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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Effect of battery longevity on costs and health outcomes associated with cardiac implantable electronic devices: a Markov model-based Monte Carlo simulation.

INTRODUCTION: The effects of device and patient characteristics on health and economic outcomes in patients with cardiac implantable electronic devices (CIEDs) are unclear. Modeling can estimate costs and outcomes for patients with CIEDs under a variety of scenarios, varying battery longevity, comorbidities, and care settings. The objective of this analysis was to compare changes in patient outcomes and payer costs attributable to increases in battery life of implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D). METHODS AND RESULTS: We developed a Monte Carlo Markov model simulation to follow patients through primary implant, postoperative maintenance, generator replacement, and revision states. Patients were simulated in 3-month increments for 15 years or until death. Key variables included Charlson Comorbidity Index, CIED type, legacy versus extended battery longevity, mortality rates (procedure and all-cause), infection and non-infectious complication rates, and care settings. Costs included procedure-related (facility and professional), maintenance, and infections and non-infectious complications, all derived from Medicare data (2004-2014, 5% sample). Outcomes included counts of battery replacements, revisions, infections and non-infectious complications, and discounted (3%) costs and life years. An increase in battery longevity in ICDs yielded reductions in numbers of revisions (by 23%), battery changes (by 44%), infections (by 23%), non-infectious complications (by 10%), and total costs per patient (by 9%). Analogous reductions for CRT-Ds were 23% (revisions), 32% (battery changes), 22% (infections), 8% (complications), and 10% (costs). CONCLUSION: Based on modeling results, as battery longevity increases, patients experience fewer adverse outcomes and healthcare costs are reduced. Understanding the magnitude of the cost benefit of extended battery life can inform budgeting and planning decisions by healthcare providers and insurers.

Calcium Administration Is Associated with Adverse Outcomes in Critically Ill Patients Receiving Parenteral Nutrition: Results from a Natural Experiment Created by a Calcium Gluconate Shortage.

STUDY OBJECTIVE: Parenteral calcium is frequently administered to critically ill patients. However, animal studies demonstrate that calcium administration during critical illness heightens inflammation and leads to shock, organ dysfunction, and mortality. We sought to evaluate the association between calcium administration and adverse outcomes in critically ill patients receiving parenteral nutrition (PN). DESIGN: Retrospective cohort examined before and during a calcium gluconate shortage. During the shortage, calcium was absent from PN, but calcium supplementation outside of PN was allowed. The shortage resulted in a natural experiment that included a group of patients who did not receive calcium. SETTING: Intensive care units (ICUs) in three teaching hospitals. PATIENTS: A total of 259 adults who received PN in the ICU for 48 hours or longer. MEASUREMENTS AND MAIN RESULTS: Patients were divided into quartiles based on amount of parenteral calcium received; the lowest quartile received no calcium. End points were in-hospital mortality, acute respiratory failure, new-onset shock, and a composite of any one of these end points. For patients not on mechanical ventilation or vasoactive support when PN started, logistic regression revealed that calcium administration was associated with mortality (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.08-5.69), acute respiratory failure (OR 2.43, 95% CI 1.28-4.60), new-onset shock (OR 2.81, 95% CI 1.22-6.44), and the combined end point (OR 2.33, 95% CI 1.31-4.16). The odds of adverse outcomes increased as the calcium dose increased. CONCLUSION: Calcium administration correlated with adverse outcomes in critically ill patients receiving PN. The data suggest that administration of parenteral calcium to critically ill patients may be harmful.

Characterization of Outer Insulation in Long-Term-Implanted Leads.

Success of pacemakers and implantable cardioverter defibrillators may be limited by premature lead failure. Lead insulation polymers, such as polyurethane (PU) and polydimethylsiloxane (PDMS), are reported to degrade over time in vivo. PU is known to undergo oxidation, whereas PDMS undergoes surface hydrolysis. Previous studies have characterized polymer degradation in vitro, in animals or in short-term human study; however, complex effects of the biochemical and mechanical environment on the lead insulation can only be fully understood by evaluating long-term-implanted leads. Therefore, we established a retrieval program to systematically characterize the chemical and surface changes in 37 of 104 retrieved pacing and defibrillator leads, implanted for ≥5 yr. Fourier transform infrared (FTIR) spectroscopy was used for chemical analysis, and a scanning electron microscope was used for surface degradation evaluation. PDMS leads were investigated for changes in the ratio of Si-O-Si to Si-C peaks, whereas PU degradation was evaluated by changes in ether (C-O-C), carbonyl (C=O), methylene (C-H), and amino (C-N/N-H) peaks. Under SEM, PDMS showed enhanced roughness but no statistical increase in Si-O-Si bonds. PU showed uniform cracking throughout the lead body and statistical changes in each of the oxidation indicative peaks. Overall, both polymers showed surface changes in the physiological environment, but PU was the only material to show chemical changes. This work is a large-scale characterization study on long-term-implanted leads that confirmed PU oxidation but not hydrolysis of PDMS in vivo. It provides important insight for manufacturers when making design improvements and for surgeons when making decisions about lead implantation.

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status.

Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT.