctors in the UK to participate in induction training in order to ease this transition and reduce the negative impact on patient outcomes. However, there is no guidance on how best to deliver these induction programmes. This review aims to evaluate the effectiveness of several induction programmes to provide insight on this. Medline and Scopus were searched for relevant literature using keywords. Duplicates were removed and inclusion criteria were created to screen the remaining literature. Five studies were included in this review and they were all quality appraised using the Medical Education Research Study Quality Instrument. Different hospital trusts utilised varying induction programmes. The most common method of assessing their effectiveness involved exploring preparedness in junior doctors post-induction through surveys. Patient outcome, anxiety levels and knowledge were also measured. Induction programmes play a vital role in preparing new foundation doctors for practice and thus improving patient outcomes. Although there may be trust-specific variation, some elements of the programme should be standardised to ensure basic requirements are met universally. New doctors should be assessed on aspects of the programme after completion to increase confidence and knowledge. Organisational considerations such as costs and staff availability need to be taken into account. The quality of future research papers could be improved through inclusion of baseline data, control groups, multi-centred studies and outcomes higher on Kirkpatrick's hierarchy.

Vasectomy Training in Family Medicine Residency Programs: A National Survey of Residency Program Directors.

BACKGROUND AND OBJECTIVES: Vasectomy is considered a permanent contraceptive method with fewer associated harms than bilateral tubal ligation. However, the number of vasectomy-trained providers may not be meeting the demand for vasectomy in the United States. We describe the vasectomy training landscape in family medicine residencies and factors related to increased procedural training. METHODS: Program-specific data were collected from the Council of Academic Family Medicine Educational Research Alliance (CERA) national survey of family medicine program directors in 2019. Program characteristics, vasectomy training (eg, time spent, procedural numbers), as well as direct and specific faculty support are described, with bivariate analyses for factors related to procedural competency, defined as more than five vasectomy procedures per resident. RESULTS: We received responses from 250 program directors (response rate=39.8%), with representation across all US regions, and program types. Nearly half (47.5%) offered less than 1 day of vasectomy didactics and/or procedural training; 38.9% of programs reported having a family medicine faculty champion for vasectomy. Only 16 programs (6.8%) reported that their average graduating residents performed more than five vasectomies. Programs with a faculty champion (OR 28.1, CI 3.6-216.4) or family medicine faculty as primary trainer (OR 17.6, CI 2.2-138.2) were more likely to graduate residents who had performed more than five vasectomies. CONCLUSIONS: Fewer than 10% of surveyed family medicine residency programs offer adequate vasectomy procedural training. Family medicine faculty who serve as primary trainers and act as faculty champions can increase vasectomy training opportunities for residents, and thereby increase the supply of vasectomy providers in the United States.

History and systematic review of wear and osteolysis outcomes for first-generation highly crosslinked polyethylene.

BACKGROUND: Highly crosslinked polyethylene (HXLPE) was introduced to reduce wear and osteolysis in total joint arthroplasty. While many studies report wear and osteolysis associated with HXLPE, analytical techniques, clinical study design and followup, HXLPE formulation and implant design characteristics, and patient populations differ substantially among investigations, complicating a unified perspective. QUESTIONS/PURPOSES: Literature on first-generation HXLPE was summarized. We systematically reviewed the radiographic wear data and incidence of osteolysis for HXLPE in hip and knee arthroplasty. METHODS: PubMed identified 391 studies; 28 met inclusion criteria for a weighted-averages analysis of two-dimensional femoral head penetration rates. To determine the incidence of osteolysis, we estimated a pooled odds ratio using a random-effects model. RESULTS: Weighted-averages analyses of femoral head penetration rates in HXLPE liners and conventional UHMWPE liners resulted, respectively, in a mean two-dimensional linear penetration rate of 0.042 mm/year based on 28 studies (n=1503 hips) and 0.137 mm/year based on 18 studies (n=695 hips). The pooled odds ratio for the risk of osteolysis in HXLPE versus conventional liners was 0.13 (95% confidence interval, 0.06-0.27) among studies with minimum 5-year followup. We identified two clinical studies of HXLPE in TKA, preventing systematic analysis of outcomes. CONCLUSIONS: HXLPE liner studies consistently report lower femoral head penetration and an 87% lower risk of osteolysis. Reduction in femoral head penetration or osteolysis risk is not established for large-diameter (>32 mm) metallic femoral heads or ceramic femoral heads of any size. Few studies document the clinical performance of HXLPE in knees.

Improving Clinical Handover on an Electronic Communication Platform: A Quality Improvement Project.

Background National guidance stipulates the essential components of a safe handover. Shift-based work and the COVID-19 pandemic has led to an increased turnover and re-deployment of staff into new clinical areas, creating challenges in delivering effective handovers. Aim The aim of this quality improvement project (QIP) was to improve adherence to a local standardised handover proforma to improve the quality and consistency of handovers. Methods Handovers were assessed by measuring the completion rates of the essential components of a safe handover as outlined in the national guidance. Data were collected from an electronic handover system which follows the Situation, Background, Assessment and Recommendations (SBAR) structure, and percentage completion rates obtained for each component assessed. Following baseline measurement, four Plan-Do-Study-Act (PDSA) cycles were completed between August 2020 and February 2021 across two junior doctor rotations and during a COVID surge rota. Results A total of 710 handovers were assessed across the four PDSA cycles. There were overall improvements in the percentage completion rates of each component compared to baseline: Under 'Situation', admission dates increased by 13.7%, estimated discharge date by 33.3% and 100% completion rate maintained for the presenting complaint. Under 'Background', past medical history remained static, with a 12.1% increase in documentation of a social history. Under 'Assessment', escalation status increased by 335%, issues list by 242% and important updates by 35.2%. Under 'Recommendations', completion rate for plans was maintained at 100%. Conclusions Our findings demonstrated an overall improvement in the majority of components of the handover proforma. Challenges remain with the rotation of junior doctors through different specialties leading to a loss of institutional knowledge and reduced longevity of the intervention's effect, exacerbated by the introduction of the COVID surge rota. A long-lasting improvement may require a shift to a completely electronic patient records system (ePR) which incorporates a handover tool.

The potential for intramuscular depot medroxyprogesterone acetate as a self-bridging emergency contraceptive.

OBJECTIVE: To examine the rate of ovulatory disruption when intramuscular depot medroxyprogesterone acetate (DMPA) is administered across graded stages of dominant follicle development. STUDY DESIGN: We assigned enrolled participants to one of three preassigned dominant follicle size groups: 12-14 mm, 15-17 mm and ≥ 18 mm. We followed dominant follicles via serial transvaginal ultrasound (TVUS) until the follicles reached their assigned size, at which time we administered DMPA. For 5 consecutive days thereafter, we followed the follicles via TVUS to observe follicle rupture and obtained serum luteinizing hormone (LH), estradiol, and progesterone concentrations. In the following 2 weeks, we collected serum progesterone concentrations twice weekly to detect possible ovulatory delay or dysfunction. We also collected serum medroxyprogesterone acetate (MPA) concentrations at 1 and 24 h after DMPA administration to examine against ovulatory outcomes. RESULTS: Twenty-six of 29 enrolled women completed the study. DMPA suppressed ovulation in 17/26 (65%) and caused ovulatory dysfunction in 1/26 (4%) participants. Larger follicles were more likely to rupture despite DMPA (12-14 mm: 0/10 (0%); 15-17 mm: 3/10 (30%); ≥ 18 mm: 6/6 (100%); p < .01). Pre-DMPA LH concentrations ranged from 13.8 to 93.7 IU/L (mean 49.0 IU/L) in cases of follicle rupture. We observed no cases of follicle rupture when DMPA was administered through cycle day 12. All 24-h MPA concentrations exceeded those needed for ovulation suppression. CONCLUSION: DMPA suppressed and additionally disrupted ovulation in 65% and 4% of observed cycles, respectively. DMPA may provide effective emergency contraception as well as ongoing contraception if administered prior to an expected ovulation and specifically before the LH surge. IMPLICATIONS: DMPA may be an alternative form of emergency contraception that can also self-bridge to ongoing contraception. As ovulation was not observed among any follicles when DMPA was given through cycle day 12, women who initiate DMPA up through cycle day 12 may not require backup contraception.

Withdrawal method inquiries and user experiences: An analysis of content posted on 4 gendered forums on Reddit.

OBJECTIVES: Limited research and guidance on the use of "withdrawal" or coitus interruptus for contraception lead to inconsistent or even inaccurate physician recommendations regarding its use. Consequently, patients rely on online communities to learn about this commonly used contraceptive method. To identify knowledge gaps and concerns between men and women, as well as explore how they use withdrawal, we examined withdrawal-related posts on the popular internet discussion forum, Reddit. STUDY DESIGN: To explore gendered variations in withdrawal-related Reddit posts, we extracted posts from the gendered forums: "TwoXChromosomes," "Askwomen," "Askmen," and "OneY" between 2010 and 2019 that contained the search terms: "coitus interruptus," "withdrawal," "pull out," "preejaculate," or "precum." We developed an initial codebook with expected codes and augmented it with emerging findings from a random sampling of 10% of posts. We revised iteratively for interrater agreement, after which researchers coded the remaining posts independently. RESULTS: Of 269 withdrawal-related queries, 19% were submitted by men; 81% referenced the contributor's own withdrawal use. Salient domains included: concerns about pregnancy risk (59%), how to effectively use withdrawal (13%), benefits/pleasure from using withdrawal (12%), impact on personal life/relationship (9%), and problems encountered, inclusive of consent (7%). Posts to female-focused forums more frequently inquired about pregnancy risk, while those on male forums more frequently inquired about withdrawal-related logistics (p < 0.001); domains were not associated with contributor gender. CONCLUSION: Withdrawal-related queries within this Reddit sample are frequently posted by women, the majority of whom want to understand their risk of pregnancy with withdrawal. Research operationalizing withdrawal and more accurately estimating withdrawal-related pregnancy risk is warranted. IMPLICATIONS: Reddit users discuss their personal experiences with withdrawal as contraception, as well as seek advice regarding its use from the online community. Pregnancy risk, logistics of use, and ongoing stigma are salient topics. Further research on pregnancy risk, operationalizing success, and approaches for discussing this behavioral method is warranted.

Reducing the Clinical and Public Health Burden of Familial Hypercholesterolemia: A Global Call to Action.

Importance: Familial hypercholesterolemia (FH) is an underdiagnosed and undertreated genetic disorder that leads to premature morbidity and mortality due to atherosclerotic cardiovascular disease. Familial hypercholesterolemia affects 1 in 200 to 250 people around the world of every race and ethnicity. The lack of general awareness of FH among the public and medical community has resulted in only 10% of the FH population being diagnosed and adequately treated. The World Health Organization recognized FH as a public health priority in 1998 during a consultation meeting in Geneva, Switzerland. The World Health Organization report highlighted 11 recommendations to address FH worldwide, from diagnosis and treatment to family screening and education. Research since the 1998 report has increased understanding and awareness of FH, particularly in specialty areas, such as cardiology and lipidology. However, in the past 20 years, there has been little progress in implementing the 11 recommendations to prevent premature atherosclerotic cardiovascular disease in an entire generation of families with FH. Observations: In 2018, the Familial Hypercholesterolemia Foundation and the World Heart Federation convened the international FH community to update the 11 recommendations. Two meetings were held: one at the 2018 FH Foundation Global Summit and the other during the 2018 World Congress of Cardiology and Cardiovascular Health. Each meeting served as a platform for the FH community to examine the original recommendations, assess the gaps, and provide commentary on the revised recommendations. The Global Call to Action on Familial Hypercholesterolemia thus represents individuals with FH, advocacy leaders, scientific experts, policy makers, and the original authors of the 1998 World Health Organization report. Attendees from 40 countries brought perspectives on FH from low-, middle-, and high-income regions. Tables listing country-specific government support for FH care, existing country-specific and international FH scientific statements and guidelines, country-specific and international FH registries, and known FH advocacy organizations around the world were created. Conclusions and Relevance: By adopting the 9 updated public policy recommendations created for this document, covering awareness; advocacy; screening, testing, and diagnosis; treatment; family-based care; registries; research; and cost and value, individual countries have the opportunity to prevent atherosclerotic heart disease in their citizens carrying a gene associated with FH and, likely, all those with severe hypercholesterolemia as well.

A Systematic Review of Cost-Effectiveness Analyses of Left Ventricular Assist Devices: Issues and Challenges.

BACKGROUND: Advanced heart failure (HF) can be treated conservatively or aggressively, with left ventricular assist devices (LVADs) and heart transplant (HT) being the most aggressive strategies. OBJECTIVE: The goal of this review was to identify, describe, critique and summarize published cost-effectiveness analyses on LVADs for adults with HF. METHODS: We conducted a literature search using PubMed and ProQuest DIALOG databases to identify English-language publications from 2006 to 2017 describing cost-effectiveness analyses of LVADs and reviewed them against inclusion criteria. Those that met criteria were obtained for full-text review and abstracted if they continued to meet study requirements. RESULTS: A total of 12 cost-effectiveness studies (13 articles) were identified, all of which described models; they were almost evenly split between those examining LVADs as destination therapy (DT) or as bridge to transplant (BTT). Studies were Markov or semi-Markov models with one- or three-month cycles that followed patients until death. Inputs came from a variety of sources, with the REMATCH trial and INTERMACS registry common clinical data sources, although some publications also used data from studies at their own institutions. Costs were derived from standard sources in many studies but from individual hospital data in some. Inputs for health utilities, which were used in 11 of 12 studies, were generally derived from two studies. None of the studies reported a societal perspective, that is, included non-medical costs such as caregiving. CONCLUSIONS: No study found LVADs to be cost effective for DT or BTT with base case assumptions, although incremental cost-effectiveness ratios met thresholds for cost effectiveness in some probabilistic analyses. With constant improvements in LVADs and expanding indications, understanding and re-evaluating the cost effectiveness of their use will be critical to making treatment decisions.

Dabigatran-Induced Acute Interstitial Nephritis: An Important Complication of Newer Oral Anticoagulation Agents.

Acute kidney injury (AKI) due to an acute interstitial nephritis (AIN) is common and can lead to increased morbidity and mortality. Medications such as antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPI) and rifampin are common offending agents. Anticoagulant-associated AIN is more frequently reported with the use of warfarin; however, only few case reports have reported an association with the use of novel oral anticoagulants (NOACs). Herein, we report the case of a 59-year-old male who developed AKI after initiating dabigatran for the treatment of atrial fibrillation. Laboratory data demonstrated elevated blood urea nitrogen (BUN) of 115 mg/dL (baseline = 35 mg/dL) and serum creatinine (Cr) of 5.06 mg/dL (baseline = 1.3 mg/dL). Urinalysis revealed eosinophiluria. Renal biopsy disclosed diffuse tubulointerstitial nephritis and eosinophils and confirmed the diagnosis of AIN. At 1 week, renal function improved (BUN/Cr = 53/2.73 mg/dL) with steroid therapy and discontinuation of dabigatran. With an increasing use of NOACs, it is important to monitor renal function to diagnose AIN in a timely fashion. Early diagnosis and prompt treatment can mitigate serious renal damage induced by dabigatran.

iNOS-mediated generation of reactive oxygen and nitrogen species by biomaterial-adherent neutrophils.

Infection due to implanted cardiovascular biomaterials is a serious complication initiated by bacterial adhesion to the surface of the implant. The release of reactive oxygen species by neutrophils, particularly superoxide anion, is a well-known bactericidal mechanism. Additionally, nitric oxide (NO) has also been identified as an important cytotoxic mediator in acute and chronic inflammatory responses with enhanced NO production by upregulation of inducible nitric oxide synthase (iNOS). The interaction of NO and superoxide anion will result in the formation of peroxynitrite (OONO-), a potent cytotoxic oxidant. In this study, we have shown that biomaterial-induced neutrophil activation does not cause upregulation of iNOS and activation of iNOS-mediated pathways. However, NO and O2- production does occur over time upon adhesion to a biomaterial and is modulated by biomaterial surface chemistry. With no stimulus, the polyethylene oxide-modified polyurethane induced greater neutrophil activation than did the control as indicated by the increased production of NO and O2- over time. Adherent-stimulated neutrophils generally produced lower amounts of NO over time in comparison with unstimulated cells. Furthermore, there is no evidence of peroxynitrite activity in unstimulated neutrophils adherent to the Elasthane 80A. However, upon stimulation with adherent Staphylococcus epidermidis, peroxynitrite formation did occur. Our results suggest that bactericidal mechanisms in neutrophils involving NO generation (NOS pathway) are further compromised than O2- producing pathways (NADPH oxidase) upon exposure to biomaterials, resulting in a diminished microbial killing capacity, which can increase the probability of device-centered infections.

S. epidermidis biofilm formation: effects of biomaterial surface chemistry and serum proteins.

Most infections due to implanted cardiovascular biomaterials are initiated by bacterial adhesion of Staphylococcus epidermidis, followed by colonization and biofilm formation on the surface of the implant. This study examined the role of serum proteins and material surface chemistry in the formation of S. epidermidis biofilm on polyurethanes (Elasthane 80A, hydrophobic) modified with polyethylene oxide (Elasthane 80A-6PEO, hydrophilic) and fluorocarbon (Elasthane 80A-6F, hydrophobic). Initial adhesion, aggregation, biofilm thickness, viability, and slime formation of S. epidermidis strain, RP62A in phosphate buffered saline (PBS), tryptic soy broth (TBS), and 20% pooled human serum was quantified. In the presence of adsorbed serum proteins, initial bacterial adhesion was suppressed significantly to <2% relative to adhesion in TSB or PBS. However, adhesion, aggregation, and proliferation increased dramatically in the 12-24 h period on Elasthane 80A and Elasthane 80A-6F, which resulted in an extensive network of biofilm. A contrasting trend was observed on the hydrophilic Elasthane 80A-6PEO surface, with minimal bacterial adhesion, which decreased steadily over 24 h. In the presence of serum proteins, an increasingly thick ( approximately 20 mum) biofilm formed on the hydrophobic surfaces over 48 h whereas the formation of a mature biofilm on the hydrophilic surface was impeded with few viable bacteria present over 48 h. Furthermore, slime was detected during the initial phase of bacterial adhesion at 2 h and increased over time with the formation of biofilm. These results have shown that while initial S. epidermidis adhesion is suppressed in the presence of adsorbed proteins, inter-bacterial adhesion possibly aided by slime production leads to the formation of a robust mature biofilm. Also, biomaterial surface chemistry affected biofilm formation and, most notably, polyethylene oxide significantly inhibited S. epidermidis biofilm formation over 48 h in vitro.